Chronic Fatigue Syndrome

Also indexed as: CFIDS, CFS

Chronic fatigue syndrome is a poorly understood disease involving many body systems. No single cause for chronic fatigue syndrome (CFS) has been identified. Therefore, it is defined by symptoms and by ruling out other known causes of fatigue. This needs to be done by a healthcare practitioner. Suggested causes include chronic viral infections, food allergy, adrenal gland dysfunction, and many others. None of these have been convincingly documented in more than a minority of sufferers. The current definition is disabling fatigue lasting more than six months that reduces activity by more than half. In some people there is also difficulty sleeping, swollen lymph nodes, and/or mild fever. When there is muscle soreness, fibromyalgia may be the actual problem. Although CFS is considered a modern diagnosis, it may have existed for centuries under other names, such as “the vapors,” neurasthenia, “effort syndrome” (diagnosed in World War I veterans), hypoglycemia, and chronic mononucleosis.

Checklist for Chronic Fatigue Syndrome

Rating Nutritional Supplements Herbs
2Stars L-carnitine
NADH
Potassium-magnesium aspartate
Vitamin B12		  
1Star DHEA
Magnesium		 Asian ginseng
Eleuthero
Licorice
3Stars Reliable and relatively consistent scientific data showing a substantial health benefit.
2Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
1Star An herb is primarily supported by traditional use, or the herb or supplement has little scientific support and/or minimal health benefit.

What are the symptoms of chronic fatigue syndrome? 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.

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

Dietary changes that may be helpful: 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 changes that may be helpful: 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 supplements that may be helpful: 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 twice per day, 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 taken three times daily 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.

Are there any side effects or interactions? Refer to the individual supplement for information about any side effects or interactions.

Herbs that may be helpful: Some research suggests that CFS may be partially due to low adrenal function resulting from different stressors (e.g., mental stress, physical stress, and even viral illness) and impacting the normal communication between the hypothalamus, pituitary gland, and the adrenal glands.28 Licorice root is known to stimulate the adrenal glands and to block the breakdown of active cortisol in the body.29 One case report described a man with CFS whose symptoms improved after taking 2.5 grams of licorice root daily.30 While there have been no controlled trials to test licorice in patients with CFS, it may be worth a trial of six to eight weeks using 2 to 3 grams of licorice root daily.

Adaptogenic herbs such as Asian ginseng and eleuthero may also be useful for CFS patients—the herbs not only have an immunomodulating effect but also help support the normal function of the hypothalamic-pituitary-adrenal axis, the hormonal stress system of the body.31 These herbs are useful follow-ups to the six to eight weeks of taking licorice root and may be used for long-term support of adrenal function in people with CFS. However, no controlled research has investigated the effect of adaptogenic herbs on CFS.

Are there any side effects or interactions? Refer to the individual herb for information about any side effects or interactions.

Other integrative approaches that may be helpful: Highly stressful situations should be avoided by people with CFS. Coping mechanisms for dealing with stress can sometimes be maximized by behavioral therapy, which has been shown helpful for people with CFS in several controlled studies.32

References:

1. De Lorenzo F, Hargreaves J, Kakkar VV. Pathogenesis and management of delayed orthostatic hypotension in patients with chronic fatigue syndrome. Clin Auton Res 1997;7:185–90.

2. Fulcher KY, White PD. Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome. Br Med J 1997;314:1647–52.

3. McCully KK, Sisto SA, Natelson BH. Use of exercise for treatment of chronic fatigue syndrome. Sports Med 1996;21:35–48 [review].

4. Blackwood SK, MacHale SM, Power MJ, et al. Effects of exercise on cognitive and motor function in chronic fatigue syndrome and depression. J Neurol Neurosurg Psychiatry 1998;65:541–6.

5. LaManca JJ, Sisto SA, DeLuca J, et al. Influence of exhaustive treadmill exercise on cognitive functioning in chronic fatigue syndrome. Am J Med 1998;105:59S–65S.

6. Paul L, Wood L, Behan WM, et al. Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome. Eur J Neurol 1999;6:63–9.

7. Clapp LL, Richardson MT, Smith JF, et al. Acute effects of thirty minutes of light-intensity, intermittent exercise on patients with chronic fatigue syndrome. Phys Ther 1999;79:749–56.

8. Shaw DL, Chesney MA, Tullis IF, Agersborg HPK. Management of fatigue: a physiologic approach. Am J Med Sci 1962;243:758–69.

9. Crescente FJ. Treatment of fatigue in a surgical practice. J Abdom Surg 1962;4:73.

10. Hicks J. Treatment of fatigue in general practice: a double-blind study. Clin Med 1964;Jan:85–90.

11. Formica PE. The housewife syndrome: treatment with the potassium and magnesium salts of aspartic acid. Curr Ther Res 1962;Mar:98–106.

12. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3:927–36.

13. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277–83.

14. Lawhorne L, Rindgahl D. Cyanocobalamin injections for patients without documented deficiency. JAMA 1989;261:1920–3.

15. Gaby AR. Literature Review & Commentary. Townsend Letter for Doctors & Patients 1997;Feb/Mar:27 [review].

16. Lapp CW, Cheney PR. The rationale for using high-dose cobalamin (vitamin B12). CFIDS Chronicle Physicians’ Forum 1993;Fall:19–20.

17. Heap LC, Peters TJ, Wessely S. Vitamin B status in patients with chronic fatigue syndrome. J R Soc Med 1999;92:183–5.

18. Kuratsune H, Yamaguti K, Takahashi M, et al. Acylcarnitine deficiency in chronic fatigue syndrome. Clin Infect Dis 1994;18(suppl 1):S62–7.

19. Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of chronic fatigue syndrome. Neuropsycholbiol 1997;35:16–23.

20. Forsyth LM, Preuss HG, MacDowell AL, et al. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol 1999;82:185–91.

21. Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet 1991;337:757–60.

22. Howard JM, Davies S, Hunnisett A. Magnesium and chronic fatigue syndrome. Lancet 1992;340:426.

23. Clague JE, Edwards RH, Jackson MJ. Intravenous magnesium loading in chronic fatigue syndrome. Lancet 1992;340:124–5.

24. Gantz NM. Magnesium and chronic fatigue. Lancet 1991;338:66 [letter].

25. Hinds G, Bell NP, McMaster D, McCluskey DR. Normal red cell magnesium concentrations and magnesium loading tests in patients with chronic fatigue syndrome. Ann Clin Biochem 1994;31(Pt. 5):459–61.

26. Kuratsune H, Yamaguti K, Sawada M, et al. Dehydroepiandrosterone sulfate deficiency in chronic fatigue syndrome. Int J Mol Med 1998;1:143–6.

27. De Becker P, De Meirleir K, Joos E, et al. Dehydroepiandorsterone (DHEA) response to i.v. ACTH in patients with chronic fatigue syndrome. Horm Metab Res 1999;31:18–21.

28. Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA 1995;274:961–7.

29. Whorwood CB, Shepard MC, Stewart PM. Licorice inhibits 11ß-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology 1993;132:2287–92.

30. Baschetti R. Chronic fatigue syndrome and liquorice. New Z Med J 1995;108:156–7 [letter].

31. Brown D. Licorice root—potential early intervention for chronic fatigue syndrome. Quart Rev Natural Med 1996;Summer:95–7.

32. Price JR, Couper J. Cognitive behaviour therapy for adults with chronic fatigue syndrome. Cochrane Database Syst Rev 2000;(2):CD001027 [review].