Chronic Fatigue Syndrome (CFS)

There is nothing you can do to speed up your recovery than to rest and wait.

There are a number of proactive things you can do to help recover.

What is chronic fatigue syndrome?

Chronic fatigue syndrome (CFS) is defined as disabling fatigue lasting more than six months that reduces activity by more than half. No single cause for CFS has been identified. Suggested causes include chronic viral infections, food allergy, adrenal gland dysfunction, and many others; but none has been convincingly documented in more than a minority of sufferers.

In addition to fatigue, there may also be muscle pain, joint pain not associated with redness or swelling, short-term memory loss, and an inability to concentrate. Some people with chronic fatigue syndrome also experience difficulty sleeping, swollen lymph nodes, and/or mild fever.

General Theories for Chronic Fatigue Causes

Theories abound about the causes of chronic fatigue syndrome. Many physicians still doubt that CFS is an actual disease but believe rather that it is a component of a psychological disorder or a symptom of other problems, similar to anemia and high blood pressure. Indeed, no primary cause has been found that explains all cases of CFS. And, there are no consistent biologic factors that would allow objective measures, such as blood tests or brain scans, to definitively diagnose CFS.

Convergence of Factors. A number of experts believe that CFS develops from a convergence of conditions that may include the following:

• Genetic factors.
• Brain abnormalities.
• A hyper-reactive immune system.
• Viral or other infectious agents.
• Psychiatric or emotional conditions.

For example, the majority of patients report some preceding moderate to serious physical (eg, a chronic viral infection) or emotional event (eg, episode of depression). Some experts theorize that such events alone or in combination coupled in people with certain neurologic and genetic abnormalities may trigger the event. Still, it is not clear what sequence of events actually leads to the fatigue and other prominent symptoms of this disorder. Nor is there any specific neurologic abnormality that experts can point to with assurance. Sudden- and Gradual-Onset CFS. One interesting theory is that CFS can be categorized as either sudden- or gradual onset, with each category having different causes. In little over half of patients, the onset is sudden, while the remaining patients have a slow onset. Some experts believe that sudden-onset CFS may be triggered by a virus or neurologic abnormality, while gradual-onset CFS might have a psychologic cause. Supporting this theory was a study that observed that MRI scans of the brains of CFS patients without an accompanying psychiatric problem showed small injuries suggesting either a viral infection or neurologic problem.

Central Nervous System and Hormone Abnormalities

Abnormalities in the central nervous system, including pinpoint spots of brain inflammation and abnormal levels of certain hormones have been reported in a number of patients with CFS, but similar findings have also been found in those without the illness.

Abnormalities in the Hypothalamus-Pituitary-Adrenal Axis. Of particular interest to researchers are higher incidences of abnormalities in the brain system known as the hypothalamus-pituitary-adrenal axis. This system produces or regulates hormones and brain chemicals that control important functions, including sleep, response to stress, and depression.

Stress Hormone Deficiencies. A number of studies on CFS patients have observed deficiencies in cortisol levels, a stress hormone produced in the hypothalamus. Deficiencies may be the reason why CFS patients have an impaired and weaker response to psychologic or physical stresses (such as infection or exercise).

Abnormalities in Neurotransmitters. Other research has reported that some patients with CFS have abnormally high levels of serotonin, a neurotransmitter (chemical messenger in the brain). Such elevated levels in the brain are associated with fatigue. Yet another study reported that deficiencies in dopamine, another important neurotransmitter, may play a role in CFS.

Infections

Because most of the features of CFS resemble those of a lingering viral illness, many researchers have focused on the possibility that a virus or some other infectious agent causes the syndrome in some cases. There are three basic theories for infection-related causes of CFS:

• One theory referred to as "hit and run" suggests that chronic fatigue syndrome might be the result of a virus or bacteria that infects the body, causes immune abnormalities, and is then eliminated. It leaves behind a damaged immune system, however, that continues to cause flu-like symptoms even in the absence of the virus.
• Another theory posits that an abnormal immune response reactivates a virus that had persisted in a latent (inactive) stage after an initial infection.
• A psychologic response to viral infections occurs in susceptible individuals.

Still, not all CFS patients show signs of infection.

Evidence that Supports a Viral Cause. The evidence for CFS having a viral cause is not based on hard evidence but on various observations that suggest an association, such as the following:

• In up to 80% of cases, chronic fatigue syndrome starts suddenly with a flu-like condition.
• In the US, outbreaks of CFS occurring within the same household, workplace, and community have been reported (but most have not been confirmed by the Centers for Disease Control.)
• A large British study of people with both diagnosed CFS and idiopathic chronic fatigue also found no evidence of infection as a direct cause of either condition, but found that previous infections may play some role.
• Some researchers are suggesting that changes in normally harmless bacteria found in the intestine may play a role in the development of CFS symptoms.
• Although no specific virus has been identified as a single cause, CFS patients typically have elevated levels of antibodies to many viruses that cause fatigue and other CFS symptoms, including Lyme disease, candida ("yeast infection"), herpesvirus type 6 (HHV-6), human T cell lymphotropic virus (HTLV), Epstein-Barr, measles, coxsackie B, cytomegalovirus, or parvovirus.

Evidence that Does Not Support an Infectious Cause.

• Most cases of CFS occur sporadically, cropping up individually without appearing to be contagious.
• There is no evidence that CFS is spread through casual contact, such as shaking hands or coughing, or by intimate sexual contact.
• No single virus has been implicated in chronic fatigue syndrome. Well-designed studies of patients who met strict criteria for chronic fatigue syndrome and of patients with idiopathic chronic fatigue have not found an increased incidence of any specific infections.

Immune System Abnormalities

CFS has sometimes been referred to as the "chronic fatigue immune dysfunction syndrome." A number of studies have found many irregularities of the immune system, although there is no consistent pattern. Some components appear to be overreactive, whereas others appear to be underreactive.

Allergies. Some, although not all, studies have reported that a majority of CFS patients have allergies to food, pollen, metals (such as nickel or mercury), or other substances. (Most allergic people, in any case, do not have CFS.) Some research indicates that people with both allergies and emotional disorders, such as anxiety or depression, may be more vulnerable to the effects of the inflammatory response. This is a harmful overreaction of the immune response, which triggers the release of a number of immune factors, that can cause fatigue, joint aches, and fever, which can also affect the hypothalamus-pituitary-adrenal system in the brain.

One theory that may help tie in some of the various factors common to CFS suggests that allergies, stress, and infections may deplete a chemical in the body called adenosine triphosphate (ATP). This chemical stores energy in cells and studies have reported a deficiency in many CFS patients. Supporting this theory was a study in which patients reported reduced CFS symptoms after they took a coenzyme called NADH, which increases ATP levels.

Autoimmune Abnormalities. The risk profile for chronic fatigue syndrome is similar to the risk profiles for a number of autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, and multiple sclerosis. These disorders also have early symptoms resembling CFS. Common to such diseases are the presence of high levels of autoantibodies, antibodies that attack the patient's own cells. Some studies are finding high levels of autoantibodies directed against substances in cell nuclei in CFS patients. Others, however, have found no evidence of an autoimmune factor.

Overactive Immune System. In one study, some patients, particularly those with severe CFS symptoms, had higher-than-normal numbers of infection-fighting white blood cells known as CD8 killer T cells, which launch attacks on invading viruses and other disease-causing microorganisms. These same people had lower-than-normal levels of another white blood cell known as the suppressor T cell, which helps to shut down the immune response once the invading organisms have been killed. In such cases, the immune system becomes persistently overactive and produces fatigue, muscle aches, and other symptoms of CFS.

Deficiencies in Natural Killer Cells. Other studies have indicated lower amounts of so-called natural killer cells in many CFS patients, which might make them more susceptible to viruses.

Neurally Mediated Hypotension

Some studies have observed that a subgroup of patients who fit the strict criteria for chronic fatigue syndrome also have a condition known as neurally mediated hypotension (NMH). NMH causes a dramatic drop in blood pressure when standing up, even for as short a time as ten minutes. It is the result of an abnormality in the central nervous system that signals the heart to slow down and lower blood pressure when a person stands up. Blood pools in the feet and legs before circulating back up to the heart. Its immediate effect can be light-headedness, nausea, and fainting. Some experts posit that a virus or infection may cause injury to the central nervous system that results in NMH. One 1999 study suggested that patients with NHM-associated chronic fatigue syndrome tend to be younger and to recover from CFS sooner than patients whose symptoms are not related to NMH. A less severe hypotension condition known as postural orthostatic tachycardia syndrome (POTS) is also associated with CFS. Not all CFS patients experience NMH and, in fact, one 2001 twin study found no higher incidence of NMH in chronic fatigue patients. Major studies need to be done and the results repeated with larger patient groups before they can be applied to the majority of CFS patients.

Physical Deconditioning and Disturbed Circadian Rhythms

Some experts believe that CFS is a disorder of the sleep-wake cycle (the circadian rhythm). Some argue that this disruption may be precipitated by some mentally or physically stressful event, such as a virus. CFS patients are unable to reset their natural rhythm, which then results in a perpetual cycle of sleep disturbances. According to one theory, this causes avoidance of activity that in turn leads to physical debilitation, which is the primary cause of CFS symptoms. Nevertheless, some studies, including one in 2001, observed that CFS patients are no more physically unfit than sedentary non-CFS peers. The results of these studies indicate then that CFS is not the result of physical unfitness, but that the limited level of activity among CFS is due to the fatigue and symptoms of disease itself.

Psychosocial Factors

Psychological, personality, and social factors are strongly associated with chronic fatigue in most, but not all patients. The complex relationship between physical and emotional factor has yet to be fully understood, however. Psychologic factors are unlikely to be a primary cause of CFS, but they may play a role in increasing susceptibility to onset or perpetuation of the disorder. In many cases, CFS also promotes psychologic and social dysfunction.

Other Theories

Muscle Defect. Patients with CFS sometimes complain that they feel so weak that it seems as if their muscles are no longer working properly. It has been proposed that a defect in skeletal muscle could be the cause of the fatigue. However, physical, chemical, and metabolic studies have not found any consistent pattern of abnormalities in the muscles of these patients.

Hyperventilation. Another theory to account for some cases of chronic fatigue syndrome is hyperventilation, the tendency to "over-breathe," which can be caused by many conditions, including asthma, hyperthyroidism, infections, and anxiety disorder. Chronic hyperventilation can cause an imbalance in oxygen and carbon dioxide, which may produce chest pain, faintness, numbness in the fingers and toes, and motor impairment. In one study, although a significant number of CFS patients experienced hyperventilation, there were no differences in CFS symptoms between patients with hyperventilation and patients who did not experience it. Hyperventilation is very unlikely to be a cause of many instances of chronic fatigue.

Abnormalities in the Vagus Nerves. One study found that after CFS patients exercise, they exhibit slight abnormalities in the activity of the vagus nerves on the heart. (The vagus nerves run down each side of the neck and end at the intestines and affect many bodily functions.)

Mutations in Mitochondria. One theory about the cause of CFS, as well as fibromyalgia and other illnesses, concerns mutations of the mitochondria, the part of each cell that supplies energy. Inherited disorders involving mutations that affect mitochondria are known to cause fatigue and muscle pain. One study reported that a specific genetic mitochondrial mutation called cytochrome b was associated with intolerance to exercise and aches and pains in a group of patients who had no known family history of mitochondrial genetic disease. In such cases, the mutation might have been due to environmental assaults, such as viruses. More work is warranted on this interesting observation to determine if such a mutation may account for some cases of CFS.

Since there is no definitive conventional therapy for CFS, doctors use a combination of lifestyle changes, including aerobic exercise, healthy diet, stress reduction, phototherapy, and psychological counseling. Prescription medications may also be used and include anti-anxiety drugs, antidepressants, hydrocortisone, and pain relievers.

Self Help:

Key nutritional supplements

• None

Other nutritional supplements that may be helpful

• Potassium aspartate-magnesium aspartate combination: 1 gram twice per day.
• Vitamin B12: 2,500–5,000 mcg given by injection every two to three days.
• L-carnitine: 1 gram taken three times daily for eight weeks.
• NADH (nicotinamide adenine dinucleotide): 10 mg per day for four weeks.

Key herbs

• None

Other herbs that may be helpful

• Licorice (Glycyrrhiza glabra) root: 2.5 grams of licorice root daily for six to eight weeks.
• Asian ginseng (Panax ginseng) and Siberian ginseng (Eleutherococcus senticosus)*: One of these herbs may be taken for six to eight weeks after licorice has been discontinued.

Lifestyle changes that may be helpful

• Exercise: Many patients report feeling better after undertaking a moderate exercise program. However, most people with CFS are sensitive to overexertion and excessive exercise may lead to consistently worsening fatigue and mental functioning. Exercise should be attempted gradually, starting with very small efforts (e.g., 30 minutes of walking a few times per week).

Dietary changes that may be helpful

• Maintain adequate salt intake: Some doctors believe that for people with CFS who have low blood pressure, salt should not be restricted. In CFS sufferers who have a form of low blood pressure triggered by changes in position (orthostatic hypotension), some have been reported to be helped by additional salt intake. People with CFS considering increasing salt intake should consult a healthcare practitioner before making such a change.

Other integrative approaches that may be helpful

• Behavioral therapy: Coping mechanisms for dealing with stress.

Dietary Modification

Some doctors believe that people with CFS who have low blood pressure should not restrict their salt intake. Among CFS sufferers who have a form of low blood pressure triggered by changes in position (orthostatic hypotension), some have been reported in a preliminary study to be helped by additional salt intake.1 People with CFS considering increasing salt intake should consult a doctor before making such a change. (See the Herb information, below, for more information on blood pressure and CFS.)

Lifestyle Modification

Exercise is important to prevent the worsening of fatigue. Many people report feeling better after undertaking a moderate exercise plan.2 3 However, most people with CFS are sensitive to overexertion, and excessive exercise may lead to consistently worsening fatigue and mental functioning.4 5 6 Exercise should be attempted gradually, starting with very small efforts. One small study found that intermittent exercise, in which patients walked for three minutes followed by three minutes of rest for a total of 30 minutes, did not exacerbate their CFS symptoms.7

Nutritional Supplement Treatment Options

The combination of potassium aspartate and magnesium aspartate has shown benefits for chronically fatigued people in double-blind trials.8 9 10 11 However, these trials were performed before the criteria for diagnosing CFS was established, so whether these people were suffering from CFS is unclear. Usually 1 gram of aspartates is taken BID, and results have been reported within one to two weeks.

Vitamin B12 deficiency may cause fatigue. However, some reports,12 even double-blind ones,13 have shown that people who are not deficient in B12 have increased energy following a series of vitamin B12 injections. Some sources in conventional medicine have discouraged such people from taking B12 shots despite this evidence.14 Nonetheless, some doctors have continued to take the limited scientific support for B12 seriously.15 In one preliminary trial, 2,500 to 5,000 mcg of vitamin B12 given by injection every two to three days led to improvement in 50 to 80% of a group of people with CFS; most improvement appeared after several weeks of B12 shots.16 While the research in this area remains preliminary, people with CFS considering a trial of vitamin B12 injections should consult a doctor. Oral or sublingual B12 supplements are unlikely to obtain the same results as injectable B12, because the body’s ability to absorb large amounts is relatively poor.

A preliminary trial has shown that people with CFS have reduced functional B-vitamin status when compared to people without the condition.17 The functional vitamin deficiency seen in this study was most pronounced for vitamin B6. Double-blind trials are needed to establish whether B-vitamin supplementation is effective in people with chronic fatigue syndrome.

L-carnitine is required for energy production in the powerhouses of cells (the mitochondria). There may be a problem in the mitochondria in people with CFS. Deficiency of carnitine has been seen in some CFS sufferers.18 One gram of carnitine TID for eight weeks led to improvement in CFS symptoms in one preliminary trial.19

NADH (nicotinamide adenine dinucleotide) helps make ATP, the energy source the body runs on. In a double-blind trial, people with CFS received 10 mg of NADH or a placebo each day for four weeks.20 Of those receiving NADH, 31% reported improvements in fatigue, decreases in other symptoms, and improved overall quality of life, compared with only 8% of those in the placebo group. Further double-blind research is needed to confirm these findings.

Magnesium levels have been reported to be low in CFS sufferers. In a double-blind trial, injections with magnesium improved symptoms for most people.21 Oral magnesium supplementation has improved symptoms in those people with CFS who previously had low magnesium levels, according to a preliminary report, although magnesium injections were sometimes necessary.22 These researchers report that magnesium deficiency appears to be very common in people with CFS. Nonetheless, several other researchers report no evidence of magnesium deficiency in people with CFS.23 24 25 The reason for this discrepancy remains unclear. If people with CFS do consider magnesium supplementation, they should have their magnesium status checked by a doctor before undertaking supplementation. It appears that only people with magnesium deficiency benefit from this therapy.

Dehydroepiandrosterone, more commonly known as DHEA, is a hormone now available as a supplement. In one report, DHEA levels were found to be low in people with CFS.26 Another research group reported that, while DHEA levels were normal in a group of CFS patients, the ability of these people to increase their DHEA level in response to hormonal stimulation was impaired.27 Whether supplementation with DHEA might help CFS patients remains unknown due to the lack of controlled research. DHEA should not be used without the supervision of a healthcare professional.

Contraindications