~Chronic Fatigue Syndrome (CSF) - Treatments and Therapy

~Chronic Fatigue Syndrome (CSF) - Treatments and Therapy

Patient Management of CFS

Physicians advise patients with CFS to pace themselves carefully and to avoid unusual emotional or physical stress. Follow a regular and manageable daily routine and take modest regular exercise under the supervision of a physician or physical therapist. In some instances, acupuncture, aquatic therapy, chiropractic, massage, self-hypnosis, stretching, tai chi, therapeutic touch, and yoga have proven helpful in managing CFS. Certain psychotherapies such as family therapy have shown promise in the development of coping skills that are necessary to counter the adverse effects of chronic illness on the family or patient's caregiver.

Prescription Medications

There are currently no FDA-approved prescription medications for use in treating CFS. There are, however, a number of medications that are used to treat the various symptoms of CFS. Many are recommended for effects that may be unrelated to their primary use. These may include antidepressants, antifungals, antihistamines, antivirals, CNS depressants (or stimulants), immunoglobulins, cardiac medications, anti-inflammatories, anticonvulsants, corticoids, and expectorants.



Ampligen is an experimental antiviral medication currently in Phase III testing for the treatment of CFS. It is considered a "second generation interferon." In clinical trials conducted outside the United States, more than 50% of test subjects taking Ampligen showed both physical and mental improvement of symptoms. Unfortunately, most of the study groups were too small for the results to be published in the scientific literature. Although some researchers in the United States remain skeptical concerning Ampligen, Hemisherx Biopharma (Philadelphia), the drug manufacturer, is hoping that the current research trials will provide enough hard data to meet the criteria of FDA approval.

  • Ginseng And Echinacea
  • Essential Fatty Acids
  • Coenzyme Q10
  • NADH
  • L-Carnitine
  • Magnesium
  • DHEA
  • Digestive Enzymes
  • Glutamine
  • Whey Protein
  • Adapton
  • Folate
  • Licorice
  • Tyrosine
  • MATÉ
A report in the Annual Review of Medicine stated that CFS "is an illness characterized by activation of the immune system, various abnormalities of several hypothalamic-pituitary axes, and reactivation of certain infectious agents" (Komaroff et al. 1998). This suggests that an individual with CFS should follow a regimen that involves protecting and enhancing the immune system with proper nutritional supplements, proteins, and hormones. Free radicals play a role in causing damage to the immune system.

A comprehensive approach to CFS would address several key areas, based on the results of laboratory tests, including:
  • Immune support (antiviral): ginseng, echinacea, essential fatty acids
  • Supplements involved in energy metabolism: CoQ10, NADH, L-carnitine, and magnesium
  • Adrenal support: DHEA, licorice, and sodium
  • Stress: glutamine and Adapton
  • Brain hormones and neurotransmitters: tyrosine
  • Homocysteine metabolism: B6, B12, folic acid, and SAMe
  • Antioxidants: glutathione, N-acetyl-cysteine, and alpha-lipoic acid
  • Fatigue: ginseng and Maté
  • Digestive support: digestive enzymes
Ginseng and Echinacea

Commission E, the group of scientists that advises the German government about herbs, endorses ginseng "as a tonic to combat feelings of lassitude and debility, lack of energy and ability to concentrate, and during convalescence" (Bahrke et al. 2000).

Ginseng is highly prized in China as an herb that increases energy. The higher grades are extremely expensive.

Echinacea has become very popular in the United States as "the herb" to take for colds and flus. It is known for its ability to stimulate the immune system and suppress infection-causing microbes.

Essential Fatty Acids

The use of essential fatty acids in CFS is controversial. It has been proposed that essential fatty acids play a role in CFS. One possible mechanism is that viruses, as part of their attack strategy, may reduce the ability of the cells to make 6-desaturated essential fatty acids (Horrobin 1990; Gray et al. 1994).

The use of essential fatty acids for postviral fatigue syndrome was examined in a double-blind, placebo-controlled study of 63 adults (Behan et al. 1990). The patients had been ill for 1-3 years after an apparent viral infection and had severe fatigue, myalgia, and a variety of psychiatric symptoms. The patients received either placebo or a preparation containing linoleic, gamma-linolenic, eicosapentaenoic, and docosahexaenoic acids (8 500-mg capsules daily) over a 3-month period. Participants were asked to assess their improvement at months 1 and 3. The treatment group showed continual improvement, whereas many in the placebo group reverted toward baseline.

Improvement with Essential Fatty Acid Treatment

TimeTreatment GroupPlacebo
1 month74%23%
3 months85%17%

The essential fatty acid composition of the subjects' red cell membrane phospholipids was analyzed at the first and last visits. The essential fatty acid levels were abnormal at the baseline and corrected by active treatment. The authors concluded that essential fatty acids provide a rational, safe, and effective treatment for patients with postviral fatigue syndrome (Behan et al. 1990).

A follow-up study of 50 patients diagnosed with CFS found no significant difference between the placebo group and those treated with Efamol marine, an essential fatty acid formula. In addition, no difference was seen in red cell membrane lipids between the patients and control group (Warren et al. 1999). These results sharply contrasted the previous study by Behan et al. (1990).

Essential fatty acids are termed "essential" because they play a vital role in health. Essential fatty acids are found in healthy oils, such as fish, flax, borage, and perilla. Unfortunately, fatty acids are damaged by heat, and many people are deficient because of the high heats used to process packaged foods.

Coenzyme Q10

Coenzyme Q10 has long been prescribed for CFS patients. CoQ10 is a potent antioxidant that aids in metabolic reactions including the process of forming ATP, the molecule the body uses for energy. Virtually every cell in the body contains CoQ10. It is concentrated in the mitochondria, the area of the cells where energy is produced.

Judy (1996) presented a study of 20 female patients with CFS who required bed rest following mild exercise and 20 healthy controls: 80% of the CFS patients were found to be deficient in CoQ10, which further decreased following mild exercise or over the course of normal daytime activity. After 3 months of CoQ10 supplementation (100 mg/day), the exercise tolerance (400 kg-meters of work) of the CFS patients more than doubled. All patients had improved: 90% had reduction and/or disappearance of clinical symptoms, and 85% had decreased postexercise fatigue (Judy 1996).


NADH (reduced B-nicotanimide dinucleotide) is a coenzyme molecule formed from vitamin B3 (niacin). NADH (along with CoQ10) is essential for the production of energy (ATP) in a process called oxidative phosphorylation.

A randomized, double-blind, placebo-controlled crossover study examined the use of NADH in CFS: 26 eligible patients diagnosed with CFS received either 10 mg of NADH or placebo for a 4-week period. Eight of 26 (31%) responded favorably to NADH in contrast to two of 26 (8%) to placebo. Based upon these encouraging results, the authors decided to conduct a larger study to establish the efficacy of NADH in CFS (Forsyth et al. 1999).

NADH (5-10 mg/day) is most effective when taken in the morning, 30 minutes before breakfast.


Several studies have found deficiencies of the amino acid L-carnitine in patients with CFS, although other studies fail to confirm this. L-carnitine is known to boost energy levels. The lack of consistency in the research literature suggests that there may be a number of marginal nutritional deficiencies that have etiologic relevance to CFS. These deficiencies may include carnitine along with the B-complex vitamins, essential fatty acids, L-tryptophan, zinc, magnesium, and others (Werbach 2000).

Studies show that carnitine given as a supplement to CFS patients results in better functional capacity and improvement of disease symptoms (Plioplys et al. 1995; Plioplys et al. 1997). Other studies have shown a dose of 1000-2000 mg daily has resulted in improvement in those with low levels of energy (Kelly 1998; Werbach 2000).


Magnesium, a mineral utilized by every cell of the body, participates in energy metabolism and protein synthesis. The body vigilantly protects blood magnesium levels, in part because 350 enzymatic processes depend upon magnesium status for activation. Magnesium is stored in tissues and bone, sharing skeletal residency with calcium and phosphorus (Dimai et al. 1998).

An article in Lancet described a randomized, double-blind, placebo-controlled study of 20 patients with CFS. The CFS patients were found to have lower red cell magnesium concentrations. In a clinical trial, 32 CFS patients received either placebo or intramuscular magnesium sulfate every week for 6 weeks. Patients treated with magnesium reported having improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham Health Profile. Red cell magnesium returned to normal in all patients on supplemental magnesium, but in only one patient on placebo. The authors concluded that these results demonstrate that magnesium may have a role in CFS (Cox et al. 1991).

One study, however, found no difference in red blood cell magnesium concentrations in samples from 89 patients with CFS when compared to an age- and sex-matched group selected from the normal population. A magnesium-loading test on six patients found no evidence of deficiency (Hinds et al. 1994).

A study of 93 patients with unexplained chronic fatigue (54% with CFS) examined the relationship between magnesium deficiency and oxidative stress. Magnesium-deficient patients (47%) had lower total antioxidant capacity in plasma which was related to serum albumin. Magnesium-deficient patients whose magnesium body stores did not improve after oral supplementation with magnesium (10 mg/kg/day) had persistently lower blood glutathione levels. The authors concluded that magnesium supplementation was followed by an improvement in magnesium body stores, in serum vitamin E, and in its interrelated stage of lipid peroxidation (Manuel y Keenoy et al. 2000).

Magnesium plays a crucial role in metabolism. It is needed for activating B vitamins, relaxing muscles, and forming ATP, the energy molecule. Fatigue, muscle cramps, and constipation are signs of magnesium deficiency. Taking too much magnesium often leads to diarrhea. The dose is increased until this occurs and then backed off to maintain a normal consistency of stools.


DHEA is a hormone secreted from the adrenal glands. It is a precursor of the sex hormones (estrogen and testosterone). DHEA-S has been shown to have beneficial effects on memory, stress, anxiety, sleep, and depression. Therefore, the deficiency of DHEA-S might be related to the symptoms in patients with CFS. DHEA has been reported to improve energy levels in chronic fatigue patients (Kuratsune et al. 1998).

One study demonstrated the value of DHEA and vitamin C infusion treatment in the control of CFS (Kodama et al. 1996).

A study of 15 subjects with CFS, 15 subjects with major depression, and 11 healthy subjects found that DHEA and DHEA-S levels were significantly lower in the CFS subjects compared to the healthy group. DHEA-S levels, but not DHEA, were lower in the depressives. The authors concluded that DHEA has a potential role both therapeutically and as a diagnostic tool in CFS (Scott et al. 1999).

Another study of DHEA levels in 22 CFS patients and 14 healthy controls found normal basal DHEA levels, but a blunted serum DHEA response curve to ACTH (adreno-corticotropic hormone) injection. ACTH normally stimulates the adrenal glands to secrete DHEA. The authors concluded that endocrine abnormalities play a role in CFS and that a relative glucocorticoid deficiency might contribute to the overall clinical picture in CFS (De Becker et al. 1999).

DHEA is contraindicated in both men and women with hormone-related cancers (refer to the DHEA Replacement Therapy protocol before embarking on DHEA therapy).

Digestive Enzymes

Enzymes are responsible for every activity of life. There are two primary classes of enzymes responsible for maintaining life functions: digestive and metabolic. The primary digestive enzymes are proteases (to digest protein), amylases (to digest carbohydrate), and lipases (to digest fat). These enzymes function as a biological catalyst to help break down food. Raw foods also provide enzymes that naturally break down food for proper absorption. Metabolic enzymes are responsible for the structuring, repair, and remodeling of every cell, and the body is under a great daily burden to supply sufficient enzymes for optimal health. Metabolic enzymes operate in every cell, every organ, and every tissue, and they need constant replenishment.

The capacity of the living organism to make enzymes diminishes with age. Some scientists believe that humans could live longer and be healthier by guarding against the loss of our much-needed enzymes. Supplementation with digestive enzymes helps the body to better absorb nutrients from food and lessens the need for the secretion of natural enzymes, thereby preserving them to assist in vital cellular metabolic functions.


Glutamine is a conditionally essential amino acid that is needed during periods of excessive stress. Glutamine is the preferred energy for enterocytes, the cells lining the gastrointestinal tract. Glutamine is also one of the three amino acids necessary to make glutathione, a potent free radical scavenger.

An article in the British Journal of Sports Medicine described a study of athletes during an intense training period before the 1992 Olympics (Kingsbury et al. 1998). The athletes were divided into three groups that differed in training fatigue and were considered separately. Group A (21 track-and-field athletes) had no lasting fatigue; group B (12 judo competitors) reported heavy fatigue at night but recovered overnight to continue training; group C (18 track-and-field athletes and one rower) had chronic fatigue and had been unable to train normally for at least several weeks. Plasma amino acid analysis showed that group A had a normal amino acid pattern, and both groups B and C had decreased plasma glutamine (average 33%) with, especially in group B, decreased histidine, glucogenic, ketogenic, and branched chain amino acids. Ten athletes in group C presented with infection.

After 3 weeks of additional protein intake, virtually all of the low glutamine levels increased to above 500 micromole/L. Total amino acids increased, and the amino acid pattern normalized: six of the 10 athletes on this protein intake returned to increased training within the 3 weeks. An analysis of the pattern in group C showed a persistent decrease in plasma amino acids (but mainly glutamine) in those with chronic fatigue and infection. Inadequate protein intake appeared to be a factor (Kingsbury et al. 1998). Supplementation with glutamine would benefit chronic fatigue patients by enhancing gut motility, improving plasma glutamine levels, and boosting glutathione.

Whey Protein

In a large proportion of people with CFS, abnormalities are often found in both humoral and cellular immunity. The exact cause of this is not fully understood. One fairly consistent finding in people with CFS is an impaired lymphocyte (T-cell) response to a challenge. That is, the lymphocyte does not respond appropriately or rapidly when presented with an immune challenge. As early research has shown, the ability of lymphocytes to react to an immune challenge is directly related to glutathione levels (Bounous et al. 1999). Continued use of glutathione by lymphocytes may lead to cellular glutathione depletion and immune failure. Because whey is the most effective way to deliver precursors for glutathione synthesis, as well as a recognized way to raise glutathione levels in humans and animals, it is theorized that whey may be especially effective for persons with CFS.


The active ingredients in Adapton (extracts from Garum armoricum, a deep sea fish called the Great Bluefish that is native to Brittany in France) are a class of unique precursors to endorphins and other neurotransmitters that exert a regulatory effect on the nervous system. Adapton is widely used throughout Europe and Japan for the treatment of a wide range of stress-induced disorders.

A study was conducted on 20 patients who had been ill with various forms of chronic fatigue for 1-3 months. Patients were registered and information was collected in accordance with the protocol of the European Fatigue Study Group, which includes scales to measure anxiety, depression, muscle fatigue, mental fatigue, sleep disorders, and headache. Four placebo capsules were given to these patients daily during the first 2 weeks of the study. Then 4 capsules of garum extract were given daily for the next 2 weeks of the study. After 2 weeks on placebo, fatigue symptoms were reduced by an average of 14%, and overall symptoms of anxiety, depression, and insomnia were reduced by 4%. On the other hand, after 2 weeks of taking garum extract, fatigue symptoms were reduced by 51%, and overall symptoms were reduced by 65%. In 2 weeks after discontinuing garum extract therapy, fatigue symptoms increased 15%, and overall symptoms increased 7%. These results demonstrate the broad-spectrum benefits of garum extract for people with chronic stress and fatigue. It is interesting to note that the beneficial effects of garum extract persisted even after the treatment was stopped (Elbaz 1988).

Other studies involved 40 patients who had also been experiencing various forms of chronic fatigue for 1-3 months. Four capsules of garum extract were prescribed daily for 2 weeks. The results, based on the Fatigue Study Group criteria, showed an average benefit of 50% for the 10 functions that most accurately measure fatigue and depression (Crocq et al. 1978; Bugard 1984).

Recognizing the challenge of managing the anxiety and depression, which often appear together and require more than one drug for effective treatment (Sussman 1993a), and also the concerns about typical drug therapy and habituation (Gabe et al. 1991; Sussman 1993b), Dorman et al. (1995) conducted a study to examine the efficacy of Garum armoricum in what was termed "free-floating" anxiety. The study subjects were otherwise healthy college students who experienced significant stress and anxiety from final examinations. The study was controlled and vigilance was maintained to watch for possible side effects. Administration of Garum armoricum resulted in a statistically significant difference in mean anxiety test scores, with the subjects taking Garum armoricum demonstrating lowered anxiety test scores during the second and third weeks. Interestingly, Dorman et al. (1995) also reported that Garum armoricum had a lingering anxiolytic (tranquilizing) effect following its use (beyond a week) in subjects who were experiencing anxiety.

In a study based on the positive results of an earlier study of Garum armoricum in the areas of weakness and fatigue-related depression and anxiety, Le Poncin et al. (2000) conducted a double-blind versus placebo study to examine the effects of Garum armoricum on memory and cognitive disorders. Their results demonstrated statistically significant positive effects, especially in the group of subjects who were 40-50 years of age. Significant improvement was noted in refreshing sleep, motivation, concentration, and memorization skills. Le Poncin et al. (2000) reported that the favorable effects on weakness and fatigue-related depression appeared to be factors in improved memory and cognitive function. Le Poncin et al. (2000) concluded that Garum armoricum had no harmful side effects, was not addictive, and had proven efficacy in their studies. Any reactions were mild, without the necessity of interrupting the treatment. Therefore, it appears that garum extract is extremely well-tolerated and is without contraindications.

A Japanese researcher reported that when garum extract reduces anxiety, it results in improved learning, including enhanced EEG (electroencephalogram) brain wave activity (Haruyama undated report).

Even though studies demonstrate that Garum armoricum extract relieves depressive symptoms and anxiety that are often associated with chronic stress and fatigue, it may not be effective or appropriate for more complex conditions, such as clinical depression or bipolar manic depression. Use of Adapton for these more complex conditions should be only under the supervision of a physician.


Folic acid is involved in red blood cell health and proper cell division, as well as other functions in maintaining healthy tissues. Folic acid has been shown to prevent neural tube defects and to function as a methyl donor to lower homocystine (Butterworth 1993). Folic acid has a role in the prevention of heart disease and some cancers.

An article in the journal Neurology described a study in which serum folate levels were measured in 60 patients with CFS. Researchers found that 50% had values below 3.0 mcg/L. The authors concluded that some patients with CFS are deficient in folic acid (Jacobson et al. 1993).


Licorice is highly valued as a medicinal herb by the Chinese and is an ingredient in almost all of the Chinese patent herbal formulas. Licorice has a sweet taste and helps combat fatigue. The active constituent in licorice, glycyrrhizin, stimulates the production of hormones, including cortisone, and stimulates the production of interferon, which boosts immunity. Licorice is an old herbal remedy that has been used medically for Addison's disease and adrenal insufficiency (Baschetti 1995a; 1995b).


Tyrosine (and phenylalanine) are amimo acid precursors of the neurotransmitters dopamine, epinephrine, and norepinephrine (which used to be called adrenaline and noradrenaline). Deficiencies in these neurotransmitters are known to cause low levels of energy.

An article in the journal Medical Science of Sports Exercise described a study of the effects of tyrosine on exercise tolerance and brain neurochemistry of mice. Tyrosine injections improved maze performance and prevented increased levels of serotonin (5-HT) in the hypothalamus after exercise. Tyrosine administration significantly improved food consumption, cognitive behavior, and activity performance. The authors concluded that tyrosine may improve exercise tolerance and delay fatigue (Avraham et al. 2001).

An article in the journal Brain Research Bulletin described a study of the effects of tyrosine on a group of 21 cadets during a demanding military combat training course: 10 subjects received 5 daily doses of a protein-rich drink containing 2 grams of tyrosine, and 11 subjects received a carbohydrate-rich drink with the same amount of calories (255 kcal). The group supplied with the tyrosine-rich drink performed better on a memory and a tracking task than the group supplied with the carbohydrate-rich drink. In addition, the supplementation of tyrosine decreased systolic blood pressure. No effects on mood were found. The authors concluded that these findings suggest that supplementation with tyrosine may, under operational circumstances characterized by psychosocial and physical stress, reduce the effects of stress and fatigue on cognitive task performance (Owasoyo et al. 1992; Deijen et al. 1999).


Commission E approves using 1-2 tsp (2-4 grams) a day of maté (Ilex paraguayensis) leaves in a brewed tea for banishing mental and physical fatigue. Ilex paraguayensis is an evergreen shrub that is found in certain areas of South America. Most of maté's energy-boosting activity comes from caffeine; however, the effect is quite different from that of coffee. The energy boost takes about 30 minutes to become apparent and lasts several hours. Flavonoids including rutin, isoquercitin, and glycosides are also found in its leaves. Maté tea is reported to be a favorite tea among dancers in Brazil and is traditionally served in a gourd. Homeopathic preparations of maté are also available in tablets, globules, or as a tincture.

Continued . . .

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