Research Bibliography for Eye Conditions
and Other Diseases

Note, to see the newer, better organized research section click here.

1. CoQ10 (2011) & Migraine Headaches

Researchers, noting that CoQ10 has been shown to be effective in preventing adult migraines, wanted to examine its helpfulness in children and teens. They also noted that CoQ10 has been seen to be deficient in many children and teens who report headaches.

In a double-blind, placebo, crossover, random study researchers analyzed 120 children and teens with frequent migraines who were given either placebo or CoQ10 for 224 days. At the half way point, treatments were reversed (the crossover) so that all patients received either placebo or CoQ10.

Both groups reported fewer, less severe, and/or shorter-lasting migraines by the end of the 224 days.

2. DHA/EPA Protects Against Inflammation
DHA, a component of omega-3s, reduces inflammation and so may reduce stress caused by inflammation in the retina seen in diabetic retinopathy. DHA is also a precursor for a biochemical compound known as neuroprotectin D1, which also helps protect against damage from inflammation and reduces cell death within the retina. Bazan, N.G. (2006). Survival signaling in retinal pigment epithelial cells in response to oxidative stress: significance in retinal degenerations. Adv Exp Med Biol, 572:531-40. Bazan, N.G., Molina, M.F., Gordon, W.C. (2011). Docosahexaenoic acid signalolipidomics in nutrition: significance in aging, neuroinflammation, macular degeneration, Alzheimer's, and other neurodegenerative diseases. Annu Rev Nutr, Aug 21;31:321-51. Mukherjee, P.K., Marcheselli, V.L., Serhan, C.N., Bazan, N.G. (2004). Neuroprotectin D1: a docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress. Proc Natl Acad Sci USA, Jun 1;101(22):8491-6 Chen, W., Esselman, W.J., Jump, D.B., Busik, J.V. (2005). Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells. Invest Ophthalmol Vis Sci, Nov;46(11):4342-7.

3. Grapeseed (2017) & Diabetic Retinopathy

4. Selenium (2012) & Cardiac Health

This study aimed to assess whether selenium deficiency played an important role in healthy cardiac function.

The researchers looked at selenoprotein P in cases of sudden cardiac death in 124 subjects. SePP levels were measured in all subjects, and glutathione peroxidase were measured in 119 people. They found that the correlation was statistically significant and concluded that selenium deficiency might play an important role in the disease.

Researchers: Li Q, Li XZ, Wang T, Zhou LW, Feng HQ, Gao L, Pei JR, Lin C, Jiang CX, Institute of Keshan Disease, Center for Endemic Disease Control, Harbin Medical University, 157 Baojian Road, Harbin, 150081, China.

Published: Biol Trace Elem Res. 2012 Oct 2

Editor's Note: Selenium deficiency is rare in the US. In China, there were many childhood deaths due to Keshan disease (selenium deficiency) which leads to an abnormality of the heart muscle. The link to selenium was discovered and supplements reversed the problem. Two other conditions, Kashin-Beck disease (joint/bone), and myxedematous endemic cretinism (mental retardation).

Therefore, selenium cannot be considered as a treatment for heart disease. Meta-analysis of the literature confirms this.
Flores-Mateo G, Navas-Acien A, Pastor-Barriuso R, Guallar E., Selenium and coronary heart disease: a meta-analysis, Am J Clin Nutr. 2006 Oct;84(4):762-73;
Ghaemian A, Salehifar E, Shiraj H, Babaee Z., A Comparison of Selenium Concentrations between Congestive Heart Failure Patients and Healthy Volunteers, J Tehran Heart Cent. 2012 Spring;7(2):53-7.

5. Causticum - Homeopathic for Inflammation

Homeopathics act by stimulating the body to naturally respond to various conditions; in the case of causticum, the body is stimulated to respond to inflammation and reduce it.

2004

In this study scientists investigated the efficacy of a 30cH solution of causticum in treating inflammation compared to control. Using lab animals, inflammation and swelling was induced and the animals who were treated with causticum 30cH significantly inhibited inflammation and swelling. Pre-treatment for 6 days did not inhibit granulation.

Researchers: A. Prado Neto Jde, F. Perazzo, et al
Published: Action of Causticum in inflammatory models, Homeopathy, January, 2004.

Causticum with other Homeopathics

2016

In another six week, randomized, placebo-controlled and double-blind study causticum was one of the ingredients included in a homeopathic combination to treat patients with osteoarthritis. The other homeopathics were Arnica montana, Bryonia alba, Kalmia latifolia, Rhus toxicodendron and Calcarea fluorica. There were 30 patients who were receiving physiotherapy for osteoarthritis of the lumbar spine.

The outcomes were determined by assessing subjective pain experienced, the Oswestry Disability Index, range of motion, and whether the patient needed pain medication.

The treatment group had less pain, better range of motion, and greater ability to function on a daily basis. But there was no difference in pain medication needed.

6. Cineraria (1982, 2011, 2013) & Cataract

2013

Fights free radicals

Researchers wanted to evaluate the capacity of cineraria maritima to fight free radicals and slow development of cataracts in lab animals.

Lab animals who had severe chemical-caused eye damage were found to have heightened levels of a number of crystals and various free radicals and other abnormalities that possibly contributed to development of cataracts.

When they were injected with cineraria extract the level of free radicals declined, and other biochemical abnormalities were reduced to nearly normal levels.

While not conclusive, this study opens the possibility that cineraria maritima may be helpful in reducing or preventing cataracts. Note that in this experiment the animals were injected with cineraria into the body rather than using eyedrops.

Researchers: T.A. Anitha, et al.

Published: Putative free radical-scavenging activity of an extract of Cineraria maritima in preventing selenite-induced cataractogenesis in Wistar rat pups, Molecular Vision, Dec. 2013.

Prevents selenite-induced cataract growth.

It has been suggested that extracts of cineraria maritima may be helpful in treating cataracts. The scientists evaluated, both in vivo and in vitro, the efficiency of the herb to preventing selenite-induced cataract growth.

2011

This study involved the in vivo subjects which were lab animals with dense cataracts induced by sodium selenite injection. In the animal who had also received injections of cineraria maritima, only 33.3% of the animals developed cataracts comparted to 100% of the animals who developed cataracts without cineraria maritima.

The study concludes that cineraria may be helpful in preventing this type of chemical-induced cataract.

Editor's note: While not conclusive, this study does show that cineraria supports the health of the lens.

Researchers: T.S. Anitha, T. Annadurai, P.A. Thomas, P. Geraldine.

Published: Prevention of selenite-induced cataractogenesis by an ethanolic extract of Cineraria maritima: an experimental evaluation of the traditional eye medication, Biological Trace Element Research, October, 2011.

1982

Dr. D.H. Chand wrote an article summarizing his experience treating various eye conditions, including cataracts, with cineraria maritima.

He commented that while the effectiveness of cineraria is well known for this use, that it should be used only in the initial stages of cataract development. He wrote that internal supplementation was needed as well depending the medical history of the patient, and might include calcarea carbonica and calceria fluorata. He cited a case in which a British patient's cataract in both eyes was cleared by silica. He recommends cataracts resulting from injuries to be treated with conium maculatum or arnica montana.

Author: D. H. Chand, Role of Homeopathy in ophthalmological conditions, Indian Journal of Ophthalmology, July, 1982.

7. Euphrasia (2017) Alone and in Combination with other Homeopathics

Euphrasia

2014

This in-vitro (in the lab) study investigated the effects of Euphrasia officinalis (eyebright) with respect to protecting human corneal epithelial cells.

They tested the protective effects against several types of toxins and using several types of preparations of the herbs. Three types of extract solvents were tested: one using heptane, one using ethanol, and one using ethyl acetate.

The extracts formulated using heptane were toxic to the cells and did not reduce free radicals. All of the extracts did decrease several kinds of inflammation in the corneal cells.

They concluded that the preparation using either ethanol or ethyl acetate extracts would be suitable for eye therapy preparations.

Researchers: R. Paduch, A. Wozniak, et al
Assessment of eyebright (euphrasia officinalis L.) extract activity in relation to human corneal cells using in vitro tests, Balkan Medical Journal, March, 2014.

Euphrasia & Chamomilla

2017

Researchers wanted to investigate the efficacy of a commercial eye drop that contains several homeopathic remedies traditionally known to be helpful for vision. In addition, they wanted to gain an understanding of the mechanics of such protection.

The eyedrop contains Chamomilla matricaria and Euphrasia officinalis (eyebright). It was tested extracted human cells from the cornea which were exposed to UVB radiation. Such exposure causes oxidative stress to the eyes as well as inflammation of the cornea.

Antioxidants protect against oxidative stress. The scientists measured the potential antioxidant action and total content of the beneficial bio-chemicals known as phenols. They also evaluated health of the cells exposed to UVB radiation, wound healing, free radical levels, oxidative damage and expression of specific genes.

They found that the drops were able to protect the corneal epithelial cells from cell death due to UVB radiation and helped wounds heal. They also found that antioxidant levels increased and inflammation decreased.

Researchers: E. Bigagli, L. Cinci, et al
Published: Pharmacological activities of an eye drop containing Matricaria chamomilla and Euphrasia officinalis extracts in UVB-induced oxidative stress and inflammation of human corneal cells, Journal of Photochemistry and Photobiology, August, 2017.

About Wellness

1. AOA (2011) Eye Q Survey Results

According to the most recent AOA Eye-Q survey there are still many misconceptions regarding eye health, which consumers take as truth.

In addition, the rising use of computers and electronic devices is a rising concern for parents - both in the classroom and outside of the classroom. However, still only 29% of parents had this concern. 62% of parents estimate their child spends 1-4 hours daily on a computer or hand-held electronic device.

The AOA restated that prolonged use of electronic devices can cause eye strain, headaches, fatigue, burning or tired eyes, loss of focus, blurred vision, double vision or head and neck pain, computer vision syndrome (CVS) (or computer eye strain syndrome.

The increased use of 3D imagery in the classroom may unmask other unlying vision problems that children may have such as lazy eye, convergence insufficiency, poor focusing skills and other visual problems. 53% of parents were concerned that 3-D viewing might be harmful to their children's eyes.

Eye care and beauty aids

The 2011 survey also found that many women don't replace old eye makeup for new frequently, and younger women often share eye makeup. Most people use skin care products but fail to protect the delicate skin around the eyes.

Diet and vision health

Nearly half (49%) think that carrots are the best food for eye health, and don't know that foods such as spinach, broccoli and apples were the best foods for vision health.

2. Exercise (2015) & Brain Volume & Aging

Learn more about Alzheimer's disease and cognitive impairment. Also see more information on exercise and the brain.

Researchers have been developing an understanding that exercise improves mental functioning, known as cognitive functioning. But what is less understood is the relationship between cognitive capacity and the size of the brain. In many cognitive disabling conditions it has been observed that the physical size of the brain shrinks.

Researchers devised research to examine this relationship. They selected 110 people who were over 65 and who were healthy. Most of them were enrolled into an exercise group and they used home-based exercise regimens as well.

The study lasted for 2 years, and for an additional 6 months the researchers monitored the subjects after they had stopped the exercise programs.

The researchers used techniques such as MRI to produce images of the participants' brains during the course of the study. They found that while brain volume normally decreases with age, in these subjects prefrontal (both sides) volume was preserved but the benefit faded after the participants ceased the exercise program. The prefrontal part of the brain, the front of the brain, is needed for planning, cognitive behavior, decision making, and how the personality expresses itself. This is the part of the brain whose failure is most immediately noticeable in patients with cognitive impairment.

The scientists also monitored the participants' cognitive functioning in areas such as attentional shift. Attentional shift simply means the ability to shift the vision and thus attention from one point to another and to maintain that attention. Normally as we age it is increasingly difficult to maintain attention to one point. These patients saw improvement in this regard. This improvement persisted during the 6 months following the 2 year exercise period.

Researchers: M. Tamura, K. Nemoto, et al
Published: Long-term mild-intensity exercise regimen preserves prefrontal cortical volume against aging, International Journal of Geriatric Psychiatry, July, 2015.

3. Lutein & Zeaxanthin (2015, 2016) Role in Vision & Disease

Learn more about zeaxanthin and Ma href="http://www.naturaleyecare.com/nutrients/antioxidants/lutein.asp">lutein.

Lutein and zeaxanthin, two important carotenoids in the eye do much more than simply defend against macular degeneration and other eye diseases.

Retinal and macular support. These carotenoid antioxidants have been found to be helpful in protecting the health of the macula and in fighting macular degeneration and other conditions involving macular health.

Retinal pigment. One of their benefits to macular degeneration is because they are retinal pigments that filter damaging UV radiation from the sun. While leafy green vegetables are important contributors of these carotenoids, the lutein and zeaxanthin supplied by red and orange foods provides better support for formation of retinal pigment.

In a cross-section study researchers assessed dietary consumption of fruits, vegetables, and eggs based on intake recalls and a carotenoid database. The carotenoids came mostly from vegetables (~80%+), eggs, and fruits (3% (lutein) & 15% (zeaxanthin). Most of the carotenoids came from the green foods, but when macular pigment density was measured it was found that the red and orange foods had a greater effect.

Editor's note: there is now a wide understanding among researchers that greater macular pigment density is associated with a lower risk of developing macular degeneration and other macular conditions.

Researchers: R. Estevez-Santiago, et al.
Published: Lutein and zeaxanthin supplied by red/orange foods and fruits are more closely associated with macular pigment optical density than those from green vegetables in Spanish subjects, Nutrition Research, November, 2016.

Glare recovery. Optometrists who are diagnosing vision problems use a standard test called a glare recovery test to determine whether the problem originates from the macula or the optic nerve. The doctor shines a bright light at the patient's eyes, or has the patient look at the eye chart through a ring of bright lights. If the macula is the source of problems the patient has difficulty in seeing through the ring of lights or takes a long time to see the eye chart letters after the bright light is shined at his eyes. If the optic nerve is involved the bright lights do not pose a problem.

When the macular pigment has greater density, glare recovery is much better and the carotenoids lutein, zeaxanthin and meso-zeaxanthin improve the thickness and density of the pigmented layer of the retina.

Researchers: J. M. Stringham, et al.
Published: Macular carotenoid supplementation improves disability glare performance and dynamics of photostress recovery, Eye and Vision, November, 2016.

Biomarker role. Biomarkers are the measurable nutrients or vitamins or other biochemicals found in the blood that help medical professionals in diagnosis.

Researchers have determined that lutein and zeaxanthin are excellent biomarker when evaluating the quality of women's diets. Over 150 post-menopause women followed a specific diet for two weeks before blood samples were tested. A number of biomarkers were measured before and after the test. They included carotenoids, B-12, tocopherols, folate, and some fatty acids. All of these except the fatty acids and tocopherols were identified as very good biomarkers that will be useful in diagnostics.

Researchers: J. W. Lampe, et al.
Dietary biomarker evaluation in a controlled feeding study in women from the Women's Health Initiative cohort, American Journal of Clinical Nutrition, December, 2016.

Cancer. Scientists have long thought that carotenoids might be helpful in reducing the risk of non-Hodgkin lymphoma, but the data has been inconsistent. Researchers performed a meta-analysis (a study of studies - which yields a sum larger sample size and more accurate results) of ten studies which met their requirements for inclusion.

They found that higher consumption of the carotenoids lutein and zeaxanthin as well as alpha- and beta-carotene were tied to a markedly lower risk of "diffuse large B-cell lymphoma, but not follicular lymphoma or small lymphocytic lymphoma/chronic lymphocytic leukemia".

Researchers: F. Chen, et al.
Carotenoid intake and risk of non-Hodgkin lymphoma: a systematic review and dose-response meta-analysis of observational studies, Annals of Hemotology, December, 2016.

Stem cell support. Many new treatments for health problems are being addressed through stem cell transplantation. The problem is that the body's immune system may reject the transplanted cells. Researchers specifically investigating stem cell transplantation treatment for liver failure determined that such stem cells are vulnerable to inflammation and oxidative stress causing high rates of cell death.

They found in in-vitro testing that pre-treatment with zeaxanthin was helpful in supporting the defense mechanism of transplanted stem cells and made them more capable of repairing liver tissue.

Researchers: Y. Liu, et al.
Published: Precise Regulation of miR-210 is Critical for the Cellular Homeostasis Maintenance and Transplantation Efficacy Enhancement of Mesenchymal Stem Cell in Acute Liver Failure Therapy, Cell Transplantation, December, 2016.

Fracture. Yet another interesting new study connects carotenoid levels in the body with risk of fracture. A meta-analysis of seven studies which included a total of over 140,000 subjects and another over-4000 specific cases found that there was a close relationship between levels of carotenoids circulating in the blood plasma with the risk of fracturing a bone.

Patients who consumed high levels of carotenoids such as lutein and zeaxanthin, as well as beta-carotene had a 28% lower chance of having a hip fracture. However there was significant variation between the different studies, so although the average demonstrates a connection, further research is needed to validate these results.

Researchers: J. Xu, C. Song, et.al.
Published: Carotenoids and risk of fracture: a meta-analysis of observational studies, Oncotarget, November, 2016.

Atherosclerosis

Other new research connects higher levels of lutein with lower incidence of atherosclerosis (coronary heart disease).

Other research For a more in-depth review of the broad range of benefits from these essential carotenoids see this article published in the International Journal of Retina and Vitreous in August, 2016.

4. Mediterranean Diet (2015)

The Mediterranean diet is widely accepted as being beneficial to vision health, heart health, immune system health, etc. Here are links to articles on the Mediterranean diet on this website.

5. Olive Oil (2011) Standards updated and beneficial effect

Read our overview on preventing eye disease and supporting generation health.

The beneficial health effects of olive oil are due to both its high content of monounsaturated fatty acids and its high content of antioxidative substances. Studies have shown that people who consumed about 2 tablespoons of virgin olive oil daily for 1 week showed less oxidation of LDL cholesterol and higher levels of antioxidant compounds, particularly phenols, in the blood.

The International Olive Oil Council (IOOC) sets standards of quality used by the major olive oil producing countries. The United States is not a member of the IOOC, and the U.S. Department of Agriculture does not legally recognize its classifications. California has set high standards for its olive oil through the California Olive Oil Council (COOC). The COOC has adopted the standards set by the International Olive Oil Council, but went one step further. The international standard for free acidity content is less than 0.8% and the COOC standard for free acidity content is less than 0.5%. If olive oil makers from California meet these standards, they can put the COOC seal of quality on their bottles.

There is a simple home test for the purity of olive oil, although it is not conclusive: refrigeration. Wikipedia says that when genuine olive oil is refrigerated, it should become thicker if not nearly solid. Blended olive oils and non-olive oils posing as olive oil will not solidify when refrigerated.

Allergies & Sensitivities

1. Taurine (2010, '14, '17) Allergies, and Inflammation

Learn more about treatment options for allergies and sensitivities.

2017

Researchers recognize that taurine is widely understood to be a potential therapy for chronic inflammation disorders. This is of interest to those suffering from allergies since inflammation caused by allergens is at the source of many symptoms.

In this study on taurine's effects on allergy symptoms scientists were evaluating the effects of taurine on biochemicals called cytokines which promote inflammation as well as other markers of inflammation-related imbalances. They examined mast cells (a type of white blood cell derived from stem cells) which were reacting to a specific type of allergic reaction.

They found that, in a dose related manner, taurine was able to inhibit the production and activity of pro-inflammatory cytokines. And in animal testing they found similar results in that animals were much less affected by allergens.

Researchers: S. Kim, H. Kim, et al
Published: The potential protective role of taurine against experimental allergic inflammation, Life Science, September, 2017.

2014

When the body experiences inflammation as a result of oxidative stress, trauma, exposure to toxins, etc, taurine is part of the response mechanism to try to reduce the negative effects of inflammation.

When some part of the body becomes inflamed due to exposure to allergens taurine undergoes a biochemical change to lessen damage from inflammation.

Upon inflammation taurine is converted to taurine chloramine and taurine bromamine. Taurine chloramin increases the action of antioxidants to protect cell tissue from damage. At the same time it inhibits the creation of cytokines and free radicals that cause inflammation.

Researchers: C. Kim, Y.N. Cha,
Published: Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects, Amino Acids, January, 2014.

Editor's Note to vegetarians: Taurine is usually abundant in the body, but it is not produced by plants and so supplementation may be appropriate. Check with your doctor.

2010

Taurine chloramine is produced by the body in response to the presence of inflammation. The biochemical acts to reduce the inflammatory response through inhibiting the action of pro-inflammatory biochemicals called cytokines, as well as directly reduce free radicals and oxidative stress.

These researchers explored the mechanics of the process, using tissue from rheumatoid arthritis patients. They found that taurine cloramine inhibits the synthesis of two interleukins that are biomarkers for inflammation. Interleukins are a kind of special protein produced by white blood cells which help to regulate inflammation. In the case of arthritis, these interleukins over-react. Taurine cloramine is able to inhibit their production.

Researchers: E. Kontny, K. Szczepariska, et al
Published: The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) production by rheumatoid arthritis fibroblast-like synoviocytes, Arthritis and Rheumatism, October, 2000.

2. Xtra Allergies and Sensitivities Bibliography Info - Early Research
Also see discussion of allergies & sensitivities research.

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Alzheimer's Disease

1. *Ashwagandha (1997-2019) & Azheimer's

Ashwagandha may be especially important for brain functioning.

Ashwagandha root extract (Indian winter cherry or Indian ginseng/withania somnifera) reverses behavioral deficits and plaque load in Alzheimer models and inhibits amyloid beta fibrillation. Its withanamides reduce accumulation of beta-amyloid peptides in AD models and are neuroprotective. Extracts of ashwagandha increase acetylcholine content (which is essential to brain health) and choline acetyl transferase activity in rats which might partly explain the cognition-enhancing and memory-improving effects. The leaves also have nootropic potential with multiple benefits including reversing Alzheimer pathologies, protecting against environmental neurotoxins, and enhancing memory.

Based on research on ashwagandha and other herbs researchers are finding that combinations often provide increased benefit by providing understanding of better use of a "combination-drugs-multi-targets" strategy in treating conditions like Alzheimer's.

Research

Witter S, Witter R, Vilu R, Samoson A. (2018). Medical Plants and Nutraceuticals for Amyloid-B Fibrillation Inhibition. J Alzheimers Dis Rep. Dec 24:2(1):239-252.
Kuboyama T, Tohda C, Komatsu K. (2014). Effects of Ashwagandha (Roots of Withania somnifera) on Neurodegenerative Diseases. Biol Pharm Bull. 2014;37(6):892-7.
Jayaprakasam B, Padmanabhan K, Nair MG. (2010). Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer's disease. Phytother Res. Jun; 24(6):859-63. No author listed. (2004). Monograph. Withania somnifera. Altern Med Rev. Jun; 9(2):211-4
Parihar MS, Hemnani T. (2003). Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity. J Biosci. Feb;28(1):121-8.
Uddin MS, Al Mamun A, Kabir MT, Jakaria M, Mathew B, et al. (2019). Nootropic and Anti-Alzheimer's Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer's Neuropathology. Mol Neurobiol. Jul;56(7):4925-4944.
Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V. (1997). Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int. Feb;30(2):181-90.
Wadhwa R, Konar A, Kaul SC. (2016). Nootropic potential of Ashwagandha leaves: Beyond traditional root extracts. Neurochem Int. May;95:109-18.
Sharma A, Kumar Y. (2019). Nature's Derivative(s) as Alternative Anti-Alzheimer's Disease Treatments. J Alzheimers Dis Rep. Nov 21;3(1):279-297.
Sahoo AK, Dandapat J, Dash UC, Kanhar S. (2018). Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer's disease. J Ethnopharmacol. Apr 6;215:42-73.

2. *Bacopa monnieri (2008-2019) & Alzheimer's

Bacopa may be especially valuable for brain functioning.

Bacopa monnieri extract (Brahmi). Bacopa monnieri is known to have neuroprotective and cognition enhancing effects and has traditionally been a therapy for Alzheimer's disease. It improves circulation to the brain, improves mood, cognitive function, and general neurological function. Bacopa extract protects neurons from beta-amyloid-induced cell death by suppressing cellular acetylcholinesterase activity, and reduces oxidative stress by inhibiting release of proinflammatory cytokines from microglial cells (in vitro). It protects cells from oxidative damage from free radicals and DNA damage in the hippocampus, reduces lipid oxidation, is comparable to donepezil (and other drugs) in reducing anticholinesterase activity.

Abdul Manap AS, Vijayabalan S, Madhavan P, Chia YY, Arya A, et al. (2019). Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies. Drug Target Insights. Jul 31;13:1177392819866412.
Shinde P, Vidyasagar N, Dhulap S, Dhulap A, Hirwani R. (2015). Natural Products based P-glycoprotein Activators for Improved B-amyloid clearance in Alzheimer's Disease: An in silico Approach. Cent Nerv Syst Agents Med Chem. 2015;16(1):50-9.
Uabundit N, Wattanathorn J, Mucimapura S, Ingkaninan K. (2010). Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer's disease model. J Ethnopharmacol. Jan 8;127(1):26-31.
Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K. (2008). Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol. Oct 30; 120(1):112-7.
Nemetcheck MD, Stierle AA, Stierle DB, Lurie DI. (2017). The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. J Ethnopharmacol. Feb 2;199:92-100.
Chaudhari KS, Tiwari NR, Tiwari NR, Sharma RS. (2017). Neurocognitive Effect of Nootropic Drug Brahmi (Bacopa monnieri) in Alzheimer's Disease. Ann Neurosci. May;24(2):111-122.

On the basis of earlier studies researchers noted bacopa's ability to inhibit toxicity from tau, concluding that it can be used as a lead formulation in treating Alzheimer's and other neurological conditions.

Dubey T, Chinnathambi S. (2019). Brahmi (Bacopa monnieri): an ayurvedic herb against the Alzheimer's disease. Arch Biochem Biophys. Nov 15;676:108153.

Researchers further identify clinical applications, actions within and against cells, phytochemistry and biological applications indicating efficacy of bacopa as a therapeutic tool against Alzheimer's disease.

Manap ASA, Vijayabalan S, Madhavan P, Chia YY, Arya A, et al. (2019). Bacopa monnieri, a Neuroprotective Lead in Alzheimer Disease: A Review on Its Properties, Mechanisms of Action, and Preclinical and Clinical Studies. Drug Target Insights. Jul 31;13:1177392819866412.

3. *Baicalein (2011, '14, '16, '17) & Alzheimer's

Baicalein may be especially helpful for brain functioning.

Baicalein is a flavonoid, one of the most common types of plant-derived nutrients. It comes from the roots of Scutellaria baicalensis and Scutellaria lateriflora. It has been much investigated with respect to cancer, glaucoma, viruses, etc, with recognized potential benefit.

Baicalein has been of great interest to investigators due to its versatility as a therapeutic agent for neurological diseases.^{1, 2} It shows therapeutic potential for Alzheimer's disease³ and significantly improves the biochemical and histopathological condition of AD in lab animals.⁴It protects synaptic functions and memory, by preventing amyloid beta impairment in the hippocampus of animal models of AD.^{5, 6} It may be that indirect action on impaired insulin signaling and glucose metabolism accounts for the protective effect.⁷

Research

1. Gasiorowski K, Lamer-Zarawska E, Leszek J, Parvathaneni K, Yendluri BB, et al. (2011). Flavones from root of Scutellaria baicalensis Georgi: Drugs of the future in neurodegeneration? CNS Neurol Disord Drug Targets. Mar;10:184-191.
2. Sowndhararajan K, Deepa P, Kim M, Park SJ, Kim S. (2017). Baicalein as a potent neuroprotective agent: A review. Biomed Pharmacother. Nov;95:1021-1032.
3. Li Y, Zhao J, Holscher C. (2017). Therapeutic Potential of Baicalein in Alzheimer's Disease and Parkinson's Disease. CNS Drugs. Aug:31(8):639-852.
4. Zhou L, Tan S, Shan YL, Wang YG, Cai W, et al. (2016). Baicalein improves behavioral dysfunction induced by Alzheimer's disease in rats. Neuropsychiatr Dis Treat. Dec 9;12:3145-3152.
5. Gu XH, Xu LJ, Liu ZQ, Wei B, Yang YJ, et al. (2016). The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease. Behav Brain Res. Sep 15;311:309-321.
6. Wei D, Tang J, Bai W, Wang Y, Zhang Z. (2014). Ameliorative effects of baicalein on amyloid-B induced Alzheimer's disease rat model: a proteomics study. Curr Alzheimer Res. 2014;11(9):869-81.
7. Chirumbolo S, Bjorklund G. (2016). Commentary: The Flavonoid Baicalein Rescues Synaptic Plasticity and Memory Deficits in a Mouse Model of Alzheimer's Disease. Front Neurol. Aug 29;7:141.

4. Acetyl-L-Carnitine (1994-2017) & Alzheimer's Disease

In pretreatment acetyl-l-carnitine has been shown to increase mitochondrial biogenesis and decrease production of free radicals. Since the late 1990s, it has been demonstrated that it slows the development of AD. It reduces the ill effects of high levels of homocysteine, lessens physical and mental fatigue, and improves cognitive functioning. It may raise the levels of nerve growth factor and increase the activity of acetylcholine (it is a precursor of acetylcholine), a neurotransmitter that is critical to healthy brain function. ALA supports neurogenesis (production of new neurons) in the brain resulting in improvements in memory and learning as well as mental status and cognitive function.

A small double-blind placebo-controlled 12 twelve-week trial, using 2250 to 3000mg daily found that neuropsychological tests (MMSE, CGI, etc) was markedly better than placebo, and did not depend on the baseline cognitive impairment. The researchers recommend it for early stages of Alzheimer's and vascular dementia.

Combined with alpha lipoic acid, it is more effective.

Research

Pettigrew JW, Klunk WE, Panchalingam K, Kanfer JN, McClure RJ. (1995). Clinical and neurochemical effects of acetyl-L-carnitine in Alzheimer's disease. Neurobiol Aging. Jan-Feb;16(1):1-4.
Brooks JO 3rd, Yesavage JA, Carta A, Bravi D. (1998). Acetyl L-carnitine slows decline in younger patients with Alzheimer's disease: a reanalysis of a double-blind, placebo-controlled study using the trilinear approach. Int Psychogeriatr. Jun;10(2):193-203.
Zhou P, Chen Z, Zhao N, Liu D, Guo ZY, et al. (2011). Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities. Rejuvenation Res. Dec;14(6):669-79.
Malaguarnera M, Gargante MP, Cristaldi E, Colonna V, Messano M. et al. (2008) Acetyl L-carnitine (ALC) treatment in elderly patients with fatigue. Arc Geron Geriatr. Mar-Apr; 46(2):181-190.
Jones LL, McDonald DA, Borum PR. (2010). Acylcarnitines: role in brain. Prog Lipid Res. Jan;49(1):61-75.
Yin YY, Liu H, Cong XB, Liu Z, Wang Q, et al (2010). Acetyl-L-carnitine attenuates okadaic acid induced tau hyperphosphorylation and spatial memory impairment in rats. J Alzheimers Dis. 2010;19(2):735-46.
Salvioli G, Neri M. (1994). L-acetylcarnitine treatment of mental decline in the elderly. Drugs Exp Clin Res. 1994;20(4):169-76.
Ames BN, Liu J. (2004). Delaying the mitochondrial decay of aging with acetylcarnitine. Ann N Y Acad Sci. Nov;1033:108-16.
Gavrilova SI, Kalyn IaB, Kolykhalov IV, Roshchina IF, Selezneva ND. (2011). [Acetyl-L-carnitine (carnicetine) in the treatment of early stages of Alzheimer's disease and vascular dementia]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(9):16-22.
Ferreira GC, McKenna MC. (2017). L-Carnitine and Acetyle-L-carnitine Roles and Neuroprotection in Developing Brain. Neurochem Res. Jun;42(6):1661-1675.

5. Aged Garlic (2001-2020) & Cognitive Impairment

Compared to regular garlic, aged garlic extract stands out as having superior beneficial effects with respect to inhibiting platelet aggregation in cardiovascular disease,¹ strengthening the immune system and boosting levels of natural glutathione,^{2, 3, 4, 5} supporting working memory and cognitive capacity, slowing cholinergic cell death due to amyloid beta accumulation,^{6, 7} being neuroprotective,⁸ and protecting neuronal PC12 cells against amyloid beta.⁹ Aged garlic extract restricts several of the cascades related to synapse deterioration and neuroinflammation,¹⁰ improves cognitive impairment, and reduces neurodegeneration caused by amyloid beta accumulation,^{11, 12} regulates cholinergic function,¹³ improves short-term recognition memory in lab animals, and slows the inflammatory response.¹⁴

A 2020 review of research determined that aged garlic has valuable potential in preventing cognitive and learning dysfunction due to its antioxidant, anti-inflammatory and modulatory effects on neurotransmitter function in the regions of the brain associated with Alzheimer's.¹⁵

1. Steiner M, Li W. (2001). Aged garlic extract, a modulator of cardiovascular risk factors: a dose-finding study on the effects of AGE on platelet functions. J Nutr. Mar; 131(3s):980S-4S.
2. Jeong YY, Park HJ, Cho YW, Kim EJ, Kim GT, et al. (2012). Aged red garlic extract reduces cigarette smoke extract-induced cell death in human bronchial smooth muscle cells by increasing intracellular glutathione levels. Phytother Res. Jan;26(1):18-25.
3. Weiss N, Papatheodorou L, Morihara N, Hilge R, Ide N. (2013). Aged garlic extract restores nitric oxide bioavailability in cultured human endothelial cells even under conditions of homocysteine elevation. J Ethnopharmacol. Jan 9;145(1):162-7.
4. Ishikawa H, Saeki T, Otani T, Suzuki T, Shimozuma K, et al. (2006). Aged garlic extract prevents a decline of NK cell number and activity in patients with advanced cancer. J Nutr. Mar;136(3 Suppl):816S-820S.
5. Morioka N, Sze LL, Morton DL, Irie RF. (1993). A protein fraction from aged garlic extract enhances cytotoxicity and proliferation of human lymphocytes mediated by interleukin-2 and concanavalin A. Cancer Immunol Immunother. Oct;37(5):316-22.
6. Thorajak P, Pannangrong W, Welbat JU, Chaijaroonkhanarak W, Sripanidkulchai K, et al. (2017). Effects of Aged Garlic Extract on Cholinergic, Glutamatergic and GABAergic Systems with Regard to Cognitive Impairment in Aβ-Induced Rats. Nutrients. Jul 1;9(7):E686.
7. Nillert N, Pannangrong W, Weilbat JU, Chijaroonkhanarak W, Sripanidkulchai K, et al. (2017). Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by β-Amyloid in Rats. Nutrients. Jan 3;9(1):E24.
8. Cemil B, Gokce EC, Kahveci R, Gokce A, Aksoy N, et al. (2016). Aged Garlic Extract Attenuates Neuronal Injury in a Rat Model of Spinal Cord Ischemia/Reperfusion Injury. J Med Food. Jun;19(6):601-6.
9. Griffin B, Selassie M, Gwebu ET. (2000). Effect of Aged Garlic Extract on the Cytotoxicity of Alzheimer β-Amyloid Peptide in Neuronal PC12 Cells. Nutr Neurosci. 2000;3(2):139-42.
10. Ray B, Cauhan NB, Lahiri DK. (2011). The "aged garlic extract:" (AGE) and one of its active ingredients S-allyl-L-cysteine (SAC) as potential preventive and therapeutic agents for Alzheimer's disease (AD). Curr Med Chem. 2011;18(22):330-13.
11. Jeong JH, Jeong HR, Jo YN, Kim HJ, Shin JH, et al. (2013). Ameliorating effects of aged garlic extracts against AB-induced neurotoxicity and cognitive impairment. SMC Complement Altern Med. Oct 18;13:268.
12. Li F, Kim MR. (2019). Effect of Aged Garlic Ethyl Acetate Extract on Oxidative Stress and Cholinergic Function of Scopolamine-Induced Cognitive Impairment in Mice. Prev Nutr Food Sci. Jun;24(2):165-170.
13. Ibid. Li. (2019).
14. Nillert N, Pannangrong W, Welbat JU, Chaijaroonkhanarak W, Sripanidkulchai K, et al. (2017). Neuroprotective Effects of Aged Garlic Extract on Cognitive Dysfunction and Neuroinflammation Induced by B-Amyloid in Rats. Nutrients. Jan 3;9(1):E24.
15. Sripanidkulchai B. (2020). Benefits of aged garlic extract on Alzheimer's disease: Possible mechanisms of action. Exp Ther Med. Feb;19(2):1560-1564.

6. Alpha Lipoic Acid (1999-2018) & Alzheimer's

Alpha lipoic acid (ALA) hs been called the "universal" antioxidant because it boosts glutathione levels in cells already within a normal range, and has potent antioxidant actions, reducing oxidative stress.

The alpha R form is the one most easily utilized by the body. Supplementation with alpha lipoic acid inhibits progress of tau protein toward fibrils of plaque, reduces cognitive decline, lipid peroxidation, inflammation, and tau-induced iron overload.

Its therapeutic potential for different neurodegenerative diseases, including Alzheimer's is due to improved mitochondrial function in Alzheimer's, and Parkinson's. It protects against age-related cognitive dysfunction for those with AD and other neurodegenerative conditions. Studies aiming to assess the neuroprotective effects of LA on behavioral outcomes show that LA can reduce memory deficits in different behavioral paradigms of AD.

Research

Farr SA, Poon HF, Dogrukol-Ak D, Drake J, Banks WA, et al. (2003). The antioxidants alpha-lipoic acid and N-acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice. J Neurochem. Mar;84(5):1173-83.
Mahboob A, Farhat SM, Iqbal G, Babar MM, Zaidi NU, et al. (2016). Alpha-lipoic acid-mediated activation of muscarinic receptors improves hippocampus- and amygdala-dependent memory. Brain Res Bull. 2016 Apr; 22():19-28.
Hiller S, DeKroon R, Hamlett ED, Xu L, Osorio C, et al. (2016). Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress. Biochim Biophys Acta. Jan;1860(1 Pt A):36-45.
Zhang YH, Wang DW, Xu SF, Zhang S, Fan YG, et al. (2018). A-Lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice. Redox Biol. Apr;14:535-548.
Packer L, Tritschler HJ, Wessel K. (1997). Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med. 1997;22(1-2):359-78.
The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview. Liu J Neurochem Res. 2008 Jan; 33(1):194-203.
Hager K, Marahrens A, Kenklies M, Riederer P, Munch G. (2001). Alpha-lipoic acid as a new treatment option for Alzheimer [corrected] type dementia. Arch Gerontol Geriatr. Jun;32(3):275-82.
Zhang H, Jia H, Liu J, Ao N, Yan B, et al. (2010). Combined R-alpha-lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease. J Cell Mol Med. Jan;14(1-2):215-25.
Zuo L, Motherwell MS. (2013). The impact of reactive oxygen species and genetic mitochondrial mutations in Parkinson's disease. Gene. Dec 10;532(1):18-23.
Khanna S, Atalay M, Laaksonen DE, Gul M, Roy S, et al. (1999). Alpha-lipoic acid supplementation: tissue glutathione homeostasis at rest and after exercise. J Appl Physiol (1985). Apr;86(4):1191-6.
Quinn JF, Bussiere JR, Hammond RS, Montine TJ, Henson E, et al. (2007). Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiol Aging. Feb;28(2):213-25.
Farr SA, Price TO, Banks WA, Ercal N, Morley JE. (2012). Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis. 2012;32(2):447-55.
Holmquist L, Stuchbury G, Berbaum K, Muscat S, Young S, et al. (2007). Lipoic acid as a novel treatment for Alzheimer's disease and related dementias. Pharmacol Ther. Jan;113(1):154-64.

7. Amla ('07, '12, 2014) & Alzheimer's

Amla (Emblica officinalis) belongs to the family Euphorbiaceae. It is an important ayurvedic medicinal herb and its fruits contain powerful antioxidant components: tannins and tannoids, vitamin C and bioflavonoids. Its anti-inflammatory, antioxidant, and other properties make it ideal for synergistic value in enhancing other nutrients and medicinal herbs. Because it helps to enhance memory and reduce memory impairment, formulations containing it may have a role in managing conditions such as Alzheimer's and other impaired-memory conditions. Amla also posses anti-cholinesterase activity further suggesting its potential for treatment of cognitive impairments induced by cholinergic dysfunction.

Research

Mani V, Parle M. (2007). Memory enhancing activity of Anwala churna (Emblica officinalis Gaertn.): An Ayurvedic preparation. Phys Behav. Jun;91(1):46-54.
Mathew M, Subramanian S. (2014). In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders. PLoS One. Jan 23;9(1):486804.
Golechha M, Bhatia J, Arya DS. (2012). Studies on effects of Emblica officinalis (Amla) on oxidative stress and cholinergic function in scopolamine induced amnesia in mice. J Environ Biol. Jan;33(1):95-100.

8. Astaxanthin ('11, '18, 2019) & Alzheimer's

Learn more about Alzheimers Disease.

Phospholipid hydroperoxides (PLOOH) is an enzyme that abnormally accumulate abnormally in the red blood cells of patients with dementia. Scientists studied whether powerful carotenoid antioxidants could be helpful. They conducted a double-blind, random, placebo-controlled trial in 30 patients to see whether astaxanthin would be helpful as a supplement. Patients were give either 6mg or 12mg of astaxanthin daily for 12 weeks. The researchers looked at astaxanthin and PLOOH levels in the elderly and middle-aged patients.

They found that astaxanthin was higher in the red blood cells (erythrocytes) of both groups who given that supplement than in the placebo group. At the same time they found that PLOOH levels decreased more strongly in the groups receiving astaxanthin. They also looked at plasma where PLOOH levels were also reduced, although less strongly.

The scientist felt that these results may indicate a valuable contribution to the prevention of dementia.

Nakagawa K, Kiko T, Miyazawa T, Carpentero BG, Kimura F, et al. (2011). Antioxidant effect of astaxanthin on phospholipid peroxidation in human erythrocytes. Br J Nutr. Jun;105(11):1563-71.

A combination of astaxanthin and DHA are more effective in reducing oxidative stress, enhancing learning, memory, and reducing tau hyperphosphorylation, and neuroinflammation than either alone.

Mattei R, Polotow TG, Vardaris CV, Guerra BA, Leite JR, et al. (2011). Astaxanthin limits fish oil-related oxidative insult in the anterior forebrain of Wistar rats: Putative anxiolytic effects? Pharmacol Biochem Behav. 2011;99:349-355.
Che H, Li Q, Zhang T, Wang D, Yang L, et al. (2018). Effects of Astaxanthin and Docosahexaenoic-Acid Acylated Astaxanthin on Alzheimer's Disease in APP/PS1 Double-Transgenic Mice. J Agric Food Chem. May 16;66(19):4948-4957.

In animal models of AD, researchers find that astaxanthin, like bexarotene (which stimulates a retinoid receptor), is protective in Alzheimer's because it modulates amyloid-beta and improves cholesterol balance in the blood-brain barrier.

Fanaee-Danesh E, Gali CC, Tadic J, Zandl-Lang M, Kober AC, et al. (2019). Astaxanthin exerts protective effects similar to bexarotene in Alzheimer's disease by modulating amyloid-beta and cholesterol homeostasis in blood-brain barrier endothelial cells. Biochim Biophys Acta Mol Basis Dis. Sep 1;1865(9):2224-2245.

You can search the National Institutes of Health database for more research on Alzheimer's. There are a number of other studies which corroborate the above notes.

9. Citicoline (2002, 2017) & Vascular Cognitive Decline

Vascular cognitive decline or impairment, known as VCI, is the second most common type of demential after Alzheimer's. Citicoline is one of the supplements being studied as part of VCI treatment.

Farooq MU, Min J, Coshgarian C, Gorelick PB. (2017). Pharmacotherapy for Vascular Cognitive Impairment. CNS Drugs. Sep;31(9):759-776.

Citicoline is a choline precursor and as such has been proposed for use in traumatic brain injury, stroke, vascular dementia, and brain aging. Due to its effects on cognitive disturbance some researchers recommend it as long-term preventive treatment for patients at high risk of Alzheimer's.

Blount PJ, Nguyen CD, McDeavitt JT. (2002). Clinical use of cholinomimetic agents: a review. J Head Trauma Rehabil. Aug; 17(4):314-21.
Gavrilova SI, Federova laB, Gantman, Kalyn laB, Kolykhalov IV. (2011). [Ceraxon (citicoline) in the treatment of the mild cognitive impairment syndrome.]. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(12):16-20.

Researchers find that it may be beneficial in both degenerative and vascular (inadequate blood supply to brain) cognitive decline because it inhibits cell death (apoptosis), increases neuroplasticity potential (adaptability), and supports acetylcholine synthesis (essential for brain functioning). It improves that effectiveness of cholinergic precursor drugs resulting in overall disease slowing.

Gareri P, Castagna A, Cotroneo AM, Putignano D, Conforti R, et al. (2017). The Citicholinage Study: Citicoline Plus Cholinesterase Inhibitors in Aged Patients Affected with Alheimer's Disease Study. J Alzheimers Dis. 2017;56(2):557-565.

10. Coffee (Quercetin) ('07, '11, '16, '18-'19) & Alzheimer's

Coffee (1-3 cups per day, recommended dosages can vary depending in certain body types). Quercetin, not caffeine, is the major neuroprotective element in coffee, consumption of which reduces the risk of Alzheimer's. Although study results are not consistent, 3 out of 5 reviewed supported coffee's favorable effects against cognitive decline, dementia, or AD.

Lee M, McGeer MG, McGeer PL. (2016). Quercetin, not caffeine, is a major neuroprotective component in coffee. Neurobiol Aging. Oct;46:113-23.

A 2007 review of observational studies suggested that coffee consumption was associated with a reduced risk of AD by approximately by 30% as compared to non-coffee consumer.

Barranco Quintana J.L. et al. (2007) Alzheimer's disease and coffee: a quantitative review.Neurol Res, 29:91-5.

Coffee combined with melatonin has been shown to have a range of benefits including antioxidative, antiapoptotic and neuroprotective effects.

Coffee and its consumption: benefits and risks. Butt MS, Sultan MT Crit Rev Food Sci Nutr. 2011 Apr; 51(4):363-73

A meta-analysis (a study of studies) found, however, that there's no direct correlation between coffee consumption and relative risk of developing Alzheimer's disease, but called for further research.

Larsson SC, Orsini N. (2018). Coffee Consumption and Risk of Dementia and Alzheimer's Disease: A Dose-Responsive Meta-Analysis of Prospective Studies. Nutrients. Oct 14;10(10):1501.

However, quercetin, an amino acid contained in coffee, does have notable beneficial effects including being neuroprotective, reducing lipid oxidation, inhibiting amyloid beta fibril formation, reducing inflammation, etc. It therefore may be considered as part of AD therapy.

Khan H, Ullah H, Aschner M, Cheang WS, Akkol EK. (2019). Neuroprotective Effects of Quercetin in Alzheimer's Disease. Biomolecules. Dec 30;10(1):59.

11. Curcumin (2005-2017) & Alzheimer's

Curcumin is the key component responsible for the major therapeutic properties attributed to turmeric that affect AD pathology and age-related mental decline. It is found to inhibit amyloid beta plaque, inhibit formation of amyloid beta oligomers and fibrils, inhibit acetylcholinesterase, mediate insulin signaling, reduce tau hyperphosphorylation, and binding to copper. It decreases the low-density lipoprotein oxidation and the free radicals that cause the deterioration of neurons.

Tang M, Taghibiglou C. (2017). The Mechanisms of Action of Curcumin in Alzheimer's Disease. J Alzheimers Dis. 2017;58(4):1003-1016.
Shehzad A, Rehman G, Lee YS (2013). Curcumin in inflammatory diseases. Biofactors. Jan-Feb; 39(1):69-77.
Kim GY, Kim KH, Lee SH, Yoon MS, Lee HJ, et al. (2005). Curcumin inhibits immunostimulatory function of dendritic cells: MAPKs and translocation of NF-kappa B as potential targets. J Immunol. Jun 15; 174(12):8116-24.

Curcumin also has strong anti-inflammatory activity attributable to its unique molecular structure. It increases neurogenesis, regulates enzymes essential for enzyme disbursement, mitochondrial regulation, gene expression oxidative stress and is also anti-mutagenic, and anti-microbial. One of the unique properties of curcumin is its ability to cross the blood-brain barrier offering an unusual opportunity to support brain health through its neuroprotective, anti-inflammatory and antioxidant properties around neurons and glial cells that is significantly associated with brain aging and injury.

Ibid. Shehzad. (2013).
Polazzi E, Monti B. (2010). Microglia and neuroprotection: from in vitro studies to therapeutic applications. Prog Neurobiol. Nov; 92(3):293-315.

Other studies show that curcumin boosts brain-derived neurotrophic factor, a type of growth hormone that helps brain cells grow. It may help delay age-related mental decline. Reports have suggested lower dementia prevalence in South Asia may be directly attributable to the amount of turmeric (an excellent source of curcumin) used in daily cooking. Studies suggest that curcumin should be considered as part of a treatment strategy as well to treat or prevent age-related neurodegenerative diseases such as AD, PD, and cerebrovascular disease.

Dong S, Zeng Q, Mitchell ES, Xiu J, Duan Y, et al. (2012). Curcumin enhances neuro genesis and cognition in aged rats: implications for transcriptional interactions related to growth and synaptic plasticity. PloS One. 7(2):e31211.
Ng TP, Chiam PC, Lee T, Chua HC, Lim L, et al. (2006). Curry consumption and cognitive function in the elderly. Am J Epidemiol. Nov 1;164(9):898-906.
Bigford GE, Del Rossi. (2014). Supplemental substances derived from foods as adjunctive therapeutic agents for treatment of neurodegenerative diseases and disorders. G Adv Nutr. Jul; 5(4):394-403.
Mourtas S, Lazar AN, Markoutsa E, Duyckaerts C, Antimisiaris SG. (2014). Multifunctional nanoliposomes with curcumin-lipid derivative and brain targeting functionality with potential applications for Alzheimer disease. Eur J Med Chem. Jun 10;80():175-83.

Food sources are primarily the turmeric spice often used in Indian and Indonesian food. The limitations of curcumin are primarily in its lack of ready absorption when taken orally and researchers are exploring ways to improve bioavailability. An older study showed that adding 20mg of piperine to 2g of curcumin improved its bioavailability markedly. About 5% of turmeric is curcumin and about 5% of black pepper (by weight) is piperine. Even 1/20th of piperine improves bioavailability. Curcumin is also fat soluble, so cook your turmeric and black pepper (freshly ground) briefly in oil before adding.

Serafini MM, Catanzaro M, Rosini M, Racchi M, Lanni C. (2017). Curcumin in Alzheimer's disease: Can we think to new strategies and perspectives for this molecule? Pharmacol Res. Oct;124:146-155.
Shoba G, Joy D, Joseph T, Majeed M, Rajendran R, et al. (1998). Influence of piperine on the pharmacokinetics of curcumin in animals and human volunteers. Planta Med. May;64(4):353-6.

Note. Curcumin taken in high dosages may be toxic, so higher doses than what is recommended above should only be done under a health professional's care. For some people, higher dosages in the amount suggested above may result in some numbness, so start with a lower amount first then work your way up to the higher dosage depending on how you feel. It may also have slight blood thinning properties so should not be taken without your doctor's supervision if on blood thinners.

Curcumin is not recommended for persons with biliary tract obstruction because it stimulates bile secretion. It is also not recommended for people with gallstones, obstructive jaundice, or acute biliary colic.

12. DHA (omega-3) (2015-2019) & Alzheimers

Learn more about protecting cognitive capacity.

Researchers investigated whether fish oil supplementation would support cognitive capacity and slow brain atrophy in aged patients. They evaluated more than 800 patients, 229 with normal cognitive capacity, 397 with mild impairment, and 193 with Alzheimer's disease. Patients were tested using standard neuropsychological testing and brain MRI's at 6 months intervals over a 4 year period - in order to determine patients' ability to retain information and the size (volume) of the brain (cerebral cortex, hippocampus, ventricular volumes).

The researchers reported that taking fish oil supplements correlated with better standard memory and cognitive ability, and with less brain shrinkage - a tangible result of the development of Alzheimer's.

The benefit of fish oil supplements was most evident in the normal test group suggesting that the DHA omega-3 fatty acid is helpful for protecting the brain's health in later life.

The study did not specify the dosage, but the World Health Organization recommends EPA and DHA dosages of 300mg to 500mg daily and ALA of 800mg to 1100mg daily.¹

Because of the close link between AD and lipid metabolism, DHA² (and EPA) are both important.^{3, 4} Modulation of lipid composition in the brain by DHA improves behavior motor function and survival.⁵ It promotes brain-derived nerve factor,⁶ supports cognition,⁷ and enhances neurogenesis. It supports cell differentiation, maturation, neuron survival, reducing inflammation, and well as reduced amyloid beta (A-β) build-up.⁸

It is possible that the phospholipid form of DHA, found in fish, but not in fish oil supplements, is more effective, especially for those people who carry APOE4, the strongest risk factor for Alzheimer's.⁹

Note. DHA is also found in fish and omega-3 fatty acid supplements, as well as algae for vegetarians.

Research

1. Daiello LA, Gongvatana A, Dunsiger S, Cohen RA, Ott BR. (2015). Association of fish oil supplement use with preservation of brain volume and cognitive function, Alzheimer's & Dementia. J Alz Ass. Feb.
2. Dyall SC. (2015). Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA, and DHA. Front Aging Neurosci. Apr 21;7:52.
3. Grimm MOW, Michaelson DM, Hartmann T. (2017). Omega-3 fatty acids, lipids, and apoE lipidation in Alzheimer's disease: a rationale for multi-nutrient dementia prevention. J Lipid Res. Nov;58(11):2083-2101.
4. Cardoso C, Afonso C, Bandarra NM. (2016). Dietary DHA and health: cognitive function aging. Nutr Res Rev. Dec;29(2):281-294.
5. Mohaibes RJ, Fiol-deRoque MA, Torres M, Ordinas M, Lopez DJ, et al. (2017). The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival. Biochem Biophy Acta Biomembr. Sep;1859(9 Pt B):1596-1603.
6. Matsuoka Y, Nishi D, Tanima Y, Itakura M, Kojima A, et al. (2015). Serum pro-BDNF/BDNF as a treatment biomarker for response to docosahexaenoic acid in traumatized people vulnerable to developing psychological distress: a randomized controlled trial. Transl Psychiatry. Jul 7;5:e596.
7. Weiser MJ, Butt CM, Mohajeri MH. (2016). Docosahexaenoic Acid and Cognition throughout the Lifespan. Nutrients. Feb 17;8(2):99.
8. Ibid. Grimm. (2017).
9. Patrick RP. (2019). Role of phosphatidylcholine-DHA in preventing APOE4-associated Alzheimer's disease. FASEB J. Feb;33(2):1554-1564.

13. Exercise (2015-17) Brain Volume & Functioning

Learn more about Alzheimer's disease and cognitive impairment.

2017

In this study researchers narrowed their focus on exercise and brain functioning to evaluate the effect of exercise on blood flow to the brain in a subset of stroke patients. Cerebrovascular disease is a narrowing of the arteries leading to the brain. It causes or contributes to conditions such as strokes which can severely damage physical functioning and cognitive capacity, decision making and cause depression.

The researchers investigated the impact of moderately-intensive exercise on about 20 stroke patients with mild "subcortical ischaemic VCI." This means that these stroke patients had an obstruction which blocked blood flow to the brain. The patients received either three times a week moderate aerobic training for six months, or the care such patients would usually receive.

At the end of the study the patients taking aerobic training had improved flanker reaction time (a test involving cognition and reaction time) and had decreased lesions in the brain white matter.

The scientists reported that such aerobic exercise was beneficial for stroke patients and that larger-scale studies should be performed to validate their investigation.

Researchers: C.L. Hsu, J.R. Best, et al
Published: Aerobic exercise promotes executive functions and impacts functional neural activity among older adults with vascular cognitive impairment, British Journal of Sports Medicine, April, 2017.

2016

Researchers investigated whether exercise could help patients who have only mild cognitive problems. Patients who have mild cognitive impairment (MCI) are at risk for developing Alzheimer's disease.

They used an MRI technique to look at the brain scans of patients who began a program of exercise four times a week and compared the results to patients who did stretching exercises only. Both groups exercised or stretched four times a week for a six month period.

One group of 16 adults averaging 63 years old performed aerobic exercise such as walking on a treadmill, using a stationary bike, or a elliptical training machine. The other group of 19 patients with an average of 67 years old performed stretching exercises.

The scientists took MRI images of all of the participants at the beginning of the study period and after six months. They found that in both groups brain volume increased, including in the part of the brain responsible for short-term memory. The aerobic group had the greatest total brain volume protection, with increased stretching of connective tissue in the brain. The patients who only performed stretching experienced some atrophy in the connective fibers in the brain - which is held to be an indicator of loss of brain volume.

In addition, the participants who engaged in aerobic exercise were found to have markedly greater improvement in the capacity to plan, make decisions, discriminate.

Researchers: S. Craft, Y. Jung, et al,
Published: Aerobic Exercise Preserves Brain Volume and Improves Cognitive Function, Radiological Society of North America, November, 2016.

2015

In an earlier study researchers investigated the relationship between cognitive capacity and the size of the brain. In many cognitive disabling conditions it has been observed that the physical size of the brain shrinks.

The study lasted for 2 years, and for an additional 6 months the researchers monitored the subjects after they had stopped the exercise programs.

14. Ginger Root (2001-2018) & Alzheimer's

Ginger root stimulates anti-Alzheimer activity, and researchers are investigating the mechanics of why.¹ Fermented with Schizosaccharomyces pombe, it reduces memory impairment by protecting neurons in the hippocampus.² Combined with peony root it inhibits amyloid beta accumulation and pathology in AD mice.³

In AD rat models of ginger root extract reverses behavioral dysfunction and reduces AD-like symptoms.⁴ In an in vitro study ginger extract increases cell survival in AD rat hippocampus and prevents formation of destructive oligomers.⁵ In biochemistry, an oligomer usually refers to a macromolecular complex. They give rise to Alzheimer's disease, and are small enough to spread easily around the brain, killing neurons and interacting harmfully with other molecules. How oligomers are formed and why is still not known.

Theoretical simulations of the mechanical process suggest that ginger acts as an inhibitor of acetylcholinesterase and is as effective as donepezil.⁶ It increases neurogenesis, raises BDNF levels, enhances cognitive function, and helps in reducing amyloid beta plaque for those with Alzheimer's.^{7, 8, 9, 10} The role of ApoE4 in amyloid pathology is supported by evidence that it binds Aβ and modulates the aggregation and clearance of Aβ.¹¹ Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes.¹²

One of the many health claims attributed to ginger is its purported ability to decrease inflammation, swelling, and pain. A dried ginger extract, [6]-gingerol,¹³ and a dried gingerol-enriched extract¹⁴ were each reported to exhibit analgesic and potent anti-inflammatory effects.¹⁵

Research

1. Azam F, Amer AM, Abulifa AR, Elzwawi MM. (2014). Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer's drugs: a computational investigation. Drug Des Devel Ther. Oct 23;8:2045-59.
2. Huh E, Lim S, Kim HG, Ha SK, Park HY, et al. (2018). Ginger fermented with Schizosaccharomyces pombe alleviates memory impairment via protecting hippocampal neuronal cells in amyloid beta(1-42) plaque injected mice. Food Funct. Jan 24;9(1):171-178.
3. Lim S, Choi JG, Moon M, Kim HG, Lee W, et al. (2016). An Optimized Combination of Ginger and Peony Root Effectively Inhibits Amyloid-B Accumulation and Amyloid-B-Mediated Pathology in ABPP/PS1 Double-Transgenic Mice. J Alzheimers Dis. 2016;50(1):189-200.
4. Zeng GF, Zhang ZY, Lu L, Xiao DQ, Zong SH, et al. (2013). Protective effects of ginger root extract on Alzheimer disease-induced behavioral dysfunction in rats. Rejuvenation Res. Apr;16(2):124-33.
5. Mathew M, Subramanian S. (2014). In vitro evaluation of anti-Alzheimer effects of dry ginger (Zingiber officinale Roscoe) extract. Indian J Exp Biol. Jun;52(6):606-12.
6. Cuya T, Baptista L, Celmar Costa Franca T. (2018). A molecular dynamics study of components of the ginger (Zingiber officinale) extract inside human acetylcholinesterase: implications for Alzheimer disease. J Biomol Struct Dyn. Nov;36(14):3843-3855.
7. Tchantchou F, Lacor PN, Cao Z, Lao L, Hou Y, et al. (2009). Stimulation of neurogenesis and synaptogenesis bilobalide and quercetin via common final pathway in hippocampal neurons. J Alz Dis. 18(4):787-98. 8. Yoo DY, Nam Y, Kim W, Yoo KY, Park J, et al. (2011). Effects of Gingko Biloba extract on promotion of neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice. J Vet Med Sci. 73(1):71-6.
9. Funakoshi H, Kanai M, Nakamura T. (2011). Modulation and alteration of anxiety-related behavior in tryptophan metabolism, promotion of neurogenesis and alteration of anxiety-related behavior n tryptophan 2,3-dioxygenase-deficient mice. Intl J Tryptophan Res. 4:7-18.
10. Hou Y, Aboukhatwa MA, Lei DL, Manaye K, Khan I, et al. (2010). Antidepressant flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice. Neurophamarcology. 58(6): 911-920.
11. Surh Y. J. Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat Res. 1999;428(1-2):305-27.
12. Grzanna R, Phan P, Polotsky A, Lindmark L, Frondoza CG. (2004). Ginger extract inhibits beta-amyloid peptide-induced cytokine and chemokine expression in cultured THP-1 monocytes. J Altern Complement Med. Dec;10(6):1009-13.
13. Young HY, Luo YL, Cheng HY, Hsieh WC, Liao JC, et al. (2005). Analgesic and anti-inflammatory activities of [6]-gingerol. J Ethnopharmacol. 2005;96(1-2):207-10.
14. Minghetti P, Sosa S, Cilurzo F, Casiraghi A, Alberti E, et al. (2007). Evaluation of the topical anti-inflammatory activity of ginger dry extracts from solutions and plasters. Planta Med. Dec;73(15):1525-30.
15. Marcus D. M, Suarez-Almazor M. E. (2001). Is there a role for ginger in the treatment of osteoarthritis? Arthritis Rheum. 2001;44(11):2461-2.

15. Ginkgo biloba (2003, '12, '16, '17) and dementia

Learn more about memory impairment and Alzheimer's disease.

Many researchers have studied Ginkgo biloba effects in supporting cognitive capacity in patients with dementia. A small six-month controlled, double-blind trial found marked improvement in verbal recall in patients with memory impairment associated with aging. The researchers used a 3D imaging technique called positron-emission tomography to look at brain wave activity and found improvements in activity in portions of the brain associated with memory in patients taking ginkgo supplements.

The researchers concluded that ginkgo's effects may be due to improved blood flow to the brain and antioxidant activity of the herb.

Ercoli, L et al. (2003). Society for Neuroscience Meeting, New Orleans, Nov.

One long-term study found no difference between ginkgo and placebo in Alzheimer's progression reduction.

Vellas B, Coley N, Ousset PJ, Berrut G, Dubois JF, et al. (2012). Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer's disease (GuidAge): a randomised, placebo-controlled trial. Lancet Neurol. Oct;11(10):851-9.

Though research is inconsistent regarding memory for those with Alzheimer's, research does support that gingko may increase neurogenesis, raise BDNF levels, enhance cognitive function and help in reducing amyloid beta plaque for those with Alzheimer's.

Yang G, Wang Y, Sun J, Zhang K, Liu J. (2016). Ginkgo Biloba for Mild Cognitive Impairment and Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Top Med Chem. 2016;16(5):520-8.
Wightman EL. (2017). Potential benefits of phytochemicals against Alzheimer's disease. Proc Nutr Soc. May;76(2):106-112.

16. Ginseng (1999, '08, '11, '16) & Alzheimer's

Asian ginseng (panax ginseng) root extract has been widely used in the far eastern countries such as China, Japan, and Korea for thousands of years as a traditional tonic for longevity, and is known for energizing the body or increasing vital energy and mood elevation with few if any side effects. Ginseng may reduce amyloid and neurofibrillary fiber build-up related to Alzheimer's.¹

A number of studies have shown that the long-term administration of Korean red ginseng extract to patients with AD, combined with conventional AD drugs, gradually improved cognitive function, as assessed using the mini-mental state examination (MMSE) and Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) tests, with minor adverse effects,^{2, 3, 4} with positive indication of frontal cortical activity, such as right temporal, parietal, and occipital areas, in elderly patients with AD.

Gintonin found in ginseng when applied to neuroblastoma cells decreased Aβ formation and attenuated Aβ-induced neurotoxicity, indicating that gintonin could affect APP processing in the brain.⁵

However a review and meta-analysis of research on ginseng and Alzheimer's reports that studies have had small sample size, questionable methodology, and missing placebos. Further research is needed.⁶

Research

1. Rege NN, Thatte UM, Dahanukar SA (1999). Adaptogenic properties of six rasayana herbs used in Ayurvedic medicine. Phytother Res. 1999;13:275-291.
2. Heo JH, Lee ST, Chu K, Oh MJ, Park HJ, et al. (2008). An open-label trial of Korean red ginseng as an adjuvant treatment for cognitive impairment in patients with Alzheimer's disease. Eur J Neurol. 2008;15:865-868.
3. Heo JH, Lee ST., Oh MJ, Park HJ, Shim JY, et al. (2011). Improvement of cognitive deficit in Alzheimer's disease patients by long term treatment with Korean red ginseng. J Ginseng Res. 2011;35:457-461.
4. Lee ST, Chu K, Sim JY, Heo JH, Kim M. (2008). Panax ginseng enhances cognitive performance in Alzheimer disease. Alzheimer Dis Assoc Disord. 2008;22:222-226.
5. Hwang SH, Shin EJ, Shin TJ, Lee BH, Choi SH, et al. (2012). Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, attenuates Alzheimer's disease-related neuropathies: involvement of non-amyloidogenic processing. J Alzheimer's Dis. 2012;31:207-223.
6. Yang G, Gong J, Lu F, Diao Q, et al. (2016). Ginseng for Alzheimer's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Curr Top Med Chem. 2016;16(5):529-35.

17. Glutathione (2012, '14, '17, '18, '19) & Alzheimer's

Glutathione (best taken sublingually or intravenously) is the most abundant antioxidant found in the brain. Glutathione is referred to as the "anti-aging antioxidant" because it is one of the few nutrients that can neutralize the full spectrum of different types of free radicals in one's body, and is one of the body's most potent antioxidants. It is comprised of three amino acids: glycine, glutamine, and cysteine. Glutathione is the most prevalent antioxidant in the brain. It is the richest non-protein thiol molecule in tissues and possesses the ability to prevent cerebral ROS accumulation.

Glutathione levels are becoming an important therapeutic target both to reduce the impacts of aging¹ as well as in the treatment of age-associated neurological diseases such as AD.² Glutathione levels are of interest to AD researchers because glutathione levels are depleted in AD patients^{3, 4, 5} and AD-caused increases in oxidative stress are attributed to reduced levels of glutathione⁶ in the temporal and parietal regions of the brain. In fact, glutathione levels in the brain are relevant AD biomarkers.^{7, 8} Scientists are examining the methods for increasing these levels as an AD therapy.⁹

Research

1. Sohal RS, Orr WC. (2012). The redox stress hypothesis of aging. Free Radic Biol Med. Feb 1; 52(3):539-555.
2. Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, et al. (2009). Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem. Mar; 390(3):191-214.
3. Rae CD, Williams SR. (2017). Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy. Anal Biochem. Jul 15;529:127-143.
4. Mazzetti AP, Fiorile MC, Primavera A, Lo Bello M. (2015). Glutathione transferases and neurodegenerative diseases. Neurochem Int. Mar;82:10-8.
5. Shukla D, Mandal PK, Ersland L, Gruner ER, Tripathi M, et al. (2018). Multi-Center Study on Human Brain Glutathione Conformation using Magnetic Resonance Spectroscopy. J Alzheimers Dis. 2018;66(2):517-532.
6. Saharan S, Mandal PK. (2014). The emerging role of glutathione in Alzheimer's disease. J Alzheimers Dis. 2014;40(3):519-29.
7. Mandal PK, Saharan S, Tripathi M, Murari G. (2015). Brain glutathione levels-a novel biomarker for mild cognitive impairment and Alzheimer's disease. Biol Psychiatry. Nov 15;78(10):702-10.
8. Mandal PK, Shukla D, Tripathi M, Ersland L. (2019). Cognitive Improvement with Gultathione Supplement in Alzheimer's Disease: A Way Forward. J Alzheimers Dis. 2019;68(2):531-535.
9. Peter C, Braidy N, Zarka M, Welch J, Bridge W. (2015). Therapeutic approaches to modulating glutathione levels as a pharmacological strategy in Alzheimer's disease. Curr Alzheimer Res. 2015;12(4):298-313.

18. Grapeseed Extract (2008, '09, '11, '13, '17, '19) & Alzheimer's

Grapeseed Extract (GSE) has potent antioxidant and neurogenesis properties, protects the central nervous system from reactive oxygen species. GSE potently inhibits the aggregation of amyloid beta peptides into amyloid fibrils (through its component, gallic acid).¹ GSE's antioxidant and anti-inflammatory flavonoids inhibit aggregation^{2, 3, 4} of amyloid beta peptides into neurotoxic soluble amyloid beta.^{5, 6, 7}.

Researchers find that grape seed proanthocyanidins reduce oxidative damage by inhibiting opening of pores in the mitochondrial membrane (such opening, stimulated by certain biochemical accumulations and depletions results in increased oxidative stress.⁸

Use of resveratrol (a grape seed component) and grape seed extract in nanoparticle form appear to be more effectively delivered to the brain as evidenced by research with human brain-like endothelial cells.⁹.

Research

1. Liu Y, Lukala TL, Musgrave IF, Williams DM, Dehle FC, et al. (2013). Gallic acid is the major component of grape seed extract that inhibits amyloid fibril formation. Bioor Med Chem Lett. Dec 1;23(23):6336-40.
2. Ono K, Condron MM, Ho L, Wang J, Zhao W, et al. (2008). Effects of grape seed-derived polyphenols on amyloid beta protein self-assembly and cytotoxicity. J Biol Chem. Nov 21;283(47):32176-87.
3. Asha Devi S, Sagar Chandrasekar BK, Manjula KR, Ishii N. (2011). Grape seed proanthocyanidin lowers brain oxidative stress in adult and middle-aged rats. Exp Gerontol. Nov;46(11):958-64.
4. Wang J, Ho L, Zhao W, Ono K, Rosensweig C, et al. (2008). Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease. J Neurosci. Jun 18;28(25):6388-92.
5. Ibid. Ono. (2008).
6. Sarkaki A, Rafiereirad M, Hossini SE, Farbood Y, Motamedi F, et al. (2013). Improvement in Memory and Brain Long-term Potentiation Deficits Due to Permanent Hypoperfusion/Ischemia by Grape Seed Extract in Rats. Iran J Basic Med Sci. 2013 Sep;16(9):1004-10.
7. Wang JY, Thomas P, Zhong JH, Bi FF, Kosaraju S, et al. (2009). Consumption of grape seed extract prevents amyloid-beta deposition and attenuates inflammation in brain of an Alzheimer's disease mouse. Neurotox Res. Jan;15(1):3-14.
8. Sun Q, Jia N, Li X, Yang J, Chen G. (2019). Grape seed proanthocyanidins ameliorate neuronal oxidative damage by inhibiting GSK-3B-dependend mitochondrial permeability transition pore opening in an experimental model of sporadic Alzheimer's disease. Aging (Albany NY). Jun 24;11(12):4107-4124.
9. Loureiro JA, Andrade S, Duarte A, Neves AR, Queiroz JF, et al. (2017). Resveral and Grape Extract-loaded Solid Lipid Nanoparticles for the Treatment of Alzheimer's Disease. Molecules. Feb 13;22(2):277.

19. Hesperidin (2011, '12, '16, '17, '19) & Alzheimer's

Hesperidin promotes nerve cell differentiation and survival,¹ and also enhances the neuroprotective capacity of astrocytes, by inducing them to secrete soluble factors involved in neuronal survival in vitro and increasing the number of neural progenitors.² It reduces cognitive impairment, oxidative stress, and cell death in animal models of Alzheimer's³ and inhibits amyloid fibril formation.⁴

A review of the research reported that in animal and clinical trials hesperidin-enriched supplements markedly enhanced cerebral blood flow, memory and cognitive capacity.⁵

Research

1. Nones J, E Spohr TC, Gomes FC. (2011). Hesperidin, a flavone glycoside, as mediator of neuronal survival. Neurochem Res. Oct; 36(10):1776-84.
2. Nones J, Spohr TC, Gomes FC. (2012). Effects of the flavonoid hesperidin in cerebral cortical progenitors in vitro: indirect action through astrocytes. Int J Dev Neurosci. Jun; 30(4):303-13.
3. Thenmozhi JA, Raja WTR, Manivasagam T, Janakiraman U, Essa MM. (2017). Hesperidin ameliorates cognitive dysfunction, oxidative stress, and apoptosis against aluminum chloride induced rat model of Alzheimer's disease. Nutr Neurosci. Jul:20(6):360-366.
4. Chakraborty S, Bandyopadhyay J, Chakraborty S, Basu S. (2016). Multi-target screening mines hesperidin as a multi-potent inhibitor: Implication in Alzheimer's disease therapeutics. Eur J Med Chem. Oct 4;121:810-822.
5. Jajialyani M, Farzaei MH, Echeverria J, Nabavi SM, Uriarte E, et al. (2019). Hesperidin as neuroprotective Agent: A Review of Animal and Clinical Evidence. Molecules. Feb 12;24(3):648.

20. Lutein & Zeaxanthin (2015, '17, '18) & Neurocognitive Functioning

Learn more about support for Alzheimer's disease.

Researchers have known for some time that the antioxidant carotenoids lutein and zeaxanthin play an important role in vision health but evidence is accumulating that they also support cognitive functioning of the brain.

Scientists investigated the role of these important carotenoids in neurocognitive functioning - the capacity of the neurological system of the brain to support interaction with the world.

Zeaxanthin inhibits amyloid beta aggregation,¹ and, combined with lutein, reduces AD mortality.² Supplementation with lutein and zeaxanthin improved cognitive function in community-dwelling, older, men and women,³ as well as with the addition of mesozeaxanthin was shown clinically and meaningfully to improve vision in AD patients.⁴

The research was accomplished making use of functional magnetic resonance imaging (fMRI). fMRI used MRI technology to measure changes in blood flow in the brain in order to evaluate brain activity. In the brain the circulation of blood and technology that measures brain activity by detecting changes associated with blood flow. This is possible because when difference parts of the brain become active there is increased blood flow to that part of the brain.

In the study about 40 older patient who were living in retirement/rest homes were asked to memorize and remember pairs of words that were not related to each other. The levels of lutein and zeaxanthin were measured in both the retinal pigment and in the blood plasma.

The researchers found that the levels of the carotenoids were significantly associated with the ability of the brain's neural network to communicate - which in turn was dependent upon blood-oxygen flow. The net result was a markedly increased capacity to accomplish the memorize/remember task.

The scientists concluded that lutein and zeaxanthin support the brain's cognitive functioning capacity through supporting the efficiency of neural networks in the brain.⁵

Other research suggests that a combination of carotenoids (such as lutein) and omega-3 essential fatty acids is more effective than either alone, although further study is needed to confirm the finding.⁶

Research

1. Lakey-Beitia J, Doens D, Jagadeesh Kumar D, Murillo E, Fernandez PL, et al. (2017). Anti-amyloid aggregation activity of novel carotenoids: implications for Alzheimer's drug discovery. Clin Interv Aging. May 15;12:815-822.
2. Min JY, Min KB. (2014). Serum lycopene, lutein and zeaxanthin, and the risk of Alzheimer's disease mortality in older adults. Dement Geriatr Cogn Disord. 2014;37(3-4):246-56.
3. Hammon BR, Miller LS, Bello MO, Lindberg CA, Mewborn C, et al. (2017). Effects of Lutein/Zeaxanthin Supplementation on the Cognitive Function of Community Dwelling Older Adults: A Randomized, Double-Masked, Placebo-Controlled Trial. Front Aging Neurosci. Aug 3;9:254.
4. Nolan JM, Loskutova E, Howard A, Mulcahy R, Moran R, et al. (2015). The impact of supplemental macular carotenoids in Alzheimer's disease: a randomized clinical trial. J Alzheimers Dis. 2015;44(4):1157-69.
5. Lindbergh CA, Mewborn CM, Hammond BR, Renzi-Hammond LM, Curran-Celentano JM, et al. (2017). Relationship of Lutein and Zeaxanthin Levels to Neurocognitive Functioning: An fMRI Study of Older Adults, J Int Neuropsychol Soc. Jan;23(1):11-22.
6. Nolan JM, Mulcahy R, Power R, Moran R, Howard AN. (2018). Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined. J Alzheimers Dis. 2018;64(2):367-378.

21. Lycopene (1989, 2018, 2019) & Cognitive Neuroprotection

Lycopene, a carotenoid, has demonstrated greater singlet oxygen quenching abilities (fights free radicals) compared with the other carotenoids, such as beta-carotene, lutein, and zeaxanthin.¹ Lycopene has been shown to exhibit neuroprotective effects by reducing oxidative stress, suppressing production of inflammatory cytokines, and reducing accumulation of amyloid plaques.^{2, 3}

Lycopene has been shown to attenuate cognitive deficits by improving inflammation in the gut-liver-brain axis as well improving glycolipid metabolism,⁴ the mechanisms by which lycopene provides neurocognitive protection as well as inhibition of neuronal apoptosis and restoration of mitochondrial function.⁵ Glycolipids help to maintain cell membrane stability and connectivity to other cells. Mitochondria are the parts of the cell that produce energy for the cell.

However a review of the literature reports that the evidence is inconclusive: there are positive relationships between lycopene levels and maintained cognition, but weak relationships between low lycopene levels and death from Alzheimer's.⁶

Research

1. Di Mascio P, Kaiser S, Sies H. (1989). Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys. Nov 1; 274(2):532-8.
2. Wang J, Li L, Wang Z, Cui Y, Tan X, et al. (2018). Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress. J Nutr Biochem. Jun; 56():16-25.
3. Liu CB, Wang R, Yi YF, Gao Z, Chen YZ. (2018). Lycopene mitigates B-amyloid induced inflammatory response and inhibits NF-kB signaling at the choroid plexus in early stages of Alzheimer's disease rats. J Nutr Biochem. Mar;53-66-71.
4. Lycopene attenuates western-diet-induced cognitive deficits via improving glycolipid metabolism dysfunction and inflammatory responses in gut-liver-brain axis. Wang J, Wang Z, Li B, Qiang Y, Yuan T, Tan X, Wang Z, Liu Z, Liu X Int J Obes (Lond). 2019 Sep; 43(9):1735-1746.
5. Chen D, Huang C, Chen Z. (2019). A review for the pharmacological effect of lycopene in central nervous system disorders. Biomed Pharmacother. Mar; 111():791-801. 6. Crowe-White KM, Phillips TA, Ellis AC. (2019). Lycopene and cognitive function. J Nutr Sci. May 29;8:3=e20.

22. Magnesium (2010, '16, '18, '19) & Alzheimer's

Learn more about alzheimers and other related conditions.

Although blood levels of magnesium do not vary between AD patients and controls, levels of magnesium in cerebrospinal fluid and hair are much lower in AD patients.¹ Magnesium can reduce the BBB permeability and promote clearance of amyloid beta from the brain.²

Researchers investigating the use of magnesium for Alzheimer's disease noted its efficacy in neurogenesis (creating new nerve cells) and neuroprotection apparently due to its ability to reduce neuroinflammation, remove toxins, inhibit amyloid beta precursors, and abnormal tau protein. However, an understanding of the mechanics of these beneficial effects remain unclear.³

Researchers have found that Magnesium-L-threonate, MgT is helpful for both long and short term memory loss. They point out that both learning and memory are impacted by diet considerations and found that, in animal models, this particular form of magnesium, which is more easily absorbed by the body than other forms, is exceptionally helpful.

They concluded that MgT helped make short-term synaptic functions more effective, and was helpful for long-term gains and stabilization in memory capacity.⁴

Research

1. Veronese N, Zurlo A, Solmi M, Luchini C, Trevisan C, et al. (2016). Magnesium Status in Alzheimer's Disease: A Systematic Review. Am J Alzheimers Dis Other Demen. May;31(3):208-13.
2. Zhu D, Su Y, Fu B, Xu H. (2018). Magnesium Reduces Blood-Brain Barrier Permeability and Regulates Amyloid-B Transcytosis. Mol Neurobiol. Sep;55(9):7118-7131.
3. Toffa DH, Magnerou MA, Kassab A, Djibo FH, Sow AD. (2019). Can magnesium reduce central neurodegeneration in Alzheimer's disease? Basic evidence and research needs. Neurochem Int. Jun;126:195-202.
4. Slutsky I, Abumaria N, Wu LJ, Huang C, Zhang L, et al. (2010). Enhancement of learning and memory by elevating brain magnesium. Neuron. Jan 28;65(2):165-77.

23. Marijuana (2007-8, 2011, 2015-16) & Alzheimers Disease

Learn more about Alzheimer's Disease

2016

Researchers have found that not only does THC, an active ingredient of marijuana, remove beta-amyloid but it reduces inflammation, a contributing problem. Beta-amyloid is the most prolific of several proteins that clump together in the brain, clogging neural pathways and causing nerve cell death.

The researchers wanted to learn more about the process by which the benefit occurs and the role of inflammation. They found that increased levels of beta-amyloid correspond with increased levels of inflammation and that beta-amyloid actually initiates a damaging inflammatory response - which was somewhat similar to the natural inflammatory response of our immune system to any bacterial or viral invader.

They were able to identify just how inflammation in the brain takes place on the molecular level. They also determined that substances naturally created by nerve cells are similar to THC. They then treated nerve cells that had a high level of beta-amyloid with THC and discovered that the inflammatory response was reduced and in turn, the beta-amyloid levels were reduced and in turn, nerve cell death decreased.

Their conclusion was that the process of brain cell death in Alzheimer's is due to an automatic catalytic inflammatory response to beta-amyloid by brain nerve cells and that this toxic inflammatory response compounds the problem. Treatment with THC was found to block the inflammatory response as well as remove the problematic protein, beta-amyloid.

Researchers: A. Currais, O. Quehenberger, et al.

Published: Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids, Aging and Mechanisms of Disease, June, 2016.

2015

Researchers report that cannabinoids, both those derived from marijuana and synthetic cannabinoids have great capacity for reducing inflammation and regulating the immune system in the central nervous system making it a useful adjunct in treatment of neuroinflammatory conditions This occurs because there are receptors in the CNS which are activated by cannabinoids ("cannabinoid receptors"). Alzheimer's characterized by both beta-amyloid accumulation and inflammation is one of these conditions that may benefit from cannabinoids.

Researchers: V. Chiurchiu, et al.

Published: Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses, Journal of Neuroimmune Pharmacology, June, 2015.

2011

The endocannabinoid system (see the 2008 study below) contains receptors that react to cannabinoids that the body produces naturally. Researchers are finding that this system is a key component in the maintenance, regulation and health of nerve cells. They are able to provide protection to nerve cells from cell damage and death by slowing damage caused by over-stimulated nerve cells and damage from oxidation and inflammation. Since a number of conditions involve the health of nerve cells, such as Alzheimer's disease the role of cannabinoids, both naturally produced by the body, and introduced as therapy may be a key to future treatment.

Researchers: A. Gowran, J. Noonan, V.A. Campbell.

Published: The multiplicity of action of cannabinoids: implications for treating neurodegeneration, CNS Neuroscience and Therapeutics, December, 2011.

2008

The central nervous system contains receptors that react to the presence of cannabinoids and the body produces a type of cannabinoid naturally. These receptors are important in helping regulate many neurophysiological processes including perception, appetite, mood, memory and experience of pain. The endocannabinoid system, throughout the body, is comprised of naturally synthesized cannabinoids, cannabinoid receptors, and enzymes that control the synthesis and degradation of cannabinoids.

Author: K. Mackie

Cannabinoid receptors: where they are and what they do, Journal of Neuroendocrinology, May, 2008.

2007

Alzheimer's is associated with accumulation of beta-amyloid protein, failure of the signaling capacity of the tau protein (abundant in the central nervous system), inflammation of the neural system, over-stimulation of brain cells causing cell death, and free radical accumulation causing oxidative stress. These hallmarks not only cause brain cell death but damage communication between brain cells. Brain cells contain cannabinoid receptors (that react to THC-like components produced by the brain) which are found to be damaged in Alzheimer's patients. The inability of these receptors to react to the THC-like components may be one contributing cause of Alzheimer's.

The researchers conclude therefore that treatment with cannabinoids, naturally derived from marijuana, may be helpful in treating Alzheimer's Disease.

Researchers: V.A. Campbell, A. Gowran

Published: Alzheimer's disease; taking the edge off with cannabinoids?, British Journal of Pharmacolory, November 2007.

24. Mediterranean Diet (2006-19) & Alzheimer's

There is a great deal of research suggesting that the Mediterranean diet reduces the incidence of dementia (including a meta-analysis of 32 studies)^{1, 2} and Alzheimer's disease.^{3, 4, 5, 6}

The benefit appears to reduce amyloid beta accumulation^{7, 8} (there is some contradictory research⁹) and improve neuroimaging biomarker profiles.^{10, 11} Researchers also note that the anti-inflammatory and anti-oxidant polyphenols in the diet reduce the risk of microglia-mediated neuroinflammation.¹²

Research

1. Petersson SD, Philippou E. (2016). Mediterranean Diet, Cognitive Function, and Dementia: A Systematic Review of the Evidence. Adv Nutr. Sep 15;7(5):889-904.
2. Safouris A, Tsiygoulis G, Sergentanis TN, Psaltopoulou T. (2015). Mediterranean Diet and Risk of Dementia. Curr Alzheimer Res. 2015;12(8):736-44.
3. Roman GC, Jackson RE, Gadhia R, Roman AN, Reis J. (2019). Mediterranean diet: The role of long-chain omega-3 fatty acids in fish; polyphenols in fruits, vegetables, cereals, coffee, tea, cacao and wine; probiotics and vitamins in prevention of stroke, age-related cognitive decline, and Alzheimer disease. Rev Neurol (Paris). Sep 11:S0035-3787(19)30773-8.
4. Mayo Clinic. Mediterranean diet: A heart-healthy eating plan. Retrieved Jun 20 2019 from http://www.mayoclinic.org/ healthylifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801.
5. Scarmeas N, Stern Y, Tang MX, Mayeux R, Luchsinger JA. (2006). Mediterranean diet and risk for Alzheimer's disease. Ann Neurol. Jun;59(6):912-21.
6. Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA, et al. (2013). Mediterranean diet, cognitive function, and dementia: a systematic review. J Epidemiology. Jul;24(4):479-89.
7. Dietary patterns: a novel approach to examine the link between nutrition and cognitive function in older individuals. Alles B, Samieri C, Feart C, Jutand MA, Laurin D, Barberger-Gateau P Nutr Res Rev. 2012 Dec; 25(2):207-22.
8. Rainey-Smith SR, Gu Y, Gardener SL, Doecke JD, Villemagne VL, et al. (2018). Mediterranean diet adherence and rate of cerebral AB-amyloid accumulation: Data from the Australian Imaging, Biomarkers and Lifestyle Study of Aging. Transl Psychiatry. Oct 30;8(1):238.
9. Hill E, Szoeke C, Dennerstein L, Campbell S, Clifton P. (2018). Adherence to the Mediterranean Diet is not related to Beta-Amyloid Deposition: Data from the Women's Healthy Aging Project. J Prev Alzheimers Dis. 5(2):137-141.
10. Vassilaki M, Aakre JA, Syrianen JA, Mielke MM, Geda YE, et al. (2018). Mediterranean Diet, Its Components, and Amyloid Imaging Biomarkers. J Alzheimers Dis. 64(1):281-290.
11. Berti V, Walters M, Sterling J, Quinn CG, Logue M, et al. (2018). Mediterranean diet and 3-year Alzheimer brain biomarker changes in middle-aged adults. Neurology. May 15;90(20):e1789-e1798.
12. Harnedo-Ortega R, Cerezo AB, de Pablos RM, Krisa S, Richard T, et al. (2018). Phenolic Compounds Characteristic of the Mediterranean Diet in Mitigating Microglia-Mediated Neuroinflammation. Front Cell Neurosci. Oct 23;12:273.

25. Melatonin (2013, '17, '18, '19) & Alzheimer's

Melatonin is a hormone produced by the pineal gland and its production runs parallel to AD progression. Quality of sleep is dependent upon melatonin, and it appears to be a safe and effective treatment for AD patients with sleep dysfunction.¹ Melatonin stimulates non amyloidogenic processing and inhibits beta amyloid precursor protein processing which culminates in amyloid aggregates - a neuroprotective function in AD pathology.² It decreases AD-like tau hyperphosphorylation, protects the cholinergic system and is anti-inflammatory. As such, it may be a useful agent in preventing and treating AD.³ Weak melatonin signaling (melatonin receptor type 1A gene) appears to contribute to the cascade of AD pathology.⁴

Not only does magnesium have a crucial role in protecting circadian rhythm, and improving signaling pathways, but it appears to limit beta amyloid accumulation, amyloid fibrillation, nerve cell death as AD progresses.⁵

Research

1. Wang YY, Zheng W, Ng CH, Ungvari GS, Wei W, et al. (2017). Meta-analysis of randomized, double-blind, placebo-controlled trials of melatonin in Alzheimer's disease. Int J Geriatr Psychiatry. Jan;32(1):50-57.
2. Shukla M, Govitrapong P, Boontem P, Reiter RJ, Satayavivad J. (2017). Mechanisms of Melatonin in Alleviating Alzheimer's Disease. Curr Neuropharmacol. 2017;15(7):1010-1031.
3. Lin L, Huang QX, Yang SS, Chu J, Wang JZ, et al. (2013). Melatonin in Alzheimer's disease. Int J Mol Sci. Jul 12;14(7):14575-93.
4. Sulkaya S, Muggalla P, Sulkava R, Ollila HM, Peuralinna T, et al. (2018). Melatonin receptor type 1A gene linked to Alzheimer's disease in old age. Sleep. Jul;41(7):zsy103.
5. Hossain MD, Uddin MD, Uddin GMS, Sumsuzzman DM, Islam MD, et al. (2019). Melatonin in Alzheimer's Disease: A Latent Endogenous Regulator of Neurogenesis to Mitigate Alzheimer's Neuropathology. Mol Neurobiol. Dec;56(12):8255-8276.

26. Mushrooms (2015-19) & Alzheimer's

Mushrooms have long been used not only as food but also for the treatment of various ailments. Studies have shown both within in vitro and mammal studies to have potential roles in the prevention of many age-associated neurological diseases including Alzheimer's,¹ including the following mushrooms:² lion's mane (Hericium erinaceus),³ reishi (Ganoderma lucidum),⁴ Sarcodon scabrosus, Antrodia camphorata, Pleurotus giganteus, maitake (Grifola frondosa), and many more. Reishi mushrooms help reduce inflammation. For example, the inhibition of COX-2 could relieve cerebral ischemic injury and slow down the progress of Alzheimer's disease or Parkinson's disease, has antioxidant effects, anti-neurodegenerative and anti-tumor benefits.^{5, 6}

Learn more about Medicinal Mushrooms in our nutrients section.

Research

1. Rahman MA, Abdullah N, Aminudin N. (2016). Interpretation of mushroom as a common therapeutic agent for Alzheimer's disease and cardiovascular diseases. Crit Rev Biotechnol. Dec;36(6):1131-1142.
2. Phan CW, David P, Naidu M, Wong KH, Sabaratnam V. (2015). Therapeutic potential of culinary-medicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolite, and mechanism. Crit Rev Biotechnol. 2015;35(3):355-68.
3. Li IC, Lee LY, Tzeng TT, Chen WP, Chen YP, et al. (2018). Neurohealth Properties of Hericium eranceus Mycelia Enriched with Erinacines. Behav Neurol. May 21;2018:5802634.
4. Huang S, Mao J, Ding K, Zhou Y, Zeng X, et al. (2017). Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease. Stem Cell Reports. Jan 10;8(1):84-94.
6. Baskaran A, Chua KH, Sabaratnam V, Ravishankar Ram M, Kuppusamy UR. (2017). Pleurotus giganteus (Berk. Karun & Hyde), the giant oyster mushroom inhibits NO production in PLS/H2O2 stimulated RAW 264.7 cells via STAT3 and COX-2 pathways. BMC Complement Altern Med. Jan 13;17(1):40.

27. Nattokinase, Serrapeptase (2009, '13, '17, '18) & Alzheimer's

Nattokinase is an enzyme extracted from a food produced by fermenting soybeans with Bacillus natto. Serrapeptase is a enzyme that breaks down proteins produced by the non-pathogenic enterobacterium Serratiaare. Both are available as nutritional supplements and may have applications as part of Alzheimer's (AD) therapy.

In animal models of AD either nattokinase or serrapeptase improves brain metabolism, increases brain-derived neurotrophic factor and insulin-like growth factor levels, increases the expression of relevant genes (ADAM9 and ADAM10), has neuroprotective value, reduces neuroinflammation, and therefore may have a therapeutic value in AD therapy. Tests of nanoencapsulation delivery find that nattokinase is able to reduce amyloid aggregation and reduce fibril formation. It is also associated with improved learning and memory and learning in animals.

Research

1. Bhatt PC, Pathak S, Kumar V, Panda BP. (2018). Attenuation of neurobehavioral and neurochemical abnormalities in animal model of cognitive deficits of Alzheimer's disease by fermented soybean nanonutraceutical. Inflammopharmacology. Feb;26(1):105-118.
2. Almed HH, Nevein NF, Karima A, Hamza AH. (2013). Miracle enzymes serrapeptase and nattokinase mitigate neuroinflammation and apoptosis associated with Alzheimer's disease in experimental model. WJPPS. 2013;3:876-891.
3. Fadi NN, Ahmed HH, Booles HF, Sayed AH. (2013). Serrapeptase and nattokinase intervention for relieving Alzheimer's disease pathophysiology in rat model. Hum Exp Toxicol. Jul;32(7):721-35.
4. Bhatt PC, Verma A, Al-Abbasi FA, Anwar F, Kumar V, et al. (2017). Development of surface-engineered PLGA nanoparticulate-delivery system of Tet1-conjugated nattokinase enzyme for inhibition of AB40 plaques in Alzheimer's disease. Int J Nanomedicine. Dec 13;12:9849-8758.
5. Ibid. Bhatt. (2018).
6. Hsu RL, Lee KT, Wang JH, Lee LY, Chen RP. (2009). Amyloid-degrading ability of nattokinase from Bacillus subtilis natto. J Agric Food Chem. Jan 28;57(2):503-8.
7. Ibid. Bhatt. (2018).

28. Olive Leaf Extract (2006, '11, '12, '16, '17) & Nerve Functioning

Learn more about brain functioning.

Olive leaf extract, oleuropein, has been extensively studied for its potential benefit in a number of conditions, including the health of the nervous system. It may be helpful in addressing problems involving impaired brain and/or nervous system functioning. It is a potential nutraceutical against Alzheimer's.

2017

Scientists discovered that oleuropein aglycone and other polyphenols derived from the waste water of olive oil mills was just as effective as olive leaf extract in combating damage to the nervous system and a dose dependant manner.

Researchers: D. Pantano, I. Luccarini, et al
Published: British Journal of Clinical Pharmacology, January, 2017.

Scientists discussed the mechanism by which olive leaf extract (oleuropein) protect against the tangled amyloid-beta protein clumps that develop over time and cause Alzheimer's disease.

They determined that oleuropein's protection against inflammation, oxidative stress, and neuroprotective effects. Oleuropein counteracts both amyloid clumping and the toxin release caused by such clumping. It inhibits development of amyloid precursors, reduces tau clumping, cell deterioration (autophagy) and nerve cell inflammation.

Martorell M, Forman K, et al. (2016). Potential Therapeutic Effects of Oleuropein Aglycone in Alzheimer's Disease. Curr Pharm Biotechnol. 2016;17(11):994-1001.

Oleuropein, binds amyloid beta 1-40 peptide molecules counteracting amyloid plaque generation and deposition. Furthermore, oleuropein inhibits tau, which aberrantly forms the amyloid-positive aggregates characteristic of AD. Thus, olive helps treat and prevent build-up of Aβ, decreased fibril formation risk, and as well is antioxidant, anti-inflammatory, anti-cancer, antimicrobial, antiviral, anti-atherogenic, hypoglycemic, hepatic-, cardiac, and neuro-protective.

Barbaro B, Toietta G, Maggio R, Arciello M, Tarocchi M, et al. (2014). Effects of the olive-derived polyphenol oleuropein on human health. In J Mol Sci. Oct 14;15(10:18508-24.

In an experimental model of spinal injury, researchers compared lab animals with real or sham spinal injury and animals treated with olive leaf extract. Some biomarkers indicative of spinal injury are increased malondialdehyde and decreased glutathione levels as well as other indicators. In this study animals receiving olive leaf extract demonstrated significate improvements in both biomarkers.

Khalatbary AR, Ahmadvand H. (2012). Neuroprotective effect of oleuropein following spinal cord injury in rats. Neurol Res. Jan;34(1):44-51.

Researchers investigated the biochemical properties of olive leaf extract (oleuropein) and its potential for inhibiting growth of amyloid deposits characteristic of Alzheimer's and other cognitive conditions.

They found that oleuropein inhibits formation of amyloid clumping =[amyloid-beta(1-42)]. It favors the formation instead of stable harmless pre-fibers (protofibrils) which are different than the typical amyloid-beta fibrils. It also protects against the release of toxins that occurs with the development of amyloid-beta clumps of plaque.

Rigacci S, Guidotti V, et al. (2011). Abeta(1-42) aggregates into non-toxic amyloid assemblies in the presence of the natural polyphenol oleuropein aglycon. Curr Alz Res. Dec;8(8):841-52.

In a related study of brain health, researchers investigated whether olive leaf extract could have a protective effect against damage caused by blood clots in the brain brought on by stroke. They compared the blood lipid levels and other biomarkers of rats fed or not fed olive leaf extract. They found that there were a number of improvements including in cholesterol, impairments in the brain nervous system, brain edema, etc were markedly improved. In addition, the brains of treated animals were better protected against damage caused by return of blood flow to previously blocked areas of the brain. The net result was reduced brain cell injury and up to 55% decrease in volume by dying brain tissue.

Mohagheghi F, Bigdeli MR, et al. (2011). The neuroprotective effect of olive leaf extract is related to improved blood-brain barrier permeability and brain edema in rat with experimental focal cerebral ischemia. Phytomedicine. Jan 15;18(2-3):170-5.

In another 2011 study involving lab animals, researchers similarly found that olive leaf extract (compared to quercetin, known to protect the nervous system) protected against damage caused by restored blood flow to parts of the brain that had been blocked by stroke. Olive leaf extract was more effective than quercetin. The researchers speculated that the benefit may have been due to olive leaf extract's capacity as an antioxidant.

Dekanski D, V. Selakovic V, et al. (2011). Protective effect of olive leaf extract on hippocampal injury induced by transient global cerebral ischemia and reperfusion in Mongolian gerbils. Phytomedicine. Oct 15;18(13):1137-43.

A notable indicator of development of Alzheimer's disease is the presence of tangles of amyloid-beta plaque. Researchers have speculated that the absence of antioxidants may be partially responsible. Researchers determined that olive leaf extract, with its strong neuro-protective effect may help to keep these clumps of plaque from forming.

Bazoti FN, J. Bergquist J, et al. (2006). Noncovalent interaction between amyloid-beta-peptide (1-40) and oleuropein studied by electrospray ionization mass spectrometry. J Am Soc Mass Spectrom. Apr;17(4):568-75.

29. Omega-3 (2010, '14, '17) Alzheimers & Brain Volume

2017

Research suggests that a combination of carotenoids (such as lutein) and omega-3 essential fatty acids is more effective than either alone, although further study is needed to confirm the finding.

Nolan JM, Mulcahy R, Power R, Moran R, Howard AN. (2018). Nutritional Intervention to Prevent Alzheimer's Disease: Potential Benefits of Xanthophyll Carotenoids and Omega-3 Fatty Acids Combined. J Alzheimers Dis. 2018;64(2):367-378.

2014

Researchers wanted to find out whether levels of omega=3 fatty acids found in red blood cells were correlated to brain volume - which normally shrinks with aging.

The Women's Health Initiative Memory Study, conducted in 2003, evaluated the amount of omega-3 fatty acids in their diet. Eight years later an assessment of EPA, DHA and brain volumes (as measured via MRI) determined that the greater the amount of omega-3s the greater (marginally) the overall brain function, and the greater (more so) the volume of the hippocampus. The hippocampus appears to be responsible for emotion, memory and the part of the nervous system which controls un-consciously directed functions such as heartbeat and metabolism.

Their conclusion is that a larger omega-3 level is tied to total brain volume and hippocampal volume in older women.

A later study connects supplementation with omega-3s to maintenance of brain volume.

Researchers: J.V. Pottala

Published: Higher RBC EPA + DHA corresponds with larger total brain and hippocampal volumes: WHIMS-MRI study, Neurology, Feb. 2014

2010

Researchers substantiated earlier indications that a diet that is rich in Omega-3 fatty acids can help protect the brain against developing Alzheimers disease. The protective powers stem from an ability to regulate the brain's natural level of zinc, which can prove toxic at elevated levels, They found that when the level of DHA in neuronal cells drops, the level of zinc rises. Omega-3 fatty acids contain a combination of EPA, DHA and alpha linoleic acid.

Previous research had shown a reduced incidence of neurodegenerative diseases in populations with a diet rich in Omega-3 fatty acids.

Researchers: Leah Aukland, et al,
Published: Omega-3 fatty acid may help prevent brain cell death, FEBS Letters, February, 2010

30. Phosphatidylserine (1989, '14, '15) & Alzheimer's

Phosphatidylserine is key to proper brain function. Combined with phosphatidic acid (from soy lecithin) it improves memory, mood, and cognition in the elderly, and has a general stabilizing effect in AD patients. In other studies, it improves mood, brain function, learning memory, and vocabulary in people with Alzheimer's. Additionally, cholinesterase and hippocampal inflammation injury decreases.

1. More MI, Freitas U, Rutenberg D. (2014). Positive effects of soy lecithin-derived phosphatidylserine plus phosphatidic acid on memory, cognition, daily functioning, and mood in elderly patients with Alzheimer's disease and dementia. Adv Ther. Dec;31(12):1247-52.
2. Funfgeld EW, Baggen M, Nedwidek P, Richstein B, Mistlberger G. (1989). Double-blind study with phosphatidylserine (PS) in parkinsonian patients with senile dementia of Alzheimer's type (SDAT). Clin Biol Res. 1989;317:1235-46.
3. Zhang YY, Yang LQ, Guo LM. (2015). Effect of phosphatidylserine on memory in patients and rats with Alzheimer's disease. Genet Mol Res. Aug 10;14(3):9325-33.

31. Polygalae radix (2017-19) & Cognitive Dysfunction

Polygalae radix is derived from Polygala tenuifolia Willd and is found typically as part of the Chinese herbal formulas Kai-xin-san or Bushen Tiansui. An extract of polygalae radix prevents cognitive deficit and neuron axon degeneration associated with amyloid plaque accumulation in a mouse model of AD although it does not influence the formation of plaque. It protects the area of growth at the tips of axons.¹ Other extracts of kai-xin-san have been tested and some are found to increase both nerve growth factor (it regulates nerve growth) and brain-derived neurotrophic expression.² These proteins control growth, stability, proliferation, and survival of nerve cells in the brain.

In a mouse model of Alzheimer's tenuifolin (a component of polygalae radix) was tested against nerve cell death and memory dysfunction. Tenuifolin reversed spatial learning and memory deficits, as well as nerve cell death in the hippocampus. It protected mitochondrial membranes and may be useful in AD therapies.³

1. Kuboyama T, Hirotsu K, Arai T, Yamasaki H, Tohda C. (2017). Polygalae Radix Extract Prevents Axonal Degeneration and Memory Deficits in a Transgenic Mouse Model of Alzheimer's Disease. Front Pharmacol. Nov 14;8:805.
2. Cao C, Xiao J, Liu M, Ge Z, Huang R, et al. (2018). Active components, derived from Kai-xin-san, a herbal formula, increase the expressions of neurotrophic factor NGF and BDNF on mouse astrocyte primary cultures via cAMP-dependent signaling pathway. J Ethnopharmacol. Oct 5;224:554-562
3. Wang L, Jin GF, Yu HH, Lu XH, Zou HZ, et al. (2019). Protective effects of tenuifolin isolated from Polygala tenuifolia Willd roots on neuronal apoptosis and learning and memory deficits in mice with Alzheimer's disease. Food Funct. Nov 1;10(11):7453-7460.

32. Pyrroloquinoline quinone (PQQ) (2017) & Alzheimer's

In Alzheimer's models Pyrroloquinoline quinone (PQQ) has been found to prevent mitochondrial dysfunction. In a mouse model of AD, a nutraceutical containing PQQ clearly improved motor dysfunction and cognitive impairment, protected mitochondrial function, reduced free radicals, and reduced membrane hyperpolarization. It slightly reduced soluble amyloid beta 42 levels which resulted in reduced tau levels.¹

In other research, with rat models of Alzheimer's, supplementation with PQQ prevented cognitive impairment and partially reversed bioenergy deficits. The researchers described PQQ as "a mitochondrial biogenesis stimulator with antioxidant and neuroprotective effects."²

Research

1. Sawmiller D, Li S, Mori T, Habib A, Rongo D, et al. (2017). Beneficial effects of a pyrroloquinoline quinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer's disease. Heliyon. Apr 4;3(4):e00279.
2. Adami PVM, Quijano C, Magnani N, Galeano P, Evelson P, et al. (2017). Synaptosomal bioenergetic defects are associated with cognitive impairment in a transgenic rat model of early Alzheimer's disease. J Cereb Blood Flow Metab. Jan;37(1):69-84.

33. Quercetin (2004, '08, '09, '13, '19) & Neurodegenerative Diseases

Quercetin is a bioflavonoid with promising potential due to its neuroprotective and antioxidant effects. It is a predominate component of coffee and accounts for many of coffee's beneficial qualities.

Studies show that quercetin protects brain cells against excitotoxicity, the damage done by repeated excitatory electrical impulses observed in AD and other neurodegenerative diseases.^{1, 2, 3, 4}

A review of the research literature reports that quercetin is neuroprotective against oxidative damage, reduces lipid oxidation, inhibits amyloid beta proteins, and counteracts inflammation and cell breakdown.⁵

The beneficial effects are mainly due to regulation of cytokines that cause inflammation by way of modulation of various signaling pathways. Researchers have been developing an understanding of the cellular and molecular mechanics of how quercetin protects against Alzheimer's.⁶

Research

1. Hynd MR, Scott HL, Dodd PR. (2004). Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochem Int. Oct;45(5):583-95.
2, Silva B, Oliveira PJ, Dias A, Malva JO. (2008). Quercetin, kaempferol and biapigenin from Hypericum perforatum are neuroprotective against excitotoxic insults. Neurotox Res. May-Jun;13(3-4):265-79.
3. Yang EJ, Kim GS, Kim JA, Song KS. (2013). Protective effects of onion-derived quercetin on glutamate-mediated hippocampal neuronal cell death. Pharmacogn Mag. Oct;9(36):302-8.
4. Dong XX, Wang Y, Qin ZH. (2009). Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacologica Sinica. Apr;30(4):379-87.
5. Khan H, Ullah H, Aschner M, Cheang WS, Akkol EK. (2019). Neuroprotective Effects of Quercetin in Alzheimer's Disease. Biomolecules. Dec 30;10(1):59.
6. Zaplatic E, Bule M, Shah SZA, Uddin MS, Kiaz K. (2019). Molecular mechanisms underlying protective role of quercetin in attenuating Alzheimer's disease. Life Sci. May 1;224:109-119.

34. Resveratrol (2005, '14, '15, '17, '18) & Alzheimers

Learn more about Alzheimer's disease.

2022 Although earlier research supported use of moderate red wine use, newer research reports that the many detriments outweigh the benefits.^{11, 12, 13} Instead, we recommend intake of resveratrol through grapes, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.

Resveratrol, a compound found in red wine, is known for its neuroprotective capacity. Because resveratrol has strong anti-inflammatory and anti-oxidative effects, researchers have hypothesized that it could be a useful treatment for neurological disorders. Resveratrol crosses the blood-brain barrier,^{1, 2} and helps to prevent neurodegeneration caused by amyloid beta peptides³ by enhancing glutathione and consequently, antioxidant status⁴ in AD, reduces inflammation,⁵ and alters AD biomarker trajectories.⁶ It is helpful against a number of AD mechanisms and metabolic pathologies.^{7, 8}

There are several biomarkers associated with Alzheimer's. Several of them are notable because as the condition worsens their presence in the body declines. In other words, as their levels get less, Alzheimer's is seen to progress in severity.

In one double-blind, placebo-controlled, randomized 1 year study of patients with moderate to mild Alzheimer's researchers assessed whether treatment with resveratrol made any noticeable difference. 119 patients were given placebo or resveratrol 500mg once a day. The doses of resveratrol were increased by 500mg every 13 weeks - and after a year the patients were taking 1000mg twice a day.

Brain MRI's and cerebral spinal fluid were sampled at the start of the study and at the end of the study. The progress of the resveratrol's absorption, distribution within the body, metabolism, and excretion was studied at start of the study, every 13 weeks, and at the end of the year.

The researchers reported that the biomarker which normally declines as Alzheimer's progresses was lost less in the patients taking resveratrol. Surprisingly, brain volume also decreased - which is possibly due to reduced inflammation in the brain.⁹

In other research scientists have been looking at the role of resveratrol in increasing anti-inflammatory activity and activating an enzyme called SIRT₁ (known as the silent information regulator-1) which decreases tau accumulation.¹⁰

Research

1. Moussa C, Hebron M, Huang X, Ahn J, Rissman RA, et al. (2017). Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer's disease. JNeuroinflammation. Jan 3;14:1.
2. Turner RS, Thomas RG, Craft S, van Dyck CH, Mintzer J, et al. (2015). A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease. Neurology. Oct 20;85:1383-1391.
3. Marambaud P, Zhao H, Davies P. (2005). Resveratrol promotes clearance of Alzheimer's disease amyloid beta peptides. J Biol Chem. Nov 11;280(45):37377-82.
4. Savaskan E, Olivieri G, Meier F, Seifritz E, Wirz-Justis A, et al. (2003). Red wine ingredient resveratrol protects from beta-amyloid neurotoxicity. Gerontology. Nov-Dec;49(6):380-3.
5. Lee JE Song J, Cheon SY, Jung W, Lee WT. (2014). Resveratrol induces the expression of interleukin-10 and brain-derived neurotrophic factor in BV2 microglia under hypoxia. Int J Mol Sci. 2014 Sep 2; 15(9):15512-29.
6. Sawda C, Moussa C, Turner RS. (2017). Resveratrol for Alzheimer's disease. Ann N Y Acad Sci. Sep;1403(1):142-9.
7. Sawda C, Moussa C, Turner RS. (2017). Resveratrol for Alzheimer's disease. Ann NY Acad Sci. Sep;1403(1):142-119.
8. Ahmed T, Javed S, Javed S, Tariq A, Samec D, et al. (2017). Resveratrol and Alzheimer's Disease: Mechanistic Insights. Mol Neurobiol. May;54(4):2622-2635.
9.Ibid. Turner. (2015).
10. Gomes BAQ, Silva JPB, Romeiro CFR, Dos Santos SM, Rodrigues CA, et al. (2018). Neuroprotective Mechanisms of Resveratrol in Alzheimer's Disease: Role of SIRT₁. Oxid Med Cell Longev. Oct 30;2018:8152373.
11. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, et al. (2018). Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. Apr 14;391(10129):1513-1523.
12. Biddinger KJ, Emdin CA, Haas ME, Wang M, Hindy G, et al. (2022). Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022 Mar 1;5(3):e223849
13. Goding Sauer A, Fedewa SA, Bandi P, Minihan AK, Stoklosa M, et al. (2021). Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiol. Apr;71(Pt A):101893.

35. Rutin (2013-16, '18, '19) & Neurodegenerative Disorders

Rutin has a potential protective role in neurodegenerative disorders, such as AD,^{1, 2, 3} due to its capacity as a potent antioxidant^{4, 5, 6} with a strong effect on processing and clumping of amyloid beta, and changes to the oxidant-antioxidant balance linked to nerve cell death.⁷

In related research rutin in a sodium solution (for better absorbability) enhanced removal of amyloid beta, supported mitochondria, and reduced neuroinflammation, making it a potential therapy for Alzheimer's.⁸

Research

1. Park SE, Sapkota K, Choi JH, Kim MK, Him YH, et al. (2014). Rutin from Dendropanax morbifera Leveille protects human dopaminergic cells against rotenone induced cell injury through inhibiting JNK and p38 MAPK signaling. Neurochemical Res. Apr;39(4):707-18.
2. Magalingam KB, Radhakrishnan A, Haleagrahara N. (2013). Rutin, a bioflavonoid antioxidant protects rat pheochromocytoma (PC-12) cells against 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. Int J Mol Med. Jul;23(1):235-40.
3. Wang YB, Ge ZM, Kang WQ, Lian ZX, Yao J, Zhou CY. (2015). Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes. Exp Ther Med. Feb;9(2):451-455.
4. Ibid. Park. (2014).
5. Yu XL, Li YN, Zhang H, Su YJ, Zhou WW, et al. (2015). Rutin inhibits amylin-induced neurocytotoxicity and oxidative stress. Food Funct. Oct;6(10):3296-306.
6. Enogieru AB, Haylett W, Hiss DC, Bardien S, Ekpo OE. (2018). Rutin as a Potent Antioxidant: Implications for Neurodegenerative Disorders. Oxid Med Cell Longev. Jun 27;2018:6241017.
7. Hablemariam S. (2016). Rutin as a Natural Therapy for Alzheimer's Disease: Insights into its Mechanisms of Action. Curr Med Chem. 2016;23(9):860-73.
8. Pan RY, Ma J, Kong XX, Wang XF, Li SS, et al. (2019). Sodium rutin ameliorates Alzheimer's disease-like pathology by enhancing microglial amyloid-B clearance. Sci Adv. Feb 27;5(2):eaau6328.

36. Saffron (2010, '15, '17, '19), Learning & Memory

Learn more about Alzheimer's Disease

Several studies report improvements in patients with neurodegenerative disorders such as Alzheimer's Disease or equal benefit as certain drugs but without side-effects. The presence of beta amyloid is a key indicator of Alzheimer's and its presence is a cause of loss of nerve synapse functionality and cell death of nerve cells.

Saffron has been found to be as effective as donepezil but with fewer side effects.¹ It is considered promising due to its anti-oxidant and neuroprotective properties.²

Researchers examined crocin (a colorant and key component of saffron) on memory and the process of cell death. They also investigated the effect on patient's capacity to remember information about their surroundings using nicotine as a control for mice in a standard Morris Water Maze. The Morris Water Maze task provides an accurate assessment of how the mind learns and remembers as well as the degree of damage to the brain.

The test found that mice given crocin demonstrated significantly improved spatial memory compared to mice given beta amyloid. In addition, they found that crocin significantly improves certain ratios and protein levels that are associated with cell death.³

A review of the literature reports that it is probably effective in a wide variety of problems including heart disease, high blood pressure, stomach problems, memory and learning problems. Research has found that saffron reduces inflammation and clogged arteries, protects the gene structure and removes toxins from cells. Additionally it increases glutamate, which is especially abundant in the brain where it is the most powerful neurotransmitter.⁴

Crocin may be especially valuable in supporting learning and memory because it is a water soluble carotenoid, a unique property.⁵

Research

1. Akhondzadeh S, Shafiee Sabet M, Harichian MH, Togha M, Cheraghmakani H, et al. (2010). A 22-week, multicenter, randomized, double-blind controlled trial of Crocus sativus in the treatment of mild-to-moderate Alzheimer's disease. Psychopharmacology (Berl). Jan;207(4):637-43.
2. Hatziagapiou K, Kakouri E, Lambrou GI, Bethanis K, Tarantilis PA. (2019). Antioxidant Properties of Crocus Sativus L. and Its Constituents and Relevance to Neurodegenerative Diseases; Focus on Alzheimer's and Parkinson's Disease. Curr Neuropharmacol. 2019;17(4):377-402.
3. Asadi F, Jamshidi AH, Khodagholi F, Yans A, Aimi L, et al. (2015). Reversal effects of crocin on amyloid β-induced memory deficit: Modification of autophagy or apoptosis markers. Pharmacol Biochem Behav. Dec;139(Pt A):47-58.
4. Khazdair MR, Boskabady MH, Hosseini M, Rezee R, Tsatsakis AM. (2015). The effects of Crocus sativus (saffron) and its constituents on nervous system: A review. Avicenna J Phytomed. Sep-Oct 2015;5(5):376-91.
5. Finley JW, Gao S. (2017). A Perspective on Crucus sativus L. (Saffron) Constituent Crocin: A Potent Water-Coluble Antioxidant and Potential Therapy for Alzheimer's Disease. J Agric Food Chem. Feb 8;65(5):1005-1020.

37. Salvia (Red Sage) (2016-17, 19) & Neuroprotection

Salvia miltiorrhiza (danshen, red sage) appears to halt the breakdown of the chemical messenger acetylcholine (ACH),¹ which levels fall in Alzheimer's disease. It may enhance cognition and protect against neurodegenerative disease² well as having a strong effect in increasing neurogenesis. Salvia miltiorrhiza (red sage, Chinese sage, or danshen) constituents have multiple neuroprotective effects including anti-amyloid beta, antioxidant, and anti-inflammation that are potentially useful in development of drugs to combat AD.³

A review of the literature focused on salvia miltiorrhiza components reports that, in addition to improving cognition and offering neuroprotection, the major bioactive ingredients (salvianolic acid A & B, and other minor components) reduce tau hyperphosylation (failure of this signaling mechanism results in tangles of tau protein), prevent amyloid beta fiber formation, and enhance fiber disaggregation. In summary, different components of salvia affect different aspects of Alzheimer pathology: APP processing, tau hyperphosphorylation, mitochondria support, and cell death - but salvianolic acid B seems to have the most potential.⁴

Research

1. Wightman EL. (2017). Potential benefits of phytochemicals against Alzheimer's disease. Proc Nutr Soc. May;76(2):106-112.
2. Lopresti AL. (2017). Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects. Drgus R D., Mar;17(1):53-64.
3. Zhang XZ, Qian SS, Zhang YJ, Wang RQ. (2016). Salvia miltiorrhiza: A source for anti-Alzheimer's disease drugs. Pharm Biol. 2016;54(1):18-24.
4. Chong CM, Su H, Lu JJ, Wang Y. (2019). The effects of bioactive components from the rhizome of Salvia miltiorrhiza (Danshen) on the characteristics of Alzheimer's disease. Chin Med. May 21;14:19.

38. Taurine (2017, '19, '20) & Cognitive Function

Taurine is of interest to researchers because of its link to cognitive function.¹ In Alzheimer mice, taurine improved cognitive impairment.²

Researchers investigated the effect of taurine in Alzheimer's treatment using functional molecular imaging, a method of taking images of molecules in living mice rather than the conventional samples of preserved tissue. They did not observe any change in amyloid beta pathology between taurine-treated and non-treated Alzheimer's mice. However, taurine therapy did increase uptake of a specific receptor in the brain (metabolic glutamate receptor type 5), thus giving it therapeutic potential against Alzheimer's.³

Research

1. Chen C, Xia s, He J, Lu G, Xie Z, et al. (2019). Roles of taurine in cognitive function of physiology, pathology, and toxication. Life Sci. Aug 15;231:116584.
2 Jang H, Lee S, Choi SL, Kim HY, Baek S, Kim Y. (2017). Taurine Directly Binds to Oligomeric Amyloid-B and Recovers Cognitive Deficits in Alzheimer Model Mice. Adv Exp Med Biol. 2017;975 Pt 1:233-241.
3. Oh SJ, Lee HJ, Jeong YJ, Nam KR, Kang KJ, et al. (2020). Evaluation of the neuroprotective effect of taurine in Alzheimer's disease using functional molecular imaging. Sci Rep. Sep 23;10(1):15551.

39. Theanine (2002, '10-'12, '14, '18, '19) & Alzheimer's

L-theanine is theanine's chemical mirror image, and is most often tested. Long-term L-theanine administration has demonstrated facilitating long-term potentiation and an increase in brain-derived neurotrophic factor (BDNF) expression in the hippocampus over three to four weeks.^{1, 2} BDNF is a protein that protects survival of nerve cells. In addition there is mounting evidence supporting a neuroprotective effect.^{3, 4, 5} L-theanine treated Alzheimer's patients experienced reduced stress-related symptoms, such as sleep disturbances as well as cognitive improvements in verbal fluency and executive function.⁶

The combination of theanine and luteolin improved AD-like symptoms by increasing hippocampal insulin signaling power and decreasing neuroinflammation and norepinephrine degradation in animal models of AD. ^{7, 8}

Theanine is found in green tea.

Research

1. Wakabayashi C, Numakawa T, Ninomiya M, Chiba S, Kunugi H. (2012). Behavioral and molecular evidence for psychotropic effects in L-theanine. Psychopharmacology (Berl). Feb; 219(4):1099-109.
2. Tamano H, Fukura K, Suzuki M, Sakamoto K, Yokogoshi H, et al. (2014). Advantageous effect of theanine intake on cognition. Nutr Neurosci. Nov; 17(6):279-83.
3. Kakuda T, Nozawa A, Sugimoto A, Niino H. (2002). Inhibition by theanine of binding of [3H]AMPA, [3H]kainate, and [3H]MDL 105,519 to glutamate receptors. Biosci Biotechnol Biochem. Dec; 66(12):2683-6.
4. Kakuda T. (2011). Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction. Pharmacol Res. Aug; 64(2):162-8.
5. Di X, Yan J, Zhao Y, Zhang J, Shi Z, et al. (2010). L-theanine protects the APP (Swedish mutation) transgenic SH-SY5Y cell against glutamate-induced excitotoxicity via inhibition of the NMDA receptor pathway. Neuroscience. Jul 14; 168(3):778-86.
6. Hidese S, Ogawa S, Ota M, Ishida I, Yasukawa Z, et al. (2019). Effects of l-theanine administration on stress-related symptoms and cognitive functions in healthy adults: A randomized controlled trial. Nutrients. 2019;11(10):2362.
7. Park S, Kim DS, Kang S, Kim HJ. (2018). The combination of luteolin and l-theanine improved Alzheimer disease-like symptoms by potentiating hippocampal insulin signaling and decreasing neuroinflammation and norepinephrine degradation in amyloid-B-infused rats. Nutr Res. Dec;60:116-131.
8. Zhu G, Yang S, Xie Z, Wan X. (2018). Synaptic modification by L-theanine, a natural constituent in green tea, rescues the impairment of hippocampal long-term potentiation and memory in AD mice. Neuropharmacology. Aug;138:331-340.

40. Vinpocetine (2015, 2019) & Alzheimer's

Vinpocetine's antioxidant and anti-inflammatory properties have been central to its role in AD treatments and it clearly improved deterioration in the cerebral cortex and hippocampus of AD isolated rats.¹ Alzheimer is also characterized by bone loss. Physical and mental activities enhance the neuroprotective capacity of vinpocetine and CoQ10 which markedly reduce neurodegeneration as evidenced by improvement in AD, oxidant, and inflammatory biomarkers in brain tissue.²

Phosphodiesterases (PDEs) are enzymes that break down the backbone of DNA or RNA. There are 11 main subtypes which act in various chronic conditions such as heart disease, Alzheimer's, and autoimmune conditions. PDEIs are synthetic or natural molecules which inhibit PDEs. One of these inhibitors is vinpocetine (PDE1-1)³ which acts against reduced plasticity and neurogenesis in AD patients. PDE1-1 has a possible positive effect on memory impairment.⁴

Research

1. Ali AA, Ahmed HI, Khaleel SA, Abu-Elfotuh K. (2019). Vinpocetine mitigates aluminum-induced cognitive impairment in socially isolated rats. Physiol Behav. Sep 1;208:112571.
2. Ali AA, Abo El-Ella DM, El-Emam SZ, Shahat AS, El-Sayed RM. (2019). Physical & mental activities enhance the neuroprotective effect of vinpocetine & coenzyme Q10 combination against Alzheimer & bone remodeling in rats. Life Sci. Jul 15;229:21-35.
3. Nabavi SM, Talarek S, Listos J, Nabavi SF, Devi KP, et al. (2019). Phosphodiesterase inhibitors say NO to Alzheimer's disease. Food Chem Toxicol. Dec;134:110822.
4. Heckman PR, Wouters C, Prickaerts J. (2015). Phosphodiesterase inhibitors as a target for cognition enhancement in aging and Alzheimer's disease: a translational overview. Curr Pharm Des. 2015;21(3):317-31.

41. Vitamin D3 (2012) & Alzheimers

Learn more about Alzheimer's disease.

Researchers have looked into how vitamin D regulation of cell functioning may help clear the brain of the main component of plaque - amyloid beta. They found that vitamin D3 may activate key genes and cellular signal networks in order to stimulate the immune system to remove the problematic protein.

Earlier research had found that immune cells in Alzheimer's patients may respond with a combination of curcumin (tumeric) and vitamin D3, but researchers didn't know why it was effective.

In this study researchers took blood samples from Alzheimer patients and healthy control subjects and then separated the important immune cells from the blood. These cells are called macrophages and they remove waste products from the brain and body. They had known from previous research that there two types of macrophages - those that are improved by vitamin D3, and those that are improved by the combination of D3 and curcumin.

They found that both kinds of macrophages opened a specific channel called "chloride channel 3" which supports taking away amyloid beta. They identified additional steps in the gene regulation process.

Their conclusion was that active forms of D3 may be important in the regulation of functioning of the macrophages in clearing plaque by directly regulating gene expressions and cell functioning ... and thus helpful in preventing dementia.

They indicated that the next step would be a clinical trial using vitamin D3.

Researchers: Dr. Milan Fiala, et al, David Geffen School of Medicine at UCLA

Published: Journal of Alzheimer's Disease, March 6, 2012.

42. Vitamin D3, Curcumin (2009) & Alzheimers

Learn more about Alzheimer's disease.

Researchers investigated reports that a combination of vitamin D3 and curcumin (a chemical in tumeric) could help stimulate the immune system to clear the brain of amyloid beta, a component of plaque in the brains of Alzheimer's patients.

Note: Later research has discovered that there are two types of macrophages that remove waste, including amyloid beta, and that one type responds well to vitamin D3 and the other responds well to the combination of vitamin D3 and curcumin.

This small study involved three controls, nine Alzheimer patients, and one patient with mild mental impairment. The researchers took blood samples and isolated the cells that transform into macrophages. They incubated the macrophages with vitamin D3, synthetic or natural curcumin and amyloid beta.

They found that the naturally occurring curcumin was not as readily absorbed as the synthetic, rendering it less effective. Editor's note this may be because natural turmeric is less easily absorbed into the body when it is uncooked. It is always recommended to dry roast or cook turmeric in oil prior to adding it to food, or taking it as an herbal remedy.

They found that the curcumin caused amyloid beta to bind more readily to macrophages and that vitamin D3 strongly stimulated the taking up and absorption of amyloid beta.

Researchers: John Cashman, et al, Human BioMolecular Research Institute, Unviersity of California, UCLA.

Published: Journal of Alzheimer's Disease, July, 2009.

43. Xtra on Alzheimers Disease: Early Research

Also see discussion of alzheimer's research

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28. Engel RR, Satzger W, Gunther W, et al. Double-blind cross-over study of phosphatidylserine vs. placebo in patients with early dementia of the Alzheimer type. Eur Neuropsychopharmacol 1992;2:149-55.
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30. Gindin J, Novickov M, Kedar D, et al. The effect of plant phosphatidylserine on age-associated memory impairment and mood in the functioning elderly. Rehovot, Israel: Geriatric Institute for Education and Research, and Department of Geriatrics, Kaplan Hospital, 1995.
31. Little A, Levy R, Chuaqui-Kidd P, Hand D. A double-blind, placebo controlled trial of high-dose lecithin in Alzheimer's disease. J Neurol Neurosurg Psychiatry 1985;48:736-42.
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33. Chatellier G, Lacomblez L. Tacrine (tetrahydroaminoacridine; THA) and lecithin in senile dementia of the Alzheimer type: a multicentre trial. Groupe Francais d'Etude de la Tetrahydroaminoacridine. BMJ 1990;300:495-9.
34. Fitten LJ, Perryman KM, Gross PL, et al. Treatment of Alzheimer's disease with short- and long-term oral THA and lecithin: a double-blind study. Am J Psychiatry 1990;147:239-42.
35. Eagger SA, Levy R, Sahakian BJ. Tacrine in Alzheimer's disease. Lancet 1991;338:50-1 [letter; comment].
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37. Fisman M, Mersky H, Helmes E. Double-blind trial of 2-dimethylaminoethanol in Alzheimer's disease. Am J Psychiatry 1981;138:970-2.
38. Imagawa M, Naruse S, Tsuji S, et al. Coenzyme Q10, iron, and vitamin B6 in genetically-confirmed Alzheimer's disease. Lancet 1992;340:671 [letter].
39. Bush AI, Pettingell WH, Multhaup G, et al. Rapid induction of Alzheimer A8 amyloid formation by zinc. Science 1994;265:1464-5.
40. Potocnik FCV, van Rensburg SJ, Park C, et al. Zinc and platelet membrane microviscosity in Alzheimer's disease. The in vivo effect of zinc on platelet membranes and cognition. S Afr Med J 1997;87:1116-9.
41. Prasad AS. Zinc in human health: an update. J Trace Elem Exp Med 1998;11:63-87.
42. Birkmayer JGD. Coenzyme nicotinamide adenine dinucleotide: New therapeutic approach for improving dementia of the Alzheimer type. Ann Clin Lab Sci 1996;26:1-9.
43. Clarke R, Smith D, Jobst KA, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449-55.
44. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000;71:993-8.
45. Joosten E, Lesaffre E, Riezler R, et al. Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease? J Gastroenterol 1997;52A:M76-M79.
46. Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998;27:485-91.
47. Hillen T, Lun A, Reischies FM, et al. DHEA-S plasma levels and incidence of Alzheimer's disease. Biol Psychiatry 2000;47:161-3.
48. Nasman B, Olsson T, Backstrom T, et al. Serum dehydroepiandrosterone sulfate in Alzheimer's disease and in multi-infarct dementia. Biol Psychiatry 1991;30:684-90.
49. Sunderland T, Merril CR, Harrington MG, et al. Reduced plasma dehydroepiandrosterone concentrations in Alzheimer's disease. Lancet 1989;2:570.
50. Yanase T, Fukahori M, Taniguchi S, et al. Serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) in Alzheimer's disease and in cerebrovascular dementia. Endocr J 1996;43:119-23.
51. Birkenhager-Gillesse EG, Derksen J, Lagaay AM. Dehydroepiandrosterone sulphate (DHEAS) in the oldest old, aged 85 and over. Ann N Y Acad Sci 1994;719:543-52.
52. Schneider LS, Hinsey M, Lyness S. Plasma dehydroepiandrosterone sulfate in Alzheimer's disease. Biol Psychiatry 1992;31:205-8.
53. Wolkowitz OM, Kramer JH, Reus VI, et al. Dehydroepiandrosterone (NPI-34133) treatment of Alzheimer's disease: a randomized, double-blind, placebo-controlled, parallel group study. Presented at the annual meeting of the American Psychiatric Association, Washington, DC, May 15-20, 1999.
54. Dukoff R, Molchan S, Putnam K, et al. Dehydroepiandrosterone administration in demented patients and non-demented elderly volunteers. Biol Psychiatry 1999;46:1533-41.
55. Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA 1997;278:1327-32.
56. Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation. Hum Psychopharmacol 1994;9:215-22.
57. Kanowski S, Herrmann W, Stephan K, et al. Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry 1996;29:47-56.
58. Maurer K, Ihl R, Dierks T, Frolich L. Clinical efficacy of Ginkgo biloba special extract EGb 761 in dementia of the Alzheimer's type. J Psychiatr Res 1997;31:645-55.
59. van Dongen M, van Rossum E, Kessels A, et al. The efficacy of ginkgo for elderly people with dementia and age-associated memory impairment: New results of a randomized clinical trial. J Am Geriatr Soc 2000;48:1183-94.
60. Wettstein A. Cholinesterase inhibitors and Ginkgo extracts-are they comparable in the treatment of dementia? Comparison of published placebo-controlled efficacy studies of at least six months' duration. Phytomedicine 2000;6:393-401.
61. Xu SS, Gao ZX, Weng Z, et al. Efficacy of tablet huperzine-A on memory, cognition, and behavior in Alzheimer's disease. Chung Kuo Yao Li Hsueh Pao 1995;16:391-5.
62. Zhang RW, Tang XC, Han YY, et al. Drug evaluation of huperzine A in the treatment of senile memory disorders. Chung Kuo Yao Li Hsueh Pao 1991;12:250-2 [in Chinese].
63. Wang Z, Ren G, Zhao Y, et al. A double-blind study of huperzine A and piracetam in patients with age-associated memory impairment and dementia. In: Kanba S, Richelson E, eds. Herbal Medicines for Nonpsychiatric Diseases. Tokyo: Seiwa Shoten Publishers, 1999, 39-50.
64. Thal LJ, Salmon DP, Lasker B, et al. The safety and lack of efficacy of vinpocetine in Alzheimer's disease. J Am Geriatr Soc 1989;37:515-20.
65. Fischhof PK, Moslinger-Gehmayr R, Herrmann WM, et al. Therapeutic efficacy of vincamine in dementia.

Anemia (Iron Deficiency)

1. Xtra Info: Anemia (iron-deficiency) Bibliography

Also see more information about anemia and nutritional recommendations.

1. Sullivan JL. Stored iron and ischemic heart disease. Circulation 1992;86:1036 [editorial].
2. Morck TA, Lynch SR, Cook JD. Inhibition of food iron absorption by coffee. Am J Clin Nutr 1983;37:416-20.
3. Mehta SW, Pritchard ME, Stegman C. Contribution of coffee and tea to anemia among NHANES II participants. Nutr Res 1992;12:209-22.
4. Kaltwasser JP, Werner E, Schalk K, et al. Clinical trial on the effect of regular tea drinking on iron accumulation in genetic haemochromatosis. Gut 1998;43:699-704.
5. Cook JD, Noble NL, Morck TA, et al. Effect of fiber on nonheme iron absorption. Gastroenterology 1983;85:1354-8.
6. Mejia LA, Chew F. Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. Am J Clin Nutr 1988;48:595-600.
7. Ajayi OA, Nnaji UR. Effect of ascorbic acid supplementation on haematological response and ascorbic acid status of young female adults. Ann Nutr Metab 1990;34:32-6.
8. Hunt JR, Gallagher SK, Johnson LK. Effect of ascorbic acid on apparent iron absorption by women with low iron stores. Am J Clin Nutr 1994;59:1381-5.
9. Schade SG, Cohen RJ, Conrad ME. Effect of hydrochloric acid on iron absorption. N Engl J Med 1968;279:672-4.
10. Bezwoda W, Charlton R, Bothwell T, et al. The importance of gastric hydrochloric acid in the absorption of nonheme food iron. J Lab Clin Med 1978;92:108-16.
11. Grindulis H, Scott PH, Belton NR, Wharton BA. Combined deficiency of iron and vitamin D in Asian toddlers. Arch Dis Child 1986;61:843-8.
12. Lawson M, Thomas M. Vitamin D concentrations in Asian children

Asthenopia (eye fatigue)

1. Astaxanthin (2002-2006) Reduces Eye Fatigue

A number of double blind controlled pilot studies suggest beneficial results from supplementation with the carotenoid astaxanthin on vision health. Thirteen subjects who received 5mg astaxanthin daily for a month showed a 54% reduction in complaints of eye fatigue¹. Another study of 9 patients in a sports vision study found that depth perception and critical flicker fusion had improved by 46% and 5% respectively following daily 6mg astaxanthin².

These and other results prompted more clinical studies to investigate optimum dose and understand why the benefits occurred.

Dosages of 4mg and 12mg were evaluated, both showing benefit in eye fatigue³. An optimum daily dosage of 6mg was determined in a study of 10 patients⁴ over the course of a month. Patients' results were evaluated by comparing eye fatigue using a standardized visual questionnaire in which a 6mg test group improved significantly at testing in 4 and 6 weeks. Later results substantiated these results in which 6mg taken for 4 weeks notedly improved eye fatigue, sore dry eyes, and blurry vision^{5, 6}.

Yet another study demonstrated the same results; this time the study was designed to demonstrate that astaxanthin supplementation is effective as a preventative. Patients who had been taking astaxanthin recovered more quickly from intense visual stimulus than those who had not.⁷ These results of preventative value of astaxanthin were substantiated by later research in another randomized, placebo-controlled, double-blind study.⁸

Footnotes:

1. Nagaki, Y, Hayasaka, S, Yamada, T, Hayasaka, Y, Sanada, M, et al. (2002). Effects of astaxanthin on accommodation, critical flicker fusions, and pattern evoked potential in visual display terminal workers. J Trad Med, 19(5):170-173.
2. Sawaki, K., et al. (2002). Sports performance benefits from taking natural astaxanthin characterized by visual acuity and muscle fatigue improvement in humans. J Clin Ther Med, 18(9):1085-1100.
3. Nakamura, A., Isobe, R., Otaka, Y., Abematsu, Y., Nakata, D., et al. (2004). Changes in Visual Function Following Peroral Astaxanthin. Japan J Clin Opthal, 58(6):1051-1054.
4. Nitta, T., Ogami, K., Shiratori, K. (2005). The effects of Astaxanthin on Accommodation and Asthenopia-Dose Finding Study in Healthy Volunteers. Clin Med, 21(5):543-556.
5. Shiratori K, Ohgami K, Nitta T, Shinmei Y, Chin S, et al. (2005). Effect of astaxanthin on accommodation and asthenopia - Efficacy identification study in healthy volunteers. J Clin Therap Med. 21(5):543-556.
6. Nagaki Y, Mihara M, Tsukuhara H, Ohno S. (2006). The supplementation effect of astaxanthin on accommodation and asthenopia. J Clin Therap Med, 22(1):41-54.
7. Takahashi, N., Kajita, M. (2005). Effects of astaxanthin on accommodative recovery. J Clin Therap Med, 21(4):431-436.
8. Iwasaki T, Tawara A. (2006). Effects of Astaxanthin on Eyestrain Induced by Accommodative Dysfunction. Atarashii Ganka,, (6):829-834

2. Carotenoids, Screen Time (2017) & Eye Fatigue

Learn more about eye fatigue.

2017

The use of smartphones, computers and mobile devices of all sorts has led to poor sleep quality and increased eye fatigue symptoms due to the exposure to blue light.

Researchers wanted to know whether supplementation with the carotenoids lutein, zeaxanthin and mesozeaxanthin, which are found to help protect the macula, would reduce negative symptoms of excessive screen time.

In a placebo controlled study researchers measured the results of such supplementation in 48 young and health adults with no vision problems over a six month period. The subjects used electronic devices for at least six hours a day.

The researchers measured, at the outset and again at the end of six months, contrast sensitivity, effect of glare, flicker sensitivity, and recovery from photostress using standard testing methods. They also evaluated amount of screen time and sleep quality with questionnaires.

They found that for the subjects taking the supplements (24mg total daily) there was marked improvement in macular optical density, sleep quality, frequency of headaches, eye strain and fatigue and visual acuity.

They determined that the quality of sleep would not have been directly related to the carotenoids but certainly could be related to less eye stress, oxidation and inflammation.

Researchers: J. Stringham, N. Stringham, et al
Published: Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure, Foods, June, 2017.

3. Lutein, blackcurrant extract (2009) may reduce visual fatigue

Learn more about computer eye strain and asthenopia (eye fatigue).

Visual fatigue such as computer eye strain caused by staring at the computer for long hours, may be eased a daily supplement containing blackcurrant fruit extract (200 mg), lutein (5 mg), and zeaxanthin (1 mg), according to a randomized, double-blind, placebo-controlled cross-over trial.

The subjects were randomly assigned to receive either the lutein supplement, or placebo, for two weeks, followed by two weeks of washout, and a further two weeks with the opposite intervention.

After completing a two hour visual proof reading task, the researchers measured signs of visual fatigue, including so-called eye fixation related potentials (EFRP).

Published: Applied Ergonomics, Volume 40, Issue 6, Pages 1047-1054, The effect of lutein supplementation on visual fatigue: A psychophysiological analysis.

Authors: A. Yagi, K. Fujimoto, K. Michihiro, B. Goh, D. Tsi, H. Nagai

4. Smartphones, Viewing Distance (2017, 2008) & Asthenopia

Learn more about eye fatigue.

2017

There have been a number of studies about how mobile device use impacts sleep due to the fact that the blue light radiation from smart phones inhibits melatonin production, which in turn inhibits sleep.

Researchers did an experimental study investigating the relationship between sleep, the distance the user holds the phone from their eyes, and eye fatigue.

In a small sample of nursing students the researchers used a subjective measure of quality of sleep and physically measured the distance between the smartphone and the users' head. The distance was measured for subjects both lying down and sitting up.

The amount of the viewing distance is directly related to the amount of eye fatigue, or asthenopia. Consequently it was expected that the viewing distance would also be related with the quality of sleep.

They noted that the viewing distance ranged from 5 1/4" to almost 13" for students who were using smartphones while sitting up. Users who were lying down tended to have a shorter viewing distance (3 3/4" to about 8 1/2").

Those subjects with the shorter viewing distance had poorer sleep and sleep efficiency.

The recommendation therefore is that a longer viewing distance causes less eye strain than a shorter viewing distance, and especially as it impacts sleep.

Researchers: M. Yoshimura, M. Kitazawa, et al
Published: Smartphone viewing distance and sleep: an experimental study utilizing motion capture technology, Nature and Science of Sleep, March, 2017.

This study evaluated the degree of eyestrain in people reading a novel excerpt from a smartphone for 60 minutes. All of the people read the same material.

The subjects were young, healthy and had normal vision. The 60 minute period was divided into six 10 minute sections and viewing distance was measured by taking a photo of the subjects every minute.

Interestingly, the viewing distance was greater for the 1st and 2nd 10 minute periods, shorter for the 3rd and 4th, and longer for the 5th. It was as though the person reading realized after about 40 minutes that they were holding the phone too close to their eyes and their eyes were getting tired.

The viewing distances began at about 10-14" and gradually decreased to 9-13" in the 2nd 10 minutes. It decreased additionally in the 3rd and 4th 10 minute periods, but increased slightly to 8-13" in the 5th period.

As would be expected the symptoms of tired eyes, and vision becoming blurry were markedly greater after the 60 minute period.

The only symptom that correlated with a change in viewing distance was identified by the users as 'uncomfortable eyes.' In other words, regardless of viewing distance, there was more eye fatigue after an hour, but for those holding the smartphone further away, the eyes felt more comfortable.

Researchers: J. Long, R. Cheung, et al
Published: Viewing distance and eyestrain symptoms with prolonged viewing of smartphones, Clinical & Experimental Optometry, March, 2017.

2008

Researchers developing the earlier mobile devices investigated on how readable characters were - these were on mobile phone liquid cystal displays.

The research is relevant in the context of eye fatigue in that they found that younger users held the phones closer to their eyes than older subjects. In short, younger users with excessive smartphone use will have more vision problems and eye fatigue than older users simply due to the fact that they tend to hold the phones closer to their eyes.

Researchers: S. Hasegawa, K. Fujikake, et al
Published: International Journal of Occupation Safety and Ergonomics, 2008.

Atherosclerosis

1. Bilberry (2012) & Atherosclerosis

Learn more about heart disease.

These researchers report that eating foods rich in the antioxidants known as anthocyanins are linked to lower risk of cardiovascular disease. Anthocyanins are the blue-purple fruits such as bilberry, blueberry and blackberry. In a previous study they found that a bilberry extract slows or stops development of lesions in mice with atherosclerosis. The reason for this improvement was not completely understood. Although it is known that the anthocyanins may alter RNA levels in genes in lab testing, studies involving live beings is limited.

Therefore, the researchers wanted to explore, in vivo (living subjects rather than test tube) why bilberry extract has such a positive effect in atherosclerosis. The study looks at what happens in the mechanics of early atherosclerosis. Atherosclerotic mice were given bilberry extract for two weeks. Testing revealed that cholesterol levels significantly dropped although the levels of antioxidants in blood plasma were unchanged.

Gene evaluation followed and the expression of 1261 genes was found to have been changed in the aorta. The scientists evaluated the function of those gene expressions and found that they played imported roles in causing oxidative stress, inflammation, transendothelial migration and angiogenesis. (Ed. note: angiogenesis is the formation of extra blood vessels - an important factor in advanced macular degeneration). The negative effects of gene expression involved in oxidative stress and 'sticky' molecules were reduced. Other genes' actions were increased, likewise providing overall positive benefit.

The study helps scientists understand why anthocyanin-rich extracts like bilberry are effective in preventing atherosclerosis.

Researchers: A. Mauray, A. Felgines, et al
Published: Bilberry anthocyanin-rich extract alters expression of genes related to atherosclerosis development in aorta of apo E-deficient mice, Nutrition, Metabolism and Cardiovascular Diseases, January, 2012

2. Diet, Inflammation (2016) & Atherosclerosis

Learn more about support for atherosclerosis

Researchers have reported that chronic inflammation in the body is a central cause of many health conditions, especially cardiovascular disease, which is one of the four leading causes of premature death.

The diet generally consumed by Westerners is high in red meat, high-fat dairy, refined sugars and grains and refined carbohydrates (as opposed to long-chain carbohydrates such as multi-grain cereal). The Mediterranean diet however, is high in whole grains, fish, vegetables (especially green vegetables) and fruit, along with low alcohol consumption and use of olive oil. This diet is associated with lower levels of inflammation in the body.

Researchers wanted to investigate the relationship between high inflammation levels in the body, indicated by the Dietary Inflammatory Index (DII) and premature mortality. Researchers investigated the diets and health of more than 8089 subjects to see whether such a relationship existed and to, in addition, see whether antioxidants would be helpful in reducing inflammation.

They conducted a random, placebo-controlled, double-blind study in which the subjects received low doses of antioxidants or a placebo over an eight year period. The subjects were aged 43 to 55 years old and their health was followed for an additional five years after the trial ended.

The subjects who had high inflammation levels had a higher death rate from heart disease or cancer compared to normal averages.

The subjects who received antioxidants did not have the same high death rate.

Researchers: L. Graffouillere, M. Deschausaux, et al.

Published: Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial, American Journal of Clinical Nutrition, March, 2016.

3. Homocystein (2004) & Heart Disease

Learn more about atherosclerosis.

A number of studies have demonstrated that patients who have coronary heart disease have higher homocysteine levels in their blood plasma than controls without heart disease. The International Task Force for Prevention of Coronary Heart Disease reported:

A meta-analysis (an averaging of many studies, or a study of studies) verified that increased homocysteine by 5 micrometer/l doubled heart disease risk. (Boushey et al.; JAMA 1995; 274:1049-1057)
Heart disease patients with a level of homocysteine lower than 9 micrometer/l had a much better life expectancy than those with levels above 20 micrometer/l. (Nygard et al., NEJM 1997; 337:230-236)
Blood levels of vitamins B6 and B12 and folate are correlated with blood homocysteine concentration levels. (ARIC Study: Folsom et al.; Circulation 1998; 98: 204-210)
Low levels of vitamin B6 are a more important risk factor than high homocysteine levels and these high levels reflect the cardiovascular risk created by vitamin B6 deficiency. (ARIC Study: Folsom et al. Circulation, 1998, 98: 204-210)
High homocysteine levels may also be a risk factor for stroke, and that the higher the level the greater the risk. (British Regional Heart Study, Perry et al. Lancet, 1995, 346: 1395-1398)
Folic acid treatment appears to be effective in reducing homocysteine levels. (Homocysteine Lowering Trialist's Collaboration. Br. Med J. 1998; 316:894-898)
Patients with homocysteine levels greater 12 micrometer/l should increase and/or supplement their dietary intake of folic acid and those with homocysteine levels greater 30 micrometer/l should receive daily doses of 400-800mg folic acid, 2-4mg vitamin B6 and 400mg vitamin B12. (Nutrition, Metabolism, and Cardiovascular Disease 1998, 8:212-271)
Mild homocystein elevation levels can be treated with attention to diet. See food sources for folic acid and vitamins B6 and B12.

4. Homocysteine (1998) Blocked Arteries & Stroke

Learn more about atherosclerosis.

Researchers have determined that higher homocysteine levels are tied to higher risk of strokes. The degree of heart blood vessel narrowing or blockage appears to be related to the level of homocysteine. Greater thicknesses of plaque thickness are connected to high homocysteine concentrations and low levels of vitamin B-12.

The researchers examined studied both blood vessels both within and outside the skull using MR angiography and found that homocysteine levels were higher in patients with 2- or 3-vessel narrowings than in those with 1-vessel blockage.

Researchers: Yoo JH, Chung CS, Kang SS.

Published: Relation of plasma homocysteine to cerebral infarction and cerebral atherosclerosis. Stroke. Dec 1998;29

5. Lutein (2001, 2011, 2017) & Atherosclerosis

Learn more about atherosclerosis.

2001

Researchers evaluated the effect of high levels of the carotenoid lutein in the circulatory system with respect to incidence of coronary artery disease in lab animals. The researchers measured the thickness of the innermost two layers of artery walls. They found that animals given an extra lutein supplement to their western diet equivalent had 44% smaller sized coronary artery lesions. Their conclusion was that supplementation with lutein and increased lutein content in the daily diet helps to protect against atherosclerosis.

Researchers: James H. Dwyer, et al, The Los Angeles Atherosclerosis Study
Published: Oxygenated Carotenoid Lutein and Progression of Early Atherosclerosis, Circulation, June, 2001

2011

Researchers again measured the thickness of the two inner walls of the coronary arteries before plaque had formed to determine whether carotenoids could be helpful. They also measured the degree of artery stiffness using carotid ultrasonography and blood levels of carotenoids.

This study involved 125 patients with early atherosclerosis and 107 control subjects who were 45 to 68 years old. The patients with early atherosclerosis had markedly lower levels of lutein in the blood. They found further that lutein levels were tied to inner artery wall thickness and that zeaxanthin and beta-carotene were associated with artery thickness and other measurements. These latter connections need to be further investigated.

Researchers: Z. Zou, X. Hu, Y. Huang, et al.
Published: High serum level of lutein may be protective against early atherosclerosis: the Beijing atherosclerosis study, Atherosclerosis, December, 2011.

2017

A study was done back in 1995 that connected low levels of the carotenoid lutein in the blood with a greater risk of developing hardening of the arteries - atherosclerosis. They had noted that patients in Northern Ireland where vegetable and fruit intake was low had a much higher rate of the condition than subjects in Southern France, where vegetables and fruit make up a large percentage of the diet.

In 1995 researchers thought that the difference was due to the ability of carotenoids to prevent free radical activity causing oxidation of fats to harden into plaque.

However, it is now accepted by most health professionals that coronary artery disease is largely caused by inflammation, and that large cells within areas of plaque damage artery lining tissue which aggravates such inflammation.

The blood carries precursor proteins which are part of the immune system known as C3 and C3a. These precursor proteins are found in much higher concentrations in patients with atherosclerosis, and the metabolism of these precursors (a normal function of the immune response) in the case of artery walls generates a "membrane attack complex (MAC)" which kills artery wall cells resulting in damage to the artery wall.

What researchers discovered is that when lutein levels are high in the blood then concentrations of C3 and C3a are reduced - indicating that the body is in a more healthy condition. Note that the high levels of C3 and C3a are also present in patients with macular degeneration.

Researchers: A. N. Howard, D. I. Thurnham
Published: Lutein and atherosclerosis: Belfast versus Toulouse revisited, Medical Hypotheses, January 2017.

6. Xtra Info: Atheroscherosis research bibliography of early research

These are earlier studies. Also see discussion of research for atherosclerosis

1. Nelson GJ. Dietary fat, trans fatty acids, and risk of coronary heart disease. Nutr Rev 1998;250-2.
2. Ascherio A, Willett WC. Health effects of trans fatty acids. Am J Clin Nutr 1997;66(suppl):1006S-10S [review].
3. Li D, Sinclair A, Wilson A, et al. Effect of dietary alpha-linolenic acid on thrombotic risk factors in vegetarian men. Am J Clin Nutr 1999;69:872-82.
4. Cunnane SC, Hamadeh MJ, Liede AC, et al. Nutritional attributes of traditional flaxseed in healthy young adults. Am J Clin Nutr 1994;61:62-8.
5. De Lorgeril M, Renaud S, Mamelle N, et al. Mediterranean alpha-linolenic-rich diet in secondary prevention of coronary heart disease. Lancet 1994;343:1454-9.
6. De Lorgeril M, Salen P, Martin J-L, et al. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction. Final report of the Lyon Diet Heart Study. Circulation 1999;99:779-85.
7. Rice RD. Mediterranean diet. Lancet 1994;344:893-4 [letter].
8. Anderson JW, Hanna TJ, Peng X, Kryscio RJ. Whole grain foods and heart disease risk. J Am Coll Nutr 2000;19(3 Suppl):291S-299S.
9. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999;69:30-42.
10. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr 1999;69:30-42.
11. Jenkins DJA, Kendall CWC, Ransom TPP. Dietary fiber, the evolution of the human diet and coronary heart disease. Nutr Res 1998;18:633-52 [review].
12. Wolk A, Manson JE, Stampfer MJ, et al. Long-term intake of dietary fiber and decreased risk of coronary hart disease among women. JAMA 1999;281:1998-2004.
13. Knopp RH, Superko HR, Davidson M, et al. Long-term blood cholesterol-lowering effects of a dietary fiber supplement. Am J Prev Med 1999;17:18-23.
14. Raloff J. Oxidized lipids: a key to heart disease? Sci News 1985;127:278.
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16. He J, Ogden LG, Vupputuri S, et al. Dietary sodium intake and subsequent risk of cardiovascular disease in overweight adults. JAMA 1999;282:2027-34.
17. Liu S, Willett WC, Stampfer MJ, et al. A prospective study of dietary glycemic load, carbohydrate intake, and risk of coronary heart disease in US women. Am J Clin Nutr 2000;71:1455-61.
18. Michael Pittilo R. Cigarette smoking, endothelial injury and cardiovascular disease. Int J Exp Pathol 2000;81:219-30 [review].
19. Wilson K, Gibson N, Willan A, Cook D. Effect of smoking cessation on mortality after myocardial infarction: meta-analysis of cohort studies. Arch Intern Med 2000;160:939-44 [review].
20. Nyboe J, Jensen G, Appleyard M, Schnohr P. Smoking and the risk of first acute myocardial infarction. Am Heart J 1991;122:438.
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23. Gabriel HH, Heine G, Kroger K, et al. Exercise and atherogenesis: where is the missing link? Exerc Immunol Rev 1999;5:96-102 [review].
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26. Kawachi I, Sparrow D, Spiro A 3rd, et al. A prospective study of anger and coronary heart disease. The Normative Aging Study. Circulation 1996;94:2090-5.
27. Thomas SA, Friedmann E, Wimbush F, Schron E. Psychological factors and survival in the cardiac arrhythmia suppression trial (CAST): a reexamination. Am J Crit Care 1997;6:116-26.
28. Angerer P, Siebert U, Kothny W, et al. Impact of social support, cynical hostility and anger expression on progression of coronary atherosclerosis. J Am Coll Cardiol 2000;36:1781-8.
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30. Tomeo AC, Geller M, Watkins TR, et al. Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis. Lipids 1995;30:1179-83.
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32. Olszewski AJ, McCully KS. Fish oil decreases serum homocysteine in hyperlipemic men. Coron Artery Dis 1993;4:53-60.
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36. Haglund O, Luostarinen R, Wallin R, et al. The effects of fish oil on triglycerides, cholesterol, fibrinogen and malondialdehyde in humans supplemented with vitamin E. J Nutr 1991;121:165-9.
37. Leng GC, Lee AJ, Fowkes FG, et al. Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease. Clin Nutr 1998;17:265-71.
38. Leaf A, Jorgensen MB, Jacobs AK, et al. Do fish oils prevent restenosis after coronary angioplasty? Circulation 1994;90:2248-57.
39. Sacks FM, Stone PH, Gibson CM, et al. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 1995;25:1492-8.
40. von Schacky C, Angerer P, Kothny W, et al. The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1999;130:554-62.
41. Sacks FM, Stone PH, Gibson CM, et al. Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group. J Am Coll Cardiol 1995;25:1492-8.
42. Salonen JT et al. Association between cardiovascular death and myocardial infarction and serum selenium in a matched-pair longitudinal study. Lancet 1982;ii:175.
43. Shamberger RJ, Willis CE. Epidemiological studies on selenium and heart disease. Fed Proc 1976;35:578 [abstract #2061].
44. Korpela H, Kumpulainen J, Jussila E, et al. Effect of selenium supplementation after acute myocardial infarction. Res Comm Chem Pathol Pharmacol 1989; 65:249-52.
45. Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia. An effect reversible with vitamin C therapy. Circulation 1999;99:1156-60.
46. Frei B. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage. Am J Clin Nutr 1991;54:1113S-8S.
47. Balz F. Antioxidant Vitamins and Heart Disease. Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.
48. Salonen JT, Nyyssonen K, Salonen R, et al. Antioxidant supplementation in atherosclerosis prevention (ASAP) study: a randomized trial of the effect of vitamin E and C on 3-year progression of carotid atherosclerosis. J Intern Med 2000;248:177-86.
49. Belcher JD, Balla J, Balla G, et al. Vitamin E, LDL, and endothelium: Brief oral vitamin supplementation prevents oxidized LDL-mediated vascular injury in vitro. Arterioscler Thromb 1993;13:1779-89.
50. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet 1996;347:781-6.
51. Rimm E. Micronutrients, Coronary Heart disease and cancer: Should we all be on supplements? Presented at the 60th Annual Biology Colloquium, Oregon State University, February 25, 1999.
52. Salonen JT, Nyyssonen K, Salonen R, et al. Antioxidant supplementation in atherosclerosis prevention (ASAP) study: a randomized trial of the effect of vitamin E and C on 3-year progression of carotid atherosclerosis. J Intern Med 2000;248:177-86.
53. Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877-81.
54. Bostom AG, Silbershatz H, Rosenberg IH, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077-80.
55. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204-10.
56. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196-9 [editorial/review].
57. Stolzen berg-Solomon RZ, Miller ER III, Maguire MG, et al. Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am J Clin Nutr 1999;69:467-75.
58. Selhub J, Jacques PF, Wilson PW, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693-8.
59. Ubbink JB, Hayward WJ, van der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.
60. Manson JB, Miller JW. The effects of vitamin B12, B6, and folate on blood homocysteine levels. Ann NY Acad Sci 1992;669:197-204 [review].
61. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204-10.
62. Hackam DG, Peterson JC, Spence JD. What level of plasma homocyst(e)ine should be treated? Am J Hypertens 2000;13:105-10.
63. Franken DG, Boers GHJ, Blom HJ, et al. Treatment of mild hyperhomocysteinemia in vascular disease patients. Arterioscler Thromb 1994;14:465-70.
64. Ubbink JB, Vermaak WJH, van der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.
65. Ubbink JB, van der Merwe A, Vermaak WJH, Delport R. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Investig 1993;71:993-8.
66. Ronzio RA. Antioxidants, nutraceuticals and functional foods. Townsend Letter for Doctors and Patients 1996;Oct:34-5 [review].
67. Hertog MGL, Feskens EJM, Hollman PCH, et al. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 1993;342:1007-11.
68. Hertog MGL, Kromhout D, Aravanis C, et al. Flavonoid intake and long-term risk of coronary heart disease and cancer in the Seven Countries Study. Arch Intern Med 1995;155:381-6.
69. Knekt P, Jarvinen R, Reunanen A, Maatela J. Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ 1996;312:478-81.
70. Rimm EB, Katan MB, Ascherio A, et al. Relation between intake of flavonoids and risk for coronary heart disease in male health professionals. Ann Intern Med 1996; 125:384-9.
71. Hertog MGL, Sweetnam PM, Fehily AM, et al. Antioxidant flavonols and ischemic heart disease in a Welsh population of men: the Caerphilly Study. Am J Clin Nutr 1997;65:1489-94.
72. Boberg M, Vessby B, Selinus I. Effects of dietary supplementation with n-6 and n-3 long-chain polyunsaturated fatty acids on serum lipoproteins and platelet function in hypertriglcyeridaemic patients. Acta Med Scand 1986;220:153-60.
73. Horrobin DF, Manku MS. How do polyunsaturated fatty acids lower plasma cholesterol levels? Lipids 1983;558-62.
74. Morrison LM, Branwood AW, Ershoff BH, et al. The prevention of coronary arteriosclerotic heart disease with chondroitin sulfate A: Preliminary report. Exp Med Surg 1969;27:278-89.
75. Morrison LM, Enrick NL. Coronary heart disease: Reduction of death rate by chondroitin sulfate A. Angiology 1973;24:269-82.
76. Bertelli AA, Giovanninni L, Bernini W, et al. Antiplatelet activity of cis-resveratrol. Drugs Exp Clin Res 1996;22(2):61-3.
77. Chen CK, Pace-Asciak. CR. Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Gen Pharm 1996;27(2):363-6.
78. Pace-Asciak CR, Rounova O, Hahn SE, et al. Wines and grape juices as modulators of platelet aggregation in healthy human subjects. Clin Chim Acta 1996;246(1-2):163-82.
79. Salonen JT, Nyssonen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men.Circulation 1992;86:803-11.
80. Van Asperen IA, Feskens EJM, Bowles CH, Kromhout D. Body iron stores and mortality due to cancer and ischaemic heart disease: a 17-year follow-up study of elderly men and women. Int J Epidemiol 1995;24:665-70.
81. Iribarren C, Sempos CT, Eckfeldt JH, Folsom AR. Lack of association between ferritin level and measures of LDL oxidation: the ARIC study. Atherosclerosis 1998;139:189-95.
82. Corti M-C, Guralnik JM, Salive ME, et al. Serum iron level, coronary artery disease, and all-cause mortality in older men and women. Am J Cardiol 1997;79:120-7.
83. Tzonou A, Lagiou P, Trichopoulou A, et al. Dietary iron and coronary heart disease risk: a study from Greece. Am J Epidemiol 1998;147:161-6.
84. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis. Circulation 1997;96:3300-7.
85. Danesh J, Appleby P. Coronary heart disease and iron status. Meta-analyses of prospective studies. Circulation 1999;99:852-4.
86. de Valk B, Marx MMJ. Iron, atherosclerosis, and ischemic heart disease. Arch Intern Med 1999;159:1542-8 [review].
87. Klipstein-Grobusch K, Launer LJ, Geleijnse JM, et al. Serum carotenoids and atherosclerosis. The Rotterdam Study. Atherosclerosis 2000;148:49-56.
88. Koscienlny J, Klubendorf D, Latza R, et al. The anti-atherosclerotic effect of Allium sativum. Atherosclerosis 1999;144:237-49.
89. Neil HAW, Silagy CA, Lancaster T, et al. Garlic powder in the treatment of moderate hyperlipidaemia: A controlled trial and a meta-analysis. J R Coll Phys 1996;30:329-34.
90. McCrindle BW, Helden E, Conner WT. Garlic extract therapy in children with hypercholesterolemia. Arch Pediatr Adolesc Med 1998;152:1089-94.
91. Isaacsohn JL, Moser M, Stein EA, et al. Garlic powder and plasma lipids and lipoproteins. Arch Intern Med 1998;158:1189-94.
92. Berthold HK, Sudhop T, von Bergmann K. Effect of a garlic oil preparation on serum lipoproteins and cholesterol metabolism. JAMA 1998;279:1900-2.
93. Lawson L. Garlic oil for hypercholesterolemia-negative results. Quart Rev Natural Med 1998;Fall:185-6.
94. Garlic powder for hyperlipidemia-analysis of recent negative results. Quart Rev Natural Med 1998;Fall:187-9.
95. Kiesewetter H, Jung F, Pindur G, et al. Effect of garlic on thrombocyte aggregation, microcirculation and other risk factors. Int J Pharm Ther Toxicol 1991;29(4):151-5.
96. Srivastava KC, Tyagi OD. Effect of a garlic derived principle (ajoene) on aggregation and arachidonic acid metabolism in human blood platelets. Prostagl Leukotr Ess Fatty Acids 1993;49:587-95.
97. Munday JS, James KA, Fray LM, et al. Daily supplementation with aged garlic extract, but not raw garlic, protects low density lipoprotein against in vitro oxidation. Atherosclerosis 1999;143:399-404.
98. Braquet P, Touqui L, Shen TS, Vargaftig BB. Perspectives in platelet activating factor research. Pharmacol Rev 1987;39:97-210.
99. Brown DJ. Herbal Prescriptions for Better Health. Rocklin, CA: Prima Publishing, 1996, 119-28.
100. Kiesewetter H, Jung F, Mrowietz C, et al. Effects of garlic on blood fluidity and fibrinolytic activity: A randomised, placebo-controlled, double-blind study. Br J Clin Pract Suppl 1990;69:24-9.
101. Jung F, Mrowietz C, Kiesewetter H, Wenzel E. Effect of Ginkgo biloba on fluidity of blood and peripheral microcirculation in volunteers. Arzneimittelforschung 1990;40:589-93.
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106. Olson BH, Anderson SM, Becker MP, et al. Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: Results of a meta-analysis. J Nutr 1997;127:1973-80.
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Attention Deficit Disorder (ADD)

1. Fats, DHA & EPA (2002, 2007) & ADHD

Learn more about ADD & ADHD.

2002

Researchers noted that a number of learning and behavioral difficulties in children have been tied to deficiencies in polyunsaturated fatty acids (PUFAs) and that these conditions may be helped through supplementation.

201 children in Australia were given fish oil supplements containing DHA and EPA.

The researchers also investigated added micronutrients because it is known that synergistic effects are helpful. The researchers studied 132 children (7-12) with learning/behavioral problems over 15 weeks. They found significant moderate to marked positive results in rating by parents of symptoms, hyperactivity, inattention, impulsivity compared to a placebo group. They also found that the addition of micronutrients made no additional difference.

Then, in a crossover, they tested the placebo group with the supplement and found that they also benefited.

They concluded that these essential fatty acids, which are not synthesized by the body, may be helpful for ADD & ADHD, and improvements may continue to 30 weeks.

Researchers: Sinn N, Bryan J., et al,
Published: Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behavior problems associated with child ADHD, Journal of Developmental and Behavioral Pediatrics, April, 2007

2002

The researchers wanted to determine whether deficiencies in highly unsaturated fats (HUFAs) may contribute to ADHD learning and behavior problems.

Editor's note: HUFAs are polyunsaturated fatty acids with a double bond; omega-3 fatty acids are HUFAs, and cannot be created by the body.

They examined 41 children 8-12 with learning problems (mostly dyslexia) and ADHD symptoms who were given HUFA supplements or placebo for 12 weeks.

The children's behavioral and learning difficulties were evaluated at the beginning and end of the period and after 12 weeks there was marked improvement in standard behavioral test scores on 7 out of 14 scales. For 3 out of 14 scales the change was statistically significant.

They concluded that HUFA supplements appear to lower ADHD symptoms in those with specific learning difficulties and that given the tolerability, safety, and simplicity of the treatment further research be completed.

Researchers: Richardson AJ, Puri BK.
Published: A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties, Progress in Neuro-Psychopharmacology and Biological Psychiatry, February, 2002

2. Xtra info: Attention Deficit Disorder ADD/ADHD Bibliography - early research

Also see discussion of attention deficit disorder (ADD & ADHD) research

1. Harley JP, Ray RS, Tomasi L, et al. Hyperkinesis and food additives: testing the Feingold hypothesis. Pediatrics 1978;61:818-21.
2. Levy F, Dumbrell S, Hobbes G, et al. Hyperkinesis and diet: a double-blind crossover trial with a tartrazine challenge. Med J Aust 1978;1:61-4.
3. Williams JI, Cram DM. Diet in the management of hyperkinesis: a review of the tests of Feingold's hypotheses. Can Psychiatr Assoc J 1978;23:241-8 [review].
4. Rowe KS, Rowe KJ. Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study. J Pediatr 1994;125:691-8.
5. Boris M, Mandel FS. Foods and additives are common causes of the attention deficit hyperactive disorder in children. Ann Allergy 1994;72:462-8.
6. Carter CM, Urbanowicz M, Hemsley R, et al. Effects of a few food diet in attention deficit disorder. Arch Dis Child 1993;69:564-8.
7. Egger J, Stolla A, McEwen LM. Controlled trial of hyposensitisation in children with food-induced hyperkinetic syndrome. Lancet 1992;339:1150-3.
8. Prinz RJ, Roberts WA, Hantman E. Dietary correlates of hyperactive behavior in children. J Consult Clin Psychol 1980;48:760-9.
9. Rosen LA, Booth SR, Bender ME, et al. Effects of sugar (sucrose) on children's behavior. J Consult Clin Psychol 1988;56:583-9.
10. Wolraich ML, Lindgren SD, Stumbo PJ, et al. Effects of diets high in sucrose or aspartame on the behavior and cognitive performance of children. N Engl J Med 1994;330:301-7.
11. Wolraich ML, Wilson DB, White JW. The effect of sugar on behavior or cognition in children. A meta-analysis. JAMA 1995;274:1617-21.
12. Milberger S, Biederman J, Faraone SV, et al. Is maternal smoking during pregnancy a risk factor for attention deficit hyperactivity disorder in children? Am J Psychiatry 1996;153:1138-42.
13. Tuthill RW. Hair lead levels related to children's classroom attention-deficit behavior. Arch Environ Health 1996;51:214-20.
14. Krigman MR, Bouldin TW, Mushak P. Metal toxicity in the nervous system. Monogr Pathol 1985;(26):58-100.
15. Starobrat-Hermelin B, Kozielec T. The effects of magnesium physiological supplementation on hyperactivity in children with attention deficit hyperactivity disorder (ADHD). Positive response to magnesium oral loading test. Magnes Res 1997;10:149-56.
16. Mitchell EA, Aman MG, Turbott SH, Manku M. Clinical characteristics and serum essential fatty acid levels in hyperactive children. Clin Pediatr 1987;26:406-11.
17. Stevens LJ, Zentall SS, Deck JL, et al. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am J Clin Nutr 1995;62:761-8.
18. Aman MG, Mitchell EA, Turbott SH. The effects of essential fatty acid supplementation by Efamol in hyperactive children. J Abnorm Child Psychol 1987;15:75-90.
19. Bhagavan HN, Coleman M, Coursin DB. The effect of pyridoxine hydrochloride on blood serotonin and pyridoxal phosphate contents in hyperactive children. Pediatrics 1975;55:437-41.
20. Coleman M, Steinberg G, Tippett J, et al. A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: a double-blind crossover comparison with methylphenidate. Biol Psychiatry 1979;14:741-51.
21. Brenner A. The effects of megadoses of selected B complex vitamins on children with hyperkinesis: controlled studies with long term followup. J Learning Dis 1982;15:258-64.
22. Haslam RHA. Is there a role for megavitamin therapy in the treatment of attention deficit hyperactivity disorder? Adv Neurol 1992;58:303-10.

Best's Disease

1. Antioxidants and Best's Disease

Learn more about Best's Disease.

There is a great deal of research about antioxidants, carotenoids, vitamins and other nutrients to support macular health for a number of macular and retinal conditions but very little about Best's Disease specifically.

Nonetheless, it is felt that following a diet that includes fish, leafy greens, and a good variety of fruits and vegetables supports good vision. To this end, supplementation with omega-3 fatty acids and antioxidants such as lutein and zeaxanthin may be helpful. These nutrients also support the health of the retinal pigmentation layer of the eye where Best's disease has its roots.

This information comes from the Australian Macular Disease Foundation.

2012
In a case study a researcher in an Ethopian eye hospital comments that because free radicals play a role in buildup of lipofuscin antioxidants which fight free radicals might be helpful. Lipofuscin is comprised of granules of yellowish brown fatty residues. It accumulates in the retinal pigment layer of the eye and with accumulation distorts the macula and damages vision.

This information came from Zelalem Addisu, Grarbet Eye Hospital, Ethiopia, 2012.

Bladder Infections

1. Xtra Info: Urinary Tract Infections Bibliography - early research

Also see discussion of bladder infections (UTI) recommendations and research.

1. Sanchez A, Reeser JL, Lau HS, et al. Role of sugars in human neutrophilic phagocytosis. Am J Clin Nutr 1973;26:1180-4.
2. MacGregor RR. Alcohol and immune defense. JAMA 1986;256:1474.
3. Barone J, Herbert JR, Reddy MM. Dietary fat and natural-killer-cell activity. Am J Clin Nutr 1989;50:861-7.
4. Horesh AJ. Allergy and infection. Proof of infectious etiology. J Asthma Res 1967;4:269-82.
5. Rudolph JA. Allergy as a cause of frequent recurring colds and coughs in children. Dis Chest 1940;6:138.
6. Berman BA. Pseudomononucleosis of allergic origin: a new clinical entity. Ann Allergy 1964;22:403-9.
7. Randolph TG, Hettig RA. The coincidence of allergic disease, unexplained fatigue, and lymphadenopathy; possible diagnostic confusion with infectious mononucleosis. Am J Med Sci 1945;209:306-14.
8. Mori S, Ojima Y, Hirose T, et al. The clinical effect of proteolytic enzyme containing bromelain and trypsin on urinary tract infection evaluated by double blind method. Acta Obstet Gynaecol Jpn 1972;19:147-53.
9. Sirsi M. Antimicrobial action of vitamin C on M. tuberculosis and some other pathogenic organisms. Indian J Med Sci 1952;6:252-5.
10. Axelrod DR. Ascorbic acid and urinary pH. JAMA 1985;254:1310-1.
11. Hussey GD, Klein M. A randomized, controlled trial of vitamin A in children with severe measles. N Engl J Med 1990;323:160-4.
12. Chandra RK. Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 1992;340:1124-7.
13. Avorn J, Monane M, Gurwitz JH, et al. Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA 1994;271:751-4.
14. Dignam R, Ahmed M, Denman S, et al. The effect of cranberry juice on UTI rates in a long term care facility. J Am Geriatr Soc 1997;45:S53.
15. Walker EB, Barney DP, Mickelsen JN, et al. Cranberry concentrate: UTI prophylaxis. J Family Pract 1997;45:167-8 [letter].
16. Sobota AE. Inhibition of bacterial adherence by cranberry juice: Potential use for the treatment of urinary tract infections. J Urol 1984;131:1013-6.
17. Schlager TA, Anderson S, Trudell J, Hendley JO. Effect of cranberry juice on bacteriuria in children with neurogenic bladder receiving intermittent catheterization. J Pediatr 1999;135:698-702.
18. Ofek I, Goldhar J, Zafriri D, et al. Anti-Escherichia coli adhesin activity of cranberry and blueberry juices. New Engl J Med 1991;324:1599 [letter].
19. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 428.
20. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. New York: John Wiley and Sons, 1996, 104-5.
21. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 317.
22. Kienholz VM, Kemkes B. The anti-bacterial action of ethereal oils obtained from horse radish root (Cochlearia armoracia L.). Arzneimittelforschung 1961;10:917-8 [in German].
23. Schindler VE, Zipp H, Marth I. Comparative clinical investigations of an enzyme glycoside mixture obtained from horse radish roots (Cochlearia armoracia L). Arzneimittelforschung 1961;10:919-21 [in German].
24. Sun DX, Abraham SN, Beachey EH. Influence of berberine sulfate on synthesis and expression of pap fimbrial adhesin in uropathogenic Escherichia coli. Antimicrob Agents Chemother 1988;32:1274-7.
25. Doan DD, Nguyen NH, Doan HK, et al. Studies on the individual and combined diuretic effects of four Vietnamese traditional herbal remedies (Zea mays, Imperata cylindrica, Plantago major and Orthosiphon stamineus). J Ethnopharmacol 1992;36:225-31.
26. European Scientific Cooperative for Phytotherapy. Proposal for European Monographs, Vol. 3. Bevrijdingslaan, Netherlands: ESCOP Secretariat, 1992.
27. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 224-5.
28. Aune A, Alraek T, LiHua H, Baerheim A. Acupuncture in the prophylaxis of recurrent lower urinary tract infection in adult women. Scand J Prim Health Care 1998;16:37-9.

Blepharitis

1. Lid Massage (2015) & Blepharitis

Learn more about this lid massage treatment.

The researchers investigated how efficient eyelid massage would be in treating blepharitis, inflammation of the eyelid. They developed a specific protocol, taught 27 patients how to perform it, and followed up their progress over a one month period.

They reported that the results demonstrated an inexpensive, self-treatment which was safe, simple and effective.

The protocol included a specific method of eyelid massage, performed for specific time periods, while under a warm shower.

Researchers: S.T. Yun, C.W. Chong, Y. Liu, K.E. Francis, S.A. Shah, I.C. Francis.

Published: Utilisation of a Novel Test to Measure Severity and Treatment Efficacy of Posterior Blepharitis, Journal of Ophthalmology, August, 2015.

Blepharospasm

1. Magnesium/Calcium (1990's, '08, '14) & Blepharospasm

Learn more about blepharospasm (eye twitch).

The research is far from conclusive about whether one's magnesium / calcium balance is treatable cause for blepharospasm. There have been a number of anecdotal reports. In each, calcium or magnesium is involved. Calcium and magnesium need to be in balance in the body because they have opposite functions. Calcium contracts muscles, magnesium relaxes muscles.

However, it is true that eye twitch is widely considered to be a symptom of a magnesium deficiency and that many people's calcium/magnesium balance is off, especially for women taking calcium for osteoporosis, or people taking medications which affect the calcium/magnesium balance.

The current daily value for magnesium is 400mg, which you can also get through high magnesium foods like dark leafy greens, nuts, seeds, fish, beans, whole grains, avocado, etc. Read more about magnesium food sources.

2014

In this article about magnesium deficiency, eye twitch is indicated as one of the symptoms.

Source: 10 signs that you're magnesium deficient, Good Health, New Zealand, 2014

2006

This case study reported that a patient who was taking a calcium-channel blocker for her dizziness developed chronic blepharospasm. A calcium channel blocker prevents calcium from entering blood vessel walls, thus allowing them to relax. She was taking cinnarizine, and so blepharospasm should be considered a side effect.

Authors: H. Alonso-Navarro, F. Jimenez-Jimenez, Tardive blepharospasm associated with cinnarizine use, Clinical Neuropharmacology, July-August, 2006.

1999

In this case study doctors discovered that a patient with pseudoblepharospasm and muscle weakness had developed antibodies against calcium and her immune system was over-reacting. She was treated with both an immune-response inhibitor and a potassium channel-blocker (which inhibits calcium channel activity). The eye muscle spasms were reduced.

This case study suggests that the calcium / magnesium balance may be of interest.

Authors: N. Kanzato, M. Motomura, et al,
Published: Lambert-Eaton myasthenic syndrome with ophthalmoparesis and pseudoblepharospasm, Muscle & Nerve, December, 1999.

1990

A French doctor reports that treating his patients with magnesium almost always reduces the symptoms, severity and duration of blepharospasm. He treated patients for six months to a year with 150mg magnesium; adjusting the amount for each patient as needed.

Author: C. Ploceniak
Published: Bruxism and magnesium, my clinical experiences since 1980, Revue de Stomatologie et de Chirurgie Maxillo-faciale, 1990.
You can read the full article here.

Cataract (lens problems)

1. Alpha lipoic acid (95, 2010, 13,15), fisetin & cataracts

See more information about cataracts.

2015
In a mouse model researchers tested whether the antioxidants alpha lipoic acid (ALA) or fisetin (a yellow colored flavanoid found in fruits and vegetables) were more effective in protecting against cataracts. Four groups of test mice were treated with fisetin, ALA, fisetin placebo, or ALA placebo. The fisetin group had the most protective results, ALA results were positive but not significant.

Kan, E., Kilickan, E., Ayar, A., Colak, R. (2015). Effects of two antioxidants; α-lipoic acid and fisetin against diabetic cataract in mice. Int Ophthalmol, Feb;35(1):115-20.

2013
An in-the-lab study of animal lenses looked at protection against induced cataracts and found that ALA could block the cataract formation by inhibiting epithelial cell death and activating the anti-oxidative process.

Researchers: Y. Li, Y.Z. Liu, J.M. Shi, S. B. Jia

Published: Alpha lipoic acid protects lens from H(2)O(2)-induced cataract by inhibiting apoptosis of lens epithelial cells and inducing activation of anti-oxidative enzymes, Asian Pacific Journal of Tropical Medicine, July, 2013.

2010
A similar animal lens study where cataract formation was chemically induced divided 45 animals into a control group, a group where cataracts were induced, and a 3rd group where cataracts were induced and the animals were also fed ALA. Again, they found that ALA inhibited the formation of cataracts.

Chen, Y., Yi, L., Yan, G., Fang, Y., Jang, Y., et al. (2010). alpha-Lipoic acid alters post-translational modifications and protects the chaperone activity of lens alpha-crystallin in naphthalene-induced cataract. Current Eye Research, Jul;35(7):620-30.

1997
Researchers found that alpha lipoic acid can reduce cataracts in diabetics and appears to be a good nutrient in protecting against all oxidative damage in brain and nerve cell disorders.

Researchers: Packer, L.,
Published: Free Radical Biological Medicine 1997

1995
Researchers found that alpha lipoic acid can prevent development of cataracts. They determined that it may offer such a protective effect by increasing the levels of other antioxidants. ALA also is helpful for nerve degeneration and injury from radiation.

Researchers: Packer, et al.

Published: Alpha-lipoic acid prevents buthionine sulfoximine-induced cataract formation in newborn rats, Free Radical Biological Medicine, August 1995.

Researchers reported that alpha lipoic acid behaves like an antioxidant reacting with a number of oxidative species. It protects membranes due to its interaction with glutathione and vitamin C, and helps recycle vitamin E. found that alpha lipoic acid can prevent development of cataracts. It also is helpful for nerve degeneration and injury from radiation.

Researchers: Packer, et al,
Published: alpha-Lipoic acid as a biological antioxidant, Free Radical Biology & Medicine, August, 1995

Another study published the same year reported that scientists found that lipoic acid treatment on cataracts in rats has measurable benefit and conclude that it may be of therapeutic use in preventing cataracts and their related complications in human eyes, not only for cataracts, but for glaucoma as well.

Researchers: F. Kilic, et al.
Published: Modelling cortical cataractogenesis 17: in vitro effect of a-lipoic acid on glucose-induced lens membrane damage, a model of diabetic cataractogenesis, Biochemical and Molecular Biology Int., October, 1995.

2. Antioxidants (1998) antioxidant vitamins and nuclear opacities: the longitudinal study of cataract.

See more about cataracts treatment and information.

Researchers evaluated the relationship between the presence of antioxidants in the eye tissue and blood levels and the risk of development of cataracts. The study was called the Longitudinal Study of Cataract and involved 764 patients.

At the beginning of the study the scientists collected dietary information, use of vitamin supplements, and blood samples measuring levels of vitamin E. In addition eye exams with specific data about lens clarity were taken including use of lens photographs which were graded according to a standard clarity protocol. This information and data was again collected on yearly follow-up visits.

The scientists wanted to determine whether nutrition was a factor in development of cataracts over time. They found that the risk of cataract formation decreased in the regular users of multivitamin supplements (1/3 decrease in risk), vitamin E supplements, and in the people with higher blood levels of vitamin E (1/2 the risk). The results were similar to earlier research and were observed only, not clinical trials.

Researchers: Leske MC; Chylack LT Jr; He Q; Wu SY; Schoenfeld E; Friend J; Wolfe J

Published: Antioxidant vitamins: the longitudinal cataract study, Ophthalmology (United States) May 1998

3. Antioxidants (1998, 2001-2, 05, 13) and Cataract Prevention

See more about cataracts treatment and information.

2013 Meta-Analysis

Research has consistently indicated that the levels of antioxidants and/or vitamins in the blood are associated with lowered risk of developing cataracts. The researchers did a meta-analysis to verify that such association is valid.

A meta-analysis is essentially a study of studies. While small studies, or studies that are lacking controls, or randomization, or are not double-blind may or may not be valid, by looking at all such studies together as though they are one larger study, statistical significance can be determined.

The researchers evaluated 13 studies involving nearly 19,000 patients. They concluded that:

Vitamin E, alpha-carotene, lutein and zeaxanthin were inversely related to age-related cataract. (The greater the levels of those nutrients, the lower the risk of cataract.)
Vitamins A and C were inversely related to cataract in Asian populations (not western peoples).
Beta-carotene, lycopene and beta-cryptoxanthin were not statistically significant.

Researchers: Y.H. Cui, C.X. Jing, H.W. Pan

Published: Association of blood antioxidants and vitamins with risk of age-related cataract: a meta-analysis of observational studies, American Journal of Clinical Nutrition, September, 2013.

2005

In 1993 researchers noted amounts of fruit and vegetables consumed by nearly 40,000 women medical professionals. Most of them were free of cataracts at that time. Ten years later their vision health was again evaluated and it was found that the women in the lowest 1/5th of fruit and vegetable consumption had the highest levels of cataract. Women in the highest 1/5th of fruit and vegetable consumption had about 10-15% lower risk of cataract.

Researchers: W. G. Christen, et al.

Published: Fruit and vegetable intake and the risk of cataract in women, American Journal of Clinical Nutrition, June 2005.

2002

Researchers report that people with healthy diets that include 18mg of beta-carotene daily, 750mg of vitamin C daily, and 600mg of vitamin E daily are able to slow the progression of cataracts. This is according to the results of the Roche European-American Cataract Trial results.

The trial involved almost 300 U.S. and U.K. patients, randomly receiving supplements or placebo. Followup was done for two years for 231 of them, for three years for another 158, and for four years for 36 more patients.

All patients began with four months of placebo; following that period they were divided into two groups for placebo or nutrients and monitored every four months.

At the beginning of the study there was no difference between control and test subjects' eyes. After two years of treatment there was a small positive effect for the non-placebo group in the U.S. and after three years positive results were noticed for non-placebo groups in the U.S. and the U.K.

Researchers: L.T. Chylack, Jr, N.P. Brown, A. Bron, M. Hurst, W. Kopcke, U. Thien, W. Schalch

Published: The Roche European American Cataract Trial (REACT): a randomized clinical trial to investigate the efficacy of an oral antioxidant micronutrient mixture to slow progression of age-related cataract, Ophthalmic Epidemiology, February, 2002

2001

Researchers find that different antioxidants can help prevent varying types of cataract as follows:

People with the highest blood concentrations if either beta- or alpha-carotene were 30-50% less likely to develop nuclear cataracts, which are those located in the central part of the lens.
People with high blood levels of lycopene (found in high concentration in cooked tomatoes) were associated with a 60% lower risk if cortical cataracts, which are those located in the outer layer of the lens.
People with high lutein concentrations were 50% less likely to develop posterior subcapular cataracts, which are those located toward the bottom rear of the lens.

So in essence the study shows that a diet rich in antioxidants can reduce the risk of cataracts.

Study 1: C.R. Gale, N.F. Hall, D.I. Phillips, et al., Plasma antioxidant vitamins and carotenoids and age-related cataract, Ophthalmology, 2001

Study 2: P.F. Jacques, L.T. Chylack Jr., S.E. Hankinson, et al., Long-term nutrient intake and early age-related nuclear lens opacities, Archives of Ophthalmology, 2001

1998

Researchers: Leske MC; Chylack LT Jr; He Q; Wu SY; Schoenfeld E; Friend J; Wolfe J
Published: Antioxidant vitamins: the longitudinal cataract study, Ophthalmology (United States) May 1998

4. B Vitamins (2015) & Cataract

Learn more about treatment of cataracts.

Researchers wanted to evaluate whether lutein and zeaxanthin with vitamins B2 (riboflavin), B3 (niacin), B6 and B12 were associated with lower risk of cataract development.

The health and dietary information of more than 3,000 subjects aged 55 to 80 years old were studied for nearly 10 years (mean) in the Age-Related Eye Disease Study (AREDS). They filled out questionnaires at the beginning of the study and lens photographs were taken each year. As the study progressed researchers assessed whether the patients had cataract surgery, and whether and how severe instances of cataracts occurred.

At the start of the study it was noted that where the diet included greater amounts of these nutrients the incidence of cataract was less, an inverse relationship. And as the study continued it was noted that these relationships continued - the greater the levels of the B vitamins mentioned, the less occurrence and severity of cataract.

To be more specific, highest levels of B6 in the diet were associated with decreased risk of moderate lens opacity. Highest dietary levels of B3 and B12 were tied to decreased risk of mild cataracts in patients who were not taking multivitamins. However, for patients taking multi-vitamins, the highest intake of folate was associated with increased risk of mild lens opacity. There were no statistically significant associations between lutein plus zeaxanthin and cataract development.

Researchers: T.S. Glaser, National Eye Institute, et al

Published: The Association of Dietary Lutein plus Zeaxanthin and B Vitamins with Cataracts in the Age-Related Eye Disease Study: AREDS Report No. 37, Ophthalmology, July, 2015.

5. Bilberry, Vitamin E (1989) & Cataracts

Learn more about cataract.

In an early study, a bilberry and vitamin E combination stopped cataract formation in 97% of the patients - without any side effects. This research has been substantiated in later studies.

Researcher: G. O. Bravetti

Published: Preventive medical treatment of senile cataract with vitamin E and Vaccinium myrtillus anthocyanosides. Clinical evaluation. Annuals of Ophthalmologic Clinical Oculogy, 1989

6. Cineraria (2013, 2011, 1982) & Cataracts

Learn more about treating cataracts.

2013

Fights free radicals

Researchers wanted to evaluate the capacity of cineraria maritima to fight free radicals and slow development of cataracts in lab animals.

When they were injected with cineraria extract the level of free radicals declined, and other biochemical abnormalities were reduced to nearly normal levels.

Researchers: T.A. Anitha, et al.

Published: Putative free radical-scavenging activity of an extract of Cineraria maritima in preventing selenite-induced cataractogenesis in Wistar rat pups, Molecular Vision, Dec. 2013.

Prevents selenite-induced cataract growth.

2011

The study concludes that cineraria may be helpful in preventing this type of chemical-induced cataract.

Editor's note: While not conclusive, this study does show that cineraria supports the health of the lens.

Researchers: T.S. Anitha, T. Annadurai, P.A. Thomas, P. Geraldine.

1982

Dr. D.H. Chand wrote an article summarizing his experience treating various eye conditions, including cataracts, with cineraria maritima.

Author: D. H. Chand, Role of Homeopathy in ophthalmological conditions, Indian Journal of Ophthalmology, July, 1982.

7. Diet (2011), Cataract Risk & Vegetarianism

Learn more about cataracts.

In this study the researchers looked into the relationship between diet and risk of cataract. The study subjects were 27,670 non-diabetic people aged 40 and more, a large proportion of whom were vegetarians.

The researchers used a testing model known as the Cox proportional hazards regression to evaluate the risk.

They found a strong correlation between the risk of cataract and the type of diet. The subjects who ate the most meat had the highest rate of cataracts, and those who ate fish, but not meat had a lower rate, vegetarians had a lower rate and vegans had the lowest rate of cataract incidence.

Researchers: Paul N Appleby, Naomi E Allen, and Timothy J Key

Published: Diet, vegetarianism, and cataract risk, Am J Clin Nutr May 2011 ajcn.004028

8. Exercise (2015) and Cataract

Learn more about cataracts and the benefits of exercise on your vision and general health.

2015

Researchers decided to investigate whether exercise could be helpful for reducing the risk of cataracts, which are the major cause of vision loss in the U.S.

They looked at cataract incidence and exercise amounts in a large population (almost 24,000 women and almost 29,000 men) in Sweden. The amount and specific type of exercise performed was obtained through self-administered questionnaires. The cataract incidence was measured through linking to registries of cataract patients. Both exercise and cataract incidence were monitored for more than 12 years, during which time 11,580 cataract cases were reported.

The researchers identified types of exercise:

walking or bicycling an hour a day versus hardly ever,
heavy manual labor versus mostly sitting,
exercise training and home or housework, and
leisure time inactivity.

The researchers reported the following results:

the top 1/5th in terms of total exercise had 13% lower risk of developing cataracts,
the more vigorous types of exercise were similarly associated with less risk,
exercise training and home/housework were not associated with risk one way or another, and
leisure time inactivity had a higher risk.

They concluded that it is long-term activity (as opposed to a burst of exercise training) that reduces risk of cataracts. And high levels of inactivity increases cataract risk.

Researchers: J. Z. Selin, N. Orsini, et al,
Published: Long-term physical activity and risk of age-related cataract: a population-based prospective study of male and female cohorts, Ophthalmology, February, 2015.

9. Glutathione (2000, '02, '11, '13, '15, '17) & Cataract

Learn more about cataracts.

The following and other studies demonstrating the effectiveness of glutathione as a powerful anti-oxidant are also important with respect to macular degeneration and other eye diseases.

2017

Furthering the understanding that glutathione is an essential antioxidant for healthy lenses, researchers in India compared glutathione and argpyrimidine in healthy lenses from an eye lens bank and diseased lenses (both nuclear and cortical) that had been removed during cataract surgery.

They found that glutathione levels were significantly lower in lenses with cataracts compared to healthy lenses. In addition they found that glutathione levels were even lower in nuclear cataract lenses compared to cortical cataract lens.

Argpyrimidine is a biochemical that is formed in the presence of sugars, a process known as glycation. Argpyrimidine levels were much higher in the diseased lenses.

Editor's Note: It's well established that diabetics, who are unable to properly process sugars, have a greater risk of developing cataracts.

Mynampati, B.K., Ghosh, S., Muthukumarappa, T, Ram, J. (2017). Evaluation of antioxidants and argpyrimidine in normal and cataractous lenses in north Indian population. Int J Ophthalmol, 10(7): 1094-1100.

2015

Polymorphisms, abnormal changes, to glutathione found in the body have been associated with increased cataract risk.

The researchers did a meta-analysis - a study of the studies that have been done - to determine the degree of accuracy in this assumption.

They evaluated the results of a total of 24 different studies that had investigated the relationship between several types of changes (GSTM1 and GSTT1) using what is known as a random-or fixed-effects model.

They found that GSTM1 null polymorphism was not associated with increased cataract risk, but that GSTT1 null was markedly tied to a particular type of cataract - posterior subcapsular - which occurs more often in patients of Asian peoples. Further investigation is needed.

Researchers: W. Sun, et al.

Published: Is there association between Glutathione S Transferases polymorphisms and cataract risk: a meta-analysis? BMC Ophthalmology, July, 2015.

Other researchers have tied low levels of glutathione in the body with formation of cataracts. Such low levels are associated with oxidation of crystallins in the lens. In order to further understand the process by which this occurs researchers compared human cataracts with cataracts from lab animals which had been caused by low levels of glutathione.

They found that a certain type of molecular bond (disulfide bond) were prominent in crystallins at young humans and in healthy mouse lenses. But at an older age in humans and in the mouse lenses that had formed cataracts a different type of molecular bond was prevalent (multimeric intermolecular disulfide bond).

Researchers: X. Fan, et al.
Published: Evidence of highly conserved beta-crystallin disulfidome that can be mimicked by in vitro oxidation in age-related human cataract and glutathione depleted LEGSKO mouse lens, Molecular Cell Proteomics, Oct. 2015.

2013

There is a link between childhood cataract and glutathione depletion in maternal malnutrition.

Kumar, D., Lim, J.C., Donaldson, P.J. (2013). A link between maternal malnutrition and depletion of glutathione in the developing lens: a possible explanation for idiopathic childhood cataract? Clin Exp Optom, Nov;96(6):523-8.

2011

The importance of vitamin C to eye health cannot be understated; concentrations of vitamin C in the lens are 20–30 times higher than those in the plasma. Vitamin C doesn't work alone: it needs glutathione to improve the use of ascorbic acid (the purist form of vitamin C) in the body. Glutathione and vitamin C are thought to work together to promote proper water balance within the lens and prevent the protein clumping that can lead to cataracts.

Ravindran, R.D., Vashist, P., Gupta S.K., Young, I.S., Maraini, G., et al. (2011). Inverse Association of Vitamin C with Cataract in Older People in India. Ophthalmology, Oct;118(10):1958-1965.

2002

Researchers find that older people had a greater drop in glutathione blood status than younger people with a corresponding increase in oxidized glutathione by-product over time suggests more oxidation and the higher risk of age-related eye diseases.

Researchers: S. P. Ayalasomayajula, et al.
Published: Induction of vascular endothelial growth factor by 4-hydroxynonenal and its prevention by glutathione precursors in retinal pigment epithelial cells. European Journal of Pharmacology, August, 2002

2000

Researchers have demonstrated that glutathione (GSH) is an essential antioxidant which is particularly concentrated in the lens of the eye. It detoxifies oxidants (free-radicals) such as H202 and dehydroascorbic acid. When there are very low levels of GHS in the lens, it has been found that even low levels of oxidants can damage the lens.

Study 1: F. J. Giblin, et al., Glutathione: a vital lens antioxidant. Journal Ocular Pharmacological Therapies, April 2000
Study 2: R.F. Brubaker, et al., Ascorbic acid content of human corneal epithelium. Investigative Ophthalmology & Visual Science, June, 2000

Also see oxidative stress and cataract for more information on 2013 glutathione research.

10. L-carnosine (1999, 2009, 2016) & Cataracts

See more about cataracts treatment and information.

2016

These researchers point out that l-carnosine is identified as an anti-cataract agent but that there is not much research to support the claim. This study dives into the mechanisms behind the anti-cataract capacity of the nutrient.

Their research evaluated both direct and indirect antioxidant properties. They found that l-carnosine is a strong inhibitor of sugar molecules' ability to bond to proteins or fats unless an enzyme is present. This is called glycation. They also found that l-carnosine has weak antioxidant and metal chelation properties.

Their conclusion is that the benefit of l-carnosine comes from the ability to restrict glycation and likely not due to antioxidant properties. They further concluded that for this reason that l-carnosine could be effective in treating diabetic eye disease.

Researchers: H. Abdelkader, M. Longman, et al,
Published: On the Anticataractogenic Effects of L-Carnosine: Is It Best Described as an Antioxidant, Metal-Chelating Agent or Glycation Inhibitor?, Oxidative Medicine and Cellular Longevity, August, 2016.

1999

Chinese and Russian researchers completed a preliminary study whose result showed that carnosine gives a pronounced effect on primary senile cataracts, the effective rate being 100%. For mature senile cataracts, the effect rate was 80%.

Researchers: A.M. Wang, et al.

Published: Use of carnosine as a natural anti-senescence drug for human beings. Department of Biochemistry and Department of Neurobiology, Harbin Medical University, China, 1999.

2009

Italian researchers report that carnosine may be valuable in preventing and treating cataracts. Carnosine is a dipeptide composed of the amino acids beta-alanine and histidine, especially found in muscle and brain tissue.

The researchers tested two forms of carnosine, d- and l-carnosine, on the primary protein that forms lens structure (from cows). The protein cultures were treated with guanidine, a compound that causes cataracts by forming fine alpha-crystallin fibers, known as fibrils. They also found that when they treated the cultures with d- or l- carnosine such fibril formation was inhibited. Adding carnosine to already existing fibrils almost completely dissolved them.

Researchers: F. Attanasio, S. Cataldo, S. Fisichella, S. Nicoletti, V.G. Nicoletti, B. Pignataro, A. Savarino, E. Rizzarelli, University of Catania.

Published: Protective effects of L- and D-carnosine on alpha-crystallin amyloid fibril formation: implications for cataract disease, Biochemistry, July 14, 2009

11. Leafy Green Veggies (2004) Protect Eyes

In the lab, researchers looked at the effects of lutein and zeaxanthin on samples of human eye lens cells. They compared the action of these antioxidants on the cells to that of vitamin E.

They treated the cells with concentrations of the antioxidants and then exposed them to ultraviolet radiation, about the same amount that a person gets with a mild tan.

Adding lutein and zeaxanthin to the cells reduced signs of ultraviolet damage by 50%-60%. Vitamin E reduced the same signs of damage by 25%-32%.

This study provides more evidence that these antioxidants found in plants such as spinach, kale, and collard greens, can help prevent cataracts by protecting the eyes from ultraviolet radiation.

Published: Chitchiumroonchokchai, C. Journal of Nutrition, December 2004; vol 134: pp 3225-3232

Learn more about cataracts.

12. Lutein (1995, 1999, 2014) and Zeaxanthin - Cataracts

Learn more about natural treatment of cataracts.

1995

Researchers found that xanthophylls lutein and zeaxanthin are the only carotenoids which are found in the lens of the eye. They also found that large levels of antioxidant vitamins, such as carotenoids in the blood plasma and in patients' diets can be connected to a lower risk of developing cataracts.

For example, a diet that includes significant amounts of spinach, a dark leafy green high in lutein and zeaxanthin was consistently connected with a smaller risk for cataract development. Correspondingly, high lipid antioxidant status is connected to healthier and longer eye lens functioning.

Why? The research suggests that xanthophylls block blue light which is phototoxic.

Likewise, there is a strong inverse connection between large intakes of dark leafy green vegetables, rich in lutein and zeaxanthin, and a lower risk for another oxidative stress related disease - cancer.

Lutein and zeaxanthin are the only carotenoids that have been reported to be present in a number of locations within the human eye: the retina, the macula, and the lens.

Published: KJ Yeum et al, "Measurement of Carotenoids, Retinoids, and Tocopherols in Human Lenses," Investigative Ophthalmology and Visual Science, December, 1995, Vol. 36. No. 13, pp. 2756-2761.

1999 Researchers found that the carotenoids lutein and zeaxanthin may be particularly effective in cataract prevention. The Harvard Medical School study included almost 80,000 females nurses and over 35,000 male health professionals. The female group completed diet questionnaires in 1980 and 1984, with follow-up until 1992. By 1992, 1471 of them had cataracts removed. The male group completed questionnaires in 1986 and with follow-up for 8 years. By 1994 they had 840 cataracts removed.

The researchers found that the 20% of nurses with the most lutein and zeaxanthin in their diet had 22% lower risk of cataract than did women with the least amounts in their diet. Among the men, the 20% with the highest intake had a 19% lower risk of cataracts compared to the 20% with the lowest intake.

There was a significant benefit due to spinach, kale and broccoli in the diet, but no confirmed results from other carotenoids or vitamin A.

Researchers: Harvard Medical School

Published: Chasan-Taber, Lisa, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. American Journal of Clinical Nutrition, Vol. 70, October 1999, pp. 509-16

Brown, Lisa, et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. American Journal of Clinical Nutrition, Vol. 70, October 1999, pp. 517-24

Mares-Perlman, Julie A. Too soon for lutein supplements. American Journal of Clinical Nutrition, Vol. 70, October 1999, pp. 431-2 (editorial)

2014

A meta-analysis is essential a review or study of studies. While a single small or in some other way insufficiently designed study may not conclusively demonstrate a particular result, by looking a many such studies reasonable conclusions can be drawn.

This meta-analysis looked at the ties between levels of the carotenoids lutein and zeaxanthin in the blood and the risk of developing cataracts in older patients. It accomplished this by evaluating pooled relative risks for lowest and highest levels of the nutrients in blood plasma and the incidence of cataract.

The researchers found marked inverse relationships between nuclear cataract (the most common type of cataract, the center of the lens hardening and yellowing) and the nutrients - in other words, the lower the levels of carotenoids lutein and zeaxanthin the greater the incidence of cataract. This was especially true of zeaxanthin levels.

The meta-analysis also concluded that higher levels of these carotenoids was also indicative of reduced incidence of cortical cataract (inside the lens capsule) and subcapsular cataract (back of the lens).

Researchers: X.H. Liu, et al.

Published: Association between lutein and zeaxanthin status and the risk of cataract: a meta-analysis, Nutrients, Jan, 2014.

13. Lutein (2003, 2015) Helps Age-Related Cataracts

Learn more about treatment for cataracts.

2015 The researchers reported that despite much literature indicating that the antioxidant lutein is associated with reduction in cataract incidence there have been very few articles reviewing such research. In this review the researchers investigate the role of damage to the lens of the eye caused by oxidative stress, how cataracts develop, and the potential beneficial effects of using lutein as both prevention and maintenance in managing cataract and the health of the retina.

Researchers: A. Manayi, et al

Published: Lutein and cataract: from bench to bedside, Critical Reviews in Biotechnology, June, 2015

2014

A meta analysis noted that levels of lutein and zeaxanthin in blood serum found that pooled results were mostly not linked to reduced cataract risk. However there was a marginally lowered risk of subcapsular cataracts, and a significantly reduced risk of nuclear cataracts.were linked to a lower risk of cortical and subcapsular types of cataracts.

Liu, X.H., Yu, R.B., Liu, R., Hao, Z.X., Han, C.C., et al. (2014). Association between lutein and zeaxanthin status and the risk of cataract: a meta-analysis. Nutrients, Jan.

2003 In a small pilot study (17 patients) over 24-months, they found that sharpness of vision and sensitivity to glare (problematic for cataract patients) were improved in patients taking lutein supplement compared to a control. The study was double-blind, placebo-controlled, and randomized. Measurements of the nutrients was done with liquid chromatography and visual performance and biochemical/blood profiles were done every three months during the study.

Researchers concluded that lutein is helpful in treatment of cataracts and that lutein, but not alpha tocopherol, improves visual function in patients with age-related cataracts

Olmedill, B., Granado, F., Blanco, I., Vaquero, M. (2003). Lutein, but not alpha tocopherol, supplementation improves visual function in patients with age-related cataracts: A 2 year double-blind, placebo controlled study. Nutrition, Jan;19(1):21-4.

Note: other research has investigated the combination of lutein and zeaxanthin and lutein, zeaxanthin and vitamin E in treating cataracts.

14. Lutein, Zeaxanthin and Vitamin E (2008) Reduce Risk of Cataracts

Learn more about natural treatment of cataracts.

In a long-term 10-year study the use of dietary supplements and presence of cataracts was assessed in more than 35,000 middle-aged U.S. women. The researchers found significant evidence that women who had diets/supplements including more zeaxanthin, lutein and vitamin E were less likely to develop cataracts than women who are lacking intake of these nutrients. The women with the highest levels of these nutrients were 18% less likely to get cataracts.

Published: Archives of Ophthalmology (Arch. Ophthalmol. 2008;126:102-9) from the Women's Health Study.

15. MSM (2015) Reduces Inflammation - Cataract

MSM is helpful for conditions where inflammation is an issue such as cataracts.

The researchers noted that while the health benefit of reducing inflammation is associated with Methylsulfonylmethane (MSM) there had been no study focusing on that capacity with regard to inflammasomes - a formation composed of multiple proteins that acts as a basis for stimulating lymphocyte development. Lymphocytes are the white blood cells that fight infection.

The researchers found that MSM did reduce some types of inflammasome activation. They also found that MSM-enriched vegetable given to lab animals had the same effect.

They concluded that MSM does present anti-inflammatory capacity, interrupts inflammasome production, and inhibits expression of pro-cytokines which promote systemic inflammation and make a disease worse through fever and tissue death.

Researchers: H. Ahn, J. Kim, M. Lee, Y. Kim, Y.W. Cho, G. Lee

Published: Methylsulfonylmethane inhibits NLRP3 inflammasome activation, Cytokine, February, 2015.

16. N-acetylcarnosine (2001-02, 2009, 2012, 2014) & cataracts

Learn more about treatment for cataracts.

A number of research studies over the years support the premise that n-acetylcarnosine in a 1% solution is effective in treating cataracts. Following are brief descriptions of studies undertaken in 2001, 2002, 2009, 2012, and 2014. Later studies investigated the mechanics of the process.

2001

Researchers investigated the efficacy of n-acetylcarnosine (NAC) in a 1% solution in treating or reducing the risk of cataract.

The study evaluated changes in lens clarity in nearly 100 subjects, 1/2 control and 1/2 treated. There were two trials - a 2 month trial and a 6 month trial. The patients were evaluated at the beginning of the study with standard measurements of vision testing for cataract with ophthalmoscopy, glare test, slit-image and retro-illumination photography.

The patients had an average age of 65 years old. The patients in each trial were given NAC (26 patients), placebo (13 patients) or untreated (10 patients) (placebo & untreated were combined into the control group).

Over six months 41.5% of the eyes showed marked improvement in lens clarity; 90% of the eyes showed a gradual improvement in lens clarity, and 88.9% of the eyes showed improvement in glare sensitivity. In general the topographic studies showed less lens density and opacity in the posterior subcapsular and cortical morphological portions of the lens.

With the study extending over two years, the researchers could report that the NAC benefit continues and is sustainable. There were no instances of a worsening of vision and in most patients tolerance of the drug was good. This form of L-carnosine appears to be suitable for nonsurgical treatment for senile cataracts.

Published: Peptides, June, 2001

2002

Researchers reported the efficacy of a 1% N-acetylcarnosine solution for 46 older patients who have cataracts - observing the degree of lens opacity/clarity after 6 months and 24 month periods.

In two related pilot trials patients with lens opacity were also tested with the same solution or a placebo, with evaluations at the beginning, and every two months for six months and in a separate trial, every six months for two years. The cataracts were assessed for vision sharpness and glare and were measured with stereo cinamatographic retro-illumination and slit-images.

After six months 90% of the patients who had received NAC showed improvement in vision sharpness, and 89% showed improvement in glare.

The improvements continued after 24 months' treatment with NAC and none had deterioration of vision - while in the control group there was significant worsening after 24 months compared to both the start measurements and the treated patients.

There were no reports of systemic or ocular side effects and the drops were well tolerated. The researchers concluded that NAC shows promise for treating and preventing cataracts.

Researchers: Babizhayev MA, et al, Innovative Vision Products, Inc., Delaware, USA

Published: Efficacy of N-acetylcarnosine in the treatment of cataracts, Drugs in Research and Development, 2002;3(2):87-103.

2009 This study was designed to substantiate and fuller examine the results found in a 2002 study on the effectiveness of 1% N-Acetylcarnosine in improving cataract.

The subjects were 75 patients ranging from 54 to 78 years of age with no history of cataract surgery or other vision conditions except cataracts and with vision of 20/40 or worse as well as 72 controls. The patients had reported symptoms of glare sensitivity and were looking for quick relief.

After nine months the researchers found that most patients' glare scores improved or returned to normal standards.

The researchers emphasized that only the natural form of NAC in L-isomeric form was used and claimed this was important for outcomes. They discussed the mechanisms of cataract improvement to include:

prevention of free-radical-induced negative effect on antioxidants in the lens (superoxide dismutase);
prevention of oxidation (carbohydrate & metal-catalyzed) on interactions with proteins in the lens;
non-enzyme induced bonding capacity of carnosine which in turn protects the lens crystalline struction (proteins) from being adversely changed;
free-radical scavenging action of aldehydes, lipid hydroperoxides, and oxygen radicals;
interaction between l-carnosine and proteasome activity; and
disaggregation of lens crystallins activity.

Researchers: Babizhayev MA, et al, Innovative Vision Products, Inc., DE

Published: N-Acetylcarnosine sustained drug delivery eye drops to control the signs of ageless vision: glare sensitivity, cataract amelioration and quality of vision currently available treatment for the challenging 50,000-patient population, Clinical Interventions to Aging, 2009

2012

Previously the effectiveness of n-acetylcarnosine was demonstrated in preliminary research. Researchers have followed up with a phase 2 placebo-controlled and double-blind study to test the validity of pilot studies.

The study performed a high-performance liquid chromatography analysis to investigate how N-acetylcarnosine is absorbed into the lens of the eye and how it promotes the presence of l-carnosine in the vitreous.

The eye's ability to absorb l-carnosine activates the back of the hypothalamus (tuberomammillary activation) which regulates normal nerve functioning including that which processes sensory input to the retina.

The introduction of N-acetylcarnosine is found to not be toxic to the structure of the eye, reduces inflammation, and may be a useful tool in vitreo-retinopathy surgery, and may be found to protect photoreceptor cells due to its antioxidant-like behavior.

Authors: M. A. Babizhayev, I.P. Khoroshilova-Maslova, A. Kasus-Jacobi

Published: Novel intraocular and systemic absorption drug delivery and efficacy of N-acetylcarnosine lubricant eye drops or carcinine biologics in pharmaceutical usage and therapeutic vision care, Fundamental & clinical Pharmacology, October, 2012.

2014

Researchers investigated the effect of combining N-acetylcarnosine, previously shown to impact lens clarity, with D-pantethine on a 1-to-1 ratio. D-pantethine is a two-molecule form of vitamin B5 (pantothenic acid).

Lab animals with cataracts induced by UV light received a 5% mixture of the above combination either into the eyes or into the body cavity. It was found that such treatment inhibited the formation of cataracts. After the 82nd day of treatment the protective effect of the combination increased significantly. The researchers measured the results using gel permeation chromatography, a technique separates substances being analyzed on the basis of their relative size - in this instance looking at proteins that cause cataracts.

The researchers concluded that the combination inhibited development of cataracts caused by exposure to UV-type A radiation.

Published: (In Russian) [Deceleration of cataract development in rats under the action of N-acetylcarnosine and D-pantethine mixture], Eksperimental'naia i klinicheskaia farmakologiia, Vol. 77, 2014.

17. Nutrition (1993) and Oxidation: Cataracts

See more about cataracts treatment and information.

Taylor A., Journal of the American College of Nutrition, 1993 Apr, 12(2):138-46 Pub type: Journal Article; Review; Review, Tutorial. (UI: 93217072)

Abstract:
Opacification of the lens, or cataract, is causally related to the precipitation of proteins or other constituents upon aging. Proteins in the lens are unusually long lived and are subject to extensive damage, including (photo) oxidation. Accumulation of damaged proteins also appears to be due in part to attenuated activity of some proteolytic pathways, which in younger tissue may serve to identify and remove such moieties. The damaged proteins accumulate, aggregate, and precipitate.

Compared with other health problems, surgery to remove cataract and related visits to physicians consume the largest proportion of the Medicare budget, i.e., $3.2 billion annually in the United States. The situation is exacerbated in many parts of the world where there is a dearth of ophthalmologists to perform the required number of procedures. Historically efforts to delay cataract assumed a low profile in ophthalmologic research.

Recent data, however, indicate that consuming elevated levels of antioxidants such as ascorbate, carotenoids, and tocopherol is associated with delayed development of various forms of cataract. The same beneficial relationship to vision pertains to plasma antioxidant status and to fruit and vegetable intake.

Thus, it seems that assuring optimal antioxidant intake can extend lens function. It has been estimated that in the United States over half of the cataract extractions and associated costs would be obviated if cataract could be delayed by 10 years. The data reviewed indicate that optimizing nutrition will help achieve that objective.

18. Propolis (2016) & Cataract

Learn more about cataracts.

Of keen importance to diabetics is that uncontrolled diabetes (poor control of blood sugar) can result in what is known as sugar cataracts. Under certain circumstances cataract formation can take place very quickly, sometimes resulting in complete loss of vision in as little as three days.

An interesting study investigated whether propolis impacted the development of sugar cataracts. Propolis is the waxy material created by bees and used to seal various leaks and cracks in the hive to keep out both cold drafts and unwanted predators such as wax moths. Most honey that comes from the store has been very finely filtered and bits of propolis are removed. However unfiltered honey, and honey that has been only coarsely filtered tend to have bits of tasteless propolis in the honey. Bees gather propolis from tree buds and flows of sap in various trees in their locale.

Propolis is also widely available as a nutritional supplement.

The study employed propolis as part of the diet of lab animals as well as the in-vitro effects of propolis in the lab. The lens of animals fed a high glucose diet were evaluated for opacity and cell death levels. The researchers found that propolis given orally with 5 ug/ML or 50 ug/ML markedly reduced both onset and progression of cataract and also offset the effects of a high glucose diet. They found that giving the animals doses of propolis daily reduced the opacity of the lens.

Both propolis and an active ingredient of propolis (caffeic acid phenethyl ester - CAPE) have been shown by researchers to have not only antioxidant properties but may have antitumor, cytotoxic, and anti-inflammatory properties. In addition it is found to normalize sugar balance in animals with type II diabetes.^{1, 2}

Control animals, who were fed purified honey - with no propolis did not have the same beneficial results.

Researchers: T. Shibata, S. Shibata, et al
Published: Propolis, a Constituent of Honey, Inhibits the Development of Sugar Cataracts and High-Glucose-Induced Reactive Oxygen Species in Rat Lenses, Journal of Ophthalmology, April, 2016.

1. M. T. Al-Hariri, Propolis and its direct and indirect hypoglycemic effect, Journal of Family and Community Medicine, 2011.
2. T. Matsui, S. Ebuchi, et al., Strong antihyperglycemic effects of water-soluble fraction of Brazilian propolis and its bioactive constituent, 3,4,5-tri-O-caffeoylquinic acid, Biological and Pharmaceutical Bulletin, 2004

19. Quercetin, Rutin, Vitamin C (2002, 2015, 2017) Flavonoids & Cataracts

2002, 2017

Like other nutrient combinations, the combination of quercetin and vitamin C or rutin and vitamin C are effective in reducing the risk of developing cataracts. Quercetin and vitamin C are an especially effective combination.

Diabetics are at greater risk of developing cataracts than other populations. Researchers evaluating the mechanics of cataract development in diabetics have noted a number of mechanisms (maillard reaction, enhanced polyol pathway, and oxidative insults, epithelial mesenchymal transition) by which this is true. The latter mechanism, epithelial mesenchymal transition, refers to epithelial cells losing their polarity and ability to adhere to neighboring cells resulting in migration and invasion in other parts of the body. In this case the process takes place in the lens.

The researchers found that the flavonoids rutin, and especially quercetin, in combination with vitamin C had a potent and beneficial effect in reducing these malefic processes.

Source

Cornish, K.M., Williamson, G., Sanderson, J. (2002). Quercetin metabolism in the lens: role in inhibition of hydrogen peroxide induced cataract. Free Radic Biol Med, Jul 1;33(1):63-70.

Du, L., Hao, M., Li, C., Wu, W., Wang, W., et al. (2017). Quercetin inhibited epithelial mesenchymal transition in diabetic rats, high-glucose-cultured lens, and SRA01/04 cells through transforming growth factor-β2/phosphoinositide 3-kinase/Akt pathway. Mol Cell Endocrinol, Sep 5;452:44-56.

2015

Another study notes that the quercetin is one of the main flavonoids in green tea - and that consumption of green tea is associated with reduced risk of cataract.

Sheng, Y., He, F., Lin, J.F., Shen, W., Qiu, Y.W. (2015). Tea and Risk of Age-Related Cataracts: A Cross-Sectional Study in Zhejiang Province, China. J Epidemiol, 26(11): 587–592.

20. Riboflavin (1991), vitamins C, E, carotene, niacin, thiamine & cataracts

See more about cataracts treatment and information.

Researchers found that increased riboflavin, vitamins C, E, and carotene, niacin, and thiamine in the diet significantly lessened the risk of all cataract types. They also found that when different antioxidant nutrients were combined the beneficial results were the greatest.

Published: Leske, et al. Arch Ophthalmol 1991 Feb;109(2):244-51.

21. Saffron (2013, 2016) and Cataract

Learn more about cataract treatment.

Diabetic cataracts are a common complication of diabetes mellitus and have been found to be improved by complementary treatment with saffron. A major component of saffron is crocin which has been found to have good antioxidant, anti-inflammation, and neuroprotective benefits in other studies.

This study evaluates the ability of crocin to inhibit proteins from bonding to sugar molecules (protein glycation) and clumping (aggregation) that leads to cataracts as a complication of diabetes.

Diabetic lab animals were treated with insulin or with insulin and saffron. Progression of cataracts was monitored and recorded on two-week intervals. The degree of cataract development was measured after eight week and the researchers found that there was a powerful inhibitory effect by crocin on cataract development.

Researchers: F. Bahmani, et al.

2016

An interesting and related study found that the saffron apocarotenoid crocin was helpful in reducing diabetic cataracts.

Researchers: F. Bahmani, et al.

Published: Inhibitory Effect of Crocin(s) on Lens α-Crystallin Glycation and Aggregation, Results in the Decrease of the Risk of Diabetic Cataract, Molecules, January, 2016.

2013

An earlier study investigated the effect of saffron therapy on lab animals with selenium-induced cataracts.

There were three groups: one receiving saline (placebo) injections, one receiving selenite, and a third receiving selenite and saffron. After three weeks cataract development was examined and it was found that the animals receiving saffron had received significant protection against cataract development induced by selenium. The levels of important lens nutrients superoxide dismutase, glutathione, glutathione peroxidase and catalase were much higher in the third group. The saffron prevented oxidation and protein clumping which cause cataracts.

Researchers: O.E. Makri, et al.

Published: Saffron administration prevents selenite-induced cataractogenesis, Molecular Vision, May, 2013.

22. Smoking (1991, 1993, 2014) - Cataracts

1991, 1993 Researchers have established that smoking cigarettes substantially increases the risk of developing age-related cataracts. Smoking accounts for about 20% of all cataract incidences.

Furthermore, for men who smoke more than a pack a day of cigarettes, the risk factor is increased to 205%. Women who smoke more than a pack a day of cigarettes are 63% more likely to develop cataracts than other women.

Cigarette smoking causes about 20 percent of all cataracts. Men who smoke more than a pack a day increase their risk for cataracts by 205 percent; for female smokers, risk increases 63 percent.

Study1: W.G. Christan, et al., Cigarette smoking and the risks of cataract. Investigative Ophthalmology, April 1991.

Study2: W. G. Christen, and J.M. Seddon, Cigarette smoking and cataract. American Journal of Preventive Medicine, September, 1993

2014 Smoking cigarettes also increases the risk of developing cataracts in young people (aged 21 to 30). Scientists evaluated the lens densities of 60 young cigarette smokers who smoked a minimum of 10 cigarettes daily for a minimum of two years. The study included another 60 healthy non-smokers of like age and gender.

The researchers found that while there was no significant difference between the subjects and the controls as to the nuclear (center) and posterior areas of the lens, however in the anterior (front) of the lens the smokers showed marked increases in lens density. In other words, smoking may increase the risk of anterior cortical (front, edges) and subcapsular cataracts in this age group.

Researchers: T. Kar, A. Ayata, Y. Aksoy, A. Kaya, M. Unal

Published: The effect of chronic smoking on lens density in young adults, European Journal of Ophthalmology, September-October, 2014.

23. Statins (2011, '13, '16, '17) & Cataract Risk

Learn more about support for the healthy eye lens.

Depending on the methodology used, there has been research suggesting that statins increase cataract use and that it does not increase the risk. The general consensus is that for heart patients, the increased risk is less than the increased risk of circulation problems without the statins.

2017

A study published on behalf of the American Heart Association reported no increased risk. The study was a meta analysis which looked at results only and did not take into account statin-years, a method used in earlier studies that measured both dosage and duration of statin use. They found that cohort studies (studies that look at the causes of diseases) found a moderate increased risk. They found that case-control studies (studies that compare a test group to a control group) did not see any increased risk. However they did note that risk was less for younger patients and greater for older patients.

S. Yu, Y. Chu, et al, Statin Use and the Risk of Cataracts: A Systematic Review and Meta-Analysis, Journal of the American Heart Association, March, 2017.

2016

A population-based study of more than 134 thousand statin patients in Italy who were newly prescribed statins over a 2 year period. The researchers identified patients who had cataract or lens extraction surgery and matched them with up to 5 random controls matched by gender, age, date of prescription, etc. The researchers used logistic regression to investigate low, medium and high usage of statins. They identified over 1,300 statin patients and over 6,600 controls, with a mean age of 70, slightly more than half of whom were men. They identified a trend of cataract development as statin dosage and duration increased.

M. Casula, D. Soranna, Statin use and risk of cataract: A nested case-control study within a healthcare database, Atherosclerosis, August, 2016.

Another 2016 study of over 6,000 patients in the US found that statins taken continuously for at least one year may have increased risk. 42% of the statin users needed cataract surgery; 34% of statin users did not need cataract surgery.

AREDS2 The large Age-Related Eye Disease Study 2, No. 8, however, did report increased risk of cataracts with statin use. AREDS2 was designed to investigate the addition of lutein and zeaxanthin and omega-3 fatty acids (found in AREDS2 to decrease macular degeneration risk). AREDS2 found that these nutrients did not make up a significant improvement for cataract patients. However the data collected allowed researchers to investigate the possible association between cataract and statin use. 42% of the cataract patients used statins. These patients were more likely to have high blood pressure or cardiovascular problems; they tended to be men, to smoke and/or have diabetes.

Both male and female statin users were found to have an increased risk of developing cataracts.

S.H. Al-Holou, W.R. Tucker, et al, The Association of Statin Use with Cataract Progression and Cataract Surgery The Age-Related Eye Disease Study 2 Report Number 8, Ophthalmology, April, 2016.

2013

This study utilized the data from a large military health care system and looked at patients who had received a minimum of a 90 day prescription of statins versus patients who had not. The researchers selected almost 14,000 statin users and almost 33,000 non-statin users.

The analysis method is known as propensity score-matching, a method, which to some mathematicians increases imbalances and bias. However in this study the patients and controls were matched in over 40 factors to eliminate bias and create 6,972 pairs of patient/control.

The showed an increased risk of cataract development of 9% to 27% and up to 34% in a study analysis. The variance in risk is associated with duration and dosage of the statin use.

J. Leuschen, E.M. Mortensen, et al, Association of statin use with cataracts: a propensity score-matched analysis, JAMA Ophthalmology, November, 2013.

2011

Investigators reviewed information from more than two million people in England and Wales, ages 30 to 84, in the QResearch medical database between 2002 and 2008. Of that group, 225,992 were new users of one of the following statins: simvastatin (Zocor), atorvastatin (Lipitor), pravastatin (Pravachol), rosuvastatin (Crestor), or fluvastatin (Lescol).

The investigators found that statin use was associated with an increased risk of cataracts in both men and women. The risk of cataracts rose within one year of starting statin treatment, persisted during treatment, and then returned to normal within a year after discontinuing the statin.

Bottom line: This study was not designed to show whether statins could cause cataracts, but it does show an association between the two. These findings conflict with other recent studies that have found that statins may prevent cataract development. More studies are needed to provide a definitive answer. In the meantime, it's important to see your eye doctor regularly to monitor for cataracts and other eye diseases.

24. Study Suggests Lutein and Zeaxanthin Offer Lens Protection
About 20 million Americans have vision-obstructing cataracts, with 500,000 new cases diagnosed annually. The estimated current cost of $3.4 billion annually to surgically extract cataracts is expected to increase along with the growing number of people over the age of 65. Among the risk factors associated with age-related cataracts, UV exposure and oxidative stress appear to be the most relevant. The lens is equipped with antioxidant mechanisms - such as glutathione peroxidase, vitamins C and E and carotenoids - to defend against the harmful effects of UV radiation and reactive oxygen species (ROS). Indeed, some epidemiologic studies suggest a reduced risk of developing various types of cataract with higher intake of vitamin C, E or lutein and zeaxanthin, the only carotenoids present in the lens and macula.

Although considerable efforts are being made to define the potential role of the xanthophylls lutein and zeaxanthin in the macula, information about their uptake and function in the lens is extremely limited. Epithelial cells, the outermost cellular layer of the lens, are exposed to UV irradiation not filtered by the cornea. UV-induced damage is mediated via production of ROS, and characterized by alterations in cell growth, morphology, changes in membrane potential, and oxidation of lipids, proteins and DNA. The present study examined the ability of xanthophylls to protect cultures of immortalized human lens epithelial cells (HLE) against UVB insult.

Results:

Cultured HLE cells accumulated xanthophylls and alpha tocopherol in a dose and time-dependent manner, with uptake of lutein exceeding that of zeaxanthin. Cultures were pretreated with either xanthophylls (2 micromoles/L) or alpha tocopherol (10 micromoles/L) for 4 hours, then exposed to 300 J/m2 UVB radiation - a dose roughly equivalent to that a person receives when they get a mild tan. Lipid peroxidation was observed to decrease by 47-57% compared with UVB-treated control cells.

The ability of xanthophylls and vitamin E to inhibit UVB-induced stress signaling was also assessed. Pretreatment with xanthophylls and alpha tocopherol inhibited UVB-induced activation of c-JUN NH2 terminal kinase and p38 activation by 50-60% and 25-32%, respectively. The concentration of Vitamin E required to significantly inhibit these stress signaling markers was roughly 10-fold higher than that of the xanthophylls, suggesting that xanthophylls are more potent for protecting HLE cells against UVB insult in this model.

Conclusions

According to the researchers from Ohio State University, their results are the first to provide physical evidence suggesting that lutein and zeaxanthin decrease damage caused by UV radiation. "In addition to protective enzymes and compounds like vitamins C and E, we think that low concentrations of lutein and zeaxanthin in the eye's lens help shield the eye from the harmful effects of UVB radiation", they stated in a post-publication interview.

Reference

Jacques PF. The potential preventive effects of vitamins for cataract and age-related macular degeneration. Int J Vitam Nutr Res 69: 198-205, 1999.

Taylor A et al. Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities. American Journal of Clinical Nutrition 75:540-9, 2002.

Chasen-Taber et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. American Journal of Clinical Nutrition 70:509-516, 1999.

Alves-Rodrigues A and Shao A. Review. The Science Behind Lutein. Toxicology Letters 150:57-83, 2004

Chitchumroonchokchai C et al. Xanthophylls and alpha tocopherol decrease UVB-induced lipid peroxidation and stress signaling in human lens epithelial cells. Journal of Nutrition 134:3225-32, 2004.

25. Sugar can impair the lens (1991)
All types of sugars, not just white sugar, can impair the eye lens ability to keep itself clear. Gaby, A.R., and Wright, J.V. Nutritional Factors in Degenerative Eye Disorders: Cataract and Macular Degeneration. Wright/Gaby Nutritional Institute, 1991.

26. Superoxide Dismutase (2013) and Cataract

Learn more about cataracts.

Researchers have established that oxidative stress plays a key role in development of cataracts, glaucoma and many other vision and health conditions.

The health of the body's natural antioxidant defense system is founded on the principle of balance - a balance of antioxidants against oxidative stressors such as UV light, toxins, etc.

Researchers investigated the activity of antioxidants that behave as enzymes to stimulate this defense system with respect to development of cataracts. They looked at levels of the enzymes superoxide dismutase, catalase, and glutathione peroxidase and the damaging biochemicals that result from oxidative stress.

The study included 60 patients with cataracts and 60 age-matched subjects with healthy eyes. The reseachers took blood samples from the 120 participants and analyzed them for content of the three antioxidant enzymes and six different toxic biochemicals which are hallmarks of oxidative stress.

They found that levels of the antioxidants, including superoxide dismutase were significantly lower in the cataract patients than in the control group with healthy eyes. They also found that the cataract patients had markedly higher levels of three of the toxic biochemicals and somewhat higher levels of the others.

Their conclusion was that a weak oxidative defense system was associated with greater oxidative stress and should be a useful target in combating development of cataracts.

Researchers: D. Chang, X. Zhang, et al,
Published: Serum Antioxidative Enzymes Levels and Oxidative Stress Products in Age-Related Cataract Patients, Oxidative Medicine and Cellular Longevity, 2013.

Also see glutathione and cataracts for more information on related research.

27. Vitamin A & C, Antioxidant Combo (2017) for Cataracts

Researchers have noted that combinations of nutrients often are more effective in combination against eye condition problems than the same nutrients taken by themselves.

The combination of vitamins A and C taken with omega-3 fatty acids is a good example.

In one such study researchers investigated a number of nutrient patterns based on diet. They were:

1. Sodium pattern: niacin, thiamin, carbohydrates, protein, zinc, vitamin B6 and sodium.
1. Fatty acid pattern: oleic acid, monounsaturated fats, polyunsaturated fats, linoleic acid, trans fatty acid, linolenic acid, vitamin E and saturated fats.
3. Mixed pattern: vitamin B12, vitamin D, cholesterol and calcium.
4. Antioxidant pattern: high intake of beta and alpha carotene, vitamin A and vitamin C.
5. Omega-3 pattern: docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)

The sodium and fatty acid patterns were linked to increased cataract risk; while the antioxidant pattern had a 79% reduced risk (compared to sodium pattern). Omega-3 pattern also reduced cataract risk.

Research: Sedaghat, F., Ghanavati, M., Nezhad, Hajian, P., Hajishirazi, S., Ehteshami, M., et al. (2017). Nutrient patterns and risk of cataract: a case-control study. Int J Ophthalmol, Apr 18;10(4):586-592.

28. Vitamin A (1944, 1992, 2014) & Cataracts

Researchers noted as early as 1944, after reviewing data from the Nutrition and Eye Disease Study, that moderate levels of Vitamin A in patients' diets were connected to a 40% lower risk of opaque lenses, or cataracts. The researchers adjusted the risk for age, sex, smoking, and heavy drinking and found that for those who were smokers, the cataract risk was reduced by 50%.

Published: Mares-Perelman, J.A., Klein, B.E.K., et al. Relationship Between Lens Opacities and Vitamin and Mineral Supplement Use, Ophthalmology 1944

1992 The Nurses Health Study was a nearly-20-year study which tracked the health of more than 50,000 female registered nurses along with their diet and levels of nutrients. Researchers noted that greater amounts of vitamin A in the diet were tied to 39% less risk of developing cataract.

In the years of follow-up additional women were added to the study as they reached age 45. The women who had the top one-fifth levels of vitamin A were those who had the 39% reduction. Consumption of spinach was most closely tied to lowered risk. In addition, the risk of cataract in women taking vitamin C was lowered by 45%. The researchers did not evaluate consumption of multi-vitamins.

Researchers: S.E. Hankinson, M.J. Stampfer

Published: Nutrient intake and cataract extraction in women: a prospective study, BMJ, August, 1992.

2014 Researchers investigated the effects of vitamin A and beta-carotene (a precursor of vitamin A) on cataract risk by summarizing the evidence from prior studies of both nutrients on cataract risk.

In this meta-analysis (a study of studies) the researchers evaluated information from 22 different studies finding significant connection between vitamin A consumption levels and incidence of cataract.

Researchers: A. Wang, Y. Jiang, D. Zhang

Published: Association of vitamin A and β-carotene with risk for age-related cataract: a meta-analysis, Nutrition, October, 2014.

29. Vitamin C (1986, 1995, 1997, 2002, 2005-06, '11) & Cataracts

Learn more about natural treatment of cataracts.

2011 A study of more than 31,000 Swedish men found that high-dose vitamin C (sometimes used in cancer therapy) can actually increase the risk of cataract, especially in older men.

Selin J. Zhen, et al.,
Published: High-dose supplements of vitamins C and E, low-dose multivitamins, and the risk of age-related cataract: a population-based prospective cohort study of men, American Journal of Epidemiology, March, 2013.

2011 A study of an Indian population evaluated the vitamin C levels in blood in over 5000 people who were 60 years old or greater. Like previous studies elsewhere in the world, the results demonstrated that vitamin C levels are associated with lower risk of cataract.

Furthermore, while low levels of the carotenoids lutein and zeaxanthin and the nutrient retinol were also tied to cataract risk, the importance of low vitamin C levels were shown to be the greatest risk factor.

Ravindran, R.D., Vashist, P., Gupta S.K., Young, I.S., Maraini, G., et al. (2011). Inverse Association of Vitamin C with Cataract in Older People in India. Ophthalmology, Oct;118(10):1958-1965.

2007

Two studies show significant reductions in cataracts for those in the highest percentage of vitamin C intake.

In the first study, Japanese researchers followed 35,000 people. They evaluated the participants for their vitamin C intake and cataract formation. They found that those in the highest 20% of vitamin C intake had a 40% reduced risk of getting cataracts.

The second study followed 177 (116 women, 61 men) participants over the age of 60. In this study, the researchers found that if you are in the top 5% of vitamin C intake, your risk is reduced some 20% compared to the lowest 5%.

But that's not all this study found. If you ingest more than 3,290 mcg daily of lutein, your risk drops 14% compared to ingesting less than 256 mcg daily. Zeaxanthin had a smaller risk reduction, but mostly in men.

Interestingly, the study also found that sunlight exposure is also a major risk factor. If you were out in the sun a lot in your early years, your risk triples compared to being closeted indoors.

Ref: International Journal for Vitamin and Nutrition Research, 2006; 76(6); Nutr, 2007 January 30.

2005 In Italy, research substantiated earlier research supporting the understanding that high levels of vitamin C in the diet which are reflected in blood plasma are associated with lower risk and incidence of both nuclear (center) and posterior subcapsular cataract.

Researchers: L. Ferrigno, et al

Published: Associations between plasma levels of vitamins and cataract in the Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract, Ophthalmic Epidemiology, April, 2005

2002 Researchers reported that females who take supplemental vitamin C while they are younger and middle-aged have a lower risk of cataract development later in life. This was another analysis from the extensive data gathered in the Nurses Health Study, which, as of 2002 had been ongoing for 26 years. They reviewed the information for nearly 500 middled aged (53-72) nurses, with especial attention to their long-term vitamin intake which had been taken from questionnaires about their diet for a 15 year period.

All of the women evaluated had eye exams; 34% of them had a type of cataract in which the fiberous cells of the cortex break down. The data revealed that those women (younger than 60) who'd had a minimum of 362mg vitamin C daily over 13 to 15 years prior had a 57% lower risk of cataract. Daily use of vitamin C for 10 years was tied to a 60% lower risk compared to women who'd had no supplemental vitamin C.

Furthermore, women who had never smoked and who had included high levels of folate and antioxidant carotenoids also had a much lower risk of cataract.

Taylor, A., Jacques, P.F., Chylack, L.T., Hankinson, S.E., Khu, P.M., et al. (2002). Long-term intake of vitamins and carotenoids and odds of early age-related cortical and posterior subcapsular lens opacities, American Journal of Clinical Nutrition, Mar;75(3):540-9

1997

The Nurses Health Study indicated that long-term consumption of vitamin C supplements can reduce the development of cataracts. This study was another long term study evaluating the diet and health of over 50,000 registered nurses. Researchers considered the connection between development of cataracts and vitamin C supplementation over 10 to 12 years in 247 56 to 71 year old nurses from the Boston area. The researchers did detailed eye exams to determine how much the eyes' lens were clouded and found that those women how had taken vitamin C supplements for over ten years had 77% fewer early lens opacities and 83% fewer moderate lens opacities.

Jacques, P.F., Taylor, A., Hankinson, S.E., Willett, W.C., Mahnken, B., et al. (1997). Long-term vitamin C supplement use and prevalence of early age-related lens opacities. American Journal of Clinical Nutrition, Oct;66(4):911-6.

1995 An analysis of some of the results from the Beaver Dam Eye Study (a long-term, large sample study of eye health and nutrition) evaluated the link between vitamin C and cataract. The researchers pointed out that the eye contains 20 times as much vitamin C as does the blood. Subjects with a high vitamin C intake were much less likely to develop cataracts than those who with low vitamin C intakes.

Researchers: C. Mares, J.A. Perlman, W.E. Brady, B.E. Klein, and others

Published: Diet and nuclear lens opacities, American Journal of Epidemiology, February, 1995

1986 There have been many studies on the role of vitamin C in preventing or reversing developing lens opacities of cataracts. Going back to 1935 this has been found to be the case.

Researchers: J. Blondin, et al.

Published: Prevention of eye lens protein damage by dietary vitamin C. Federal Proceedings 45, 1986

30. Vitamin E (1991, 1993, 2008, 2015) - Cataracts

Learn more about natural treatment for cataracts.

1991 Several studies connected significantly lower risk of developing cataracts along with oxidative stress in the eye tissue with higher vitamin E intake. The risk factor was about 40-45% less risk of developing the condition.

Study1: J.M. Robertson, et al, A possible role for vitamins C and E in cataract prevention, American Journal Clinical Nutrition, 1991

Study2: M.C. Leske MC, et al, The lens opacities case control study: risk factors for cataract. Archives of Ophthalmology, 1991

1993 Another study reported the same results. Researchers found that when levels of vitamin E were lower in blood plasma, the risk of developing both cortical and nuclear cataracts was about two times as great. Higher levels of vitamin E were associated with less likelihood of developing cataracts. Cortical cataracts involve the cortex of the lens, the outside edge of the lens while nuclear cataracts, the most common type of cataract, involve changes to the center of the lens.

Researchers: Vitale, et al.

Published: Epidemiology, May, 1993

2008 A very large 2008 study of over 35,000 American middle-aged women consisted of a 10 year survey of their dietary supplements and incidence of cataract. This study again found that vitamin E played an important role in preventing cataracts, but also that women who had more lutein, and zeaxanthin in their diet along with vitamin E were even less likely (18%) to develop cataracts.

Researchers: W. Christen

Published: Dietary carotenoids, vitamins C and E, and risk of cataract in women: a prospective study, Archives of Ophthalmology, January 2008

2015 A meta-analysis (a study of studies) looked at the ties between cataract development and vitamin E as researched in studies conducted up to 2014.

The studies that they looked at included samples of people of all ages, not only elderly patients and thus this meta analysis was not restricted to age related cataracts.

They found that levels of vitamin E in the diet, taken via supplemental vitamin E, and levels of vitamin E in the bloodstream were tied to lower risk of cataract in percentages that were statistically significant. As the levels of vitamin E dropped, the incidence of cataract increased.

Researchers: Y. Zhang, W. Jiang, Z. Xie, W. Wu, D. Zhang

Published: Vitamin E and risk of age-related cataract: a meta-analysis, Public Health Nutrition, October, 2015.

31. Vitamin E, C, (1997) alpha-lipoic acid and taurine

A 1997 study demonstrated that vitamins E and C, alpha-lipoic acid, and taurine appear to help protect the eye from lens damage which is caused by low level radiation. Bantseev, et al. Biochem Mol Biol Int 1997 Sept;42(6):1189-97.

See more information about cataracts

Celiac Disease

1. Xtra Info: Celiac Disease research bibliography - early research

These are earlier studies. Also see discussion of research on celiac disease

1. Srinivassan U, Leonard N, Jones E, et al. Absence of oats toxicity in adult coeliac disease. BMJ 1996;313:1300-1.
2. Jantauinen EK, Pikkarainen PH, Kemppainen TA, et al. A comparison of diets with and without oats in adults with celiac disease. N Engl J Med 1995;333:1033-7.
3. Greenberger JN, Isselbacher KJ. Disorders of absorption. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison's Principles of Internal Medicine, 14th ed. New York: McGraw-Hill, 1998, chapter 285.
4. Faulkner-Hogg KB, Selby WS, Loblay RH. Dietary analysis in symptomatic patients with coeliac disease on a gluten-free diet: the role of trace amounts of gluten and non-gluten food intolerances. Scand J Gastroenterol 1999;34:784-9.
5. Holmes GKT, Prior P, Lane MR, et al. Malignancy in coeliac disease-effect of a gluten free diet. Gut 1989;30:333-8.
6. Mora S, Barera G, Ricotti A, et al. Reversal of low bone density with a gluten-free diet in children and adolescents with celiac disease. Am J Clin Nutr 1998;67:477-81.
7. Mora S, Barera G, Beccio S, et al. Bone density and bone metabolism are normal after long-term gluten-free diet in young celiac patients. Am J Gastroenterol 1999;94:398-403.
8. McFarlane XA, Bhalla AK, Robertson DAF. Effect of a gluten free diet on osteopenia in adults with newly diagnosed coeliac disease. Gut 1996;39:180-4.
9. Baker PG, Read AE. Reversible infertility in male coeliac patients. BMJ 1975;2:316-7.
10. Sewell P, Cooke WT, Cox EV, Meynell MJ. Milk intolerance in gastrointestinal disorders. Lancet 1963;2:1132-5.
11. Haeney MR, Goodwin BJF, Barratt MEJ, et al. Soya protein antibodies in man: their occurrence and possible relevance in coeliac disease. J Clin Pathol 1982;35:319-22.
12. Mike N, Haeney M, Asquith P. Soya protein hypersensitivity in coeliac disease: evidence for cell mediated immunity. Gut 1983;24:A990.
13. Ament ME, Rubin CE. Soy protein-another cause of the flat intestinal lesion. Gastroenterology 1972;62:227-34.
14. Auricchio S, Follo D, de Ritis G, et al. Does breast feeding protect against the development of clinical symptoms of celiac disease in children? J Pediatr Gastroenterol Nutr 1983;2:428-33.
15. Udall JN, Colony P, Fritze L, et al. Development of gastrointestinal mucosal barrier. II. The effect of natural versus artificial feeding on intestinal permeability to macromolecules. Pediatr Res 1981;15:245-9.
16. Connon JJ. Celiac disease. In: Shils ME, Olson JA, Shike M, eds. Modern Nutrition in Health and Disease, 8th ed. Philadelphia: Lea & Febiger, 1994, 1062.
17. Crofton RW, Glover SC, Ewen SWB, et al. Zinc absorption in celiac disease and dermatitis herpetiformis: a test of small intestinal function. Am J Clin Nutr 1983;38:706-12.
18. Solomons NW, Rosenberg IH, Sandstead HH. Zinc nutrition in celiac sprue. Am J Clin Nutr 1976;29:371-5.
19. Rude RK, Olerich M. Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. Osteoporos Int 1996;6:453-61.
20. Russell RM, Smith VC, Multak R, et al. Dark-adaptation testing for diagnosis of subclinical vitamin-A deficiency and evaluation of therapy. Lancet 1973;2:1161-4.
21. Basha B, Rao S, Han ZH, Parfitt, AM. Osteomalacia due to vitamin D depletion: neglected consequence of intestinal malabsorption. Am J Med 2000;108(4):296-300.
22. O'Mahony S, Howdle PD, Losowsky MS. Review article: management of patients with non-responsive coeliac disease. Aliment Pharmacol Ther 1996;10:671-80 [review].
23. Hallert C, Astrom J, Walan A. Reversal of psychopathology in adult celiac disease with the aid of pyridoxine (vitamin B6). Scand J Gastroenterol 1983;18:299-304.
24. Patel RS, Johlin FC Jr, Murray JA. Celiac disease and recurrent pancreatitis. Gastrointest Endosc 1999;50:823-7.
25. Carroccio A, Iacono G, Montalto G, et al. Pancreatic enzyme therapy in childhood celiac disease. A double-blind prospective randomized study. Dig Dis Sci 1995;40:2555-60.

Central Serous Choroidopathy

1. Lutein (2012, 2014) & Central Serous Chorioretinopathy (CSR)

Learn more about central serous choroidopathy.

2014

Researchers have been investigating the effects of antioxidants in treating retinal conditions such as central serous choroidopathy (CSR) because many of these nutrients are helpful as therapies for similar retinal conditions.

Scientists wanted to evaluate the efficacy of lutein nutritional therapy as measured by both levels of lutein in blood plasma, and on the optical density of the retinal pigments in CSR patients. The latter was accomplished using standard autofluorescence spectrometry testing.

This was a placebo-controlled and double-blind study in which 20 patients with CSR were given 20mg daily lutein and 19 other CSR patients were given placebo.

Blood lutein levels and macular pigment density was measured at the beginning of the study period, after 1 month, and again after 4 months.

Blood lutein levels increased markedly after 1 month and after 4 months compared to controls, but the macular pigment densities did not improve significantly. But patients who initially had poor blood lutein levels avoid further thinning of the macular pigment density.

Researchers: M. Sawa, F. Gomi, et al.
Published: Effects of a lutein supplement on the plasma lutein concentration and macular pigment in patients with central serous chorioretinopathy, Investigative Ophthalmology & Visual Science, July, 2014.

2012

In another placebo-controlled study with similar results patients with CSR given high-dose antioxidants. The treated patients did not experience significant changes in visual acuity and macular pigment thickness, but the amount of leakage between tissues did decrease. Like the lutein study above, high-dose antioxidants appears to keep the condition from worsening emphasizing the importance of early diagnosis.

Researchers: M. Ratanasukon, et al.
Published: High-dose antioxidants for central serous chorioretinopathy; the randomized placebo-controlled study, BMC Ophthalmology, July, 2012.

2. Melatonin (2015) for Central Serous Chorioretinopathy (CSR)

Learn more about central serous choroidopathy (CSR).

Researchers investigated whether melatonin could have therapeutic benefit for patients with CSR. CSR is a condition characterized by rapid onset of blurry vision and other symptoms in one eye in men aged 20-50.

In this small study 8 patients with CSR were treated with melatonin for a month and 5 control patients were treated with placebo. Prior to the trial all of the patients were given standard vision acuity tests and the thickness of the center of the macula was measured.

After a month 7 out of 8 of the patients had improved vision according to standard tests. Three out of the 5 patients had complete resolution. There were no changes for the control group.

The improvements were in both better vision acuity and better macular thickness as measured through standard testing.

The researchers concluded that melatonin is both safe and effective as a treatment for this condition.

Researchers: A. J. Gramajo, G. E. Marquez, et al.
Published: Therapeutic benefit of melatonin in refractory central serous chorioretinopathy, Eye, August, 2015.

Choroidal Neovascularization

1. AREDS, AREDS2: (2001, 2006, 2013) Antioxidants & Choroidal Neovascularization

See more about preventing choroidal neovascularization.

AREDS, 2001

The original AREDS trial discovered that patients who have macular degeneration can somewhat lower the risk of the condition degenerating to the more severe wet macular degeneration, known as choroidal neovascularization (CNV) with supplementation of zinc and antioxidants.

The benefits of the nutrients were seen only in people who began the study at high risk for developing choroidal neovascularization, (advanced macular degeneration), and in that group those taking antioxidants and zinc had the lowest risk of developing advanced stages of AMD.

In advanced AMD in addition to drusen, patients have in one or both eyes, either:

A breakdown of light-sensitive cells and tissue in the central retinal area (advanced dry form); or
Abnormal, fragile blood vessels under the retina that leak fluid or bleed (advanced wet form)

The researchers found that antioxidant/zinc supplementation in patients with advanced dry macular degeneration or vision loss because of wet macular degeneration in a single eye had a 20% of having their condition worsen within five years compared to 28% of patients taking a placebo.

The formulation used in the AREDs study contained several antioxidant vitamins, which are nutrients that can help maintain healthy cells and tissues. They also contained zinc, which is an important mineral incorporated into many body tissues:

500 milligrams of vitamin C;
400 international units of vitamin E;
15 milligrams of beta-carotene;
80 milligrams of zinc as zinc oxide;
2 milligrams of copper as cupric oxide

It has been known from earlier studies that people with diets rich in green, leafy vegetables have a lower AMD risk, but it is hard to gain the therapeutic levels needed through diet alone. Therefore the supplements were needed.

The study also showed that people who take a daily multivitamin can lower the risk of vision loss by adding the same high levels of antioxidants and zinc as in the study.

Researchers: National Institutes of Health, National Eye Institute,
Published: Archives of Ophthalmology, October, 2001

AREDS2, 2006

The same researchers at NIH who performed the AREDS study in 2001 wanted to determine whether adding omega-3 fatty acids, lutein and zeaxanthin to the AREDS formulation (vitamins C & E, zinc & beta-carotene) would be of value for aging patients with eye disease. Because beta-carotene is counter-indicated for smokers, they were also investigating alternatives to that nutrient.

In AREDS2, a 5 year study involving more than 4000 patients, the revised recommended formulation, based on the new research concluded that the optimal combination was as follows:

500mg of vitamin C
400 IU vitamin E
2mg copper
25mg zinc (lower level)
1000mg of omega-3 fatty acids
beta-carotene deleted

The researchers concluded that the omega-3s did not improve the formulation, but because they are known to be helpful they are retained in the recommendations.

Researchers: National Institutes of Health, National Eye Institute

Published: 2006

AREDS update, 2013

This report further established the long-term value of these nutrients. Patients taking the formulation during the 5-year AREDS2 trial were 25-30% less likely to develop advanced macular degeneration. It further concluded that long term use of the AREDS2 formulation was safe and protective against advanced AMD.

Researchers: NEI Intramural Research Program with support from National Institute of Neurological Disorders and Stroke; the National Institute on Aging; the National Heart, Lung, and Blood Institute; the National Center for Complementary and Alternative Medicine; and the NIH Office of Dietary Supplements.

Published: JAMA Ophthalmology, May, 2013.

2. DHA (2012-13) and choroidal neovascularization

Learn more about choroidal neovascularization.

These studies looked at omega-3 fatty acids, specifically DHA and its effect on protection against macular degeneration.

DHA is concentrated in the retina of the eye and is modestly inversely related to AMD. The intake of fish, the food source of DHA, was also inversely related, with participants eating more fish having a lower rate of macular degeneration incidence.

2012

Researchers found that DHA could help prevent more advanced forms of retinal problems.

It is well known that the proper functioning of the retina gets worse with age. A substance, known as A2E, a component of the toxic material lipofuscin, accumulates in retinal pigment cells. Researchers analyzed the effect of giving DHA (docosahexaenoic acid) supplements to mice who had A2E in the cells of their retinas. This done of periods ranging from 1 to 18 months, and took into account the proportion of DHA versus fatty acids, and diets without DHA.

The scientists found that A2E accumulations were reduced, and was tied to better retina functioning for mice who already had retina degeneration, and slowed this limitation for mice with more advanced retina problems.

They concluded that DHA in the diet could have a broad preventative therapeutic effect.

Researchers: Blake Dornstauder, et al
Published: Investigations in Ophthalmology and Visual Science, April, 2012

2013 A randomized and double-blind research study assessed the effectiveness of DHA in preventing advanced, or wet, macular degeneration in which additional blood vessels grow behind the macula, forcing distortion. Over a three year period 55 to 85 year old patients who had early lesions of wet macular degeneration were given 840mg daily DHA and 270mg daily EPA (eicosapentaenoic acid), or an olive oil placebo.

The scientists found that wet macular degeneration incidence was markedly reduced in the patients who received DHA over the period, and who also showed a continued high EPA plus DHA index during that time.

Researchers: E.H.Souied, C. Delcourt, et al.
Published: Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: The Nutritional AMD Treatment 2 Study Ophthalmology February, 2013.

3. Exercise () and Choroidal Neovascularization

2016

In a long term Australian study 1990 to 1994 initial data was collected from almost 21,000 participants and graded according to the vigor of the exercise - e.g., walking, vigorous and non-vigorous exercise. Fifteen years later, from 2003 to 2007, retinal photographs were taken of the participants and were graded according to early, intermediate or advanced macular degeneration (choroidal neovascularization). The data was also adjusted according to the participants' age, gender, smoking habits, ethnic heritage, diet and alcohol use.

Exercise was associated with lower odds of intermediate and advanced AMD. After controlling for factors that could bias the results, there was evidence of improvement (related to gender). Frequent vigorous exercise was associated with a 22% decrease in the odds of intermediate AMD (95% CI 4% to 36%) in women, but no association was found for men. They concluded that further research will be helpful.

Researchers: M.B. McGuinness, et al,
Past physical activity and age-related macular degeneration: the Melbourne Collaborative Cohort Study, British Journal of Ophthalogy, October, 2016.

2006

Over a period of 15 years, researchers evaluated the visual health of nearly 4,000 participants. The study began in 1988-1990 and the participants were evaluated every five years.

Incidence of early, intermediate and advanced forms of AMD were determined by use of color photos of the retina. Physical activity during the 15 year period was assessed by self-reporting in questionnaires.

The researchers adjusted the data for age, gender, arthritis history, blood pressure, BMI, smoking habits and education. They found that people with an active lifestyle, with regular activity at least three times a week were less likely to develop the advanced form of macular degeneration, wet AMD. They did not find that physical activity levels were associated with the less severe forms of the condition.

Researchers: M.D. Knudtson, et al,
Published: Physical activity and the 15-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study, British Journal of Ophthalomogy, December, 2006.

4. Gut Bacteria (2016) & CNV

2016
Microbiota & High Fat Diet

The risk of developing advanced macular degeneration (choroidal neovascularization (CNV)) is greatly increased, especially for men, in the presence of obesity. Being overweight is the second most severe risk factor after smoking. In a study of over 21,000 people it was found that each increase in .1 in waist/hip ratio was associated with a 13% increase in the risk of developing macular degeneration.¹

However the mechanisms that cause this association are not strongly understood so researchers decided to investigate. Our ability to digest food and gain nutritional benefit from the food we eat depends on the ability of our digestive system to break down the food into nutrients. This takes place in the large and small intestines and rests on the health of the microbiota that lives in our gut.

But in the presence of fat molecules, the process is slowed or inhibited. People who are obese tend to have high-fat diets, and this inhibition on our healthy gut microbiota restricts the delivery of nutrients to the body and to the eyes and becomes a risk factor for AMD. Imbalances in the gut microbiota influence not only digestion but metabolism, toxins in bacterial cells, and the immune system's response.

Researchers find that gut imbalanced or maladapted gut microbiota increases the permeability of the gut resulting in chronic inflammation. And we know from other research² that increased inflammation is present in cases of advanced macular degeneration.

In this study the scientists started by looking at the link between high fat diets and CNV. In lab animals they found a clear association between excessive weight gain and CNV development.

Next they disassociated the weight gain factor from the imbalanced gut microbiota community by feeding normal weight animals with antibiotics to damage the gut microbiota. They examined the gut flora profile to establish that the microbiota had been negatively impacted.

They found that certain large molecules (mononuclear phagocytes that are known to contribute to CNV were increased in the imbalanced digestive systems of the mice, and that they promote inflammation.

Finally, they were able to determine that the high fat diets increase advanced macular degeneration (CNV) because the resulting imbalanced gut microbiota aggravated inflammation which in turn aggravated CNV.

Researchers: E.M. Andriessen, A.M. Wilson, et al,
Published: Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization, EMBO Molecular Medicine, December, 2016.

Footnotes

1. M. Adams, J. Simpson, et al., Abdominal obesity and age‐related macular degeneration, American Journal of Epidemiology, 2011.
2. Vinod P. Mitta, MD, MPH; et al, C-Reactive Protein and the Incidence of Macular Degeneration, JAMA Ophthalmology, 2013

5. Lutein & Zeaxanthin (2008, 2016): Choroidal Neovascularization

Learn more about the choroidal neovascularization.

Scientists have established that macular pigments are located in the retina. Lutein (in the periphery of the macula) and zeaxanthin (in the central area of the macula) make up these carotenoid macular pigments discussed in the following studies.

2016

This study focused on the role of macular pigment in which lutein, zeaxanthin and meso-zeaxanthin are highly concentrated and where they work to do a number of tasks in addition to filtering blue light. Lutein is the primary carotenoid in the periphery of the macula, zeaxanthin more toward the center, and meso zeaxanthin in the very center of the macula.

These carotenoids help vision in several ways.

Many studies have demonstrated that the three carotenoids improve recovery from macular degeneration, especially protecting against onset of late or advanced macular degeneration (wet AMD or choroidal neovascularization (CNV)), and reducing risk for those who are genetically pre-disposed towards the condition.
Lutein and zeaxanthin reduce glare discomfort and glare recovery time.
They improve the functioning of the macula through comprising the pigment layer which filters blue light.
They positively impact the speed at which the optic nerve transmits information to the rest of the brain.
Lutein levels have been found to improve vision adaption from light to dark and from dark to light.
Research also shows promising results between higher levels of the carotenoids and lower risk of diabetic retinopathy and retinopathy of prematurity.
There have been mixed results concerning the relationship of the carotenoids and cataracts.

Researchers: Veronica Castro Lima, et al.
Published: Macular pigment in retinal health and disease, International Journal of Retina and Vitreous, August, 2016.

2008

A longitudinal study substantiated earlier conclusions.

Over 10 years researchers evaluated the diets and antioxidant supplementation and the long-term risk of age-related macular degeneration in over 2400 patients.

Subjects with greater levels of lutein and zeaxanthin intake had a reduced risk of the advanced form of wet macular degeneration, and those patients with intake levels above the median level had a lower risk of soft drusen, the fatty deposits that are characteristic of AMD.

The researchers reported that high consumption of these nutrients through diet and/or supplementation significantly reduced the risk of developing macular degeneration. It also confirmed findings about other nutrients from the first AREDS study.

Researchers: J.S.L. Tan, J.J. Wang, V. Flood, E. Rochtchina, W. Smith, P. Mitchell, Centre for Vision Research, University of Sidney, Australia
Published: Dietary Antioxidants and the Long-term Incidence of Age-Related Macular Degeneration: The Blue Mountains Eye Study, Ophthalmology, February 2008

6. Resveratrol (2015) & Neovascularization

Learn more about choroidal neovascularization.

2022 Although earlier research supported use of moderate red wine use, newer research reports that the many detriments outweigh the benefits.^{1, 2, 3} Instead, we recommend intake of resveratrol through grapes, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.

2015

In a number of health conditions a consequence, often due to low nutrient and/or oxygen levels available to tissue, is that new blood vessels form in an attempt to supply the lack. This new growth is called neovascularization.

In vision the most commonly known example is in advanced or wet macular degeneration in which additional blood vessels grow behind the macula in an attempt to supply more nutrients to the retina. The condition is known as choroidal neovascularization. The consequence is that the cells of the retina become distorted and vision deteriorates.

Note: A number of approaches address the problem - the most important being prevention. See macular support information..

Researchers wanted to determine whether resveratrol, a phytonutrient that acts like an antioxidant, could be helpful in reducing neovascularization.

In the lab human pigment cells were treated with various concentrations of resveratrol and then grown in an environment deprived of adequate oxygen. The results were evaluated by measuring specific biomarkers which are indicative of neovascularization.

The resveratrol significantly inhibited the tell-tale biomarkers; the degree of inhibition depended on dosage.

Additionally, mice with choroidal neovascularization were given resveratrol orally. Similarly, resveratrol inhibited neovascularization depending on dosage.

Researchers: C.S. Lee, E.Y. Choi, et al
Published: Resveratrol Inhibits Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Pathological Neovascularization, Yonsei Medical Journal, November, 2015.

Another study looked at the mechanics of how resveratrol reduces neovascularization. The gene SIRT1 regulates growth of new blood cells. The researchers wanted to evaluate how resveratrol, which activates SIRT1, interacted with signaling pathways in the body that stimulate growth of new blood vessels. They found that resveratrol inhibited neovascularization caused by lab-controlled oxygen-deprived cell tissue. It also inhibited the secretion of a signaling protein (VEGF) that stimulates neovascularization in cell-tissue compromised by cobalt chloride. Finally, it reduced the over activity of other VEGF-related biochemical changes and reactions.

These results suggest not only the value of resveratrol, but the value of targeting the SIRT1 gene in treating choroidal neovascularization.

Researchers: H. Zhang, S. He, et al
Published: SIRT1 mediated inhibition of VEGF/VEGFR2 signaling by Resveratrol and its relevance to choroidal neovascularization, Cytokine, December, 2015.

Footnotes
1. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, et al. (2018). Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. Apr 14;391(10129):1513-1523.
2. Biddinger KJ, Emdin CA, Haas ME, Wang M, Hindy G, et al. (2022). Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022 Mar 1;5(3):e223849
3. Goding Sauer A, Fedewa SA, Bandi P, Minihan AK, Stoklosa M, et al. (2021). Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiol. Apr;71(Pt A):101893.

Chronic Fatigue

1. Xtra Info: Chronic Fatigue Syndrome bibliography - early research

Also see discussion of chronic fatigue syndrome (CFS) and research

1. De Lorenzo F, Hargreaves J, Kakkar VV. Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome. Clin Auton Res 1997;7:185-90.
2. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. Br Med J 1997;314:1647-52.
3. McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of chronic fatigue syndrome. Sports Med 1996;21:35-48 [review].
4. Blackwood SK, MacHale SM, Power MJ, et al. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry 1998;65:541-6.
5. LaManca JJ, Sisto SA, DeLuca J, et al. Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome. Am J Med 1998;105:59S-65S.
6. Paul L, Wood L, Behan WM, et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol 1999;6:63-9.
7. Clapp LL, Richardson MT, Smith JF, et al. Acute effects of thirty minutes of light-intensity, intermittent exercise on patients with chronic fatigue syndrome. Phys Ther 1999;79:749-56.
8. Shaw DL, Chesney MA, Tullis IF, Agersborg HPK. Management of fatigue: a physiologic approach. Am J Med Sci 1962;243:758-69.
9. Crescente FJ. Treatment of fatigue in a surgical practice. J Abdom Surg 1962;4:73.
10. Hicks J. Treatment of fatigue in general practice: a double-blind study. Clin Med 1964;Jan:85-90.
11. Formica PE. The housewife syndrome: treatment with the potassium and magnesium salts of aspartic acid. Curr Ther Res 1962;Mar:98-106.
12. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3:927-36.
13. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277-83.
14. Lawhorne L, Rindgahl D. Cyanocobalamin injections for patients without documented deficiency. JAMA 1989;261:1920-3.
15. Gaby AR. Literature Review & Commentary. Townsend Letter for Doctors & Patients 1997;Feb/Mar:27 [review].
16. Lapp CW, Cheney PR. The rationale for using high-dose cobalamin (vitamin B12). CFIDS Chronicle Physicians' Forum 1993;Fall:19-20.
17. Heap LC, Peters TJ, Wessely S. Vitamin B status in patients with chronic fatigue syndrome. J R Soc Med 1999;92:183-5.
18. Kuratsune H, Yamaguti K, Takahashi M, et al. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 1994;18(suppl 1):S62-7.
19. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsycholbiol 1997;35:16-23.
20. Forsyth LM, Preuss HG, MacDowell AL, et al. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol 1999;82:185-91.
21. Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991;337:757-60.
22. Howard JM, Davies S, Hunnisett A. Magnesium and chronic fatigue syndrome. Lancet 1992;340:426.
23. Clague JE, Edwards RH, Jackson MJ. Intravenous magnesium loading in chronic fatigue syndrome. Lancet 1992;340:124-5.
24. Gantz NM. Magnesium and chronic fatigue. Lancet 1991;338:66 [letter].
25. Hinds G, Bell NP, McMaster D, McCluskey DR. Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome. Ann Clin Biochem 1994;31(Pt. 5):459-61.
26. Kuratsune H, Yamaguti K, Sawada M, et al. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med 1998;1:143-6.
27. De Becker P, De Meirleir K, Joos E, et al. Dehydroepiandorsterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Horm Metab Res 1999;31:18-21.
28. Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA 1995;274:961-7.
29. Whorwood CB, Shepard MC, Stewart PM. Licorice inhibits 11beta-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology 1993;132:2287-92.v 30. Baschetti R. Chronic fatigue syndrome and liquorice. New Z Med J 1995;108:156-7 [letter].
31. Brown D. Licorice root-potential early intervention for chronic fatigue syndrome. Quart Rev Natural Med 1996;Summer:95-7.
32. Price JR, Couper J. Cognitive behavior therapy for adults with chronic fatigue syndrome. Cochrane Database Syst Rev 2000;(2):CD001027 [review].

Colds and Flu

1. Garlic (2001) Colds & Flu

Learn more about colds and flu.

Garlic may be helpful in preventing colds and flu due to its anti-bacterial properties. One researcher thinks that taking garlic may reduce chances of catching a cold by half.

In a 2001 study in England, 146 volunteers took either a placebo or capsule of an allicin-containing garlic supplement daily for 90 days during the winter. 24 colds were recorded among those taking the supplement, compared to 65 amongst those taking the placebo.

The study also found that those taking the supplement who did catch a cold were more likely to make a speedier recovery than those taking the placebo and the chances of re-infection following a cold were significantly reduced.

Researcher: Peter Josling, director the Garlic Centre in East Sussex.

2. Vitamin D (1994-2017) & Flu

Learn more about preventing colds and flu.

2017

The researchers noted that influenza and similar illnesses have a strong seasonal association and that the role of vitamin is widely accepted to be important in defending against flu.

They investigated how UV radiation and vitamin D can affect such illness. They compared how the body's immune system, through its molecular and cellular structure acts on pathogens and the process of immunity.

Both UV radiation and vitamin D have an effect on creating antimicrobial agents in the body (peptides) and how they affect the ability of the immune system to adapt to new pathogens.

They found that vitamin D has a larger effect compared to UV radiation. This is because it modulates the response of the body through a wide range of tissues.

Researchers: Abhimanyu, A.K. Coussens
Published: The role of UV radiation and vitamin D in the seasonality and outcomes of infectious disease, Photochemical and Photobiological Sciences, January, 2017.

2016

Vitamin D has a strong capacity to strengthen the immune system and resistance to influenza by preventing the release to too-large amounts of the biochemicals that attract white blood cells to infectious locations in the body. Staying indoors too much lowers vitamin D levels so vitamin D supplementation is more important in the winter and for those who spend much time indoors.

Researchers: B. Acharya, K. Thapa
Published: Journal of Napal Research Council, January 2016

2011 - D boosts the immune response

In this study the researchers wanted to know whether Vitamin D helped boost the bodies' immune response. In the lab, they found that gingival cells that were treated with Vitamin D displayed an improved ability to produce an endogenous antibiotic that was able to kill more bacteria than untreated cells.

Researchers: L. McMahon, K. Schwartz, O. Yilmaz, E. Brown, L. K. Ryan, G. Diamond.

Published: Vitamin D-Mediated Induction of Innate Immunity in Gingival Epithelial Cells. Infection and Immunity, 2011

2009

Researchers investigated the relationship between vitamin D levels in the body and respiratory tract infections and the role of vitamin D in preventing illness.

Vitamin D supports general immune system health by increasing production of anti-microbial peptides which are biochemicals found within different kinds of white blood cells and keratinocytes. Vitamin D supports the ability of the immune system to adapt to invading microbes, and helps to maintain the balance of T-helper cells. T-helper cells are an essential part of the immune system and its adaptive response. They stimulate production of antibodies to fight illness.

It's easily noticed that sickness is more common in the winter when there is less sunlight and the body creates less vitamin D naturally. Researchers evaluating health of almost 19,000 children and adults found higher levels of vitamin D in the body are associated with lower rates of respiratory tract infections.

They found that 24% of patients with low vitamin D levels (25-OHD levels) had recent respiratory tract infections while only 17% of patients with high vitamin D levels had respiratory tract infections.

The researchers commented on a number of other studies which marked an association between higher levels of vitamin D consumption with lower rates of respiratory tract infections. These included in young Finnish solders (Laaski,2007), children (Linday, 2004 and Rehman, 1994), postmenopausal women (Aloia, 2007). They also noted that patients with tuberculosis had low vitamin D levels (iu, 2006).

The full article is here.

Researchers: A.A. Ginde, J.M. Mansbach, et al,
Published: Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey, Archives of Internal Medicine, February, 2009

Computer Eye Strain

1. AOA (2007) Advises Daily Computer Users of the Risk of Computer Vision Syndrome

Learn more about computer eye strain

Americans who use computers daily should be aware of the risk of computer vision syndrome (CVS), more commonly known as computer eye strain, which gives rise to dry eyes, eye strain, neck and back pain, light sensitivity and fatigue. These symptoms can result from individual visual problems, poor work station configuration or improper work habits.

In responses to the American Optometry Association's (AOA) 2007 Eye-Q survey of 1,005 Americans 18 years and older, it was found that most people (82%) frequently work with a computer or a handheld electronic device and 42% spent three+ hours a day doing so. Most Americans (78%) do not have their computer monitor positioned at the correct height (below eye level).

Pre-existing uncorrected vision problems like hyperopia and astigmatism, inadequate eye focusing or eye coordination abilities and age-related eye issues may contribute to CVS, and the constant refocusing effort required while working at a computer stresses the eye muscles, affecting individuals' comfort and productivity.

After prolonged computer or handheld device use, subjects experienced:

41% - eye strain
45% - neck or back pain

While many of these symptoms are temporary, some may continue experiencing visual problems, such as such as blurred distance vision, even after computer work has stopped. Yet only 11% of respondents said that they currently use special computer glasses or computer screen filters to help reduce glare and discomfort.

Also see Glaucoma warning for computer users
See more information on care and prevention of computer eye strain.
And related, see information on care and treatment of Dry Eyes
2015 Eye-Q Survey Results

2. Astaxanthin (2002) & Computer Eyestrain

Learn more about computer eye strain.

2002

Researchers evaluated the effects of astaxanthin on several markers used to identify computer vision syndrome and eye health. These are accommodation (the ability of the eye to adjust to changes in distance), critical flicker fusion (the ability to perceive flickering light as a steady color), and pattern visual evoked potential (the brain's response to perceiving light). People who worked daily at computers were the subjects and received astaxanthin. Controls received no supplements or placebo. As controls, 13 non-VDT workers received no supplementation (Group A). Twenty-six VDT workers were randomized into 2 groups: Group B consisted of 13 subjects who received oral astaxanthin, 5 mg/day, for 4 weeks, and Group C consisted of 13 subjects who received an oral placebo, 5 mg/day, for 4 weeks. No significant difference in age was noted among the 3 groups. A double-masked study was designed in Groups B and C. Accommodation amplitude in Group A was 3.7± 1.5 diopters. Accommodation amplitudes (2.3±1.4 and 2.2±1.0 diopters) in Groups B and C before supplementation were significantly (p<0.05) lower than in Group A. Accommodation amplitude (2.8±1.6 diopters) in Group B after astaxanthin treatment was significantly (p<0.01) larger than before supplementation, while accommodation amplitude (2.3±1.1 diopters) in Group C after placebo supplementation was unchanged. The CFFs and amplitude and latency of P100 in PVEP in Group A were 45.0±4.2 Hz, 6.5±1.8μV, and 101.3±6.5 msec, respectively. The CFFs in Groups B and C before supplementation were significantly (p<0.05) lower than in Group A. The CCFs in Groups B and C did not change after supplementation. Amplitudes and latencies of P100 in PVEP in Groups B and C before supplementation were similar to those in Group A and did not change after supplementation. Findings of the present study indicated that accommodation amplitude improved after astaxanthin supplementation in VDT workers.

3. Eye Fatigue (2002-2009 Studies) Reducing with Astaxanthin

A number of research studies show the benefit of supplementing with Astaxanthin in reducing asthenopia (eye fatigue), computer eye strain and related symptoms.

2009

A study looking at the effects of nutrients on lifestyle-related eye problems (such as macular degeneration, aggravated by the blue light from electronic devices) pointed out that astaxanthin is one of the carotenoids that are valuable in reducing inflammation that causes such conditions (Ishida, 2009).

2006

Iwasaki & Tawara (2006) also confirmed the same tendencies of subjective eye fatigue complaints in a randomized double-blind placebo controlled double-crossover study.

2005

Furthermore, questionnaire results obtained by Shiratori et al., (2005) and Nagaki et al., (2006), also confirmed the previous findings that astaxanthin supplementation at 6 mg for 4 weeks improved symptoms associated with tiredness, soreness, dryness and blurry vision.

A study by Takahashi & Kajita (2005), also demonstrated that astaxanthin attenuates induced-eye fatigue, as opposed to treating eye fatigue, which suggests prevention rather than treatment. Astaxanthin treated groups (asthenopia negative) were able to recover quicker than the control group after heavy visual stimulus.

2004

A study by Nakamura (2004), demonstrated significant improvements in reducing asthenopia and positive accommodation for the 4 mg (p<0.05) and 12 mg (p<0.01) groups. However, it was not until Nitta et al., (2005), who established the optimum daily dose at 6 mg (n=10) for a period of 4 weeks by comparing eye fatigue using a visual analogue scale (VAS) based questionnaire and accommodation values. Overall, the 6 mg group improved significantly better at week 2 and 4 of the test period.

2002

A study by Nagaki, 2002, demonstrated that subjects (n=13) who received 5 mg astaxanthin per day for one month showed a 54% reduction of eye fatigue complaints.

In a sports vision study (Sawaki, 2002), researchers demonstrated that depth perception and critical flicker fusion had improved by 46% and 5% respectively on a daily dose of 6 mg (n=9). The effect of astaxanthin on visual performance prompted a number of other clinical studies to evaluate the optimum dose and identify the mechanism of action.

See a additional research on eye fatigue.

Sources

Nagaki, Y, Hayasaka, S, Yamada, T, Hayasaka, Y, Sanada, M, et al. (2002). Effects of astaxanthin on accommodation, critical flicker fusions, and pattern evoked potential in visual display terminal workers. J Trad Med, 19(5):170-173.
Nakamura, A., Isobe, R., Otaka, Y., Abematsu, Y., Nakata, D., et al. (2004). Changes in Visual Function Following Peroral Astaxanthin. Japan J Clin Opthal, 58(6):1051-1054.
Takahashi, N., Kajita, M. (2005). Effects of astaxanthin on accommodative recovery. J Clin Therap Med, 21(4):431-436.
Ishida, S., (2009). Lifestyle-related diseases and anti-aging ophthalmology: suppression of retinal and choroidal pathologies by inhibiting renin-angiotensin system and inflammation. Nippon Ganka Gakkai Zasshi, Mar;113(3):403-22
Sawaki, K., et al. (2002). Sports performance benefits from taking natural astaxanthin characterized by visual acuity and muscle fatigue improvement in humans. J Clin Ther Med, 18(9):1085-1100.

4. Lutein (2009) and Computer Eye Strain

Learn more about computer eye strain

This study noted improvements, after taking lutein in visual performance in 37 (age 22-30) subjects who had long-term exposure to computer monitors after taking lutein in a 6mg or 12mg daily dose. The subjects were observed following 12 weeks of lutein supplementation. Three groups were measured: 12 patients taking 6mg of lutein daily, 13 patients taking 12mg of lutein daily, and 12 patients taking a placebo. There was a trend towards improved visual acuity and measures of contrast sensitivity in the subjects taking lutein versus the placebo group. The researchers reported that the 12mg level of lutein consumption produced statistically significant beneficial effects on the visual performance. There was no change in sensitivity to glare, but there was marked improvement in sensitivity to visual contrast.

L. Ma, X. M. Lin, et al. (2009). A 12-week lutein supplementation improves visual function in Chinese people with long-term computer display light exposure, British Journal of Nutrition, July

Another study found that, combined with zeaxanthin and black currant seed oil, lutein helps protect the retina and eye lens from damage by filtering out light, and it has been shown to help reduce eyestrain.

Yagi, A., Fujimoto, K., Michihiro, B., Goh, D., Tsi, H. (2009). The effect of lutein supplementation on visual fatigue: A psychophysiological analysis. Applied Ergonomics, Nov;40(6):1047-54.

5. Omega-3 Fatty Acids (2015) & Computer Eye Syndrome

Learn about managing computer eye strain.

2016

This study recommended 1,000mg-2,000mg per day dosage for omega-3 in treating dry eye syndrome (one of the symptoms of computer eyestrain).²
2015

In order to evaluate the efficacy of omega-3 fatty acids in treating computer eye syndrome, researchers used standard measures of dry eye symptoms - the Schirmer test, the time it takes the tear film to degrade, and conjunctival impression cytology, which is a test to evaluate the surface cells of the surface of the eye. ¹

Almost 500 patients who had been using computer for at least 3 hours a day for at least a year were randomly divided into a test group and a control group. The control group was given capsules containing olive oil. The test group were given capsules containing 180mg EPA and 120mg DHA.

After 3 months there was a distinct difference in the test scores demonstrating that oral omega-3s are helpful for dry eye symptoms that result from computer eye strain.¹

Another study with older women showed reduced risk of dry eye syndrome with a high dietary intake of omega-3 fatty acids.³

1. Bhargava, R., Kumar, P., Phogat, H., Kaur, A., Kumar, M. (2015). Oral omega-3 fatty acids treatment in computer vision syndrome related dry eye, Con Lens Ant Eye, Jun;38(3):206-10.
2. Gatell-Tortajada, J. (2016). Oral supplementation with a nutraceutical formulation containing omega-3 fatty acids, vitamins, minerals, and antioxidants in a large series of patients with dry eye symptoms: results of a prospective study. Clin Interv Aging, May 19;11:571-8.
3. Ribelles, A., Galbis-Estrada, C., Parras, M.A., Vivar-Llopis, B. Marco-Ramirez, C., et al. (2015). Ocular Surface and Tear Film Changes in Older Women Working with Computers, Biomed Res Int, 2015:467039.

6. Zeaxanthin (2002, 2018) & UV / Blue Light Protection
Learn more about computer eye strain.

2018

One difficulty in testing whether the carotenoids are effective in protecting against blue light has been that mice, most commonly used in this sort of testing, do not have carotenoids in their retinas. Researchers were able to genetically create a mouse model that does require carotenoids for blue light protection and thus were able to establish that these nutrients do assist the eye in protecting against blue light and UV radiation.

Widjaja-Adhi, Mak, Ramkumar, S., and von Lintig, J. (2018). Protective role of carotenoids in the visual cycle. Faseb J., Jun 8:fj201800467R.

Another study also reports that the carotenoids such as zeaxanthin protect the eye through both their antioxidant capacity which prevents blue light and UV radiation (phototoxic) damage.

Madhavan, J., Chandrasekharan, S., Priya, M.K., Godavarthi, A. (2018). Modulatory Effect of Carotenoid Supplement Constituting Lutein and Zeaxanthin (10:1) on Anti-oxidant Enzymes and Macular Pigments Level in Rats. Pharmacogn Mag, Apr-Jun;14(54):268-274.

2002

Researchers report that zeaxanthin is one of the important carotenoids that increase macular density, which is linked to protecting the macula from the damage caused by blue light and UV radiation. It accomplishes this by absorbing blue light that comes in through the lens. The macula in primates is colored yellow due to the presence of lutein and zeaxanthin.

Krinksy, N.I., Landrum, J.T., Bone, R.A. (2003). Biologic mechanisms of the protective role of lutein and zeaxanthin in the eye. Annu Rev Nutr, 23:171-201.

Crohn's Disease

1. Xtra Info: Crohn's Disease Bibliography - Early Research
Also see discussion of Crohn's disease and research.

1. Mayberry JF, Rhodes J. Epidemiological aspects of Crohn's disease: a review of the literature. Gut 1984;886-99.
2. Heaton KW, Thornton JR, Emmett PM. Treatment of Crohn's disease with an unrefined-carbohydrate, fibre-rich diet. BMJ 1979;2(6193):764-6.
3. Brandes JW, Lorenz-Meyer H. Sugar free diet: a new perspective in the treatment of Crohn disease? Randomized, control study. Z Gastroneterol 1981;19:1-12.
4. Shoda R, Masueda K, Yamato S, Umeda N. Epidemiologic analysis of Crohn's disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn's disease in Japan. Am J Clin Nutr 1996;63:741-5.
5. Riordan AM, Hunter JO, Cowan RE, et al. Treatment of active Crohn's disease by exclusion diet: East Anglian Multicentre Controlled Trial. Lancet 1993;342:1131-4.
6. Alic M., Baker's yeast in Crohn's disease-can it kill you? Am J Gastroenterol 1999;94:1711 [letter/review].
7. Wantke F, Gotz M, Jarisch R. Dietary treatment of Crohn's disease. Lancet 1994;343:113 [letter].
8. O'Morain C, Segal AW, Levi AJ. Elemental diet as primary treatment of acute Crohn's disease: a controlled trial. Br Med J (Clin Res Ed) 1984;288:1859-62.
9. Gorard DA, Hunt JB, Payne-James JJ, et al. Initial response and subsequent course of Crohn's disease treated with elemental diet or prednisolone. Gut 1993;34:1198-202.
10. Teahon K, Pearson M, Levi AJ, Bjarnason I. Practical aspects of enteral nutrition in the management of Crohn's disease. JPEN J Parenter Enteral Nutr 1995;19:365-8.
11. Raouf AH, Hildrey V, Daniel J, et al. Enteral feeding as sole treatment for Crohn's disease: controlled trial of whole protein v amino acid based feed and a case study of dietary challenge. Gut 1991;32:702-7.
12. Rigaud D, Cosnes J, Le Quintrec Y, et al. Controlled trial comparing two types of enteral nutrition in treatment of active Crohn's disease: elemental versus polymeric diet. Gut 1991;32:1492-7.
13. Park RH, Galloway A, Danesh BJ, et al. Double-blind controlled trial comparing elemental and polymeric diets as primary therapy in active Crohn's disease. Eur J Gastroenterol Hepatol 1991;32:1492-7.
14. McDonald PJ, Fazio VW. What can Crohn's patients eat? Eur J Clin Nutr 1988;42:703-8.
15. Gaby AR. Commentary. Nutr Healing 1998;January:1,10-1 [review].
16. Persson PG, Ahlbom A, Hellers G. Diet and inflammatory bowel disease: a case-control study. Epidemiology 1992;3:47-52.
17. Cottone M, Rosselli M, Orlando A, et al. Smoking habits and recurrence in Crohn's disease. Gastroenterol 1994;106:643-8.
18. Leichtmann GA, Bengoa JM, Bolt MJG, Sitrin MD. Intestinal absorption of cholecalciferol and 25-hydrocycholecalciferol in patients with both Crohn's disease and intestinal resection. Am J Clin Nutr 1991;54:548-52.
19. Harris AD, Brown R, Heatley RV, et al. Vitamin D status in Crohn's disease: association with nutrition and disease activity. Gut 1985;26:1197-203.
20. Driscoll RH, Meredith SC, Sitrin M, Rosenberg IH. Vitamin D deficiency and bone disease in patients with Crohn's disease. Gastroenterol 1982;83:1252-8.
21. Vogelsang H, Ferenci P, Resch H, et al. Prevention of bone mineral loss in patients with Crohn's disease by long-term oral vitamin D supplementation. Eur J Gastroenterol Hepatol 1995;7:609-14.
22. Mate J, Castanos R, Garcia-Samaniego J, Pajares JM. Does dietary fish oil maintain the remission of Crohn's disease: a case control study. Gastroenterology 1991;100:A228 [abstract].v 23. Belluzzi A, Brignola C, Campieri M, et al. Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease. N Engl J Med 1996;334:1557-60.
24. Lorenz R, Weber PC, Szimnau P, et al. Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease-a randomized, placebo-controlled, double-blind cross-over trial. J Intern Med Suppl 1989;225:225-32.
25. Lorenz-Meyer H, Bauer P Nicolay C, et al. Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn's disease. A randomized controlled multicenter trial. Study Group Members (German Crohn's Disease Study Group). Scand J Gastroenterol 1996;31:778-85.
26. Belluzzi A, Brignola C, Campieri M, et al. Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients. Dig Dis Sci 1994;39:2589-94.
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Diabetes Mellitus

1. Alpha Lipoic Acid (2006) & Diabetes Mellitus
Learn more about diabetes.

2011

In this study the researchers evaluated the effectiveness and safety of alpha lipoic acid function in protecting against nerve damage in diabetic patients.

The 4-year, double-blind, randomized study assessed 460 diabetic patients with mid to moderate nerve damage as a result of their diabetic condition.

The researchers found that, while ALA did not produce results in one goal of the study (NIS, NIS-LL, and 7 neurophysiologic tests), it did result in a significant improvement of nerve damage impairments and prevented further degradation. In addition it was well tolerated.

Researchers: Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schutte K, Dyck PJ., Institute for Clinical Diabetology, German Diabetes Center at the Heinrich Heine University, Germany
Published: Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial, Diabetes Care, September, 2011

2006

Researchers evaluated whether oral alpha lipoic acid would improve insulin sensitivity in type 2 diabetic patients.

The researchers treated 12 patients over four weeks, and 12 subjects with normal glucose tolerance served as a control group. After four weeks, the insulin sensitivity of the diabetics was significantly improved (M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min (mean+/-sD), p<0.01; and IsI from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per mIU/l x 100 (mean+/-sD), p<0.05.) The difference was not significantly different between the treated patients and the control group after the end of the period.

Researchers: Kamenova P., et al,
Published: Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid, Hormones (Athens). October, 2006

2. Bilberry (2017) & Diabetes
Learn more about diabetes.

2017

Scientists have been exploring the multiple benefits of bilberry (vaccinium myrtillus L.) for many years. The herbal extracts of bilberry have been found to beneficial in:

reducing inflammation,

reducing oxidative stress,

reducing cancerous lesions,

protecting the nervous system,

protecting the cardiovascular system, and

reducing metabolic syndrome (implicated in type 2 diabetes)

These researchers evaluated the ability of bilberry extracts to inhibit enzymes that convert starches into sugars. Part of the problem of type 2 diabetes is that the body is unable to process sugar, and so the actions of these enzymes becomes important.

First, they determined total phenolic content by spectroanalysis and the phenolic acid composition of the extracts. The ability of the extracts to inhibit certain enzymes was evaluated.

They found that the content of phenolic compounds varied:

from 1299.60 mg to 510.88 mg GAE/100 g for organic extracts,

and from 453.63 mg to 290.83 mg GAE/100 g for aqueous extracts.

They found that the major phenolic acids present, gallic acid and chlorogenic acid prevailed. In addition methanol and aqueous extracts were found which are effective inhibitors of a-glucosidase, an enzyme that converts starch to sugar.

The researchers concluded that the ability of these extracts to inhibit a-glucosidase presents an opportunity for type 2 diabetics to manage, through diet, their glycaemic levels.

Researchers: D. Karcheva-Bahchevanska, P. Lukova, et al
Published: Effect of Extracts of Bilberries (Vaccinium myrtillus L.) on Amyloglucosidase and a-Glucosidase Activity, Folia Medica, June 2017.

3. Diabetes Mellitus (2001 - 2006) Research
Learn more about diabetes
.

Androne L, Gavan NA, Veresiu IA, Orasan R. In vivo effect of lipoic acid on lipid peroxidation in patients with diabetic neuropathy. In Vivo. 2000;14(2):327-330.

Melhem MF, Craven PA, Derubertis FR. Effects of dietary supplementation of alpha-lipoic acid on early glomerular injury in diabetes mellitus. J Am Soc Nephrol. 2001;12:124-133.

Melhem MF, Craven PA, Liachenko J, et al. Alpha-lipoic acid attenuates hyperglycemia and prevents glomerular mesangial matrix expansion in diabetes. J Am Soc Nephrol. 2002;13:108-116.

Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition. 2001;17(10):888-895.

Ziegler D, Ametov A, Barinov A, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: The SYDNEY 2 trial. Diabetes Care. 2006;29:2365-70.

4. Diet, Antioxidants (2016) & Diabetes Mellitus
Learn more about support for diabetes and diabetic retinopathy.

Researchers have reported that chronic inflammation in the body is a central cause of many health conditions, especially diabetes, which is one of the four leading causes of premature death.

The diet generally consumed by Westerners is high in red meat, high-fat dairy, refined sugars and grains and refined carbohydrates (as opposed to long-chain carbohydrates such as multi-grain cereal). The Mediterranean diet however, is high in whole grains, fish, vegetables (especially green vegetables) and fruit, along with low alcohol consumption and use of olive oil. This diet is associated with lower levels of inflammation in the body.

Researchers wanted to investigate the relationship between high inflammation levels in the body, indicated by the Dietary Inflammatory Index (DII) and premature mortality. Researchers investigated the diets and health of more than 8089 subjects to see whether such a relationship existed and to, in addition, see whether antioxidants would be helpful in reducing inflammation.

They conducted a random, placebo-controlled, double-blind study in which the subjects received low doses of antioxidants or a placebo over an eight year period. The subjects were aged 43 to 55 years old and their health was followed for an additional five years after the trial ended.

The subjects who had high inflammation levels had a higher death rate from heart disease or cancer compared to normal averages.

The subjects who received antioxidants did not have the same high death rate.

Researchers: L. Graffouillere, M. Deschausaux, et al.

Published: Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial, American Journal of Clinical Nutrition, March, 2016.

5. Exercise (2012) & Diabetes
Learn more about Diabetes mellitus

A long term study of 1826 patients examined the effect of exercise on their likelihood of developing diabetes. The study participants did not have either diabetes or cardiovascular problems at the onset of the study.

Over five years of followup, the researchers measured the amount of activity the of the participants by monitoring the number of steps they took during the day. The people with in the lowest 1/4 of the range, with less than 3,500 steps per day, had a much higher likelihood of developing diabetes and 243 new cases of diabetes were identified in that group. When the remainder of the group's activity was measured and compared to the lowest 1/4 - it was determined that the group with the lowest amount of activity had a 75% chance of developing diabetes.

Researchers: Amanda M. Fretts, PHD, Barbara V. Howard, PHD, Barbara McKnight, PHD, Glen E. Duncan, PHD, Shirley A.A. Beresford, PHD, Darren Calhoun, PHD, Andrea M. Kriska, PHD, Kristi L. Storti, PHD and David S. Siscovick, MD

Published: Modest Levels of Physical Activity Are Associated With a Lower Incidence of Diabetes in a Population With a High Rate of Obesity, Diabetes Care August 2012 vol. 35 no. 8 1743-1745

6. Ginseng (1995) & Diabetes
Learn more about diabetes.

Researchers examined the effectiveness of ginseng for non-insulin dependent patients.

This was a double-blind, placebo-controlled study of thirty six patients who had recently been diagnosed as non-insulin dependent were treated for 8 weeks with 100 or 200mg panax ginseng daily. The researchers evaluated the results via psychophysical testing, glucose and fat levels in blood, body weight and amino terminal propeptide concentration.

The study found better fasting blood-glucose levels, improved psychophysical performance, and better mood. Better hemoglobin A1C values also result from the 200mg dosage. The placebo reduced body weight and altered the serum fats, but did not change fasting blood glucose.

Editors Note: A 2011 study using Korean red ginger with 15 overweight patients and for only 30 days did not find the same result.

Researchers: Sotaniemi EA, Haapakoski E, Rautio A., Department of Internal Medicine, University of Oulu, Finland.

Published: Ginseng therapy in non-insulin-dependent diabetic patients, Diabetes Care. 1995 Oct;18(10):1373-5.

7. Gymnema Sylvestre (2010) & Diabetes
Learn more about diabetes.

The researchers wanted to evaluate the traditional herb Gymnema sylvestre (GS) as a possible anti-diabetic agent, which has been used in India for centuries.

They used a high molecular weight GS extract with type II diabetic patients, looking at plasma insulin, glucose, and C-peptide, for a 60 day period. They found marked increased in circulating insulin and C-peptide which were tied to reductions in fasting and after-meals blood glucose.

They also did in vitro measurements with human islets of Langerhans which also stimulated insulin secretion from the human beta cells.

They concluded that these in vivo and in vitro examinations indicated that the herb may be an alternative therapy for diabetic hyperglycemia.

Researchers: Al-Romaiyan A, Liu B, Asare-Anane H, Maity CR, Chatterjee SK, Koley N, Biswas T, Chatterji AK, Huang GC, Amiel SA, Persaud SJ, Jones PM., Diabetes Research Group, King's College London, London, SE1 1UL, UK

Published: A novel Gymnema sylvestre extract stimulates insulin secretion from human islets in vivo and in vitro, Phytother Res. 2010 Sep;24(9):1370-6.

8. Tumeric (2012) & Type 2 Diabetes
Learn more about treatment of diabetes mellitus.

A 2012 study examined whether turmeric (curcumin) would be helpful in preventing type 2 diabetes. The double-blind, randomized study utilized curcumin extract and included 240 subjects who were given either curcumin extract or a placebo for 9 months. The patients were prediabetic - they had levels of blood glucose that were determined to be higher than normal, but not high enough to be considered diabetes.

The researchers monitored beta-cell functioning, insulin levels and resistance and other measures. After the 9 month period, 16.5% of the placebo patients had developed type 2 diabetes, but none in the curcumin group developed the condition. In addition other measures in the curcumin group improved including overall functioning of beta cells.

Beta cells are the cells in the pancreas that maintain and release insulin, which in turn, regulates the amount of sugar in the blood. They produce a number of byproducts which control related processes.

Researchers: Somlak Chuengsamarn, MD, Suthee Rattanamongkolgul, MD, Rataya Luechapudiporn, PHD, Chada Phisalaphong, PHD and Siwanon Jirawatnotai, PHD

Published: Curcumin Extract for Prevention of Type 2 Diabetes, Diabetes Care July 6, 2012

9. Xtra Info: Diabetes Mellitus Bibliography through 2000
Also see Research discussion for diabetes mellitus

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258. Shanmugasundaram ERB, Rajeswari G, Baskaran K, et al. Use of Gymnema sylvestre leaf extract in the control of blood glucose insulin-dependent diabetes mellitus. J Ethnopharmacol 1990;30:281-94.
259. Bunyapraphatsara N, Yongchaiyudha S, Rungpitarangsi V, Chokechaijaroenporn O. Antidiabetic activity of Aloe vera L juice II. Clinical trial in diabetes mellitus patients in combination with glibenclamide. Phytomedicine 1996;3:245-8.
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Diabetic Retinopathy

1. Alpha lipoic acid ('97, '99, '06. '13) - Diabetic Retinopathy
See more information about cataracts treatment and information and diabetic retinopathy treatment and information.

Oxidative stress is known to be a factor in many eye conditions (and other health conditions as well). These studies noted that alpha-lipoic acid (ALA) reduces oxidative in addition to other benefits.

2013

The researchers evaluated the literature and recent studies and reviews the current understanding of the role of alpha-lipoic acid, a natural antioxidant. They pointed out that ALA prevents both micro- and macro- damage to blood vessels resulting from over production of free radicals by mitochondria, and protects the pericytes that surround and protect the cells that line blood vessels, including the fine capillaries in our eyes. They opined that ALA acts through multiple mechanisms to reduce oxidative stress, improve insulin sensitivity (in patients with type-2 diabetes), and reduces vascular endothelial growth factor (a protein that stimulates extraneous blood vessel growth.

Nebbioso, M., Pranno, F., Pescosolido, N. (2013). Lipoic acid in animal models and clinical use in diabetic retinopathy. Expert Opin Pharmacother, Sep;14(13):1829-38.

2006

In an animal model extraneous capillary blood vessel growth is elevated (micro-neovascularization); in addition there is pericyte loss. Pericytes surround the cells that line blood capillaries and help to regular blood flow. Animals treated with the R form of alpha lipoic acid have reduced micro-neovascularization and increased amounts of pericytes which protect fine capillaries. In addition, there is reduced oxidative stress and normalization of other functions that govern capillary blood flow.

Lin, J., Bierhaus, A., Bugert, P., Dietrich, N., Feng, Y., et al. (2006). Effect of R-(+)-alpha-lipoic acid on experimental diabetic retinopathy. Diabetologia, May;49(5):1089-96.

1997

Researchers found that alpha lipoic acid has the capacity to lessen formation of diabetic cataracts, as well as diabetic retinopathy, and therefore appears to be an ideal neuroprotective supplement in the treatment of all brain and neural disorders aggravated or caused by free radical processes.

Packer, L., Tritschler, H.J., Wessel, K. (1997). Neuroprotection by the metabolic antioxidant alpha-lipoic acid. Free Radic Biol Med, 1997;22(1-2):359-78

2. Astaxanthin (2008, 2016, 2018) & Diabetic Retinopathy
Researchers have found that astaxanthin supplementation reduces cataract formation and diabetic retinopathy (both preventable forms of blindness in people with diabetes) in lab animals and has protective actions of microalgae against endogenous and exogenous advanced glycation end products (AGEs) in human retinal pigment epithelial cells.

2018

Scientists are increasingly able to detect just why the carotenoids are helpful in diabetic eye disease. In this study lab animals with chemical-induced diabetic retinopathy exhibited improvement in a number of markers with even short-term astaxanthin supplementation. Blood samples had increased levels of a particular antioxidant enzyme (heme oxygenase-1,HO-1). In the retina structure certain biochemicals (cellular retinaldehyde binding protein and glutamine synthetase) were observed in the Müller cells.

Baccouche, B., Benlarbi, M., Barber A.J., Ben Chaouacha-Chekir, R. (2018). Short-Term Administration of Astaxanthin Attenuates Retinal Changes in Diet-Induced Diabetic Psammomys obesus. Curr Eye Res, Sep;43(9):1177-1189.

2016

There are a number of types of damage that result from excessive glucose in the eyes: diabetic retinopathy (damage to the retina), diabetic nephropathy (damage to the kidneys), and diabetic neuropathy (damage to the nerves). They are different types of damage, but all result from the inability of the body to process sugar.

This review looks at the potential benefits of the carotenoids that are not precursors of vitamin A. Because they are not vitamins there is no recommended intake for them and thus they may be overlooked. They are lutein, zeaxanthin, lycopene, and astaxanthin. All are able to reduce oxidative stress, inflammation (which affects pancreas dysfunction and reduced insulin sensitivity).

Astaxanthin is thought to be 10 times more powerful than other "eye-beneficial" compounds such as beta-carotene. Astaxanthin is helpful in diabetic complications due to its antioxidant capacity which fights free radicals and reduces oxidative stress causing inflammation.

Astaxanthin and other carotenoids appear to be helpful in diabetic retinopathy but there is not enough research to unqualifiedly claim that; however it should be an important part of the diabetics diet along with other substances that help to control glucose levels.

Murillo, A.G., Fernandez, M.L. (2016). Potential of Dietary Non-Provitamin A Carotenoids in the Prevention and Treatment of Diabetic Microvascular Complications. Adv Nutr, Jan 15;7(1):14-24.

2008

This study investigated the use of astaxanthin along with flavangenol (french maritime pine bark) in alleviating diabetic retinopathy in lab animals. The researchers found that the combination is more effective than either nutrient alone, and that each nutrient is better than no supplementation in the controls.

Nakano, M., Orimo, N., Katagirim N., Tsubata, M., Takahashi, J., et al. (2008) Inhibitory effect of astaxanthin combined with flavangenol on oxidative stress biomarkers in streptozotocin-induced diabetic rats. Int J Vitam Nutr Res, 2008 Jul-Sep;78(4-5):175-82.

3. Bilberry (1981, '87, '95, '02, '15) & Diabetic Retinopathy
See more about diabetic retinopathy treatment and information.

The family of anthocyanosides are natural antioxidants, which most famously include bilberry (Vaccinium myrtillus), a European type of blueberry. Holistic doctors have known about the benefits of anthocyanosides (decreasing blood vessel leakage and increasing antioxidant levels) since the 1970s or earlier, but in the last few years it has received a lot of attention due to new research.

2015

This study aimed to determine whether bilberry actually helped to prevent retinal difficulties caused by diabetes. The damage results from impaired blood vessel functioning and consequent growth of extraneous capillary growth (neovascularization or micro-neovascularization) which distort and damage the retina. Bilberry was given to lab animals with uncorrected diabetes for six weeks. The treatment reduced bio-markers of diabetic retinopathy which included neovascularization, and degradation of three different zonula occludens (protein protectors of capillaries). The researchers reported that bilberry may delay or prevent the onset of early diabetic retinopathy.

Kim, J., Kim, C.S., Lee, Y.M., Sohn, E., Jo, K., et al. (2015). Vaccinium myrtillus extract prevents or delays the onset of diabetes--induced blood-retinal barrier breakdown. Int J Food Sci Nutr, Mar;66(2):236-42.

2002

Blueberries also contain significant amounts of valuable anthocyanins. Although research had previously been done with lab animals, these scientists wanted to find out whether the benefits extended to humans. Subjects given a high-fat meal with freeze-dried blueberry powder that contained 25 different types of anthocyanins. Nineteen of those anthocyanins were consequently detected in the blood samples of the subjects. In addition an increase in antioxidants in the blood samples was detected.

Mazza, G., Kay, C.D., Correll, T., Holub, B.J. (2002). Absorption of anthocyanins from blueberries and serum antioxidant status in human subjects. J Agric Food Chem, 50:7731-7.

1995

Researchers have noted that bilberry extracts could improve vision sharpness and help faster adaption to changing light conditions. European physicians already recommend bilberry extracts for other eye complaints such as retinitis pigmentosa, and diabetic retinopathy.

One study assessed the effectiveness of a bilberry extract (anthocyanosides) in animals finding that vascular permeability is decreased. This means that blood barrier permeability is normalized.

"Bilberry Fruit," The Lawrence Review of Natural Products, October 1995, Pages 1-2.

1987

In a small trial, 79% of 37 patients for whom ophthalmologists could detect visible diabetic retinal abnormalities gained some benefit from taking 160 mg of bilberry extract twice daily, compared to 0% improvement in a placebo control group. Furthermore, 86% of those with abnormalities of angiography findings showed moderate to considerable improvement.

Perossini, et al. (1987). Annali Di Ottalmologia E Clinica Oculistica.

1981

Thirty one patients with various types of retinopathy who were put on anthocyanosides showed a positive influence on both vascular permeability and resistance to hemorrhage. Those with diabetic retinopathy had the largest effect. Long term use of these plant nutrients is helpful in improving vascular permeability.

Sharrer A., Ober M. (1981). Anthocyanosides in the treatment of retinopathies. Klin Monatsbl Augenheilkd, May;178(5):386-9.

4. Carotenoids (1999) & glucose tolerance

Learn more about diabetic retinopathy.

Oxidative stress is one result of diabetes is characterized. Consequently there is an impact on vision.

Researchers took a look at data from part of the Third National Health and Nutrition Examination Survey (1988-1991) and assessed alpha- and beta-carotene, cryptoxanthin, lutein/zeaxanthin, and lycopene concentrations in people aged 40-74 with a normal blood sugar levels, high blood sugar levels, recently diagnosed diabetes, and previously diagnosed diabetes. This data was adjusted for age, sex, race, education, serum cotinine, serum cholesterol, body mass index, physical activity, alcohol consumption, vitamin use, and carotene and energy intake.

The researcher's conclusions were that low blood serum carotenoid levels were directly related to increased risk for diabetes and insulin resistance.

Published: Ford, et al. Am J Epidemiol 1999 Jan 15;149(2):168-76

5. Chromium (1995) supplements
See more about diabetic retinopathy treatment and information.

Researchers found that 73% of type I and II diabetics who were given chromium supplements were able to reduce their requirement for insulin or oral hypoglycemic medications. Taking chromium and niacin together reduced fasting blood sugar levels and improved glucose tolerance. Note to readers - never change your medications for diabetes without checking with your doctor first.

Published: J Trace Elem Exp Med 1995: 8:183-90; Urberg M, Zemel MB, Metabolism 1987; 36:896-99

6. Chromium, Vit. E, Magnesium (1997), etc & diabetic retinopathy
Learn more about diabetic retinopathy treatment and information.

Researchers feel that some trace minerals such as chromium and magnesium, high-dose vitamin E, soluble fiber, and possibly taurine may be likely to lessen risk for macrovascular disease (retinopathy) in diabetics.

Published: McCarty, Med Hypothesis 1997 Aug;49(2):143-52

7. CoQ10 (2007, 2015) Benefit for Diabetic Retinopathy

High levels of free radicals are found in patients with diabetic retinopathy. Research suggests that powerful antioxidants like CoQ10 may be helpful.

2015

This study was designed to investigate the levels of free radicals circulating in the blood of patients with nonproliferative diabetic retinopathy before and after supplementation with CoQ10 and two other nutrients known to be helpful for patients at risk for diabetic retinopathy.

Two groups were tested, a control group and a test group given a combination of 50 mg pycnogenol, 30 mg Vitamin E and 20 mg CoQ10. They found that the group given the combination of nutrients experienced significantly lowered levels of free radicals.

Domanico, D., Fragiotta, S., Cutini, A., Carnevale, C., Zompatori, L., et al. (2015). Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up. Indian J Ophthalmol, Jan;63(1):9-14.

8. Ginkgo Biloba (1988) and Diabetic Retinopathy
Learn more about diabetic retinopathy treatment and information.

According to a 1988 double blind study in France, gingko biloba can help improve diabetic retinopathy by improving the flow of blood to the brain and extremities.

Reference: Lanthony P, Cosson JP. Evolution of color vision in diabetic retinopathy treated by extract of Ginkgo biloba. Journal For Ophthalmology 1988;11:671-74 [in French].

9. Glutathione ('00, '11, '13, '14, '18) & Diabetic Retinopathy

2018

It is now well established that high levels of free radicals (reactive oxygen species) are present in diabetics, as a result of reduced and/or compromised antioxidants in the body such as glutathione.

Santiago, A.R., Boia, R., Aires, I.D., Ambrosio, A.F. and Fernandes, R. (2018). Sweet Stress: Coping with Vascular Dysfunction in Diabetic Retinopathy. Front Physiol, 2018;9:820.

2014

One of the therapeutic approaches to managing diabetes mellitus and preventing onset of complications like diabetic retinopathy is that of attention to reducing oxidative stress through the antioxidants like glutathione, carotenoids (like lutein and zeaxanthin), and other antioxidants like lipoic acid.

Safi, S.Z., Qvist, R., Kumar, S., Batumalaie, K. and Ismail, I.S.B. (2014). Molecular Mechanisms of Diabetic Retinopathy, General Preventive Straties, and Novel Therapeutic Targets. Biomed Red Int., 2014:801269.

2013

Researchers investigated the differences and relationship between glutathione levels and different forms of insulin-related difficulties. They compared patients with type 2 diabetes, impaired glucose tolerance, and people normal fasting glucose blood levels with respect to glutathione levels. The patients with diabetes had the lowest levels of glutathione. (Note. Glutathione levels also decrease with aging). The researchers concluded that glutathione deficiency was a significant factor in the development of diabetes. High blood sugar levels (hyperglycemia causes oxidative stress and glutathione's ability to reduce free radicals appears to be at least part of the reason for improvement.
Kalkan, I.H., Suher, M. (2013). The relationship between the level of glutathione, impairment of glucose metabolism and complications of diabetes mellitus. Pak J Med Sci, 29(4):Jul-Aug.

2011

Glutathione is one of the super antioxidants that neutralizes the full range of free radicals. Patients with uncontrolled type 2 diabetes are unable to adequately synthesize glutathione because of a lack of natural precursors in the body. Supplementing with amino acids, which are GSH precursors, supports GSH synthesis and reduces oxidative damage and inflammation.

Sekhar, R.V., McKay, S.V., Patel, S.G., Guthikonda, A.P. Reddy, V.T., et al. (2011). Glutathione Synthesis Is Diminished in Patients With Uncontrolled Diabetes and Restored by Dietary Supplementation With Cysteine and Glycine. Diabetes Care, Jan; 34(1):162–167.

2000

Researchers noted that free radicals forming in diabetes patients which accumulate with time may contribute to the development of diabetic retinopathy.

Gurler, B., Vural, H., Yilmaz, N., Oguz, H., Satici, A., et al. (2000). The role of oxidative stress in diabetic retinopathy. Eye (Lond), Oct;14 Pt 5:730-5.

10. Goji Berry (2011, '14, '16) Supports Pigmented & Photoreceptor Cells
Learn more about diabetic retinopathy.

Goji berries, traditionally used in China for more than 2000 years, appear to have a wide variety of health benefits. While a great deal of preliminary research has been accomplished, researchers are now looking to a more detailed analysis of its potential benefit in the area of vision therapy.

2016

Researchers wanted to investigate the impact of treatment with goji berry extract on photoreceptor cells which are implicated in the development of diabetic retinopathy. The study involved photoreceptor tissue that was exposed to chemical damage (MNU) that would normally kill or damage the photoreceptor cells. This is known as cell apoptosis - or cell death.

The scientists fed lab animals with a water solution of lycium barbarum polysaccharides, and extract from goji berry. Polysaccharides are carbohydrates consisting of sugar molecules bonded together. The condition of photoreceptor cells was examined 24 hours and again at 7 days after injection of MNU.

They found that the outer layer of photoreceptor cells, closest to the front of the eye was well protected. Along with other biochemical level analysis they concluded that the polysaccharides from goji did, in fact, have a protective role.

Researchers: Y. Zhu, Q. Zhao, et al,
Published: Lycium barbarum polysaccharides attenuates N-methy-N-nitrosourea-induced photoreceptor cell apoptosis in rats through regulation of poly (ADP-ribose) polymerase and caspase expression, Journal of Ethnopharmacology, September, 2016

2014

Damage due to a weakened blood/retina barrier is related to the development of diabetic retinopathy.

This study investigated the changes in the blood/retinal barrier under conditions of chronic hyperglycemia with goji extract supplementation.

The researchers noted that human retinal pigment cells (which protect the retina from damage) offer weak protection to the blood/retina barrier in the presence of glucose. Treatment with an extract of goji reversed this weakness and increased the protective effect.

The researcher noted that this is a possible prevention approach for diabetic retinopathy.

Researchers: B. Pavan, A. Capuzzo, et al,
Published: High glucose-induced barrier impairment of human retinal pigment epithelium is ameliorated by treatment with Goji berry extracts through modulation of cAMP levels, Experimental Eye Research, March, 2014.

A study investigated the broad range of potential benefits of goji berries. One result is that they lower blood sugar levels and increase insulin sensitivity. This is accomplished by improving glucose metabolism, increasing insulin production, and supporting beta cell growth in the pancreas. These results make goji of interest for treatment of diabetic retinopathy.

Researchers: J. Cheng, Z.W. Zhou, et al,
Published: An evidence-based update on the pharmacological activities and possible molecular targets of Lycium barbarum polysaccharides, Drug Design, Development and Theory, December, 2014

2011

A specific receptor encoded by a specific gene is involved in the development of diabetic retinopathy. It is called the peroxisome proliferator activated receptor-gamma (PPAR-y) and it is encoded by the PPARG gene.

Diabetic retinopathy occurs when the retinal pigment cells in the eye are damaged; but the amino acid taurine, which is abundant in goji berries seems to be of benefit to people with the condition.

Researchers wanted to know why - the mechanism - of the process of taurine being beneficial for diabetic retinopathy patients. They investigated the action of a goji berry extract on a specific type of retinal cell (retinal ARPE-19 cell line) and identified the receptor which links to taurine and which is potentially responsible for taurine's protection against diabetic retinopathy.

In animal models the researchers were able to verify that cells that could be damaged by inflammation due to high glucose contact were protected by taurine in the goji berries.

They concluded that the taurine content of goji is at least partially responsible for its protective effect.

Researchers: M.K. Song, N.K. Salam, et al,
Published: Lycium barbarum (Goji Berry) extracts and its taurine component inhibit PPAR-_-dependent gene transcription in human retinal pigment epithelial cells: Possible implications for diabetic retinopathy treatment, Biochemical Pharmocolory, November, 2011.

11. Grape Seed Extract (2016, 2017) & Diabetic Retinopathy
Diabetic retinopathy has long been considered to be a vascular condition, that is, caused by damage to microcapillaries in the eyes due to elevated glucose. It is also considered to be a neurodegenerative condition in that damaged photoreceptor cells may contribute to damaged microcapillaries.

2017

In this study researchers investigated the underlying molecular mechanism of damaged photoreceptors. They used grape seed proanthocyanidin extract to improve functioning of thioredoxin (a protein that acts as an antioxidant and is important for cell-to-cell communication). Doing so would help prevent and treat neurodegenerative diseases. An in vitro test found that grape seed extract upregulated thiordoxin and decreased cell death. In vivo, in lab animals, damage to photoreceptor cells was inhibited by grape seed extract treatment.

Ren, X., Lu, H., Wang, N., Zhang, C., Ji, Y., et al. (2017). Thioredoxin is implicated in the anti apoptotic effects of grapeseed proanthocyanidin extract during hyperglycemia. Mol Med Rep, Nov;16(5):7731-7737.

2016

This study investigated whether grape seed extract could protect the retina in diabetics. Animals with diabetes were divided into three groups, healthy, diabetic, and diabetic animals treated with grape seed extract. The retinas of the diabetic animals became damaged, but the retinal structure of those treated with grape seed extract improved. The researchers concluded that grape seed extract may protect the retina against hyperglycemic damage. This result may be due to activating the Nrf2 pathway (a gene encoding that regulates antioxidant proteins).

Sun, Y., Xiu, C., Liu, W., tao, Y., Wang, J., Qu, Y.I. (2016). Grape seed proanthocyanidin extract protects the retina against early diabetic injury by activating the Nrf2 pathway. Exp Ther Med, Apr;11(4):1253-1258.

12. Gymnema Sylvestre (2005) and Diabetes Study
Learn about information on Diabetes and Diabetic Retinopathy.

A small study (India, 2005) examined the effects of an extract of Gymnema sylvestre on high blood sugar. Twenty-two people with type 2 diabetes were given extract for 18 to 20 months as a supplement to their regular medical regimen of oral anti-hyperglycemic agents.

During that period, an some them apparently showed reductions in blood glucose and A1c's. A few were reportedly able to discontinue their conventional anti-hyperglycemic drug and manage their blood glucose levels with the extract alone. Moreover, raised insulin levels were apparently found in the blood of the patients.

The authors, who published related research in 1990 in the same journal, believe that beta cell regeneration is the source of the improvement; however, members of the scientific community have previously questioned both their findings and their conclusions.

Published: 2005, Journal of Ethnopharmacology

13. Gymnema Sylvestre (2006) & Diabetic Retinopathy
Learn more about treatment for diabetic eye disease.

The researcher investigated how multiple pharmacological effects of specific compounds become a requirement in classifying their effectiveness. This is because the multiple effects treat a variety of symptoms in any one condition making them more (or less) effective.

In this evaluation one of the conditions the researcher looked at was diabetic retinopathy/diabetes mellitus where continued hyperglycemia causing blood circulation complications. Gymnemic acid, contained in Gymnema sylvestre leaves has anti-hyperglycemic, anti-sweet, inhibits glucose uptake, and inhibits glycosidase in the gut. These multiple effects render it effective in alleviating type 2 diabetes-related symptoms such as diabetic retinopathy.

Published: Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions, Yakugaku Zasshi, March, 2006

Researcher: I. Kimura

14. Magnesium & Other Trace Elements (1978, 1985) & Diabetic Retinopathy
Learn more about diabetic retinopathy.

1985

Researchers have found that, in type I diabetes (insulin-dependent) the metabolism of several trace elements is different, leading researchers to conclude that these nutrients (or lack of them) might have specific functions in the development of the disease.

Magnesium deficiency is the most evident and also may heighten the risk of both ischemic heart disease and severe retinopathy.

Increased urinary loss of zinc is another common result of diabetes. Chromium increases tissue sensitivity to insulin and raises HDL cholesterol and the HDL:LDL ratio.

Selenium is critical to protecting the cell against oxidative damage by peroxides produced from lipid metabolism.

Researchers: T. Tuvemo, et al,
Published: The role of trace elements in juvenile diabetes mellitus, Pediatrician 1983-85

1978

Researchers have been evaluating the blood chemistry of diabetic patients for many years, searching for associations between various deficiencies and the disease.

In this study researchers evaluated the levels of magnesium in the blood plasma in 71 early-onset diabetes patients who had been taking insulin shots daily to 10 to 20 years and who had developed diabetic retinopathy.

They found that patients with higher levels of magnesium had less severe cases of diabetic retinopathy compared to patients with low levels of magnesium. Their conclusion was that low magnesium levels are an added risk factor for diabetic retinopathy in diabetic patients.

Researchers: P. McNair, et al,
Published: Hypomagnesemia, a risk factor in diabetic retinopathy, Diabetes November, 1978.

15. Omega-6 (1998) - diabetic retinopathy
Learn more about diabetic retinopathy treatment and information and diabetes mellitus.

Researchers have found that omega-6 fatty acids are helpful in managing diabetes and diabetic retinopathy. Evening primrose, borage and black currant oil are good sources of Omega-6 essential fatty acids including gamma-linolenic acid (GLA). Supplementation with GLA may offer a method to bypass the disturbance in omega-6 essential fatty acid metabolism associated with diabetes and diabetic retinopathy.
Researchers: A.M. Petrosian, J.E. Haroutounian

Published: Advances in Experimental Medicine & Biology, 1998

16. Pine Bark (2015, 2007, 2009) Helps Diabetic Retinopathy
Learn more about diabetic retinopathy.

A number of diseases involve inflammation and impairment of endothelial layers (that line blood vessels): these include not only heart disease but diabetic retinopathy. The endothelium is the inner lining of blood vessels. Such dysfunction is generally defined as there being an imbalance between the ability of blood vessels' ability to contract and expand.

Various studies have determined that the relationship between obesity, inflammation and other risk factors is a critical factor in such endothelial dysfunction which causes diabetic retinopathy.¹

2015

Drawing on earlier research demonstrating that pycnogenol supports vision improvement in diabetic retinopathy by improving microcirculation and reducing swelling, researchers investigated combining this nutrient with other antioxidants as a therapeutic approach.

In patients with nonproliferative diabetic retinopathy, scientists evaluated treatment with 50mg pycnogenol, 30mg vitamin E and 20mg CoQ10. Sixty eight patients were divided into two groups, one receiving the supplement and one receiving placebo. The researchers evaluated levels of free radicals and macular thickness at the beginning of the study period, after three months, and after six months.

In the test group both measures improved; in the placebo group the free radicals level worsened, and macular thickness did not change.

The researchers report that this is the first study to find that free radical levels are reduced, and that retinal thickness is also affected.

Researchers: D. Domanico, S. Fragiotta, et al
Published: Circulating levels of reactive oxygen species in patients with nonproliferative diabetic retinopathy and the influence of antioxidant supplementation: 6-month follow-up, Indian Journal of Ophthalmology, January, 2015.

2009

Researchers have been investigating alternative means of alleviating diabetic retinopathy as diabetes becomes more widespread in the world. Earlier studies have found that pine bark can be effective in very early stages of diabetic retinopathy. This study looks at effectiveness a little later in development when retinal edema begins to appear but before bleeding or other changes occur in the macula.

In a small study 24 patients were assessed as to the degree of retinal swelling and thickness of the retina layer. They were treated with pycnogenol (maritime pine bark) for 3 months and then the measurements were repeated.

The 24 patients were compared to 22 controls with similar conditions who were treated with placebo. The patients given pine bark showed statistically significant improvement in degree of retinal swelling compared to placebo patients (very little change). Likewise, they experienced a marked increase in microcirculation compared to placebo.

The researchers reported that the primary positive result was that visual acuity (sharpness) improved in 18 out of 24 patients receiving treatment from 14/20 to 17/20 after only two months of treatment. There was no change in the placebo group.

The researchers concluded that pine bark, taken early, may improve microcirculation and reduce swelling - both of which help to improve vision.

Researchers: R. Steigerwalt, G. Belcaro, et al
Published: Pycnogenol improves microcirculation, retinal edema, and visual acuity in early diabetic retinopathy, Journal of Ocular Pharmacology and Therapeutics, December, 2009.

2007

A two week study found that extract of French maritime pine bark (pycnogenol supported the ability of blood vessels to appropriately dilate for adequate blood supply. However, placebo used in the study did not affect vasodilation.

The researchers concluded that pycnogenol would be useful in treating diseases involving endothelial dysfunction.

K. Nishioka, T. Hidaka, et al. (2007). Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans, Hypertension Research, September.

1. M. Tomic, S. Ljubic, et al, The role of inflammation and endothelial dysfunction in the pathogenesis of diabetic retinopathy, Collegium Antropologicum, April, 2013.

17. Resveratrol (2014-15, 2017) & Diabetic Retinopathy
Learn more about support for diabetic retinopathy

2022 Although earlier research supported use of moderate red wine use, newer research reports that the many detriments outweigh the benefits.^{1, 2, 3} Instead, we recommend intake of resveratrol through grapes, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.

2017

Researchers find that one reason the polyphenol resveratrol is beneficial for eye health is that it has the ability to cross the semi-permeable blood-brain and blood-ocular barriers.

A study measured the concentration of trans-resveratrol, taken orally, in human eyes. It is metabolized so rapidly by the digestive system that it can be detected in blood samples within 10 minutes of ingestion.

Scientists determined that trans-resveratrol and three metabolites of resveratrol (especially resveratrol-3-O-sulfate) were found in eye tissue (conjunctiva, aqueous humor and vitreous humor) following taking the nutrient orally. The measurements of resveratrol levels in eye tissue in this study helps to define dosages in future treatment of ocular disease.

Researchers: S. Wang, Z. Wang, et al,
Published: Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes, Journal of Ophthalmology, March, 2017.

2015

Researchers wanted to evaluate whether the nutrient resveratrol anti-inflammatory capacity would be helpful in the retinas of diabetic lab animals.

Diabetic rats were given oral resveratrol for four months. The treatment not only improved their glucose tolerance without changing blood insulin levels, but improved the health of their retinas.

The researchers commented that whether resveratrol so benefits the patient indirectly or directly merits further research.

Researchers: F. Ghadiri Soufi, E. Arbabi-Aval, M. Rezaei Kanavi, H. Ahmadieh.

Published: Anti-inflammatory properties of resveratrol in the retinas of type 2 diabetic rats, Clinical and Experimental Pharmacology and Physiology, January, 2015

2014

Moderate alcohol consumption (especially red wine) has been associated with improved cardiovascular functioning because its high polyphenol content improves vascular flexibility, reduces inflammation and inhibits formation of new blood vessels. Polyphenols are micronutrients with many recognized benefits.

The beneficial relationship of polyphenols to blood vessels has suggested it as a beneficial nutrient for the eyes -- where good microcirculation is essential to delivery nutrients to eye tissue, and inhibition of new blood vessels that can distort the retina is also important.

Researchers find that the polyphenol resveratrol behaves as an antioxidant, anti-inflammatory agent, restricts new blood vessels and is an anti-tumour agent. For this reason is has great potential in ocular disease.

Researchers: C. Bola, H. Bartlett, et al
Published: Resveratrol and the eye: activity and molecular mechanisms, Graefes Archives for Clinical and Experimental Ophthalmology, May, 2014.

Footnotes
1. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, et al. (2018). Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. Apr 14;391(10129):1513-1523.
2. Biddinger KJ, Emdin CA, Haas ME, Wang M, Hindy G, et al. (2022). Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022 Mar 1;5(3):e223849
3. Goding Sauer A, Fedewa SA, Bandi P, Minihan AK, Stoklosa M, et al. (2021). Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiol. Apr;71(Pt A):101893.

18. Saffron (2010, 2015) and Diabetic Retinopathy
Learn more about diabetic retinopathy.

A complication of diabetes is diabetic neuropathy, often associated with diabetic retinopathy, or diabetic eye disease.

2015

Researchers investigated the effects of crocin and safranal which are the primary components of the herb saffron and found that they provide protection to the nervous system. They specifically looked at the neuroprotective effect on peripheral neuropathy in diabetic lab animals.

They found that saffron, provided in addition to insulin improved the biochemical changes above those changes with insulin alone. The results were investigated via biopsy as well as looking at blood glucose levels and other standard measurements. The researchers felt that the neuroprotective effects of the saffron components might be linked to their anti-hyperglycemic and antioxidant capacity.

Researchers: A.A. Farshid, E. Tamaddonfard

Published: Histopathological and behavioral evaluations of the effects of crocin, safranal and insulin on diabetic peripheral neuropathy in rats, Avicenna Journal of Phytomedicine, September, 2015.

In another study researchers pointed out that protein glycation is one of the most important reasons for diabetes complications (such as diabetic retinopathy).

In this study researchers tested a combination of crocetin (the central core of crocin) and certain amino acids as a preventative for diabetes complications in diabetic lab animals. They found that the combination effectively reduced inflammation, blood sugar levels, bonding of proteins to sugar molecules (contributes to cataracts) and oxidation.

They suggested it could be a new drug to prevent diabetic complications.

Researchers: S. Mahdavifard, et al.

Published: The synergistic effect of antiglycating agents (MB-92) on inhibition of protein glycation, misfolding and diabetic complications in diabetic-atherosclerotic rat, European Journal of Medicinal Chemistry, December, 2015.

2010

An earlier study also found that saffron could be useful in combating the symptoms of diabetic neuropathy, often associated with diabetic retinopathy due to its antioxidant effects.

Researchers: S.H. Mousavi, et al.

Published: Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells, Cellular and Molecular Neurobiology, March, 2010.

19. Taurine - (1999) diabetic retinopathy
Learn more about diabetic retinopathy.

The condition diabetic retinopathy results because having diabetes increases the demands on the eye for various nutrients. The retina's need for taurine is one of the nutrients involved. Glucose rapidly and specifically decreases taurine levels in retina cells.

Giving patients taurine supplements not only helps manage diabetic retinopathy, but taurine also appears to lessen the development of "sugar cataracts" because of its anti-oxidant qualities.

Published: Stevens et al, Am J Physiol 1999 Oct;277(4 Pt 1):E760-E771

Reference also: Malone JI, Benford SA, Malone J Jr, Diabetes Complications

20. Vitamin B12 (1958) diabetic retinopathy
Learn more about diabetic retinopathy.

Patients with Type I diabetes, "juvenile diabetes," are often subject to retinal complications such as diabetic retinopathy. In an early study, about 1/2 of 15 patients with type I diabetic retinopathy who received vitamin B12 at the same time as they took their daily insulin shot experienced complete recovery from signs of retinal problems after 12 months.

Published: Kornerup T, Strom L. Acta Paediatr 1958.

21. Vitamin C, E, Beta Carotene, Selenium (1987) - ARMD
Learn more about diabetic retinopathy.

Researchers found in a clinical study of patients with macular degeneration or diabetic retinopathy. In the trial 60% of the people received 500 mg of vitamin C, 400 IU of vitamin E, 15,000 IU of beta carotene and selenium supplements. These people showed slower development of their condition and or a lessening of symptoms.

Published: South Med J; 1987

22. Vitamin D (2015) & Diabetic Retinopathy
Learn more about diabetic retinopathy.

The researchers sought to find out whether vitamin D plays any part in the development of diabetic retinopathy, or diabetic eye disease in type II diabetics.

Diabetic patients in groups of 139 with diabetic retinopathy and 144 patients without the condition were evaluated. The researchers found that deficient levels of vitamin D and D3 were tied to incidence of diabetic retinopathy. Further, they found that patients with more severe diabetic eye disease were the most deficient in those D vitamins.

Researchers: N. Alcubierre, J. Valls, E. Rubinat, G. Cao, A. Esquerda, A. Traveset, M. Granado-Casas, C. Jurjo, and D. Mauricio.

Published: Vitamin D Deficiency Is Associated with the Presence and Severity of Diabetic Retinopathy in Type 2 Diabetes Mellitus, Journal of Diabetes Research. May, 2015

23. Vitamin E (1993) Diabetic Retinopathy
Learn more about diabetic retinopathy and diabetes.

Researchers found that vitamin E helps support glucose tolerance diabetics who are not insulin-dependent. This should result in fewer complications from diabetes mellitus, such as diabetic retinopathy.

Published: Paolisso, G, et al. Am J Clin Nutr 1993; 57:650-56

Note: A 2015 study found that vitamin E combined with CoQ10 and maritime pine bark (pycnogenol) is helpful in reducing free radicals in patients with nonproliferative diabetic retinopathy. See the CoQ10 study for more information.

24. Yoga (2012) Decreases Inflammation
Learn more about rheumatoid arthritis.

In a randomized, controlled trial, researchers looked at the biological mechanisms responsible for effects such as stress reduction, which have been well documented.

Researchers studied caregivers for dementia patients who did 12 minutes of yoga daily for 8 weeks compared to a control group who listened to relaxing music for the same time period. About 16% of caregivers begin to themselves have health problems after they begin to spend the time, attention and energy to care for someone else.

The scientists found in the yoga participants a change in 68 gene responses including adjustments for caregiver burden, sex, and body mass index. These changes manifested as reduced inflammation - a common symptom/issue for patients with depression, heart disease, diabetes and rheumatoid arthritis.

Editor's Note: This particular study looked at subjects performing Kirtan Kriya yoga, but any form of classic yoga, involving a variety of postures which give movement and enhance energy flow to all parts of the body will yield similar results. With respect to vision, inflammation is a major issue in diabetic retinopathy, optic neuritis (swollen optic nerve), and macular edema.

Researchers: Black, Cole, Irwin, Breen, St. Cyr, Nazarian, Shalsa, Lavretsky, University of California.

Published: Psychoneuroendocrinology, July 14, 2012 (online)

Dry Eyes

1. Black Currant Seed Oil (1986) - dry eyes
Learn more about dry eye treatment and information.

Researchers have completed a controlled study which investigates the immune-system enhancing effects of black currant seed oil, which is an excellent source of omega-3 and omega-6 fatty acids.

Both this study involving 40 patients and previous research suggests that the combination of omega-3 and omega-6 fatty acids which is found in black currant seed supports increased prostaglandin (a fatty compound with hormone-like effects) PGE1 (a type of prostaglandin), which both stimulates acqueous tear secretion and reduces the production of another prostaglandin, PGE2, which causes inflammation that contributes to dry eyes.

Researchers: Oxholm P., et al.

Published: Patients with Sjogren's Syndrome Treated For 2 Months with Evening Primrose Oil. Scandinavian Journal of Rheumotology 1986.

2. Dry Eyes (2012) Tied to Migraine Headaches
Learn more about holistic treatment of dry eyes.

Researchers have long suspected that there may be a connection between dry eyes and migraine headaches - this study investigates that tie by investigating the relationship between tear capacity and migraine symptoms in patients.

See the summary of the migraines & dry eyes study.

Published: Cornea. 2012 Jun 15, Dry Eyes and Migraines: Is There Really a Correlation?

3. Dry eyes (2016-17) Linked to Meibomian Gland Dysfunction
Learn more about dry eye cause and treatment.

Researchers have long understood that post-menopausal women experience an increase in dry eye symptoms. Dry eyes are caused by insufficient tear film, or insufficient meibum to protect the tear film from evaporation.

2017

Researchers were investigating the connection between hormonal changes in post-menopausal women and dry eye symptoms. The test subjects were nearly 50 post-menopausal women with dry eye ranging in age from 59 to 69 years old. They were 6 to 20 years past menopause and were not receiving hormone therapy.

The researchers looked at a number of standard tests and assessments used to evaluate dry eye conditions. They looked at the condition of the surface of the cornea, how comfortable eyes felt to the patients, how thick the tear fluid was and how rapidly the tear film broke up. They also investigated the health of the meibomian gland.

These glands are located above and below the eyes close to the eye lashes. They secrete meibum. Meibum is a thin oily substance that floats on top of the tear film helping to keep it from evaporating. Every time we blink the tear film and its protective meibum coating is redistributed evenly over the surface of the cornea.

The researchers found that the level of estrogen in the blood seems to be a main factor in the health of the meibomian glands, and that the resulting meibomian gland dysfunction as estrogen levels decrease is associated with increased dry eye symptoms.

Researchers: B. Golbiowski, N. Badarudin, et al
Published: Does endogenous serum oestrogen play a role in meibomian gland dysfunction in postmenopausal women with dry eye?< British Journal of Ophthalmology, February, 2017.

2016

A previous study investigated the possible role of both testosterone and estrogen in postmenopausal women with dry eye. Nearly 200 postmenopausal women with an average age of 61 were included in the study.

They looked at blood levels of both hormones, the integrity of the meibomian glands and the thickness of the meibum layer on the surface of the eye.

There was no clear association between the hormone levels and the thickness of the meibum layer.

However, there was a significant link between "meibomian gland dropout (MG dropout)" and hormone levels. MG dropout refers to the deterioration or complete loss of the tissue that makes up the meibomian glands. As testosterone levels increased (relative to declines in estrogen), MG dropout also increased. The change was not so significant for estrogen levels alone decreasing.

Researchers: A.F. Ablamowicz, J.J. Nichols, et al
Published: Association Between Serum Levels of Testosterone and Estradiol With Meibomian Gland Assessments in Postmenopausal Women, Investigations in Ophthalmology and Visual Science, February, 2016.

Editor's Note: a related study also found that meibomian gland deterioration was severe in patients wearing silicone hydrogel contact lenses.¹

Footnote
1. M.C. Lin, T.H. Yeh, Mechanical Complications Induced by Silicone Hydrogel Contact Lenses, Eye Contact Lens, 2013, online in Medscape

4. Eye drops (1988) without preservatives
Eye drops used without preservatives have been shown to enhance corneal healing and improve dry eye problems. Laflamme, M.Y., and Swieca, R. A comparative study of two preservative-free tear substitutes in the management of severe dry eye. Canadian Journal of Ophthalmology 23 (1988): 174-76.

Editor's Notes: Preservatives in many products can aggravate dry eye symptoms, and even kill corneal cells. Eye drops that promise to "get the red out" will reduce circulation in the eye, decrease production of the tear film, and worse, eventually make your eyes even drier.

The most popular products featuring eye drops without preservatives are the homeopathic eye drops for women and the homeopathic eye drops for men -- both as effective aides for Dry Eyes.

5. Green Tea Extract (2017) & Dry Eye
Learn more about dry eyes.

Research has associated malfunctioning meibomian glands with dry eye syndrome.

This study looked at green tea extract as to its helpfulness in meibomian gland problems.

The study was a double-blind, placebo controlled and randomized study of 60 patients. All used a standard treatment of eye drops three times a day for a month. The test group also received topical green tea three times a day for a month.

The symptoms of the test group improved significantly compared to the control group which suggested improved health of the meibomian glands. Furthermore, no side effects were noted.

Researchers: M. Nejabat, S.A. Reza, M. Zadmehr, et al
Published: Efficacy of Green Tea Extract for Treatment of Dry Eye and Meibomian Gland Dysfunction; A Double-blind Randomized Controlled Clinical Trial Study, Journal of Clinical and Diagnostical Research, February, 2017.

6. Hormone Replacement Therapy (2001) and Dry Eyes
See more information about treating dry eyes.

Researchers report that women taking hormone replacement therapy (HRT) especially the type that employs only estrogen are at increased risk of experiencing dry eye syndrome.

The researchers evaluated the medical histories of over 25,000 women from the Women Health Study. They gathered formation of HRT treatment at the beginning of the evaluation period, after one year, and after three years along with data on dry eye syndrome after four years.

They found marked correlation between HRT and dry eye syndrome. Women who had never received HRT had the lowest rate of dry eye syndrome - 5.9% and the women who used estrogen HRT had the highest rate of 9.1%. Women who used estrogen plus progesterone/progestin treatment had a rate of 6.7%.

They statistically concluded that each 3 year continuation of HRT treatment was tied to a 15% increase in dry eye risk symptoms.

Researchers: Debra Schaumberg, MD et al.

Published: Dry-Eye Syndrome: An Overlooked Side Effect of HRT, Journal of the American Medical Association, November, 2001.

7. Lactoferrin (2015-16) Helpful for Dry Eye, Anti-Inflammation, Anti-Microbial
Learn more about dry eye syndrome.

Dry eye syndrome is one of the most common complaints to eye doctors. And patients who have cataract surgery frequently experience dry eye. Some people dislike having to use eye drops.

Researchers evaluated the use of lactoferrin, taken orally rather than in eye drops, to relieve the symptoms of dry eye, especially after cataract surgery.

Lactoferrin is a glycoprotein that binds to iron¹. Glycoproteins are proteins with a sugar attached to them and they float around in cell membranes. They are naturally found in tears produced by the eyes' tear glands. They have anti-microbial and anti-inflammatory properties.

It's been noted that patients with chronic dry eyes have low levels of lactoferrin in their tear film which accounts for the typical redness and soreness experienced by those with dry eye syndrome.

In this randomized controlled trial 64 patients who did not already have dry eye syndrome and who were to have cataract (small incision type of surgery) were divided into those who received 350gm of postoperative lactoferrin and those who did not.

The researchers assessed the degree of dry eye symptoms after surgery by measuring several standard tests for dry eye: tear film break-up and a Schirmer test at day 7, 14, 30 and 60 after surgery.

They found that there was a statistically significant benefit to the patients who were given lactoferrin after surgery by both the tear film measurement and the Schirmer test. Both the quality and quantity of tears improved markedly.

Researchers: J. Devendra, S. Singh

Published: Effect of Oral Lactoferrin on Cataract Surgery Induced Dry Eye: A Randomised Controlled Trial, Journal of Clinical and Diagnostic Research, October, 2015.

Lactoferrin & Inflammation

Another study found that lactoferrin may be a useful therapy in controlling the release of neutrophil extracellular traps (NETs) that help support the immune system. Because of that capacity they may contribute to therapies in autoimmune or inflammatory-based diseases.

Researchers: K. Okubo, et al.

Published: Lactoferrin Suppresses Neutrophil Extracellular Traps Release in Inflammation, EBioMedicine, July 2016.

Lactoferrin's Other Actions

Lactoferrin is one of a group of biochemicals known as dinucleoside polyphosphates. These biochemicals are found not only in tears but in the aqueous humour in the eyeball and in the retina. Researchers have determined on the surface of the eye they stimulate tears, release of mucin and help wound healing. Lactoferrin has the additional capacity of being an anti-microbial agent.

Researchers: G. Carracedo, A. Crooke, et al.

Published: The role of dinucleoside polyphosphates on the ocular surface and other eye structures, Progress in Retinal and Eye Reseach, July, 2016.

Footnote

1. R. Lauterbach, Lactoferrin - a glycoprotein of great therapeutic potentials, Developmental Period Medicine, 2016.

8. Menstrual Cycle (2014) Linked to Dry Eyes
Learn more about dry eye syndrome

Many women notice that at certain times during their menstrual cycle they have more difficulty with dry eyes and red, irritated eyes. Researchers have linked dry eyes with changes in hormonal levels during the menstrual cycle.

2014

Scientists understand that hormonal changes can be linked to tear production. Researchers compared the condition of the surface of the eye in pre-menopausal women with a similar group of men as a control group.

Normally, your tear glands secret tears and when you blink the tears are spread in a film over the surface of your eye. On top of this tear film is a very thin oily layer of meibum, secreted by the meibomian gland, that helps keep the tear film from evaporating.

You experience dry eyes when either the tear film is insufficient, the meibomian gland is not producing enough meibum, you are not blinking, or any combination of these factors.

In the study the test subjects were given ophthalmologic exams which included an assessment of how fast the thin tear film which covers and protects the eyes deteriorated, and the condition of the surface of the eye. These exams were repeated on day 2, 12 and 21.

For the female patients the condition of the ocular surface was poorer on day 21 than in day 2 or 12; there was no significant change in the male patients. Additionally, both the tear film breakup time and the overall dryness of the surface of the eye coincided. Further, the blood levels of estrogen also coincided with the changes in the cornea's dryness levels.

Researchers: E. Cavdar, A. Ozkava, et al
Published: Changes in tear film, corneal topography, and refractive status in premenopausal women during menstrual cycle, Contact Lens & Anterior Eye, June, 2014.

2007

In this study researchers looked at the changes in tear production and the dryness of the surface of the eye in various specific phases of the menstrual cycle. In a group of 29 women, 14 of whom experienced dry eye symptoms, researchers evaluated tear production, tear film stability, just how dry the surface of the eye was and the kinds of cells making up the conjunctiva. In addition the amount of inflammation was measured.

The women's eyes were evaluated over the course of two menstrual cycles. Exams and samples were taken during the follicular phase, the first part of the menstrual cycle when immature eggs in the ovary mature, ending with ovulation. Exams and measurements were also taken in the luteal phase, which begins with ovulation and until menstrual begins. During this time the egg is ready for fertilization.

During the follicular phase the body produces high levels of estrogen. During the luteal phase the body produces more progesterone.

The researchers reported that dry eye symptoms were significantly higher during the peak of estrogen production in the follicular phase. In patients with dry eye, the dry eye symptoms worsen during this period.

Researchers: P. Versura, M. Fresina, et al,
Published: Ocular surface changes over the menstrual cycle in women with and without dry eye, Gynecological Endocrinology, August, 2007.

9. MSM (2015) Reduces Inflammation - Dry Eye
MSM is helpful not only for dry eyes, but other conditions where inflammation is an issue such as Sjogren's syndrome, cataracts, keratoconus and other conditions.

The researchers noted that while the health benefit of reducing inflammation is associated with Methylsulfonylmethane (MSM) there had been no study focusing on that capacity with regard to inflammasomes - a formation composed of multiple proteins that acts as a basis for stimulating lymphocyte development. Lymphocytes are the white blood cells that fight infection.

The researchers found that MSM did reduce some types of inflammasome activation. They also found that MSM-enriched vegetable given to lab animals had the same effect.

They concluded that MSM does present anti-inflammatory capacity, interrupts inflammasome production, and inhibits expression of pro-cytokines which promote systemic inflammation and make a disease worse through fever and tissue death.

Researchers: H. Ahn, J. Kim, M. Lee, Y. Kim, Y.W. Cho, G. Lee

Published: Methylsulfonylmethane inhibits NLRP3 inflammasome activation, Cytokine, February, 2015.

10. Omega-3 (2005, 2016) and Dry Eyes
Learn more about dry eyes support

2016

Researchers know that omega-3 fatty acids are valuable in vision health, and that previous research has demonstrated that high intakes of omega-3s taken in foods (like fish) contribute as much as 66% reduction in dry eye syndrome in a large sample of women who ate 5-6 servings of tuna weekly.¹

Researchers wanted to know whether a particular formulation of omega-3s were effective for dry eyes - a condition apparently only indirectly related to the health of the retina and nervous system functions.

In a placebo-controlled, double-blind study about 100 participants randomly received re-esterized omega-3s or placebo. The distinction is interesting. There is much concern because fish rich in omega-3s may also have high levels of contaminants such as mercury unless properly processed by the manufacturer. Most fish oils add ethyl alcohol to detoxify at least some contaminants.

The definitions get confusing: Re-esterized fish oil is derived from crude fish oil which is altered with ethanol and then distilled under heat to remove contamination. It results in concentrated omega-3 molecules in an ethyl ester "package" which has been criticized as less stable.²

This study involving 're-esterized' fish oil included a process to remove the alcohol and create a more natural form of omega-3 which is both better tolerated by the body when taken orally and which is more readily absorbed.

The indicators of dry eye syndrome in the patients were measured at the beginning of the study, at the 6th week, and at the 12th week. Standard tests for dry eye were used including the tear osmolarity, the Schirmer test, corneal staining and others.

The participants were asked to continue their normal diets and that they should continue their normal usage and brand of artificial tears. Right before they came for each testing session they were asked to discontinue use of contacts and artificial tears.

Results

The primary concern was tear osmolarity, that is, the saltiness of tear fluid. Osmolarity in the omega-3 group decreased significantly compared to the control group.

Omega-3 index scores (the % of DHA and EPA in red blood cells) also improved significantly in the omega-3 group compared to the control group.

Tear break up time (TBUT) refers to how fast the tear film protecting the surface of the cornea begins to break up. Normally, each time you blink the tear film is redistributed across the eye. If it breaks up quickly then you have to blink a lot to maintain the even distribution. This measurement also displayed a signifiant improvement.

Levels of inflammation are measured by an MMP-9 test (matrix metalloproteinase-9). Again, the omega-3 group shows significant improvement.

The ocular disease surface index (OSDI) scores the overall severity level of chronic dry eye. This score improved for the omega-3 group.

Corneal staining, Schirmer score, MGD stage - for these tests there were improvements but they were not as significant.

Of particular interest was that many of the signs and symptoms of chronic dry eye improved relatively quickly, as early as 6 weeks.

Researchers: Alice T. Epitropoulous, MD, Eric D. Donnenfeld, MD, et al
Published: Effect of Oral Re-esterified Omega-3 Nutritional Supplementation on Dry Eyes, Cornia, September, 2016.

2005

Researchers found that women with a higher dietary omega-3 fatty acid consumption are at lower risk of experiencing dry eye syndrome. Data from the large Women's Health Study included the self-reported diets of more than 32,400 health professionals as well as their health history. The women were aged between 45 and 84 years old. The study was a cross-sectional study meaning that it took a large sample from a population at a single point in time.

The collected data revealed that the higher the intake of omega-3 fatty acids, the lower the risk of developing dry eye syndrome. The researchers adjusted for age, inclusion in hormone therapy, demographics and total fat intake in the diets. Adjustments were also made for presence of other conditions such as hypertension, diabetes, and joint-related conditions.

Researchers: K. A. Trivedi, et al,
Published: Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women, American Journal of Clinical Nutrition, October, 2005.

Footnotes
1. B. Miljanovic, K.A. Trivedi, et al., Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women. American Journal of Clinical Nutrition, 2005
2. Larry J. Alexander, OD, Is There Really a Difference Between Re-esterified Triglyceride and Ethyl Ester Fish Oil?, Advanced Ocular Care, January/February, 2011.
3. J. Dyerberg, P. Madsen, et al., Bioavailability of marine n-3 fatty acid formulations. Prostaglandins, Leukotrienes and Essential Fatty Acids, 2010.

11. Omega-6 (1980) Evening primrose oil & dry eyes
In a small pilot study published in 1980, 17 patients with dry eye syndrome were treated with evening primrose oil. They were chosen to be part of the study due to lack of tear secretion, chronic need of eyedrops, the Schirmer Test, and a clinical exam. Patients received 500 mg capsules of evening Primrose oil, 50 mg vitamin B6 and 1 g vitamin C 3x a day.

Result
Ten of the 17 patients showed substantial improvement of both symptoms and Schirmer test in 2-6 weeks. 3 additional patients reported improved symptoms even though the Schirmer Test was unimproved. The authors felt that this treatment is effective in many, but not all cases.

1. Horrobin DF, Campbell A. McEwen CG: Treatment of the Sicca Syndrome with E.F.A., Pyroxidine and Vitamin C. Prog Lipid Res 8(4):253-4, 1981.
2. Horrobin DR Campbell A. Sjogren's Syndrome and the Sicca Syndrome: the Role of Prostaglandin E1 Deficiency. Treatment with Essential Fatty Acids and Vitamin C. Medical Hypothesis. 6:225-232 1980.

Editor's Note: See more information about our preferred nutritional recommendations dry eyes.

12. Omega-6 (1980), Vitamins B6 and C - Dry Eyes
Learn more about dry eye treatment and information.

Researchers carried out some preliminary studies using the supplemental intake of essential fatty acids, vitamin B6 and vitamin C to treat dry eyes. The rationale for this treatment was based on the biosynthesis of prostaglandin E1 (PGE1), which is necessary for acqueous tear secretion by the tear glands. Patients received 2 x 500 mg capsules of Evening Primrose Oil (omega-6), 50 mg of vitamin B6 and 1 gram of Vitamin C three times daily.

The results showed that 10 of the 17 patients had substantial improvement of symptoms and Schirmer Test in 2-6 weeks, 3 patients reported improved symptoms though without improved Schirmer testing. The authors' conclusion was that this treatment approach is effective in many cases.

Researchers: D.F. Horrobin, A. Campbell, C.G. McEwen.

Published: Srogren's Syndrome and the Sicca Syndrome: The Role of Essential Fatty Acids and Vitamin C, Medical Hypothesis, March, 1980.

13. Omega-6 Fatty Acid Helps Relieve Dry Eyes For Contact Lens Users Study 2008
The purpose of this study was to evaluate the effects of oral treatment with omega-6 fatty acids in the form of evening primrose oil (EPO) on subjective symptoms, ocular surface signs and tear film characteristic in patients with contact lens-associated dry eye.
A total of 76 female soft contact lens wearers were treated for six months either with EPO or placebo (olive oil). Subjects underwent three examinations (baseline, three and six months). At each examination, subjects were given a questionnaire relating to lens comfort and dry eye symptoms, and they underwent a series of tests of tear film characteristics (tear meniscus height, break-up time), meibomian gland function (lipid layer thickness and quality) and ocular surface parameters (hyperemia and staining).
The EPO group showed a significant improvement in the specific symptom of "dryness" at three and six months and also a significant improvement in overall lens comfort at six months. Tear meniscus height was increased in the EPO group at six months relative to baseline, although all other objective signs were unchanged. This study provides evidence for a beneficial effect of particular orally administered omega-6 fatty acids in alleviating dry eye symptoms and improving overall lens comfort in patients suffering from contact lens-associated dry eye.
SOURCE: Kokke KH, Morris JA, Lawrenson JG. Oral omega-6 essential fatty acid treatment in contact lens associated dry eye. Cont Lens Anterior Eye 2008;31(3):141-6.

14. Pregnancy (2015) and Dry Eye Syndrome
Learn more about dry eyes.

For women, hormonal changes during the menstrual cycle, during pregnancy, and post-menopause can cause or contribute to dry eyes.

2015

In this study scientists evaluated the condition of the surface of the eyes in 270 women, 165 of whom were healthy and pregnant. None of the women had any existing eye conditions. They wanted to determine whether and to what degree various factors changed during pregnancy.

They were interested in investigating degree of dry eye as well as changes in intraocular pressure.

The researchers used a number of standard tests including the Schirmer's test which measures whether the tear glands secrete enough tears to keep the eye moist and tear film break up time, which measures how rapidly the thin tear film that protects the surface of the eye deteriorates.

Under normal conditions we blink every few seconds to redistribute the tear film over the surface of the eye as well as the thin layer of oily meibum which protects it. However, if there are not enough tears being produced, then dry eye can result.

The researchers didn't notice anything significant in intraocular pressure changes. However they did notice that both the tear film break up time decreased slightly, and the production of tears decreased significantly.

Researchers: W.A. ibraheem, A.B. Ibraheem, et al
Published: Tear Film Functions and Intraocular Pressure Changes in Pregnancy, Alternative Journal of Reproductive Health, December, 2015.

2016

In this study, which was looking at IVF pregnancies, the researchers noticed that in the third trimester the number of women with at least one dry eye significantly increased.

Researchers: J.K. Parihar, J. Kaushik
Published: The effect of assisted reproductive technology on ocular assessments, Clinical & Experimental Optometry, November, 2016.

15. Vitamin A & Cyclosporine A (2008) - Dry Eye Syndrome
Learn more about natural treatment of dry eyes.

A 2008 study shows that using eyedrops with Vitamin A Palmitate can improve symptoms of blurred vision and tear film after just 4 weeks of usage. It was a prospective, randomized, controlled, parallel group study whose purpose was to compare the efficacy of vitamin A (retinyl palmitate) and cyclosporine A 0.05% eye drops in treating patients with dry eye disease.

In 3 identical clinical trials, 150 patients with dry eye disease were treated either 2x daily with cyclosporine A 0.05%, or 4x daily with retinyl palmitate 0.05%, or neither. In addition, preservative-free artificial tears were given 4x daily in every group. Corneal dye staining observation, Schirmer tear tests, tear film break-up times, dry eye symptom scores, and impression cytologic analysis results were obtained before treatment and at the first, second, and third months after treatment began.
Results:
Both vitamin A eye drops and topical cyclosporine A 0.05% treatments led to significant improvement in blurred vision, tear film break-up times, Schirmer I score results, and impression cytologic findings in patients with dry eye syndrome (P < .05) compared to the control group treated with preservative-free artificial tears alone.
Conclusions:
Both vitamin A eye drops and topical cyclosporine A 0.05% treatments are effective for the treatment of dry eye disorder.
Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul, Korea

Published: published online 09 October 2008

Researchers: Choun-Ki Joo, Department of Ophthalmology, KangNam St Mary's Hospital, #505 Ban-Po Dong, Seocho-Ku, Seoul 137-040, Korea

Note: two recommended products for dry eyes which contain vitamin A as retinyl palmitate are BioTears and VivaDrops.

16. Vitamin D (2015, 2016) & Dry Eyes
Learn more about dry eyes.

2016

A large study evaluated more than 17,000 patients older than 19 in Korea. They were selected randomly from the Korean National Health and Nutrition Examination Survey 2010-2012. The researchers associated low levels of vitamin D with greater incidence of dry eye syndrome.

Note: another study also investigated a large sample from the same survey, and found only a weak connection between vitamin D and dry eye syndrome. However this study did not take into account many factors including gender, region of residence, other health conditions, and amount and type of exercise.

Researchers: S.Y. Yoon, et al
Published: Low Serum 25-Hydroxyvitamin D Levels Are Associated with Dry Eye Syndrome, PLoS One, January, 2016

Researchers found not only that dry eye syndrome is associated with low levels of vitamin D, but that the evaporative type of dry eye syndrome is linked to specific changes in the structure of the cornea.

They found that the density of corneal nerve cells was lower in patients with dry eye; that corneal nerve cells were shorter and thinner, and total area covered by nerve cells was less. In addition, the branch nerves supplying the cornea were also less dense.

Researchers: R. Shetty, et al
Published: Corneal Dendritic Cell Density Is Associated with Subbasal Nerve Plexus Features, Ocular Surface Disease Index, and Serum Vitamin D in Evaporative Dry Eye Disease, BioMed Research International, February, 2016.

2015

Because it is known that the cornea contains receptors to recognize vitamin D and an enzyme catalyst for vitamin D, researchers wanted to know whether the vitamin is also tied to dry eye syndrome.

Scientists assessed the eye condition of 50 women (not menopausal) who were deficient in vitamin D. They used a number of standard tests that measure relevant information including the OSDI test, a standard measure of chronic dry eye, a test of eye pain, a health assessment questionnaire, and a scale which assesses the impact of fatigue on one's life.

Compared to control, the patients with vitamin D deficiency had markedly poorer results for all of these scales - with 52% having dry eye, 74% having weaker general health, and 70% having chronic dry eye.

Symptoms of dry eye: inadequate tear film, unstable tear film, and pain were correlated with deficiency of vitamin D.

Researchers: P. Yildirim, et al.

Published: Dry eye in vitamin D deficiency: more than an incidental association. International Journal of Rheumatic Disease, 2015.

Electromagnetic Pollution (EMF)

1. Cell Phone Radiation (2011, 2016) Linked to Brain Tumors
Learn more about EMF pollution

2016

A landmark study will be published in 2017, but due to the unexpectedness and seriousness of the results, they were been reported to the highest levels of the National Institutes of Health in May of 2016. The carefully designed and controlled study generated results contrary to expectations and stimulated additional reviews by the NIH which found no serious problems in the methodology or data of the study.

The study evaluated the effect of the type of radiation emitted by modern cell phone in lab animals, where cancer can develop in about two years. The ongoing study took place in an underground lab shielded from external radiation and involved 2500 rats.

It was a controlled clinical trial using rats and mice who were exposed to a specific kind of radiation beginning before birth and continuing for two years. They were exposed to 9 hours of radiation from time to time over each day: 10 minutes, followed by a 10 minute break for 18 hours. Each animal was exposed for a two year period. The animals were exposed to the most common types of wireless technologies.

Male rats who had been exposed to the radiation had higher rates of gliomas. Gliomas are a tumor of the cells that surround the nerve cells in the brain. These cells provide not only structural support but deliver oxygen and nutrients to the nerve cells.

Male rats also had higher rates of schwannoma of the heart. Schwannomas are usually benign tumors that generally appear in the myelin sheath that protects hearing-related nerves. The schwannomas of the heart were very rare and were malignant. These two types of tumors did not appear in the control animals who were not exposed to the radiation.

Researchers: U.S. National Toxicology Program, M. Wyde, et al.

Report of Partial findings from the National Toxicology Program Carcinogenesis Studies of Cell Phone Radiofrequency Radiation in Hsd: Sprague Dawley® SD rats (Whole Body Exposure), BioRxiV, May, 2016

2011

In 2011 the International Agency for Research on Cancer (part of WHO) included radiation from cell phones as a possible carcinogen.

Source: Wall Street Journal

A 2011 National Institutes of Health Study showed that a 50-minute cell phone radiation exposure was connected to increased brain glucose metabolism in the region closest to the antenna. The researchers have preliminary indication of long-term effects. Glucose metabolism, is an indicator of brain activity and this finding raises concerns that if cell phone radiation is effecting glucose levels, it may also be effecting neurotransmitters and neurochemical activities.
Researchers: Nora D. Volkow et al, Director of the National Institute on Drug Abuse of the National Institutes of Health

Published: "Cell Phone Radiofrequency Radiation Exposure and Brain Glucose Metabolism," JAMA Feb 23, 2011

Older Studies

Three studies from Europe, one of which combined data from 13 countries found ties between cell phone radiation exposure resulting from heavy cell phone use and brain tumors. Some of these studies were problematic because they used older models of cell phones that are no longer in use and which emitted higher levels of radiation, and the time span of the studies was 5 to 20 years, while cancer can take much longer to develop.

2. EMF Pollution (2011) & Brain Functioning
Learn more about EMF Pollution.

A 2011 paper¹ published confirms that very weak varying electric fields in brain tissue significantly affect neural functioning.

This is the first conclusive evidence that suggests that exposure to EMFs (especially the very high electric fields underneath high voltage overhead power lines as well as low-frequency magnetic fields from mobile phones) may well cause problems that many have suspected.²

The possibility that low level fields have such an impact has been dismissed by scientists, even though doctors have used very high pulsed magnetic fields known as Transcranial Magnetic Stimulation (TMS) to "reset the brain" for many years.The actual mechanism by which TMS works was not proven, but was thought to depolarize the synapses. The 2011 research suggests that a more subtle electric field effect synchronising mechanism is at work. The fact that synchronisation effects have now been found at very low electric field levels has potentially large implications for general EMF exposure guidelines.

The brain displays continual electrical activity with countless overlapping electric fields, generated by the neural circuits of scores of communicating neurons.

New research suggests that at least low frequency electric fields do much more and may represent an additional important form of neural communication.

Anastassiou CA, Perin R, Markram H, Koch C. Ephaptic coupling of cortical neurons. Nat Neurosci. 2011 Feb;14(2):217-23. Epub 2011 Jan 16

Alasdair and Jean Philips Electromagnetic Fields: A Human EMC Problem? (May 2006)

3. EMF Pollution (2012) Brain Areas Related to Learning, Memory, Alzheimers Impacted by EMF Exposure
Learn more about EMF pollution

A 2012 Greek study has measured changes in animal brain proteins after exposure to RF electromagnetic fields, similar to the kind of microwave radiation emitted from cell phones, portable phones, WiFi and wireless computer equipment.

The parts of the brains used for learning and memory were impacted by microwave radiation, including the hippocampus, cerebellum and frontal lobe, at exposures below the ICNIRP (International Commission on Non-Ionizing Radiation Protection) safety guidelines. A total of 143 proteins in the brain were changed over a period of 8 months, providing new evidence for a potential relationship between everyday cell phone use, wireless transmitters and wireless computer equipment and electrosensitivity symptoms, such as headaches, dizziness and sleep disorders, as well as with tumors, Alzheimer's and even metabolic effects.

The study simulated 3 hours of cell phone exposure over eight months, 8 hours of DECT portable phone exposure over eight months, and included a sham exposure control group.

Several proteins employed in the proper functioning of the neurons and proteins of the brain metabolism were impacted in nearly all of the brain regions studied.

This is important. According to wikipedia.com, "The key to neural function is the synaptic signaling process, which is partly electrical and partly chemical. The electrical aspect depends on properties of the neuron's membrane. Like all animal cells, every neuron is surrounded by a plasma membrane, a bilayer of lipid molecules with many types of protein structures embedded in it. A lipid bilayer is a powerful electrical insulator, but in neurons, many of the protein structures embedded in the membrane are electrically active." (italics ours)

One of the researchers, Adamantia Fragopoulou said, "Our study is important because it shows for the first time protein changes in the mouse brain after EMF exposure and in particular in very crucial regions like hippocampus, cerebellum and frontal lobe, all involved in learning, memory and other complicated functions of the mammalian brain. We have demonstrated that 143 proteins are altered after electromagnetic radiation, including proteins that have been correlated so far with Alzheimer's, glioblastoma, stress and metabolism. In its perspective, this study is anticipated to throw light in the understanding of such health effects like headaches, dizziness, sleep disorders, memory disorders, brain tumors, all of them related, to the function of the altered brain proteins."

Here's the link to the full abstract.

Researchers: Adamantia Fragopoulou and Lukas Margaritis

Published: "Brain proteome response following whole body exposure of mice to mobile phone or wireless DECT base radiation," Electromagnetic Biology and Medicine, Early Online: 1-25, 2012

Enlarged Prostrate

1. Xtra Info: Enlarged Prostate (Benign Prosatic Hyperplasia ) Bibliography
Also see discussion of enlarged prostate (benign prosatic hyperplasia) and research.

Lees AM, Mok HYI, Lee RS, et al. Plant sterols as cholesterol-lowering agents: clinical trials in patients with hypercholesterolemia and studies of sterol balance. Atherosclerosis 1977;28:325-38.

Pelletier X, Belbraouet S, Mirabel D, et al. A diet moderately enriched in phytosterols lowers plasma cholesterol concentrations in normocholesterolemic humans. Ann Nutr Metab 1995;39:291-5.

Jones PJ, Raeini-Sarjaz M, Ntanios FY, et al. Modulation of plasma lipid levels and cholesterol kinetics by phytosterol versus phytostanol esters. J Lipid Res 2000;41:697-705.

Grundy SM, Ahrens EH Jr, Davignon J. The interaction of cholesterol absorption and cholesterol synthesis in man. J Lipid Res 1969;10:304-15 [review].

Berges RR, Windeler J, Trampisch HJ, et al. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995;345:1529-32.

Kiriakdis S, Stathi S, Jha HC, et al. Fatty acid esters of sitosterol 3beta-glucoside from soybeans and tempeh (fermented soybeans) as antiproliferative substances. J Clin Biochem Nutr 1997;22:139-47.

Awad AB, Chan KC, Downie AC, Fink CS. Peanuts as a source of beta-sitosterol, a sterol with anticancer properties. Nutr Cancer 2000;36:238-41.

Berges RR, Windeler J, Trampisch HJ, et al. Randomised, placebo-controlled, double-blind clinical trial of beta-sitosterol in patients with benign prostatic hyperplasia. Lancet 1995;345:1529-32.

Klippel KF, Hiltl DM, Schipp B. A multicentric, placebo-controlled, double-blind clinical trial of beta-sitosterol (phytosterol) for the treatment of benign prostatic hyperplasia. Br J Urol 1997;80:427-32.

Eye Infections

1. Eyebright (2015) - Eye Infection
A 2015 study investigated the chemical composition and anti-microbial capacity of an essential oil of eyebright (Euphrasia rostkoviana) - looking at micro-organisms that cause eye infections. The micro-organisms evaluated were:

Enterococcus faecalis

Escherichia coli

Klebsiella pneumoniae

Staphylococcus aureus

S. epidermidis

Pseudomonas aeruginosa

Candida albicans

The study was the first to access the chemical composition of eyebright essential oil, finding more than 70 constituents.

The essential oil was effective against all micro-organisms except Pseudomonas aeruginosa. The most effective activity was against gram-positive bacteria.

Researchers: Novy. P, et al, of Czech University of Life Sciences, Prague

Published: Composition and Antimicrobial Activity of Euphrasia rostkoviana Hayne Essential Oil, Evidence-Based Complementary & Alternative Medicine, April, 2015.

Learn more about eyebright and eye infections.

Our product Advanced Eye & Vision Support Formula contains Eyebright (Euphrasia stricta).

Fuch's Dystrophy

1. Free radicals (2010) implicated in Fuchs endothelial corneal dystrophy (FECD)
Learn more about Fuch's Dystrophy treatment and information.

A research study published in 2010 indicates that free radical damage is a contributor in the development of Fuchs endothelial corneal dystrophy (FECD), a potentially blinding disease characterized by the programmed cell death of epithelial cells in the eye's cornea (the clear tissue in the front of the eye). This is the most common reason for corneal transplant surgery.

Although genetic factors in FECD have been identified, mechanisms involved in its development were unclear. For their study, the researchers compared corneal epithelial tissue samples from FECD patients who received corneal transplants to samples derived from subjects who did not have the disease. They discovered a reduction in the level of antioxidants in the majority of FECD specimens and increased DNA damage.

They therefore concluded that oxidative stress - stress by free radicals plays a key role in development of Fuchs endothelial corneal dystrophy. The finding is significant for the nearly 4% of the population over 60 who are affected by FECD.

The researchers recommended that patients who are at risk supplement with a multivitamin, consume more leafy green vegetables and wear ultraviolet protection.

References:
Published: The American Journal of Pathology, November, 2010.
Researchers: Ula V. Jurkunas, MD and her colleagues at the Schepens Eye Research Institute in Boston

Glaucoma (optic nerve problems)

1. Alpha lipoic acid ('97, '98, 2013-14) & Glaucoma
Learn more about treatment options for glaucoma.

Researchers have long suspected that stress from oxidation caused by free radicals may be a contributing factor in development of glaucoma due to damage to the optic nerve.

2014
In a small animal study the route to the trabecular meshwork, which helps to regulate drainage and intraocular pressure was surgically blocked by sponges for several minutes. This involved the space containing lymph between the sclera which surrounds a membrane which in turn surrounds the eyeball. As a result of this procedure the capacity of the trabecula to regulate intraocular pressure was impacted (this process is known medically as a 'filtering bleb') resulting in scarring of the conjunctiva. This is important because many medications used to treat glaucoma and cancers cause conjunctiva scaring, also known as conjunctival fibrosis.

There were three test groups: control, animals treated with mitomycin-C (a chemical used to treat cancers and in glaucoma surgery), and animals treated with alpha lipoic acid (ALA). The control and mitomycin-C treated animals were found to have failed filtering blebs; only 1/3 of the group treated with ALA had the problem. The researchers reported that ALA reduced scarring, inflammation, and accumulation of waste materials in the eye, those protecting the eye from some side effects of this medication.

Researchers: M. Ekinci, et al.

Published: Reduction of conjunctival fibrosis after trabeculectomy using topical α-lipoic acid in rabbit eyes
2013
Scientists evaluated the contribution of stress in glaucoma development in lab animals. Mice with glaucoma were given alpha lipoic acid (ALA) - some were given ALA at age 6 months to interrupt glaucoma development and a prevention diet in which mice were raised on a diet supplemented with ALA prior to glaucoma development.

They measured changes in the genes and proteins for both groups (after 4 months and 11 months of ALA in the diet), with an eye to oxidative stress, nerve cell structure, and number, integrity, and transport of axons. Both groups of mice showed improvement in gene and protein expression, protection of retinal ganglions (nerve cells) and transport compared to controls.

They concluded that such supplementation has a utilitarian value in reducing free radical stress and improving the survival of nerve cells in the optic nerve.

Researchers: D.M. Inman, W. S. Lambert, D.J. Calkins, and P.J. Horner.

Published: Alpha Lipoic acid antioxidant treatment limits glaucoma-related retinal ganglion cell death and dysfunction, PLoS One, June 2013.

1998

Researchers investigating the antioxidant benefits of alpha lipoic acid provided either 75mg daily for 2 months, or 150mg daily for one month to subsets of 75 open-angle glaucoma patients. There were 31 control subjects who received placebo. They found that, both biochemically, and in terms of visual acuity, the group receiving the larger dosage had the best results.

Published: Alpha Lipoic Acid; Alternative Medicine Review, August, 1998

1997

The authors reviewed current research about the capacity of alpha lipoic acid to protect nerve cells from damage. Alpha lipoic acid is able to cross the blood-brain barrier to protect both nerve cells and the extracellular environment. It is a potent antioxidant regenerating through re-cycling other antioxidants such as vitamins C and E in order to raise glutathione levels within the cells and as such is an ideal nutrient in treating tissue damage due to oxidation from free radicals.

Its benefits are to be found in treating a number of related conditions caused by changes in blood flow, damage due to over active neurotransmitter receptors, problems with functioning of mitochondria (cell energy center), and other causes of damage to brain or nerve cell tissue.

Alpha lipoic acid helps the liver to produce glutathione, the most important antioxidant for vision health.

Authors: L. Packer, H.J. Tritschler, and K. Wessel.

Published: Neuroprotection by the metabolic antioxidant alpha-lipoic acid, Free Radical Biology & Medicine, 1997.

1995

Some earlier research on the benefits of alpha lipoic acid:

Helps with visual acuity and color perception. (Filina, et al, Vestnik Oftalmologii, October-December, 1995).

Has strong protective properties for nerve cells. (Journal of Cerebral Blood Flow and Metabolism, July, 1995).

2. Antioxidants (2016, 2008) & Glaucoma
See more information about glaucoma treatment and information.

2016

An independent review of the literature and recent research finds that the problems that give rise to blockage of the trabecular meshwork and glaucoma are largely related to and/or aggravated by oxidative stress. The review suggests that new research look more closely into the role of various specific antioxidants and their efficacy in addressing the problem.

Researchers: J. Zhao, et al,
Published: Oxidative stress in the trabecular meshwork, International Journal of Molecular Medicine, October 2016.

Researchers investigate the role of antioxidants in fighting glaucoma. They point out that the degeneration of the optic nerve in glaucoma causes problems above and beyond the eye itself. Since the optic nerve is a direct connection with the visual cortex and the rest of the brain, such degeneration can extend there. They point out that neurons are destroyed because of oxidative stress, inflammation of the optic nerve, and damage due to overstimulation of the optic nerve. They point to use of antioxidants as one of a variety of therapies that are not being used to delay further worsening of the condition although lowering intraocular pressure is the only direct focus. It is felt that more adequately protecting the optic nerve in the first place is the best means of reversing or halting progression of glaucoma.

Researchers: A.C. Gauthier, J. Liu
Published: Neurodegeneration and Neuroprotection in Glaucoma, The Yale Journal of Biology and Medicine, March, 2016.

2008

An independent study finds that the antioxidants vitamin E and N-acetyl cysteine (NAC) may reduce the progression of glaucoma. Additionally noted is that effectively reducing or even reversing oxidation may facilitate a healing response in the trabecular meshwork or outflow pathway in the eyes of glaucoma patients. A key suspect in the progression of POAG is local oxidative stress. Oxidative free radicals and reactive oxygen species (ROS) are reported to trigger degeneration in the trabecular meshwork, subsequently leading to increases in IOP and glaucoma.
"The finding of a protective effect of vitamin E and N-acetyl cysteine (a key component of glutathione) adds to the growing evidence that antioxidants are beneficial in POAG and are worthy of further investigation." Dr. Yuan He
Reference: Yuan He, et al. Mitochondrial Complex I defect induces ROS release and degeneration in trabecular meshwork cells of POAG patients: Protection by antioxidants, Invest Ophthalmol Vis Sci 49:1447-58, 2008.

3. Bilberry/Pine Bark (2008, 2010, 2015) & Glaucoma
Learn more about glaucoma.

2015

A study tested the effect of a supplement (ProVens^®) containing extracts of maritime pine bark, green tea, and blueberry (similar to bilberry). These extracts contained antioxidant proanthocyanidins (pine bark), polyphenols (green tea) and anthocyanins (blueberry). All three types of nutrients are amount the family of antioxidants called bioflavonoids comprised of the colorant material of different plant forms.

The patients received the supplement once a day. The dosage was 50mg pine bark, 100mg green tea, and 3mg blueberry. The patients in the trial had either high intraocular pressure (IOP) (35) or open-angle glaucoma (11 - who had been treated with prostaglandin analogs.

IOP was measured by standard methods at the beginning of the trial period, after one month and after three months.

There was statistically significant reduction in IOP in the patients with high IOP (from ave. 24.2mmHg to ave. 20.9mmHG) within the three month period. In the patients with open-angle glaucoma there was also a reduction (from ave. 18.4mmHG to ave 17.0mmHG) within three months. No side effects were reported for either group.

The researchers concluded that this supplement formulation could be an effective method to help control high IOP.

Researchers: M. Karhanova, M. Eliasova, et al
ProVens^® in the Therapy of Glaucoma and Ocular Hypertension, Ceska a Slovinska Oftalomogie, Winter, 2015.

2010

An earlier study examined the effects of a formulation called Mirtogenol which combines French maritime pine bark and bilberry. The group studied consisted of 79 patients living with "asymptomatic ocular hypertension". The participants were separated into three groups:

received 80 mg of Mitroselect bilberry extract and 40 mg of Pycnogenol daily

applied a medicinal eye drop (Latanoprost)

utilized both treatments

The trial lasted a total of 24 weeks and yielded the following results:

The Mirtogenol group lowered their intraocular pressure (IOP) from 38.1 to 29 mmHg or 24%.

The Latanoprost patients found an IOP reduction from 37.7 to 27.2 mmHg or 28%.

The combination group began with an IOP of 38 mmHg and ended with an IOP of 23 mmHg - a 40%

Healthy or normal eye pressure should range between about 10 to 21 mmHg.

In conclusion, the authors reported that, "The combination of both was more effective for lowering IOP and the combination yielded better retinal blood flow. No serious side effects occurred during the study, apart from standard side effects in patients related to Latanoprost". According to the National Institutes of Health, Latanoprost may cause the following adverse reactions in some users: dry eyes, eye color changes, irritation and redness of the eyelids.

Researchers: Robert D Steigerwalt, Jr, Gianni Belcaro, Paolo Morazzoni, Ezio Bombardelli, Carolina Burki, and Frank Schonlau

Published: Mirtogenol potentiates latanoprost in lowering intraocular pressure and improves ocular blood flow in asymptomatic subjects, Clinical Ophthalmology, 2010.

2008

A 2008 Italian study tested thirty-eight subjects with elevated pressures. 20 were treated with bilberry and French maritime pine bark, the rest were given nothing. Visual acuity, IOP, and ocular blood flow were measured after 2, 3 and 6 months. After two months the mean IOP decreased. No side effects were observed and ocular blood flow improved.

An improved ocular blood flow may contribute to the prevention of glaucoma.

The researchers also looked at the arteries of the eyes with color Doppler imaging and saw better flood flow in the subjects receiving the treatment. This suggests that fluids in the eye were being restored.

One of the researchers, Steigerwalt, said, "Our study is the first demonstration showing that dietary intervention can help to control IOP and increase ocular blood flow in asymptomatic subjects and if taken in time, may prevent an evolution to higher pressure and symptomatic glaucoma."

Published: Molecular Vision 2008; 14:1288-1292, "Effects of Mirtogenol on ocular blood flow and intraocular hypertension in asymptomatic subjects"

Reference: Authors: Robert Steigerwalt Jr, Belcaro Gianni, Morazzoni Paolo, Ezio Bombardelli,2 Carolina Burki, Frank Schonlau , University of Chieti-Pescara in San Valentino, Italy

4. Carotenoids (1994) and green leafy vegetables
See more information about holistic glaucoma treatment and information.

Holistic eye doctors know that green leafy vegetables are good for vision health.

In addition to beta carotene, researchers have found that other carotenoids, lutein and zeaxanthin, which found in dark green leafy vegetables are more essential to vision health. Several published studies indicate that lutein and zeaxanthin supplements may slow vision loss due to glaucoma, and in some cases improve eyesight.

Published: Science News, Volume 146, 1994.

5. Coleus forskohlii ('84, '87, 2015, 2016) & Glaucoma
Learn more about glaucoma.

Forskolin is the ingredient from the coleus forskohlii plant that has been found to be helpful for glaucoma.

2016

A clinical trial of a glaucoma supplement¹ containing the active ingredient forskolin from coleus forskohlii, along with a form of taurine, carnosine (found in N-actyl-carnosine), folic acid, B1, B2, B6, and magnesium investigated whether it was effective as a glaucoma treatment.

The patients were already taking medication to lower too-high intraocular pressure. They added the food supplement to their daily intake for a year.

Standard testing was performed at the beginning, and at 3, 6, 9 and 12 months. Testing measured the electrical activity of light-stimulated retinal cells, sensitivity of the center of the macula (the fovea) to stimulation, and the width of the visual field.

The researchers found:

That the effect of the nutrients taken orally (rather than as eyedrops) was measurable,

That intraocular pressure dropped (additionally to the lowering due to their medication,

And that, at least initially, the nutrients were able to modify the nerve cells in the retina.

Researchers: M.G. Mutolo, et al,
Published: Oral Administration of Forskolin, Homotaurine, Carnosine, and Folic Acid in Patients with Primary Open Angle Glaucoma: Changes in Intraocular Pressure, Pattern Electroretinogram Amplitude, and Foveal Sensitivity, Journal of Ocular Pharmacology and Therapeutics, April, 2016.

Editor's note: Coleus is just one of several herbs that are traditionally known to support vision health and that have the ability to positively influence the health of the optic nerve.

1. We don't know the name of the supplement, but the ingredients are almost identical to our optic nerve support packages.

2015

A study investigated the effects of 1% forskolin eye drops in 90 patients with an intraocular pressure of more than 24mm Hg. The patients used the eyedrops three times a day. The intraocular pressure was measured at the beginning of the study period and after 1, 2, 3 and 4 weeks. From the beginning of the study period to the 4th weeks the average IOP dropped 4.5mm Hg to 5.4mm Hg in the right and left eyes, respectively.

The researchers concluded that 1% forskolin eyedrops can be safely used as an alternative to beta blockers.

Researchers: M. Majeed, et al,
Published: Efficacy and safety of 1% forskolin eye drops in open angle glaucoma - An open label study, Saudi Journal of Ophthalmology, July 2015.

1987

A small placebo-controlled study investigated the effects of forskolin on intra-ocular pressure in 10 healthy subjects. First they received oxybuprocaine eyedrops for local anaesthesia. Some then received 1% forskolin eyedrops and others received placebo and IOP was measured hourly. A marked reduction in IOP was noted in those receiving either test and placebo.

Next a different anaesthetic was used, proxymetacaine - and again the subjects were treated with either test or placebo. In this instance, forskolin resulted in significant reduction compared to placebo, and it was concluded that the first anesthetic used, oxybuprocaine, itself had an effect on IOP.

Researchers: B H Meyer, A A Stulting, F O Muller, H G Luus, M Badian,
Published: The effects of forskolin eye drops on intra-ocular pressure, South African medical journal, June, 1987.

1984

A small double-blind, placebo-controlled study found that .3%, .6% & 1.% effectly lowered the intraocular pressure (IOP) in healthy subjects. The .3% concentration resulted in a 22.8% decrease; the .6% concentration resulted in a 27.8% decrease after 3 hours, and the 1% concentration resulted in a 26.5% decrease after 4 hours.

Further, the researchers found that the higher concentrations were about as effective as the lower concentrations, but lasted longer, with the 1% concentration lasting 7 hours, but the .3% concentration only lasting 4 hours.

The subjects noticed only very short term, minor sensations like itching or burning.

Researchers: Badian M, Dabrowski J, Grigoleit HG, Lieb W, Lindner E, Rupp W.,
Published: Effect of forskolin eyedrops on intraocular pressure in healthy males [in German], Klin Monbl Augenheilkd, December, 1984.

6. Computer Use (2004) & Glaucoma
Spending too much time looking at a computer screen may raise your risk of the vision-robbing eye disease glaucoma, particularly if you're nearsighted, according to a new Japanese study.

Glaucoma is a group of eye diseases that ultimately cause damage to the optic nerve. It can lead to blindness if not treated.

Heavy computer users who were farsighted or nearsighted seemed to have a higher risk for visual field abnormalities, say the researchers.

Source: Journal of Epidemiology and Community Health, December 2004; vol 58: pp 1021-1027

See an article with more detail about this glaucoma study and computer eye strain.

See more information on glaucoma care and treatment.

7. Depth Perception (2006) Deficits in Glaucoma Suspects
Learn more information about glaucoma treatment and information.

A 2006 study investigated depth perception in glaucoma suspects compared to glaucoma patients and controls. Glaucoma suspects (n=16), patients (n=18), and normal age-matched controls (n=19) aged 40- 65 years were prospectively evaluated for depth perception deficits using the Frisby Test. Stereoacuity was measured by stereothreshold in seconds of arc for each group.

Glaucoma suspects showed significantly increased mean stereothreshold compared to age-matched normals (144.1 +/- 35.2 vs. 26.6 +/- 3.7 seconds of arc). The mean stereothreshold in glaucoma patients was also increased compared to age-matched normals (148.1 +/- 33.8 vs. 26.6 +/- 3.7 seconds of arc).
Glaucoma suspects show depth perception deficits. Evidence of impaired stereovision in glaucoma suspects suggests that binocular interactions are disrupted in the absence of visual field defects using standard automated perimetry.

SOURCE: Gupta N, Krishnadev N, Hamstra SJ, Yucel Y. Depth Perception Deficits in Glaucoma Suspects. Br J Ophthalmol. 2006 May 3; [Epub ahead of print].

8. Diet (2008, 2016) Glaucoma Risk Reduction through Nutrition
2016

Researchers evaluated dietary data from the Nurses' Health Study which comprised almost 64,000 women over 28 years, as well as data from the Health Professionals Follow-up Study which comprised over 41,000 men over a 26 year period. Because the presence of oxygen, supplied to the eye as nitric oxide, has been reported to be a positive factor in the development of primary open angle glaucoma. Nitrates in green leafy vegetables contribute significantly to oxygen in the blood and so the diets of these more than 100,000 subjects was evaluated with respect to the incidence of glaucoma. The subjects were followed every two years over the 26 or 28 year period.

The researchers found that the subjects with the highest 1/5th levels of green leafy vegetables in their diets had up to 30% less risk of glaucoma incidence compared to the subjects with the lowest 1/5th amounts of the nitrate-rich green leafy vegetables. The lowered risk rate was especially significant for early paracentral glaucoma with early vision field loss where the risk was 40 to 50% less.

Researchers: J. H. Kang, W. C. Willett, et al.

Published: Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma: A Prospective Analysis From the Nurses' Health Study and Health Professionals Follow-up Study, JAMA Opthamology, January 2016.

2008

Several studies published in 2008 looked at glaucoma risk and nutrition and found a possible relationship between eating fruits and vegetables and lowered glaucoma risk.

Study I

The first study investigated whether specific nutrients might account for an apparent relationship between glaucoma risk and fruit and vegetable consumption. The researchers also investigated potential links between glaucoma risk and antioxidants, calories, fat, protein, and carbohydrates obtained from natural food sources. The study evaluated data from the Study of Osteoporotic Fractures Research Group¹.

Summary I:

Glaucoma risk was decreased 69% in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month.

Glaucoma risk was decreased 64% in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week.

Glaucoma risk was decreased 47% in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month.

Researcher: Anne L. Coleman, MD, PhD, professor of ophthalmology in the Jules Stein Eye Institute of the David Geffen School of Medicine at the University of California Los Angeles and professor of epidemiology in the UCLA School of Public Health, study published in the American Journal of Ophthalmology, 2008

Study II

The second study drew data from the same research¹.

Summary II:

This study further analyzed the results of the first study above regarding the effects of nutrition on the African-American community who have a higher percentage of glaucoma.

The data included 584 black women of whom 13% had glaucoma in at least one eye.

Three or more servings per day of all fruits or fruit juices decreased the odds of glaucoma by 79% compared to consuming less than one serving per day.

Eating more than two servings per week of fresh oranges and peaches was associated with less glaucoma risk.

Eating more than one serving per week of green collards or kale decreased the odds of glaucoma by 57% compared to 1 serving per month or less.

There was a protective trend for glaucoma in those eating more fruit or fruit juices), fresh oranges, fresh peaches, spinach), and green collards or kale.

Higher intakes of some nutrients were also associated with decreased risk: vitamin A; folate; a-carotene; beta-carotene; and lutein/zeaxanthin.

The researcher notes that it's dangerous to draw too many conclusions from the nutrition-related data found so far, saying that the studies are exploratory and there are clear associations, but not conclusive proof, that, for example, eating collards prevented glaucoma. There could be environmental differences or differences in how their bodies metabolize nutrients. But the association was worth pursuing.

Researcher: JoAnn A. Giaconi, MD, assistant clinical professor of ophthalmology at the Jules Stein Eye Institute at UCLA. Published: Giaconi JA, et al. IOVS 2008;49; ARVO E-abstract 5453.

Coleman AL, Stone KL, Kodjebacheva G, Yu F, Pedula KL, Ensrud KE, Cauley JA, Hochberg MC, Topouzis F, Badala F, Mangione C; Study of Osteoporotic Fractures Research Group

9. East Baltimore Eye Survey (1988)
Learn more information about glaucoma treatment and information.

A 3-year survey examined 5,308 individuals in East Baltimore. They found that approximately 40 percent of people with glaucoma have normal, not elevated, internal eye pressure. It is also confirmed that many people with elevated IOP never develop the optic nerve damage consistent with glaucoma (Beaver Dam Study had the same conclusion).

10. Exercise (2004) & Glaucoma
Research has shown that glaucoma patients who take a brisk, 40-minute walk five days a week for three months can reduce the pressure in their eyes by approximately 2.5 millimeters - similar to the reduction seen when using beta-blockers.

Reference: Passo, M.S. et. al. Regular exercise lowers intraocular pressure in glaucoma patients. Investigative Ophthalmology 35. In ARVO Abstracts, March 15, 1994.

Read more information on prevention strategies for glaucoma.

11. Exercise ('91, '95, '09, 2016) & Glaucoma
Learn more about glaucoma.

The fact that exercise is very helpful in managing glaucoma is of special importance because heavy computer users (who tend to be sedentary) are at greater risk of developing the condition.

2016

Many researchers have reported that in the short term exercise reduces intraocular pressure in glaucoma patients. This study investigated whether this was true for longer periods.

Researchers surveyed the self-reported exercise levels of 24 glaucoma patients over three years. Eleven of the patients had continued exercise habits; the remaining 23 did not. They found that the patients who maintained a program of regular exercise had much slower progression of their condition.

Researchers: S. Yokota, Y. Takihara, et al,
Published: The relationship between self-reported habitual exercise and visual field defect progression: a retrospective cohort study, BMC Opthalmology, August, 2016.

2009

These researchers looked at data from the National Runners' Health Study in order to evaluate the relationship between vigorous physical activity, (ie, degree of cardiac fitness) in athletes and glaucoma risk.

The eye health of nearly 30,000 male runners, who did not have diabetes (a glaucoma risk factor), and who raced and ran regularly, was followed over a period of 7.7 years. The researchers were looking at the dose-response relationship, the pattern of physiological reaction, of their exercise to glaucoma risk.

In addition, the researchers took into account the runners' age, consumption of fish, meat, alcohol and fruit, and whether they smoked or had high blood pressure.

Over the 7.7 year followup period, 200 glaucoma cases were reported. The slowest men, who also were the men who ran the least, had the highest % of glaucoma cases, while the men who ran the most and were fastest had the lowest risk, or no cases of glaucoma at all.

It is particularly interesting that the researchers actually treated running in terms of dosage, with risk decreasing 37% per meter per second in better running speeds, using the slowest men in 10-km races as a baseline:

In those who ran 3.6 to 4.0 meters/second there was 29% risk reduction.

In those who ran 4.1-4.5 meters/second there was a 54% risk reduction.

In those who ran 4.6-5.0 meters/second there was a 51% risk reduction.

In 781 men who exceeded 5.0 meters/second, there were no glaucoma cases.

These relationship held true when adjusted for performance in long races versus shorter daily runs.

The results suggest that vigorous physical activity may very well reduce glaucoma risk.

Researcher: Paul T. Williams
Published: Relationship of incident glaucoma versus physical activity and fitness in male runners. Med Sci Sports Exerc 2009;41(8):1566-1572

1995

In a small study researchers found that both people with normal intraocular pressure and people with elevated intraocular pressure experienced reductions when they exercised. And the greater the degree of exercise, the greater the reduction. The patients with elevated pressure experienced greater reductions than those with more normal levels.

Normal - walking: -2.4mmHg

Normal - jogging: -3.9mmHg

Normal - running: -4.0mmHg

Elevated - walking: -7.7mmHg

Elevated - jogging: -10.9mmHg

Elevated - running: -12.9mmHg

It was apparent that for everyone the exercise, whether mild or vigorous had a beneficial effect, especially for the glaucoma patients.

Researchers: I.A. Quereshi
Published: The Effects of Mild, Moderate and Severe Exercise in Glaucoma Patients, The Japanese Journal of Physiology, 1995

1991

In another small study researchers found that sedentary glaucoma patients who walk briskly for 40 minutes, five days a week can reduce their intraocular pressure by about 4.6mm Hg. This is with regular aerobic exercise for three months. The result is about the same reduction that can be expected by using beta-blocker medications for glaucoma. When the patients returned to their previous routine without the aerobic exercise their intraocular pressures again increased.

Researchers: Passo, M.S. et. al.
Published: Exercise training reduces intraocular pressure among subjects suspected of having glaucoma, Investigative Ophthalmology, March, 1991.

12. Flavonoids (2015) & Glaucoma
See the descriptions of different bioflavonoids on Glaucoma.

Meta-analysis of flavonoids (on Ginkgo page)

Green tea

Bilberry

Coleus

Other good dietary sources of flavonoids are parsley, black tea, citrus fruit, wine, cocoa and peanuts.

13. Forskolin and Rutin (2012) Reduces IOP
Learn more about Glaucoma and treatment for the optic nerve.

2012

Patients with glaucoma are routinely provided with prescriptions to help reduce their elevated IOP. But sometimes that is not sufficient and surgery is required. In this small study (52 subjects, 45 control) patients who were planning surgery were given oral dosage of forskolin and rutin in addition to their topical drug treatment during the 30 days prior to surgery.

The combination, augmenting their prescription drugs, resulted in a further 10% reduction in their IOP. The researchers concluded: "Forskolin and rutin given as oral treatment appear to contribute to a better control and a further small reduction of IOP in patients who were poorly responsive to multitherapy treatment."

Published: Vetrugno M, Uva MG, Russo V, Iester M, Ciancaglini M, et al. (2012). Control in Primary Open Angle Glaucoma Patients Under Maximum Tolerated Medical Therapy. J Ocul Pharmacol Ther. Oct;28(5):536-41.

Another study found that the same combination, forskolin and rutin can blunt spikes in IOP that may occur after Nd-YAG laser iridotomy, avoiding serious damage to the optic nerve.

Laser iridotomy is a procedure in which doctors create a microscopic opening in the iris to provide drainage in glaucoma patients with narrow or closed angles.

Published: Nebbioso M, Belcaro G, Librando A, Rusciano D, Steigerwalt RD, et al. (2012). Forskolin and rutin prevent intraocular pressure spikes after Nd:YAG laser iridotomy. Panminerva Med. Dec;54(1 Supple 4):77-82.

14. Ginkgo biloba (1999, '03, '06, '15), Glaucoma & Intraocular Pressure
Learn more information about glaucoma treatment and information.

2015

25% of Ginkgo biloba is comprised of antioxidant flavonoids. Because of their antioxidant, anti-inflammatory and nerve-protecting capacity they have been used in treatment for glaucoma, including normal-pressure glaucoma. Conventional treatments for normal tension glaucoma and open-angle glaucoma do not always prevent progression of the condition.

While there have been many small studies on the effect of flavonoids in general and Ginkgo in particular, the results have been conflicting, although many of them indicated positive benefits for patients with normal tension glaucoma.

This meta-analysis and review of the best of these small studies did find a statistically that flavonoids did help protect or improve the peripherial field vision in patients with glaucoma, particularly those with more several loss of visual field. The study found improved ocular blood flow, and apparent improved retinal nerve cell functioning.

Researchers: S. Patel, J.J. Mathan, et al,
Published: The effect of flavonoids on visual function in patients with glaucoma or ocular hypertension: a systematic review and meta-analysis, Graefes Archive for Clinical & Experimental Ophthalmology, November, 2015.

2006

This study examined the effects of Ginkgo on intraocular pressure in young rabbits with (steroid-induced) glaucoma (ocular hypertension).

The rabbits received topical TobraDEX and/or 5 mcg of Ginkgo biloba extract 4x daily for 2 weeks, and their intraocular pressure was measured periodically.

The trabecular meshwork (TM), the network of fibers near the base of the cornea, was examined. Ginkgo biloba extract had reduced the accumulated material clogging the TM, but suppressed the intraocular pressure. In general better TM cell health resulted.

In addition, the researchers examined lab-cultured human TM cells and found that ginkgo markedly reduced degradation of meshwork cells and reduced production of DEX-induced myocilin that can clog the meshwork. Ginkgo biloba extract also controlled the expression of related proteins but not other stress-related genes. Furthermore, it reduced direct damage to the TM cells from steroids.

The researchers concluded that Ginkgo biloba extract suppressed the high intraocular pressure caused by the steroids and protected the meshwork cells against steroid damage.

Published: Jia LY, Sun L, Fan DS, et al. Effect of Topical Ginkgo biloba Extract on Steroid-Induced Changes in the Trabecular Meshwork and Intraocular Pressure. Arch Ophthalmol 2008;126(12):1700-1706.

2003

A early clinical trial suggests that ginkgo biloba extract has possibilities.

The research looked at the effect of ginkgo biloba extract on pre-existing visual field damage in normal tension glaucoma.

In normal tension glaucoma damage occurs to the optic nerve and visual field are present despite intraocular pressure measurements being 'normal'. The exact mechanisms behind the damage are unknown, but there are two primary factors:

reduced blood flow to the optic nerve

versus relatively high intraocular pressure

The researchers felt that because some patients with normal tension glaucoma can experience narrowing of the peripherial field despite conventional medical treatment, the value of other treatments is worthy of investigation. Since Ginkgo biloba has been shown to improve blood flow at a tissue level, it was an obvious candidate for selection in such investigations.

In a randomized, double-blind, placebo-controlled, crossover trial, 27 patients with bilateral visual field damage (less peripherial vision) resulting from normal tension glaucoma received Ginkgo biloba extract or a placebo. Visual field tests were performed at the beginning of the trial and at the end of each 4-week period.

The researchers measured any changes in the visual field and the development of any ocular or systemic complications. After Ginkgo biloba treatment, a significant improvement in visual field indices was recorded, but there were no significant changes found in intraocular pressure, blood pressure or heart rate.

No ocular or systemic side effects were noted in any patient during the trial. The authors concluded that Ginkgo biloba extract can improve pre-existing visual field damage in some individuals with normal tension glaucoma. However, they observed that the exact explanation is not currently understood.

Researchers: Quaranta L, Bettelli S, Uva MG et al.
Published: Effect of Ginkgo biloba extract on preexisting visual field damage in normal tension glaucoma. Ophthalmology February, 2003.

1999

Researchers found a possible benefit from treatment with Ginkgo biloba for existing glaucoma patients. The benefit comes from Ginkgo's ability to improve blood flow in the eye. The trial was a crossover trial in which 11 patients received a series of different therapies in order to compare them. The treatments were:

40 mg daily Ginkgo biloba extract 2 days followed by a two week rest period,

placebo for 2 days

Treatment with Ginkgo improved diastolic velocity in the main artery in the eye while placebo caused no change. Ginkgo did not change blood pressure, heart rate or intraocular pressure in this short trial.

Researchers: H.S. Chung, et al,
Published: Ginkgo biloba extract increases ocular blood flow velocity, Journal of Ocular Pharmacology and Therapeutics, June, 1999.

15. Glaucoma (2004) linked to Heavy Computer Use
Spending too much time looking at a computer screen may raise your risk of the vision-robbing eye disease glaucoma, particularly if you're nearsighted, according to a new Japanese study. Glaucoma is a group of eye diseases that ultimately cause damage to the optic nerve. It can lead to blindness if not treated. Heavy computer users who were farsighted or nearsighted seemed to have a higher risk for visual field abnormalities, say the researchers. Source: Journal of Epidemiology and Community Health, December 2004; vol 58: pp 1021-1027

16. Glaucoma (2006) Glaucoma & Other Diseases
Despite intense research, the pathogenesis of primary open-angle glaucoma (POAG) is still not completely understood. There is ample evidence for a pathophysiological role of elevated intraocular pressure; however, several systemic factors may influence onset and progression of the disease.

Systemic peculiarities found in POAG include alterations of the cardiovascular system, autonomic nervous system and immune system, as well as endocrinological, psychological and sleep disturbances. An association between POAG and other neurodegenerative diseases, such as Alzheimer disease and Parkinson disease, has also been described. Furthermore, the diagnosis of glaucoma can affect the patient's quality of life.

SOURCE: Pache M, Flammer J. A sick eye in a sick body? systemic findings in patients with primary open-angle glaucoma. Surv Ophthalmol 2006;51(3):179-212.

Learn more information about glaucoma.

Heavy computer users are at greater risk for glaucoma. Read this computer use and glaucoma warning.

17. Glutathione (2005, 2013) Levels Low in Glaucoma Patients
Learn more about glaucoma.

Scientists have suspected that many eye conditions are related to low antioxidant levels in eye tissue. Glaucoma is one of the conditions for which this is true.

Glutathione is an antioxidant that can protect against damage from free radicals. It isn't considered an essential nutrient because the body can create it through a metabolism process involving specific amino acids. But one of the amino acids needed, cysteine, is rare in foods and its presence or lack becomes a limited factor in availability of glutathione in the body.

2017

Read about the role of oxidative stress on glaucoma risk.

2013

Following up on earlier research, scientists wanted to compare glutathione levels in patients with primary open angle glaucoma and patients with normal tension glaucoma. Such a study would help to identify antioxidants rather than IOP as a primary cause of glaucoma.

The subjects were 34 primary open angle glaucoma patients, 30 normal tension glaucoma patients and 53 control subjects.

Patients with closed angle glaucoma, secondary glaucoma, or a history of eye surgery or other vision condition were excluded.

The participants all received blood analysis, blood pressure testing and IOP measurements.

The participants were age- and gender-matched.

Regardless of age both groups of patients with glaucoma had markedly lower levels of glutathione in their blood. These results indicate for the first time that the health of the antioxidant defense system is a key component to glaucoma risk.

Researchers: D. Gherghel, S. Mroczkowska, et al,
Published: Reduction in Blood Glutathione Levels Occurs Similarly in Patients With Primary-Open Angle or Normal Tension Glaucoma, Glaucoma, May, 2013.

2005

Researchers wanted to evaluate how much glutathione was in the blood plasma of glaucoma patients compared to glutathione levels in people without optic nerve problems. The patients were all newly diagnosed with glaucoma and had IOP measurements of higher than 21 mmHg as well as other indicators of the condition. Patients with narrow angles, secondary open-angle glaucoma, previous surgery or other vision conditions were excluded. The study included 21 glaucoma patients with primary open-angle glaucoma and 34 sex- and age-matched controls.

A blood analysis found that the glaucoma patients had markedly less glutathione in their blood plasma. They also found that in the control group the men had higher levels of glutathione than the women and the younger people had higher levels than the older subjects. There were no differences in blood pressure, which had also been measured.

The researchers concluded that the low levels of glutathione suggested an overall low quality of the antioxidant defense system. This is important because scientists now understand that the ability of the body to fight off free radical damage is a matter of balance between free radicals and antioxidants in the body.

Researchers: D. Gherghel, H.R. Griffiths, et al,
Published: Systemic Reduction in Glutathione Levels Occurs in Patients with Primary Open-Angle Glaucoma, Glaucoma, March, 2005.

18. Green Tea (2010) Green Tea Can Help Combat Glaucoma
Researchers in China say that green tea may protect against eye diseases such as glaucoma.
The researchers confirmed that substances found in green tea, which is known for its antioxidant and disease-fighting properties, were absorbed in the lens, retina and other eye tissue. Until this research it was not actually known whether green tea substances actually passed from the gastrointestinal tract into eye tissue.
The researchers analyzed the eye tissue of laboratory rats that drank green tea and found that several "catechins" in green tea that contain antioxidants -- including vitamin C, vitamin E, lutein and zeaxanthin -- were absorbed by the eye in significant amounts.
The researchers said green tea catechins reduced harmful oxidative stress in the eye for up to 20 hours, saying, "Our results indicate that green tea consumption could benefit the eye against oxidative stress."

Reference: Chi Pui Pang of the Chinese University of Hong Kong and Hong Kong Eye Hospital, study published in the April, 2010, Journal of Agricultural and Food Chemistry

19. Homocysteine (2004) levels in glaucoma
Learn more information about glaucoma treatment and information.

"Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma"

In a study published in 2004, researchers wanted measure homocysteine levels in open-angle pseudoexfoliation glaucoma patients. Pseudoexfoliation, according to wikipedia, is an eye-disease "characterized by the accumulation of microscopic granular amyloid-like protein fibers."

The researchers looked at total homocysteine levels in the aqueous humor and plasma of 29 patients with pseudoexfoliation glaucoma and 31 control patients with cataract.

They observed elevated (200%) homocysteine levels in the glaucoma patients. Additionally, the ratio of plasma to aqueous humor was much lower in these patients.

The researchers concluded that high levels of homocysteine in the aqueous humor may trigger the abnormal fiber accumulation.

Researchers: Bleich S, Roedl J, Von Ahsen N, Schlotzer-Schrehardt U, Reulbach U, Beck G, Kruse FE, Naumann GO, Kornhuber J, Junemann AG., Dept. of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen, Germany. stefan.bleich@psych.imed.uni-erlangen.de

Published: PMID: 15234308 [PubMed - indexed for MEDLINE]

20. Homocysteine (2008) Levels in Glaucoma Patients
Researchers investigated the connection between levels of homocysteine in glaucoma patient's tears and blood. They were looking for the relationship between homocystein, dry eye syndrome and B vitamins in open-angle glaucoma patients. The small study included 36 patients and 36 controls. Homocysteine levels were measured a process known as liquid chromatography which is a technique that divides material into its component parts.

They found that the open-angle glaucoma patients had higher homocystein levels in both their tears and blood compared to controls. Furthermore, the patients who also had dry eye syndrome had even higher homocysteine levels. There was no connection to vitamin B levels.

Learn more impact on health of high levels of homocysteine.

Researchers: J.B., Roedl, et al

Published: Increased homocysteine levels in tear fluid of patients with primary open-angle glaucoma. Ophthalmic Research, 2008

21. Leafy Greens (2016) Nitrate Content Helps Glaucoma
Learn more about glaucoma options and read the blog article on this glaucoma and leafy greens research.

Nitric oxide has long been identified as a molecule which acts as a messenger within the central nervous system, which means that it delivers signals in the brain and through the optic nerve. In this capacity it helps to regulate the blood flow in the retina and the ability of the eye to regulate pressure within the vitreous humor through the outflow of the trabecular meshwork at the front of the eye.

We know that when the trabecular meshwork becomes blocked then outflow is blocked, intraocular pressure within the eyeball increases and the optic nerve is negatively affected.

So one obvious target in looking for treatments for high intraocular pressure is to take a closer look at the levels of nitric oxide in the body.

The very large Nurses' Health Study (nearly 64,000 women over 28 years) and the Health Professionals Follow-up Study (41,000 men over 26 years) has long been a source of data on various health conditions. Both studies include long-term assessment of participants' diets.

When looking specifically at glaucoma incidence the researchers identified that in almost 2 million person-years there were 1483 cases of primary open-angle glaucoma (POAG). The participants were classified by high intraocular pressure (lower than 22mmHg or higher than 22mmHg). They were also classified by what type of visual field loss existed (peripheral only or elsewhere in the visual field).

Then the participants were divided into 5 lowest to the highest nitrate rich diets. Comparing the lowest 1/5th group to the highest 1/5th group, the researchers found that they were much more likely to have developed POAG.

Visual field loss The higher levels of nitrate rich foods were more effective in protecting against early visual field loss in other parts of the visual field than the periphery (paracentral field loss).

Intraocular Pressure There was a similar difference between patients who'd had a higher level of nitrate rich foods in their diet and who tended to have more normal intraocular pressure, although not as great a difference as visual field loss protection.

Researchers: J. H. Kang, W. C. Willett, et al
Published: Association of Dietary Nitrate Intake With Primary Open-Angle Glaucoma: A Prospective Analysis From the Nurses' Health Study and Health Professionals Follow-up Study, JAMA Ophthalmology, March, 2016.

Editor's note: There's a great deal of discussion about nitrates which are added to meats as a preservative. Vegetables actually contain higher levels. We suspect that the beneficial effects of nitrates naturally taken in leafy greens are based on the relationship between those molecules and the other components, such as carotenoids, antioxidants, enzymes, vitamins and minerals, etc.

22. Lipoic acid / Vitamin B (1991) - Glaucoma
Learn more about holistic treatment of glaucoma.

Researchers looked at tyrosine (an amino acid) metabolism with respect to the effects of lipoic acid in patients with primary open-angle glaucoma. There were two control groups, one consisting of glaucoma patients not given lipoic acid and patients with ocular hypertension.

In the majority of glaucoma patients administration of lipoic acid did not result in improvement of tyrosine metabolism. Tyrosine metabolism normalized in the patients given lipoic acid, and various parameters that were measured improved.

Both the researchers' findings and the data in published studies further recommend using lipoic acid combined with vitamins B1, B2, B5, B6, and vitamin C for glaucoma treatment.

Published: Filina, AA & Sporova, NA. Vestn Oftalmol 1991 May-Jun;107(3):19-21

23. Magnesium (1995) glaucoma
Learn more about holistic treatment of glaucoma.

Scientists found that glaucoma patients with either open angle glaucoma or normal-tension glaucoma who received 2x a day supplements of magnesium for 4 weeks experienced improvement of the width of peripherial vision and reduced peripheral vasospasms, which have been tied to glaucoma, stroke and heart attack.

Published: Gasper, et al; Ophthalmologica 1995;209(1):11-3

24. Mini-Strokes (2009) May Cause Vision Loss for Those with Normal Tension Glaucoma
Learn more about glaucoma recommendations.

The study looked at incidence of glaucoma in people with normal rather than high ocular pressure, known as normal-tension glaucoma. They found that people who experience cerebral infracts (silent mini-strokes) may be more likely to have normal-tension glaucoma.

When 286 people with normal-tension glaucoma were studied, the researchers found that there was a higher than expected incidence of silent cerebral infarcts among those patients whose loss of vision progressed more rapidly.

Published: Ophthalmology, July, 2009.

Researchers: Dr. Dexter Y.L. Leung and others, Glaucoma Service, Hong Kong Eye Hospital

25. Natural Occurring Growth Factor May Regenerate Retinal Nerve Fiber

Researchers, building on earlier Glaucoma Foundation research, found that oncomodulin, a naturally occurring growth factor, stimulates the regeneration of injured retinal nerve fibers. The optic nerve doesn't normally regenerate after injury. However, through unknown mechanisms, macrophage activation in the eye stimulates retinal ganglion cells (RGCs) to regenerate long axons beyond the site of the injury.

Oncomodulin appears to stimulate this regeneration process, offering future hope for reversing optic-nerve damage due to glaucoma, tumors, or traumatic eye injury.

Research: 2008: Boston's Children's Hospital and Harvard Medical School

26. Omega-3 (1973) glaucoma
Learn more about holistic treatment of glaucoma.

Researchers have found that Eskimos, who have a high level of omega-3 from fish oils correspondingly have less occurences of open angle glaucoma.

Published: Albrick, P.H., Angle closure surveys in Greenland Eskimos, Canadian Journal of Ophthalmology 8 (1973): 260-64.

27. Oxidative Stress (2016, 2017) & Glaucoma
Learn more about treatment of glaucoma.

2017

These researchers point out that most therapies for glaucoma address high intraocular pressure since it is known that high IOP can contribute to optic nerve damage. But one of the important risk factors is the oxidative damage caused by free radicals to retinal nerve cells and the optic nerve.

Patients with normal tension glaucoma are typically treated with the use of prescription eyedrops to reduce intraocular pressure because IOP, but it is believed for most that the real issue is damage due to free damage resulting from oxidative stress and free radicals.

Editor's note: For those whose circulation is healthy to the eyes and antioxidants needed are freely available to the retina and optic nerve, this serves to neutralize free radicals, so helping the eyes stay healthy can be done through a good diet, regular exercise, management of chronic stress and targeted supplementation.

Oxidative stress = imbalance

The researchers note that oxidative stress is essentially an imbalance between accumulations of free radicals and the body's own antioxidant defenses. Glutathione levels in blood plasma are markedly lower in patients with glaucoma.^{1, 2} This is true whether or not high intraocular pressure is present.

Drugs which have antioxidant properties, and those that target enzymes that contribute to oxidative stress appear to prevent retinal deterioration due to glaucoma in animal models.

The researchers investigated the effect of various ways of reducing oxidative damage to retinal and optic nerves in lab animals. They accomplished this through a number of experiments. In one, they removed a gene that triggers excessive cellular response that causes oxidative damage. Removal of this gene made the mice less susceptible to glaucoma.

Alpha-lipoic acid. One of the antioxidants that has previously been tested in animal models is alpha-lipoic acid which protects retinal nerve cells from oxidative damage.

Superoxide dismutase. The researchers also tested a number of nutrients or drugs with antioxidant properties to see if incidence and severity of glaucoma was lessened. One of these was superoxide dismutase.

Other antioxidants. The researchers also successfully tested use of valproic acid, which is a fatty acid used to treat epilepsy. They found that is reduced oxidative damage by apparently increasing the activity of both superoxide dismutase and glutathione peroxidase in the retina.

The researchers also tested the drug Candesartan (for hypertension) and spermidine, which is found in soybeans and mushrooms. They found good results for both.

Researchers: A. Kimura, K. Namekata, et al,
Published: Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis, Oxidative Medicine and Cellular Longevity, February, 2017.

2016

Researchers evaluated the blood plasma of patients with primary open-angle glaucoma who required antiglaucomatous surgery even though their IOP was be managed with drugs. They also tested the blood patients who had required cataract surgery. Based on increased activities of certain biochemicals their conclusion was that the disorders were oxidative disorders.

Researchers: W. Rokicki, et al,
Published: Oxidative stress in the red blood cells of patients with primary open-angle glaucoma, Clinical Hemmorheology and Microcirculation, January, 2016.

1. D. Gherghel, et al, Systemic reduction in glutathione levels occurs in patients with primary open-angle glaucoma, Investigative Ophthalmology and Visual Science, 2005.
2. D. Gherghel, et al, Reduction in blood glutathione levels occurs similarly in patients with primary-open angle or normal tension glaucoma, Investigative Ophthalmology and Visual Science, 2013

28. Psychological Stress (2013, 1977, 1987) and Glaucoma
Learn more about holistic treatment of glaucoma.

For more than 20 years researchers have suspected that emotional stress may be connected to incidence of glaucoma.

2013

These researchers demonstrated that there is a markedly higher level of insomnia, anxiety and depression in glaucoma patients. While stress is probably a causative factor, it is also a result.

Researchers: A. Agorastos, C. Skevas, et al
Published: Depression, anxiety, and disturbed sleep in glaucoma, Journal of Neuropsychiatry and Clinical Neurosciences, Summer, 2013.

1987

Knowing that earlier literature suggested a connection between stress and glaucoma, researchers considered the relationship between stress and intraocular pressure.

Stress appears to be a significant factor in acute closed-angle glaucoma. And suspicion increases that it also plays an important part in incidence of open-angle glaucoma. Many attacks of acute glaucoma occur during times of greatest personal emotional or stress. This is because the pupil dilates when one is upset or excited narrowing the angle of the lens and the iris. This probable role is leading to use of conventional methods of stress reduction such as meditation, biofeedback and relaxation techniques.

Researcher: B.G. Shily
Published: American Journal of Optometry and Physiological Optics, November, 1987.

1977

Researchers found that stress may be connected to glaucoma risk. After reviewing incidence of above average stress in patients, researchers have indicated that high stress leads to a 3times higher risk for high eye pressure. High levels of pressure have been connected to glaucoma (although glaucoma can also occur with 'normal' levels of eye pressure.

Published: Grignolo, F.M. et. al. Variations of intraocular pressure induced by psychological stress. Klinische Monatsblaten Augenheilkd 170 (1977): 562-69.

29. Replacing Immune Cells May Impede Onset of Glaucoma
A study in the Journal of Experimental Medicine (2003;197[10]:1335-1344) found that inflammatory immune response, which is suppressed in the normal eye, might be an early step in the onset of pigment dispersion glaucoma. Pigment dispersion glaucoma occurs when the iris begins to shed melanin into the front part of the eye. This is followed by increasing pressure within the eye, which strangles the optic nerve and kills the retinal cells attached to it.
The researchers examined the eyes of model mice with pigment dispersion glaucoma before the visible onset of the disease and found that the diseased eyes failed to successfully suppress T-cells--white blood cells that cause the iris to shed pigment. This failure preceded clinical evidence of pigment dispersion. They also found that the eyes contained bone marrow-derived white blood cells that were programmed to cause inflammatory responses. Jun Song Mo, M.D., the study's lead author, told the press, "It is relevant that one of the two genes known to be responsible for pigment dispersion glaucoma in mice is active in these same white blood cells."
The research team concluded that the eyes of the genetically predisposed mice lost immune privilege before the pigment dispersion began.
"What this suggested to us," said J. Wayne Streilein, M.D., senior author of the study, "is that maybe the first thing that the genes for pigment dispersion glaucoma do is break down immune privilege and leave the eyes vulnerable to inflammation."
The researchers tested their theory of inappropriate immune response even further by replacing the bone marrow of mice predetermined to develop pigment dispersion glaucoma with bone marrow from normal mice. Following the procedure, the team found that the immune-privileged status was maintained in the eyes, inflammation never developed and pigment dispersion failed to occur.
"These results are very exciting and encouraging. We feel that this is a major breakthrough in understanding how this disease is triggered and may be cured," said Streilein. "We are eager to understand more completely the interrelationship between loss of immune privilege and development of glaucoma. Moreover, we are also interested to know whether a similar immune dependency might occur in other blinding eye diseases, such as macular degeneration and retinitis pigmentosa"--AR

30. Resveratrol (2015, 2017) & Glaucoma
Learn more about glaucoma.

2022 Although earlier research supported use of moderate red wine use, newer research reports that the many detriments outweigh the benefits.^{1, 2, 3} Instead, we recommend intake of resveratrol through grapes, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.

2017

Resveratrol is a micronutrient of the polyphenol family which became recognized in the early 2000s for its beneficial effect on heart disease. This was due to its ability to provide antioxidant and anti-inflammatory functions as well as improving blood vessel flexibility and ability to relax.

It was also identified as being able to inhibit extra blood vessels that can grown in the eye when oxygen is restricted and thus distort the retina.

Oxidative stress⁴ has been targeted in treatment options. Resveratrol's effectiveness as an antioxidant has therefore been suggested in cases of both glaucoma and optic neuritis.

One reason that resveratrol seems to be effective in ocular conditions is that it has the ability to cross the semi-permeable blood-brain and blood-eye tissue barriers. Taken orally, researchers have found that resveratrol shows up in the blood system in as little as 10 minutes due to its rapid metabolism by the digestive system.

Researchers measured levels of trans-resveratrol as well as three metabolites in eye tissue in samples taken during eye surgery for various conditions. The patients took resveratrol orally prior to surgery and samples were carefully preserved to retain accurate levels of the micronutrient.

They found resveratrol in several of the eye tissues which indicates that it is able to cross the semi-permeable barriers and so be bio-available to eye tissue. Thus its antioxidant and other beneficial capacities are available in combating oxidative stress in the eye.
Researchers: S. Wang, Z. Wang, et al, Published: Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes, Journal of Ophthalmology, March, 2017.
2015

Noting that resveratrol has previously been found to be helpful in heart disease and osteoporosis, scientists wanted to investigate its effect on nerve tissue, specially retinal ganglion cells. They measured how long-term intake of resveratrol protects against ganglion cell dendrite loss or damage.

In lab mice exposed to a condition that causes nerve cell dendrite length loss, those animals who had been on a resveratrol-supplemented diet for a year experienced significantly less dendrite length less and complexity compared to the animals on the control diet.

The finding is important because in glaucoma and other optic nerve atrophy conditions there is loss of nerve cell tissue, degradation of dendrites and loss of synapses. Hence the potential protective role of resveratrol can be a valuable adjunct to treatment.

Researchers: J.D. Lindsey, K.X. Duong-Polk, et al,
Published: Protection of injured retinal ganglion cell dendrites and unfolded protein response resolution after long-term dietary resveratrol, Neurobiological Aging, May, 2015.

1. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, et al. (2018). Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. Apr 14;391(10129):1513-1523.
2. Biddinger KJ, Emdin CA, Haas ME, Wang M, Hindy G, et al. (2022). Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022 Mar 1;5(3):e223849
3. Goding Sauer A, Fedewa SA, Bandi P, Minihan AK, Stoklosa M, et al. (2021). Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiol. Apr;71(Pt A):101893.
4. A. Kimura, K. Namekata, et al, Targeting Oxidative Stress for Treatment of Glaucoma and Optic Neuritis, Oxidative Medicine and Cellular Longevity, February, 2017.

31. Saffron (Crocin) (2016) & Retinal Nerve Cells
Learn more about glaucoma.

2016

A hallmark of glaucoma is the cell death of nerve cells in the retina (retinal ganglion cells). Their death is caused by any number of factors; one of which is oxidative stress. The carotenoids are known to reduce oxidative stress, and crocin in particular appears to be effective with respect to retinal nerve cell health. Crocin comes from the spice saffron.

The mechanics of how and why the protective effect occurs however, is not clear and researchers wanted to figure out the process.

The study focused on particular nerve cells called "RGC-5 cells" and treated them with hydrogen peroxide which, in test conditions, mimics oxidative stress and thus mimics the development of glaucoma. The researchers added crocin in various concentrations to test whether it was capable of protecting the RGC-5 cells from damage from the hydrogen peroxide. The researchers analyzed the results from several different angles: looking at levels of free radicals, looking at health of the mitochondria and various proteins and other cell components.

They found that crocin did protect the cells from cell death, slowed the release of the enzyme (LDH), and supported cell health. LDH is released by the body when damage to tissue results for that reason is a biomarker (indicator) of tissue damage.

The researchers also determined that crocin activated NF-kB (nuclear factor kappa-light-chain-enhancer of activated B cells). KF-kB is a complex protein that controls how the cell reacts to stress, the nature of the cellular immune response, etc. In other words balanced and correct regulation of KF-kB in nerve cells determines how well the cell will survive hostile conditions.

Researchers: B. Lv, T. Chen, et al,
Published: Crocin protects retinal ganglion cells against H2O2-induced damage through the mitochondrial pathway and activation of NF-κB, International Journal of Molecular Medicine, January, 2016.

Another study looked at a process called microglial activation with respect to how crocin protects retinal nerve (ganglion) cells.

Microglial activation is the cells inflammatory immune response to damage such as oxidative damage. Researchers found that through a complex process crocin successfully inhibiting the signaling that usually triggers inflammation which in turn can damage the retinal nerve cells.

The researchers point out that glaucoma is a group of neurodegenerative eye diseases which are marked by loss of retinal nerve cells and conclude that crocin successfully and effectively protects the nerve cells.

Researchers: B. Lv, F. Huo, et al,
Published: Crocin Upregulates CX3CR1 Expression by Suppressing NF-κB/YY1 Signaling and Inhibiting Lipopolysaccharide-Induced Microglial Activation, Neurochemical Research, August, 2016.

32. Smoking (2009) Additional Risk Factor in Elder Women for Glaucoma
Learn more about glaucoma recommendations.

Researchers sampled the fluid in the eye and blood of 120 female glaucoma patients (age 40-90) who were smokers (40), ex-smokers (40) and non-smokers (40). Both inflammation and cell death processes were studied using techniques of enzyme immunoassay and western blot procedures. They looked at the interleukin-6 (a protein that stimulates immune responses in the body) as a marker of inflammation marker and caspase-3 (a protein involved in stages of cell death) and poly (ADP-ribose) polymerase 1 (a protein involved in DNA repair and cell death) as apoptosis (cell death) "markers".

They found that Inflammation and cell death marker levels increased in samples taken from the women who smoked and concluded that smoking could be an important additional risk factor for glaucoma progression in elderly women.

Published: Zanon-Moreno V, Garcia-Medina JJ, Zanon-Viguer V, et al. Smoking, an additional risk factor in elder women with primary open-angle glaucoma. Mol Vis 2009;15:2953-2959.

33. Studies Show Relationship of Blood Pressure and Glaucoma
Glaucoma may continue to progress after the reduction of IOP to targeted levels. Research is providing increasing support for the idea that vascular risk factors may be the cause.

Several population-based studies have suggested that low diastolic perfusion pressure is associated with an increased incidence of open-angle glaucoma (OAG). Perfusion pressure is defined as the difference between arterial and venous pressure, which, in the eye, by convention equals IOP. Blood pressure and IOP are therefore the principal components of ocular perfusion pressure (perfusion pressure = blood pressure - IOP).

Choi J, Kim KH, Jeong J, et al. Circadian fluctuation of mean ocular perfusion pressure is a consistent risk factor for normal-tension glaucoma. Invest Ophthalmol Vis Sci. 2007;48:104-111.

Tielsch JM, Katz J, Sommer A, et al. Hypertension, perfusion pressure, and primary open-angle glaucoma. A population-based assessment. Arch Ophthalmol. 1995;113:216-221.

Leske MC, Connell AM, Wu SY, et al. Risk factors for open-angle glaucoma. The Barbados Eye Study. Arch Ophthalmol. 1995;113:918-924.

Hulsman CA, Vingerling JR, Hofman A, et al. Blood pressure, arterial stiffness, and open-angle glaucoma: the Rotterdam study. Arch Ophthalmol. 2007;125:805-812.

Perfusion pressure can be affected by IOP and blood pressure, but which is really the most important? In a given patient, it could be IOP alone, blood pressure alone, or a combination of the two.

34. Superoxide Dismutase (2016, 2017) & Glaucoma
Learn more about glaucoma.

2017

Reseachers compared levels of antioxidants including the enzyme superoxide dismutase in patients with cataracts and glaucoma to patients with cataracts only.

They found that activity of this enzyme was significantly lowered in the patients who had both cataracts and glaucoma.

Researchers: W. Rokicki, J. Zalejska-Fiolka, et al,
Published: Differences in serum oxidative status between glaucomatous and nonglaucomatous cataract patients, BMC Ophthalmology, February, 2017.

2016

Patients with open angle glaucoma have lower blood serum levels of antioxidants. Researchers decided to evaluate one of these important antioxidants, superoxide dismutase, in terms of its genetic expression. Genetic expression means how information contained in the gene is used by the body to produce a correctly functioning result - in this case, produce a given level of superoxide dismutase in the blood serum.

Super dismutase is an enzyme that divides the superoxide free radical into either oxygen or hydrogen peroxide. The body, of course, need oxygen. Hydrogen peroxide damages cells. So superoxide dismutase is important in the antioxidant defense system of the body.

In this experiment the researchers The purpose of the evaluation was to determine whether superoxide dismutase would function effectively as a biomarker for glaucoma.

They analyzed genetic expression of genes from patients who had been diagnosed with glaucoma and a control group: 15 patients and 11 controls. They found that superoxide dismutase expression was markedly less in the glaucoma patients compared to the controls, and that correspondingly, superoxide dismutase levels in blood serum were also much lower.

Researchers: L. Canizales, L. Rodriguez, et al,
Published: Low-level expression of SOD1 in peripheral blood samples of patients diagnosed with primary open-angle glaucoma, Biomarkers in Medicine, December, 2016.

Another study measured indicators of oxidative stress in glaucoma patients compared to cataract patients. The study carefully selected 30patients who had surgery for glaucoma due to primary open angle glaucoma even though they had been managing intraocular pressure.
The control group was comprised of 25 patients who had cataract surgery.

The study evaluated levels of several antioxidants including superoxide dismutase and found that the levels in the two groups were similar, but that levels of the damaging malondialdehyde (MDA) were higher in the glaucoma group. This suggests that the antioxidants were insufficiently expressed in these patients.

Researchers: W. Rokicki, J. Fiolka-Zalesjska, et al,
Published: Oxidative stress in the red blood cells of patients with primary open-angle glaucoma, Clinical Hemorheology and Microcirculation, January, 2016.

35. Taurine (2003 Study)
Taurine, an amino acid concentrated in the eye and found in the optic nerve, may help counter excess levels of nerve-damaging glutamate in the body. An acute dose has been clinically shown to promote blood flow during oxidative stress by restoring vessels' ability to dilate.
Fennessy FM, et al. Taurine and vitamin C modify monocyte and endothelial dysfunction in young smokers. Circulation 107:410-15, 2003.

36. Thyroid Problems Linked to Glaucoma 2002 Study
Researchers at the University of Alabama at Birmingham believe that thyroid disorders may increase the risk of glaucoma. Their study, published in the British Journal of Ophthalmology, reviewed data from the 2002 National Health Interview Survey to quantify the association between a self-reported diagnosis of glaucoma and a self-reported history of thyroid problems.
Of the 12,376 survey participants, 4.6% reported glaucoma, and 11.9% reported a history of thyroid problems. The prevalence of glaucoma among those who reported thyroid problems was 6.5% compared with 4.4% among those who did not report thyroid problems. This association between glaucoma and thyroid problems remained after adjusting for differences in age, gender, race and smoking status.
The results of this study lend support to the hypothesis that thyroid disorders may increase the risk of glaucoma. Although further research on the topic is expected, study authors suspect that hypothyroidism may diminish outflow in the eye.
SOURCE: The association between thyroid problems and glaucoma, Cross, et al, British Journal of Ophthalmology 2008;92:1503-1505.

37. Vascular changes (1993) and glaucoma
Learn more about holistic treatment of glaucoma.

Changes in the vascular (blood) system in the eyes, which limit nutrient-bearing blood flow to the nerve tissue in the eyes may be the primary cause of glaucoma.

Researchers looked at disc haemorrhages and retinal vein occlusions in the eye and concluded that they were all different manifestations of the same cause, restricted flow of blood in the eye.

Published: Acta Ophthalmol (Copenh) 1993 Aug;71(4):433-44

38. Vascular obstruction (1993) - glaucoma cause
Learn more about holistic treatment of glaucoma.

1993

Between 1980 and 1991 an eye doctor collected data about open angle glaucoma. This data was analyzed with a view to identifying disc haemorrhages and retinal vein occlusions. Disc haemorrhages can occur in patients without glaucoma, but in patients with glaucoma the condition is indicative of likely progression of the condition. Similarly incidence of retinal vein occlusions is a risk factor glaucoma and can occur in patients who already have glaucoma.

The researchers found a connection between the three, which in all categories, increased with duration.

It was felt that mixed incidents suggested that the haemorrhages and occlusions were manifestations of the same vascular disease, the only difference being the size of the blood artery or vein.

The researchers concluded that the various vascular obstructions damaged ability of the tissues to pick up nutrition and therefore might be the primary cause of glaucoma.

Published: Sonnsjo & Krakau, Acta Ophthalmol (Copenh) 1993 Aug;71(4):433-44

39. Vitamin B1 (1979) & chronic open angle glaucoma
Learn more about holistic treatment of glaucoma.

Researchers looked at blood levels of Vitamin C and Thiamine (B1) in glaucoma patients. They found that the patients with chronic open angle glaucoma patients had a far lower thiamine blood level than controls and related poor absorption of that thiamine. However there were not distinct differences between the controls and the vitamin C blood levels.

Asregadoo, Ann Ophthalmol 1979 Jul;11(7):1095-1100

40. Vitamin B12 (1965) and glaucoma
Learn more about holistic treatment of glaucoma.

This early study, later substantiated by a 1992 Vitamin B12 & Glaucoma Study found that glaucoma patients where were treated with vitamin B12 for over a 5 year period had improved visual acuity (sharpness) and better overall management of the condition

Published: Glacome, 1992; ; Oftalmol Zh. 1965; 20(6); Klin Oczna 1974 Nov;44(11):1183-7

41. Vitamin B12 (1992) - glaucoma
Learn more about holistic treatment of glaucoma.

Research indicates that a statistically significant number of glaucoma patients with long-term supplementation of Vitamin B12 - 1,500 mcg of vitamin B12 over five years - found improvement in or no further deterioration to eyesight due to glaucoma. This was true although eye pressure remained constant.

Published: Sakai, T. Murata, M., and Amemiya, T. Effect of long-term treatment of glaucoma with vitamin B12. Glaucoma 14 (1992): 167-70.

42. Vitamin B3 (2017) & Glaucoma
Learn more about glaucoma.

Glaucoma involves damage to the optic nerve thought to be caused by high intraocular pressure (due to blocked drainage). Recent research has also found that oxidative stress caused by free radicals may be an even more important contributing factor. (Zhao, et al, Gauthier, et al. 2016)

Glaucoma is a particular risk to those who are myopic and spend long hours on the computer.

2017

These researchers pointed out that abnormalities in energy-producing part of cells, mitochondria, take place well before nerve damage can be detected by an eye doctor. In the retina there is a molecule called nicotinamide adenine dinucleotide (NAD) which is critically important in both cellular energy production and in the body's protection against oxidative stress (which has also been implicated in causing glaucoma).

Vitamin B3 is a precursor of NAD and has protective effects against glaucoma. In addition, the gene which regulates production of the enzyme Nmnat1 was found to be both protective and effective as a therapy for glaucoma.

Application of vitamin B3 was very simple - it was added to the animals' drinking water.

production of the molecule NAD, which is important for cellular energy production, slows down as we age. Lowered energy production within cells, and within nerve cells means that they are more vulnerable to stress - such as that caused by high intraocular pressure.

The researchers tested various doses and found that the highest dose protected against 93% of glaucoma incidences in mice that were genetically prone to developing glaucoma.

Researchers: P.A. Williams, J.M. Harder, S.W. John,et al
Published: Vitamin B3 modulates mitochondrial vulnerability and prevents glaucoma in aged mice, Science, February, 2017.

2008

It should be noted that in a single published case study in 2008, it was determined that in an elderly man, taking 500mg of niacin (vitamin B3) experienced a rise in intraocular pressure --- which decreased when B3 intake was stopped.

This is only a single instance, but it does mark the need for thorough testing of B3 use. This patient had a history of glaucoma and the rise may have been due to an interaction with his other medications.

Researchers: E.H. Tittler, et al.
Published: Oral niacin can increase intraocular pressure, Ophthalmic Surgery, July-August, 2008.

43. Vitamin C (1969) and Glaucoma
Learn more about holistic treatment of glaucoma.

In several studies, researchers found that Vitamin C, in larger doses, have lowered intraocular eye pressure - this is important for glaucoma. This happened through several body mechanisms, including increased blood osmolarity (a measure of pressure, as in osmosis), lower aqueous production, improved movement of fluids in the eye and collagen support.

Published: Acta Ophthalmology Scand, 1969.

44. Vitamin C (1995) Glaucoma
New Study shows supplementing with Vitamin C can significantly lower intraocular pressure (IOP) for those with elevated pressure.
The purpose of the study was to determine and compare pressure before the use of vitamin C and after the daily intake of maximum amounts of vitamin C taken three times a day.
The study had the participants take an average of 10 grams of vitamin C per day (or the limit below what would cause loose stools) in 3 divided dosages. The study evaluated thirty patients (16 men and 14 women).
The results of the study showed the average reduction of intraocular pressure to be 10mm per patient (the greatest lowering of pressuring being 13mm). These patients were only using Vitamin C as a pressure lowering mechanism (no glaucoma medication was being taken).
Every patient in this study experienced some level of lowering of IOP, with no toxicity shown from taking these levels of vitamin C. Also, positive side effects included the following: clearing of sinusitis, allergy symptoms, laxative effect, cholesterol lowering, arthritis improvement, diuretic effect for heart disease patients, and other improvements associated with vitamin C intake of several grams per day level.
Ref: The Journal of Orthomolecular Medicine Vol. 10, No.2, 1995

45. Vitamin C (2014) Supports Trabecular Meshwork
See more information about glaucoma.

Antioxidants such as vitamin C have been found useful in both protecting nerve cells from damage and improving the health of optic nerve cells in case of lab animal glaucoma.

Researchers wanted to investigate the antioxidant properties and how it functions in protecting the trabecular meshwork. The trabecular meshwork is a fine mesh of cells that regulate the flow of fluid in and out of the eye and glaucoma is thought to be sometimes caused by blockage in the meshwork.

Researchers treated cultures of lab animal trabecular meshwork cells with increasing concentrations of ascorbic acid (vitamin C) and the antioxidant effect was assessed by observing cell health.

The scientists found that ascorbic acid acts in two ways to support meshwork cells. First, it was correlated with lower levels of damaging free iron and protein, and second, in several different ways, it reduced the presence of unwanted damaging proteins.

The researchers concluded that lowered vitamin C levels in blood and in the vitreous humour inside the eye can contribute to meshwork outflow blockage due to aging and contribute to development of glaucoma.

Researchers: P.Xu, Y. Lin, K. Porter, P.B. Liton

Published: Ascorbic acid modulation of iron homeostasis and lysosomal function in trabecular meshwork cells, Journal of Ocular Pharmacology and Therapeutics, March-April, 2014.

46. Vitamin E (2008) Neuroprotection by Vitamin E in Glaucoma
See other glaucoma vitamins & supplements.

Learn more information about glaucoma treatment and information.

Vitamin E is known as a major fat-soluble antioxidant. It intercepts free radicals preventing chain reactions of lipid destruction. However the discovery of complex molecules that control vitamin E metabolism fostered the idea that the vitamin E may be more than an antioxidant.

Vitamin E is now known to affect the expression and activity of immune and inflammatory cells, and to enhance dilation of blood vessels. It is also known to inhibit the activity of protein kinase C (PKC), a family of enzyme-like proteins enzyme that control other proteins and which plays a role in development of glaucoma. PKC inhibitors have been shown to relax the trabecular meshwork and to affect matrix metalloproteinase and PGF2 alpha, both of which can degrade cell structure).
Vitamin E and PKC could also have a vaso-regulatory effect in the retina. In different experimental models, retinal vascular dysfunction due to hyperglycemia was reportedly prevented by vitamin E via the diacylglycerol-PKC pathway^1,2.
These findings prompted researchers at Istanbul University to evaluate the clinical potential of vitamin E in glaucoma patients. They reported prevention of visual field loss in this preliminary study, and conclude that vitamin E deserves further attention in preventing glaucomatous damage³.
Study Design and Methods
Thirty glaucomatous patients (60 eyes) with controlled IOP, were randomly divided into three groups. Group (A) received no vitamin E, while groups (B) and (C) were given a daily dose of 300 and 600 mg of vitamin E respectively, as d-alpha tocopheryl acetate for 12 months. Blood levels of vitamin E were measured via HPLC.
Disease progression for each subject was monitored via visual field measurements and color Doppler imaging of ophthalmic and posterior ciliary arteries at baseline, and at 6 and 12 months. Retinal blood flow of ophthalmic and posterior ciliary arteries was evaluated, and resistivity and pulsatility indexes were obtained. Mean deviation values for Fastpac visual fields were recorded at all time points, and the difference in mean deviation values calculated. The change in mean deviations of Groups (B) and (C) were compared with Group (A), and the Mann-Whitney U-test was employed for statistical analysis.
Results
There were no significant differences between the groups in mean ages, IOP, best corrected visual acuities of 10/10 ratios and disease etiologies. The average differences between the pulsatility indexes (PI) and resistivity indexes (RI) of both ophthalmic arteries and posterior ciliary arteries of both supplemented groups were significantly lower than those of the non-supplemented groups at 6 months and 1 year. RI decreases observed in posterior ciliary arteries at both time points, and PI decreases observed in ophthalmic arteries at the 6th month were statistically significant.
Compared with those receiving vitamin E, non-treated subjects showed a statistically significant reduction in visual field (change in mean deviation) at 6 and 12 months).

Kunisaki M et al. Vitamin E prevents diabetes-induced abnormal retinal blood flow via the diacylglycerol-protein kinase C pathway. Am J Physiol 269:239-46, 1995.

Lee IK et al. d-alpha tocopherol prevents hyperglycemia induced activation of the diacylglycerol (DAG)-protein kinase C pathway in vascular smooth muscle cells by an increase in DAG kinase activity. Diabetes Res Clin Pract 45:183-90, 1999.

Engin KN et al. Clinical evaluation of the neuroprotective effect of alpha tocopherol in glaucomatous damage. Eur J Ophthalmol 17:528-33, 2007.

Gout

1. Myrobalan (2016) and Gout
Learn more about gout.

Two species of a tropical plant, Black Myrobalan (Terminalia chebula) and Beleric (Terminalia bellirica) were investigated for their efficacy in lowering uric acid levels in patients with hyperuricemia as compared to a medication commonly prescribed for the condition.

In a double-blind, placebo-controlled pilot study researchers gave 110 patients with high uric acid levels placebo, twice a day Myrobalan (500mg T. chebula, 500mg or 250mg T. bellirica), or 40mg of the drug febuxostat. They found that Myrobalan was as effective as the drug, that T. bellirica was more effective than T. chebula, and that the larger dose of T. bellirica was more effective than the smaller dose.

During the trial some of the patients taking febuxostat reported side effects such as nausea, but none of the patients taking Myrobalan reported any problems nor was their blood chemistry negatively impacted.

Researchers: P. Usharani, C. Nutalapati, et al,
Published: A randomized, double-blind, placebo-, and positive-controlled clinical pilot study to evaluate the efficacy and tolerability of standardized aqueous extracts of Terminalia chebula and Terminalia bellerica in subjects with hyperuricemia, Clinical Pharmacology, June, 2016.

Editor's Note

We find the study interesting because although high uric acid levels in the blood are associated with gout:

these high levels develop before symptoms of gout appear, and

high uric acid levels are also associated with higher risk of heart disease, cerebrovascular disease, and early death.

The body normally makes biochemicals called purines which play important roles in DNA and RNA functioning. They are found mostly in red meats and organ meats and moderate amounts in poultry, fish, and some vegetables.

However, when the diet includes large amounts of red meat and organ meats such as liver, sweetbreads, game meats, some fish like sardines, then almost all of the excess is converted to uric acid. Over the long term the excess is converted to a needle-like salt giving rise to excruciating pain in the big toe and other joints.

Gout medications, such as febuxostat have side effects, especially impacting liver health, but which can include heart problems and strokes, so there has been a search for safer alternatives.

2. Xtra Info: Gout Bibliography - early research
Also see discussion of gout and research

1. Ralston SH, Capell HA, Sturrock RD. Alcohol and response to treatment of gout. BMJ 1988;296:1641-2.
2. Scott JT. Alcohol and gout. BMJ 1989;298:1054.
3. Emmerson BT. Effect of oral fructose on urate production. Ann Rheum Dis 1974;33:276-80.
4. Blau LW. Cherry diet control for gout and arthritis. Tex Rep Biol Med 1950;8:309-11.
5. Loenen H, Eshuis H, Lowik M, et al. Serum uric acid correlates in elderly men and women with special reference to body composition and dietary intake (Dutch Nutrition Surveillance System). J Clin Epidemiol 1990;43:1297-303.
6. Oster KA. Xanthine oxidase and folic acid. Ann Intern Med 1977;87:252-3.
7. Boss GR, Ragsdale RA, Zettner A, Seegmiller JE. Failure of folic acid (pteroylglutamic acid) to affect hyperuricemia. J Lab Clin Med 1980;96:783-9.
8. Stein HB, Hasan A, Fox IH. Ascorbic acid-induced uricosuria: a consequence of megavitamin therapy. Ann Intern Med 1976;84:385-8.
9. Bindoli A, Valente M, Cavallini L. Inhibitory action of quercetin on xanthine oxidase and xanthine dehydrogenase activity. Pharmacol Res Commun 1985;17:831-9.
10. Busse W, Kopp D, Middleton E. Flavonoid modulation of human neutrophil function. J Allergy Clin Immunol 1984;73:801-9.

Hay Fever

1. Xtra Info: Hay Fever Bibliography - Early Research
Also see discussion of hay fever and research. Related condition: allergies and sensitivities.

1. Speer F. Multiple food allergy. Ann Allerg 1975;34:71-6.
2. Buczylko K, Kowalczyk J, Zeman K, et al. Allergy to food in children with pollinosis. Rocz Akad Med Bialymst 1995;40:568-72.
3. Ogle KA, Bullock JD. Children with allergic rhinitis and/or bronchial asthma treated with elimination diet. Ann Allergy 1977;39:8-11.
4. Holmes HM, Alexander W. Hay fever and vitamin C. Science 1942;96:497.
5. Ruskin SL. High dose vitamin C in allergy. Am J Dig Dis 1945;12:281.
6. Fortner BR Jr, Danziger RE, Rabinowitz PS, Nelson HS. The effect of ascorbic acid on cutaneous and nasal response to histamine and allergen. J Allergy Clin Immunol 1982;69:484-8.
7. Balabolkin II, Gordeeva GF, Fuseva ED, et al. Use of vitamins in allergic illnesses in children. Vopr Med Khim 1992;38:36-40.
8. Cazzola P, Mazzanti P, Bossi G. In vivo modulating effect of a calf thymus acid lysate on human T lymphocyte subsets and CD4+/CD8+ ratio in the course of different diseases. Curr Ther Res 1987;42:1011-7.
9. Kouttab NM, Prada M, Cazzola P. Thymomodulin: Biological properties and clinical applications. Med Oncol Tumor Pharmacother 1989;6:5-9 [review].
10. Marzari R, Mazzanti P, Cazzola P, Pirodda E. Perennial allergic rhinitis: prevention of the acute episodes with Thymomodulin. Minerva Med 1987;78:1675-81.
11. Gopalakrishnan C, Shankaranarayan D, Nazimudeen SK, et al. Effect of tylophorine, a major alkaloid of Tylophora indica, on immunopathological and inflammatory reactions. Ind J Med Res 1980;71:940-8.
12. Mittman P. Randomized double-blind study of freeze-dried Urtica dioica in the treatment of allergic rhinitis. Planta Med 1990;56:44-7.
13. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1988, 219 [review].
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High Cholesterol

1. Olive Leaf Extract (2011, 2015) & High Cholesterol
Learn more about high cholesterol.

2015

In a preliminary study of volunteers with hypertension received olive leaf extract with 15% oleuropein and their diastolic and systolic pressure, blood antioxidant level, nitric oxide and lipid levels in blood plasma were measured. Not only did the researcher notice a reduction in blood pressure, but and other improved biomarkers, but LDL cholesterol (the "bad" cholesterol and triglycerides were lowered which markedly improved the CHO/HLD ratio.

Researchers: C. Cabrera-Vique, M. Navarro-Alarcon, et al, Hypotensive Effect of an Extract of Bioactive Compounds of Olive Leaves: Preliminary Clinical Study, Nutrition Hospitalaria, July, 2015.

In another study researchers found that olive leaf extract lowered LDL and total cholesterol in rats who were fed a high-cholesterol diet. There were two test groups. One group was fed a standard "rat-chow." The other was fed a diet with 2% cholesterol-enriched chow. Both diets continued for eight weeks.

Some rats in each group were fed olive leaf extract at doses of either 50 or 100 mg daily. As a control, other rats were fed an common cholesterol medication.

The blood lipid profile was analyzed after eight weeks. Both total cholesterol and LDL levels were increased in the cholesterol fed animals who did not receive either treatment. For both of the treated groups total and LDL cholesterol levels were reduced.

Researchers: E. Olmez, K. Vural, et al
Published: Olive Leaf Extract Improves the Atherogenic Lipid Profile in Rats Fed a High Cholesterol Diet, Phytotherapy Research, October, 2015.

2011

In a study evaluating the comparative effect of olive leaf extract to a common medication in hypertensive patients, reductions in cholesterol triglycerides were also observed in the group receiving the olive leaf extract.

A four week period with no medication to either group preceded the study period. The treatment period was eight weeks in duration. A dosage of 500 mg two times a day was given over the eight week period to one group, and normal dosage of Captopril to the other group.

Evaluations of blood lipid profile was measured after each four week period and it was found that there was a marked lowering in the triglyceride level in the group receiving the olive leaf extract.

Researchers: E. Sasalit, N. Agus, et al
Published: Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril, Phytomedicine, February, 2011.

2. Omega-3 fatty acids protect bypass patients (2005)
A report published in the May 17 2005 issue of the Journal of the American College of Cardiology summarized the findings of Italian researchers that giving omega-3 fatty acids to patients before and after coronary artery bypass graft surgery helps protect them from atrial fibrillation, a type of heart arrhythmia that is often associated with the procedure.

3. Plant Sterols (2009) & Cholesterol
Learn more about managing High Cholesterol

Plant sterols are naturally-occurring steroid compounds found in plants and are frequently used to enrich foods or are available as dietary supplements. Good sources of these compounds (also known as phytosterols) are found in nuts, cereals, vegetables, fruits and berries. Carefully designed vegetarian diets can produce high levels of phytosterols in the diet.

Phytosterols were first found to help reduce cholesterol as early as 1953, and have been marketed in many forms since then.

Researchers have found that the greatest benefit is when plant sterols are consumed in smaller amounts more often during the day rather than in one larger amount daily. In this study, the scientists tested giving one group of study participants 1 larger dose each morning and another group, three smaller doses daily.

The study began with a control phase wherein the subjects were on a precise weight-maintaining diet and no supplementary plant sterols. In the second phase, they were on the same diet but had 1.8 grams of plant sterols added at breakfast. In the third phase, again the same diet, but this time 1.8 grams divided 3 ways for each of three meals.

It was found that with consumption three times a day LDL cholesterol dropped by 6%.

Researchers: Lichtenstein, and colleagues at the Cardiovascular Nutrition Laboratory at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University in Boston, MA.

Published European Journal of Clinical Nutrition, 2009

4. Tocotrienols (1993, 2012) & High Cholesterol
Learn more about high cholesterol.

2012

The researchers point out that most studies testing vitamin E as a cholesterol lowering supplement find it unsuccessful. However, tocotrienols, which are compounds of the same molecular formula, but different structure (isomers) as vitamin E have been found to lower LDL levels.

In this animal study rabbits on a cholesterol diet for 60 days supplements with several forms (alpha, beta, delta and gamma) of tocotrienols and a control. They found that the functions of the left ventricle (aortic flow and developed pressure) improved marked recovery with the alpha and gamma forms, but not the delta form.

Their conclusion was that the two tocotrienols isomers, alpha and gamma are helpful.

Researchers: Das S, Mukherjee S, Lekli I, Gurusamy N, Bardhan J, Raychoudhury U, Chakravarty R, Banerji S, Knowlton AA, Das DK, Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT

Published: Mol Cell Biochem. 2012 Jan;360(1-2):35-45. Epub 2011 Sep 15

Researchers evaluated the role of tocotrienols in controlling cholesterol levels in a lab environment.

They incubated several types of cells with gamma-tocotrienol and found that it inhibited the development of several kinds (mevalonate) of cholesterol. They observed 50% to 80% inhibition over different lengths of time periods.

Their conclusion was that tocotrienols have an effect on the mevalonate pathway in cells of mammals, which is the mechanism creating LDL type of cholesterol.

Researchers: Parker RA, Pearce BC, Clark RW, Gordon DA, Wright JJ, Department of Metabolic Diseases, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey

Published: Tocotrienols regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase., J Biol Chem. 1993 May 25;268(15):11230-8

5. Xtra Info: High Cholesterol Bibliography
Also see discussion of high cholesterol and research.

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295. Silagy C, Neil A. Garlic as a lipid-lowering agent-a meta-analysis. J R Coll Physicians London 1994;28:39-45.
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297. Kono S, Shinchi K, Ikeda N, et al. Green tea consumption and serum lipid profiles: a cross-sectional study in Northern Kyushu, Japan. Prev Med 1992;21:526-31.
298. Yamaguchi Y, Hayashi M, Yamazoe H, et al. Preventive effects of green tea extract on lipid abnormalities in serum, liver and aorta of mice fed an atherogenic diet. Nip Yak Zas 1991;97(6):329-37.
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Hypertension

1. Bioflavonoids (2015, 2016) & Hypertension
Learn more about high blood pressure.

2016

Previous research has established that various individual antioxidants and other phytochemicals are able to reduce blood pressure. In this pilot study, researchers evaluated the effect of a combination of such nutrients. All are in the family of bioflavonoid bionutrients.

They investigated a combination of these extracts:

300mg grape seed/skin,

100mg green tea,

60mg resveratrol, and

60mg quercetin, ginkgo biloba and bilberry.

In a placebo-controlled, double-blind, crossover trial 18 subjects with high blood pressure 130mmHg systolic or 85Hg diastolic were tested. A crossover trial is one in which subjects are given first one test item and then after time for it to wash out of the system, are given a different one. The two results can then be compared for the same subjects - rendering it a more realistic result given the differences in each person's physiology.

The subjects received the nutritional supplement or placebo for 28 days; there was a 2-week washout period, and then the other test item was given for another 28 days. At the beginning of the study period and at the end of each 28 day period blood pressure was measured.

Regardless of whether placebo was given in the first 28 days or the second 28 days, blood pressure was unchanged. However for the nutritional supplement, diastolic pressure lowered an average of 4.4mmHg, systolic pressure was unchanged, and the arterial pressure was reduced generally.

In addition, enzyme activity was measured at each point in the trial. Enzymes implicated in serum angiotensin was similar in both products, but nitrite concentrations were significantly increased after supplementation. In addition the cells that line blood vessels increased.

Noting the type of reaction of cells from the aorta when treated with these polyphenols the researchers were able to determine the mechanics of the process. Nitric oxide production changes stimulated by eNOS activation causing the reduced blood pressure. They concluded that such supplements may have clinical relevance as stand-alone or adjunct therapy to help reduce blood pressure.

Researchers: S. Biesinger, H. Michaels, et al
Published: A combination of isolated phytochemicals and botanical extracts lowers diastolic blood pressure in a randomized controlled trial of hypertensive subjects., European Journal of Clinical Nutrition, January, 2016.

2015

A previous study focused on the bioflavonoid anthocyanins, which are important in helping to normalize a number of health-effecting factors such as oxidative stress and inflammation.

These scientists investigated whether two juices rich in anthocyanins could lower high blood pressure. The study was a randomised, placebo-controlled, double-blind study lasting 12 weeks. The study included 134 healthy patients aged 50-70 years:

72 with high normal range blood pressure (130/85 to 139/78mmHg)

62 with stage 1-2 hypertension (140/90 to 179/109)

The subjects drank 500 ml daily of one of the 3 combinations for 12 weeks:

a commercial juice based on red grapes, cherries, chokeberries and bilberries (245.5 mg/100g)

a similar juice but enriched with extracts of black currant press residue (305.2mg/100g)

a placebo juice (76mg/100g)

Blood pressure was measured at the beginning of the study period, at six weeks and at 12 weeks. Systolic pressure was markedly reduced in both of the juices with higher levels of the nutrients compared to the placebo juice. This was true for the entire study group, but especially for the patients with stage 1 or 2 hypertension.

The researchers concluded that these nutrient-rich berry juices containing high levels of polyphenols may help to lower high blood pressure, especially in patients with hypertension.

Researchers: T. Tjelle, L. Holtung, et al
Published: Polyphenol-rich juices reduce blood pressure measures in a randomised controlled trial in high normal and hypertensive volunteers, British Journal of Nutrition, October, 2015.

2. Coleus forskohlii (2011) & Hypertension
Learn more about high blood pressure.

Researchers in India tested 49 patients with high blood pressure, dividing them into two groups, one of whom received one of two forms of coleus forskohlii in tablet form. Eight of the patients did not complete the treatment. The patients were also advised to follow correct diets, avoid stale food, reduce salt intake, avoid spicy foods, and take mild exercise.

While both forms of the herb were helpful, one was more effective, in which a decoction was made from the herb, filtered, and again heated making it more concentrated. The concentrations ranged from 2.50mg/500mg to 2.31mg/700mg in the two forms.

The groups had 12.07% and 10.75% improvements in systolic blood pressure and 9.80% and 8.65% in diastolic pressure (sitting posture). The groups had 12.99% and 13.25% improvements in systolic pressure and 10.10% and 10.75% diastolic pressure (lying down).

Researchers: Madhavi Jagtap, H. M. Chandola, and B. Ravishankar

Published: Ayu. 2011 Jan-Mar; 32(1): 59-65.

3. CoQ10 ('01, '02, 2015) & Hypertension
Learn more about hypertension and diabetes.

2015

Scientists report that high blood pressure increases certain biochemicals (cytokines) and stimulates an inflammatory response in the body. This study addresses the effect of CoQ10 in reducing cytokine levels and decreasing inflammation.

The test subjects were 60 patients with mild hypertension. The study lasted for 3 months and was randomized, double-blind, and placebo-controlled. The test group patients received 100mg CoQ10 daily. The placebo group received 100mg of lactose. Blood pressure and biomarkers for high blood pressure were tested at beginning and at the end of the 3 month period.

CoQ10, taken daily, reduced some pro-inflammatory markers but did not significantly change cytokines.

Researchers: N.B. Nesami, H. Mozaffari-Khosravi, et al
Published: International Journal for Vitamin and Nutrition Research, 2015.

2002

The researchers wanted to look at supplementing with coenzyme Q10 (CoQ10) for subjects with both high blood pressure and type II diabetes.

They assigned 74 type II diabetes and high cholesterol patients to 4 groups in a random, double-blind, placebo-controlled study. For 12 weeks the groups took 100mg COQ10 (2x daily), or 200mg fenofibrate (1x daily) or both or neither. Fenobribrate is a drug more commonly used for high cholesterol. They evaluated the results by looking at blood pressure, long-term glycemic control and oxidative stress.

They found that there was a 3x increase in blood levels of CQ10 concentration and that systolic and diastolic blood pressure were markedly reduced. They found that fenofibrate did not change blood pressure. They also found that the improvements would possibly improve long-term blood sugar balance but did not result in reduced oxidative stress as measured by F2-isotopes.

Researchers: J.M. Hodgson, G.F. Watts, et al
Published: Coenzyme Q10 improves blood pressure and glycaemic control: a controlled trial in subjects with type 2 diabetes, European Journal of Clinical Nutrition, November, 2002.

2001

This was a 12 week double-blind, random, placebo-controlled study treating 46 men and 37 women with high blood pressure. They were given COQ10 for 12 weeks.

The reduction in systolic blood pressure was 17.8 +/- mm Hg. None of the subjects had experienced feeling dizzy when they stood up suddenly. The researchers determined that COQ10 was safely used as an alternative treatment option.

Researchers: B.E. Burke, R. Neuenschwander, et al
Published: Randomized, double-blind, placebo-controlled trial of coenzyme Q10 in isolated systolic hypertension, Southern Medical Journal, November, 2001.

4. COQ10 (2012) & Hypertension in Metabolic Syndrome Patients
Learn more about hypertension (high blood pressure).

The researchers wanted to find out whether coenzyme Q10 would be helpful as an additional, or adjunct, treatment for high blood pressure patients with metabolic syndrome.

This was a double-blind, randomized, place-controlled study of 30 metabolic syndrome patients who had high blood pressure and who were already using high blood pressure medication.

While they noted that COQ10 on its own may be helpful, they found that it did not enhance the effects of other high blood pressure medication.

Researchers: Young JM, Florkowski CM, Molyneux SL, McEwan RG, Frampton CM, Nicholls MG, Scott RS, George PM, Lipid and Diabetes Research Group, Diabetes Research Institute, Christchurch Hospital Campus, New Zealand

Published: A randomized, double-blind, placebo-controlled crossover study of coenzyme Q10 therapy in hypertensive patients with the metabolic syndrome, Am J Hypertens. 2012 Feb;25(2):261-70. doi: 10.1038/ajh.2011.209

5. Fish Oil (2012) & Hypertension
Learn more about hypertension.

2012

Studies of diet have indicated that a daily meal of fish can lower blood pressure; this study looks at salmon, a fatty fish, 3 times a week is helpful.

324 subjects, 20-40 years old, received one of 4 energy-restricted diets: salmon (with 2.1g omega-3 fatty acids), cod (with .3g omega-3 fatty acids), fish oil capsules (1.3g omega-3 fatty acids), or sunflower seeds (the control). Body weight, diastolic and systolic blood pressure, and DHA was measured at the beginning of the study and after 8 weeks.

After evaluating the results, the researchers concluded that salmon consumption 3 times a week can lower diastolic blood pressure similar to fish oil, and more than lean fish over 8 weeks in young overweight adults.

Researchers: A. Ramel, J. Martinez, et al
Published: Moderate consumption of fatty fish reduces diastolic blood pressure in overweight and obese European young adults during energy restriction, Nutrition, February, 2010

Other researchers wanted to evaluate the veracity of the belief that fish oil is helpful in reducing blood pressure.

They evaluated 17 studies involving more than 1500 hypertensive and normal blood pressure subjects. They found, in 8 studies, a statistically significant reduction in systolic and diastolic blood pressure in hypertensive patients. They found, in 9 studies, a non-significant reduction in normal blood pressure subjects.

Their conclusion was that in high blood pressure patients there is a small but statistically significant benefit, but that it should not be recommended as an alternative to blood pressure lowering medication.

Researchers: F. Campbell, H. Dickinson, et al
Published: A systematic review of fish-oil supplements for the prevention and treatment of hypertension, European Journal of Preventive Cardiology, January, 2012

6. Olive Leaf Extract (2011, 2015-16) Lowers High Blood Pressure
Learn more about high blood pressure (hypertension).

2016

Researchers tested treatment of oleuropein enriched olive oil extract on three groups of lab animals. One untreated group naturally had high blood pressure, one untreated group had been bred to have high blood pressure and the third group was an group of spontaneously hypertensive rats treated with oleuropein.

After five weeks of treatment the treated group had lowered systolic blood pressure, heart rate, and kidney and heart over-activity. The treatment also reversed impaired functioning of the aorta. It reduced aortic free radicals.

Researchers: M. Romero, M. Toral, et al
Published: Antihypertensive effects of oleuropein-enriched olive leaf extract in spontaneously hypertensive rats, Food & Function, January, 2016.

2015

In a preliminary study hypertensive volunteers received olive leaf extract with 15% oleuropein and their diastolic and systolic pressure, blood antioxidant level, nitric oxide and lipid levels in blood plasma were measured. At the end of the study period the researchers observed a decrease in both diastolic and systolic pressure, increased nitric oxide levels, and cholesterol of LDL and triglycerides were lowered which markedly improved the CHO/HLD ratio.

Researchers: C. Cabrera-Vique, M. Navarro-Alarcon, et al, Hypotensive Effect of an Extract of Bioactive Compounds of Olive Leaves: Preliminary Clinical Study, Nutrition Hospitalaria, July, 2015.

2011

Captopril is a drug often given to patients with high blood pressure. In this study researchers compared the effects of captopril with the effects of olive leaf extract, whose active ingredient is oleuropein.

This was a double-blind clinical study looking at both reduction of hypertension and safety compared to captopril.

A four week period with no medication to either group preceded the study period. The treatment period was eight weeks in duration. A dosage of 500 mg two times a day was given over the eight week period to one group, and normal dosage of captopril to the other group.

Both groups had stage one hypertension which means systolic pressure of 140 to 159 mmHg and/or a diastolic pressure of 90 to 99 mmHg.

Evaluations took place on a weekly basis for blood pressure and additionally the blood lipid profile was measured after each four week period.

At the end of the study period both groups had a reduction of both diastolic and systolic blood pressure.

Additionally, there was a significant reduction in the triglyceride level in the group receiving the olive leaf extract.

Researchers: E. Sasalit, N. Agus, et al
Published: Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: comparison with Captopril, Phytomedicine, February, 2011.

7. Pine Bark (2007) - hypertension
See more about hypertension treatment and information.

2007

A number of diseases involve inflammation and impairment of endothelial layers: these include not only some vision conditions but hypertension and heart disease. The endothelium is the inner lining of blood vessels. Such dysfunction is generally defined as there being an imbalance between the ability of blood vessels' ability to contract and expand.

Various studies have determined that the relationship between obesity, inflammation and other risk factors is a critical factor in such endothelial dysfunction which causes circulation problems such as hypertension.

A two week study found that extract of French maritime pine bark (pycnogenol) supported the ability of blood vessels to appropriately dilate for adequate blood supply. However, placebo used in the study did not affect vasodilation.

The researchers concluded that pycnogenol would be useful in treating diseases involving endothelial dysfunction.

Researchers: K. Nishioka, T. Hidaka, et al
Pycnogenol, French maritime pine bark extract, augments endothelium-dependent vasodilation in humans, Hypertension Research, September, 2007.

8. Xtra Info: Hypertension Bibliography - early research
Also see discussion of hypertension and research.

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73. Irvine MJ, Logan AG. Relaxation behavior therapy as sole treatment for mild hypertension. Psychosomatic Med 1991;53:587-97.
74. Johnston DW, Gold A, Kentish J, et al. Effect of stress management on blood pressure in mild primary hypertension. BMJ 1993;306:963-6.
75. Patel CH. Yoga and bio-feedback in the management of hypertension. Lancet 1973;2:1973-5.
76. Schneider RH, Staggers F, Alexander C, et al. A randomized controlled trial of stress reduction for hypertension in older African Americans. Hypertension 1995;26:820-9.
77. Patel C, Marmot MG, Terry DJ, et al. Trial of relaxation in reducing coronary risk: four year follow up. BMJ 1985;290:1103-6.
78. Lee HS, Kim JY. Effects of acupuncture on blood pressure and plasma renin activity in two-kidney one clip goldblatt hypertensive rats. Am J Chin Med 1994;22:215-9.
79. Chiu YJ, Chi A, Reid IA. Cardiovascular and endocrine effects of acupuncture in hypertensive patients. Clin Exper Hypertens 1997;19:1047-63.
80. Peng L, Feng-yen S, An-zhong Z. The effect of acupuncture on blood pressure: the interrelation of sympathetic activity and endogenous opioid peptides. Acupunct Electrother Res 1983;8:45-56.
81. Zhou Y, Wang Y, Fang Z, et al. Influence of acupuncture on blood pressure, contents of NE, DA and 5-HT of SHR and the interrelation between blood pressure and whole blood viscosity. Chen Tzu Yen Chiu 1995;20:55-61 [in Chinese].
82. Radzievsky SA, Lebedeva OD, Fisenko LA, Majskaja SA. Function of myocardial contraction and relaxation in essential hypertension in dynamics of acupuncture therapy. Am J Chin Med 1989;17:111-7.
83. Williams T, Mueller K, Cornwall MW. Effect of acupuncture-point stimulation on diastolic blood pressure in hypertensive subjects: a preliminary study. Phys Ther 1991;71:523-9.
84. Weihai Y, Hongxu L. Clinical observation on the immediate hypotensive effect of zanzhu point. J Tradit Chin Med 1996;16:273-4.
85. Utsunomiya N, Shigematsu Y, Ikeda K, et al. Fall in high blood pressure after applying acupuncture to SHR. Jpn Heart J 1978;19:594.
86. Yiping Z, Qiong C, Zhengming H, Yinong C. Experimental research on treatment of hypertension with acupuncture. J Tradit Chin Med 1993;13:277-80.
87. Tam K-C, Yiu H-H. The effect of acupuncture on essential hypertension. Am J Chin Med 1975;3:369-75.
88. Kraft K, Coulon S. Effect of a standardized acupuncture treatment on complains, blood pressure and serum lipids of hypertensive, postmenopausal women. A randomized, controlled clinical study. Forsch Komplementarmed 1999;6:74-9 [in German].
89. Rongxing Z, Yanhua Z, Lu Y. Hypotensive effect of ototherapy in relation to symptomatic and dispositional types of patients. J Tradit Chin Med 1992;12:124-8.
90. Kangmei C, Shulian Z, Ying Z. Clinical application of traditional auriculoacupoint therapy (continued). J Tradit Chin Med 1993;13:152-4.
91. Rongxing Z, Yanhua Z, Jialiang W, et al. Anti-hypertensive effect of auriculo-acupoint pressing therapy- clinical analysis of 274 cases. J Tradit Chin Med 1991;11:189-92.
92. Peng Y, Fenglan L, Xin W. Treatment of essential hypertension with auriculopressure. J Tradit Chin Med 1991;1117-21.
93. Tran T, Kirby J. Effects of upper cervical adjustments upon the normal physiology of the heart. ACA J Chiro 1977;XI:S58-62.
94. McGuiness J, Vicenzino B, Wright A. The influence of a cervical mobilization technique on respiratory and cardiovascular function. Manual Therapy 1997;(2):216-20.
95. Vicenzino B, Cartwright T, Collins D. Cardiovascular and respiratory changes produced by lateral glide mobilization of the cervical spine Manual Therapy 1998;3(2):67-71.
96. Dulgar G, Hill D, Sirucek A, et al. Evidence for possible anti-hypertensive effect of basic technique apex contact adjusting. J Chiro 1980;14:S97-S102.
97. Nansel D, Jansen R, Cremata E, et al. Effects of cervical adjustments on lateral-flexion passive end-range asymmetry and on blood pressure, heart rate and plasma catecholamine levels. J Manipulative Physiol Ther 1991;14:450-6.
98. Fichera AP, Celander DR. Effect of osteopathic manipulative therapy on autonomic tone as evidenced by blood pressure change and activity of the fibrinolytic system. J Am Osteopath Assoc 1969;68:1036-8.
99. McKnight M, DeBoer KD. Preliminary study of blood pressure changes in normotensive patients under chiropractic care. J Manipulative Physiol Ther 1988;11:261-6.
100. Yates RG, Lamping DL, Nancy LA, Wright C. Effects of chiropractic treatment on blood pressure and anxiety: a randomized, controlled trial. J Manipulative Physiol Ther 1988;11:484-8.
101. Morgan JP, Dickey JL, Hunt HH, Hudgins PM. A controlled trial of spinal manipulation in the management of hypertension. J Am Osteopath Assoc 1985;85(5):308-12.
102. Mannino J. The application of neurologic reflexes to the treatment of hypertension. J Am Osteopath Assoc 1979;79:225-31.
103. Wagnon RJ, Sandefur RM, Ratliff CR. Serum aldosterone changes after specific chiropractic manipulation. Am J Chiropr Med 1988;1(2):66-70.
104. Goodman R. Hypertension and the atlas subluxation complex. Chiropractic: J Chiropractic Res Clin Invest 1992;8(2)30-2.

Indigestion

1. Anti-acids (2012) & Clostridium difficile risk
Learn more about natural indigestion recommendations

The Canadian Health Ministry is warning people about the possible risk of potentially dangerous clostridium difficile-related diarrhea from use of prescription anti-acids, known as "protein-pumps". Protein-pumps are used to treat acid reflux, and stomach and small intestine ulcers.

While there is not yet conclusive evidence, a number of different studies strongly suggest a connection between prescription anti-acids and clostridium difficile problems, especially in vulnerable people: the elderly, those with severe underlying illness, hospitalization, or those taking antibiotics.

Symptoms include severe watery or bloody diarrhea, fever, loss of appetite, nausea, and abdominal pain or tenderness.

Here's a list of drugs (sold in Canada):

Dexlansoprazole (Dexilant)

Esomeprazole (Nexium and its generic equivalent)

Omeprazole (Losec and its generic equivalents)

Lansoprazole (Prevacid and its generic equivalents)

Pantoprazole (Pantoloc and Panto IV, and their generic equivalents)

Pantoprazole/magnesium (Tecta)

Rabeprazole (Pariet and its generic equivalents)

These products may also be found in combination with other drugs, for example: Vimovo contains esomeprazole

2. Indigestion (2005): Heartburn Remedy Side Effects
Learn more about natural indigestion recommendations

Antacid preparations such as (Prilosec, Prevacid, Nexium, Pepcid, and Zantac) inhibit the acids in the stomach helpful to digestion. However, there are other consequences as well. The use of these antacids leaves users more at risk for serious Clostridium difficile infections as well as diarrhea.

The Centers for Disease Control reports that more and more cases of Clostridium difficile are being reported by non-hospitalized healthy adults. Some scientists wonder whether this rise in C. difficile infection rates is tied to heavy use of antacids.
Published: Journal of the American Medical Association, 2005.

Editor's Note: Try digestive enzymes during meals.

3. Xtra Info: Indigestion Research Bibliography
Also see discussion of indigestion (stomach ache, acid stomach) and research.

1. Suarez F, Levitt MD, Adshead J, Barkin JS. Pancreatic supplements reduce symptomatic response of healthy subjects to a high fat meal. Dig Dis Sci 1999;44:1317-21.
2. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician's Guide to Herbal Medicine. 3rd ed, Berlin: Springer, 1998, 168-73.
3. Ritter R, Schatton WFH, et al. Clinical trial on standardized celandine extract in patients with functional epigastric complaints: Results of placebo-controlled double-blind trial. Comp Ther Med 1993;1:189-93.
4. Benninger J, Schneider HT, Schuppan D, et al. Acute hepatitis induced by greater celandine (Chelidonium majus). Gastroenterol 1999;117:1234-7.
5. Kraft K. Artichoke leaf extract--recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts. Phytomedicine 1997;4:370-8 [review].
6. Kirchhoff R, Beckers C, Kirchhoff GM, et al. Increase in choleresis by means of artichoke extract. Phytomedicine 1994;1:107-15.
7. Westphal J, Horning M, Leonhardt K. Phytotherapy in functional upper abdominal complaints. Results of a clinical study with a preparation of several plants. Phytomedicine 1996;2:285-91.
8. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 425-6.
9. Tewari JP, Srivastava MC, Bajpai JL. Pharmacologic studies of Achillea millefolium Linn. Indian J Med Sci 1994;28(8):331-6.
10. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics, 2d ed. New York: John Wiley and Sons, 1996, 303.
11. Bradley PR. British Herbal Compendium, vol. 1. Great Britain: British Herbal Medicine Association, 1990, 218-9.
12. Forster HB, Niklas H, Lutz S. Antispasmodic effects of some medicinal plants. Planta Med 1980;40:303-19.
13. May B, Kuntz HD, Kieser M, Kohler S. Efficacy of a fixed peppermint/caraway oil combination in non-ulcer dyspepsia. Arzneimittelforschung 1996;46:1149-53.
14. Westphal J, Horning M, Leonhardt K. Phytotherapy in functional upper abdominal complaints. Results of a clinical study with a preparation of several plants. Phytomedicine 1996;2:285-91.
15. Madisch A, Heydenreich CJ, Wieland V, et al. Treatment of functional dyspepsia with a fixed peppermint oil and caraway oil combination as compared to cisapride. Arzneimittelforschung 1999;49;925-32.
16. Fiegel VG, Hohensee F. Experimental and clinical screening of a dry, water extract of tiliae libri. Arzneimittelforschung 1963;13:222-5 [in German].
17. Sadek HM. Treatment of hypertonic dyskinesias of Oddi's sphincter using a wild Tilia suspension. Hospital (Rio J) 1970;77:141-7 [in Portuguese].
18. Langer M. Clinical observations on an antispastic factor extracted from Tiliae silvestris alburnum. Clin Ter 1963;25:438-44 [in Italian].
19. Thamlikitkul V, Bunyapraphatsara N, Dechatiwongse T, et al. Randomized double blind study of Curcuma domestica Val for dyspepsia. J Med Assoc Thai 1989;72:613-20.
20. Mills SY. Out of the Earth: The Essential Book of Herbal Medicine. London: Viking Press, 1991, 448-51.
21. Weiss RF. Herbal Medicine. Beaconsfield, UK: Beaconsfield Publishers Ltd, 1985.
22. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 425-6.
23. Weiss RF. Herbal Medicine. Beaconsfield, UK: Beaconsfield Publishers Ltd, 1988, 185-6.
24. Blumenthal M, Busse WR, Goldberg A, et al. (eds). The Complete German Commission E Monographs: Therapeutic Guide to Herbal Medicines. Austin: American Botanical Council and Boston: Integrative Medicine Communications, 1998, 198.
25. Micklefield GH, Redeker Y, Meister V, et al. Effects of ginger on gastroduodenal motility. Int J Clin Pharmacol Ther 1999;37:341-6.
26. Goso Y, Ogata Y, Ishihara K, Hotta K. Effects of traditional herbal medicine on gastric acid. Biochem Physiol 1996;113C:17-21.
27. Reed PI, Davies WA. Controlled trial of a carbenoxolone/alginate antacid combination in reflux oesophagitis. Curr Med Res Opin 1978;5:637-44.

Insomnia

1. Calcium (2009) & Insomnia
Learn more about insomnia.

Researchers have found that mild calcium deficiency, often associated with menopause, can contribute to insomnia along with other related conditions such as nerve sensitivity and irritability.

The authors write that deficiencies in calcium and magnesium can cause one to awaken after several hours sleep and have difficulty getting back to sleep.

Sources:
Insomnia: Studies Confirm Calcium And Magnesium Effective, Medical News Today; 2009
Bookman Press 1998; 2000-02-08; Vitamins: Calcium.
Prescription for Nutritional Healing, Phyllis A. & James F. Balch, MD, 2003

2. Lemon Balm (2004) & Insomnia
Learn more about insomnia.

Though the sample size was small, including 18 healthy volunteers, this study was a double-blind, placebo-controlled, randomized, balanced crossover experiment, which is the top level of scientific methodology. 18 healthy volunteers received two doses of M. Officinalis extract (300 mg, 600 mg). They were tested for modulation of moods, stress measurements and cognitive performance both before they took the dose and one hour after. Then there was a 7 day washout period to make sure no traces of the Melissa remained in their physiology and a placebo was administered with the same tests.

The participants showed significantly lower negative moods effect of the stress test, higher self-ratings of calmness, and increased speed of mathematical processing with no reduction of accuracy after ingestion of the 300mg dose of Melissa.

Researchers: Kennedy, D. O., Little W, Scholey A. B.

Published: Attenuation of Laboratory-Induced Stress in Humans after Acute Administration of Melissa Officinalis (Lemon Balm), (2004 Psychosomatic Medicine 66 (4): 607-13.

3. Lemon Balm (2011) & Insomnia
Learn more about insomnia.

Twenty subjects with mild to moderate anxiety disorders and sleep disturbances were involved in a 15 day study of a Melissa Officinalis extract. Using clinician rating criteria, the treatment reduced anxiety by 18%, anxiety-related symptoms by 15% and lowered insomnia by 42%. This is a good preliminary study showing evidence to continue studying Melissa Officinalis as a treatment for stress related symptoms. Further studies which use blind, balanced controls and placebo groups will strengthen the evidence.

Researchers: Cases J, Ibarra A, Feuillere N, Roller M, Sukkar SG.

Published: Pilot trial of Melissa Officinalis L. leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances, Med J Nutrition Metab. 2011 Dec;4(3):211-218.

4. Magnesium (2006) & Insomnia
Learn more about insomnia.

Taking a supplement with melatonin, magnesium and zinc improved their sleep and quality of life.

Research: "Rapid recovery from major depression using magnesium treatment" Eby GA, Et al. A double-blind placebo controlled trial included 57 patients with insomnia in a long-term care facility in Italy. Med Hypotheses. 2006;67(2):362-70. Epub 2006 Mar 20

5. Melatonin (2009) & Insomnia
Learn more about insomnia.

This is a review of existing research on the use of a form of melatonin for insomnia in older patients. The researchers concluded that melatonin does improve both insomnia and quality of life, does not have the addictive and other side effects of prescription sleeping aids, can be used with other medications, and does not have any adverse effects on patients who have or do use other drugs.

Researchers: Zisapel N. Department of Neurobiology, Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

Published: Controlled release melatonin (Circadin) in the treatment of insomnia in older patients: efficacy and safety in patients with history of use and non-use of hypnotic drug, Harefuah, 2009 May;148(5):337-41, 348

6. Melatonin, Magnesium, Zinc (2011) & Insomnia
Learn more about insomnia.

A double- blind controlled trial involved 43 patients with primary insomnia. Patients took a food supplement with melatonin, magnesium and zinc every night one hour before bed. The control group took a placebo. The group taking the supplement had considerable improvement in ease of going to sleep, staying asleep, quality of sleep and daytime functionality.

Researchers: Rondanelli M, Opizzi A, Monteferrario F, Antoniello N, Manni R, Klersy C., Section of Human Nutrition and Dietetics, Faculty of Medicine, University of Pavia, Pavia, Italy.

Published: The effect of melatonin, magnesium, and zinc on primary insomnia in long-term care facility residents in Italy: a double-blind, placebo-controlled clinical trial; J Am Geriatr Soc., 2011 Jan;59(1):82-90.

7. Valerian, Lemon Balm (2006) & Insomnia
Learn more about insomnia.

918 children in multiple centers were treated successfully. Dyssomnia is a form of insomnia caused by disruptions in physiological functioning often due to environmental factors. Although this research was conducted by a pharmaceutical company it is worth noting that European pharmaceutical companies and doctors have long accorded the same respect to aromatherapy, herbal and homeopathic treatments as given to allopathic treatment in the U.S. Also this study cannot be considered of primary importance because it was not a blind trial with a control group, but it did included 918 subjects. Similar studies conducted by universities and hospitals rarely have this large a group.

Researchers: Muller SF, Klement, Et al. Schwabe Pharmaceuticals, Karlsruhe, Germany.

Published: A combination of valerian and lemon balm is effective in the treatment of restlessness and dyssomnia in children, Phytomedicine. 2006 Jun;13(6):383-7.

8. Vitamin B12 (1996) & Insomnia

Learn more about insomnia.

Researchers evaluated results of treating 106 patients who suffered from various forms of insomnia with a combination of vitamin B12, bright light, chronotherapy and/or hypnotism. 32% of the patients experienced moderate to marked improvement. This study did not evaluate use of B12 alone, and other research has suggested that B12 alone does not bring about statistically significant improvements.

Nonetheless, since B12 supports the nervous system, it may well be that a B12 deficiency contributes to insomnia as a secondary condition.

Research: A multicenter study of sleep-wake rhythm disorders: therapeutic effects of vitamin B12, bright light therapy, chronotherapy and hypnotics., Yamadera H., et al.; Psychiatry Clin Neurosci. 1996 Aug;50(4):203-9.

9. Vitamin B6 (2013, 2014) and Insomnia
Learn more about insomnia.

2014
Researchers investing the biochemistry of sleep identify vitamin B6 as one of the precursors to serotonin. Serotonin is a precursor to melatonin, which is recognizes as one of the primary biochemicals that regulate the circadian rhythm and support good sleep.

Researchers: Y. Yang, et al

Published: Strategies of Functional Foods Promote Sleep in Human Being, Current Signal Transduction Therapy, December, 2014.

2013
Noting that poor sleep quality is linked to mortality, researchers investigated diet and nutrition in nearly 2000 men and women over the age of 65. The quality of their sleep was categorized as good, fair or poor.

For both men and women the better the sleep the lower the mortality. For men they found that a good variety in diet was associated with better sleep. They found that women with poor sleep quality had markedly lower vitamin B6 and vegetable consumption and concluded that vitamin-B6 deficiency was a greater indicator of mortality than sleep.

Researchers: Y.C. Huang, et al

Published: Sleep quality in the survival of elderly taiwanese: roles for dietary diversity and pyridoxine in men and women, Journal of the American College of Nutrition., 2013.

Iritis

1. Curcumin, Echinacea (2010, 2006) & Iritis
Learn more about iritis

Recent studies on anterior uveitis, also known as iritis, demonstrate that both echinacea and curcumin (tumeric) may be helpful.

Efficacy of curcumin in the management of chronic anterior uveitis

Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis

Keratoconus

1. Magnesium (2005) & Keratoconus
Learn more about keratoconus.

Early research into probable causes of keratoconus determined that one likely factor was magnesium deficiency. Reports pointed out that magnesium deficiency could negatively impact how the cornea works.

A number of white papers were reviewed in 2005 which collectively indicated that the connection is significant - that magnesium deficiencies cause molecular and cellular abnormalities which are similar to the abnormalities in cells comprising the cornea in keratoconus patients. The abnormal structures occur both within cells and in the spaces outside the cells. The changes include thinning and breaking down of membranes, cell and collagen fiber degeneration, mitochondria swelling, and biochemical abnormalities in synthesis of protein.

Reviewer: A. Thalasselis, Institute of Vision, Mar del Plata, Argentina.

Published: The possible relationship between keratoconus and magnesium deficiency, Thalasselis A., Ophthalmic & Physiological Optics, Jan. 2005, 25(1), pp 7-12.

2. MSM (2015) Reduces Inflammation - Keratoconus
MSM is helpful for conditions where inflammation is an issue such as keratoconus.

The researchers noted that while the health benefit of reducing inflammation is associated with Methylsulfonylmethane (MSM) there had been no study focusing on that capacity with regard to inflammasomes - a formation composed of multiple proteins that acts as a basis for stimulating lymphocyte development. Lymphocytes are the white blood cells that fight infection.

The researchers found that MSM did reduce some types of inflammasome activation. They also found that MSM-enriched vegetable given to lab animals had the same effect.

They concluded that MSM does present anti-inflammatory capacity, interrupts inflammasome production, and inhibits expression of pro-cytokines which promote systemic inflammation and make a disease worse through fever and tissue death.

Researchers: H. Ahn, J. Kim, M. Lee, Y. Kim, Y.W. Cho, G. Lee

Published: Methylsulfonylmethane inhibits NLRP3 inflammasome activation, Cytokine, February, 2015.

Leber's Hereditary Optic Neuropathy

1. Antioxidants (2007, 2011) & Leber's
Learn more about Leber's.

A number of studies associate antioxidants with improvements in the treatment of eye disease, particular conditions of the optic nerve such as Leber's.

These provide some potential lines of future research in looking at treatment for Leber's Hereditary Optic Neuropathy (LHON).

These studies include:

Providing nerve cell stability and reducing free radical damage due to toxins including environmental toxins, smoking, and alcohol abuse. These anti-oxidants include vitamins and natural plant extracts, such as Vitamins A, C & E, Co- Ginkgo biloba, curcumin (tumeric).¹

A metabolite of vitamin E is Alpha-tocotrienol-quinone which has some reversing-symptoms benefit in trials in early onset vision loss.2

Other treatments, such as brimonidine, are under consideration in protection of the optic nerve with mixed results.³
Finally, gene therapy has been used experimentally.

Footnotes:

1. Ritch R. 2007. Natural compounds: evidence for a protective role in eye disease. Can J Ophthalmol. 2007 Jun;42(3):425-38

2. Shrader, W. D.; Amagata, A.; Barnes, A.; Enns, G. M.; Hinman, A.; Jankowski, O.; Kheifets, V.; Komatsuzaki, R. et al. 2011. Alpha-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging. Bioorganic & Medicinal Chemistry Letters 21 (12): 3693-3698

3. Newman NJ, Biousse V, David R, Bhatti MT, Hamilton SR, Farris BK, Lesser RL, Newman SA, Turbin RE, Chen K, Keaney RP. 2005. Prophylaxis for second eye involvement in leber hereditary optic neuropathy: an open-labeled, non-randomized multicenter trial of topical brimonidine purite. Am J Ophthalmol. Sep;140(3):407-15

2. Gene Therapy (2009) for Leber's Disease
In a 2009 Phase I clinical trial, researchers injected a benign virus carrying a connected copy of an essential gene into a teenage boy's retina. This patient had lost vision due to a genetic disorder called "Leber's Congenital Amaurosis (LGA).
The result was improved vision as the gene therapy enabled the body to make new rods and cones (which normally are irreplaceable once lost).
Other young patients given the same procedure also were able to see better. All the children that underwent this procedure gained enough vision to walk independently.

Published: The Lancet, 2009, by Albert M Maguire MD and others, University of Pennsylvania School of Medicine

Learn more about Lebers Hereditary Optic Neuropathy including complementary nutritional and other recommendations.

3. Smoking (1999) & Lebers Risk Factors
Learn more about Leber's Hereditary Optic Neuropathy.

Smoking has long been identified as a factor in higher risk for many diseases and vision conditions. This research identified smoking as a causative factor for Leber's as well.

Leber's is a hereditary condition, passed through the mother, where mitochondria mutate in the retinal nerves, causing loss of central vision.

In this study researchers matched family members, analyzing both combined male/female family groups and subgroups of men, where there was an inherited risk of Leber's. They found a significant connection between smoking and incidence of Leber's in all the subgroups, with a higher rate in males. The connection was higher in older aged groups and where smoking rates were higher.

The researchers concluded that the amount of smoking and number of years which subjects had been smoking were also correlated with higher risk of Leber's symptoms.

Researchers: K. Tsao, P. Aitken, and D. Johns

Published: Smoking as an aetiological factor in a pedigree with Leber's hereditary optic neuropathy, British Journal of Ophthalmology, 1999 May; 83(5): 577-581.

4. Toxins & Nutrition(1998) & Leber's
Learn more about Leber's.

Researchers have identified both exposure to toxins and nutritional deficiencies as been connected to incidence of mitochondria-mutated conditions such as Leber's.

In Cuba, in the 1990's an epidemic affected 50,000 patients with symptoms common to both lazy eye due to alcohol/tobacco toxins and Leber's. There was characteristic damage leading to these conclusions. The patients exhibited both vitamin deficiencies and mitochondrial damage from methanol and cyanide toxins.

The researchers were particularly interested in determining why impaired production of cellular energy led to this kind of damage, and why, within the nervous system, why the optic nerve's ganglion cells were especially vulnerable.

The researchers comprehensively evaluated both the patients via neuro ophthalmologic exams, as well as blood, cerebrospinal fluid, DNA, and, from deceased patients, the nerves running down the back of the leg and the eye and optic nerve itself. Blood folic acid levels were low, and blood formate levels were high. These were then tested via animal models.

Finding: These patients' vision conditions improved when their nutritional deficiencies were corrected, and their exposure to toxins ceased.

The researchers concluded that mitochondria (noting that the mitochondria in cells of the eye are most vulnerable) can be damaged either genetically or by way of nutritional deficiencies or exposure to toxins. There is a threshold, once passed, which results in irreversible damage.

Researcher: Sudan, A., et. al

Published: Acquired mitochondrial impairment as a cause of optic nerve disease., Trans Am Ophthalmol Soc. 1998;96:881-923.

Light Sensitivity

1. Lutein, Zeaxanthin (2008) and Light Sensitivity
Researchers have found that the carotenoids lutein and zeaxanthin which support the health of the eye are effective in the manner in which they help alleviate many vision problems such as good vision under glaring lights, which is related to the general sensitivity of the eye to bright light. Lutein and zeaxanthin were found to be markedly associated with improvements eyesight in glare conditions and the ability of the eye to recovery from the stress produced by such glare. Glare types include bright sunlight, computer monitor light, and car headlights at night.
The study included forty healthy people (mean age of 23.9) whose lutein and zeaxanthin levels were evaluated for six months. After six months of lutein and zeaxanthin supplementation, the levels of pigments in their maculas improved and they experienced a reduction in the harmful effects of glare.

Researchers: James M. Stringham, et al

Published: Macular Pigment and Visual Performance Under Glare Conditions, Optometry and Vision Science, Feb., 2008.

Macular Degeneration

1. Acetyl-L-carnitine, omega-3 fatty acids, CoQ10 (2005) & Macular Degeneration Drusens
This study looked at positive changes in patients with early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10.

This study was double-blind (neither the 106 patients nor the researchers knew the who was receiving which treatment), random and included placebos. The purpose was to determine the effectiveness of a combined acetyl-L-carnitine, N3 fatty acids, and CoQ10 on the visual capacity and changes within the eye (in the fundus) in early age-related macular degeneration). The patients were divided into a test group and a control group.

"The primary efficacy variable was the change in the visual field mean defect (VFMD) from baseline to 12 months of treatment, with secondary efficacy parameters: visual acuity (Snellen chart and ETDRS chart), foveal sensitivity as measured by perimetry, and fundus alterations as evaluated according to the criteria of the International Classification and Grading System for AMD."

The treated group had significant improvement by the end of the study. In addition, in the treated group 2% experienced deterioration in VFMD, and 17% of the placebo group showed clinically significant deterioration.

The researchers also found that the lessening of the drusen-covered area of treated eyes was also statistically significant as compared to placebo patients.

The results indicated that an appropriate combination of compounds which affect mitochondrial lipid metabolism, may improve and subsequently stabilize visual functions, and it may also improve fundus alterations in patients affected by early AMD.

Published: Ophthalmologica. 2005 May-Jun;219(3):154-66.

2. Antioxidants (1990s, 2002, 2004, 2008) & macular degeneration
See more about macular degeneration treatment and information.

See research on specific antioxidants:

AREDS formulations

Astaxanthin

Lutein & Zeaxanthin

Lutein

Meso-Zeaxanthin

Zeaxanthin

1991
An 18-month study found that patient who had macular degeneration and who regularly and daily included antioxidants were two and a half times more likely to see improvement in their vision with standardized testing. They were also four times less likely to experience vision degradation in their weak eye compared to other patients who took the antioxidants less regularly.

Published: Journal of Cataract and Refractive Surgery, Mar 1991.

1996
A study found that patients with age related macular degeneration had lower levels of vitamin E, magnesium, zinc, vitamin B6 and folic acid in their daily diet. When patients took antioxidants twice a day their vision improved compared to patients taking a placebo.

Researchers: Richer, et al
Published: Journal of American Optometry Association, January, 1996

2002
A study reported that the antioxidant carotenoids lutein and zeaxanthin protects against AMD by way of antioxidant free radical fighting and screening of damaging UV and blue light. The researchers used Raman spectroscopy to compare the levels of macular pigment in test subjects. The study involved 63 AMD patients and 138 healthy eye patients and found that patients with AMD had 32% less lutein and zeaxanthin (where not taking supplement). Once patients began to consume the carotenoids with 4mg/daily lutein the levels of macular pigments increased substantially.

Researchers: P. Bernstein, University of Utah
Published: Ophthalmology, 2002;109:1780-1878

2004
The researchers looked at macular degeneration research from previous years and found consistent deficiencies in micronutrients in cases of wet macular degeneration. Wet macular degeneration is an advanced form, also known as choroidal neovascularization because new blood vessels form distorting the macular area of the retina.

They evaluated the connection between diet and nutrition and incidence of AMD. Although the initial evidence appeared to be inconsistent, it has become evident that stress in the eye from oxidative damage is an important factor in development of AMD. The researchers conclude that antioxidants can have an important role in slowing or preventing macular degeneration.

Researchers, R. Hogg, et al, Institute of Clinical Science, Belfast
AMD and micronutrient antioxidants, Current Eye Research, December, 2004.

2008
In this study researchers investigated why antioxidants support retinal health. They discovered a connection between several conditions which, combined, cause damage to the retina contributing to macular degeneration. Antioxidants disrupt this process and support the health and integrity of essential photoreceptor cells in the retina.

Synergies occur when separate processes or compound complement each other to enhance the result - beneficial or destructive. The scientists found that the building of a compound identified as A2E reacts with mitochondria within cells (mitochondria are the power source of cellular energy). A2E is a byproduct of cell activity which is not removed naturally by the body.

They found that when A2E exists in cells where oxidative stress due to exposure to damaging UV or blue light is also present that A2E disrupts the action of producing energy in mitochondria. Loss of cellular energy means that waste disposal and photoreceptor maintenance is weakened.

It is a continuing cycle - photoreceptor cells are weakened and die (and are not replaced) and further stress results compounded by the presence of A2E.

Antioxidants fight the resulting damage by protecting the eye from oxidative stress.

Researchers: H. Vollmer-Snarr, et al, University of Brigham Young.
Published: The age lipid A2E and mitochondrial dysfunction synergistically impair phagocytosis by retinal pigment epithelial cells, Journal of Biological Chemistry, November, 2008.

2008
A combination of low levels of antioxidants and exposure to the sun's blue light (as distinguished from ultra violet light) may increase risk of macular degeneration. Blue light alone is not tied to macular degeneration, however researchers have found that there is a consistent and significant connection between with age-related macular degeneration and patients in the lowest quartile nutritional intake of vitamin C, vitamin E, zeaxanthin, and dietary zinc.

The likelihood for neovascular age-related macular degeneration were even more among those patients with the lowest combined antioxidant levels, particularly the combination of vitamin C, zeaxanthin, and vitamin E. The researchers found similar connections in patients with early age-related macular degeneration.

Researchers agree that there is a risk to the eyes from sun exposure, but what interesting is that different wavelengths of light inflict damage on different parts of the eye.

The cornea and lens absorb "invisible" ultraviolet light and are damaged (cataracts) by ultra violet light. The retina absorbs visible light, including blue light, and this study demonstrated that not only can the retina be damaged by blue light, but that blue light exposure combined with low antioxidant levels causes retinal damage, including macular degeneration.

Researchers: Fletcher AE, et al
Published: Sunlight exposure, antioxidants, and age-related macular degeneration, Archives of Ophthalmology, October, 2008

3. AREDS, AREDS2: (2001, 2006, 2013) Antioxidants & Macular Degeneration
See more about macular degeneration treatment and information.

AREDS, 2001

The original AREDS trial discovered that patients who have macular degeneration can somewhat lower the risk of the condition degenerating to the more severe wet macular degeneration with supplementation of zinc and antioxidants. The clinical trial was called the Age-Related Eye Disease Study (AREDS) and it was a placebo-controlled and random. It reviewed the health records of over 4,700 women and men aged 55 to 80 over a 6.3 year period on average. The patients were given one of four treatments:

zinc alone;

antioxidants alone;

antioxidants and zinc;

a placebo

The benefits of the nutrients were seen only in people who began the study at high risk for developing advanced AMD, and in that group those taking antioxidants and zinc had the lowest risk of developing advanced stages of AMD.

The three stages of AMD analyzed in this study are:

Early AMD. People have, in one or both eyes, either several small drusen or a few medium-sized drusen with no vision loss.

Intermediate AMD. Those with intermediate AMD have, in one or both eyes, either many medium-sized drusen or one or more large drusen and little or no vision loss.

Advanced AMD. In addition to drusen, people with advanced AMD have, in one or both eyes, either:

A breakdown of light-sensitive cells and tissue in the central retinal area (advanced dry form); or

Abnormal, fragile blood vessels under the retina that leak fluid or bleed (advanced wet form)

The researchers found that antioxidant/zinc supplementation in patients with advanced dry macular degeneration or vision loss because of wet macular degeneration in a single eye had a 20% of having their condition worsen within five years compared to 28% of patients taking a placebo.

The formulation used in the AREDs study contained several antioxidant vitamins, which are nutrients that can help maintain healthy cells and tissues. They also contained zinc, which is an important mineral incorporated into many body tissues:

500 milligrams of vitamin C;

400 international units of vitamin E;

15 milligrams of beta-carotene;

80 milligrams of zinc as zinc oxide;

2 milligrams of copper as cupric oxide

It has been known from earlier studies that people with diets rich in green, leafy vegetables have a lower AMD risk, but it is hard to gain the therapeutic levels needed through diet alone. Therefore the supplements were needed.

The study also showed that people who take a daily multivitamin can lower the risk of vision loss by adding the same high levels of antioxidants and zinc as in the study.

Researchers: National Institutes of Health, National Eye Institute,
Published: Archives of Ophthalmology, October, 2001

Editor's Note: Cancer prevention studies have found that high doses of beta carotene increase the risk of developing lung cancer in cigarette smokers and recommend against taking beta carotene to prevent advanced macular degeneration. However, later studies have apparently debunked the idea saying that the studies were flawed. There needs to be more research to substantiate the claim.

AREDS2, 2006

The same researchers at NIH who performed the AREDS (Age Related Eye Disease Study) in 2001 wanted to determine whether adding omega-3 fatty acids, lutein and zeaxanthin to the AREDS formulation (vitamins C & E, zinc & beta-carotene) would be of value for aging patients with eye disease. Because beta-carotene is counter-indicated for smokers, they were also investigating alternatives to that nutrient.

In AREDS2, a 5 year study involving more than 4000 patients, the revised recommended formulation, based on the new research concluded that the optimal combination was as follows:

500mg of vitamin C

400 IU vitamin E

2mg copper

25mg zinc (lower level)

1000mg of omega-3 fatty acids

beta-carotene deleted

The researchers concluded that the omega-3s did not improve the formulation, but because they are known to be helpful they are retained in the recommendations.

Researchers: National Institutes of Health, National Eye Institute

Published: 2006

AREDS update, 2013

In 2013 researchers considered the value of the AREDS2 formulation for cataracts, finding that like the original formula, none of the modifications reduced cataract progression.

This report further established the long-term value of these nutrients. Patients taking the formulation during the 5-year AREDS2 trial were 25-30% less likely to develop advanced macular degeneration. It further concluded that long term use of the AREDS2 formulation was safe and protective against advanced AMD.

Researchers: NEI Intramural Research Program with support from National Institute of Neurological Disorders and Stroke; the National Institute on Aging; the National Heart, Lung, and Blood Institute; the National Center for Complementary and Alternative Medicine; and the NIH Office of Dietary Supplements.

Published: JAMA Ophthalmology, May, 2013.

4. Aspirin (2013) Use Increases Risk of AMD
Researchers investigating frequency of aspirin use with vision health found that there was a higher risk of developing macular degeneration (AMD) when aspirin was used daily.

The study was based on a questionnaire given to 2,389 Australians over a 15 year period.

The scientists found that, even with age, sex, smoking, heart disease history, high blood pressure, and body mass index, those people who used aspirin regularly had a great risk of developing advanced AMD. 9.3% of those using aspirin on a regular basis developed advanced AMD compared to 3.7% who did not.

Researchers: Liew G, Mitchell P, Wong TY, et al.

Published: The association of aspirin use with age-related macular degeneration. Journal of American Medical Association Internal Medicine 2013;173(4):258-64.

5. Astaxanthin (2008, 2013) & Macular Degeneration
Learn more about macular degeneration recommendations.

2012 Researchers, noting the large presence of carotenoids in the macula as well as other research which links free radical damage to macular degeneration, studied whether carotenoids in dietary supplements would be helpful.

In the study 145 patients with age related macular degeneration were randomly assigned to one of two groups. The test group was given lutein (10 mg), zeaxanthin (1 mg), astaxanthin (4 mg) in an antioxidant/vitamin nutritional supplement for two years.

The results were measured by gauging changes in visual acuity after one year and again after two years. The researchers also looked at perception of visual contrasts. National Eye Institute visual function questionnaire (NEI VFQ-25) scores were reviewed after 1 and 2 years.

Those people in the group receiving the antioxidant/vitamin supplement showed significant improvement in visual acuity (vision sharpness). In addition, the researchers concluded that people given lutein/zeaxanthin and astaxanthin together with other nutrients were more likely to report significant improvements.

Researchers: Parisi V, et al.
Published: Carotenoids and antioxidants in age-related maculopathy, European Journal Ophthalmology. March, 2012

2013 The researchers investigated whether the carotenoid, astaxanthin, a powerful antioxidant, would protect the retina from damage caused by light. Lab animals were exposed to strong white light to stimulate damage to their retinas. Five days later the degree of damage was assessed using standardized methods. In addition a marker which indicates cell death was evaluated. In a separate study using cell tissue, light was again used to cause retinal tissue damage and the results were examined.

In both cases, in vivo and in vitro the supplementation with or application of astaxanthin protected against increases of those signals of cell death and retinal damage.

The researchers concluded that astaxanthin was effective in protecting against damage from light due to its antioxidant effect.

Researchers: T. Otsuka, et al
Published: Protective effects of a dietary carotenoid, astaxanthin, against light-induced retinal damage, Journal of Pharmaceutical Science, October, 2013.

6. Bacterium, Gene (2005) Play Roles in Elderly Vision Loss
See more about macular degeneration treatment and information.

Researchers at the Massachusetts Eye and Ear Infirmary found C. pneumoniae in the diseased eye tissue of five of nine people with wet AMD but not in the eyes of 20 people without AMD. The findings offer more evidence that AMD may be caused by inflammation, the researchers said.

The study appears in the November issue of the journal Graefe's Archive for Clinical and Experimental Ophthalmology.

"We found that C. pneumoniae infection led to increased production of vascular endothelial growth factor (VEGF), the key protein involved in wet AMD. That C. pneumoniae infection of human eye cell types increases VEGF production is therefore significant and could explain in part why VEGF levels are increased in many people with wet AMD," Kalayoglu said.

"Our hypothesis is that C. pneumoniae may be the key link between CFH and AMD. That is, patients with CFH variations may be particularly susceptible to the damaging effects of chronic infection, and an infectious organism like C. pneumoniae may be particularly effective in accelerating inflammation and driving progression of AMD in these patients," Kalayoglu said.

7. Bilberry extract (2005) & AMD, and Cataracts
Learn more about macular degeneration treatment and information and cataracts.

A 2005 Russian study looked at antioxidants' effect on damaging free radicals for cataracts and macular degeneration.

Bilberry's flavonoids are known as potent antioxidants, scavenging free radicals. They are effective for many age-related ocular disorders. The scientists looked at senescence-accelerated (accelerated biological aging) OXYS rats who were suffering from early senile cataract and macular degeneration. Young rats were given control diets or those supplemented with 25% bilberry extract or vitamin E. At 3 months testing showed that more then 70% of control OXYS rats had cataract and macular degeneration while the supplementation of BE completely prevented impairments in the lenses and retina.

The vitamin E had no significant effects but both antioxidants decreased lipid peroxides in the retina and serum of OXYS rats. The results suggest that the OXYS rat strain is the useful model for testing treatment for macular degeneration and cataracts and that long-term supplementation with bilberry extract is effective in prevention of macular degeneration and cataract.

Researchers: Fursova AZh, Gesarevich OG, Gonchar AM, Trofimova NA, Kolosova NG.

Published: Dietary supplementation with bilberry extract prevents macular degeneration and cataracts in senesce-accelerated OXYS rats, Adv Gerontol. 2005;16:76-9.

8. Cardiovascular Risk Factors (2008) and AMD
See more about macular degeneration treatment and information.

This 2008 study assessed the association of cardiovascular risk factors and ocular perfusion pressure with early and advanced age-related macular degeneration (AMD) in Latinos. Data were collected from a population-based sample of self-identified adult Latinos using standardized protocols for assessing blood pressure and intraocular pressure (IOP) measurement and stereoscopic macular photography. Hypertension was defined as either a history of hypertension or systolic blood pressure (SBP) higher than 140 mmHg +/- diastolic blood pressure (DBP) 85 mmHg or higher. Ocular perfusion pressure (OPP) was defined as the difference between mean arterial blood pressure and IOP. AMD was diagnosed from photographic grading by masked trained graders.
Gradable retinal photographs were available in 5,875 participants. After adjusting for age, gender and cigarette smoking, higher DBP and uncontrolled diastolic hypertension were associated with exudative AMD. Higher OPP was associated with a decreased risk of geographic atrophy (GA). Low pulse pressure was associated with a lower risk of exudative AMD. Obesity was associated with increased retinal pigment.
These data suggest that in Latinos, cardiovascular risk factors may play a role in advanced AMD. Given that Latinos have a high prevalence of cardiovascular risk factors, an intervention aimed at reducing these risk factors may also have a beneficial impact on the risk of having early and advanced AMD.
SOURCE: Fraser-Bell S, Wu J, Klein R, et al. Cardiovascular risk factors and age-related macular

9. CoQ10 (2003, 2005) Supports Retinal Function
Learn more about macular degeneration.

2005 Researchers wanted to expand on earlier research which reported that CoQ10 helped retinal functioning in macular degeneration patients. They wanted to find out whether a combination of other known supportive nutrients would improve retinal functioning more than CoQ10 alone. In a random, placebo-controlled, double-blind trial scientists tested combinations of acetyl-L-carnitine, omega-3 fatty acids along with coQ10.

In the placebo group 17% of the patients showed a worsening of visual acuity. In the treated group only 2% of the patients demonstrated worsening of visual acuity.

The researchers noted that compounds which affect mitochondrial fat metabolism (mitochondria are the energy producing part of a cell) appear to stabilize and even improve vision in patients with early-stage macular degeneration.

Researchers: J. Feher, B. Kovacs, et al.

Published: Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10, Ophthalmologica, May-June, 2005.

2003 Researchers reported that CoQ10 may improve the function of cell tissue in the retinal pigment and those improve function of the retina in those with age-related macular degeneration.

In this small study, 14 patients who had been diagnosed with early age-related macular degeneration received a formulation with CoQ10, acetyl-L-carnitine, polyunsaturated fatty acids, and vitamin E. A matched control group received vitamin E alone. Followup testing occurred at 3, 6, 9, 12, and 24 months.

Those receiving the formulation had all retinal and vision functions slightly improved after three months and they remained level throughout the two-year study period, while degeneration and visual function among participants in the control group continued to slowly decline.

Researchers: Dr. Janos Feher, and associates, University of Rome, Italy

Published: Feher J, Papale A, Mannino G, Gualdi L, Balacco Gabrielli C. Mitotropic compounds for the treatment of age-related macular degeneration. The metabolic approach and a pilot study. Ophthalmology, September-October, 2003

10. DHA (2001, 2012-13) and macular degeneration
Learn more about macular degeneration treatment and information.

These studies looked at omega-3 fatty acids, specifically DHA and its effect on protection against macular degeneration.

2001

Eating fish, especially tuna fish, may protect against age-related macular degeneration (AMD) (considered in 2001 to be untreatable).

Over several years, investigators questioned study participants about their diets and calculated the types of fat and total fat they ate. Those who ate more fat overall increased their risk of AMD, while those who ate fish reduced their risk of developing the eye disease.

Diets containing saturated fats from animals and unsaturated fats from vegetables were associated with modest increases in the risk of developing AMD, although long-chain fats from fish, especially tuna fish, actually reduced the risk. A specific fish fat, called docosahexaenoic acid (DHA), may help protect and promote healthy retinal function.

DHA is concentrated in the retina of the eye and is modestly inversely related to AMD. The intake of fish, the food source of DHA, was also inversely related, with participants eating more fish having a lower rate of macular degeneration incidence.

Researchers: Cho, Eunyoung, et al.
Published: Prospective study of dietary fat and the risk of age-related macular degeneration, American Journal of Clinical Nutrition, 2001

Editor's note: tuna is high on the food chain and contains high levels of mercury. DHA is better from other fish sources such as wild-caught salmon and smaller oily fish such as sardines and herring which are low on the food chain.

2012

It is well known that the proper functioning of the retina gets worse with age. A substance, known as A2E, a component of the toxic material lipofuscin, accumulates in retinal pigment cells. Researchers analyzed the effect of giving DHA (docosahexaenoic acid) supplements to mice who had A2E in the cells of their retinas. This done of periods ranging from 1 to 18 months, and took into account the proportion of DHA versus fatty acids, and diets without DHA.

The scientists found that A2E accumulations were reduced, and was tied to better retina functioning for mice who already had retina degeneration, and slowed this limitation for mice with more advanced retina problems.

They concluded that DHA in the diet could have a broad preventative therapeutic effect.

Researchers: Blake Dornstauder, et al
Published: Investigations in Ophthalmology and Visual Science, April, 2012

2013

A randomized and double-blind research study assessed the effectiveness of DHA in preventing advanced, or wet, macular degeneration in which additional blood vessels grow behind the macula, forcing distortion. Over a three year period 55 to 85 year old patients who had early lesions of wet macular degeneration were given 840mg daily DHA and 270mg daily EPA (eicosapentaenoic acid), or an olive oil placebo.

The scientists found that wet macular degeneration incidence was markedly reduced in the patients who received DHA over the period, and who also showed a continued high EPA plus DHA index during that time.

Researchers: E.H.Souied, C. Delcourt, et al.
Published: Oral docosahexaenoic acid in the prevention of exudative age-related macular degeneration: The Nutritional AMD Treatment 2 Study Ophthalmology February, 2013.

11. DHEA (2006) Age-related Macular Degeneration
Learn more about macular degeneration treatment and information.

DHEA (dehydroepiandrosterone sulphate) is a natural steroid that is produced in the body by the adrenal glands, the brain, and the gonads. It has been found to have some benefits, but there have been some studies indicating a number of at least short term side effects to the heart, mood, natural cycles, upset hormone balance, and skin and hair problems.

In some countries it is available only by prescription, and it is banned in athletic competitions.

Nonetheless, researchers have been interested in this biochemical because people with a number of conditions, including AMD and Alzheimer's have low levels.

A study published in 2007 found low levels of DHEA inversely related to AMD presence and severity. However, a larger 2013 study contradicted this finding.

2013

This study evaluated the relationship between incidence of wet macular degeneration (the advanced form of AMD, also known as exudative macular degeneration) as well as the levels of C-reactive protein and fats in blood plasma.

It was a cross-sectional study, meaning that it took a 'snapshot' of a number of subjects at one point in time. The study included 141 men and women controls aged about 67 to 75 years as well as 142 patients with wet macular degeneration. In both groups blood samples were taken and the levels of DHEA, CRP, total cholesterol and LDL cholesterol were measured. In addition, body mass index was measured.

The levels of DHEA were not significantly different between the control group and the patient group. The other measures did show differences.

2006

Researchers measured DHEA levels in 67 men and women with wet macular degeneration compared to 75 men and women with dry AMD and 64 people who had not been diagnosed with the condition. The control group was age matched.

They found that the lower the levels of DHEA the greater the severity of the macular degeneration in both men and women.

Researchers: C. Tamar, et al,
Published: Serum dehydroepiandrosterone sulphate level in age-related macular degeneration, American Journal of Ophthalmology, February, 2007

12. Early Age-Related Maculopathy (2006) in Eyes After Cataract Surgery
Learn more about macular degeneration treatment and information.

Patients aged 60 years and older who had undergone cataract surgery at Westmead Hospital, Sydney, Australia during 2001 to 2003 were examined for age-related maculopathy (ARM). Interviews using standardized questionnaires and stereo retinal photography were performed. Retinal photographs were graded using the Wisconsin ARM grading system. The proportions with ARM were compared between surgical and non-surgical eyes, and between this surgical cohort and the Blue Mountains Eye Study population.

Of the 622 eligible patients, 73% were re-examined, after a mean of 2.8 years. Surgical eyes had a higher proportion of early ARM compared to non-surgical eyes and to the early ARM prevalence found in Blue Mountains Eye Study participants of similar age.

This study found an increased prevalence of early ARM in surgical eyes of patients one to three years after cataract surgery. Whether this increase in early ARM prevalence leads to an increased prevalence of late ARM warrants further investigation.

SOURCE: Pham TQ, Cugati S, Rochtchina E, et al. Early age-related maculopathy in eyes after cataract surgery. Eye 2006; Jan 27 [Epub ahead of print].

13. Eggs (2006) for Elder Eyes | Macular Degeneration
In a 2006 study, published in the Journal of Nutrition, 33 people age 60 or older were divided into two groups. During the first five weeks, one group ate one egg per day while the other group ate no eggs; both groups stopped eating eggs for a period of time and then the groups were reversed for another five weeks.

In the egg-eating groups, blood levels of lutein and zeaxanthin rose 26% in the first phase of the study and 38% in the second phase. Neither group experienced any significant change in their cholesterol levels.

One regular egg per day, despite having relatively little lutein and zeaxanthin, was enough to raise these antioxidant levels in seniors without raising their cholesterol levels. This finding suggests that eggs - and possibly eggs from chickens that eat grass and other fresh vegetation in particular ("grass-fed") - could be a part of a healthy diet for older people trying to prevent macular degeneration.

(J Nutr 2006;136:2519-24)

14. Exercise (1990, 2016) & Macular Degeneration Prevention
Learn more about macular degeneration treatment and information.

2016

This long-term study conducted from a large population in Melbourne, Australia finds the same results as data from the Beaver Dam Study in the U.S. (below).

From 1990 to 1994 initial data was collected from almost 21,000 participants and graded according to the vigor of the exercise - e.g., walking, vigorous and non-vigorous exercise. Fifteen years later, from 2003 to 2007, retinal photographs were taken of the participants and were graded according to early, intermediate or advanced macular degeneration. The data was also adjusted according to the participants' age, gender, smoking habits, ethnic heritage, diet and alcohol use.

The researchers found incidence of early AMD in 21% of the subjects, intermediate in 13%, and advanced AMD in .6% of the participants.

There was no connection between overall physical activity and AMD onset. However they did find a difference when comparing frequent exercise (more than 3 times a week) and infrequent exercise (1-2 times a week). The female frequent exercisers had a 22% lower risk of intermediate AMD, but there was no similar association for men.

Exercise was associated with lower odds of intermediate and late AMD. After controlling for factors that could bias the results, there was evidence of improvement (related to gender). Frequent vigorous exercise was associated with a 22% decrease in the odds of intermediate AMD (95% CI 4% to 36%) in women, but no association was found for men. They concluded that further research will be helpful.

Researchers: M.B. McGuinness, et al,
Past physical activity and age-related macular degeneration: the Melbourne Collaborative Cohort Study, British Journal of Ophthalogy, October, 2016.

2006

The researchers felt that heart disease and macular degeneration (AMD) appeared to share common risk factors, but there had been little research to support the idea. Because it was known that physical activity improves the cardiovascular risk profile this study intended to investigate the relationship.

Over a period of 15 years, researchers evaluated the visual health of nearly 4,000 participants. The study began in 1988-1990 and the participants were evaluated every five years.

Incidence of early, intermediate and advanced forms of AMD were determined by use of color photos of the retina. Physical activity during the 15 year period was assessed by self-reporting in questionnaires.

The researchers adjusted the data for age, gender, arthritis history, blood pressure, BMI, smoking habits and education. They found that people with an active lifestyle, with regular activity at least three times a week were less likely to develop the advanced form of macular degeneration, wet AMD. They did not find that physical activity levels were associated with the less severe forms of the condition.

Researchers: M.D. Knudtson, et al,
Published: Physical activity and the 15-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study, British Journal of Ophthalomogy, December, 2006.

15. Fats (2009) & Macular Degeneration
Learn more about macular degeneration treatment and information.

Two studies indicate that omega-3 fatty acids, fish, nuts and olive oil, help protect against macular degeneration, and trans fatty acids, increase the risk of developing AMD.
Researchers at the University of Sydney, Australia analyzed data from 2,454 people in the Blue Mountains Eye Study of men and women aged 49 and older. Those who consumed one serving of fish per week were shown to have a 31% lower adjusted risk of developing early AMD compared with those who consumed less.
Researchers at the Centre for Eye Research Australia analyzed data from 6,734 men and women aged 58 to 69 in the Melbourne Collaborative Cohort Study. Dietary questionnaires completed over 4 years were analyzed for their diet. Follow up exams found 2,872 cases of early age-related macular degeneration and 88 cases of late disease.

A high intake of trans-unsaturated fats was associated with a significant increase in late macular degeneration, with the top 25% in amount of trans-fats consumption had a 76% greater risk than those whose intake was among the lowest 25%.
They also found that olive oil was a protection against late disease. Those who consumed at least 100 milliliters (about 3.5 oz) per week olive oil were found to have a 52% lower risk of late AMD than those who consumed less than 1 milliliter per week.

For early AMD, those whose omega-3 fatty acid intake was among the top 25% had a 15% lower risk compared with those whose intake was among the lowest 25%.
Trans fatty acids increase cholesterol levels and inflammation, both of which affect the eyes' blood vessels, while omega-3 fatty acids may help protect the retina. Although the main fats contained in olive oil were not connected to macular degeneration risk, the oil contains antioxidants and anti-inflammatory compounds that could be protective. "A diet low in trans-unsaturated fat and rich in omega-3 fatty acids and olive oil may reduce the risk of AMD," the authors concluded.

Reference: May, 2009 issue of the American Medical Association journal Archives of Ophthalmology
Source: Lef.org

16. Fish & Fat in Diet (2000-01, 2007) & Macular Degeneration
Learn more about other support for macular degeneration.

2000
Researchers determined that in 3,600 patients (aged 49 and older) who ate fish more than once a week had 50% and as seldom as 1 to 3 times a month the risk of developing advanced macular generation compared to patients eating fish less than once a month. Fish in the diet didn't significantly change the risk of early (dry) macular degeneration. It is thought that the omega3 fatty acids contained in fatty fish are responsible for the decreased risk.

Patients consuming high amounts of saturated fats and cholesterol in their diets were 2.7 times as likely to develop wet (advanced) macular degeneration, also known as choroidal neovascularization.

Researchers: Smith, et al. Archives of Ophthalmology, March, 2000

2001
The researchers investigated the relationship between risk of macular degeneration and consumption of different kinds of fat.

More than 300 patients, aged 55-80, who suffer from advanced macular degeneration (wet type). There were about 500 control subjects who did not have AMD, but had other ocular diseases. The study evaluated fat intake and was adjusted for other risk factors such as smoking cigarettes.

The researchers found that highest (top 1/5) consumption of vegetable oils was connected to about 2 1/4 times greater risk of developing AMD compared to those people whose consumption of vegetable oils was in the lowest 1/5th.

Highest consumption of linoleic acid (omega6 found in vegetable oils) was connected to greater risk of AMD.

In patients whose diet was high in omega-3 fatty acids or fish, and where linoleic acid was low, the risk was lower.

And in patients who diet was high in omega-3s and linoleic acid was high, there was little correlation to risk.

The researchers concluded that consumption of high levels of fats, which includes monounsaturated, polyunsaturated, lineoic acid and vegetable oils, as opposed to total fat, is connected to greater risk of AMD. However diets that were high in omega-3 fatty acids and fish had a lower risk of developing AMD if lineoic acid was low.

Researchers: J.M. Seddon, et al.,
Published: Dietary fat and risk for advanced age-related macular degeneration, Archives of Ophthalmology, August, 2001.

Editor's Note: The high consumption of vegetable oils and grains, along with meats and eggs eaten from animals fed grains has dramatically thrown our omega-3 to omega-6 ratio out of balance, resulting too much omega-6 fatty acids which tend to be inflammatory. We believe it will eventually be proven that the high levels of omega-6 fatty acids in our diet with high levels of refined carbohydrates eaten are the main causes besides genetics of heart disease, stroke and autoimmune diseases.

2007
The POLANUT study in France evaluated the effect of fat in the diet and the risk of developing macular degeneration. Researchers evaluated diet histories of about 700 patients who had developed macular degeneration.

The survey distinguished between white (low-fat) and fatty fish (such as tuna and salmon). The researchers also looked at retinal photographs taken some years prior.

The researchers separated the subjects into early and advanced macular degeneration and determined the lower 1/5, middle 3/5ths and upper 1/5 of the group based on the fat and fish intake.

They found that AMD risk increased with intake of total fat, especially with intake of saturated fats. General fish intake, on the other hand was not associated with development of AMD. Fatty fish, consumed more than once a month, were tied to lower AMD risk.

Researchers: C. Delcourt, I. Carriere, et al
Published: Dietary fat and the risk of age-related maculopathy: the POLANUT Study, European Journal of Clinical Nutrition, February, 2007.

17. Ginkgo Biloba (1986, 2002) and macular degeneration
Learn more about macular degeneration treatment and information.

An early French double blind study in 1986 found that Ginkgo Biloba could help people with macular degeneration, possibly due to its benefit of improving blood circulation to the brain.

Researchers: D.A. Lebuisson, L. Leroy, G. Rigal

Published: Treatment of senile macular degeneration with Ginkgo biloba extract. A preliminary double-blind, drug versus placebo study, Presse Med 1986 (article in French)

Additional Controlled trials in 2002 also found that ginkgo extracts support vision quality in patients who take them for a six month period. This has been verified in both human and animal studies. Ginkgo appears to support the action of antioxidants.

Researchers: P. Fies, A. Dienel

Published: Ginkgo extract in impaired vision - treatment with special extract EGb 761 of impaired vision due to dry senile macular degeneration, Wien Med Wochenschr, 2002 (article in German)

18. Glutathione (1988, 1993, 2002) & Macular Degeneration
Learn more about macular degeneration.

Researchers have known for a long time that patients suffering from macular degeneration have 58% less of the antioxidant glutathione that patients who are healthy. Glutathione is a powerful antioxidant that fights free radicals and helps protect the retina from damage from UV radiation and blue light.

Researcher: P. Sternberg

Presented: Treating Age-Related Macular Degeneration, Science Writers Seminar in Ophthalmology: Research to Prevent Blindness. 1988.

A 1993 study investigated whether glutathione (GSH) had an effect on oxidative injury (by free radicals) to human retinal pigment tissue cells by free radicals in the retina.

In a lab situation, cultured human eye cells were treated with GSH or its amino acid precursors, and any changes were noted after 30, 60, and 120 minutes.

The researchers determined that added GSH provided protection and that the amino acid precursors for GSH, glutamate, N-Acetyl-Cysteine, and L-glycine, and selenium also protected against injury at higher concentrations.

Researchers: Sternberg, Davidson, Jones, et al.

Published: Investigations in Ophthalmology and Visual Science, December, 1993

In 2002 another group of researchers looked at the role of glutathione in protecting the retina's pigment cells. 4-hydroxynonenal type of fat found in the body that is readily damaged by oxidative stress. It had been known that it was implicated in other age-related conditions such as Alzheimer's, but wanted to see whether it contributed to the damaging extra blood vessels that develop in advanced macular degeneration.

They also wanted to see whether the powerful antioxidant glutathione, naturally found in the eye, played a role in protecting the eye from such damage.

They found that in early AMD glutathione protected pigment cells in the retina are protected from dying prematurely by inhibiting damage caused by 4-hydroxynonenal.

Researchers: S.P. Ayalaxomayajula, U.B. Kompella

Published: Induction of vascular endothelial growth factor by 4-hydroxynonenal and its prevention by glutathione precursors in retinal pigment epithelial cells, European Journal of Pharmacology, August, 2002

19. Glycemic Index (2007) & macular degeneration
Learn more about macular degeneration treatment and information.

Age-related macular degeneration (AMD) appears to share several carbohydrate-related mechanisms and risk factors with diabetes-related diseases, including retinopathy and cardiovascular disease (CVD). The objective of a 2007 study was to test the hypothesis that dietary glycemic index (dGI), which has been related to the risk of diabetes and CVD, is associated with the risk and severity of AMD in non-diabetic elderly populations. Dietary information was obtained from 4,099 participants aged 55 to 80 years (56 percent women) who participated in the Age-Related Eye Disease Study (AREDS). A total of 8,125 eligible eyes at baseline were classified into one of five AMD groups according to the size and extent of drusen, the presence of geographic atrophy and neovascular changes.

Compared with eyes in the first quintile of dGI, eyes in the fourth and fifth quintiles had a significantly or suggestively higher risk of large drusen, geographic atrophy and neovascularization. A significant positive relation between dGI and severity of AMD was noted. There was a 49 percent increase in the risk of advanced AMD (geographic atrophy plus neovascularization) for participants who had a dGI higher than the sex median (women, 77.9 or greater; men, 79.3 or greater). This result indicated that 20 percent of prevalent cases of AMD would have been eliminated if the AREDS participants consumed diets with a dGI below the median.

The association between dGI and AMD from the AREDS cross-sectional analysis at baseline suggests that a reduction in the dGI, a modifiable risk factor, may provide a means of diminishing the risk of AMD.

SOURCE: Chiu CJ, Milton RC, Gensler G, Taylor A. Association between dietary glycemic index and age-related macular degeneration in nondiabetic participants in the Age-Related Eye Disease Study. Am J Clin Nutr 2007;86(1):180-8.

20. Goji Berry (2011) Components Eye Pigmentation
Learn more about macular degeneration.

2011

Goji berry contains a high level of antioxidants, particularly zeaxanthin which is an essential carotenoid antioxidant that accumulates in the macula.

The Chinese traditionally use a kind of milky tea containing goji berries and this double-blind, randomized study evaluated its effect on the integrity of the macula and blood plasma levels of zeaxanthin. 150 patients aged 65 to 70 years old were divided into two groups, one receiving the milk/goji formulation and one receiving placebo. Both groups received their dosage for 90 days.

At the beginning and at the end of the study period the patients received an ophthalmic exam to note the integrity of the pigmented layer of the eye (which protects the macula) and the number of drusen. Soft drusen, present in dry macular degeneration are yellowish fatty deposits on the macula. Untreated they multiply and eventually distort the structure of the macula resulting in vision loss.

The researchers found that daily supplementation with the milk/goji formulation increased the levels of zeaxanthin in the blood and protected from additional drusen formulation or loss of pigmentation.

This study was of fairly short duration, but nonetheless indicates a possible benefit from the nutrients contained in goji berry.

Researchers: P. Bucheli, K. Vidal, et al,
Published: Goji berry effects on macular characteristics and plasma antioxidant levels, Optometry and Visual Science, February, 2011.

21. Gut Bacteria (2016) & Advanced Macular Degeneration
Learn more about macular degeneration.

2017
Microbiota and High-Glycemia Diet

Researchers have noted in the past that the inability of the body to properly process sugar, leading to advanced glycation (bonding of sugar molecules with proteins and other molecules), and contributes to development of macular degeneration.

Researchers analyzing the process of glycation, resulting increased inflammation and development of macular degeneration found that high-glycemia diets contribute to AMD risk and low-glycemic diets reduce the risk and may even stop or reverse AMD development.

The researchers concluded that the health of gut microbiota was a factor in the ability of the body to process sugars and that this ability was hampered in a high-glycemia diet.

Researchers: S. Rowan, S. Jiang, et al
Published: Involvement of a gut-retina axis in protection against dietary glycemia-induced age-related macular degeneration, Proceedings of the National Academy of Science, USA, May, 2017.

2016
Microbiota & High Fat Diet

The risk of developing advanced macular degeneration (choroidal neovascularization (CNV)) is greatly increased, especially for men, in the presence of obesity. Being overweight is the second most severe risk factor after smoking. In a study of over 21,000 people it was found that each increase in .1 in waist/hip ratio was associated with a 13% increase in the risk of developing macular degeneration.¹

However the mechanisms that cause this association are not strongly understood so researchers decided to investigate. Our ability to digest food and gain nutritional benefit from the food we eat depends on the ability of our digestive system to break down the food into nutrients. This takes place in the large and small intestines and rests on the health of the microbacterial community that lives in our gut.

But in the presence of fat molecules, the process is slowed or inhibited. People who are obese tend to have high-fat diets, and this inhibition on our healthy gut microbiota restricts the delivery of nutrients to the body and to the eyes and becomes a risk factor for AMD. Imbalances in the gut microbiota influence not only digestion but metabolism, toxins in bacterial cells, and the immune system's response.

Researchers find that gut imbalanced or maladapted gut microbiota increases the permeability of the gut resulting in chronic inflammation. And we know from other research² that increased inflammation is present in cases of advanced macular degeneration.

In this study the scientists started by looking at the link between high fat diets and CNV. In lab animals they found a clear association between excessive weight gain and CNV development.

Next they disassociated the weight gain factor from the imbalanced gut microbiota community by feeding normal weight animals with antibiotics to damage the gut microbiota. They examined the gut flora profile to establish that the microbiota had been negatively impacted.

They found that certain large molecules (mononuclear phagocytes that are known to contribute to CNV were increased in the imbalanced digestive systems of the mice, and that they promote inflammation.

Finally, they were able to determine that the high fat diets increase advanced macular degeneration (CNV) because the resulting imbalanced gut microbiota aggravated inflammation which in turn aggravated CNV.

Researchers: E.M. Andriessen, A.M. Wilson, et al,
Published: Gut microbiota influences pathological angiogenesis in obesity-driven choroidal neovascularization, EMBO Molecular Medicine, December, 2016.
Footnotes

1. M. Adams, J. Simpson, et al., Abdominal obesity and age‐related macular degeneration, American Journal of Epidemiology, 2011.
2. Vinod P. Mitta, MD, MPH; et al, C-Reactive Protein and the Incidence of Macular Degeneration, JAMA Ophthalmology, 2013

22. Homocysteine (2004, 2005, 2015) & Macular Degeneration
Learn more about macular degeneration.
2004 Researchers have for some time suggested a connection between high homocysteine levels and wet macular degeneration, the advanced form of AMD.

In one study researchers evaluated 59 patients in a university outpatient ophthalmology clinic with a mean age of 78 years who had wet AMD. They were compared for plasma homocysteine levels with 58 patients who had dry AMD and a mean age of 76.3 years and an aged-matched control group of 56 people with healthy eyes.

After an 8 hour fast, a blood sample was obtained from each participant and levels of plasma homocysteine were measured.

Results: Homocysteine levels were higher by 27.9% in the wet AMD than in the dry AMD group, and by 21.9% than in the control group. Hyperhomocysteinemia was found in 44.1% of the study group, in 22.4% of the dry AMD group, and in 21.4% of the control group.

Published: American Journal of Ophthalmology, 2004 Jan;137(1):84-9.

Researchers: Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S, Weinberger D, Sela BA.,Department of Ophthalmology, Rabin Medical Center, Petah Tiqva, Israel

2004-2005 In clinical studies elevated homocysteine is associated with a number of degenerative eye diseases including: macular degeneration, glaucoma, diabetic retinopathy, and optic neuropathy and ocular complications from behcet disease.

It is also associated with accelerating the progression of the aging process. - being a major cause or contributing factor to heart disease, abnormal clotting, dementia, depression , multiple sclerosis, Parkinsons Disease, miscarriage and psoriasis.

Aging, excessive stress, and deficiencies in choline, taurine, n-acetyl-cysteine affect homocysteine levels in the blood.

References:
1. Elevated homocysteine levels in aqueous humor of patients with pseudoexfoliation glaucoma. Bleich S, Roedl J, et al. American Journal of Ophthalmology, July, 2004
2. Plasma homocysteine and total thiol content in patients with exudative age-related macular degeneration. Coral K, Raman R, et al, Eye, April, 2005

2015 Because there have been some inconsistencies in the reports of the relationship of homocysteine levels and risk of advanced macular degeneration taking into consideration vitamin B levels, researchers wanted to evaluate those results.

They reviewed eleven studies involving over a thousand each patients with AMD and controls with healthy eyes. The results substantiated that higher homocysteine levels are associated with wet (advanced) macular degeneration. Of those studies three (152/98 patients/controls) also looked at the B vitamins. The meta analysis results demonstrated that with high homocysteine and AMD, vitamin B12 was also low. The researchers also point out that AMD is a condition in which there are many contributing factors - that vitamin B12 and homocysteine are not the sole indicators.

Researchers: P. Huang, F. Wang, et al.,
Published: Homocysteine and the risk of age-related macular degeneration: a systematic review and meta-analysis, Scientific Reports, July, 2015.

23. Laser therapy (2008) improves vision in patients with Age-related Macular Degeneration
Learn more about macular degeneration recommendations

Researchers conducted a clinical trial on 203 patients with age-related macular degeneration (AMD) and measured whether symptoms and distortions improved after low level laser therapy treatment and continuing for a period of between 3 and 36 months.

They found that the occurrence of metamorphopsia (distorted vision), scotoma (partially diminished vision), and dyschromatopsia (distortion of color vision) was reduced.

In patients with wet AMD, edema and bleeding improved. The improved vision was maintained for 3-36 months after treatment. Visual acuity in the control group remained unchanged. No adverse effects were observed in those undergoing therapy.

Researchers: University of Heidelberg, Germany

Published: Photomed Laser Surg 2008 Jun 26(3) 241-5

24. Leafy Greens (1988, 1999) & Macular Degeneration
Learn more about treatment options and other research for macular degeneration

1988 Researchers found that including dark leafy greens like spinach and collard greens in two to four meals a week reduced the risk of developing macular degeneration by 46%. If patients eat these dark leafy greens five-six times a week the decreased risk percentage is even greater.

Researchers: J. Goldberg, et al.

Published: Factors associated with age-related macular degeneration: An analysis of data from the First National Health and Nutrition Examination Survey. American Journal of Epidemiology 128, 1988

Editor's Note: Lutein and Zeaxanthin are the two carotenoids found in collard greens and spinach. When taken as supplements, they are best taken separately from beta-carotene because they compete for absorption.

1999 A preliminary study showed the patients consuming lutein from either spinach or supplements demonstrated some improvement of some of the early vision loss from the dry form of macular degeneration.

Published: Richer, Journal American Optometry Association; January, 1999

25. Limiting Refined Carbohydrates May Stall Macular Degeneration
Limiting carbohydrates in the diet may help slow the progression of age-related macular degeneration (AMD), according to a recent study by researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. The study builds on a recent analysis that found that men and women older than 55 years who consumed diets with higher-than-average dietary glycemic index foods appeared to have an increased risk for early and later stages of AMD. Dietary glycemic index determines how quickly carbohydrates are broken down into glucose: Foods with a high glycemic index are associated with a faster rise and subsequent drop in blood sugar than those with a low glycemic index.
In the study, investigators analyzed diet questionnaires completed by 4,757 non-diabetic men and women participating in the nationwide Age-Related Eye Disease Study (AREDS), an eight-year study that included participants ages 55 to 80 with varying stages of AMD. They examined the participants' carbohydrate intake over one year and used the data to calculate the participants' dietary glycemic index. Results showed that those who consumed the greatest amount of refined carbohydrates were 17 percent more likely to develop blinding AMD than the group that consumed the least. Based on this data, the investigators believe that limiting dietary refined carbohydrates in at-risk elderly people could reduce the number of advanced AMD cases by 8 percent in five years. The authors note, however, that their findings warrant randomized controlled clinical trials.
SOURCE: Chiu CJ, Milton RC, Klein R, et al. Dietary carbohydrate and the progression of age-related macular degeneration: A prospective study from the Age-Related Eye Disease Study. Am J Clin Nutr 2007;86(4):1210-8.

26. Low selenium levels and smoking (1998)
There is a borderline association between age-related macular degeneration and both low serum selenium levels and current smoking status. Doc Ophthalmol 1992;81(4):387-400 Mayer, et al. Acta Ophthalmol Scand 1998 Feb;76(1):62-7

27. Lutein & Zeaxanthin ('08) & Risk Reduction in Age-Related Eye Disease
Learn more about macular degeneration recommendations

Lutein and zeaxanthin are the only carotenoids that concentrate in the macula. There is evidence of three mechanisms by which lutein and zeaxanthin may afford protection against AMD: by absorbing blue light, by quenching free radicals and by increasing membrane stability.

Many previously published studies which have examined the relationship between AMD and these carotenoids have reported an inverse association between the disease and intake of lutein plus zeaxanthin. These carotenoids are commonly obtained from leafy green vegetables, corn, egg yolks, broccoli, peas, squash - as well as from supplements.
The authors of the Carotenoids in Age-Related Eye Disease Study (CAREDS) now report that a stable intake of these carotenoids over time could reduce the risk of AMD by about 43% in healthy women under 75.
Design and Methods
CAREDS is an ancillary study of the Women's Health Initiative (WHI), a prospective cohort study. CAREDS was designed, in part, to evaluate the relationship between lutein/zeaxanthin and the prevalence of intermediate AMD. Over 1780 women aged 50-79 who had high or low intake of lutein plus zeaxanthin at WHI enrollment were recruited into CAREDS 4-7 years later, when the presence of AMD was determined by fundus photographs.
To maximize extremes in intake of these carotenoids in the study sample, women with intakes of lutein plus zeaxanthin above the 78th (high) and below the 28th (low) percentiles at baseline in the WHI were recruited. Dietary assessments were performed by means of food frequency questionnaires administered at the study's start and over the previous 15 years. Logistic regression analyses examined the prevalence of AMD, after accounting for potential covariates.
Results
While an association between dietary intake of these carotenoids and AMD was not observed in the overall study population, secondary analyses disclosed a statistically significant protective effect in women younger than 75 with stable intakes of lutein and zeaxanthin.
Higher intakes of lutein/zeaxanthin (2, 868 mcg or more daily) compared to lower consumption (792 mcg daily) in women with stable intakes resulted in a substantial 43% lower risk of intermediate AMD (odds ratios [0.57; 95% confidence interval, 0.34-0.95]). The younger women (< 75 years) did not have a history of chronic diseases such as cardiovascular disease and diabetes that are often associated with diet changes and instable intakes of lutein/zeaxanthin rich foods.
Similar protective associations were observed for large drusen. While not statistically significant, associations in this sub-sample were in the protective direction for the more advanced lesions of pigmentary abnormalities, as well as for the exploratory outcome, advanced AMD.
The researchers observed the strongest inverse associations between intermediate AMD and high intake of vegetables in general, as well as of green vegetables. Blood levels of the carotenoids were not associated with risk of AMD.
Comments
According to lead author Dr. Suzen Moeller of the University of Wisconsin, the findings are consistent with a broad body of evidence from observational and experimental studies suggesting that these carotenoids may protect against AMD. There was evidence that diet instability may have biased the associations and, together with the possibility of selective mortality bias, may explain our inability to detect the hypothesized association in the full study population, wrote Dr Moeller.

Published: Moeller SM et al. Age-Related Macular Degeneration and Lutein and Zeaxanthin in the Carotenoids in Age-Related Eye Disease Study (CAREDS). Archives of Ophthalmology 124:1151-1162, 2006.

28. Lutein & Zeaxanthin ('90s, '00- '08, '16): Macular Degeneration
Learn more about the macula.

Scientists have established that macular pigments are located in the retina. Lutein (in the periphery of the macula) and zeaxanthin (in the central area of the macula) make up these carotenoid macular pigments discussed in the following studies.

2016

This study focused on the role of macular pigment in which lutein, zeaxanthin and meso-zeaxanthin are highly concentrated and where they work to do a number of tasks in addition to filtering blue light. Lutein is the primary carotenoid in the periphery of the macula, zeaxanthin more toward the center, and mesozeaxanthin in the very center of the macula.

These carotenoids help vision in several ways.

Many studies have demonstrated that the three carotenoids improve recovery from macular degeneration, especially protecting against onset of late or advanced macular degeneration (wet AMD), and reducing risk for those who are genetically pre-disposed towards the condition.

Lutein and zeaxanthin reduce glare discomfort and glare recovery time.

They improve the functioning of the macula through comprising the pigment layer which filters blue light.

They positively impact the speed at which the optic nerve transmits information to the rest of the brain.

Lutein levels have been found to improve vision adaption from light to dark and from dark to light.

Research also shows promising results between higher levels of the carotenoids and lower risk of diabetic retinopathy and retinopathy of prematurity.

There have been mixed results concerning the relationship of the carotenoids and cataracts.

Researchers: Veronica Castro Lima, et al.
Published: Macular pigment in retinal health and disease, International Journal of Retina and Vitreous, August, 2016.

2008

A longitudinal study substantiated earlier conclusions.

Over 10 years researchers evaluated the diets and antioxidant supplementation and the long-term risk of age-related macular degeneration in over 2400 patients.

Subjects with greater levels of lutein and zeaxanthin intake had a reduced risk of the advanced form of wet macular degeneration, and those patients with intake levels above the median level had a lower risk of soft drusen, the fatty deposits that are characteristic of AMD.

The researchers reported that high consumption of these nutrients through diet and/or supplementation significantly reduced the risk of developing macular degeneration. It also confirmed findings about other nutrients from the first AREDS study.

Researchers: J.S.L. Tan, J.J. Wang, V. Flood, E. Rochtchina, W. Smith, P. Mitchell, Centre for Vision Research, University of Sidney, Australia
Published: Dietary Antioxidants and the Long-term Incidence of Age-Related Macular Degeneration: The Blue Mountains Eye Study, Ophthalmology, February 2008

2006

A longitudinal study of women aged 50-79 in Iowa, Wisconsin and Oregon evaluated the relationship between lutein and zeaxanthin in their diet and macular degeneration incidence.

Four to seven years later the same women were included in the Carotenoids in Age-Related Eye Disease Study and the incidence of AMD was determined in almost 1800 women by means of retinal photographs.

Although the incidence of AMD was not greatly different for the groups with high and low levels of carotenoids in their diet, the researchers found that when they evaluated only those younger women (<75) who also had a stable consumption of the two carotenoids, and who also had no other history of the kind of diseases related to diet, it was found that the AMD risk was markedly reduced.

Researchers: Suzen M. Moeller, PhD, et al, CAREDS Research Study Group
Published: Archives of Opthalmology, 2006

2005

The paper summaries understandings about lutein and zeaxanthin to date.

Both lutein and zeaxanthin are carotenoids given yellow color by the pigment lutea, meaning yellow. They are found in the periphery and center of the macula respectively. Other major carotenoids such as lycopene or beta-carotene are not found in macular tissue. Researchers understand that these macular pigments probably protect the retina against damage from light and that studies demonstrate evidence that increasing intake of these carotenoids lowers the risk of developing macular degeneration by protecting the eye against oxidative damage. They acts as filters to damaging blue light and they block certain oxidative actions.
Published: Developments in Ophthalmology, 2005

Researchers: E. J. Johnson, et al

Published: Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density, American Journal of Clinical Nutrition, June, 2000.

2003

In this study researchers evaluated the connection between blood plasma levels of lutein and zeaxanthin and AMD in 380 UK men and women aged 66 to 75 years old. They used the Wisconsin Age-Related Maculopathy Grading System to compare early and late macular degeneration and blood samples.

They found that the risk of both early or late starting age-related macular degeneration was higher in patients with lower blood plasma concentrations of zeaxanthin. Compared with those in the highest 1/3, people whose plasma concentration was in the lowest 1/3 had 2 times higher odds for risk of age-related macular degeneration.

Researchers: Catharine R. Gale, et al., Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
Published: Investigative Ophthalmology and Visual Science. 2003

2000

This understanding, that these important carotenoid antioxidants are important for macular health, further developed in later research in which seven subjects again consumed spinach and corn in their daily diets for another nearly 4 months. In this study at the beginning of the study period and at 4, 8 and 15 weeks, and 2 months after the study's end, blood samples, cells from the inside of cheeks and fat tissue were assessed, as well as measuring macular pigment density.

Zeaxanthin was greater after 4 weeks than after the beginning, but did not peak further than that level. Lutein peaked at 8 weeks. There were differences in the relationship of these carotenoid levels in the different types of tissue - with negative correlations for women and positive correlations for men - indicating that sex differences in lutein metabolism may be important in considering tissue interactions and pigment density.

1999

Zeaxanthin comprises up to 75% of the total carotenoids in the center of the macula. Lutein comprises 67% or more of the peripheral area of the macula. Concentrations of these carotenoids in other tissues of the body are much lower. It has been determined that these pigments increase in both tissue and blood by way of diet and supplementation. Evidence points to a correlation between macular pigment density and a reduction in the risk for age-related macular degeneration.

Researchers: John T. Landrum, et al
Published: Analysis of Zeaxanthin Distribution within Individual Human Retinas, Methods In Enzymology, 1999.

1997

Researchers investigated the amount and condition of macular pigment in 13 patients who were on a diet including daily spinach and corn for up to almost 4 months. The pigments in the macula are responsible for protection against damaging UV radiation from the sun which is a contributing factor in macular degeneration.

The daily servings of corn and spinach add 11.2mg lutein and .6mg zeaxanthin to the daily diet - which compared to a 'normal' diet, was 3x (lutein) and 4x (zeaxanthin) the nutrient amounts the patients would have received otherwise. They found in 80% of the patients who followed the diet an average increase in pigment density of 19% - with the minimum increase being 13%.

Researchers: Hammond, et al
Published: Dietary modification of human macular pigment density, Investigations in Ophthalogy and Visual Science, August, 1997.

1995

Researchers analyzed lab data for different antioxidant carotenoids which help protect the eye from oxidative damage due to blue light. They found that lutein and zeaxanthin, which form the macular pigment have the strongest protecting effects.

Researchers: D.M. Snodderly, et al.
Published: American Journal of Clinical Nutrition, December, 1995

1994

Researchers noted that lutein and zeaxanthin, which come from dark leafy greens are tied to reduced macular degeneration risk. Patients with the highest levels of these carotenoids in their diet had a 43% lower risk of developing AMD. These pigments filter blue light from the retina and protect it from oxidative damage.

Researchers: Seddon, et al.
Published: Journal of the American Medical Association, November, 1994

29. Lutein (1990s, 2002, 2004) and ARMD
Learn more about macular degeneration recommendations

1993

Researchers found that carotenoids, lutein in particular, help protect against development of macular degeneration. With higher levels of carotenoids in the blood stream, a higher antioxidant index, and higher levels of micronutrients in the blood, AMD risk is lowered, especially for wet macular degeneration - the most severe form of the conditions. These findings support the theory that sunlight's damaging UV radiation is a contributing cause of macular degeneration and that carotenoids.

Researchers: The Eye Disease Case-Control Study Group
Published: Antioxidant Status and Neovascular Age-Related Macular Degeneration, Archives of Ophthalmology, January, 1993

1994

Researchers found that consumption of 6mg daily lutein was associated with a 57% decreased in the risk of developing macular degeneration.
Researchers: Seddon, J.M., U.A. Ajani, et al.
Published: Dietary carotenoid, vitamins A, C, E, and advanced age-related macular degeneration, Journal of the American Medical Association, 1994.

1997

In a small pilot study researchers looked at macular pigment density. This is important because pigment density is, in turn, correlated to risk of macular degeneration. They found that macular pigment density increased in 2 subjects who were given 30mg free lutein daily for four and a half months. Macular pigments protect the retina from the damaging effects of blue light and consequently may protect against macular degeneration. Supplementing with 30mg daily lutein brought about a 10-fold increase in lutein levels in the blood in the first 10 to 20 days.

Researchers: Landrum, et al.
Experimental Eye Research, July, 1997

1997

A larger study also looked at macular pigment density. Researchers found that macular pigment density is positively correlated with lutein and zeaxanthin in the blood. Subjects were given about four times the lutein and two to three times the zeaxanthin as in a normal healthy diet. 77% of the patients experienced increases in macular pigment density.

Raising macular pigment density in patients reduces the likelihood that the patient's eye condition will advance to the advanced wet macular degeneration, also known as choroidal neovascularization since there is substantial evidence that macular pigment protects the retina and retinal pigment epithelium against light damage.

Researchers: B.R. Hammond, et al.
Published: Dietary Modification of Human Macular Pigment Density,Investigative Ophthalmology & Visual Science, August 1997

1997

This paper discussed the risk factors, including the role of lutein in protecting the eye from the damaging effects of the sun's light and thus in lowering the risk of developing macular degeneration. They noted that Low levels of lutein in the eye are correlated with higher risk of development of macular degeneration. They note that it has been known for a long time that carotenoids protect against photo-oxidation in plants from damage by blue light, which supports creation of free radicals in the retina. The yellow pigments in the macular pigment counter this damage.

They also actively protect the macula's nerve tissue from the damage, perhaps by passively by shielding tissues behind the outer layer of the eye from excessive blue light.

The researchers concluded that long-term lutein supplementation could result in a significant increase in the level of pigmentation within the macula. In evaluating tissues from human donor eyes, both controls and those diagnosed with AMD they found that AMD eyes had on average approximately 30% less of the total carotenoids found in the controls. The difference in amounts of pigments is not only in the macular area of the retina - indicating that lowered levels of pigment are not a result of degeneration, but more likely a contributing cause.

When subjects were given 30mg of lutein per day the levels of lutein in the blood raised 10-fold within the 1st week and remained high.

Macular pigmentation increase appears to-be a slow process--this amounted to a 15% increase in the pigment level after 72-days of lutein supplementation. A relationship has been established between blood levels of lutein and corresponding increases in the concentration of lutein in the macular of the human eye.

Author: J.T. Landrum, et al
Published: The Macular Pigment: A Possible Role in Protection from Age-Related Macular Degeneration, Advances in Pharmacology, 1997, Volume 38, Pages 537-556.

1999

Another study addressed increasing lutein-rich foods in the diet to protect vision.

Researchers found that patients experienced benefits in vision quality by increasing lutein-rich foods such as dark leafy greens in their diet.

The diets of 15 dry macular degeneration patients were supplemented with an additional five ounces of sauteed spinach 4-7 times weekly. At the beginning of the study the patients were measured with standardized tests of visual acuity in low light, low-contrast, and recovery from glare. Follow-up testing occurred from 2 to 12 months after the study began.

After 90 days the researchers saw improvements in visual acuity and marked improvements in vision were often detected in follow-up tests, even though patients did not notice changes. Partial or complete resolution of metamorphopsia (distorted vision) and scotomas (blind spots) was reported in seven of eight applicable cases.

The conclusion was the treatment of macular degeneration through diet should receive more attention because it is simple, inexpensive and may apply to a broad range of macular degeneration-related problems.

Lutein and zeaxanthin are carotenoids found in leafy green vegetables such as spinach and kale and are concentrated in retinal macular pigment. Concentrations accumulate when those foods are included regularly in the diet.

Researchers: Dr. Stuart Richer, et al, Atlanta
Presented: resented at Southern Council of Optometrists 1999 annual meeting,

2002

While most research has been on patients with the dry form of macular degeneration, these researchers did a controlled study with 72 patients with the wet form of macular degeneration (neovascularization) and 60 controls. They investigated consumption of antioxidants through diet, and other risk factors for AMD such as smoking, genetics, and exposure to sunlight.

They calculated antioxidant intake based on accepted practices as described in the Framingham Eye Study of the late 70s.

Consistent with earlier research, they found low intake rates for antioxidants generally and lutein specifically. The incidence of AMD in patients was twice as high when they had low rates of consuming antioxidants, especially lutein.

Researchers: E.L. Snellen, et al

Published: Neovascular age-related macular degeneration and its relationship to antioxidant intake., Acta Ophthamologia Scandanavica, August, 2002

2004

Singapore Polytechnic researchers tested a group of seven older subjects with early stage AMD, and six subjects of the same age with healthy eyesight. Each subject received 10 mg of lutein supplements daily for 18 to 20 weeks.

Macular pigment optical density (MPOD low density is considered a risk factor) and blood plasma concentrations of lutein were measured before and after the study. The MPOD average increased significantly in both groups as lutein levels rose. Researchers concluded both a diseased macula may accumulate and synthesize lutein effectively, and people with healthy macula gain benefits from lutein as well.

Researchers: Singapore Polytechnic
Published: Journal Experimental Eye Research, July, 2004

2004

In another 2004 study researchers studied 90 subjects with dry AMD who were divided into three groups and randomly assigned to receive 10 mg of lutein daily, or 10 mg of lutein combined with other nutrients that are known to enhance vision health (such as bilberry, zinc, quercetin, N-acetylcysteine, and others), or a placebo.

Several measurements were taken over the course of a one year test period. Changes in macular pigment optical density (low density is a risk factor) were recorded; contrast sensitivity was evaluated; and visual perception was assessed with eye chart exams.

At the end of the trial, the researchers found clear improvements in both the lutein and the lutein-plus-nutrients group, but no noteworthy changes in the placebo group. Even those subjects who had advanced AMD showed improvement with the additional lutein intake. Larger and longer studies are needed to confirm the findings.

Researchers: Department of Veterans' Affairs, Medical Center Eye Clinic in Chicago
Published: April 2004 issue of the journal Optometry

30. Lutein (1992) macular degeneration and cataracts
Learn more about macular degeneration recommendations.

Highlights from the Eye Disease Case Control Study Group, 1992

Lower risk of neovascular AMD was connected to higher levels of carotenoids in the blood serum samples ... (pg. 1704)

Higher risk of neovascular AMD was tied to cigarette smoking, and higher levels of serum cholesterol ... (pg. 1704)

Persons with higher carotenoid levels (sum of serum lutein/zeaxanthin, b-carotene, a-carotene, cryptoxanthin, and lycopene levels) had significantly reduced risks of neovascular AMD. This finding is important because of suggestions that AMD occurs after cumulative oxidative insults and that higher levels of micronutrients with antioxidant capability may decrease the risk of AMD.

Reference: The Eye Disease Case-Control Study Group, "Risk Factors for Neovascular Age-Related Macular Degeneration," Archives of Ophthalmology, December, 1992, Volume 110, Pages 1701-1708.

31. Lutein, Omega-3 (2008) & Macular Degeneration
Learn more about macular degeneration.

2008

Researchers studied the ability of lutein and omega-3 (DHA) to enhance macular pigments to protect against macular degeneration and other macular conditions.

The study was a four month, placebo-controlled study involving nearly 50 women who were given either placebo, DHA, lutein, or lutein plus DHA. They chose these nutrients because DHA is found in the healthy retina and lutein is found in the healthy maculas.

The dosages of lutein (12 mg/day) and DHA (800 mg/day) were evaluated for their effect on levels in blood plasma and in the optical density of the macular pigment.
Both supplements alone helped to increase their concentration levels in the eye. Both lutein and DHA together displayed a synergistic benefit with the greatest difference on serum concentrations and pigment density when taken together.

Reseachers: E. J. Johnson, Hae-Yun Chung, et al,
Published: The influence of supplemental lutein and docosahexaenoic acid on serum, lipoproteins, and macular pigmentation, American Journal of Clinical Nutrition, May, 2008.

Editor's note: this earlier study has been validated by others; but other carotenoids zeaxanthin and meso-zeaxanthin are also very important to protect the macula.

32. Lycopene (1995) & Macular Degeneration
Learn more about macular degeneration recommendations.

Researchers investigated the potential connection between tocopherols and carotenoids level in blood serum and incidence of age-related macular degeneration (ARMD) by viewing and grading photographs of the retina.

The subjects had retinal pigment abnormalities including soft drusen, late ARMD or neovascular and exudative macular degeneration) and were paired with controls (matched for age, sex, and whether or not they smoked) without evidence of these conditions.

Average levels of various carotenoids were similar in cases and controls. Average levels of vitamin E were lower in people with exudative macular degeneration. But once the difference was controlled for cholesterol levels, the difference was not significant.

What was significant was that researchers found that where they found low (lowest 1/4 of subjects) lycopene levels the subjects were twice as likely to have macular degeneration.

They concluded that low levels of lycopene were related to ARMD.

Researchers: Julie A. Mares-Perlman, et al
Published: Archives of Ophthalmology, December, 1995

Editor's Note: Consumption of high levels of lutein and lycopene has also been associated with lower cancer rates for lung and prostate cancer.

33. Macular Degeneration 2005 Study Shows Benefits of Nutrients
This randomized, double-blind, placebo-controlled study enrolled 106 patients with bilateral macular degeneration. The subjects received either a nutrient combination (consisting of 200 mg of acetyl-L-carnitine, 780 mg of omega-3 fatty acids, and 20 mg of coenzyme Q10) or a placebo daily for 12 months, and underwent visual testing every three months. Treatment improved visual field defects in both eyes. Only one of 102 eyes treated deteriorated during the 12-month study, compared to 14 of 110 placebo-treated eyes. Moreover, the area of the eye's fundus covered by drusen (degenerated retinal pigment cells that are a precursor to macular degeneration) in the treated group decreased by 15% to 23%, while increasing by more than 10% in the placebo group.
The nutrients were selected based on their biological activities. Specifically, acetyl-L-carnitine facilitates fatty acid oxidation, omega-3 fatty acids regulate neural and sensory development in the retina, and coenzyme Q10 is critical to the generation of energy in the mitochondria. The results suggest that supporting mitochondrial health may be useful in preventing and managing macular degeneration.
Reference
* Feher J, Kovasc B, Kovacs I, Schvoller M, Papale A, Balacco Gabrieli C. Improvement of visual functions and fundus alterations in early age-related macular degeneration treated with a combination of acetyl-L-carnitine, n-3 fatty acids, and coenzyme Q10. Ophthalmologica. 2005 May-Jun;219(3):154-66.

34. Mediterranean Diet (2015-2017) & Macular Degeneration
Learn more about prevention of macular degeneration.

The Mediterranean diet food pyramid has vegetables, fruits, legumes, whole grains and nuts and seeds making up the bulk of the diet. Seafood and fish comprise a much smaller part; poultry, eggs and dairy products a smaller part yet; and red meats and sweets are the smallest tip of the pyramid. The diet also includes drinking plenty of water and moderate wine consumption.

2017

This study assessed the diets and macular health of more than 5,000 randomly selected elderly subjects from seven countries (Estonia, France, Greece, Italy, Norway, Spain, and the United Kingdom.

The participants all received eye examinations and retinal photographs which were then graded according to the International Classification System which assigns values the severity of AMD and presence of drusen. Drusen are the yellowish fatty deposits at the macula which are hallmarks of AMD. The participants also completed a food intake questionnaire which was graded according to their Mediterranean Diet Score (MDS).

The higher the MDS score the less severe the AMD. For patients with very early AMD there was little correlation with the MDS; there was a weak inverse relationship between the MDS and the presence of large drusen. Comparing the patients with the highest and lowest MDS, the risk of AMD was 20% less.

Researchers: R.E. Hogg, J.V. Woodside,
Published: Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study, Opthalmology, January, 2017.

2016

These researchers looked at populations in two Portuguese towns, one inland and one coastal. Subjects from the inland town had higher rates of macular degeneration, and pointed to the needed to investigate why geographic location was important.

Researchers: M.L. Cachulo, I. Lains, et al,
Published: Age-related macular degeneration in Portugal: prevalence and risk factors in a coastal and an inland town. The Coimbra Eye Study - Report 2, Acta Ophthalmologica, September, 2016.

2015

For some time researchers and medical practitioners have understood that adhering to a Mediterranean diet lowers the risk of heart disease and other health conditions, even though research does not use an actual Mediterranean diet but an "alternate Mediterranean diet" in which high-ALA margarine is employed instead of olive oil.

This study was a follow-up of over 2,500 patients who had been participants in the AREDS and AREDS2 studies. It is unknown whether this study again used a type of margarine instead of olive oil.

Editor's note: In Greece, the true source of this diet, no one uses margarine. Every town grows their own olives and makes their own olive oil. Margarine is not a natural product and contains additional artificial flavorings, preservatives and other additives to create the texture of butter.

The researchers evaluated the patients' diets over a thirteen year period looking at their consumption of alternate Mediterranean diet components: vegetables, fruits, whole grains, beans, fish, meats, alcohol, and the kinds of fats consumed and assigned a score based on the closeness to the target diet.

They also assigned scores for ten different genetic components that included vulnerabilities to macular degeneration. They assessed the diet score, the genetic score and the combination of diet and genetic scores to determine results.

The researchers found that a high diet scores were associated with the lowest risk of advanced macular degeneration (taking into account age, gender, other health or vision conditions). The high diet score carried even more weight when the genetic risk score was low. When patients had two genes associated with genetic risk, making that genetic risk greater, there was no connection with the diet scores in preventing advanced macular degeneration.

Their conclusion was that if genetic risk is not a strong issue, then the greater the consumption of a Mediterranean diet the lower the risk of developing advanced macular degeneration.
Researchers: Benedicte M.J. Merle, et al.
Published: Adherence to a Mediterranean diet, genetic susceptibility, and progression to advanced macular degeneration: a prospective cohort study, American Journal of Clinical Nutrition, November, 2015.

35. Melatonin (2005, 2009, 2013, 2020) and Macular Degeneration
Learn more about macular degeneration treatment and information.

2020 In lab animals with the characteristics of nonexudative age-related macular degeneration (NE-AMD) researchers investigated evidence that oxidative stress causes damage to retinal pigment epithelium and the retina. Melatonin, an antioxidant was found to protect visual function, reduce Bruch's membrane thickening, and reverse the decrease in RPE and melanin content and immunoreactivity.

Researchers: Dieguez, H.H., Gonzalez, F.M.F., Aranda, M.L., Calanni, J.S., Keller, S.M.I, et al.
Published: (2020). Melatonin protects the retina from experimental nonexudative age-related macular degeneration in mice. J Pineal Res. Mar 4;312643.

In another 2020 study, noting the link between impaired mitochondria generation and age-related macular degeneration, researchers investigated the value of melatonin's mitochondrial support capacity. " The mitochondrial respiratory system is considered a major site of [free radical] generation." The scientists found that melatonin reduces oxidative stress in mitochondria, and additionally reduces inflammation and cell death in the retina.

Researchers: Mehrzadi. S., Hemati, K., Reiter, R.J., Housseinzadeh, A.
Published: (2020). Mitochondrial dysfunction in age-related macular degeneration: melatonin as a potential treatment. Expert Opin Ther Targets. Apr;24(4):359-378.

2013 In another study Russian researchers reported similar results. Noting that melatonin content in the body declines as we age, the scientist state that this decline is a leading mechanism of aging, including development of macular degeneration.

Melatonin has been considered as a treatment for AMD on the basis of studies on its effect on the retinal pigment epithelium (RPE). In this new study the researchers utilized lab animals with AMD to evaluated the effect of melatonin on the mechanics of development of macular degeneration.

They found that melatonin supplementation decreased retinal deterioration and improved some (not all) of the physical changes that come with retinal deterioration. However it did prevent changes in RPE structure and function and reduced the degree of neovascularization (growth of new blood vessels in the back of the retina which distort the retina/macula).
They found also that melatonin halted Importantly, Melatonin prevented destruction of cells in the retina, including retinal neurons. These results suggested melatonin as a possible therapeutic treatment for macular degeneration.

Researchers: N.A. Stefanova, et al.
Published: Potential of melatonin for prevention of age-related macular degeneration: experimental study (in Russian), Advances in Gerontology, 2013.

2009

This double-blind study assessed whether melatonin levels were a significant issue in cases of age-related macular degeneration (AMD) patients. The researchers measured 6-sulfatoxymelatonin levels (aMT6s), which is the major metabolite of melatonin in 43 patients' urine, and compared it to 12 gender-matched controls. Variation in the diluteness of urine were taken into account by measuring the urinary creatinine level and aMT6s levels were expressed as aMT6s/creatinine.

The researchers found that the level of urinary aMT6s/creatinine in AMD patients was significantly lower than that of the controls. In addition, the researchers adjusted the resulting data for other factors such as age, smoking, cancer, and coronary heart disease that have been known to influence the aMT6s level. The researchers also examined the odds-ratio of urinary aMT6s and comparing AMD patients to controls was 0.65), indicating that urinary aMT6s level in AMD patients was lower than in controls even after multivariate adjustment. Urinary aMT6s level in AMD patients was 40% lower than in age-and gender-matched controls.

The researchers concluded that the significance of the result and the role of melatonin in AMD cases requires further investigation.

Researchers: Richard Rosen, et al
Published: Urinary 6-sulfatoxymelatonin level in age-related macular degeneration patients. Molecular Vision, August, 2009

2005 Researchers investigated the relationship between melatonin intake and macular degeneration progression. One hundred subjects who had either early or advanced AMD received a melatonin supplement which also contained zinc and selenium for a three month period. Another 55 patients continued the experiment for 6, 12 or 24 months. They were evaluated using standardized measures of macular degeneration progress at regular intervals.

The researchers found that during the initial two to three months of treatment the patients' vision remained stable. Most of the patients who continued for more than six daily use of the supplement had the health of the back of the eye improve markedly.

Researchers: Chanxian Yi, et al
Published: Effects of Melatonin in Age-Related Macular Degeneration, Annuals of the New York Academy of Science, 2005

36. Meso-Zeaxanthin (1990s, 2003, 2007) & Macular Degneration
Learn more about support for macular degeneration.

Exploration of the carotenoid meso-zeaxanthin has determined that it is an important pigment in the macula in addition to lutein and zeaxanthin. Like zeaxanthin, meso-zeaxanthin comprises 25% of the macular pigments. Lutein is the other 50% of macular pigments.

2003 Scientists evaluated levels of carotenoids lutein, zeaxanthin, and meso-zeaxanthin in the retina of donated eyes in patients both with and without macular degeneration.¹ The study substantiated other research² which has reported that these carotenoids are critical to maintain the health of the macula.

2003 Other studies pointed to the source of meso-zeaxanthin, which cannot be directly consumed as part of one's diet, but which is produced through conversion, in the retina, from lutein.²

If taken as a supplement, meso-zeaxanthin is absorbed into the blood stream and effectively increases macular pigment levels. Vrabec T, Tantri A et al. Autosomal dominant Stargardt-like macular dystrophy: identification of a new family with a mutation in the ELOVL4 gene. Am J Ophthalmol. 2003;136(3):542-5

Researchers also found that patients who suffer from macular degeneration have 30% less meso-zeaxanthin in their macula compared to patients with healthy eyes.³ Such deficiency may be due to either not enough lutein in the diet or the inability of the retina to convert lutein to meso-zeaxanthin.

1. M. Michaelides, D. Hunt, et al., The genetics of inherited macular dystrophies. Journal of Medical Genetics, 2003
2. S.M. Meyers, T. Grene, et al., A twin study of age-related macular degeneration. American Journal of Ophthalmology, 1995
3. T. Vrabec, A. Tantri, et al., Autosomal dominant Stargardt-like macular dystrophy: identification of a new family with a mutation in the ELOVL4 gene, American Journal of Ophthalmology, 2003

2007 More research substantiates that meso-zeaxanthin is important in preventing macular degeneration. Researchers found that the carotenoid helps to increase the density of macular pigments that protect the retina from damaging sunlight.

In a small 4 month study patients daily received 20mg meso-zeaxanthin along with smaller amounts of lutein and zeaxanthin. An like-sized control group took a placebo. They found that levels of all three carotenoids increased in the blood and macular pigment density increased. There were no changes in the patients receiving placebo.

Researchers: R.A. Bone, et al, Florida International University
Published: Macular pigment response to a supplement containing meso-zeaxanthin, lutein and zeaxanthin, Nutrition and Metabolism, 2007

37. Mesozeaxanthin, Lutein & Zeaxanthin (2014, 17) Multiple Benefit
Learn more about how to support the health of the macula.

Now that it is well established that lutein, zeaxanthin and mesozeaxanthin are important nutrient therapies for macular degeneration, researchers have been investing their relationship to various functions of the eye.

2017

Contrast Sensitivity

Researchers wanted to see whether adding the three nutrients to consumption and the resulting improvement in optical density of the macular pigment would enhance perception of contrasts which takes place in the eye through a process known as lateral inhibition.

Lateral inhibition occurs when a neuron which is stimulated reduces the activity of its immediate neighbors. The resulting slowed action and reaction means that there's more of a contrast in stimulation perceived as an increase in visual perception. It apparently helps to sustain perception in color differences.

In the study nearly 60 young and healthy people were part of a 1-year, double-masked, placebo-controlled study. The density of their macular pigment was determined by way of heterochromatic flicker photometry. This is a procedure that measures the individual's ability to perceive subtle changes in color. The degree of lateral inhibition was also measured with a computerized program. The researchers measured contrast sensitivity with a simple a/b choice testing.

The study participants were given either placebo or the three carotenoids. Researchers noted significant changes in all three test measurements after only 6 months. After 12 months further significant gain was reported for contrast sensitivity and lateral inhibition.

The researchers also reported that the improvements in contrast sensitivity could not be explained by optical filtering alone, but involve the eye's ability to perceive edges.

Researchers: J.M. Stringham, K.J. O'Brien, et al
Published: Contrast Sensitivity and Lateral Inhibition Are Enhanced With Macular Carotenoid Supplementation, Investigations in Ophthalmology and Visual Science, April, 2017.

Sleep, Visual Performance, Physical Symptoms

With the dramatic increase in electronic device usage there are increasing reports of damaged vision and other problems that correlate to the exposure to blue light emitted by such devices.

Researchers investigated the effect of the three carotenoids on overall visual performance, sleep quality and various physical symptoms.

Nearly 50 young and healthy subjects received baseline measurements in each of the three categories: vision, sleep, physical symptoms - in the face of excessive screen-time on electronic smartphones, tablets and/or laptops. Some of the subjects were given placebo, others received a supplement of lutein, zeaxanthin and mesozeaxanthin.

At baseline and after 6 months:

Visual performance was measured contrast sensitivity, critical flicker fusion (the point at which flicker is not-detectable), disability glare (lowered visibility of an object in the presence of another glaring light source), and photostress recovery (how long it takes for normal vision to recover after being exposed to a bright light).

Physical symptoms were evaluated by means of a questionnaire about sleep habits, headaches, eye strain, and eye fatigue.

Macular pigment optical density was measured with heterochromatic flicker photometry.

Signficant improvements were noted in all three categories for the subjects receiving the carotenoid supplementation. The researchers did note that the sleep quality was not directly related to macular pigment, but felt that improvements in that regard were due to overall reduction in inflammation and oxidative stress.

Researchers: J.M. Stringham, N.T. Stringham, et al
Published: Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure, Foods, June, 2017.

2015

Basic Carotenoid Therapeutic Effect

Researchers compared the impact of treatment with different macular carotenoid formulations on macular pigment and visual function in early age-related macular degeneration. This is the dry form of macular degeneration which is very responsive to nutrient supplementation. The study involved more than 50 subjects who received one of the following formulations.

Group 1 received 20mg/day lutein, 2mg/day zeaxanthin

Group 2 received 10 mg/day lutein, 2 mg/day zeaxanthin, 10mg/day mesozeaxanthin

Group 3 received 3 mg/day lutein, 2 mg/day zeaxanthin, 17mg/day mesozeaxanthin.

There was significant improvement for all of the three formulations, especially in group 3 where letter contrast sensitivity was the greatest.

Researchers: S. Sabour-Pickett, S. Beatty, et al
Supplementation with three different macular carotenoid formulations in patients with early age-related macular degeneration, Retina, September, 2014.

38. Microcurrent Stimulation (93, 97, 02, 09, 2015) & ARMD
Learn more about macular degeneration, retinitis pigmentosa and diabetic retinopathy.

2015

In a small clinical study of 17 patients aged average 83 years old low-frequency microcurrent stimulation, applied on closed eyelids, improvement in visual acuity resulted.

Some of the patients suffered from wet macular degeneration, the more advanced form of macular degeneration. For these patients, although there were promising results, such results were not statistically significant.

However, for the patients with dry macular degeneration, 52% of the patients showed improvement while 26% of the patients showed continued deterioration, and the remainder showed no change.

It should be noted that the treatment was performed only once a week, while in other studies with better results, daily treatment is utilized.

These results support the need for further research using a larger sample with double-blind controls. Nonetheless, this small study, even once a week, and even with such a small sample size did display positive results.

Researchers: L. Chaikin, et al.

Published: Microcurrent stimulation in the treatment of dry and wet macular degeneration, Journal of Clinical Ophthalmology, December, 2015

2009

Microcurrent stimulation is an application of electrotherapy used in this study of patients with macular degeneration. The researchers were looking into appropriate design models for the electrotherapeutic device and the treatment protocol. The factors include the skin interface, reliability, constraints, protocol, and safety.

In FDA guided and supervised clinical studies on patients dry macular degeneration, 61% of a 400 patients treated with electrotherapy (MSC) had improvements in vision sharpness of 2 or more lines on the Snellen chart. The average intensities of electric current of 60 to 125 muA range were used for this level of result. It is expected that with additional improvements in waveforms, frequency choices, protocols and device applications, these sorts of improvements can be expected in patients with early stages of diabetic retinopathy, retinitis pigmentosa, and dry macular degeneration.

Editor's Note: The current and frequencies used in our MCS 100ile unit is consistent with the 5 research studies done summarized on our website, and as the most research behind it regarding macular degeneration.

Researchers: O'Clock GD, Jarding JB.

Published: Electrotherapeutic device/protocol design considerations for visual disease applications, Engineering in Medicine and Biology Society, 2009. EMBC 2009. Annual International Conference of the IEEE. 2009:2133-6.

2002

In a small 18 month pilot study Dr. Paul treated 94 patients' eyes suffering from AMD, Stargardt's or retinitis pigmentosa with microcurrent stimulation. 68% of those patients experienced an improvement in visual function and visual acuity.

For the patients with dry macular degeneration (36 eyes) 72% had improvement using the Snellen acuity chart with an average improvement of 2 to 3 lines which were readable after the treatment period.

The patients with retinitis pigmentosa (34 eyes) had a 53% improvement rate.

The patients with Stargardt's (24 eyes) had an 83% improvement rate.

Reseachers: Edward Paul, O.D., Ph.d. Visiting Professor of Ophthalmology, Chairman, Department of Continuing Medical Education St. Lukes University School of Medicine.

Presented: The Treatment of Retinal Disease With MCS and Nutritional Supplementation, International Society for Low-Vision Research and rehabilitation at the Low Vision Congress in Gothenberg, Sweden 2002.

1997-Halloran

In a two year study involving 114 patients researchers investigated effects of microcurrent stimulation on patients with macular degeneration, retinitis pigmentosa and other retina problems.

Of 18 patients with AMD, 16 showed improvement.

Of 78 patients with retinitis pigmentosa, 62 showed improvement.

Of 18 patients with other retinal problems, 16 showed improvement.

14 other patients showed no improvement, but their condition stabilized and did not get worse as expected.

2 other patients continued to lose vision, but at a slow rate.

Researchers: Grace Halloran, PhD, et al.

Published: Bioelectrical Stimulation in an Integrated Treatment for Macular Degeneration, Retinitis Pigmentosa, Glaucoma, CMV, and DR; Fourth Annual Symposium on Biologically Closed Electrical Circuits, Mankato University, MN, October, 1997

1997-Wallace

Researchers treated 43 patients who had dry macular degeneration with microcurrent stimulation (200 micro-amps, 20 minutes per session). A total of 65 eyes were treated. We do not know how frequently the treatments were give, but there were a total of 36 sessions.

54% of the patients had an improvement of 1 to 4 lines of on the Snellen acuity chart; 31% improved 2 to 4 lines. In addition the visual fields increased for all patients both vertically and horizontally (85% horizontal improvement, 70% vertical improvement).

Humphrey 30-2 threshold fields significantly improved for 55% of those treated. These field improvements imply changes in receptor and ganglion cell function, with implications for treating Retinitis Pigmentosa as well. Fluorescein angiography documented improved blood flow and scar reduction. These positive outcomes show the potential of Micro-current therapy in the treatment of macular degeneration and retinal disease.
Researchers: Larry B. Wallace, O.D. FCSO

Published: Treatment for Macular Degeneration Utilizing Micro-Current Stimulation, Journal of Optometric Phototherapy, March, 1997

1997-Miller

Miller treated 120 patients with macular degeneration or Stargardt's disease with microcurrent stimulation. 83% of the patients showed improvement in reading a visual acuity chart of 2 or more lines. 11 of the patients had Stargardt's and of those patients 100% had improvement of 2 or more lines of visual acuity. One patient had x-linked retinoschisis who also had 2 lines of improvement for both eyes. Of the 49 patients with wet macular degeneration 88% saw improvement, while of the 60 patients with dry macular degeneration 77% showed improvement. Note that other studies have found results to be better for patients with the dry form of macular degeneration.

Researcher: Damon P. Miller, MD.

Published: organicmd.com.

1993

In a seven year long clinical research study Drs. Jarding and Michael evaluated the results of treating patients with macular degeneration with microcurrent stimulation. The study involved 400 eyes. 78% of the eyes showed from 1-9 lines of improvement in reading a visual acuity chart. More than 50% improved from 2-9 lines of the chart. 2 of the patients who had retinal vein occlusions accompanied by macular swelling experienced dramatic improvement.

The doctors also treated these patients with specific nutrients.

Reseachers: Leland Michael, et al.

Published: Nutritional supplementation, electrical stimulation and age related macular degeneration. Journal of Orthomological Medicine, 1993.

Note: In a second 1998 report Merrill, Jarding & Zehner updated this research. This article reports on the changes in nutrients tested in 1998.

39. Omega 3 (2006) & Macular Degeneration
This article discusses two key studies about the relationship between omega-3 intake and macular degeneration.

Design of the Studies:

Observational prospective study -- mean follow of 5 years

Observational retrospective study

Participants:

2895 adults > 49 years of age at baseline for whom baseline food frequency questionnaire (FFQ) data were available.

681 elderly male twins of whom 222 had age-related macular degeneration (AMD) and 459 did not.

Main Outcome Measures:

FFQ data were analyzed, looking for variables associated with the risk of AMD.

Subjects were grouped by smoking status and by quantity and quality of dietary fat intake.

Key Findings:

Subjects in the highest quintile of omega-3 fatty acid intake had a 59% lower risk for AMD compared with those in the lowest quintile of intake (95% CI, 0.22-0.75). Those eating fish once per week had a 42% reduction in risk compared with those with a minimal fish intake (95% CI, 0.37-0.90). Those consuming fish > three times per week had a 75% reduced risk (95% CI, 0.06-1.00).

After multivariate analysis, those consuming fish > twice per week had a statistically significant 37% reduction in risk compared with those consuming less than one serving per week. Those with a median intake of 350 mg of omega-3 oil (the top quartile of intake) had an adjusted 45% lower risk of AMD compared with those consuming only 60 mg/day (the lowest quintile of intake, p=0.02). The protection associated with EPA/DHA intake occurred primarily in those consuming relatively low levels of linoleic acid (adjusted odds ratio of 0.23, p<0.001). Current smokers had almost twice the risk for AMD compared with those who never smoked (p=0.06).

Practice Implications:

Allopathic treatment for AMD is relatively ineffective for most patients. Until now, most of the emphasis in prevention and treatment in the realm of natural medicine has focused on the use of lutein and zinc, though a small body of evidence suggested fish consumption might reduce the risk of AMD (Arch Ophthalmol 2000;118:401-4). Both new studies confirm a strong and consistent inverse correlation between EPA, DHA, and fish consumption and AMD.

The study by Chua and colleagues also tracked alpha-linolenic acid (ALA) intake -- the vegetarian omega-3 oil that partially bioconverts to EPA. In terms of 5-year risk for early AMD, ALA showed the same protective effect, as did EPA/DHA. However, though this difference was not statistically significant, for late AMD, those in the lowest quintile of ALA intake had a lower risk than those consuming more ALA. Until more is known, therefore, there is little reason to assume ALA has the same protective effect that EPA and DHA appear to have.

Chua's findings regarding associations between total fat, monounsaturated fatty acids, trans fatty acids, polyunsaturated fatty acids [PUFA], and saturated fatty acids, and AMD risk conflict with previously published research (Arch Ophthalmol 2003;12:1728-37). Therefore, we don't know enough about the possible effects of these variables to alter clinical practice.

Findings from the study by Seddon and colleagues, suggest that cessation from smoking combined with a modest increase in fish or omega-3 fatty acid intake would literally cut the risk for AMD in half. Implementing appropriate changes could save vision in many elderly people. But what sense do these findings make?

Experimental reports show that DHA protects against retinal oxidative damage. Also, an inflammatory component to AMD has been reported, and EPA and DHA have known antiinflammatory actions. That said, for the most part we still do not understand how EPA and DHA protect against AMD.

Despite a lack of understanding, encouraging patients to increase intake of fatty fish makes sense. After considering the favorable risk-to-benefit ratio, an argument can also be made for discussing supplementation of EPA/DHA with AMD patients. Optimal dosing remains unclear, but even a few hundred milligrams per day of EPA plus DHA would reach well into the dietary intake reported by those experiencing a protective effect.

References

1. B. Chua, V. Flood, et al. Dietary fatty acids and the 5-year incidence of age-related maculopathy. Archives of Ophthalmology, July 2006
2. J.M. Seddon, S. George, et al, Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration. Archives of Ophthalmology, July, 2006.

Author: Steve Austin, N.D.

40. Omega 3 Fatty Acids (1992, 2003, 2008-12, 2014) & ARMD
Learn more about macular degeneration and treatment options.

1992

While it is known that a low fat diet which gets only 10% of its calories from fat, and which excludes red meat and milk products lessens AMD risk (Anderson, R.E., et al, 1984), it has been found that the omega-3 fatty acids are essential for healthy vision.

Omega-3 essential fatty acids, especially found in fatty fish like salmon or sardines are important in preventing macular degeneration and their deficiency increases the risk of developing macular degeneration. 85% of AMD patients over age 70 had improved vision when they were given omega-3s for four weeks.

Researchers: W.E. Conner, M. Neuringer, and S. Reisbick
Published: Essential fatty acids: The importance of n-2 fatty acids in the retina and the brain, Nutrition Reviews 50 (1992): 21-29.

Editor's Note: The best sources of omega-3 EFA's are the flesh of cold water marine fish as well as black currant oil, flaxseed oil and hemp seed.

2003

Fish is a good source of omega-3 fatty acids, especially fatty fish like salmon. Researchers reported that higher consumption omega-3 fatty acids are associated with lowered risk of advanced macular degeneration. The results were adjusted for nutrient and non-nutrient risk factors, according to data evaluated from the AREDS study in 2001, which involved more than 4,500 60 to 80 year old patients.

The risk was significantly decreased in the highest 1/5th of the study group based on their omega-3 consumption.

More than two servings a week of fish was linked to lower wet macular degeneration risk compared to no fish in the diet.

Omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may protect the retina by through expression of genes, retinal cell differentiation, and survival. The ability of fatty acids to reduce inflammation may be a contributing factor.
Researchers: J. P. SanGiovanni, et al, National Eye Institute, Association for Research in Vision and Opthalmology
American Medical Association, Archives of Ophthalmology, 2007

2008

Researchers performed a meta analysis (essentially a study of more than 270 studies and papers that evaluated the relationship of omega-3, eating fish, and risk of macular degeneration.

They found that high levels of omega-3 in the diet were tied to a 38% reduction in the risk of developing advanced macular degeneration. Eating fish two times a week as tied to both early and advanced macular degeneration.

Researchers: E.W. Chong, et al.
Published: Dietary omega-3 fatty acid and fish intake in the primary prevention of age-related macular degeneration: a systematic review and meta-analysis, Archives of Opthalmology, June, 2008.

2009

A longitudinal study investigated whether higher omega-3 intake is associated with a lower risk of developing macular degeneration. The study investigated the progression of the condition in over 1800 people over a twelve year period. Diet information was taken from a questionnaire at the outset of the research.

The researchers found that patients who reported the greatest omega-3 consumption were 20% less likely than others to develop macular degeneration over the 12 year period.

Researchers: John Paul SanGiovanni, et al,
Published: Omega-3 Long-chain polyunsaturated fatty acid intake and 12-y incidence of neovascular age-related macular degeneration and central geographic atrophy: AREDS report 30, a prospective cohort study from the Age-Related Eye Disease Study 2009, American Journal of Clinical Nutrition, December, 2009.

2009

This study investigated omega-3 (EPA & DHA) effect on lab animals with AMD.

Researchers evaluated the direct effects of omega-3s on lab animals and found that if their diet was high in omega-3s, macular degeneration lesions developed more slowly, and in some cases, improved. In the animals where improvement was found there was also less inflammation present and greater quantities of anti-inflammation molecules.

Researchers: Tuo, et al.,
Published: A High Omega-3 Fatty Acid Diet Reduces Retinal Lesions in a Murine Model of Macular Degeneration, American Journal Of Pathology, 2009

2010

This study added shellfish to the helpful omega-3 sources.

Researchers evaluated food questionnaires from 2520 participants on Maryland's eastern shore regarding their weekly fish and shellfish consumption. Photos of their retinas were taken at the outset of the study to create a baseline and graded according to standardized procedures.

They found that while consumption was not greatly different for different categories of macular degeneration, those subjects who had more advanced stages of AMD were less likely to have included fish and shellfish in their diets. The researchers found no correlation between intake of crab and oysters (which contain much zinc).

Researchers: B.K. Swenor, S.K. West, et al., Salisbury Eye Evaluation Study
Published: The impact of fish and shellfish consumption on age-related macular degeneration, Ophthalmology, December, 2010.

2011

This large long term (ten years) study reviewed the diet of nearly 40,000 women, health professionals, with an average age of 54.6 years. More than 38,000 of the participants were free of AMD, measured by incident AMD and a reduction of 20/30 or worse. 235 cases of AMD were confirmed in the ten years of follow-up. Comparing the women with the highest and lowest 30% of docosahexaenoic acid intake (an omega-3 fatty acid) the relative risk was .66 (2/3rds) lower. Women who ate 1 or more servings of fish a week, compared to those with less than one serving per month, had a risk of .58. Consumption of other omega-3 fatty acids had similar results.

Their conclusion substantiated earlier findings that a diet that regularly including omega-3 fatty acids significantly lowered risk of age related macular degeneration in women.

Researchers: William G. Christen, ScD; Debra A., et al.
Published: Dietary omega-3 fatty acid and fish intake and incident age-related macular degeneration in women. Archives of Ophthalmology, 2011.

2014

Scientists have found that omega 3 fatty acids have the capacity to actually regulate formation of blood vessels - an important factor in development of macular degeneration. This occurs because of the nutrient's ability to encourage immune cell movement toward the site of extra formations of blood vessels that distort vision in the condition. The results indicate very promising potential for omega 3 as a nutritional therapy - not only for AMD, but for other conditions involving inflammation and creation of additional blood vessels.

Researchers: from Massachusetts Eye and Ear/Schepens Eye Research Institute, Harvard Medical School and other institutions.
Published: Cytochrome P450-generated metabolites derived from omega-3 fatty acids attenuate neovascularization, Ryoji Yanai, et al, Proceedings of the National Academy of Sciences, June 2014.

41. Omega 3 Fatty Acids (2005) & Macular Degeneration
The Lewin Group was commissioned in early 2005 by the Dietary Supplement Education Alliance (DSEA) to critically review the research literature concerning Omega-3 fatty acids, lutein and zeaxanthin. Visual impairment is one of the top four reasons for loss of independence. Age-related diseases of the eye are common and costly (35% of individuals aged 75 and older have AMD).
For example, eighteen percent of all hip fractures among seniors are attributed to age-related vision loss (hip fracture patients have a substantially increased risk of death for at least 6 years post-fracture). The Lewin Report addresses several hundred studies on the benefits of Omega-3 fatty acids dating back nearly thirty years, including several comprehensive reviews.
In addition, in 2004, the FDA issued a qualified health claim for reduced risk of coronary heart disease (CHD) associated with foods containing Omega-3 fatty acids. Earlier, in 2000 the FDA announced a similar qualified health claim for reduced risk of CHD for dietary supplements containing EPA and DHA Omega-3 fatty acids.
Key findings of the Lewin report support the supplementation of omega-3 fatty acids, lutein, and zeaxanthin in helping preserve vision and supporting people to be able to maintain independent living.
For full article, go to http://www.nowfoods.com/?action=itemdetail&item_id=41654

42. Omega-3 and vitamin D (2007) 40% lower risk of macular degeneration
Omega-3 & vitamin D tied to lower risk of macular degeneration
This study reviewed the relationship between consumption of omega-3 fatty acids and omega-3 rich fish and the risk of developing age-related macular degeneration. The researchers concluded that the risk could be lowered by 40%.

The study further supports other research finding that increasing the proportion of omega-3 to omega-6 fatty acids in the diet is important. A high proportion of omega-6 fatty acids (arachidonic acid AA) is associated with an increased risk of AMD.

Published: Association Between Vitamin D and Age-Related Macular Degeneration in the Third National Health and Nutrition Examination Survey, 1988 Through 1994, Archives of Ophthalmology, May 125, 2007 Volume 125, Pages 671-679

Authors: N. Parekh, R.J. Chappell, A.E. Millen, D.M. Albert, J.A. Mares

43. Omega-3 Fatty Acid Intake Reduces Risk of Macular Degeneration 2008 Studies
According to a meta-analysis(1) published in the June issue of Archives of Ophthalmology, a higher intake of the omega-3 fatty acids EPA and DHA reduced the risk of age-related macular degeneration (AMD). In analyzing 9 studies that included roughly 88,900 participants, the Australian authors report that higher intakes of EPA and DHA cut the risk of early AMD substantially and yielded a 38% risk reduction for advanced AMD.
Most recently, a study published in the August issue of the American Journal of Clinical Nutrition is the first in Europeans to show a beneficial association between neovascular AMD and the consumption of oily fish (e.g. mackerel, tuna, salmon, sardines, and herring)(2). The study, funded in part by the European Commission and the Macular Disease Society UK, is consistent with results from studies in the US and Australia.
Study Design and Methods
The EUREYE study is a cross-sectional population-based study in persons aged 65 years or older in 7 centers located from north to south Europe. Participants in the cross-sectional population-based EUREYE study underwent fundus photography and were interviewed by using a food-frequency questionnaire. Fundus images were graded by the International Classification System for Age Related Maculopathy.
Questionnaire data were converted to nutrient intakes with the use of food-composition tables. Survey logistic regression was used to calculate odds ratios (ORs) and 95% CIs of energy-adjusted quartiles of EPA or DHA with neovascular AMD, taking into account potential confounders.
Results
Dietary intake data and fundus images were available for 105 cases with neovascular AMD and for 2170 controls without any features of early or late AMD.
Eating oily fish at least once per week compared with less than once per week was associated with a halving of the odds of neovascular AMD (OR = 0.47; 95% CI: 0.33, 0.68; P = 0.002). Compared with the lowest quartile, there was a significant trend for decreased odds with increasing quartiles of either DHA or EPA. Odds ratios in the highest quartiles were 0.32 (95% CI: 0.12, 0.87; P = 0.03) for DHA and 0.29 (95% CI: 0.11, 0.73; P = 0.02) for EPA.
In short, habitual consumption of oily fish at least once a week was linked to a 50% reduction in the risk of developing wet AMD. Further, people who consumed at least 300 mg per day of DHA and EPA were 69% less likely to have wet AMD then those consuming less.

44. Polyunstaturated Fats (2009) High in Diet Increase Risk of Macular Degeneration
Learn more about macular degeneration treatment and information.

Less polyunsaturated fat in one's diet may help protect against age-related macular degeneration (AMD), according to results of the Carotenoids in Age-Related Eye Disease Study.
The investigators tracked nearly 2,000 women aged 50-79 as part of the larger Women's Health Initiative Observational Study. Via questionnaires and retinal photography, they concluded that women who consumed the highest levels of dietary polyunsaturated fats were about two times as likely to develop AMD compared to those women who consumed the least. Mono-unsaturated fatty acids were associated with a lower risk of AMD.
Reference: Arch Ophthalmol. 2009 Nov;127(11):1483-93.

Editor's Note: The types of fats in one's diet play a major role in eye and overall body health. Avoid polyunsaturated oils such as vegetables oils (do not cook with these oils). Use high quality olive oil in your diet on your salads and food such as adding it to your steamed vegetables (with a little balsamic vinegar or lemon - delicious).

45. Poor Circulation and Aged Related Macular Degeneration Study 2009
2014

Previous research has suggested that there are similar patterns in people who have macular degeneration (AMD) and cardiovascular disease (CVD). But it was unknown whether having AMD could predict having stroke or heart disease.

Reviewers systematically pulled data about AMD status and the estimates of risk of CVD as well as the methods used to evaluate both. They looked at 13 studies including more than a million and a half people. More than 155,000 of those people had CVD (stroke or heart disease).

They found that there was a 15% increased risk of cardiovascular disease in those with early macular degeneration. The increased risk was much greater (66%) for those with late AMD.

Researchers: J. Wu, M. Uchino, et al
Published: Age-related macular degeneration and the incidence of cardiovascular disease: a systematic review and meta-analysis, PLoS One, March, 2014

2009

A large study found strong evidence that older people who have age-related macular degeneration (AMD) are at increased risk for coronary heart disease (CHD), although not for stroke. This result adds to mounting evidence that AMD and cardiovascular disease may share some risk factors: smoking, high blood pressure, inflammatory indicators such as C-reactive protein, genetic variants such as complement factor H, and disease mechanisms.

The Cardiovascular Health Study (CHS) followed the health of more than 1,700 white or African American participants for about seven years. The subjects did have heart disease or stroke at beginning of the study.

The incidence of CHD was 25.76 percent in patients with AMD, compared with 18.9 percent in those without AMD. The association between AMD and CHD was somewhat stronger in people age 69 to 78 than age 79 and up.

Data were adjusted to take into consideration factors like hypertension, diabetes, and smoking.

46. Pro-vitamin A and E
There was an inverse relationship between dietary pro-vitamin A carotenoid and vitamin E consumption and the incidence of large macular drusen, and between zinc and the incidence of pigmentary abnormalities. Am J Epidemiol 1998 Jul 15;148(2):204-14

47. Refined Carbohydrates Diet (2006), Cataracts and Macular Degeneration
Learn more about macular degeneration treatment and information and cataracts information.

Since the mid 1990s Research have been indicating that diets high in the complete vitamins, minerals and antioxidant nutrients lower the risk of degenerative eye diseases. Studies additionally suggest an association between consumption of high glycemic carbohydrate foods, cataracts and macular degeneration.

April 2006 Journal of Clinical Nutrition Study

526 participants without a previous macular degeneration diagnosis were included. Long-term dietary information was based on data from an average of 4 food-frequency questionnaires collected over a 10-year period before the assessment of ARMD. Dietary glycemic index (GI), a measure of carbohydrate intake quality, was related to ARMD (specifically to retinal pigmentary abnormalities), whereas total carbohydrate intake was not.

May 2006 Journal of Clinical Nutrition Study

A food-frequency questionnaire was used to obtain dietary information from 3377 participants in the Age-Related Eye Disease Study (AREDS) focusing on glycemic index and the presence of cortical or nuclear opacities (symptomatic of cataracts). It was found that the patients with the highest dietary intake of high glycemic foods had the highest prevalence opacities. This study was one of a few studies reporting this association in non-diabetic persons and it was the first study that has indicated a solid relationship between dietary GI and the risk of cataracts.

Published:

Dietary glycemic index and carbohydrate in relation to early age-related macular degeneration. Chiu J, Hubbard L, Armstrong J, et al. American Journal of Clinical Nutrition. 2006 Apr;83(4):880-6

Dietary carbohydrate intake and glycemic index in relation to cortical and nuclear lens opacities in the Age-Related Eye Disease Study Chiu J, Milton R, et al. American Journal of Clinical Nutrition. 2006 May;83(5):1177-84.

48. Resveratrol (2005, 2017) & Macular Degeneration
Learn more about macular degeneration recommendations

2022 Although earlier research supported use of moderate red wine use, newer research reports that the many detriments outweigh the benefits.^{1, 2, 3} Instead, we recommend intake of resveratrol through grapes, grape juice, peanuts, cocoa, and berries of Vaccinium species, including blueberries, bilberries, and cranberries.

2017

Scientists report that resveratrol, taken orally, shows up in blood samples within 10 minutes of ingestion and is able to cross the semi-permeable blood-brain and blood-ocular barriers making it a valuable micronutrient for ocular conditions such as macular degeneration.

Researchers measured the trans-resveratrol (and its metabolites) concentrations in human eyes.

The researchers noted that the antioxidant, anti-inflammatory agent abilities of resveratrol, along with its capacity to inhibit formation of extra blood vessels make it valuable as a nutrient for macular degeneration.

Scientists determined that trans-resveratrol and three metabolites of resveratrol (especially resveratrol-3-O-sulfate) were found in eye tissue ) after taking dosages orally. Theese measurements help to define dosages in future treatment of ocular disease.

Researchers: S. Wang, Z. Wang, et al,
Published: Tissue Distribution of trans-Resveratrol and Its Metabolites after Oral Administration in Human Eyes, Journal of Ophthalmology, March, 2017.

2005

Researchers have found that moderate wine drinking and antioxidant-rich diets may decrease risk of age-related macular degeneration. Development of this and other retinal conditions, such as proliferative vitreoretinopathy (PVR), is associated with oxidative stress in the retinal pigment epithelium (RPE), where the health of the retina is maintained by providing structural and nutritional support.

The researchers indicate that resveratrol, a red wine polyphenol, may be responsible, in part, for these health benefits. To test this hypothesis, the antioxidant and antiproliferative effects of resveratrol were examined in a human RPE cell line (designated ARPE-19). The results suggest that resveratrol can reduce oxidative stress and hyperproliferation of the RPE.

Researchers: R.E. King, K.D. Kent, et al,
Published: Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition, Chemico-Biological Interacttions, January, 2005.

Footnotes
1. Wood AM, Kaptoge S, Butterworth AS, Willeit P, Warnakula S, et al. (2018). Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies. Lancet. Apr 14;391(10129):1513-1523.
2. Biddinger KJ, Emdin CA, Haas ME, Wang M, Hindy G, et al. (2022). Association of Habitual Alcohol Intake With Risk of Cardiovascular Disease. JAMA Netw Open. 2022 Mar 1;5(3):e223849
3. Goding Sauer A, Fedewa SA, Bandi P, Minihan AK, Stoklosa M, et al. (2021). Proportion of cancer cases and deaths attributable to alcohol consumption by US state, 2013-2016. Cancer Epidemiol. Apr;71(Pt A):101893.

49. Saffron (2010-2016) and Macular Degeneration
Learn more about support for macular degeneration.

2016

One study focused on saffron's impact on P2X purinoceptor 7 (P2RX7). A P2RX7 receptor is a type of protein found in genes that occurs in retina as well as other parts of the nervous system. It is a cause of cell death, is part of receptor communication and is linked to inflammation. In the eye it is associated with vision loss, and in other parts of the body it is tied to osteoporosis, nerve pain and possibly diabetes.

Researchers have reported that saffron protects the photoreceptors of the retina from damage from sunlight.

In macular degeneration patients P2RX7 degrades retinal flicker sensitivity. This refers to the frequency at which flickering appears to be steady to the human eye. The rods of the photoreceptors are responsible for detecting movement, and so retinal flicker sensitivity becomes a means of measuring the health of the photoreceptors.

In this 2016 study the scientists found that saffron improves the health of retinal and retinal photoreceptors cells. The support appears to come through saffron's ability to inhibit certain types of bioelectrical currents that cause damage.

Researchers: L. Corso, A. Cavallero, D. Baroni, et al

Published: Saffron reduces ATP-induced retinal cytotoxicity by targeting P2X7 receptors, Purinergic Signaling, March 2016.

2015

The study reviews addition of saffron and vitamin D to the AREDS and AREDS2 formulas. It finds that saffron contains safranal, crocin and crocetin which are similar to the carotenoid zeaxanthin, and which are strong antioxidants. These components may be helpful in treatment of a wide range of conditions including macular degeneration, Alzheimer's, and cardiac conditions.

Researchers: G.K. Broadhead, et al.

Published: Dietary modification and supplementation for the treatment of age-related macular degeneration, Nutrition Reviews, July, 2015; Efficacy and Safety of Saffron Supplementation: Current Clinical Findings, Critical Reviews in Food Science and Nutrition, April, 2015.

2014

This study also found that saffron improved retinal flicker sensitivity which ties saffron's neuroprotective capacity to improved vision in retinal degenerative conditions such as macular degeneration. Researchers found an improvement of 2 lines measured by the standard Snellin chart in patients taking 20mg daily saffron over a 14 month period.

The researchers reported that although the reason that saffron components worked was still being investigated that it is reasonable to come to the conclusion that the components are able to reduce cell death and preserve vision.

Researchers: S. Bistri, R. Maccarone, B. Falsini

Published: Saffron and retina: neuroprotection and pharmacokinetics, Visual Neuroscience, September, 2014.

Another study published in 2014 noted that crocetin, one of the potent colorants of saffron, has value as an antioxidant, tumor fighting carotenoid, memory enhancer and depressant and anxiety fighter. At the same time it presents no major toxicity.

Researchers: S. H. Alavizadeh, H. Hosseinzadeh

Published: Bioactivity assessment and toxicity of crocin: a comprehensive review, Food and Chemical Toxicology, February, 2014

2013

This study evaluated the benefit of saffron in patients with early macular degeneration with respect to different risk genotypes. The researchers measured macular sensitivity and flicker sensitivity. 36 patients were given 20 mg/daily over an average of 11 months. After 3 months of such supplementation improvements were noted for both measurements without any difference based on the risk genotype. In other words, improvement was found without respect to type of hereditary risk.

Macular sensitivity was measured via the snellen chart, the standard vision chart. After three months of taking the saffron supplement subjects had a significant increase in visual acuity (improvement in sharpness of vision) of one full line on the snellen chart (14.3% improvement from baseline test).
Researchers: D. Marangoni, et al.

Published: Functional effect of Saffron supplementation and risk genotypes in early age-related macular degeneration: a preliminary report, Journal of Translational Medicine, September, 2013.

2012

Saffron contains crocin and crocetin which are carotenoids that act as powerful antioxidants. In traditional ayurvedic medicine saffron is known to have an anti-inflammatory effect.

The researchers wanted to follow-up on previous studies that suggested that saffron could have benefits for patients with macular degeneration. In a 14 month long clinical trial 29 patients were given saffron tablets, 20mg daily. They were evaluated every three months during the trial and improvement was noted after three months. The improvement continued until the study was ended and treatment stopped, when macular changes tended to revert to the previous weakness.

Researchers: M. Piccardi, et al.

Published: A longitudinal follow-up study of saffron supplementation in early age-related macular degeneration: sustained benefits to central retinal function, Evidence Based Complementary Alternative Medicine, July, 2012.

2010

This 2010 exploratory study of 25 early AMD patients found that short term supplementation with saffron improves flicker sensitivity. This research was further explored and replicated with more recent research. The patients were given 20mg/daily saffron or placebo, with baseline measurements of focal electroretinograms.

Of particular interest was that the researchers commented that saffron may support vision in ways in unexpected ways beyond their antioxidant properties. For example later research with saffron and memory finds that the crocin in saffron apparently acts to protect nerve synapses in the brain.

Researchers: B. Falsini, M. Piccardi, et al.

Influence of saffron supplementation on retinal flicker sensitivity in early age-related macular degeneration, Investigations in Opththalmological and Visual Science. 2010

50. Smoking (1994, 2006, 2015, 2016) & Macular Damage
Learn more about treatment for macular degeneration.

For the past several decades it has been known that the risk to smokers in developing macular degeneration was significant; depending on the particular study the risk factor was held to be from two to six times greater for smokers than for non-smokers.

2016 Researchers found that if patients with macular degeneration stop smoking early enough some of the damage caused by smoking is reversable. In addition they found that the connection between Alzheimer's and AMD is strengthened by the damaged caused by smoking.

Researchers: Sha Sha Yu, et al.
Published: Links between the Brain and Retina: The Effects of Cigarette Smoking-Induced Age-Related Changes in Alzheimer's Disease and Macular Degeneration, Frontiers in Neurology, July, 2016

Other researchers found that the seriousness of macular degeneration cases is greater in patients who smoke. Smokers who have a genetic predisposition to AMD are more likely to develop the condition than non-smokers with the same genetic risk.

Researchers: D. Stanislovaitiene, et al
Published: SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area, Ophthalmic Genetics, July, 2016

2015 Researchers decided to investigate chromosome 1 genotype (the largest chromosome with about 249 million DNA pairs) and damage, including smoking in tissue from the macula of smokers.

They found that the macula tissue of smokers had increased levels of genetic damage in the Bruch's membrane, one of the layers of the retina, and in the choroidal stroma (the layer of the retina containing blood vessels). Smoking was also associated with markedly elevated C-reactive protein, an indicator of inflammation. Finally, the macula tissue of smokers demonstrated high levels of stress due to free radicals (oxidative stress) in the pigmented layers of the macula (RPE).

Researchers: T.D. Keenan, M. Toso, C. Pappas, L. Nichols, P.N. Bishop, G.S. Hageman
Published: Assessment of Proteins Associated With Complement Activation and Inflammation in Maculae of Human Donors Homozygous Risk at Chromosome 1 CFH-to-F13B, Investigative Ophthalmology and Visual Science, July, 2015.

2006 This study investigated the relationship between pack-years. For example 20 pack years equals 20 cigarettes, or 1 pack per day for 20 years.

Researchers took a closer look at the ramifications of smoking and development of macular degeneration. The study was done with Caucasian subjects where 435 patients were compared to 280 controls. All of the patients had retinal photographs taken and the presence of advanced wet macular degeneration (choroid neovascularization) and advanced dry macular degeneration (geographic atrophy) was noted. The subjects completed a smoking history questionnaire.

Smokers, former smokers and non-smokers were compared. There were differences, but they were not statistically significant. But there was a significant association when pack-years were taken into consideration. Smokers with a 40 pack year history were about 3 1/2 times as likely to develop advanced dry macular degeneration and 2 1/2 times as likely to develop advanced wet macular degeneration. Smokers who quit smoking had better odds, and those who hadn't smoked in 20 years had similar results as non-smokers.

Researchers: J.C. Khan, D.A. Thurlby, et al.
Published: Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk for both geographic atrophy and choroidal neovascularization, British Journal of Ophthalmology, January, 2006.

1994 Smokers with early macular degeneration who consumed the lowest amounts of carotenoids were nearly 6 times as likely to develop advanced macular degeneration than those consuming the highest amounts.

Researchers: Seddon, et al.
Published: Journal of the American Medical Association, 1994

51. Statin Drugs and Macular Degeneration (2006)
Contrary to the expectations of some scientists, cholesterol-lowering 'statin' drugs (such as Lipitor or Zocor) do not appear to stave off age-related macular degeneration (AMD) in the eye. In fact, a review of data from the Cardiovascular Health Study suggests that taking a statin may slightly increase the risk of age-related macular degeneration.

SOURCE: Archives of Ophthalmology, January 2006.

Learn more about macular degeneration recommendations and about other drugs that harm the eyes.

52. Statins May Increase Chances of Getting Macular Degeneration
January 13th 2006
Recent recommendations for the aggressive use of medications to lower low-density lipoprotein (LDL) cholesterol levels has contributed to a rising trend in the use of statin drugs. A study published in the January 2006 Archives of Ophthalmology evaluates the use of these drugs, specifically with regard to the risk of age-related macular degeneration (AMD).
The investigators collected data from the Cardiovascular Health Study, a population-based prospective study, to address the relationship between the use of statins and other cholesterol-lowering medications and AMD. Fundus photographs were taken in 1997 and 1998 on 4249 statin users and non-statin users in the study. 2755 of these participants were available to be classified as cases (AMD) or controls (no AMD).
The results of this study suggests no association exists between cholesterol-lowering medications and AMD progression. However, there was a suggestion that statin use might increase the risk of developing AMD. These findings are corroborated in several similar studies, including the first National Health Examination and Nutrition Survey. This evidence may seem a bit contrary to some and more than disappointing to the pharmaceutical companies who are now using the popular atherosclerotic-like theory of AMD to justify detailing statin drugs as AMD medications in ophthalmic offices.
The Doctors Klein (Beaver Dam Study) recently proposed the idea that high LDL levels and low HDL levels may actually offer protection from AMD by down-regulating LDL receptors in the Retinal Pigment Epithelium (RPE), thereby reducing the contribution of cholesterol to drusen. This line of reasoning implies that by lowering serum cholesterol levels with statins; an increased amount of cholesterol may be taken up by the RPE cells with a subsequent increased deposition in drusen and an increased risk of AMD.
References:
3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors and the Presence of Age-Related Macular Degeneration in the Cardiovascular Health Study. McGwin G, Kayvon M, et al. Arch Ophthalmol. January 2006;124(1):33-37 [abstract not yet catalogued in the National Library of Medicine]
A case control study of age related macular degeneration and use of statins. Smeeth L, Cook C, et al. Br J Ophthalmol. 2005 Sep;89(9):1171-5 [abstract]
The association of cardiovascular disease with the long-term incidence of age-related maculopathy: the Beaver Dam eye study. Kelin R, Klein BE, et al. Ophthalmology. 2003 Apr;110(4):636-43 [abstract]
The Use of Cholesterol-lowering medications and Age-related macular degeneration McGwin Jr G, Xie A, et al. Ophthalmology 2005;112:488-494 [abstract]
Cholesterol lowering drugs and risk of age related maculopathy: prospective cohort study with cumulative exposure measurement. van Leeuwen R, Vingerling JR, Hofman A, et al. BMJ 2003;326:255-256 [abstract]
Relation of statin use to the 5-year incidence and progression of age-related maculopathy. Klein R, Klein BE, et al. Arch Ophthalmol. 2003 Aug;121(8):1151-5 [abstract]

53. Stem Cell Transplants Show Some Success in Restoring Vision
Could an out-patient surgical procedure for cure of age-related macular degeneration (AMD) with stem cells transfer become commonplace in the next decade?

During a recent visit to discuss the possibility of conducting human trials of retinal stem cell transplants in India, Professor Pete Coffey, from University College London (UCL) Institute of Ophthalmology, London, United Kingdom; reportedly told the Times of India:

"... some cases, the transplants were so successful that the patients were able to read, cycle and use a computer. By 2011, we will make it a 45-minute out patient operation."

Professor Pete Coffey and his colleagues at the UCL Institute of Ophthalmology in London, UK, have previously written:

"Retinal pigment epithelial (RPE) transplantation aims to restore the subretinal anatomy and re-establish the critical interaction between the RPE and the photoreceptor, which is fundamental to sight."1

"Diseases that have been treated with RPE transplantation demonstrating partial reversal of vision loss include primary RPE dystrophies ... photoreceptor dystrophies as well as complex retinal diseases such as atrophic and neovascular age-related macular degeneration (AMD).

"Unfortunately, in the human trials the visual recovery has been limited at best and full visual recovery has not been demonstrated."

"Autologous full-thickness transplants have been used most commonly and effectively in human disease but the search for a cell source to replace autologous RPE such as embryonic stem cells, marrow-derived stem cells, umbilical cord-derived cells as well as immortalised cell lines continues."

Reference: da Cruz L, Chen FK, Ahmado A, Greenwood J, Coffey P. : RPE transplantation and its role in retinal disease. Prog Retin Eye Res. 2007 Nov;26(6):598-635.

54. Supplements (2003) AMD Outcomes - Lifestyle, Supplement May Improve Outcomes in AMD
Research indicates changes in lifestyle, including having a lower body mass index, exercising and taking a dietary supplement, may reduce the risk and/or the severity of age-related macular degeneration (AMD), which affects 30% of people 75 years or older. A study of 261 patients age 60 or older with signs of non-advanced AMD, published in the Archives of Ophthalmology (2003;121[6]:785-792).
Patients were followed for an average of 4.6 years, and their height, weight and blood pressure were measured annually. The data indicated that study participants with a high body mass index (BMI >25) were more than twice as likely to have their AMD worsen than were those with lower weight. Patients who exercised vigorously at least three times a week had a 25% reduction in the risk that the severity of the disease would increase.

55. Supplements (2007) Improve Visual Acuity in Subjects with Dry Macular 2007
Learn more about macular degeneration treatment and information.

Combined Supplements Improve Visual Acuity in Subjects with Dry Macular Degeneration

This was a controlled, double blind (though not randomized) intervention trial. The subjects included 37 adults with age-related macular degeneration (AMD). The control was similar patients from a previous report matched for inclusion and exclusion conditions.

Study Medication and Dosage: The patients received retinol (10,000 IU/d), beta-carotene (28,640 IU/d), vitamin C (452 mg/d), vitamin E (200 IU/d), zinc (56 mg/d), copper (1.6 mg/d), taurine (400 mg), EPA (180 mg/d), DHA (120 mg/d), lutein (8 mg/d), and zeaxanthin 400 mcg/d). The control subjects had also received vitamin C (400 mg/d), vitamin E (200 IU), zinc (40 mg), and beta-carotene (300 IU/d), but none of the other supplements.

Changes from the start of the study period in visual function were measured using a variety of standard research tools (e.g., Best-Corrected Visual Acuity (BCVA) via the Early Treatment Diabetic Retinopathy Study (ETDRS) chart, contrast sensitivity, and retinal imaging).

77% of the subjects receiving the full complement of supplements demonstrated stabilization or improvement at 6-months. These same subjects saw small improvements in visual acuity that achieved statistical significance (p<0.05). As expected, mean visual acuity declined in the control group.

Conventional medicine has little to offer many patients with this common eye condition. Progressive deterioration is the norm, though the rate of deterioration can vary significantly. Dry AMD is the most common form. Previous research has suggested the possibility that a wide variety of nutritional supplements help patients with AMD, such as lutein, fish oil, zinc, antioxidants, or some combination thereof. This trial combines most of these supplements at easily attainable dose levels. The outcome--a halting of progression and the beginnings of a reversal--give healthcare practitioners a potential treatment plan from which to get started.

Interestingly, a standard control group was not part of the trial design not due to the cost, but rather because the independent review board determined that evidence supporting nutritional supplementation is now so strong that the standard of care demands some nutritional supplementation.

Published: Cangemi FE. TOZAL study: an open case control study of an oral antioxidant and omega-3 supplement for dry AMD. BMC Ophthalmology 2007;7:3-12.

Author: Steve Austin, N.D.

56. Taurine (2016, 2017) Protects the Retina
Learn more about macular degeneration.

2017

Taurine is abundant in the retina, as well as in the brain, heart and reproductive organs. It has anti-inflammatory capacity and is a potent antioxidant. It is the most common amino acid in the fetal brain, and is the second most common amino acid in the adult brain. It is most abundant in those parts of the body which respond to electrical stimulation.¹ The retina's role is to electro-chemically transmit information from the world to the brain.

Taurine falls into the category of compounds known as osmolytes. Osmolytes affect osmosis - the ability of solutions in a cell or surrounding fluid to cross into or out of cells. When cells are exposed to ultraviolet radiation the retina responds by accumulating osmolytes.

Researchers were interested to find out whether the osmolyte taurine could protect the ganglion (nerve) cells in the retina from damage by ultraviolet B radiation.

The scientists were able to gauge the amount of cell death under the influence of ultraviolet B radiation by measuring taurine osmolyte changes which occur naturally to protect the retinal cells.

They found that taurine was 'remarkably' able to prevent cell death caused by UVB radiation.

Researchers: W. Dayang, P. Dongbo,
Published: Taurine prevents ultraviolet B induced apoptosis in retinal ganglion cells, Cutaneous and Ocular Toxicology, June, 2017.

2016

About Taurine

This article includes an overview of the data and research on taurine, particular with respect to its neuroendocrine effects. They provide a background on its structure, mechanics of metabolism, effects and therapeutic potential.

They report that taurine has broad anti-inflammatory capacity and has been effective in treating a number of conditions, ranging from heart failure to diabetes, and that it appears to protect against damage from alcohol and a variety of toxins.

The structure of taurine, different from other essential amino acids, means that it is not tied to proteins but is free-floating within cells and ready and is recognized as a neuromodulator with many roles.

The levels of taurine are greatest in cells that respond to electrical stimulation. This includes the central nervous system, the retina, the heart. It is also found in large quantities in the pineal bland and pituitary gland. It is the second most abundant amino acid in the adult brain.

Taurine is known to help regulate nerve cell activity as an agonist (bio-chemical that causes actions). Little is known about its action on the human sympathetic nervous system (which stimulates the flight or fight response). Its effect on hormonal secretions is also little known.

What is well known, however, is that it is an excellent and potent antioxidant which fights free radicals and protects the brain (and the retina) against oxidative stress. Oxidative stress is now recognized by scientists to be a major cause of most eye disease.²
Healthy elderly patients (older than 61) are found to have up to a 49% decrease in taurine levels compared to younger healthy people. Taurine deficiencies are noted in a wide range of disease of bone, blood, CNS, circulation, heart, digestion, and, of course, the retina.

It may be a preventative for retinal and macular conditions, conditions involving cognitive capacity and other neuro-physical conditions.

Authors: J. Caine, MD, T. Geracioti, MD
Published: Taurine, energy drinks, and neuroendocrine effects, Cleveland Clinic Journal of Medicine, December, 2016.

Photoreceptor Protection

Taurine deficiency is known to damage photoreceptors, causing retinal ganglion (nerve cell) damage and death. The photoreceptors are comprised of rod and cone cells. The cone cells are responsible for color vision and work best in bright light. This study looked at the results of taurine depletion on two types of cone cells.

The retinas of one group of lab animals with taurine depletion were examined. The researchers found marked reductions in blood levels of taurine associated with strong impairment to visual function. The retinas of the taurine-deficient group were thinner, both types of cone cells were affected; cones detecting blue and blue-violet light were more severely impacted. There was marked retinal ganglion loss in both types of cone cells.

Researchers: W. Hadj-Said, N. Froger, et al,
Investigations in Ophthalmology and Visual Science, September, 2016.

1998

Researchers reported that taurine deficiency contributed to deterioration of the retina and that supplementation with taurine has been somewhat successful in treating and preventing retinal changes.

Published: Alternative Medicine Review, April 1998;
Oftalmol Zh, 1989
Brain Research Reviews, May-August, 1991; Journal of Neuroscience Research, 1987.

Footnotes

1. Taurine, energy drinks and neuroendocrine effects, Cleveland Clinic Journal of Medicine, 2016.
2. See Antioxidants and Eye Disease.

57. Taurine (2017, 2014) Reduces Inflammation
Learn more about treatment options for macular degeneration.

2017

Researchers recognize that taurine is widely understood to be a potential therapy for chronic inflammation disorders. This is of interest to vision professionals since inflammation from oxidative stress is one cause of many eye diseases.

In this study scientists were evaluating the effects of taurine on biochemicals called cytokines which promote inflammation as well as other markers of inflammation-related imbalances. They examined mast cells (a type of white blood cell derived from stem cells) which were reacting to a specific type of allergic reaction.

They found that, in a dose related manner, taurine was able to inhibit the production and activity of pro-inflammatory cytokines. And in animal testing they found similar results in that animals were much less affected by allergens.

Researchers: S. Kim, H. Kim, et al
Published: The potential protective role of taurine against experimental allergic inflammation, Life Science, September, 2017.

2014

When the body experiences inflammation as a result of oxidative stress, trauma, exposure to toxins, etc, taurine is part of the response mechanism to try to reduce the negative effects of inflammation. This is important in vision care because scientists increasingly understand that inflammation is a major contributing cause to many, if not most, eye diseases.

When some part of the body becomes inflamed - whether it is the retina in eye conditions, the blood vessels in circulatory problems, the joints in arthritic conditions, taurine undergoes a biochemical change to lessen damage from inflammation.

Upon inflammation taurine is converted to taurine chloramine and taurine bromamine. Taurine chloramin increases the action of antioxidants to protect cell tissue from damage. At the same time it inhibits the creation of cytokines and free radicals that cause inflammation.

Researchers: C. Kim, Y.N. Cha,
Published: Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects, Amino Acids, January, 2014.

58. Vitamin D3 (2007, 11, 12, 15) & macular degeneration
Learn more about macular degeneration recommendations.

2007
Researchers have found that low levels of vitamin D3 in the body are connected to an increase in the presence of macular degeneration. The researchers assessed consumption of milk, fish, and vitamin D supplements. Patients who consumed less milk had more risk of early macular degeneration. Patient who consumed less fish had more risk of advanced macular degeneration. Patients who did not drink milk but who took vitamin D supplements had less risk of early macular degeneration.

The researchers concluded that vitamin D likely helps prevent against macular degeneration but that more investigation is needed to verify these results.

Researchers: Parekh N, Chappell RJ, Millen AE, Albert DM, Mares JA.
Published: Association Between Vitamin D and Age-Related Macular Degeneration in the Third National Health and Nutrition Examination Survey, 1988 Through 1994. Arch Ophthalmol. May 2007;125: 661-669.

2011
Researchers furthered the research on vitamin D and macular degeneration risk factors in this study which reported that supplementation with vitamin D could lower AMD risk in women who were younger than age 75.

Researchers evaluated vitamin D in blood level data from over 1,300 women who were participants in the Women's Health Initiative Study. They found not only that vitamin D was helpful in women younger than 75, but that those women who included the most vitamin D in their diets had a 59% reduced risk of developing AMD compared to other women whose diets included the least amount of vitamin D. The vitamin D intake did not include D due to being in sunlight.

Researchers, Amy E. Millen, PhD, et al.
Published: Vitamin D and Macular Degeneration, Archives of Ophthalmology, 2011

2012

Researchers, noting that vitamin D3 supports the immune system, helps remove amyloid beta and generally protect vision, reported that the outer retina of the eye with a high metabolic demand requires adequate nutrition. Lab animals treated with vitamin D3 displayed marked reductions in inflammation, levels of amyloid beta, and retinal macrophage quantities. Macrophages are large cells that surround and remove waste materials. High levels of macrophages indicate accumulations of waste. Inflammation and accumulation of waste are risk factors for macular degeneration and the lab animals displayed significant improvements in vision.

Researchers: V. Lee, E. Rekhi, et al.

Published: Vitamin D rejuvenates aging eyes by reducing inflammation, clearing amyloid beta and improving visual function, Neurobiology of Aging, October, 2012.

2015
This study looked at the mechanics of vitamin D's beneficial influence on preventing AMD. Researchers have determined that genetic risk is strongly tied to development of macular degeneration due to the behavior of a specific gene variant causing an immune response to the presence of protein and fat build-ups in the eye resulting in inflammation and the growth of new blood vessels (angiogenic) that distort the macula.

Noting that vitamin D has anti-inflammation and anti-angiogenic capacities, they wanted to find out whether vitamin D would lessen the immune response to protein and fat (drusen). They reported that vitamin D deficiency does increase AMD risk, and that this risk is the greatest in those people with the greatest genetic risk.

Researchers: Amy E. Millen, et al.
Published: Association Between Vitamin D Status and Age-Related Macular Degeneration by Genetic Risk. JAMA Ophthalmology, 2015

59. Vitamins A, C, and E (1994) -Macular Degeneration
Learn more about macular degeneration treatment and information. Also see information on food sources for dietary nutrients.

Researchers investigated the relationship between consumption of carotenoids and vitamins A, C, and E, which have a positive impact on advanced age-related macular degeneration.

The study included 356 U.S. patients (ages 55-80) with advanced macular degeneration and 520 controls. Risk due to other factors, such as smoking was taken into account.

The researchers found that those who ate foods in the top 1/5th of amounts of carotenoids, (ie, lutein and zeaxanthin), had a 43% lower risk of age-related macular degeneration than those who took the least amounts. The vitamins did not have a statistically significant lowered risk, although the patients who got their vitamin C from foods rather than supplements had a slighter lower risk. Dark leafy greens were the most significant food in terms of lowering the risk of advanced macular degeneration.

Researchers: Johanna M. Seddon, et al
Published: Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group, Journal of the American Medical Association, November, 1994

60. Vitamins B6 & B12, folic acid (1991, 2009) - lower risk of macular degeneration
Learn more about macular degeneration recommendations

1991 In patients with macular degeneration where the fatty deposits known as drusen have become 'soft', a vitamin B6 deficiency was found. Drusen are associated with aging and are a few hard drusen are considered normal, but macular degeneration is associated with more soft drusen.

Researchers: B. Lane, et al., Annuals of the Meeting of the American College of Nutrition, 1991

2009 In the first rigorous trial to show a benefit against macular degeneration from the supplements folic acid and 2 B-vitamins. Researchers found that women who took the combination for several years had a significantly lower chance of developing the condition.

Women who took a combination of folic acid and vitamins B6 and B12 had a 35 percent to 40 percent lower risk of developing age-related macular degeneration compared to a matched control group of women who took a placebo.

The finding was unexpected. In the Women's Antioxidant & Folic Acid Cardiovascular Study the researchers had been evaluating the benefits of these nutrients on the risk for heart attacks and strokes in at-risk women.

The study included over 5,000 women who were 40 or older. Most of these women had not previously been diagnosed with macular degeneration. The women were given the vitamin B trio or placebo and tested at the beginning of the study period and again after an average of 7.3 years. At that time 55 cases of AMD had developed in the women who had been taking the B vitamins, and 82 cases in the placebo group.

These three B-vitamins, particularly folic acid, have been shown to reduce high levels of the naturally occurring compound, homocysteine. Research has implicated elevated plasma levels of homocysteine in the development of vascular diseases including choroidal neovascularization in exudative AMD.

Researchers: W.G. Christen, et al,
Published: Folic acid plus B-vitamins and age-related macular degeneration in a randomized trial in women. Archives of Internal Medicine, February, 2009.

61. Zeaxanthin ('03, '06, '10, 2011) and macular degeneration
Learn more about macular degeneration treatment and information and about food sources for zeaxanthin.

2011

A 2011 study confirms that vision is improved in the elderly with early macular degeneration by adding Zeaxanthin as a nutritional supplement. Zeaxanthin is a carotenoid.

The Zeaxanthin and Visual Function Study demonstrates that dietary Zeaxanthin improved vision, including improvement in night blindness and seeing fine detail.

The one year study involved elderly veterans who were given 8mg of Zeaxanthin daily. The researcher found improvement in the ability to drive at night, and an average improvement of 1.5 lines or 8.5 letters on an eye chart, and the disappearance of blind spots.

Some of the people were additionally given 9 mg of lutein daily.

Zeaxanthin and lutein are two carotenoids (part of a family of antioxidants that give fruits and vegetables their color) found in the retina and macula of the eye. Zeaxanthin protects the cones, or photoreceptors responsible for central vision, color perception, and fine detail.

Since the average daily diet in the U.S. does not include enough fresh fruits and vegetables, it is difficult, particularly for the elderly, to maintain healthy macular pigment levels to protect their vision.

Researchers: Stuart Richer, PhD, OD, et al
Published: Randomized, double-blind, placebo-controlled study of zeaxanthin and visual function in patients with atrophic age-related macular degeneration: the Zeaxanthin and Visual Function Study (ZVF) FDA IND #78, 973, Optometry, November, 2011

2010

An earlier study also found that zeaxanthin supplementation can increase the density of pigments in the macula pigment. The increased density helps protect the macula from the damage caused by blue light and sunlight.

Reference: The Zeaxanthin and Visual Function Study in Atrophic Age Related Macular Degeneration (ZVF-FDA IND #78,973) - MP and Foveal Shape Discrimination: S.P. Richer1, et al.

2006

One of the early studies on the effect of zeaxanthin levels in the blood and incidence of AMD found a very strong inverse association. Patients with high levels of zeaxanthin in their blood plasma had a 93% reduced risk of developing AMD compared to patients with low zeaxanthin levels. Further, the researchers reported that, globally, patients with high levels of lutein and zeaxanthin had a 79% reduced risk.

Previous research had investigated the benefits of lutein and zeaxanthin combined -- this study focused on zeaxanthin alone.

They also found a strong inverse relationship between nuclear cataract (only that type of cataract) and zeaxanthin levels. Those with high levels of zeaxanthin had a 75% lower chance of developing nuclear cataracts. In contrast, lutein levels were not associated with cataract risk.

The scientists pointed out that the rationale for the important role of zeaxanthin lies in the fact that in healthy eyes the proportion of zeaxanthin compared to lutein is much greater in the center of the retina - the macula. They also found that while both lutein and zeaxanthin protect against oxidative stress from UV light exposure, zeaxanthin appears to be a better protector.

Researchers: C. Delcourt, I. Carriere, et al,
Published: Plasma Lutein and Zeaxanthin and Other Carotenoids as Modifiable Risk factors for Age Related Maculopathy and Cataract: the POLA study, IOVS, June 2006.

2003

In another study scientists reported that patients with high blood plasma levels of zeaxanthin had a 50% reduced risk of developing macular degeneration compared to subjects with low levels. These findings were even more striking for the top 1/5th of the group whose natural Mediterranean diet provided them with higher levels of the nutrients daily. These findings were correct after adjusting for risk factors such as age and genetics.

Researchers: C. Gale, N, F. Hall, et al,
Published: Lutein and zeaxanthin status and risk of age-related macular degeneration, Investigative Ophtalmology and Visual Science, June, 2003.

62. Zinc & Vitamin E (1997, 1999) & Macular Degeneration
Learn more about macular degeneration.

1999

In a study of patients over 60, paired with a control group of over-60 adults, researchers evaluated some of the risk factors for macular degeneration. They found a marked connection between incidence of AMD and low blood plasma levels of zinc and vitamin E. In addition they found that the lower the level of vitamin E, the greater the severity of AMD. They also validated that sun exposure causing UV damage was a factor in the severity and risk of AMD.

Researchers: Belda, et al, Serum vitamin E levels negatively correlate with severity of age-related macular degeneration, Mechanisms of Aging and Development, March, 1999.

1997

In one study, researchers compared levels of vitamins A, C, E, carotinoid, zinc, selenium and b-FGF in 35 patients with macular degeneration with those of 66 controls. They found that zinc and vitamin E levels were markedly lower in the AMD group and concluded that subnormal blood plasma levels of zinc and vitamin E are correlated to development of macular degeneration.

Ishihara, et al, Antioxidants and angiogenetic factor associated with age-related macular degeneration (exudative type), Nippon Ganka Gakkai Zasshi, March, 1997

63. Zinc (1988, 1996, 2017) and Macular Degeneration
Learn more about zinc and macular degeneration.

The mineral zinc plays an important role in the bioavailability and behavior of certain zinc-dependent enzymes in the eye. Reseachers have found associations between low zinc levels and retinal and macular degradation.

2017

A review of the many studies and trials finds consensus in the understanding that low zinc levels are tied to retinal and macular problems and that supplementation including zinc is associated with slowing the advance of the condition.

While antioxidant supplementation has beneficial results for some people, and omega-3 supplementation needs to be further researchers, the benefit from supplementing with C, E, beta-carotene and zinc is now known. Genetic factors may affect the benefit of the other nutrients.

The AREDS study in 2001 first identified the relationship between zinc levels and AMD. The study participants were followed over the course of many years and zinc alone or in combination with antioxidants slowed the progression of advanced AMD.

Results from AREDS2 in 2006 confirmed zinc's importance and substituted lutein and zeaxanthin for beta-carotene.

Like antioxidants, zinc is very much present in the retina, especially in the macula.

Seafood and meat products generally supply enough zinc for the diet (recommended 11mg/day for men and 8mg/day for women). It is present in beans, grains and nuts, but absorption is poor and the body does not store zinc effectively. High doses of zinc interfere with copper absorption, so the AREDs formulation includes 2 mg/day of copper.

Zinc apparently operates by contributing to the beneficial action of many enzymes in the eye and helps to suppress inflammation.

Reviewers: A. Carneiro and J.P. Andrade,
Published: Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review, Oxidative Medicine and Cellular Longevity, January, 2017.

1996

That zinc deficiencies contribute to retina/macular deterioration was one of the results from the data collected by the large Beaver Dam study which was published in 1996. The Beaver Dam study was a longitudinal study over ten years that investigated the dietary and other habits of nearly 5000 patients with macular degeneration.

Researchers: J.A. Mares Perlman, et al.

Published: Association of zinc and antioxidant nutrients with age-related maculopathy. Archives of Ophthalmology, August, 1996

1988

Researchers investing the effect of supplementation with zinc in macular degeneration patients found that the patients receiving zinc had markedly less loss of vision.

Researchers: D.A. Newsome, et al, Louisiana State University

Published: Oral zinc in macular degeneration, Archives of Opthalmology, 1988.

Macular Hole

1. Hyaluronan (2009, 2014-2016) & Macular Holes
Learn more about macular holes
.
Several studies, taken together, suggest a connection between low levels of hyaluronan in the vitreous and incidence of macular hole.

2016

One of the causes of macular holes is retinal detachment.

In a small study researchers found that patients with retinal detachment have low levels of hyaluronan and increased activity of the enzyme hyaluronidase which degrades hyaluronan. They did also note that patients with macular holes, but no retinal detachment did not have the same low levels of hyaluronan.

Researchers: K. Kaprinis, et al,
Published: Decreased hyaluronan concentration during primary rhegmatogenous retinal detachment, European Journal of Ophthalmology, November, 2016.

Editor's Note: While there is not a direct connection between hyaluronan absence and incidence of macular hole, it is true that retinal detachment is considered one of the causes of macular holes. We feel that macular holes may be caused by a number of imbalances and hyaluronan absence may be one of these contributing factors.

2014

There is a close relationship between the health of the structure of the vitreous (the gel-containing center sphere of the eye) and the formation of macular holes. Researchers note that when the vitreous degrades macular holes form.

In one study researchers found that the structure of the vitreous is weakened when vitreous tissue is submerged in enzymes that cause hyaluronic acid (and other macro-molecules) to deteriorate. In other words, the destruction of hyaluronic acid in the vitreous body weakens the structure of the vitreous. Following such submersion the vitreous structure contained significantly less hyaluronic acid.

Their conclusion was that the macromolecule hyaluronan acts synergistically with collagen and proteoglycans to support vitreous health.

Researchers: B.A. Filas, Q. Zhang, et al,
Published: Enzymatic degradation identifies components responsible for the structural properties of the vitreous body, Investigative Ophthalmology & Visual Science, January, 2014.

2009

During surgery for 26 patients with macular holes and 52 patients with diabetic retinopathy, doctors collected samples of the vitreous fluid. Upon analysis they found that in all of the macular hole patients and in half of the diabetic retinopathy patients the hyaluronan levels were signficantly lower the older the patient. They also found that after surgery high-molecular hyaluronan levels appeared to not increase in the vitreous fluid following surgery.

Researchers: H. Itakura, S. Kishi, et al
Published: Decreased vitreal hyaluronan levels with aging, Ophthalmologica, October, 2009.

Editor's Note: Hyaluronic acid or substances containing large amounts of hyaluronic are commonly used in surgery to repair macular holes due to their protective value.^{1, 2}

1. M. Hirano, et al, Case report: successful closure of a large macular hole secondary to uveitis using the inverted internal limiting membrane flap technique, BMC Ophthalmology, July, 2015.
2. M. F. Abdelkader, H.M. Moharram, Internal Limiting Membrane Closure of Idiopathic Macular Hole, Journal of Clinical & Experimental Ophthalmology, 2015.

2. Lutein, Zeaxanthin & Meso-Zeaxanthin (2016) & Macular Holes
Learn more about macular holes.

Macular Pigment

Researchers investigated the relationship between the thickness of pigmented layer (macular pigment optical density (MPOD)) in the eye, known as macular pigment and macular holes. This is accomplished by means of fluorescence scanning in which light wavelengths are utilized to identify the thickness/density of the macular pigment. The researchers found that the thinner the overall layer of pigment, the more frequent the incidence of macular holes.

Researchers: L. Sauer, S. Peters, et al.,
Published: Monitoring macular pigment changes in macular holes using fluorescence lifetime imaging ophthalmoscopy, Acta Ophthalmologica, October, 2016.

Antioxidants and Macular Pigment

2016

Researchers find that lutein and zeaxanthin that come from the consumption of red and orange vegetables and fruits are closely associated with the thickness of the macular pigment.

Reseachers: R. Estevez-Santiago, et.al.
Published: Lutein and zeaxanthin supplied by red/orange foods and fruits are more closely associated with macular pigment optical density than those from green vegetables in Spanish subjects, Nutritional Researcher, November, 2016.

Another study concurs with this finding. In a double-blind, placebo-based trial nearly 60 young men added one of the following antioxidant combinations to their diet for 12 months:

10mg lutein 1mg zeaxanthin, 1mg meso-zeaxanthin

20mg lutein, 2mg zeaxanthin, 2mg meso-zeaxanthin

placebo

The researchers were primarily investigating glare recovery vision but they did assess the macular pigment thickness/density at the beginning, at six months, and at the end of the one year period.

The macular pigment was found to have increased markedly in both of the groups receiving the antioxidants.

Researchers: J. M. Stringham, et. al.
Published: Macular carotenoid supplementation improves disability glare performance and dynamics of photostress recovery, Eye & Vision, November, 2016.

A long-term study of more than 200 patients with macular degeneration investigated the macular pigment optical density. Increases in pigment density correlated with supplementation with lutein.

Researchers: V. Meyer Zu Westrup, et. al,
Published: Changes of macular pigment optical density in elderly eyes: a longitudinal analysis from the MARS study, International Journal of Retina and Vitreous, June, 2016.

A third study links the macular pigment density with lutein and zeaxanthin intake. This study measured macular pigment in the macula in patients with AMD. Lutein and zeaxanthin were associated with greater MPOD closed to the center of the fovea area of the macula. Adding DHA to the diet increased MPOD to a wider area of the fovea.

Researchers: S. Fujimura, K. Ueda, et al.
Published: Preliminary analysis of the relationship between serum lutein and zeaxanthin levels and macular pigment optical density, Clinical Ophthalmology, October, 2016.

Editor's Note: Because the incidence of macular holes is associated with the thickness of the macular pigment, and because these antioxidants are associated with supporting macular pigment thickness, it may be reasonably concluded that supplementation with lutein, zeaxanthin and meso-zeaxanthin may help to reduce the risk and re-occurrence of macular holes.

Male Infertility

1. Diet (2016, 2017) & Male Infertility
Learn more about male infertility.

2017

Mediterranean Diet. Researchers investigated whether the Mediterranean diet would have a beneficial effect on male fertility/infertility. It was already known that diets high in vegetables, fruits, whole grains, and fish and decreasing diet components of meat and processed foods are good for overall health.

To find out whether this diet would be helpful researchers assessed the diets of 225 men, aged 26-55 at a fertility clinic. More than half of the men were overweight and more than 20% smoked cigarettes. Participants in the study completed a questionnaire about their diet. Instead of asking subjects to recall their diet this type of "food frequency questionnaire" provides a limited list of foods and drinks and the user notes which items they consume and how much/how often. This method produces information with which the researchers can accurately judge information from different people. The method uses a scoring technique known as the MedDietScore.

The researchers then divided the results into three DietMedScore groups: upper 1/3, middle 1/3 and lower 1/3 measuring how closely the diet resembled the Mediterranean diet.

They found that the men in the upper 1/3 range had the greatest sperm concentration, sperm count, sperm motility (movement), and sperm morphology (size and shape). Normal sperm have an oval head and long tail.

The men in the lowest 1/3 range had the lowest sperm concentration, sperm count, sperm motility, and abnormal sperm shape and size.

The research is not perfect because it represents a measurement taken at a single time rather than over a long period of time. Nonetheless the results substantiate earlier research on the same topic: that diets featuring whole grains, more fruits and vegetables and legumes produce better sperm quality.

Researchers: D. Karayiannis, M.D. Kontogianni, et al.
Published: Association between adherence to the Mediterranean diet and semen quality parameters in male partners of couples attempting fertility, Human Reproduction, January, 2017.

2016

BPA and Type of Dietary Fat. Researchers determined through lab animal testing that diets rich in butterfat and bisphenol A (BPA) damaged the quality of the animals' sperm.

Researchers investigated the effects of BPA, a known endocrine disruptor in combination with different diets. They gave lab animals BPA with diets including butterfat, high levels of butterfat or olive oil, all compared to with and without BPA.

They found that the animals receiving BPA, high butterfat diets, or BPA plus high butterfat diets had poor sperm-generating capacity. But the animals who received diets rich in olive oil or olive oil plus BPA did not have this problem.

Researchers: P. Tarapore, M. Hennessy, et al.
Published: High butter-fat diet and bisphenol A additively impair male rat spermatogenesis, Reproductive Toxicology, September, 2016.

Antioxidants & Low-Fat Diet. Researchers investigated lab animal sperm quality with respect to antioxidant consumption and calorie restriction in their diets.

Animals were fed for nearly three months on:

an uncontrolled diet,

a fat-restricted diet,

an uncontrolled diet with astaxanthin, vitamins E & C, or

an restricted diet with astaxanthin, vitamins E & C.

After three months the fourth group which was fed a low-fat diet with antioxidant supplementation had markedly better sperm count and better sperm motility.

Researchers: A. Vahidinia, A.R. Rahbar, et al.
Published: Journal of Dietary Supplements, May, 2016.

Vegetarian Diet. Loma Linda, California, inhabited mostly by vegetarians has been designated a blue zone based on the above average health of its population. In order to do a sperm quality study comparing a large number of vegetarians with a large number of non-vegetarians, scientists focused on the vegetarians living in Loma Linda.

Men following a strictly vegetarian diet, lacto-ovo, or vegan had the lowest sperm concentration, and motility.

Researchers: E.M. Orzylowska, J. D. Jacobson, et al.
Published: Food intake diet and sperm characteristics in a blue zone: a Loma Linda Study, European Journal of Obstetrics, Gynecology and Reproductive Biology, August, 2016.

Migraine Headaches

1. Butterbur (2012) & Migraine Headache
Learn more about treatment for migraine headaches.

Researchers used random, double-blind controlled reviews of a number of drug treatments for migraine headaches, and graded them according to US preventive agency standards. They also reviewed other published studies and got expert opinions for those drugs for which there were no controlled trials.

They found a number of products which can be effective, depending on the particular needs of any given patient. They looked at effectiveness, side effects, and other disorders that the patient might have. Based on their review, they gave strong recommendations to 4 herbal extracts, nutrients or supplements (butterbur, riboflavin, coenzyme Q10, and magnesium citrate) and 7 drugs (topiramate, propranolol, nadolol, metoprolol, amitriptyline, gabapentin, candesartan) which are used for other conditions such as angina, depression, epilepsy, and high blood pressure.
Published: Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1-59, Canadian Headache Society guideline for migraine prophylaxis. Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, Gladstone J, Becker WJ; Canadian Headache Society Prophylactic Guidelines Development Group.
Researchers: from University of Calgary and the Hotchkiss Brain Institute, Calgary, AB, Canada.

2. CoQ10 (2005) & Migraines
Learn more about migraine headaches.

Researchers have known that riboflavin behaves in a similar manner to coenzyme Q10 (CoQ10) and that it helps with migraines. In a double-blind, random, controlled study, researcher compared use of a placebo and CoQ10 in 42 migraine sufferers, and found that CoQ10 was effective. It helped with frequency of migraines, number of days that patients felt headaches and/or nausea. No problems were noted. The placebo helped 14.4% of patients, and CoQ10 helped 47.6% of patients.

Researchers: Sandor and associates, Headache and Pain Unit, Neurology Department, University Hospital Zurich, Frauenklinikstrasse 26, 8091 Zurich, Switzerland.

Published: Neurology. 2005 Feb 22;64(4):713-5. Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial. Sandor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L, Agosti RM, Schoenen J.

3. Migraine (2011): Review of Treatments
An article published in Headache Currents in 2011 details the research for treatment of migraine headaches.

Nutraceuticals - feverfew, vitamin B2 (riboflavin), magnesium, CoQ2, and alpha lipoic acid have been found effective to various degrees.

Behavioral therapies - biofeedback, relaxation training and cognitive behavioral therapy

Physical therapies - acupuncture, oxygen therapy

Read more about migraine therapy research including details of the above findings.

Researchers: Christina Sun-Edelstein, MD; Alexander Mauskop, MD

Published: Alternative Headache Treatments: Nutraceuticals, Behavioral and Physical Treatments, Headache Currents, March, 2011.

4. Migraine Headaches (2012) & Dry Eye Connection
Learn more about holistic treatment of migraine headaches and dry eyes.

Researchers have long suspected that there may be a connection between dry eyes and migraine headaches - this study investigates that tie by investigating the relationship between tear capacity and migraine symptoms in patients.

This study had the object of observing and comparing the symptoms of 33 patients who had migraines and 33 controls who had no migraines and no eye conditions. All of the patients were given a complete eye exam including a variety of test to validate or exclude dry eye conditions. Patients who had been experiencing migraines were identified as to whether or not they experienced migraine auras and the intensity of the pain they experienced based on a standard assessment test.

The researchers determined that 51% of the migraine patients had migraines with aura, 33% had no auras, and 15% had basilar migraine (a variation of migraine, mostly experienced by young people and sometimes including dizziness, ringing in the years, speech slurring, and severe headache).

There were distinct differences in the dry eye assessments and the researchers concluded that dry eye disease was significantly more likely to be seen in patients who also suffered from migraines. They thought that it is possible that some migraine headaches might be worsened by dry eye syndrome.

Published: Cornea. 2012 Jun 15, Dry Eyes and Migraines: Is There Really a Correlation? Koktekir BE, Celik G, Karalezli A, Kal A.

Researchers: Department of Ophthalmology, Faculty of Medicine, Selcuk University, Konya, Turkey Departments of Neurology Ophthalmology, School of Medicine, Baskent University, Ankara, Turkey.

5. Vitamin B2 (2004) and Migraine Headaches
Learn more about migraine headaches

These researchers wanted to evaluate the usefulness and effectiveness of vitamin B2 (also known as riboflavin) as a migraine headache preventative. The study they conducted was an open-label trial (ie, not blind or double-blind) in a clinic for outpatients. A baseline was established for patients with a history of migraine headaches, noting how often they'd been having attacks, how long they lasted, how strong they were, and what drugs had been used to counter the migraine attacks. The patients were given 400mg vitamin B2 daily and their reports of headaches were monitored at three and six months after the treatment began.

After both three months and again after six months, the frequency was lowered by 1/2 from about 4 days/monthly to 2 days/monthly. The use of other drugs (that had not worked well) was reduced from 7 a month to 4.5 a month.

However, the duration and strength of the headaches did not change very much.

Researchers: Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhaupl KM, Arnold G.

Published: Eur J Neurol. 2004 Jul;11(7):475-7. High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open study in a tertiary care centre.

Myopia (nearsightedness)

1. Myopia (2012) Increasing in Asian Children
Learn more about recommendations for myopia (nearsightedness).

The children of East Asian countries and cities are now under higher and higher pressure to do well in their education. As an consequence health issues related to a life dedicated to close-up work for vision are increasing. Myopia is now a major health concern now, to 80-90% of school graduates. The risk of glaucoma and other conditions that threaten sight is greater in patients with high myopia (10-20% of secondary school graduates).

This is a trend seen on other parts of the world as well. Increasing time spent indoors is associated with the higher incidence of myopia in educated populations.

Researchers: Prof Ian G Morgan PhD a b , Prof Kyoko Ohno-Matsui MD c, Prof Seang-Mei Saw PhD d e

Published: The Lancet, Volume 379, Issue 9827, 5/5/12.

2. Prevalence rate of nearsightedness in schoolchildren in rural Mongolia

Learn more about recommendations for myopia (nearsightedness)

The amount of myopia, or nearsightedness, among some young Asian populations is reportedly increasing to near epidemic proportions. But rural populations, such as rural Mongolia are emerging economies with limited eye care resources.

The purpose of this study was to define a level of nearsightedness for school-aged children in rural Mongolia. The total prevalence of nearsightedness (more than -0.5 D spherical equivalent) was 5.8%. Female students exhibited a significantly higher prevalence of nearsightedness in comparison to male students: 8% compared with 3%, respectively. The prevalence rate of nearsightedness in Mongolia is, so far, low in comparison to other Far Eastern countries.

Published: Optom Vis Sci. 2006 Jan;83(1):53-6.

3. Refractive status of indigenous people in the Amazon region of Brazil
This interesting study investigated the vision of the illiterate indigenous people of the upper Rio Negro region of the Amazon rain forest in northwestern Brazil.

Researchers studied the vision of 486 people, 259 of whom were indigenous people, between 12 and 59 years of age. The subjects were considered to be indigenous if there were at least three generations of indigenous ancestry with no folkloric suggestion of other ancestors.

Nearsightedness was rare among, only 2.7% of the indigenous subjects, had nearsightedness of -1.00 D or more and 1.6% (four people) had bilateral nearsightedness of -1.00 D or more.

Those 2.7% and 1.6% of the subjects with myopia were the only educated indigenous people examined. The other Brazilians included in the study had higher rates of nearsightedness (6.4% of eyes and 5.1% of subjects bilaterally). Of these, the older less-educated adults had a very low prevalence of nearsightedness (3.2% of eyes and 2.0% of subjects), whereas the younger, slightly educated Brazilians had a higher prevalence of Nearsightedness (11.3% of eyes and 9.7% of subjects).

The low amount of myopia in the illiterate indigenous people is consistent with other studies and suggests that myopia is related to literacy and all that comes with literacy. The generational change among the local mixed race Brazilians further supports this conclusion.

Published: Optom Vis Sci. 2005 Apr;82(4):267-72

Researchers: Thorn F, Cruz AA, Machado AJ, Carvalho RA.
New England College of Optometry, Boston, Massachusetts

4. Sunlight can help children avoid myopia: Aussie researchers 2009
Children should spend two to three hours a day outside to prevent them becoming short-sighted, says a study by the Australian Research Council Centre of Excellence in Vision Science.
A comparison of children of Chinese origin in Australia and Singapore, which has the highest rate of myopia in the world, found the only significant difference was the time spent outdoors.
Ian Morgan from the ARC Vision Centre yesterday said exposure to daylight appeared to play a critical role in limiting the growth of the eyeball, which is responsible for myopia or short-sightedness.
Professor Morgan said it had been apparent for a couple of hundred years that more educated people were short-sighted, but the research suggested spending some hours a day outdoors could counteract the myopic effects of study.
"Video games are as ineffective as reading on vision," he said. "Computers are pretty neutral, watching television doesn't seem to affect vision. The only difference we could find is the amount of time spent outdoors.
The research says about 30 per cent of six-year-olds in Singapore are short-sighted enough to need glasses, compared with only 3 per cent of Chinese-Australians.
Both groups spend the same amount of time studying, playing video games, watching television and reading books. But Singapore children spend an average 30 minutes a day outdoors compared with two hours in Australia.
Professor Morgan said similar trends were seen in India, with 5 per cent of rural-dwelling Indians being short-sighted compared with 10 per cent of their urban cousins and 65 per cent of those living in Singapore.
Myopia is increasing in urban areas around the world, and is described as an epidemic in parts of east Asia, with Singapore the world capital.
Australia has a level of myopia more commonly found in the Third World, with only 0.8 per cent of six-year-olds of European origin being short-sighted.
They spend on average three hours a day outdoors.

Night Blindness

1. Bilberry (2005) and Night Blindness
Learn more about night blindness

Researchers validated earlier studies that supplementation with bilberry fruit extract (Vaccinium myrtillus) can be helpful for night vision in people who are nearsighted. It should be noted that some studies do not find this result.

The intent of the study was find out whether earlier reports that bilberry had this beneficial effect were validated, and to measure the effect specifically on nearsightedness people. They 60 patient with either moderate or mild myopia were given either 100 mg of a bilberry extract (including 85% anthocyanosides) twice daily or a placebo over a 4 week period

The group receiving bilberry supplementation did in fact show much better improvement in eye symptoms than those receiving the placebo. It was found that those receiving bilberry also were increasingly sensitive to contract, an important component of good night vision. No night vision improvement was found in those receiving the placebo.

No side effects were found from taking the bilberry supplement.

Published: Puriﬁed high-dose anthocyanoside oligomer administration improves nocturnal vision and clinical symptoms in myopia subjects, British Journal of Nutrition (2005;93:895-9)

2. Taurine (1987) & Night Blindness
Learn more about support for night blindness.

Researchers have long known that taurine is necessary for proper functioning of the photoreceptor cells in the retina. The photoreceptors consist of cones, which work well in bright light, sense color and are responsible for most depth perception, and rods, which work well in dim light and do not support detection of shapes/sizes (depth perception) very well. The center of the retina is mostly cones, the edges are mostly rods.

Taurine helps damaged cells in the retina regenerate and is partially responsible for maintaining the integrity of the pigmented cells as well as the photoreceptors.

People with poor night vision, known as night blindness or nyctalopia cannot see well in dim light and have a hard time adapting to sudden changes in lighting.

Researchers have found in both in-vivo and in-vitro experiments that deficiencies in taurine are associated with weakness in both the structure and function of photoreceptor cells. While the protective mechanism of taurine is not clearly understood the connection is certainly there.

In in-vivo studies researchers reported that it is well established that photoreceptors are damaged when taurine deficiencies reach a critical level. This is measured by evaluating the bioelectrical response of the cells via an electroretinogram (ERG) which shows much lower activity on several kinds of electrical impulses measured. Accompanying this lowered response is the fact that photoreceptor membranes swell, become disorganized, and increasingly damaged as the deficiency continues.

Ryan J. Huxtable, et al, editors, The Biology of Taurine: Methods and Mechanisms, "Taurine and Photoreceptor Structure: Biochemical and Electrophysiological Studies," H. Pasantes-Morales, et al, Boston, MA Springer, 1987.

3. Trace Elements (2011) & Night Blindness
Learn more about night blindness.

Although night blindness is most often considered a side effect or symptom of other eye diseases in developed countries, in developing countries where childhood nutritional deficiencies are common vitamin A deficiency is associated with night blindness.

Knowing the vitamin A deficiency was the most direct cause of night blindness, the researchers wanted to evaluate deficiencies of trace elements in children who have night blindness.

They compared levels of zinc, coper and iron in the hair, blood and urine of children aged 3-12 with night blindness as compared to controls of matched age and gender who did not have night blindness.

They found that the children with night blindness had markedly lower levels of iron, zinc and copper in their hair and blood.¹

In a separate project, the researchers assessed levels of zinc, magnesium, calcium, potassium, sodium, arsenic, cadmium and lead in the blood, hair and urine of children aged 3 to 12 with matched controls who did not have night blindness.

The researchers found that arsenic, cadmium, sodium, and lead were markedly higher in the samples. These elements, of course, have a toxic effect on the body to begin with. The researchers found lower levels of zinc, calcium, potassium and magnesium in hair and blood, but higher levels of those elements in urine samples.²

1. H.I. Afridi, T.G. Kazi, et al., Evaluation of status of zinc, copper, and iron levels in biological samples of normal children and children with night blindness with age groups of 3-7 and 8-12 years., Biological Trace Element Research, September, 2011.
2. H.I. Afridi, T.G. Kazi, et al., Evaluation of essential trace and toxic elements in biological samples of normal and night blindness children of age groups 3-7 and 8-12 years, Biological Trace Element Research, October, 2011.

4. Vitamin A (2000, 2005) & Night Blindness
Learn more about night blindness.

2005

Previous research has demonstrated that vitamin A supplementation can reverse the effects of night blindness. In this study researchers wanted to evaluated whether a diet contained small amounts of vitamin A would also have a beneficial effect.

The researchers compared supplementing with vitamin A in food sources versus supplementing with vitamin A, measuring the results by evaluating both dark adaption and plasma (blood) retinol levels in Napali women who suffered from night blindness.

The women were divided into six groups, receiving various forms of vitamin A in vitamin A-fortified rice, retinyl palmitate, amaranth leaves, goat liver, or carrots. They were evaluated weekly via degree of pupil dilation and blood retinol levels. The groups were also compared to women who were not experiencing night blindness.

The researchers found that night blindness diminished most in the group receiving goat liver compared to the vitamin A-fortified rice group. The blood retinol level change was greater in those receiving retinyl palmitate and liver groups than in the vegetable groups, and greater in the group receiving goat liver than in the group receiving vitamin A-fortified rice.

The researchers concluded that all of the methods decreased night blindness, and those methods with better results were not significantly so. Both dietary vitamin A and vitamin A supplementation were effective.

Researchers: M. Haskell, P. Pandey, et al
Published: American Journal of Cliniical Nutrition, February, 2005

2000

Researchers examined the effectiveness of treating Napali women with vitamin A and beta-carotene supplements to counter the effects of night blindness, known to researchers as "dark-adaptation threshold."

298 pregnant women aged 15-45 who experienced varying degrees of night blindness were tested in a placebo-controlled study examining the benefits of supplementation with vitamin A and beta-carotene. Almost half of them were also tested three months after they gave birth. The results were compared to 100 similarly aged American women who were not pregnant. The degree of night blindness was evaluated by looking at the amount of light needed for the pupils of the eyes to constrict after suddenly being exposed to light. The effectiveness was also evaluated by measuring blood retinol concentrations.

The researchers found that the women who were give vitamin A performed better than those receiving a placebo. The American women had better natural night vision than did the Nepali women.

The researchers concluded that successful adaption to changes in light were closely tied to serum (blood) retinol levels and markedly improved with vitamin A supplementation.

Researchers: N. Congdon, M. Dreyfuss, et al
Published: Responsiveness of dark-adaptation threshold to vitamin A and beta-carotene supplementation in pregnant and lactating women in Nepal, American Journal of Clinical Nutrition, October, 2000

5. Zinc (2001) & Night Blindness
Learn more about night blindness.

It is known that vitamin A deficiency contributes to night blindness. It is especially a problem in developing nations where nutritional deficiencies may be common.

Researchers wanted to assess whether zinc played a role in night blindness or in the functioning of vitamin A. They examined about 200 women who were reporting night blindness during their pregnancies. They were divided, randomly, into six groups to receive specific nutrients for a three week period:

Vitamin A and placebo

Vitamin A and 25mg zinc

Beta-carotene (beta-carotene is a precursor to vitamin A)

Beta-carotene and 25mg zinc

Zinc and placebo

Two placebos

The women were assessed as to how well they could see in dim light, how well they could adapt to changes in light, and blood samples were taken at the beginning and at the conclusion of the study. Their use of the supplements and daily reportings of night blindness were taken at home by visiting medical professionals twice a week during the 3-week period.

They found that supplementing with zinc improved the levels of zinc in the blood, but did not, by itself improve night vision. Women receiving both zinc and vitamin A with previous low levels of zinc reported improvement in their night vision, reported four times as often as reported by the women receiving placebo. They also had a small improvement in how well they could see in dim light.

The researchers concluded that zinc may improve the effect of vitamin A in improving night blindness.

Researchers: P. Christian, S.K. Khatry, et al
Published: Zinc supplementation might potentiate the effect of vitamin A in restoring night vision in pregnant Nepalese women, American Journal of Clinical Nutrition, June, 2001.

Ocular Herpes

1. Eyebright (2014) & Corneal Cell Health
This 2014 in vitro study investigated the toxicity, free-radical fighting capacity and effect on the body's immune response of three extracts of eyebright (Euphrasia officinalis). The research found that the effects depending upon the concentration of eyebright and the type of solvent used in the extraction. These were tested on human cells from the cornea.

Three solvents were tested: heptane, ethanol, and ethyl acetate. The heptane extracts were toxic to the corneal cells and did not fight free radicals. All of the extracts had an anti-inflammatory effect.

Conclusion: The researchers found that the effects of eyebright were encouraging as an adjunct to eye care when extracts were from use of ethanol and ethyl acetate, but not heptane.

Researchers: Paduch R., et al, of several Universities in Lublin, Poland.

Published: Assessment of eyebright (euphrasia officinalis L.) extract activity in relation to human corneal cells using in vitro tests, Balkan Medical Journal, March, 2014.

Learn more about eyebright.

Optic Neuritis

1. Antioxidants (2007) and Optic Neuritis
Learn more about treatment options for swollen optic nerve.

There have been a number of studies suggesting that oxidative stress may be a factor in incidence of optic neuritis, a condition in which the optic nerve becomes swollen and inflamed. Most people recover but because the condition is one of the first symptoms of multiple sclerosis, researchers have been using lab animals with optic neuritis to test possible treatments for multiple sclerosis.

In one such study researchers looked at the degradation and loss of nerve cell axons, the long slender arms of nerve cells that connect to synapses with other nerve cells. Their focus was the effect of oxidative stress on the mitochondria, which are the energy sources within each cell.

Treatment for the condition was done by addressing oxidative stress. The scientists found that a particular ribozyme that suppressed proper gene expression was associated with myelin fiber injury even without inflammation. When this ribozyme was suppressed in turn lessening oxidative stress they observed that nerve fiber damage was reduced by over 50% and nerve ganglion loss was reduced four-fold.

This research suggests that reducing oxidative stress in the mitochondria may be a means of reducing deterioration of the optic nerve. Because antioxidants are known to reduce oxidative stress they may have a beneficial impact on optic neuritis.

Researchers: X. Qi, A.S. Lewis, et al
Published: Suppression of mitochondrial oxidative stress provides long-term neuroprotection in experimental optic neuritis, Investigations in Ophthalmology and Visual Science, February, 2007.

2. Blueberry (2015) Effect on Optic Neuritis
Learn more about optic neuritis.

Optic neuritis is a side effect or symptom of juvenile idiopathic arthritis (JA), an autoimmune condition affection children younger than 16. A compound known as etanercept is often used to treat this condition.

Researchers wanted to investigate non-harmful nutrients as possible primary treatments. They were investigating the effects of the natural remedies that reduce inflammation (one cause of optic neuritis) and so tested the combination blueberry juice and etanercept.

They divided 201 patients with JA into three random groups. The severity of their condition was measured using standardized tests. One group received etanercept, another received etanercept and 50ml blueberry juice daily, and another group received etanercept and a placebo juice.

Six months later the children were re-evaluated. The group receiving blueberry juice had significantly reduced or ceased side effects and symptoms. Blueberry juice modified measurable markers of severity or improvement.

Researchers: Y. Zong, et al,

Published: Blueberry Improves the Therapeutic Effect of Etanercept on Patients with Juvenile Idiopathic Arthritis: Phase III Study, Tohoku Journal of Experimental Medicine, October, 2015.

3. Gypenosides (2014) & Optic Neuritis
Learn more about support for the optic nerve support.

The cell death of nerve cells during an onset of optic neuritis can, untreated, lead to blindness. Inflammation and oxidative stress contribute to the damage caused by optic neuritis. Scientists have been researching the efficacy of a number of natural treatments, including gypenosides, the major component of Gynostemma pentaphyllum Makino, a chinese medicinal plant.

Because inflammation and oxidative stress are important factors in the conditions, researchers investigated the qualities of this gypenosides because it also supports the immune system, reduces inflammation, and fights oxidative stress caused by free radicals.

The researchers propose that the compound has potential neuroprotective and immune system supporting effects.

Researchers: K. Li, et al

Gypenosides might have neuroprotective and immunomodulatory effects on optic neuritis, Medical Hypotheses, May, 2014

4. Lipoic Acid (2011) & Optic Neuritis
Learn more about treatment options for optic neuritis.

Optic neuritis is a condition in which the optic nerve becomes inflammed and swollen, sometimes due to autoimmune conditions, inflammatory conditions, various infections or trauma. It is considered one of the first symptoms of development of multiple sclerosis.

Researchers have found that lipoic acid, which behaves like an antioxidant, is effective in treating lab animals who have a type of optic neuritis which is modeled to be similar to optic neuritis in human patients.

The researchers tested the effect of lipoic in both early and late suppression models, in other words, in incidences where the damage to the optic nerve was less or greater. The test mice received daily injections of either lipoic acid or sterile saline solution. The controls with early optic neuritis had about 14% damage to the optic nerve (as noted by viewing a microscopic cross section of the optic nerve), the test mice with early optic neuritis had about 2% damage - a marked improvement.

In the controls and mice in the late suppression model, the controls had almost 25% of the optic nerve damaged, while the test mice had only about 8% damage - again, a marked difference.

In addition the mice treated with lipoic acid had optic nerves with many fewer attached glycoproteins and leukocyte markers in both early and late models.

The researchers concluded that it will be worthwhile to investigate the effectiveness of lipoic acid in patients with acute optic neuritis.

Researchers: P. Chaudhary, G. Marracci, et al.
Published: Lipoic acid decreases inflammation and confers neuroprotection in experimental autoimmune optic neuritis, Journal of Neuroimmunology, April, 2011.

5. Micronutrient Deficiency (2014) & Optic Neuritis
Learn more about optic neuritis.

Researchers examined the micronutrient blood levels in 36 optic neuritis (ON) patients compared to 38 healthy controls. The patients were 18 to 63 years old, a third had a form of optic neuritis in which the myelin covering protecting the nerve is inflammed and degraded. Two thirds of the patients had isolated optic neuritis in which they've experienced a first attack involving a single lesion on the optic nerve. (Learn more about how MRI can assist in prognosis by determining the exact location of such a lesion.) All of the patients had retrobulbar neuritis (in which the back of the nerve is damaged).

The researchers used a technique known as atomic absorption spectroscopy to evaluate patients' concentrations of zinc, iron, copper and cadmium in the blood.

Results:
They found that cadmium elevations were higher and lower levels of iron in both of the ON groups compared to the control group. They found that the patients with demyelinated nerve cells had higher levels of copper and that there was insignificant difference in levels of zinc. Their conclusion was that the levels of these elements in blood may be tied to the process of inflammation which causes optic neuritis.

Researchers: K. Kaźmierczak, G. Malukiewic, H. Lesiewska-Junk, A. Laudencka, M. Szady-Grad, J. Klawe, and K. Nowicki

Published: Blood plasma levels of microelements in patients with history of optic neuritis, Current Eye Research, January, 2014 Jan;39(1):93-8
.

Osteoarthritis

1. Boswellia serrata (2011) & Osteoarthritis
Learn more about osteoarthritis.

The researchers treated 56 diagnosed with osteoarthritis who were divided into 2 groups. There was no placebo control group.

One group received boswellia in a capsule form, 6g daily, and the other received both the capsule form and also a cream containing boswellia.

After 2 months improvement in symptoms were observed in both groups, however the details are unknown.

Researchers: Gupta PK, Samarakoon SM, Chandola HM, Ravishankar B., Senior Medical Officer, Dehradun, Uttarakhand, India.

Published: Ayu. 2011 Oct;32(4):478-82.

Editor's Note: There is another study, Efficacy and tolerability of Boswellia serrata extract in treatment of osteoarthritis of knee--a randomized double blind placebo controlled trial. Phytomedicine. 2003 Jan;10(1):3-7. Tis was a small randomized, controlled cross-over, double-blind study on 30 patients over 8 weeks with beneficial results including reduced pain, better range of motion, reduced knee swelling, and the ability to walk greater distances.

2. Diet, Inflammation (2016) & Arthritis
Learn more about support for arthritis related conditions.

Researchers have reported that chronic inflammation in the body is a central cause of many health conditions, especially arthritis-related conditions.

The diet generally consumed by Westerners is high in red meat, high-fat dairy, refined sugars and grains and refined carbohydrates (as opposed to long-chain carbohydrates such as multi-grain cereal). The Mediterranean diet however, is high in whole grains, fish, vegetables (especially green vegetables) and fruit, along with low alcohol consumption and use of olive oil. This diet is associated with lower levels of inflammation in the body.

Researchers wanted to investigate the relationship between high inflammation levels in the body, indicated by the Dietary Inflammatory Index (DII) and premature mortality. Researchers investigated the diets and health of more than 8089 subjects to see whether such a relationship existed and to, in addition, see whether antioxidants would be helpful in reducing inflammation.

They conducted a random, placebo-controlled, double-blind study in which the subjects received low doses of antioxidants or a placebo over an eight year period. The subjects were aged 43 to 55 years old and their health was followed for an additional five years after the trial ended.

The subjects who had high inflammation levels had a higher death rate from heart disease or cancer compared to normal averages.

The subjects who received antioxidants did not have the same high death rate.

Researchers: L. Graffouillere, M. Deschausaux, et al.

Published: Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial, American Journal of Clinical Nutrition, March, 2016.

3. Glucosamine sulfate, Chondroitin Sulfate (2009) & Osteoarthritis
Learn more about osteoarthritis.

The trial is known as the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT, sponsored by NIH and was developed because controversy remains as to of the efficacy of glucosamine sulfate in the treatment of knee and hip osteoarthritis. this meta-study evaluated a number of studies on the effect of glucosamine and chondroitin sulfate formulations on development of the condition.

This trial compared a number of agents: a combination of glucosamine and chondroitin sulfates, and celecoxib; placebo; glucosamine hydrochloride; and chondroitin sulfate. The study was a double-blind 6 month study of patients with osteoarthritis in the knee. It found that glucosamine hydrochloride and chondroitin alone or in combination did not effectively reduce pain in knee osteoarthritis patients.

However the study did suggest that the combination of glucosamine hydrochloride and chondroitin sulfate may be helpful for those with moderate to severe osteoarthritis of the knee.

Editor's Note: glucosamine hydrochloride and glucosamine sulfate are both salts, but not the same.

The researchers pointed out that while in the past research had been based mostly on symptoms, newer research examines the capacity of glucosamine sulfate and chondroitin sulfate to change structure, possibly slightly offsetting the narrowing of joint space which gives rise to pain. They concluded that glucosamine sulfate, but not glucosamine hydrochloride, may have small to moderate effect on symptoms (debated by other researchers) but that there is compelling evidence that glucosamine sulfate and chondroitin sulfate may slow the progression of osteoarthritis.

Reseachers: Bruyere O, Reginster JY, WHO Collaborating Center for Public Health Aspect of Osteoarticular Disorders, University of Liege, Liege, Belgium

Published: Glucosamine and chondroitin sulfate as therapeutic agents for knee and hip osteoarthritis, Drugs Aging. 2007;24(7):573-80.

4. MSM (2012) & Osteoarthritis
Learn more about osteoarthritis.

Because MSM (methylsulfonylmethane) is commonly believed to relieve inflammation the researchers wanted to examine the effectiveness and safety of the ingredient.

In this animal model study, appropriately modeling human osteoarthritis, they looked at cartilage formation and break-down. For cartilage formation, rats and mice were give a control or one of several MSM containing diets. Consumption of the MSM ingredient did not affect cartilage growth and the weights of body, liver and spleen were markedly lower in one of the groups receiving MSM.

They did find that the MSM ingredient did significantly decrease cartilage deterioration - doing so more markedly the higher the dose.

They concluded that MSM did protect cartilage, but that intake of large amounts of MSM brought about atrophy of several organs.

Researchers: Ezaki J, Hashimoto M, Hosokawa Y, Ishimi Y., Department of Food Function and Labeling, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo, 162-8636, Japan.

Published: Assessment of safety and efficacy of methylsulfonylmethane on bone and knee joints in osteoarthritis animal model, J Bone Miner Metab. 2012 Aug 10.

5. Niacinamide (1996) & Osteoarthritis
Learn more about osteoarthritis.

This NIH study examined the effects of niacinamide (Vitamin B3) on osteoarthritis in a placebo-controlled, double-blind study.

The researchers looked at 72 OA patients who were given either niacinamide or placebo for 12 weeks. They assessed the results by measuring impact and pain, range of motion and flexibility of joints, sed rate, blood count, liver functioning, uric acid, cholesterol and fasting blood sugar.

Overall impact showed an improvement by 29% in the patients on niacinamide and got worse by 10% for those on the placebo. While pain levels did not change, the niacinamide patients were able to reduce their inflammation-lowering medications by 13%. Erythrocyte sed rate decreased by 22% and joint mobility improved by 4.5 degrees compared to the placebo group. There were some mild side effects in 40% of the niacinamide group.

The researchers concluded that niacinamide may have a role in treating OA and that further evaluation is warranted.

Jonas WB, Rapoza CP, Blair WF, Office of Alternative Medicine, National Institute of Health, Bethesda, MD 20892, USA.

The effect of niacinamide on osteoarthritis: a pilot study, Inflamm Res. 1996 Jul;45(7):330-4.

6. Olive Leaf Extract (2012, 2015, 2017) & Osteoarthritis
Learn more about osteoarthritis

2017

Many studies have determined that olive leaf extract is both anti-inflammatory and is a strong antioxidant. Researchers studies extracts of olive leaf as well as extracts of the same active component from olive oil.

Using human cartilage cells in a lab setting, scientists induced inflammation through application of large fat/sugar molecules. Resulting biochemical markers verified the presence of inflammation. They found that in these osteoarthritis models that the extract had a strong anti-inflammatory effect in a dose dependent manner.

Researchers: H. Nsir, M.A. Szychinska, et al,
Published: Polar and apolar extra virgin olive oil and leaf extracts as a promising anti-inflammatory natural treatment for osteoarthritis, Acta Histochemica, May, 2017.

2015

Researchers investigated the possible beneficial effect of consuming either oleuropein or the bioflavonoid rutin in animals with osteoarthritis.

In this study 60 guinea pigs were divided into four groups and received either a standard diet or a diet enriched with oleuropein, rutin, or rutin/curcumin. After 35 weeks the animals with the standard diets developed osteoarthritis lesions and inflammation as well as relevant biomarkers. Biomarkers are the presence of specific biochemicals known to be associated with specific symptoms or conditions.

The oleuropein and rutin with or without curcumin all reduced the osteoarthritis progression. In addition the combination of oleuropein and rutin suggested potential for future research.

Researchers: M.N. Horcajada, C. Sanchez, et al
Published: Oleuropein or rutin consumption decreases the spontaneous development of osteoarthritis in the Hartley guinea pig, Osteoarthritis and Cartilage, January 2015.

2012

Knowing that olive leaf extract has been found to reduce arthritis symptoms researchers wanted to see whether it was also effective for osteoarthritis and investigated both the reason it was effective and the mechanism.

Olive leaf extract is known to have both anti-inflammatory and antioxidant capacity. By testing mice with osteoarthritis in their paws scientists were able to determine that the benefit arose due to the strong anti-inflammatory mechanism.

They concluded that it may be beneficial for humans due to its anti-inflammation ability.

Researchers: D. Gong, C. Geng, et al
Published: Mechanisms of olive leaf extract-ameliorated rat arthritis caused by kaolin and carrageenan, Phytotherapy Research, March, 2012

Editor's Note: Similar results were found with respect to rheumatoid arthritis.

7. Osteoarthritis (2005): Glucosamine Sulfate and Ginger
Learn more about osteoarthritis recommendations

Studies show that for some people suffering from osteoarthritis, certain supplements can bring effective pain relief.

Osteoarthritis (OA) is a form of arthritis that causes painful inflammation of the joints and loss of cartilage, and can be particularly troublesome in relation to larger joints that support our body such as the knees and hips.

A 2005 study compared Celebrex to glucosamine and chondroitin sulfate supplements. These essential cartilage components, in supplement form, have been shown to slow and even reverse the degenerative effects of osteoarthritis. The researchers found that for cases of moderate to severe pain, the combination of glucosamine and chondroitin sulfate was comparable to the effectiveness of Celebrex.

A 2001 study showed that supplementing with ginger extract may effectively relieve some types of arthritis pain. Researchers tested 250 volunteers with osteoarthritis by giving them a ginger dietary supplement or a placebo. Two thirds of those given the ginger pills reported relief from pain significantly more than those taking the placebo.

Studies:

2005, presented at annual scientific meeting of the American College of Rheumatology (ACR), which was funded by the National Institutes of Health.

2001, published in the journal Osteoarthritis, Professor Altman of the University of Miami School of Medicine presented his findings to the British Medical Association in London.

8. Xtra Info: Osteoarthritis Research Bibliography
Also see osteoarthritis discussion

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Osteoporosis

1. Isoflavones, ('90s, 2010, 2016) & Osteoporosis
Learn more about osteoporosis.

2016

Researchers have been reporting that free radicals play an important role in bone loss resulting in osteoporosis. Although there has been some investigation into medicinal plants in the past for bone loss treatment, there is now renewed interest.

Researchers looked at medicinal plants known to have antioxidant effects that appear to protect from bone loss. With lab animals they tested a natural formula containing soy isoflavones, horsetail, lactoferrin and vitamin D3.

They evaluated PBMC blood cells and C2C12 muscle cells as well as bone density as expressed through the bone matrix. Bone consists of bone cells surrounded by matrix which is composed of collagen, inorganic salts and calcium carbonate.

The goal of the study was to look at the in-vitro and in-vivo (via diet) protection provided by the formula after a 3 week treatment with the formula. They reviewed a number of biomarkers for bone density. They noticed a significant improvement in the animals who'd received the treatment and in the in-vitro testing.

Reseachers: L. Menghini, C. Ferrante, et al
Published: A natural formula containing lactoferrin, Equisetum arvensis, soy isoflavones and vitamin D3 modulates bone remodeling and inflammatory markers in young and aged rats, Journal of Biological Regulators and Homeostatic Agents, October, 2016.

2010

The author reports that calcium loss as measured through urine excretion is greater in people who take in protein through animal protein compared to protein intake through soy protein. There is evidence that soy isoflavones may protect against bone loss. The direct cause and effect however has not been adequately studied.

The highest levels of isoflavones are found in soybeans, but they are also in other legumes. Fermentation, as in tofu, decreased the isoflavone level somewhat but they are more bioavailable in fermented foods.

Author: S. Bawa
Published: Journal of Osteoporois, March, 2010.
Here's the link to the full article which discusses the mechanics.

1999

The author identifies ipriflavone, an isoflavone derived from a soy isoflavone as being protective against bone loss due to a number of causes including steroid use, lack of activity, and various hormone changes.

Author: K.A. Head
Published: Ipriflavone: an important bone-building isoflavone, Alternative Medicine Review, February, 1999.

1998

Researchers evaluated the effects of soy protein containing isoflavones on blood chemistry and bone mineral density in nearly 70 older women with high-cholesterol. With respect to the bone density results they found that there was improvement in the lumbar spine at levels of 2.25 grams of isoflavone per gram of protein.

Researchers: S.M. Potter, et al, Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women, American Journal of Clinical Nutrition, December, 1998.

2. Vitamin D (2017) & Osteoporosis
Learn more about osteoporosis.

2017

Understanding that vitamin D is be helpful for patients with osteoporosis, researchers investigated use of vitamin D in patients who were receiving drug treatment (denosumab). They compared used of vitamin D and calcium with patients with both osteoporosis and rheumatoid arthritis.

Denosumab is a drug therapy for post-menopausal women with osteoporosis. It was approved for clinical use in 2010.¹ Osteoporosis is caused by an imbalance between the degree to which minerals are absorbed from bones into the body and minerals are formed in the bones resulting in a net loss.

The study was a 12 month look at patients with osteoporosis who also had rheumatoid arthritis, and who were taking denosumab compared to placebo. There were 21-22 people in each test group.

A number of standard testing was performed to measure the condition of bone structure including bone mineral density at both the lumbar part of the spine and the bone at the hips. Researchers also took into account other factors such as other biochemical markers, an overall health assessment, and an activity assessment.

Measurements were made at hip and lumbar were taken at the beginning of the study and every four months.

The researchers reported that compared to the denosumab-only group, the group receiving both vitamin D and calcium had substantial improvement. The improvement in the hip bone measurements was significant.

Researchers: Y. Nakamura, T. Suzuki, et al
Published: Vitamin D and Calcium Are Required during Denosumab Treatment in Osteoporosis with Rheumatoid Arthritis, Nutrients, April, 2017.

Footnote

1. M.R. McClung, Denosumab for the treatment of osteoporosis, Osteoporosis and Sarcopenia, March 2017.

3. Xtra Info: Osteoporosis Research Bibliography
Also see osteoporosis discussion.

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37. Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med 1994;330:387-92.
38. Chow R, Harrison JE, Notarius C. Effect of two randomised exercise programmes on bone mass of healthy postmenopausal women. Br Med J 1987;295:1441-4.
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40. Salamone LM, Cauley JA, Black DM, et al. Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. Am J Clin Nutr 1999;70:97-103.
41. Reid IR, Ames RW, Evans MC, et al. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Am J Med 1995;98:331-5.
42. Hosking DJ, Ross PD, Thompson DE, et al. Evidence that increased calcium intake does not prevent early postmenopausal bone loss. Clin Ther 1998;20:933-44.
43. Owusu W, Willett WC, Feskanich D, et al. Calcium intake and the incidence of forearm and hip fractures among men. J Nutr 1997;127:1782-7.
44. Rulm LA, Sakhaee K, Peterson R, et al. The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized, placebo-controlled study. Am J Ther 1999;6:303-11.
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53. Gennari C, Adami S, Agnusdei D, et al. Effect of chronic treatment with ipriflavone in postmenopausal women with low bone bass. Calcif Tissue Int 1997;61(Suppl 1):S19-22.
54. Gennari C, Agnusdei D, Crepaldi G, et al. Effect of ipriflavone- a synthetic derivative of natural isoflavones- on bone mass loss in the early years after menopause. Menopause 1998;5(1):9-15.
55. Ohta H, Komukai S, Makita K, et al. Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res 1999;51:178-83.
56. Melis GB, Paoletti AM, Bartolini R, et al. Ipriflavone and low doses of estrogens in the prevention of bone mineral loss in climacterium. Bone Miner 1992;19 (Suppl 1):S49-56.
57. Gambacciani M, Ciaponi M, Cappagli B, et al. Effects of combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women. Maturitas 1997;28:75-81.
58. Hanabayashi T, Imai A, Tamaya T. Effects of ipriflavone and estriol on postmenopausal osteoporotic changes. Int J Gynaecol Obstet 1995;51:63-4 [letter].
59. Alexandersen P, Toussaint A, Christiansen C, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA 2001;285:1482-88.
60. Brot C, Jorgensen N, Madsen OR, et al. Relationships between bone mineral density, serum vitamin D metabolites and calcium: phosphorus intake in healthy perimenopausal women. J Intern Med 1999;245:509-16.
61. Sahota O. Osteoporosis and the role of vitamin D and calcium-vitamin D deficiency, vitamin D insufficiency and vitamin D sufficiency. Age Ageing 2000;29:301-4.
62. Dawson-Hughes B, Dallal GE, Krall EA, et al. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med 1991;115:505-12.
63. Adams JS, Kantorovich V, Wu C, et al. Resolution of vitamin D insufficiency in osteopenic patients results in rapid recovery of bone mineral density. J Clin Endocrinol Metab 1999;84:2729-30.
64. Nordin BEC, Baker MR, Horsman A, Peacock M. A prospective trial of the effect of vitamin D supplementation on metacarpal bone loss in elderly women. Am J Clin Nutr 1985;42(3):470-4.
65. Lips P, Graafmans WC, Ooms ME, et al. Vitamin D supplementation and fracture incidence in elderly persons. Ann Intern Med 1996;124:400-6.
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67. Droisy R, Collette J, Chevallier T, et al. Effects of two 1-year calcium and vitamin D3 treatments on bone remodeling markers and femoral bone density in elderly women. Curr Ther Res 1998;59:850-62.
68. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327:1637-42.
69. Maki BE, Holliday PJ, Topper AK. A prospective study of postural balance and risk of falling in an ambulatory and independent elderly population. J Gerontol 1994;49:M72-84.
70. Pfeifer M, Begerow B, Minne HW, et al. Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Mineral Res 2000;15:1113-8.
71. Van Papendorp DH, Coetzer H, Kruger MC. Biochemical profile of osteoporotic patients on essential fatty acid supplementation. Nutr Res 1995;15:325-34.
72. Kruger MC, Coetzer H, de Winter R, et al. Calcium, gamma-linolenic acid and eicosapentaenoic acid supplementation in senile osteoporosis. Aging 1998;10:385-94.
73. Hart JP. Circulating vitamin K1 levels in fractured neck of femur. Lancet 1984;ii:283 [letter].
74. Tamatani M, Morimoto S, Nakajima M, et al. Decreased circulating levels of vitamin K and 25-hydroxyvitamin D in osteopenic elderly men. Metabolism 1998;47:195-9.
75. Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 1999;69:74-9.
76. Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 2000;71:1201-8.
77. Knapen MH, Hamulyak K, Vermeer C. The effect of vitamin K supplementation on circulating osteocalcin (Bone Gla protein) and urinary calcium excretion. Ann Intern Med 1989;111:1001-5.
78. Orimo H, Shiraki M, Fujita T, et al. Clinical evaluation of Menatetrenone in the treatment of involutional osteoporosis- a double-blind multicenter comparative study with 1-alpha-hydroxyvitamin D3. J Bone Mineral Res 1992;7(Suppl 1):S122.
79. Iwamoto I, Kosha S, Noguchi S, et al. A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy. Maturitas 1999;31:161-64.
80. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res 2000;15:515-21.
81. Craciun AM, Wolf J, Knapen MH, et al. Improved bone metabolism in female elite athletes after vitamin K supplementation. Int J Sports Med 1998;19:479-84.
82. Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 1999;69:74-9.
83. Cohen L, Laor A, Kitzes R. Magnesium malabsorption in postmenopausal osteoporosis. Magnesium 1983;2:139-43.
84. Cohen L, Kitzes R. Infrared spectroscopy and magnesium content of bone mineral in osteoporotic women. Isr J Med Sci 1981;17:1123-5.
85. Geinster JY, Strauss L, Deroisy R, et al. Preliminary report of decreased serum magnesium in postmenopausal osteoporosis. Magnesium 1989;8:106-9.
86. Dimai HP, Porta S, Wirnsberger G, et al. Daily oral magnesium supplementation suppresses bone turnover in young adult males. J Clin Endocrinol Metab 1998;83:2742-8.
87. Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnesium Res 1993;6:155-63.
88. Abraham GE, Grewal H. A total dietary program emphasizing magnesium instead of calcium. J Reprod Med 1990;35:503-7.
89. Sahap AO. Zinc and senile osteoporosis. J Am Geriatr Soc 1983;31:790-1.
90. Relea P, Revilla M, Ripoll E, et al. Zinc, biochemical markers of nutrition, and type I osteoporosis. Age Ageing 1995; 24:303-7.
91. Elmstahl S, Gullberg B, Janzon L, et al. Increased incidence of fractures in middle-aged and elderly men with low intakes of phosphorus and zinc. Osteoporos Int 1998;8:333-40.
92. Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr 1994;124:1060-4.
93. Eaton-Evans J, McIlrath EM, Jackson WE, et al. Copper supplementation and bone-mineral density in middle-aged women. Proc Nutr Soc 1995;54:191A.v 94. Baker A, Turley E, Bonham MP, et al. No effect of copper supplementation on biochemical markers of bone metabolism in healthy adults. Br J Nutr 1999;82:283-90.
95. Nielson FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J 1987;1:394-7.
96. Meacham SL, Taper LJ, Volpe SL. Effect of boron supplementation on blood and urinary calcium, magnesium, and phosphorus, and urinary boron in athletic and sedentary women. Am J Clin Nutr 1995;61:341-5.
97. Hunt CD, Herbel JL, Nielsen FH. Metabolic responses of postmenopausal women to supplemental dietary boron and aluminum during usual and low magnesium intake: boron, calcium, and magnesium absorption and retention and blood mineral concentrations. Am J Clin Nutr 1997;65:803-13.
98. Nielson FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J 1987;1:394-7.
99. Gold M. Basketball bones. Science 1980;80:101-2.
100. Raloff J. Reasons for boning up on manganese. Science News 1986;Sep 27:199 [review].
101. Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr 1994;124:1060-4.
102. Carlisle EM. Silicon localization and calcification in developing bone. Fed Proc 1969;28:374.
103. Hott M, de Pollak C, Modrowski D, Marie PJ. Short-term effects of organic silicon on trabecular bone in mature ovariectomized rats. Calcif Tissue Int 1993;53:174-9.
104. Eisinger J, Clairet D. Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: a retrospective study. Magnes Res 1993;6:247-9.
105. Ferrari S, Zolezzi C, Savarino L, et al. The oral strontium load test in the assessment of intestinal calcium absorption. Minerva Med 1993;84:527-31.
106. McCaslin FE, Janes JM. The effect of strontium lactate in the treatment of osteoporosis. Proc Staff Meetings Mayo Clinic 1959;34(13):329-34.
107. Skoryna SC. Effects of oral supplementation with stable strontium. Can Med Assoc J 1981;125:703-12.
108. Gaby AR. Preventing and Reversing Osteoporosis. Rocklin, CA: Prima Publishing, 1994, 88-9 [review].
109. Gaby AR. Preventing and Reversing Osteoporosis. Rocklin, CA: Prima Publishing, 1994, 88-9 [review].
110. Prior JC. Progesterone as a bone-trophic hormone. Endocr Rev 1990;11:386-98.
111. Lee JR. Osteoporosis reversal: the role of progesterone. Int Clin Nutr Rev 1990;10:384-91.
112. Riis BJ, Thomsen K, Strom V, Christiansen C. The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss. Am J Obstet Gynecol 1987;156:61-5.
113. Leonetti HB, Longo S, Anasti JM. Transdermal progesterone cream for vasomotor symptoms and postmenopausal bone loss. Obstet Gynecol 1999;94:225-8.
114. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 2000;53:561-8.
115. Kadota S, Li JX, Li HY, et al. Effects of cimicifugae rhizome on serum calcium and phosphate levels in low calcium dietary rats and on bone mineral density in ovariectomized rats. Phytomed 1996/97;3(4):379-85.

Peptic Ulcers

1. Xtra Info: Stomach Ulcers Bibliography - early research
Also see the discussion of ulcers.

1. Katchinski BD, Logan RFA, Edmond M, Langman MJS. Duodenal ulcer and refined carbohydrate intake: a case-control study assessing dietary fiber and refined sugar intake. Gut 1990;31:993-6.
2. Suadicani P, Hein HO, Gyntelberg F. Genetic and life-style determinants of peptic ulcer. A study of 3387 men aged 54 to 74 years: The Copenhagen Male Study. Scand J Gastroenterol 1999;34:12-7.
3. Yudkin J. Eating and ulcers. BMJ 1980;Feb 16:483 [letter].
4. Sonnenberg A. Dietary salt and gastric ulcer. Gut 1986;27:1138-42.
5. Cheney G. Rapid healing of peptic ulcers in patients receiving fresh cabbage juice. Cal Med 1949;70:10.
6. Doll R, Pygott F. Clinical trial of Robaden and of cabbage juice in the treatment of gastric ulcer. Lancet 1954;2:1200.
7. Thaly H. A new therapy of peptic ulcer: The anti-ulcer factor of cabbage. Gaz Med Fr 1965;72:1992-3.
8. Dunaevskii GA, Migonova DK, Rozka IM, Chibisova SM. Value of preserved juice of white cabbage in the complex therapy of peptic ulcer. Vopr Pitan 1970;29:29-33.
9. Noess K. Ulcer-fiber-cabbage and vitamin U. Tidsskr Nor Laegeforen 1986;106:693-4.
10. Grimes DS, Goddard J. Gastric emptying of wholemeal and white bread. Gut 1977;18:725-9.
11. Rydning A, Berstad A, Aadland E, Odegaard B. Prophylactic effect of dietary fiber in duodenal ulcer disease. Lancet 1982;2(8301):736-9.
12. Rydning A, Berstad A. Fiber diet and antacids in the short-term treatment of duodenal ulcer. Scand J Gastroenterol 1985;20:1078-82.
13. Kern RA, Stewart G. Allergy in duodenal ulcer: incidence and significance of food hypersensitivities as observed in 32 patients. J Allergy 1931;3:51.
14. Reimann HJ, Lewin J. Gastric mucosal reactions in patients with food allergy. Am J Gastroenterol 1988;83:1212-9.
15. Allison MC, Howatson AG, Caroline MG, et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs. N Engl J Med 1992;327:749-54.
16. Lenz HJ, Ferrari-Taylor J, Isenberg JI. Wine and five percent ethanol are potent stimulants of gastric acid secretion in humans. Gastroenterology 1983;85:1082-7.
17. Cohen S, Booth GH Jr. Gastric acid secretion and lower-esophageal-sphincter pressure in response to coffee and caffeine. N Engl J Med 1975;293:897-9.
18. Feldman EJ, Isenberg JI, Grossman MI. Gastric acid and gastrin response to decaffeinated coffee and a peptone meal. JAMA 1981;246:248-50.
19. Dubey P, Sundram KR, Nundy S. Effect of tea on gastric acid secretion. Dig Dis Sci 1984;29:202-6.
20. Korman MG, Hansky J, Eaves ER, Schmidt GT. Influence of cigarette smoking on healing and relapse in duodenal ulcer disease. Gastroenterology 1983;85:871-4.
21. Patty I, Benedek S, Deak G, et al. Controlled trial of vitamin A therapy in gastric ulcer. Lancet 1982;2(8303):876 [letter].
22. Patty I, Tarnok F, Simon L, et al. A comparative dynamic study of the effectiveness of gastric cytoprotection by vitamin A, De-Nol, sucralfate and ulcer healing by pirenzepine in patients with chronic gastric ulcer (a multi-clinical and randomized study). Acta Physiol Hung 1984;64:379-84.
23. Pfeiffer CJ, Cho CH, Cheema A, Saltman D. Reserpine-induced gastric ulcers: protection by lysosomal stabilization due to zinc. Eur J Pharmacol 1980;61:347-53.
24. Jimenez E, Bosch F, Galmes JL, Banos JE. Meta-analysis of efficacy of zinc acexamate in peptic ulcer. Digestion 1992;51:18-26.
25. Frommer DJ. The healing of gastric ulcers by zinc sulphate. Med J Aust 1975;2:793-6.
26. Nishiwaki H, Kato S, Sugamoto S, et al. Ulcerogenic and healing impairing actions of monochloramine in rat stomachs: effects of zinc L-carnosine, polaprezinc. J Physiol Pharmacol 1999;50:183-95.
27. Arakawa T, Satoh H, Nakamura A, et al. Effects of zinc L-carnosine on gastric mucosal and cell damage caused by ethanol in rats. Correlation with endogenous prostaglandin E2. Dig Dis Sci 1990;35:559-66.
28. Cho CH, Ogle CW. A correlative study of the antiulcer effects of zinc sulphate in stressed rats. Eur J Pharmacol 1978;48:97-105.
29. Frommer DJ. The healing of gastric ulcers by zinc sulphate. Med J Aust 1975;2:793-6.
30. Kashimura H, Suzuki K, Hassan M, et al. Polaprezinc, a mucosal protective agent, in combination with lansoprazole, amoxicillin, and clarithromycin increases the cure rate of Helicobacter pylori infection. Aliment Pharmacol Ther 1999;13(4):483-7.
31. Shive W, Snider RN, DuBilier B, et al. Glutamine in treatment of peptic ulcer. Texas State J Med 1957;Nov:840.
32. Yan R, Sun Y, Sun R. Early enteral feeding and supplement of glutamine prevent occurrence of stress ulcer following severe thermal injury. Chung Hwa Cheng Hsing Shao Shang Wai Ko Tsa Chih 1995;11:189-92.
33. Salim AS. The relationship between Helicobacter pylori and oxygen-derived free radicals in the mechanism of duodenal ulceration. Internal Med 1993;32:359-64.
34. Salim AS. Allopurinol and dimethyl sulfoxide improve treatment outcomes in smokers with peptic ulcer disease. J Lab Clin Med 1992;119:702-9.
35. Goso Y, Ogata Y, Ishihara K, Hotta K. Effects of traditional herbal medicine on gastric mucin against ethanol-induced gastric injury in rats. Comp Biochem Physiol 1996;113C:17-21.
36. Beil W, Birkholz W, Sewing KF. Effects of flavonoids on parietal cell acid secretion, gastric mucosal prostaglandin production and Helicobacter pylori growth. Arzneimittelforschung 1995;45:697-700.
37. Brogden RN, Speight TM, Avery GS. Deglycyrrhizinated licorice: A report of its pharmacological properties and therapeutic efficacy. Drugs 1974;8:330-9.
38. D'imperio N, Piccari GG, Sarti F, et al. Double blind trial in duodenal and gastric ulcers. Cimetidine and deglycyrrhizinized liquorice. Acta Gastro-Enterologica Belgica 1978;41:427-34.
39. Morgan AG, Pacsoo C, McAdam WAF. Maintenance therapy: a two year comparison between Caved-S and cimetidine treatment in the prevention of symptomatic gastric ulcer recurrence. Gut 1985;26:599-602.
40. Bardhan KD, Cumberland DC, Dixon RA, Holdsworth CD. Clinical trial of deglycyrrhizinized liquorice in gastric ulcer. Gut 1978;19:779-82.
41. Gaby AR. Deglycyrrhizinated licorice treatment of peptic ulcer. Townsend Letter for Doctors 1988;July:306 [editorial/review].
42. Al-Said MS, Ageel AM, Parmar NS, Tariq M. Evaluation of mastic, a crude drug obtained from Pistacia lentiscus for gastric and duodenal anti-ulcer activity. J Ethnopharmacol 1986;15:271-8.
43. Huwez FU, Al-Habbal MJ. Mastic in treatment of benign gastric ulcers. Gastroenterol Japon 1986;21:273-4.
44. Huwez FU, Thirlwell D, Cockayne A, Ala'Aldeen DA. Mastic gum kills Helicobacter pylori. New Engl J Med 1998;339:1946 [letter].
45. Hills BA, Kirwood CA. Surfactant approach to the gastric mucosal barrier: Protection of rats by banana even when acidified. Gastroenterology 1989;97:294-303.
46. Sikka KK, Singhai CM, Vajpcyi GN. Efficacy of dried raw banana powder in the healing of peptic ulcer. J Assoc Phys India 1988;36(1):65 [abstract].
47. Beil W, Birkholz C, Sewing KF. Effects of flavonoids on parietal cell acid secretion, gastric mucosal prostaglandin production and Helicobacter pylori growth. Arzneimittelforschung 1995;45:697-700.
48. Sivam GP, Lampe JW, Ulness B, et al. Helicobacter pylori--in vitro susceptibility to garlic (Allium sativum) extract. Nutr Cancer 1997;27:118-21.
49. Chung JG, Chen GW, Wu LT, et al. Effects of garlic compounds diallyl sulfide and diallyl disulfide on arylamine N-acetyltransferase activity in strains of Helicobacter pylori from peptic ulcer patients. Am J Chin Med 1998;26:353-64.
50. Ernst E. Is garlic an effective treatment for Helicobacter pylori infection? Arch Intern Med 1999;159:2484-5 [letter].
51. Graham DY, Anderson SY, Lang T. Garlic or jalapeno peppers for treatment of Helicobacter pylori infection. Am J Gastroenterol 1999;94:1200-2.
52. Chang HM, But PPH. Pharmacology and Applications of Chinese Materia Medica vol 1. Singapore: World Scientific Inc., 1986, 521.
53. Mills SY. Out of the Earth: The Essential Book of Herbal Medicine. New York: Viking Arkana, 1991, 544-7.
54. Weiss RF. Herbal Medicine. Gothenburg, Sweden: Ab Arcanum and Beaconsfield, UK: Beaconsfield Publishers Ltd, 1988, 334-5.
55. Bresnick WH, Rask-Madsen C, Hogan DL, et al. The effect of acute emotional stress on gastric acid secretion in normal subjects and duodenal ulcer patients. J Clin Gastroenterol 1993;17:117-22.
56. Lam SK, Hui WM, Shiu LP, Ng MM. Society stress and peptic ulcer perforation. J Gastroenterol Hepatol 1995;10:570-6.
57. Piper DW, Tennant C. Stress and personality in patients with chronic peptic ulcer. J Clin Gastroenterol 1993;16:211-4.
58. Stewart DN, de R. Winser DM. Incidence of perforated peptic ulcer. Effect of heavy air raids. Lancet 1942;2:259-61.
59. Spicer CC, Stewart DN, de R. Winser DM. Perforated peptic ulcer during the period of heavy air raids. Lancet 1944;1:14.
60. Aoyama N, Kinoshita Y, Fujimoto S, et al. Peptic ulcers after the Hanshin-Awaji earthquake: Increased incidence of bleeding gastric ulcers. Am J Gastroenterol 1998;93:311-6.

Pterygium

1. Curcumin (2017) and Pterygium
Learn more about pterygium.

2017

Researchers invested whether curcumin, the active component of turmeric might be useful in treating pterygium due to its capacity to inhibit cell growth.

In the lab they grew cell tissue which produces pterygiums in humans. They incubated it with curcumin, measuring growth at different time periods and at different concentrations. They found that incubation for 48 hours significantly inhibited growth and caused cell death of the pterygium tissue.

They concluded that curcumin may potentially be useful in treating pterygium in the 'near future.'

Researchers: C.W. Lu, J.L. Hao, L. Yao, et al
Published: International Journal of Molecular Medicine, April, 2017.

Editor's note: this is very new (2017) and the dosage is unknown outside of a lab situation, however, we should keep an eye on the potential use.

Noting that curcumin has been historically extensively used to treat many conditions, researchers discussed making curcumin more bioavailable. The authors point out that a number of studies find value in treating corneal diseases, conjunctivitis, anterior uveitis, pterygium and others. This is because of its anti-inflammatory, anti-allergy, anti-oxidative stress, anti-osmotic capacity. In addition, it helps limit the oxidation of oily lipids, regulates calcium balance, isolates free radicals, helps moderate protein changes in cataracts, and protects the eye in glaucoma.

Researchers: X.F. Liu, J.L. Hao, et al
Published: Frontiers in Pharmacology, February, 2017.

Editor's note: regarding bioavailability, curcumin is not water soluble and so if you are adding turmeric to your food for therapeutic purposes you should briefly saute it in oil first.

2007

Researchers investigated the value of curcumin in treating pterygium tissue and restricting the re-growth of pterygiums after surgery.

In a study incubating pterygium cell tissue with curcumin the scientists found that, depending on dosage and time of incubation, that curcumin acted to inhibit growth of the tissue and induce cell death (apoptosis) of the pterygium tissue.

Researchers: M. Zhang, F. Bian, et al
Published: Journal of Huazhong University of Science and Technology, June, 20017.

2. Dry Eye & Pterygium Incidence (2014)
Learn more about pterygium.

2017

Noting the frequent association between dry eye and pterygium, researchers decided to find out whether there was also an association between pterygium and malfunction of the meibomian gland, which is a cause of dry eye.

The meibomian gland produces meibum, an oily substance which spreads over the surface of the cornea, on top of the tear film and helps protect the integrity of the tear film. In dry eye if the meibomian glands are not producing enough meibum then tears evaporate rapidly from the surface of the eye causing soreness, redness, irritation and tearing.

These researchers felt that meibomian gland malfunction might be a missing link between the two conditions. Indeed, they did find just that. Patients with pterygium were significantly more likely to have problems with the effectiveness of their meibomian glands.

Researchers: H. Wu, Z. Lin, et al
Published: Meibomian Gland Dysfunction Correlates to the Tear Film Instability and Ocular Discomfort in Patients with Pterygium, Scientific Reports, March, 2017.

2014

Noting that dry eye often occurs simultaneously with pterygium researchers investigated the rate of tear film break up and the concentration of the tear film components - both of which are factors in dry eye syndrome.

They found that tear film breakup was faster in patients with pterygium and that tear osmolarity was greater. Pterygium patients also had greater redness of the conjunctiva.

Researchers: M. Ozsutcu, B. Arslan, et al,
Published: Tear osmolarity and tear film parameters in patients with unilateral pterygium, Cornea, November, 2014.

Another study of 92 patients between 29 and 78 years old with pterygium found similar results. As in the other 2014 study the size of the pterygium was not correlated with tear break up or osmolarity.

Researchers: K. Kampitak, et al,
Published: Journal of Medical Association of Thailand, May, 2014.

3. Green Tea (2017) and Meibomian Gland
Learn more about pterygium.

Certain research studies have associated malfunctioning meibomian glands with dry eye syndrome. Others have looked to meibomian dysfunction as being a missing link between dry eye and pterygium since the two conditions often co-exist. And, in fact, there has been such an association between meibomian gland problems and pterygium.

This study looked at green tea extract as to its helpfulness in meibomian gland problems.

The study was a double-blind, placebo controlled and randomized study of 60 patients. All used a standard treatment of eye drops three times a day for a month. The test group also received topical green tea three times a day for a month.

The symptoms of the test group improved significantly compared to the control group which suggested improved health of the meibomian glands. Furthermore, no side effects were noted.

Researchers: M. Nejabat, S.A. Reza, M. Zadmehr, et al
Published: Efficacy of Green Tea Extract for Treatment of Dry Eye and Meibomian Gland Dysfunction; A Double-blind Randomized Controlled Clinical Trial Study, Journal of Clinical and Diagnostical Research, February, 2017.

Retinal Detachment

1. Ginkgo Biloba (2004) and Retinal Detachment
Learn more about retinal detachment information and treatment.

Both animal and human studies, published in 1994 and substantiated in 2004 have revealed that Ginkgo extract can help to prevent retinal detachment, while increasing antioxidant activity in patients' blood, tears and plasma.

References:

Karazhaeva MI, Saksonova EO, Klebanov GI, Liubitskii OB, Gur'eva NV. [The use of flavonoid antioxidants in the complex treatment of patients with peripheral vitreo-chorioretinal dystrophies and dystrophic retinal detachment] [Article in Russian]. Vestn Oftalmol. 2004 Jul-Aug;120(4):14-8.

Baudouin C, Ettaiche M, Imbert F, Droy-Lefaix MT, Gastaud P, Lapalus P. Inhibition of preretinal proliferation by free radical scavengers in an experimental model of tractional retinal detachment. Experimental Eye Research. 1994 Dec;59(6):697-706.

Retinitis Pigmentosa

1. Acupuncture (2014) & Retinitis Pigmentosa
Learn more about complementary treatment for retinitis pigmentosa.

Retinitis pigmentosa, with its progressive degradation of the photoreceptor cells in the retina leads to profound vision loss. Patients have been self-reporting some improvements and a group of researchers conducted a pilot study to accurately measure whether there was, and how much, measurable improvement.

Researchers had previously studied the use of electroacupuncture in lab animals with similar conditions with good results. Several published case studies reported improvement in human patients in visual acuity and/or visual field area and sensitivity. In addition, over 400 patients self-reported such improvements over a 15 year period. These early studies lay the groundwork for more rigorous research methods.

A naturopathic physician developed a protocol specifically for retinitis pigmentosa, based on his extensive clinical experience. Twelve patients who had confirmed retinitis pigmentosa were part of the study and were treated using the standardized electroacupuncture treatment in 10 1/2 hour sessions over a two week period. Standard pre- and post-treatment tests measured the severity of the condition before and after treatment.

In addition the patients had been taking and continued to take nutrients that support the photoreceptors, such as lutein and vitamin A.

Vision testing after treatment consisted visual functioning testing one week and one month, as well as every 1 to 1 1/2 months for the next 10 to 12 months to assess how long the benefit continued.

Results Six of the twelve patients had significant, measurable vision improvements following treatment. Three out of nine patients were found to have a 13- to 53-fold improvement in a test known as the dark-adapted full-field stimulus threshold (FST) which continued for at least 10 to 12 months. This was a significant finding.

Dark adaption testing (how fast the eye is able to adjust seeing from bright to dim light) also improved by an average of 48.5% after one week, also a significant finding.

Other testing procedures revealed other improvements as well.

This sample was too small to draw conclusions about individual responses to treatment but the researchers report that age of onset of night vision loss may be a factor.

For more information you can read the entire study at NIH.gov. It discusses in some detail other research in the area of acupuncture and vision.

Researchers: Ava K. Bittner, OD, PhD, Jeffrey M. Gould, MEd LAc, Andy Rosenfarb, ND LAc, et al.

Published: A pilot study of an acupuncture protocol to improve visual function in retinitis pigmentosa patients, Clinical and Experimental Optometry, May, 2014.

2. Antioxidants (2006) Protect Cones in Animal Model
Why the negative affect of high dose vitamin E on RP function? It is possible that high dose vitamin E might have inhibited the absorption or transport of vitamin A, since patients receiving high doses had slight but significant decreases in serum A levels compared with those receiving lower doses in the 1993 Harvard study.
However, further exploratory studies of combined antioxidants in RP patients may be warranted. A recent study in an animal model of RP found that high dose antioxidants (vitamins E, C, alpha lipoic acid others) significantly reduced oxidative damage in cones, increased cone cell density and preserved cone function. These results, according to the Johns Hopkins authors, suggest that the gradual cone death that occurs after rod cells die is due to oxidative damage, and that antioxidants could provide benefit.
Komeima K, et al. Antioxidants reduce cone cell death in a model of retinitis pigmentosa. PNAS 103:1130-35, 2006.

Learn more about retinitis pigmentosa.

3. Artificial Retina (2011) Project
Learn about retinitis-pigmentosa treatment and information.

Scientists through the US Department of Energy are testing artificial retinas that they hope can restore partial sight to people who've lost their vision to the most common causes of blindness.
The Sylmar, Calif., company produced the devices for the U.S. Energy Department's Artificial Retina Project. The department has been engaged in biological research since the atomic bomb tests of the 1950s raised fears of radiation poisoning.
The current version is being tested on 17 blind people in the U.S. and Europe, and more patients are being enrolled. At a retina conference in October, patients reported improvements in orientation and mobility. They were able to find a door from 20 feet away and to follow a line on the floor for 20 feet, Mech reported.
Meanwhile, researchers in the Energy Department's National Laboratories are creating a third-generation artificial retina. Much smaller than its predecessors, the device will contain 200 or more electrodes on a thin, flexible film that curves to fit the shape of the retina. Human tests are scheduled to begin in 2011.

According to WHO estimates, the five most common causes of blindness around the world in 2002 were: cataracts (47.9%), glaucoma (12.3%), age-related macular degeneration (8.7%), corneal opacity (5.1%), and diabetic retinopathy (4.8%).

4. Fish Oil (2004) Retinitis Pigmentosa Treatment with fish oils & DHA
Learn more about retinitis pigmentosa recommendations

Researchers wanted to find out whether DHA (docosahexaenoic acid) will slow the course of retinal degeneration in patients with retinitis pigmentosa who are receiving vitamin A.

208 patients with retinitis pigmentosa, 18 to 55 years old, were randomly assigned to DHA plus vitamin A given as retinyl palmitate (DHA + A group) or control fatty acid plus 15 000 IU/d of vitamin A (control + A group) and followed up over 4 years. Seventy percent of the patients in each group were taking vitamin A, 15 000 IU/d, prior to entry. We compared rates of decline in ocular function in the DHA + A vs control + A groups among the subgroups defined by use or nonuse of vitamin A prior to entry. We also determined whether decline in ocular function was related to red blood cell phosphatidylethanolamine docosahexaenoic acid level, dietary omega-3 fatty acid intake, or duration of vitamin A use. Main outcome measures were Humphrey Field Analyzer visual field sensitivity, 30-Hz electroretinogram amplitude, and visual acuity. RESULTS: Among patients not taking vitamin A prior to entry, those in the DHA + A group had a slower decline in field sensitivity and electroretinogram amplitude than those in the control + A group over the first 2 years (P =.01 and P =.03, respectively); these differences were not observed in years 3 and 4 of follow-up or among patients taking vitamin A prior to entry. In the entire cohort, red blood cell phosphatidylethanolamine docosahexaenoic acid level was inversely related to rate of decline in total field sensitivity over 4 years (test for trend, P =.05). This was particularly evident over the first 2 years among those not on vitamin A prior to entry (test for trend, P =.003). In the entire control + A group, dietary omega-3 fatty acid intake was inversely related to loss of total field sensitivity over 4 years (intake, <0.20 vs > or =0.20 g/d; P =.02). The duration of vitamin A supplementation prior to entry was inversely related to rate of decline in electroretinogram amplitude (P =.008).

CONCLUSIONS: For patients with retinitis pigmentosa beginning vitamin A therapy, addition of docosahexaenoic acid, 1200 mg/d, slowed the course of disease for 2 years. Among patients on vitamin A for at least 2 years, a diet rich in omega-3 fatty acids slowed the decline in visual field sensitivity.
Published: Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment: subgroup analyses. Arch Ophthalmol. 2004 Sep;122(9):1306-14.

Researchers: Berson EL, Rosner B, Sandberg MA, Weigel-DiFranco C, Moser A, Brockhurst RJ, Hayes KC, Johnson CA, Anderson EJ, Gaudio AR, Willett WC, Schaefer EJ. Berman-Gund Laboratory for the Study of Retinal Degenerations, Harvard Medical School, 243 Charles Street, Boston, MA

5. Lutein (2003) and Increased Visual Acuity
Learn more about retinitis pigmentosa recommendations.

In an informal study, a researcher analyzed information from a small online email questionnaire and determined that lutein, which is in dark green leafy vegetables and egg yolks may help people with retinitis pigmentosa (RP) and other degenerative eye conditions.

Three quarters of the 16 study participants with retinal degenerative conditions reported that taking daily supplements lutein, over a six-month period significantly helped their vision. Lutein is an antioxidant needed by the retina to resist damaging effects of blue light and free radicals.

Study participants were recruited after a member of an international retinal degeneration patient e-mail list noted that some of her contacts said their vision improved with lutein supplementation.

The participants took lutein supplements with breakfast daily for 6 months, 40 mg/day for 9 weeks and then 20 mg/day for the remainder. One half of the participants also took 500 mg/day of DHA, vitamin B complex and digestive enzymes. Ten of the participants who already were taking vitamin A and/or beta carotene continued those supplements. They tested their vision on eye charts sent as e-mail attachments and on wall charts they were instructed to create, and returned data via weekly e-mails to the study coordinators.

Most patients saw improvement in vision sharpness and visual field size. The blue-eyed patients, more at risk, had larger gains in vision than the dark-eyed participants. Also, those who took vitamin A and/or beta carotene supplements prior to the study appeared to benefit more than those who did not. The long-term effects of lutein supplements on the progression of RP should be studied,
Researchers: Johns Hopkins University, Gislin Dagnelie, Ph.D., and others, Hopkins' Wilmer Eye Institute

Published in the March issue of Optometry:Journal of the American Optometric Association.

6. Lutein and Retinitis Pigmentosa (2006)
Nutrient Supplementation for RP
Retinitis pigmentosa (RP) refers to a group of inherited progressive retinal dystrophies characterized by photoreceptor degeneration. The rods are affected initially, followed by gradual death of the cones. It's estimated that 1 in 4,000-5,000 people have RP worldwide. Since no generally accepted medical or surgical treatment can stop the course of the disease, researchers have undertaken studies with various nutritional supplements in hopes of improving visual function or slowing disease progression. Along with vitamin A, DHA and an omega-3 rich diet, lutein has recently been reported to be of potential benefit in RP.
Lutein May Benefit Visual Field and Acuity Spurred by previous studies suggesting lutein as a potential treatment with positive effects on macular pigment density, researchers from the Wilmer Eye Institute conducted a double-blind, randomized placebo-controlled trial with a cross-over design (1). Thirty four adult RP patients were randomized to 2 groups and followed for 48 weeks. One group received lutein supplements (10 mg/day for 12 weeks followed by 30 mg/day) for the first 24 weeks, then placebo for the following 24 weeks. The second group received placebo prior to lutein. Both groups were given a multi-vitamin and mineral supplement.
Lutein supplementation had a significant effect on central visual field. Visual acuity also improved slightly, though no effect on contrast sensitivity was observed. Comparing the development of vision measures against the natural loss expected to occur over 48 weeks, most measures showed reduced decline. These reductions were significant for normal illumination visual acuity and contrast sensitivity. The results, according to the authors, suggest that lutein supplementation improves visual field and may also modestly improve visual acuity.
H, et al. Lutein supplementation in retinitis pigmentosa: PC-based vision assessment in a randomized double-masked placebo-controlled clinical trial. BMC Ophthalmology 6:23, 2006.

7. Lutein plus vitamin A (2010) may slow vision loss due to Retinitis Pigmentosa
Learn more about retinitis pigmentosa recommendations.

In a randomized, controlled, double-blind study, researchers found that supplementing with lutein and vitamin A may slow development of retinitis pigmentosa.

They found that use of a daily supplement of 12 milligrams of lutein formulated with 15,000 IU of vitamin A was linked to protection of mid-peripheral vision.

This new data suggests that 40 year olds with retinitis pigmentosa who take vitamin A plus lutein would have their mid-peripheral field for an extra 21 years when compared to people not taking the combination. Previous studies have found vitamin A slows the decline in retinal function and vision loss, and this study indicates that combining vitamin A with lutein is better.

Since there has been some concern with regard to smokers and lutein supplementation, this study looked only at non-smokers.

Published: Archives of Ophthalmology, 2010, Vol. 128, Issue 4, Pages 403-411 "Clinical Trial of Lutein in Patients With Retinitis Pigmentosa Receiving Vitamin A"

Researchers: E.L. Berson, B. Rosner, M.A. Sandberg, C. Weigel-DiFranco, R.J. Brockhurst, et al.

8. Microcurrent Stimulation (1997, 2002, 2009) & Retinitis Pigmentosa
Learn more about treatment for retinitis pigmentosa.

Several studies on microcurrent stimulation treatment for macular degeneration also tested the methodology on patients with retinitis pigmentosa or the author commented on predicted outcomes for retinitis pigmentosa patients.

See these studies for more information.

Jarding, et al, Published, 2009 (implications for RP)

Edward Paul, OD, PhD, Published, 2002

Larry B. Wallace, O.D. FCSO, 1997 (implications for RP)

Grace Halloran, PhD, 1997

9. Omega 3 & 6 (1988-92) - retinitis pigmentosa
Learn more about retinitis-pigmentosa treatment and information.

Studies on Omega-3 and Omega-6 fatty acids

Both Omega-3 and -6 Fatty Acids are essential nutrients for normal development in mammals. Omega-6 Fatty Acids are necessary primarily for growth, reproduction and the maintenance of skin integrity. Omega-3 Fatty Acids are involved in the development and function of the retina and cerebral cortex and other organs such as the testes. (1)

Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are essential Omega-3 Fatty Acids found in abundance in cold water fish and their oils. DHA is an essential nutrient for achieving optimal brain and eye function. (2) It comprises about 60% of the rod outer segments in the photoreceptor cells that we see with. (3) Brain tissue is about 60% fat, 25% of which is DHA. DHA levels correlate with visual and mental performance and several neurological and visual disorders, including retinitis pigmentosa.

Cells in the retina, brain and other parts of the nervous system have connecting arms that transport electrical currents, sending visual information from the retina to the brain and messages from the brain through out the body. DHA supplementation ensures the optimal composition of cell membranes necessary for the most effective transmission of these signals.

A 1990 study demonstrated that DHA with EPA given in the form of fish oil exerts a beneficial dose-dependent effect on coronary circulation with reduced triglycerides, total cholesterol, and blood pressure while causing no significant increase in bleeding time.(4 )

Editor's note: We believe DHA' use in wet macular degeneration is unparalleled since its main work in the body is to heal and support blood vessel walls.

Research:
1. Connor WE; Neuringer M.; Prog Clin Biol Res; 1988: 282; 275-94.
2. Neuringer M, Anderson G. J., Connor WE, "The essentiality of n-3 fatty acids for the development and function of the retina and brain," Ann Rev Nutr., 1988; 8: pp/17-41.
3. Salem et al, 1996; P Martinez et al, 1992).
4. Haglund et al, "Effects of a new fish oil concentrate on triglycerides, cholesterol, fibrinogen and blood pressure" Nutritional Research 1990; 227:347-53.

10. Omega-3 Fatty Acids and Retinitis Pigmentosa (2004)
While a 4 year long study published in 2004 reported that 1,200 mg of supplemental DHA along with high dose vitamin A did not slow the course of RP overall, further subgroup analysis showed benefit for those starting vitamin A supplementation for the first time (5-6). In addition, those study participants taking vitamin A (but not DHA) who also had a higher dietary omega-3 intake experienced substantial benefit. The rate of visual field decline was retarded by 40-50% yearly in those whose omega-3 intakes were equivalent to 1-2 servings of fatty fish weekly.
Berson EL, et al. Further evaluation of docosahexaenoic acid in patients with retinitis pigmentosa. 12:1306-14, 2004.

11. Vitamin A (2004), DHA, Omega-3 Fatty Acid and Retinitis Pigmentosa
Learn more about retinitis-pigmentosa treatment and information.

A 4 year long study published in 2004 reported that 1,200 mg of supplemental DHA along with high doses of vitamin A did not slow the progress of retinitis pigmentosa overall. However further subgroup analysis showed benefit for those who were taking vitamin A supplementation for the first time. In addition, those study participants taking vitamin A (but not DHA) who also had a higher dietary omega-3 fatty acid intake experienced substantial benefit. The rate of visual field decline was retarded by 40-50% yearly in those whose omega-3 intakes were equivalent to 1-2 servings of fatty fish weekly.

Berson EL, et al. Clinical trial of docosahexaenoic acid in patients with retinitis pigmentosa receiving vitamin A treatment. Arch Ophthalmol 122:1297-305, 2004.

12. Vitamin A (2018, 2016, 2006) & Retinitis Pigmentosa
Learn more about retinitis pigmentosa.

2018

The researchers report that use of vitamin A is effective in some forms of retinitis pigmentosa (RP) but not others and is in fact, sometimes contraindicated as in the case of RP caused by Stargardt's disease.

In 1993, Berson, et al reported a protective effect for vitamin A and a detrimental effect of vitamin E. In 2004, Berson, et al reported in one study that adding DHA didn't slow progression, but in another, that it did. In a third trial in 2010, they added lutein and concluded that A, lutein, and fish oil combined were effective. However, the methodology of these studies has been criticized, and the outcomes were based on secondary results rather than primary results. Furthermore, the RP patients were not genotyped and there is increased evidence that vitamin A should be avoided in some RP patients.

At the same time, vitamin A is effective in some cases - it just should not be prescribed broadly for all RP patients.

Athanasiou, D., Aguila, M., Bellingham, J., Wenwen, L., McCulley, C., Reeves, P.J., et al. (2018). The molecular and cellular basis of rhodopsin retinitis pigmentosa reveals potential strategies for therapy. Prog Retin Eye Res, Jan;62:1-23.

See also

Sofi, F., Sodi, A., Franco, F., Murro, V., Biagini, D. (2016). Dietary profile of patients with Stargardt's disease and Retinitis Pigmentosa: is there a role for a nutritional approach? BMC Ophthalmol. Jan 22;16:13.
Hartong, D.T., Berson, E.L., Dryja, T.P. (2006). Retinitis pigmentosa. Lancet, Nov 18;368(9549): 1785-809.

13. Vitamins A / E (1993) & Retinitis Pigmentosa
Learn more about retinitis pigmentosa recommendations.

Researchers found significant benefit in providing vitamin A supplements and a potential adverse effect of vitamin E on 600 patients with retinitis pigmentosa. Large doses of vitamin A did not result in greater benefit.

They speculated that among patients with specific rod-specific gene defects vitamin A supplementation may provide benefit. No toxicity was seen for vitamin A or E. High dose vitamin A is not recommended for pregnant women or women planning to become pregnant due to the possibility of birth defects
Researchers: Berson, Rosner, Sandberg, Hayes, Nicholson, Weigel-DiFranco, and Willette, 1993.

Published: Archives of Ophthalmology (June 1993), volume 111(6), pages 761-772.

14. Vitamins E, C, alpha lipoic acid and Retinitis Pigmentosa (2006)
A 2006 study in an animal model of RP found that high dose antioxidants (vitamins E, C, alpha lipoic acid others) significantly reduced oxidative damage in cones, increased cone cell density and preserved cone function. These results, according to the Johns Hopkins authors, suggest that the gradual cone death that occurs after rod cells die is due to oxidative damage, and that antioxidants could provide benefit.

Komeima K, et al. Antioxidants reduce cone cell death in a model of retinitis pigmentosa. PNAS 103:1130-35, 2006.

Learn more about retinitis-pigmentosa.

Rheumatoid Arthritis

1. Fish Oil (2003) & Rheumatoid Arthritis
Learn more about rheumatoid arthritis.

These researchers noted that fish oils are an excellent source for omega-3 fatty acids, and that they have a beneficial effect of reducing inflammation. Fish oils have shown this beneficial result in double-blind, random, trials with placebo controls, for rheumatoid arthritis, but have not received the marketing that pharmaceutical drugs have and so remain unknown to many health professionals.

Researchers: Cleland LG, James MJ, Proudman SM.

Published: The role of fish oils in the treatment of rheumatoid arthritis, Drugs. 2003;63(9):845-53.

2. Olive Leaf Extract (2011, 2016) & Arthritis
Learn more about rheumatoid arthritis

2016

This study looked at combining olive leaf extract with a standard therapy for patients with early and long-term rheumatoid arthritis. It assessed amount of cell damage and inflammation. Patients were evaluated at the beginning of the study and assigned to one of several groups. Early phase patients received either solely the prescription drug or the drug plus olive leaf extract. Long phase patients received the combinations of the drug plus olive leaf extract.

After three weeks the early-phase group receiving the combined therapy had markedly reduced symptoms and positive changes in a number of biomarkers. In the early-phase group receiving only the prescription drug some biomarkers remained unchanged and other improvements occurred only after an additional three weeks. For the late-phase group, there were only modest improvements after six weeks.

The researchers concluded that adding olive leaf extract to the prescription drug supported quicker and better benefits, although these changes were more marked in patients with early-phase rheumatoid arthritis - in other words, damage had not progressed as far.

Researchers: A. Cabarkapa, L. Zivkovic, et al
Dry Olive Leaf Extract in Combination with Methotrexate Reduces Cell Damage in Early Rheumatoid Arthritis Patients-A Pilot Study, Phytotherapy Research, October, 2016.

2011

Knowing of the anti-inflammatory capacity of olive leaf extract (oleuropein), researchers wanted to investigate the capacity of the extract to reduce inflammation causing and/or aggravating rheumatoid arthritis.

In mice with arthritis caused by collagen, animals treated with olive leaf extract exhibited a marked reduction in bio-markers indicative of the condition. Animals were treated with the extract 25 days after their arthritis had developed, and symptoms improved starting the next day and continuing until the study's end ten days later.

The biomarkers involved were cytokines which increase when inflammation is present. These biomarker levels significantly decreased.

Researchers: D. Impellizzeri, E. Esposito, et al
Published: Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis caused by injection of collagen type II in mice, Journal of Pharmacology and Experimental Therapeutics, December, 2011

Editor's Note: Similar results were found with respect to osteoarthritis.

3. Taurine (2017, 2014 , 2010) Reduces Inflammation
Learn more about rheumatoid arthritis.

2017

Researchers recognize that taurine is widely understood to be a potential therapy for chronic inflammation disorders. Inflammation from oxidative stress is one cause of many health conditions.

In this study scientists were evaluating the effects of taurine on biochemicals called cytokines which promote inflammation as well as other markers of inflammation-related imbalances. They examined mast cells (a type of white blood cell derived from stem cells) which were reacting to a specific type of allergic reaction.

They found that, in a dose related manner, taurine was able to inhibit the production and activity of pro-inflammatory cytokines. And in animal testing they found similar results in that animals were much less affected by allergens.

Researchers: S. Kim, H. Kim, et al
Published: The potential protective role of taurine against experimental allergic inflammation, Life Science, September, 2017.

Editor's Note to vegetarians: Taurine is usually abundant in the body, but it is not produced by plants and so supplementation may be appropriate. Check with your doctor.

2014

When the body experiences inflammation as a result of oxidative stress, trauma, exposure to toxins, etc, taurine is part of the response mechanism to try to reduce the negative effects of inflammation.

When some part of the body becomes inflamed - whether it is the retina in eye conditions, the blood vessels in circulatory problems, the joints in arthritic conditions, taurine undergoes a biochemical change to lessen damage from inflammation.

Upon inflammation taurine is converted to taurine chloramine and taurine bromamine. Taurine chloramin increases the action of antioxidants to protect cell tissue from damage. At the same time it inhibits the creation of cytokines and free radicals that cause inflammation.

Researchers: C. Kim, Y.N. Cha,
Published: Taurine chloramine produced from taurine under inflammation provides anti-inflammatory and cytoprotective effects, Amino Acids, January, 2014.

2010

Taurine chloramine is produced by the body in response to the presence of inflammation. The biochemical acts to reduce the inflammatory response through inhibiting the action of pro-inflammatory biochemicals called cytokines, as well as directly reduce free radicals and oxidative stress.

These researchers explored the mechanics of the process, using tissue from rheumatoid arthritis patients. They found that taurine cloramine inhibits the synthesis of two interleukins that are biomarkers for inflammation. Interleukins are a kind of special protein produced by white blood cells which help to regulate inflammation. In the case of arthritis, these interleukins over-react. Taurine cloramine is able to inhibit their production.

Researchers: E. Kontny, K. Szczepariska, et al
Published: The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) production by rheumatoid arthritis fibroblast-like synoviocytes, Arthritis and Rheumatism, October, 2000.

4. Vitamin D ('04, '07-08') & Rheumatoid Arthritis
Learn more about treatment of rheumatoid arthritis

2008

Noting that vitamin D increasingly is being recognized as having many benefit effects, these researchers determined that noting vitamin D deficiency in rheumatoid arthritis patients is important and frequently exists. There's no agreement that vitamin D deficiency alone causes RA, but it is a factor and symptoms are relieved with increased vitamin D intake.

They further noted that the difficulty is in determining just how to correct the deficiency, concluding that high-dose vitamin D given orally, weekly, can quickly correct the deficiency and then it should be followed by lower doses to keep an adequate level in the system.

Researchers: P. Leventis, S. Patel
Published: Clinical aspects of vitamin D in the management of rheumatoid arthritis, Rheumatology (Oxford). November, 2008.

2007

Researchers discovered that vitamin D receptors were contained in a variety of cells comprising the immune system (dendritic cells) and that they could produce this component. This gave rise to the suggestion that vitamin D plays a role in the regulation of the immune system.

Vitamin D is developed in the body by exposure to sunlight. Low levels of vitamin D in the blood may be due, not only to limited sunlight exposure, but genetic factors and nutrition.

Following these conclusions, researchers looked for correlations in rheumatoid arthritis patients and found that they have low blood levels of vitamin D, and that their condition is more severe in the winter when light levels are lower.

Researchers have also found that consuming greater amounts of vitamin D was correlated with marked improvement, not only in RA symptoms, but in the health of the immune system.

Researchers: M. Cutolo, K. Otsa, et al
Published: Vitamin D in rheumatoid arthritis, Autoimmununity Reviews, November, 2007.

2004

Researchers, noting that vitamin D regulates calcium balance and perhaps the immune system, wanted to determine the relationship between consumption of vitamin D and rheumatoid arthritis.

They evaluated data from a study of 29,368 women, aged 55-69, who were rheumatoid arthritis patients (RA), using a food frequency form the patients had filled out, which included vitamin D supplementation.

152 cases were tracked over the following 11 years and found that the greater the vitamin D intake, the lower the risk of RA.

Researchers: L.A. Merlino, J. Curtis, et al; Iowa Women's Health Study.
Published: Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study, Arthritis and Rheumatology, January, 2004.

5. Xtra Info: Rheumatoid Arthritis Bibliography - early research
Also see discussion of rheumatoid arthritis and recommendations

1. Levy JA, Ibrahim AB, Shirai T, et al. Dietary fat affects immune response, production of antiviral factors, and immune complex disease in NZP/NZW mice. Proc Natl Acad Sci 1982;79:1974-8.
2. Jacobsson I, Lindgarde F, Manthorpe R, et al. Correlation of fatty acid composition of adipose tissue lipids and serum phosphatidylcholine and serum concentrations of micronutrients with disease duration in rheumatoid arthritis. Ann Rheum Dis 1990;49:901-5.
3. Lucas CP, Power L. Dietary fat aggravates active rheumatoid arthritis. Clin Res 1981;29:754A [abstract].
4. Skoldstam L. Fasting and vegan diet in rheumatoid arthritis. Scand J Rheumatol 1987;15:219-21.
5. Nenonen M, Helve T, Hanninen O. Effects of uncooked vegan food- "living food" - on rheumatoid arthritis, a three month controlled and randomised study. Am J Clin Nutr 1992;56:762 [abstract #48].
6. Warmbrand M. How Thousands of My Arthritis Patients Regained Their Health. New York: Arco Publishing, 1974.
7. Panush RS, Carter RL, Katz P, et al. Diet therapy for rheumatoid arthritis. Arthrit Rheum 1983;26:462-71.
8. KjeldsenKragh J, Haugen M, Borchgrevink CF, et al. Controlled trial of fasting and one year vegetarian diet in rheumatoid arthritis. Lancet 1991;338:899-902.
9. Linos A, Kaklamani VG, Koukmantaki Y, et al. Dietary factors in relation to rheumatoid arthritis: a role for olive oil and cooked vegetables. Am J Clin Nutr 1999;70:1077-82.
10. Kremer JM, Lawrence DA, Jubiz W, et al. Dietary fish oil and olive oil supplementation in patients with rheumatoid arthritis. Clinical and immunologic effects. Arthritis Rheum 1990;33:810-20.
11. Hafstrom I, Ringertz B, Gyllenhammar H, et al. Effects of fasting on disease activity, neutrophil function, fatty acid composition, and leukotriene biosynthesis in patients with rheumatoid arthritis. Arthritis Rheum 1988;31:585-92.
12. Skoldstam L, Magnusson KE. Fasting, intestinal permeability, and rheumatoid arthritis. Rheum Dis Clin North Am 1991;17:363-71 [review].
13. KjeldsenKragh J, Haugen M, Borchgrevink CF, et al. Controlled trial of fasting and one year vegetarian diet in rheumatoid arthritis. Lancet 1991;338:899-902.
14. Kjeldsen-Kragh J, Haugen M, Borchgrevink CF, Forre O. Vegetarian diet for patients with rheumatoid arthritis--status: two years after introduction of the diet. Clin Rheumatol 1994;13:475-82.
15. KjeldsenKragh J, Haugen M, Borchgrevink CF, et al. Controlled trial of fasting and one year vegetarian diet in rheumatoid arthritis. Lancet 1991;338:899-902.
16. Seignalet J. Diet, fasting, and rheumatoid arthritis. Lancet 1992;339:68-9 [letter].v 17. Abuzakouk M, O'Farrelly C. Diet, fasting, and rheumatoid arthritis. Lancet 1992;339:68 [letter].
18. Panayi GS. Diet, fasting, and rheumatoid arthritis. Lancet 1992;339:69 [letter].
19. Cordain L, Toohey L, Smith MJ, Hickey MS. Modulation of immune function by dietary lectins in rheumatoid arthritis. Br J Nutr 2000;83(3):207-17.
20. Zeller M. Rheumatoid arthritis- food allergy as a factor. Ann Allerg 1949;7:200-5,239.
21. Darlington LG, Ramsey NW, Mansfield JR. Placebo controlled, blind study of dietary manipulation therapy in rheumatoid arthritis. Lancet 1986;i:236-8.
22. Beri D, Malaviya AN, Shandilya R, Singh RR. Effect of dietary restrictions on disease activity in rheumatoid arthritis. Ann Rheum Dis 1988;47:69-72.
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45. Kremer JM, Jubiz W, Michalek A, et al. Fishoil fatty acid supplementation in active rheumatoid arthritis. Ann Int Med 1987;106(4):497-503.
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48. Van der Tempel H, Tulleken JE, Limburg PC, et al. Effects of fish oil supplementation in rheumatoid arthritis. Ann Rheum Dis 1990;49:76-80.
49. Cleland LG, French JK, Betts WH, et al. Clinical and biochemical effects of dietary fish oil supplements in rheumatoid arthritis. J Rheumatol 1988;15(10):1471-5.
50. Kremer JM, Lawrence DA, Petrillow GF, et al. Effects of high dose fish oil on rheumatoid arthritis after stopping nonsteroidal antiinflammatory drugs. Arthritis Rheum 1995;38:1107-14.
51. Lee TH, Hoover RL, Williams JD, et al. Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 1985;312(19):1217-24.
52. Nordstrom DC, Honkanen VE, Nasu Y, et al. Alpha-linolenic acid in the treatment of rheumatoid arthritis. A double-blind, placebo-controlled and randomized study: flaxseed vs. safflower seed. Rheumatol Int 1995;14:231-4.
53. Siemandi H. The effect of cis-9- cetyl myristoleate (CMO) and adjunctive therapy on arthritis and auto-immune disease: a randomized trial. Townsend Letter for Doctors and Patients. 1997;Aug/Sept:58-63.
54. American Medical Association. Dimethyl sulfoxide. Controversy and Current Status-1981. JAMA 1982;248:1369-71.
55. Jimenez RAH, Willkens RF. Dimethyl sulfoxide: A perspective of its use in rheumatic diseases. J Lab Clin Med 1982;100:489-500.
56. Jacob SW, Wood DC. Dimethyl sulfoxide (DMSO). Toxicology, pharmacology, and clinical experience. Am J Surg 1967;114:414-26.
57. Barton-Wright EC, Elliott WA. The pantothenic acid metabolism of rheumatoid arthritis. Lancet 1963;ii:862-3.
58. General Practitioner Research Group. Calcium pantothenate in arthritic conditions. Practitioner 1980;224:208-11.
59. Gibson RG, Gibson SLM, Conway V, Chappell D. Perna canaliculus in the treatment of arthritis. Practitioner 1980;224:955-660.
60. Audeval B, Bouchacourt P. Etude controle en double aveugle contra placebo de l'extrait de moule Perna canaliculus dans las gonarthrose. Gazette Medicale 1986;38:111-6.
61. Huskisson EC, Scott J, Bryans R. Seatone is ineffective in rheumatoid arthritis. BMJ 1981;282:1358-9.
62. Caughey DE, Grigor RR, Caughey EB, et al. Perna canaliculus in the treatment of rheumatoid arthritis. Eur J Rheumatol Inflamm 1983;6:197-200.
63. Larkin JG, Capell HA, Sturrock RD. Seatone in rheumatoid arthritis: a six-month placebo controlled study. Ann Rheum Dis 1985;44:199-201.
64. Highton TC, McArthur A. W. Pilot study on the effect of New Zealand green mussel on rheumatoid arthritis. N Z Med J 1975;81:261-2.
65. Gibson SLM, Gibson RG. The treatment of arthritis with a lipid extract of Perna canaliculus: a randomized trial. Comp Ther Med 1998;6:122-6.
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67. Aaseth J, Munthe E, Forre O, Steinnes E. Trace elements in serum and urine of patients with rheumatoid arthritis. Scand J Rheumatol 1978;7:237-40.
68. Simkin PA. Oral zinc sulphate in rheumatoid arthritis. Lancet 1976;ii:539-42.
69. Peretz A, Neve J, Jeghers O, Pelen F. Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases. Am J Clin Nutr 1993;57:690-4.
70. Job C, Menkes CJ, de Gery A, et al. Zinc sulphate in the treatment of rheumatoid arthritis. Arthrit Rheum 1980;23:1408.
71. Simkin PA. Treatment of rheumatoid arthritis with oral zinc sulfate. Agents Actions 1981;8(suppl):587-96.
72. Tarp U, Overvad K, Hansen JC, Thorling EB. Low selenium level in severe rheumatoid arthritis. Scand J Rheumatol 1985;14:97-101.
73. Aaseth J, Munthe E, Forre O, Steinnes E. Trace elements in serum and urine of patients with rheumatoid arthritis. Scand J Rheumatol 1978;7:237-40.
74. Peretz A, Neve J, Duchateau J, Famaey JP. Adjuvant treatment of recent onset rheumatoid arthritis by selenium supplementation: preliminary observations. Br J Rheumatol 1992;31:281-2 [letter].
75. Tarp U, Overvad K, Thorling EB, et al. Selenium treatment in rheumatoid arthritis. Scand J Rheumatol 1985;14:364-8.
76. DiSilvestro RA, Marten J, Skehan M. Effects of copper supplementation on ceruloplasmin and copper zinc superoxide dismutase in free-living rheumatoid arthritis patients. J Am Coll Nutr 1992;11:177-80.
77. Jones AA, DiSilvestro RA, Coleman M, Wagner TL. Copper supplementation of adult men: effects on blood copper enzyme activities and indicators of cardiovascular disease risk. Metabolism 1997;46:1380-3.
78. Medical News. Copper boosts activity of anti-inflammatory drugs. JAMA 1974;229:1268-9.
79. Sorenson JRJ. Copper complexes-a unique class of antiarthritic drugs. Progress Med Chem 1978;15:211-60 [review].
80. Walker WR, Keats DM. An investigation of the therapeutic value of the 'copper bracelet' - dermal assimilation of copper in arthritic/rheumatoid conditions. Agents Actions 1976;6:454-9.
81. Blake DR, Lunec J. Copper, iron, free radicals and arthritis. Brit J Rheumatol 1985;24:123-7 [editorial].
82. Newnham RE. Arthritis or skeletal fluorosis and boron. Int Clin Nutr Rev 1991;11:68-70 [letter].
83. Balagot RC, Ehrenpreis S, Kubota K, et al. Analgesia in mice and humans by D-phenylalanine: Relation to inhibition of enkephalin degradation and enkephalin levels. Adv Pain Res Ther 1983;5:289-93.
84. Hartung EF, Steinbroker O. Gastric acidity in chronic arthritis. Ann Intern Med 1935;9:252.
85. Cohen A, Goldman J. Bromelain therapy in rheumatoid arthritis. Pennsylvania Med J 1964;67:27-30.
86. Park EH, Kahng JH. Suppressive effects of propolis in rat adjuvant arthritis. Arch Pharm Res 1999;22:554-8.
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88. Etzel R. Special extract of Boswellia serrata in the treatment of rheumatoid arthritis. Phytomed 1996;3:91-4 [review].
89. Singh GB, Singh S, Bani S. New phytotherapeutic agent for the treatment of arthritis and allied disorders with novel mode of action. 4th International Congress on Phytotherapy, Munich, Germany, Sep 10-3, 1992.
90. Chopra A, Lavin P, Patwardhan B, Chitre D. Randomized double blind trial of an Ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 2000;27:1365-72.
91. Sander O, Herborn G, Rau R. [Is H15 (resin extract of Boswellia serrata, "incense") a useful supplement to established drug therapy of chronic polyarthritis? Results of a double-blind pilot study. Z Rheumatol 1998 ;57:11-6 [in German].
92. Deal CL, Schnitzer TJ, Lipstein E, et al. Treatment of arthritis with topical capsaicin: A double-blind trial. Clin Ther 1991;13:383-95.
93. Bone K. The story of devil's claw: Is it an herbal antirheumatic? Nutrition and Healing 1998;October:3,4,8 [review].
94. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: A double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 1991;33:91-5.
95. Deodhar SD, Sethi R, Srimal RC. Preliminary studies on antirheumatic activity of curcumin (diferuloyl methane). Ind J Med Res 1980;71:632-4.
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98. Randall C, Meethan K, Randall H, Dobbs F. Nettle sting of Urtica dioica for joint pain- an exploratory study of this complementary therapy. Compl Ther Med 1999;7:126-31.
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100. Upton R, Petrone C, eds. Willow bark (Salix spp.) monograph. Santa Cruz, CA: American Herbal Pharmacopoeia, 1999.
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103. Zeylstra H. Filipendila ulmaria. Br J Phytotherapy 1998;5:8-12.
104. Dhondt W, Willaeys T, Verbruggen LA, et al. Pain threshold in patients with rheumatoid arthritis and effect on manual oscillations. Scand J Rheumatol 1999;28:88-93.

Sjogren's Syndrome

1. Green tea (2017, 2008) may protect against Sjogren's syndrome
Learn more about Sjogrens treatment and information.

2017

Green tea extract improves meibomian gland function which, while probably not protecting against the cause of Sjogren's may help relieve symptoms.

Nejabat, M., Reza, S.A., Zadmehr, M., Yasemi, M., Sobhani, Z. (2017). Efficacy of Green Tea Extract for Treatment of Dry Eye and Meibomian Gland Dysfunction; A Double-blind Randomized Controlled Clinical Trial Study. J Clin Diagn Res, Feb;11(2):NC05-NC08.

2008

Green tea extract could help prevent the development of Sjogren's syndrome.

In Sjogren's the salivary and tear glands are invaded by a type of white blood cell, rendering them less effective. Researchers investigated whether and how a green tea component, polyphenol epigallocatechin-3-gallate (EGCG), strengthens normal human salivary acinar cells. They studied the effect of the compound in mice and found that those that received an oral green tea extract experienced significantly less damage to their salivary glands, with reduced lymphocyte infiltration, as well as lower blood total auto-antibody levels, compared to those that did not receive the compound.

The researchers suspect that EGCG activates our defense system against a protein produced by the white blood cells during inflammation, and which causes cell-death. "The salivary gland cells treated with EGCG had much fewer signs of cell death caused by TNF-alpha," Dr. Hsu observed. "We don't yet know exactly how EGCG makes that happen. That will require further study. In some ways, this study gives us more questions than answers."

Gillespie, K., Kodani, I., Dickinson, D.P., et al. (2008). Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren’s syndrome, an autoimmune disease. Life Sci, Oct 24;83(17-18):581-588.

2. Inflammation & Antioxidants (2016) & Sjogrens
Learn more about support for Sjogrens syndrome.

Researchers have reported that chronic inflammation in the body is a central cause of many health conditions and is associated with premature mortality. Sjogrens is also characterized by underlying chronic inflammation.

The diet generally consumed by Westerners is high in red meat, high-fat dairy, refined sugars and grains and refined carbohydrates (as opposed to long-chain carbohydrates such as multi-grain cereal). The Mediterranean diet however, is high in whole grains, fish, vegetables (especially green vegetables) and fruit, along with low alcohol consumption and use of olive oil. This diet is associated with lower levels of inflammation in the body.

Researchers wanted to investigate the relationship between high inflammation levels in the body, indicated by the Dietary Inflammatory Index (DII) and premature mortality. Researchers investigated the diets and health of more than 8089 subjects to see whether such a relationship existed and to, in addition, see whether antioxidants would be helpful in reducing inflammation.

They conducted a random, placebo-controlled, double-blind study in which the subjects received low doses of antioxidants or a placebo over an eight year period. The subjects were aged 43 to 55 years old and their health was followed for an additional five years after the trial ended.

The subjects who had high inflammation levels had a higher death rate from heart disease or cancer compared to normal averages.

The subjects who received antioxidants did not have the same high death rate.

Researchers: L. Graffouillere, M. Deschausaux, et al.

Published: Prospective association between the Dietary Inflammatory Index and mortality: modulation by antioxidant supplementation in the SU.VI.MAX randomized controlled trial, American Journal of Clinical Nutrition, March, 2016.

3. MSM (2015) Reduces Inflammation - Sjrogren's
MSM is helpful for conditions where inflammation is an issue such as Sjogren's syndrome.

The researchers noted that while the health benefit of reducing inflammation is associated with Methylsulfonylmethane (MSM) there had been no study focusing on that capacity with regard to inflammasomes - a formation composed of multiple proteins that acts as a basis for stimulating lymphocyte development. Lymphocytes are the white blood cells that fight infection.

The researchers found that MSM did reduce some types of inflammasome activation. They also found that MSM-enriched vegetable given to lab animals had the same effect.

They concluded that MSM does present anti-inflammatory capacity, interrupts inflammasome production, and inhibits expression of pro-cytokines which promote systemic inflammation and make a disease worse through fever and tissue death.

Researchers: H. Ahn, J. Kim, M. Lee, Y. Kim, Y.W. Cho, G. Lee

Published: Methylsulfonylmethane inhibits NLRP3 inflammasome activation, Cytokine, February, 2015.

4. Omega-6 (1986) and Sjogren's Syndrome
Learn more about Sjogren's treatment and information.

In a small 1986 study, 28 patients with primary Sjogren's Syndrome were studied in a "cross-over" clinical study, and given essential fatty acids (EFA), either Efamol (evening primrose oil) which is comprised of 73% cis-linoleic acid and 9% gammalinolenic acid, or a placebo for an short term eight week term.

Improvement was noted in that 68% of the Sjogren's patients experienced decreased dry eye symptoms, which are one of the symptoms of Sjogren's.

Researchers: P. Oxholm, R. Manthorpe, J.U. Prause, and D. Horrobin

Published: Patients with Primary Sjogrn's Syndrome Treated for 2 Months With Evening Primrose Oil, Scandinavean Journal of Rheumatology, 1986

Stargardt's Disease

1. Avoid Vitamin A (2016) for Stargardt's
Learn more about complementary treatment for Stargardt's disease.

For most vision conditions vitamin A plays an important and necessary role. This article discusses how vitamin A plays opposing roles in Stargardt's disease, where it should be avoided, and retinitis pigmentosa, where it is helpful.

Usually vitamin A helps to increase macular pigmentation increasing protection to the retina. But in Stargardt's patients it increases the rate of toxic waste accumulation because vitamin A cannot be properly metabolized. In these patients the nutrient lutein also increases pigmentation in the retina but does not cause vision degradation.

The researchers evaluated the dietary habits and consumption of vitamin A in 24 patients with Stargardt's and retinitis pigmentosa. The patients were evaluated using standardized testing procedures that indicate either condition. In both groups the age that symptoms of the condition appeared were taken into consideration as indicators of the severity of the condition - where the condition appears at a younger age it is more severe.

The researchers looked at eating habits involving 109 foods over a yearly period as opposed to seasonal or a few weeks' eating habits. They asked how often the patients ate each of the listed foods - whether daily, weekly, monthly, etc.

Comparing recommended dietary intakes to food consumption of these patients diets they found that both groups consumed more total fat, less from polyunsaturated fats, low levels of fiber, high levels of cholesterol, and low levels of some minerals and vitamins -- particularly calcium, potassium, magnesium, vitamin D, B6, and folic acid.

Over 58% of the Stargardt's patients consumed more vitamin A than recommended for that condition, with one patient consuming so much vitamin A as to be considered toxic. That patient had especially poor vision. The 6 patients who consumed very low levels of vitamin A had much better visual acuity.

The RP patients with high levels of vitamin A had later onset of the condition.
Intake of fatty acids was also evaluated. Both patient groups, RP and Stargardt's had diets with insufficient EPA and DHA.

The small sample size imposes some limitations in conclusions but these conclusions agree with animal and other studies investigating vitamin A intake in Stargardt's patients. Diets low in vitamin A and with sufficient other nutrients are recommended.

Researchers: Francesco Sofi, et al.
Published: Dietary profile of patients with Stargardt's disease and Retinitis Pigmentosa: is there a role for a nutritional approach? BMC Ophthalmology, January, 2016.

2. DHA (2010) and Stargardt: Omega-3 Fatty Acids
Learn more about Stargardt's.

In a small study scientists analyzed the efficacy of using DHA (an omega-3 fatty acid) in patients who had been diagnosed with late-onset Stargardt's disease.

The 20 patients were given DHA over a 6 month period and they were tested, before and after the period with a standard eye exam, including visual acuity and an electroretinogram (a test that measures the electrical activity of cells in the retina). There was some improvement (in 4 of 20 patients) but it was not statistically significant.

The researchers concluded that while there was little short-term benefit that DHA did seem to have a beneficial effect on some measures of vision health.

Researchers: Giuseppe Querques, Pascale Benlian, Bernard Chanu, et al

Published: DHA supplementation for late onset Stargardt disease: NAT-3 study, Clinical Ophthalmology, June, 2010.

3. Microcurrent Stimulation (1997, 2002) & Stargardt's Disease
Learn more about treatment for Stargardt's disease..

Several studies on microcurrent stimulation treatment for macular degeneration also tested the treatment method on patients with Stargardt's disease.

See these studies for more information.

Edward Paul, OD, PhD, Published, 2002

Damon Miller, MD, 1997

Uveitis

1. Bilberry (2010) and Uveitis
Learn more about uveitis

Researchers have found that mice with uveitis who were treated with bilberry extract had increased antioxidant levels in blood and improvements in blood levels of vitamin C and antioxidant enzymes such as glutathione peroxidase and superoxide dismutase (SOD). This uveitis in mice was induced by toxins, and represented a useful animal model of human eye inflammation.

The bilberry extract, given orally, reduced elevated nitric oxide and malonidaldehyde levels (both toxins in the blood), and increased the ability of the blood to absorb oxygen as well as increasing glutathione, vitamin C, and SOD levels in the blood, as well as other beneficial changes in blood chemistry.

Researchers: N. Yao, F. Lan, R.-R. He, H. Kurihara; Institute of Traditional Chinese Medicine and Natural Products, Jinan University, Guangzhou 510632, China.

Published: Journal of Agricultural and Food Chemistry, March 2010. Protective Effects of Bilberry (Vaccinium myrtillus L.) Extract against Endotoxin-Induced Uveitis in Mice.

2. Curcumin (2010) and Uveitis
Learn more about uveitis

Researchers have known for some time that tumeric (curcumin) is helpful for inflammatory conditions. A one year study evaluated the effectiveness of tumeric supplements in preventing relapses of uveitis.

The researchers looked at 3 groups of uveitis patients: those with autoimmune uveitis, those with herpetic uveitis, and other forms of uveitis. They evaluated frequency and severity of relapses and overall quality of life.

They found that the specific product which contained curcumin had the capacity to reduce symptoms after a few weeks in more than 80% of the 122 patients.

Their study also demonstrated promising results for other vision inflammatory-related conditions such as dry eye, diabetic retinopathy, glaucoma, and pathological conditions of the macula such as macular degeneration, choroidal neovascularization, cellophane maculopathy, and retinitis pigmentosa.

This study substantiates the findings of a small 1999 study: (Efficacy of curcumin in the management of chronic anterior uveitis. Phytother Res. 1999. Department of Ophthalmology, K.G. Medical College, Lucknow, India.

Researchers: Pia Allegri, Antonio Mastromarino, and Piergiorgio Neri

Published: Clin Ophthalmol. 2010; 4: 1201-1206.

3. Echinacea (2006) and Uveitis
Learn more about uveitis

A small pilot study examined the value and safety of echinacea in mild forms of uveitis.

The researchers evaluated the results of treating 51 patients with steroid-dependent, low-grade, autoimmune, anterior or intermediate uveitis. The patients had been taking oral prednisone. 31 of the patients received 150mg echinacea two times a day, and 20 continued with the conventional steroid treatment. After 9 months, follow up demonstrated that almost 90% of the patients receiving echinacea showed improvement and vision acuity and reduction of symptoms.

Researchers: Neri PG, Stagni E, Filippello M, Camillieri G, Giovannini A, Leggio GM, Drago F., Department of Neurosciences - Ophthalmology Section, Polytechnic University of Marche, Ancona, Italy.

Published: J Ocul Pharmacol Ther. 2006 Dec;22(6):431-6., Oral Echinacea purpurea extract in low-grade, steroid-dependent, autoimmune idiopathic uveitis: a pilot study.

4. Essential Fatty Acids (2004, 2010) & Uveitis
Learn more about treatment of uveitis.

Researchers investigated whether any of the essential fatty acids would be helpful in treating chronic inflammation of the uvea (iris, ciliary body, choroid) which is known as uveitis. The condition is a factor for other serious eye diseases such as cataracts, glaucoma, and macular degeneration.

2010

Lab animals with uveitis (caused by endotoxin treatment) were given oral doses of eicosapentaenoic acid (EPA) one of the omega-3 essential fatty acids.

Editor's Note: Krill oil supplies the omega-3 fatty acids, EPA, DHA & vitamin A.

After 24 hours the animals showed marked decreases in levels of white blood cells being attracted to the damaged tissue ("leukocyte adhesion"), and certain protein levels indicative of inflammation in the retina and the choroid/RPE tissues were also reduced. In addition, phosphorylation was reduced.

These results led the reseachers to conclude that EPA can be very helpful in preventing and treating eye diseases of inflammation.

Researchers: Misa Suzuki, Kousuke Noda, et al.

Published: Eicosapentaenoic acid suppresses ocular inflammation in endotoxin-induced uveitis, Molecular Vision, July, 2010.

2004

The omega-6 fatty acid - linoleic acid - can be either helpful for inflammatory conditions or problematic if given in too-large quantities.

Uveitis is considered a "type 2" autoimmune condition. Linoleic acid suppresses the overproduction of some biochemicals which characterize psoriasis, alopecia areata (hair loss), rheumatoid arthritis, MS, Crohn's, type 2 diabetes, and some kinds of uveitis. However, too high a dosage of linoleic acid may aggravate some of these disorders.

Researcher: M.R. Namazi

The beneficial and detrimental effects of linoleic acid on autoimmune disorders, Autoimmunity, February, 2004.

Editor's Note: The ratio of omega-6:omega-3 in the diet is important for your health. Humans may evolved with a ratio of 1:1 (omega-6:omega-3). 2-3:1 lessens symptoms of rheumatoid arthritis and a similar ratio would be suggested for uveitis. Learn more about the omega-6:omega-3 ratio.

5. Lutein (2011, 2015) & Uveitis
Learn more about treating uveitis.

2015

Researchers investigated the role of the antioxidants lutein and zeaxanthin on uveitis in lab animals.

The combination of the two powerful antioxidants acted to reduce certain cell extracts and lysates and inhibited signal pathways that are characteristic of uveitis.

The researchers concluded that these antioxidants should be explored for managing uveitis conditions.

Researchers: S.C. Chao, T. Vagaggini, et al.

Published: Effects of Lutein and Zeaxanthin on LPS-Induced Secretion of IL-8 by Uveal Melanocytes and Relevant Signal Pathways, Journal of Ophthalmology, November, 2015.

2011

Researchers have studied how antioxidants can support healing for the inflammatory condition uveitis. Lutein is known for its protection of the retina and other tissues of the eye. This study investigates how lutein functions in lab animals with uveitis.

Test mice were give lutein in their drinking water for five consecutive days, while controls were given plain drinking water before uveitis was induced.

The animals who received the lutein had significantly lower levels of nitric oxide and malondialdehyde content (both are indicative of inflammation).

Furthermore, the animals who received lutein demonstrated increased activity and ability to absorb vitamin C, glutathione, superoxide dismutase and glutathione peroxidase. Lutein also improved the expression of other necessary mineral in the mice.

The researchers concluded that Lutein's antioxidant properties contributed to fighting the inflammatory response characteristic of uveitis.

Researchers: R.R. He, B. Tsoi, et al.

Published: Antioxidant properties of lutein contribute to the protection against lipopolysaccharide-induced uveitis in mice, Chinese Medicine, October, 2011.

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Myopia (nearsightedness)

Night Blindness

Ocular Herpes

Optic Neuritis

Osteoarthritis

Osteoporosis

Peptic Ulcers

Pterygium

Retinal Detachment

Retinitis Pigmentosa

Rheumatoid Arthritis

Sjogren's Syndrome

Stargardt's Disease

Uveitis

Research Bibliography for Eye Conditions
and Other Diseases