Fatigue: the Most Common Symptom




Fatigue is one of the most frequent symptoms that brings a patient to the doctor. The causes are numerous and, in fact, it can accompany almost any illness. The presence of fatigue is, however, an important indicator of serious disease. In 1979 Dr. Cuyler Hammond's report on the 20 year long Cancer Prevention Study, which surveyed over a million Americans, found that a positive answer to the question "do you fatigue easily?" was predictive of a higher death rate from disease, including cancer, than any other question!

Chronic fatigue Syndrome (CFS) is not a new disease; however in the past few years it has seemingly increased in frequency and severity. After a large number of cases were reported in 1984 at Incline Village, Nevada, the National Institute of Health assigned a full time researcher. When calls for information went over 1000 per month, Center for Disease Control launched a million dollar investigation and assigned a hot-line number (404-332-4555).

A national conference was held in San Francisco in mid-1989 and a formal definition of CFS was accepted by CDC, giving it new disease status. This includes 11 symptoms and 3 physical signs but essentially it is defined as newly occurring persistent or relapsing fatigue that reduces activity below 50 percent of normal for at least six months. Flu-like symptoms, including fever, sore throat, painful lymph nodes and muscle weakness and pain, as well as headache, insomnia, irritability and mood depression also occur. The consensus was that CSF is a disease, possibly reflects a new organism or virus and occurs in about 5 percent of patients with fatigue.

The diagnosis of fatigue syndrome is only the latest in a long list of labels to denote this common symptom. In the late 19th Century and until the 1940's it was called neurasthenia, a French word that translates literally, weak nerves. This term was removed from the manual of psychiatric diagnosis only a decade ago and replaced by the diagnosis, depression. Hypochondriasis is another label traditionally offered in explanation of those who suffer chronic fatigue. Faced with a disabling condition and no apparent diagnosis, the doctor of the past was commonly tempted to resort to a psychologic diagnosis.

Doctor’s offices are now equipped to diagnose viruses and so doctors are more likely to consider viruses in puzzling cases. Epstein Barr, Herpes and Cytomegalo viruses have all been researched but found to be present no more in fatigue patients than the rest of us. So strongly does the CSF case profile fit the syndrome of viral illness, including sore throat and swollen lymph nodes in many cases, that UCSF virologist Jay Levy suggests that it is "a new agent, not readily recoverable or we would have found it."

Patients seem to identify with the concept of "stress." In a survey of almost 300 fatigue patients in San Francisco, over half blamed stress. This is unlikely to be the cause though it can evidently aggravate the syndrome of disabling fatigue. When present stressful circumstances are obvious; however, stress is an ever-present part of life and we are designed to adapt and become stronger thereby—and we do if we are not first sick, toxic or depleted.

In this regard, a survey by Dr. Carol Jessop, of 1100 CSF patients, 80 percent reported recurrent infections as children, acne as adolescents and chronic bowel problems, hives, headaches and anxiety attacks. Over 90 percent had high cholesterol levels. This certainly points to pre-existing illness, depletion and toxicity. She also reported recovery in about 60 percent after treatment with a sugar free diet and ketoconazole (Nizoral) for presumed yeast infection (Candida).

This intriguing finding has persuaded many that Candida is a cause of CSF and that the removal of dietary sugars removes the favorite food of the yeast organism so that it will be less likely to relapse after drug treatment. The high frequency of responders to Nizoral has encouraged many doctors to prescribe this sometimes dangerous drug on presumptive evidence, ie. no actual identification of yeast organisms. This has generated a very heated controversy, not yet resolved.

It is as likely that the success of Nizoral is due to its chemical action, which blocks cortisone synthesis. Isn't that a paradox? CSF is aggravated by stress and yet here is a treatment that works by interfering with the anti-stress hormone! How can that be? One possible way is via the amino acid, tryptophan, which breaks down into a toxic by-product, xanthurenic acid. Cortisone promotes this directly by enzyme activation. Viral infections do so indirectly via gamma interferon, which stimulates the same enzyme, tryptophan oxidase. The effect is to shunt tryptophan into the manufacture of xanthurenic acid, which is known to cause auto-immune symptoms, such as muscle inflammation and pain. It also can cause diabetes, ie. blood sugar disturbance; hence the success of therapy that restricts sugars. And by blocking cortisone Nizoral prevents the production of toxic xanthurenic acid.

Modern medicine relies on differential diagnosis to assure completeness in reviewing possible causes of disease. There are ten general categories to be considered: 1) nutrition; 2) metabolic; 3) toxic; 4) infection; 5) allergy; 6) intestinal malabsorption; 7) cancer; 8) trauma; 9) genetic; 10) psychologic. Each of these categories of illness can cause fatigue and a complete discourse would fill a textbook. I put nutrition first because it is the most common cause of general fatigue and always a factor in treatment.

Nutrition surveys in our country document widespread deficiency of folic acid, vitamin B6, magnesium and zinc, all of which influence energy and immune power. Iron and vitamin B1 are both crucial to energy and endurance and both are commonly at risk, especially in women and adolescents. Vitamin A deficiency must be considered in all who are chronically ill or taking medication. Vitamin C deficiency causes severe fatigue early on, within a few weeks at low intake. In the many Americans who do not eat fresh, uncooked fruits and vegetables or take vitamin pills, this is a problem.

Amino acids can be important, especially methionine, which is often low in vegetarian diets and in those actively reducing intake of animal products. Coenzyme Q is often remarkably helpful in these cases. Lysine is at risk in those whose diets consist mostly of cooked foods, especially foods cooked in the presence of sugars. Essential Fatty Acids, particularly the omega-3 variety, are generally low in our diet and their replenishment is often followed by a boost in energy level. Vitamin E, which is depleted by diets high in polyunsaturates, is also an energy booster.

Nutrition deficiency is aggravated by any intestinal disorder. Food intolerances, particularly milk and wheat, commonly cause chronic inflammation. Infection with the parasite, Giardia lamblia, often found in public water supplies in America if unfiltered, can cause chronic bowel inflammation. Intestinal diagnosis is often hard to pin down and symptoms are not always severe enough to be diagnosable. However chronic irritation can cause malabsorption and measurement of vitamins, minerals and amino acids is often the most sensitive evidence.

Environmental pollution has been suspect in CSF, particularly since some researchers have found cell membrane damage similar to effects of the organic chlorine pesticides, such as DDT, chlordane, lindane and dioxins, chemicals that linger in the body for decades. In my own series of 100 patients, fatigue was not increased in the high organochlorine group. However I have seen chronic fatigue in patients with low cholinesterase levels, an indication of sensitivity to malathion and other organophosphates, the most common pesticides now in use. A blood test to measure cholinesterase in plasma and red blood cells is indicated in CSF.

Treatment of fatigue states is most likely to be effective if directed to a specific diagnosis; hence laboratory testing is recommended. In addition to the nutrient factors above, there are tests to identify metabolic problems, such as: thyroid excess or deficiency, hypoglycemia or diabetes, parathyroid disorder, adrenal excess or deficiency and other hormonal disorders.

Specific testing is also available to identify toxic metals. such as mercury from dental amalgam and house paints; aluminum from antacids, medications and cooking with fluoridated water in aluminum containers. Lead pollution is decreasing in the United States since the Lead Paint Control Act of 1974 but the hazard from remodeling, earthenware and pewter is still present. The hair mineral test panel is the most convenient and inexpensive screening test for exposure to lead and mercury. It can also measure fluoride.

©2007 Richard A. Kunin, M.D.