AREDS, AREDS2: (2001, 2006, 2013) Antioxidants & Macular Degeneration


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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:

  1. zinc alone;
  2. antioxidants alone;
  3. antioxidants and zinc;
  4. 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.