Chronic fatigue syndrome (CFS) has been a subject of controversy for many years. Medical authorities were once quite skeptical regarding whether it even existed. However, in 1988, the Centers for Disease Control and Prevention (CDC) officially recognized CFS. Today, CFS is defined essentially as follows: Unexplained, persistent, or relapsing fatigue with a definite beginning; it is not the result of exertion; it is not relieved by rest; and it results in significant reduction of activities.
In addition, at least four of the following symptoms persist or recur for 6 or more consecutive months of the illness:
Frequently, symptoms of CFS follow a viral infection; some individuals with CFS describe their symptoms as a flu that never goes away.
The cause (or causes) of CFS remains unknown. Because its symptoms somewhat resemble those of mononucleosis (caused by the Epstein-Barr virus), for a time the disease was called chronic Epstein-Barr syndrome. However, further investigation disclosed that evidence of past or current Epstein-Barr infection is no more common in individuals with CFS than in the general population. Nonetheless, this erroneous and misleading term still crops up in literature on CFS.
Other syndromes with a similar pattern of symptoms to CFS include fibromyalgia, multiple chemical sensitivities (MCS), and food allergies; some consider these conditions to be closely related to each other, but there is no real evidence to support this hypothesis.
There is no dramatically effective treatment for CFS. Antidepressants (such as Prozac and Zoloft) may improve energy and mood; older antidepressants (such as amitriptyline) may improve sleep; antihistamines and decongestants can help allergic symptoms that frequently occur in CFS; and nonsteroidal anti-inflammatory drugs (such as ibuprofen and naproxen) may help pain.
Other approaches to CFS that have been tried include magnesium injections,1-3 corticosteroid treatment,4-9 and a graded (incremental) exercise program either alone or with the antidepressant fluoxetine.10-13,32 A randomized study involving 641 people with CFS found that those who participated in a graded exercise program had less fatigue and improved functioning compared to those who received two common forms of treatment (specialized medical care or adaptive pacing therapy).35
For a time, researchers expressed some excitement over initial findings that deliberately raising blood pressure might help individuals with CFS. However, a double-blind, placebo-controlled study of 25 people given a 6-week course of fludrocortisone and increased dietary sodium to raise blood pressure found no improvement in CFS symptoms.14
One study performed in Hong Kong provides weak evidence that acupuncture might be helpful for chronic fatigue syndrome.34 Further research included a single-blind study of 127 people with CFS compared acupuncture to sham acupuncture. Acupuncture was associated with improvements in physical and mental fatigue, and physical function. It is difficult to determine how successful acupuncture was because of the studies' limitations.36
There are some promising natural treatments for CFS, but the scientific evidence for them is not yet strong.
In a double-blind, placebo-controlled study, 63 people were given either a combination of essential fatty acids containing evening primrose oil (a source of GLA) and fish oil, or liquid paraffin placebo over a 3-month period.15 At 1 and 3 months, participants in the treatment group reported significant improvement in CFS symptoms as compared to the placebo group. The researchers also found that at the beginning of the study many participants had abnormal essential fatty acid levels, and these improved with treatment.
However, in 1999, researchers tried to replicate this study with 50 other people, using more precise means of measuring CFS symptoms.16 The results showed no difference between individuals given essential fatty acids and those given placebo (sunflower oil). These researchers also found no difference in fatty acid levels between individuals with CFS and individuals without CFS who served as controls.
Nicotinamide adenine dinucleotide (NADH) is a naturally occurring chemical that plays a significant role in cellular energy production. NADH supplements have been tried in hopes they might improve energy levels in athletes and in individuals with chronic fatigue.
A double-blind, placebo-controlled crossover trial that followed 26 people given 10 mg of NADH for a 4-week period showed some improvement in symptoms during NADH treatment as compared to the period of placebo treatment (31% versus 8%).17 However, larger studies will have to be performed to actually prove a benefit with this supplement.
Carnitine is a substance the body uses to convert fatty acids to energy. Early studies reported decreased carnitine levels in people with CFS.18 Based on these, an unblinded crossover trial (8 weeks with each treatment, and a 2-week "washout" period in between) enrolled 30 individuals with CFS to evaluate the potential benefits of carnitine supplements.19 The results suggest potential benefit with this supplement.
However, this study was severely flawed. One problem was that, rather than using a placebo group for comparison purposes, researchers chose to investigate the antiviral drug amantadine. This drug has no proven efficacy in CFS, and it caused so many side effects that more than half of the participants dropped out during the period they were taking amantadine. This high dropout rate makes statistical interpretation of the results unreliable. In addition, the lack of blinding in the study also impairs the trustworthiness of the results.
A double-blind, placebo-controlled study available only in the form of a press release (at the time of this writing) reportedly found dark chocolate helpful for CFS.33
Traditional Chinese herbal medicine is part of a comprehensive and unique approach to healing developed over many centuries in Asia. A double-blind, placebo-controlled study of 29 people suggests that the use of an herbal formula originating in this system may be helpful for CFS.27
A test tube study of echinacea and Panax ginseng found that both increased cellular immune function in cells taken from people with CFS.20 However, many herbs and supplements can cause measurable changes in immune function, and such observations do not prove that there will be an actual benefit in people with the disease.
Based on the theory mentioned above that CFS might be related to low blood pressure, the herb licorice has been recommended for CFS by some herbalists. Licorice raises blood pressure (and causes other potentially harmful effects) when taken in high doses for a long time. However, there is no evidence that it works for CFS, and other treatments to raise blood pressure have proven ineffective for CFS.24
Although some authorities have suggested that CFS might be caused by deficiencies of multiple vitamins and minerals, a double-blind, placebo-controlled study of 42 people found no significant improvement in CFS symptoms when a vitamin-mineral supplement was given four times daily after meals for 3 months.25 Another trial failed to find benefit with a multivitamin/mineral supplement as well.26
A fairly substantial (96-participant) double-blind, placebo-controlled study failed to find Eleutherococcus senticosus("Siberian ginseng") helpful for people with CFS.28 Over the 2-month study period, both eleutherococcus and placebo reduced fatigue symptoms, but there was no statistically significant difference. (The researchers managed to find some benefit by resorting to statistically questionable after-the-fact procedures.)
A special bran extract marketed for enhancing immunity failed to prove more effective than placebo for CFS symptoms (although placebo was quite effective).31
People with CFS may at times attribute their symptoms to chemical exposures, thereby relating chronic fatigue syndrome to another loosely defined condition known as multiple chemical sensitivities, or MCS. One study evaluated people with chronic fatigue syndrome who believed that certain chemical triggers affected their mental function, causing mental sluggishness and confusion.30 The results showed decreased mental function on testing following exposure to supposed chemical triggers; however, the decrease was the same whether the actual chemical or a substitute placebo was used. In other words, it was the belief that a substance causes harm, rather than actual harm caused by the substance, that produced the symptoms.
1. Durlach J. Chronic fatigue syndrome and chronic primary magnesium deficiency (CFS and CPMD). Magnes Res. 1992;5:68.
2. Howard JM, Davies S, Hunnisett A. Magnesium and chronic fatigue syndrome [letter]. Lancet. 1992;340:426.
3. Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991;337:757-760.
4. Cleare AJ, Heap E, Malhi GS, et al. Low-dose hydrocortisone in chronic fatigue syndrome: a randomised crossover trial. Lancet. 1999;353:455-458.
5. Jeffcoate WJ. Chronic fatigue syndrome and functional hypoadrenia—fighting vainly the old ennui [letter]. Lancet. 1999;353:424-425.
6. Dessein PH, Shipton EA. Hydrocortisone and chronic fatigue syndrome [letter]. Lancet. 1999;353:1618.
7. Baschetti R . Hydrocortisone and chronic fatigue syndrome [letter] Lancet. 1999;353:1618.
8. Rea T, Buchwald D. Hydrocortisone and chronic fatigue syndrome [letter]. Lancet. 1999;353:1618-1619.
9. Shepherd C. Hydrocortisone and chronic fatigue syndrome [letter]. Lancet. 1999;353:1619-1620.
10. Deale A, Chalder T, Wessely S. Commentary on: randomised, double-blind, placebo-controlled trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry. 1998;172:491-492.
11. Wearden AJ, Morriss RK, Mullis R, et al. Randomised, double-blind, placebo-controlled treatment trial of fluoxetine and graded exercise for chronic fatigue syndrome. Br J Psychiatry. 1998;172:485-490.
12. Lynch S, Fraser J. Fluoxetine and graded exercise in chronic fatigue syndrome [letter]. Br J Psychiatry. 1998;173:353.
13. Everitt BS. Analysis of drop-out data in treatment trials [letter]. Br J Psychiatry. 1998;173:271.
14. Peterson PK, Pheley A, Schroeppel J, et al. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome. Arch Intern Med. 1998;158:908-914.
15. Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990;82:209-216.
16. Warren G, McKendrick M, Peet M. The role of essential fatty acids in chronic fatigue syndrome. A case-controlled study of red-cell membrane essential fatty acids (EFA) and a placebo-controlled treatment study with high dose of EFA. Acta Neurol Scand. 1999;99:112-116.
17. Forsyth LM, Preuss HG, MacDowell AL, et al. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy. 1999;82:185-191.
18. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsychobiology. 1997;35:16-23.
19. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsychobiology. 1997;35:16-23.
20. See DM, Broumand N, Sahl L, et al. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency patients. Immunopharmacology. 1997;35:229-235.
21. Himmel PB, Seligman TM. A pilot study employing dehydroepiandrosterone (DHEA) in the treatment of chronic fatigue syndrome. J Clin Rheumatol. 1999;5:56-59.
22. Cunha BA. Beta-carotene stimulation of natural killer cell activity in adult patients with chronic fatigue syndrome. CFIDS Chronicle Physicians' Forum. 1993:18-19.
23. Heath M, Klein NC, Cunha BA. Dose dependent effects of beta carotene therapy in chronic fatigue syndrome [abstract]. Clin Res. 1994;42:345A.
24. Peterson PK, Pheley A, Schroeppel J, et al. A preliminary placebo-controlled crossover trial of fludrocortisone for chronic fatigue syndrome. Arch Intern Med. 1998;158:908-914.
25. Martin RWY, Ogston SA, Evans JR. Effects of vitamin and mineral supplementation on symptoms associated with chronic fatigue syndrome with Coxsackie B antibodies. J Nutr Med. 1994;4:11-23.
26. Brouwers FM, Van Der Werf S, Bleijenberg G, et al. The effect of a polynutrient supplement on fatigue and physical activity of patients with chronic fatigue syndrome: a double-blind randomized controlled trial. QJM. 2002;95:677-683.
27. Kuratsune, H. Effect of Kampo Medicine, “Hochu-ekki-to,” on chronic fatigue syndrome. Clinic and Research. 1997;74:1837-1845.
28. Hartz AJ, Bentler S, Noyes R, et al. Randomized controlled trial of Siberian ginseng for chronic fatigue. Psychol Med. 2004;34:51-61.
29. Williams G, Waterhouse J, Mugarza J, et al. Therapy of circadian rhythm disorders in chronic fatigue syndrome: no symptomatic improvement with melatonin or phototherapy. Eur J Clin Invest. 2002;32:831-837.
30. Smith S, Sullivan K. Examining the influence of biological and psychological factors on cognitive performance in chronic fatigue syndrome: a randomized, double-blind, placebo-controlled, crossover study. Int J Behav Med. 2003;10:162-173.
31. McDermott C, Richards SC, Thomas PW, et al. A placebo-controlled, double-blind, randomized controlled trial of a natural killer cell stimulant (BioBran MGN-3) in chronic fatigue syndrome. QJM. 2006 Jun 29 [Epub ahead of print].
32. Edmonds M, McGuire H, Price J. Exercise therapy for chronic fatigue syndrome. Cochrane Database Syst Rev. 2004;(3):CD003200.
34. Yiu YM, Ng SM, Tsui YL, et al. A clinical trial of acupuncture for treating chronic fatigue syndrome in Hong Kong.] Zhong Xi Yi Jie He Xue Bao. 2007;5:630-633.
35. White P, Goldsmith K, Johnson A, et al. Comparison of adaptive pacing therapy, cognitive behaviour therapy, graded exercise therapy, and specialist medical care for chronic fatigue syndrome (PACE): a randomised trial. Lancet. 2011 Feb 17. [Epub ahead of print]
36. Ng SM, Yiu YM, et al. Acupuncture for chronic fatigue syndrome: a randomized, sham-controlled trial with single-blinded design. Altern Ther Health Med. 2013;19(4):21-26.
Last reviewed September 2014 by EBSCO CAM Review Board
Last Updated: 9/18/2014