For the diagnosis and risk factors for CFS, see Chronic Fatigue Syndrome.

Treatments for Chronic Fatigue Syndrome

CFS is a disease which undoubtedly has multiple causes.  So, it is not surprising that a wide variety of treatments have been tried.  Some might have helped; others showed no benefit.  Unfortunately, none seem to have been adequately studied.

Carnitines are perhaps the best researched treatment for CFS although that amounts to only several small studies.  Exercise is an important part of treatment, although it has a high drop-out rate.  Doxycycline might help some cases, although no research is available.  Staphylococcus toxoid has a couple positive studies.  Magnesium helped in one study and it is a great supplement that probably everyone should take.  However, another uncontrolled study found chronic fatigue patients worse on magnesium.  Vitamin D might correct some CFS cases.  Yogurt might help. Since autoimmune factors are involved in at least some cases, I would recommend avoidance of beef, pork, lamb, dairy, chicken, and turkey, since meat and dairy avoidance helps almost all autoimmune diseases.  Unfortunately, there is no research on meat avoidance for CFS to date, so maybe I am wrong.  Research does suggest that seafood and/or fish oil might help CFS and its healthy for preventing many other illnesses.  CoQ10 might help. 

What doesn't help are acyclovir, cholinesterase inhibitors, DHEA, fluoxetine, ginseng, high colonic enemas, gamma globulin, multi-vitamins, steroids, and terfenadine.

Acyclovir No Benefit in DB: N Engl J Med. 1988 Dec 29;319(26):1692-8

Carnitine Clearly Better Than Amantidine for Chronic Fatigue Syndrome: Carnitine is essential for mitochondrial energy production. Disturbance in mitochondrial function may contribute to or cause the fatigue seen in Chronic Fatigue Syndrome (CFS) patients. In a randomized crossover study of 30 CFS patients, each received 2 months of L-carnitine and amantadine with 2 weeks washout in between. Amantadine was poorly tolerated with only 15 were able to complete the treatment. In those completing, there was no significant difference in any clinical parameter. However, with L-carnitine significant clinical improvement in 12 of the 18 studied parameters. The greatest improvement took place between 4 and 8 weeks. Only 1 patient was unable to complete due to diarrhea. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Plioplys AV, Plioplys S. Mercy Hospital Chicago. Neuropsychobiology. 1997;35(1):16-23

Carnitine Helped Fatigue from Hepatitis C Treatment: Hepatitis C virus (HCV) leads to chronic hepatitis in 80% of cases. Treatment is based on interferon (IFN)-alpha, effective in less than 50%; many responders relapse after interferon withdrawal. IFN-induced fatigue is common. In a 50-patient DB PC study, all received leucocytic IFN-alpha 3 million IU thrice a week; half received carnitine 2 g/day. Fatigue was less for carnitine at both 1 and 3 months (p<.01) and also much less severe (p<.0005). L-carnitine decreases severity and type of fatigue induced by interferon-alpha in the treatment of patients with hepatitis C. Neri S, Pistone G, Saraceno B, Pennisi G, Luca S, Malaguarnera M., University of Catania, Catania, Italy. Neuropsychobiology. 2003;47(2):94-7

Carnitines Appear to Help CFS: In a 24-week open, but randomized study of 30 chronic fatigue patients given 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, or the combination, considerable improvement was reported in 59% of acetylcarnitine, 63% propionylcarnitine and 37% for the combo. Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37%, respectively. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Vermeulen RC, Scholte HR., Amsterdam, Netherlands. Psychosom Med. 2004 Mar-Apr;66(2):276-82

Carnitines: Acetyl L-Carnitine Helped Fatigue in Multiple Sclerosis: Acetyl L-carnitine (ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome. In a 36-patient DB crossover study of 3 months each of amantadine (100 mg twice daily) or ALCAR (1 g twice daily). Beck Depression Inventory didn’t change. Six withdrew because of adverse reactions (5 amantadine and 1 ALCAR). ALCAR was better for the Fatigue Severity Scale (p = 0.039). Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. Tomassini V, Pozzilli C, et al. University of Rome, Italy. J Neurol Sci. 2004 Mar 15;218(1-2):103-8

Cholinesterase Inhibitor Failed to Help Chronic Fatigue Syndrome: In a large DB PC study of 434 patients in Europe with chronic fatigue syndrome, galantamine 2.5 mg/day vs. 5.0 mg vs. 7.5 mg vs. 10 mg vs. placebo found that after 16 weeks, there were no statistically significant differences between any of the galantamine or placebo groups. Effect of galantamine hydrobromide in chronic fatigue syndrome: a randomized controlled trial. Blacker CV, Greenwood DT, et al. University of Exeter, England. JAMA. 2004 Sep 8;292(10):1195-204

CoQ10 Said to Help: In a study by Judy (1996) of 20 females with Chronic Fatigue Syndrome who required bed rest following mild exercise and 20 healthy controls, 80% of the Chronic Fatigue Syndrome 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 Chronic Fatigue Syndrome patients more than doubled. All patients had improved: 90% had reduction and/or disappearance of clinical symptoms, and 85% had decreased postexercise fatigue (Judy WV 1996). CDC website 10/4/04. Ed: While I did find two early studies by Judy with CoQ10, PubMed doesn't list this one.

CoQ10, DHEA, Ginseng Used: In an uncontrolled, prospective study of 155 adults with chronic fatigue, 87% were female and 79% were middle-aged. The median duration of fatigue was 6.7 years. The percentage of users who thought a treatment helpful was greatest for coenzyme Q10 (69% of 13 subjects), dehydroepiandrosterone (DHEA) (65% of 17 subjects), and ginseng (56% of 18 subjects). Treatments at 6 months that predicted subsequent fatigue improvement were vitamins (p = .08), vigorous exercise (p = .09), and yoga (p = .002). Magnesium (p = .002) and support groups (p = .06) were strongly associated with fatigue worsening from 6 months to 2 years. Prospective observational study of treatments for unexplained chronic fatigue. Bentler SE, Hartz AJ, Kuhn EM. University of Iowa. J Clin Psychiatry. 2005 May;66(5):625-32.

Dexamphetamine Helped CFS in Very Small, Short Study: In a 6-week DB PC study of 20 CFS patients, Fatigue Severity Scale scores improved in nine of 10 dexamphetamine vs. four on 10 placebos. A pilot randomized controlled trial of dexamphetamine in patients with chronic fatigue syndrome. Olson LG, Ambrogetti A, Sutherland DC. University of Newcastle, Australia. Psychosomatics. 2003 Jan-Feb;44(1):38-43

Dehydroepiandrosterone (DHEA) was reported in preliminary studies to improve symptoms in some patients. However, in subsequent studies, this finding has not been confirmed. CDC website, 10/04

Doxycycline Said to Help Mycoplasma-Positive CFS and Fibro: In studies using polymerase chain reaction, mycoplasma blood infection has been detected in about 50% of patients with CFS and/or FMS, including patients with Gulf War illnesses and symptoms that overlap with one or both syndromes. Such infection is detected in only about 10% of healthy individuals. Most patients with CFS/FMS who have mycoplasma infection appear to recover and reach their pre-illness state after long-term antibiotic therapy with doxycycline, and the infection can not be detected after recovery. It is not clear whether mycoplasmas are associated with CFS/FMS as causal agents, cofactors, or opportunistic infections in patients with immune disturbances. Mycoplasma blood infection in chronic fatigue and fibromyalgia syndromes. Endresen GK., University of Oslo, Norway. Rheumatol Int. 2003 Sep;23(5):211-5 

Doxycycline Used: At least one physician at ImmuneSupport.com writes that he uses doxycycline for CFS in view of the mycoplasma evidence, but he admits that many doctors do not accept this approach. Oddly enough, even though carnitines have the most favorable research with CFS, it is mentioned only in passing at this alternative medicine favorable website. The CDC discourages antibiotics.

Exercise Helps CFS Significantly as Did Fluoxetine and Education: In an analysis of the five best studies found using exercise to help CFS patients, at 12 weeks, those receiving exercise therapy were less fatigued than controls (SMD -0.77). Physical functioning was significantly improved with exercise (SMD -0.64) but there were more dropouts (RR 1.73). Depression was non-significantly improved with exercise (WMD -0.58).Participants receiving exercise therapy were less fatigued than those receiving the antidepressant fluoxetine at 12 weeks (WMD -1.24). Participants receiving both exercise + fluoxetine were less fatigued than those receiving exercise therapy alone, although the difference did not reach significance (WMD 3.74).When exercise therapy was combined with patient education, those receiving the combination were less fatigued than those receiving exercise therapy alone (WMD 0.70). Exercise therapy for chronic fatigue syndrome. Edmonds M, McGuire H, Price J. Cochrane. 2004;(3):CD003200 

Fish Oil: EFA Benefit/ No Benefit: A dramatic 85% benefit was reported in a 63-patient DB PC study of gamma-linolenic, EFA, and DHA 4 g/d in Acta Neurol Scand. 1990 Sep;82(3):209-16, Univ Glasgow; However, in 50 CFS patients in a DB PC study for 3 months, no benefit was found. Sheffield. Acta Neurol Scand. 1999 Feb;99(2):112-6.

Folate/B-12 No Benefit: This was reported in a DB PC study in the Arch Intern Med. 1989 Nov;149(11):2501-3.  Several physicians on the internet use B-12 injections for CFS as of October, 2004, although no one refers to any research for this practice. One does use oral B-12 at 1000 mcg/day, which should be just as good as injections and less expensive. Still, there’s no research.

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

IgG Helped/Didn’t Help: In a 40 patient DB PC study using 2g/kg/m, benefit was reported. Am J Med. 1990 Nov;89(5):561-8; But, Am J Med. 1990 Nov;89(5):554-60 in another DB PC study of 30 patients, no benefit was found although the dose was a lower 1g/kg/m. Both studies lasted 6 months. 

Magnesium IM Helped: 20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy controls. When 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks or to placebo, 80% felt better with the magnesium vs. 18% with placebo. Magnesium levels returned to normal in treated by not in placebo. Red blood cell magnesium and chronic fatigue syndrome. Cox IM, Campbell MJ, Dowson D. University of Southampton, UK. Lancet. 1991 Mar 30;337(8744):757-60. Ed: I see no reason why oral magnesium at 250 mg twice a day would work just as well.  Magnesium is a great supplement that everyone should take. According to the CDC, an early CFS study found reduced red blood cell magnesium sulfate in CFS patients, but two subsequent studies have found no difference between patients and healthy controls.  

Moclobemide Slight Benefit: In a DB PC study of 90 CFS patients, those given the anti-depressant moclobemide had 51% report improvement vs. 33% with placebo.  The benefit was seen in the first two weeks. J Clin Psychiatry. 2000 Sep;61(9):643-8.

Multivitamin & Mineral Supplement No Benefit: DB PC several vitamins, minerals and (co)enzymes, or placebo, twice daily for 10 weeks found no signif diff. Netherlands. QJM. 2002 Oct;95(10):677-83

NADH Said to Help Chronic Fatigue Syndrome: In a small, short 26-patient DB PC crossover study of 4 weeks of 10 mg/day of the reduced form of nicotinamide adenine dinucleotide (NADH) i.e., ENADA the stabilized oral absorbable form, or placebo with a 4 week intervening washout period, 8 of 26 (31%) responded favorably to NADH in contrast to 2 of 26 (8%) to placebo. Nicotinamide adenine dinucleotide aids mitochondrial energy production through ATP generation which may form the basis of its potential effects.  Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Forsyth LM, Preuss HG, et al. Georgetown University. Ann Allergy Asthma Immunol. 1999 Feb;82(2):185-91. Ed: Nicotinamide 25 mg is available for $14 for 60 tablets or a 2 month supply. However, it is sold for $10.75 for 8 tablets and promoted on a truly weird website where I first saw it mentioned.

NADH No Lasting Benefit for Chronic Fatigue: 31 patients with chronic fatigue syndrome (CFS) were randomly assigned to either nicotinamide adenine dinucleotide (NADH) or nutritional supplements and psychological therapy for 24 months. The twelve patients who received NADH had a dramatic reduction in symptoms the first trimester (p < 0.001). However, scores in subsequent trimesters were similar in both groups. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. Santaella ML, Font I, Disdier OM. University of Puerto Rico. P R Health Sci J. 2004 Jun;23(2):89-93

Phenelzine Low Dose Helped: In a DB PC study of CFS patients given 15 mg/day, phenelzine patients reported more improvement. Psychopharmacology (Berl). 1996 Apr;124(3):226-30. 

Primrose Oil: Of herbal treatments, the CDC writes that only primrose oil was evaluated in a controlled study, and the beneficial effects noted in CFS patients have not been independently confirmed. CDC website 10/4/04. 

Siberian Ginseng No Help for CFS: In a DB PC 2-month study of 96 CFS patients, fatigue among subjects assigned to both placebo and Siberian ginseng was substantially reduced, but differences were not statistically significant. Authors played around with the statistics after the fact to claim some patients might have been helped out. Randomized controlled trial of Siberian ginseng for chronic fatigue. Hartz AJ, Bentler S, Noyes R, Hoehns J, Logemann C, Sinift S, Butani Y, Wang W, Brake K, Ernst M, Kautzman H. University of Iowa. Psychol Med. 2004 Jan;34(1):51-61

SSRI Citalopram Used for CFS in Poor Quality Iowa Study: In a very poorly designed study, 31 CFS patients citalopram, 20 to 40 mg/day, for 2 months were compared to 76 similar subjects "taking an ineffective treatment." Fatigue for subjects taking citalopram was significantly and substantially reduced, p <.05. but not in the other group. The effectiveness of citalopram for idiopathic chronic fatigue. Hartz AJ, Bentler SE, Brake KA, Kelly MW. University of Iowa. J Clin Psychiatry. 2003 Aug;64(8):927-35. Ed: What an embarassment for the University of Iowa to have such a study published.

SSRI Fluoxetine Didn't Help Except for Depression: In a DB PC study of exercise with or without fluoxetine, the fluoxetine did not help CFS symptoms except for depression. Br J Psychiatry. 1998 Jun;172:485-90. There was a higher drop out rate with exercise.; Fluoxetine didn’t help in another DB PC. Lancet. 1996 Mar 30;347(9005):858-61

Staphylococcus Toxoid Helped CFS and Fibro: In a 6 months DB PC study of 100 patients with fibromyalgia and CFS, the staphylococcus toxoid preparation Staphypan Berna (SB) was given in weekly injections containing 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 0.9 ml, and 1.0 ml or coloured sterile water, followed by booster doses given 4-weekly until endpoint. Intention-to-treat analysis showed 65% responders in the SB group compared to 18% in the placebo group (P<0.001). Mean change score on the CPRS was 10.0 with SB and 3.9 with placebo (P<0.01). An increase in CPRS symptoms at withdrawal was noted in the SB group. Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial. Zachrisson O, Regland B, Jahreskog M, Jonsson M, Kron M, Gottfries CG. Goteborg University, Sweden. Eur J Pain. 2002;6(6):455-66

Steroids No Help for CFS: In a 6-month DB PC crossover study of 100 CFS patients with 3 months in each phase, the combination of 5 mg/d of hydrocortisone and 50 microg/d of 9-alfa-fludrocortisone did no better than placebo in patient-reported fatigue (mean difference, 0.1) or well-being (mean difference, -0.4). Combination therapy with hydrocortisone and fludrocortisone does not improve symptoms in chronic fatigue syndrome: a randomized, placebo-controlled, double-blind, crossover study. Blockmans D, Persoons P, Van Houdenhove B, Lejeune M, Bobbaers H. Leuven, Belgium. Am J Med. 2003 Jun 15;114(9):736-41

Steroids: Hydrocortisone Somewhat Helpful: In a smaller and shorter DB PC study of 32 patients treated for 28 days with crossover, hydrocortisone 5-10 mg/d led to a 28% response rate vs. 9% with placebo.  The average score of 25 at baseline decreased 3.3 with placebo, and 7.2 with cortisone. Cleare, London, Lancet 99;353:455 

Terfenadine No Benefit in DB: J Allergy Clin Immunol. 1996 Jan;97(1 Pt 1):119-26  

Yogurt Might Help CFS: CFS patients have marked alterations in microbial flora, including lowered levels of bifidobacteria and small intestinal bacterial overgrowth (SIBO). CFS patients are also under increased oxidative stress, have a type 2 helper cell dominate cytokine profile, frequently report allergies, have altered essential fatty acid (EFA) status and may have malabsorption of certain micronutrients. Lactic acid bacteria (LAB) have the potential to influence the immune system in CFS patients by supporting T helper cell 1 driven cellular immunity and may decrease allergies. In addition LAB are strong antioxidants, may improve EFA status, can enhance absorption of micronutrients by protecting the intestinal epithelial barrier, and have been used to treat SIBO. Chronic fatigue syndrome: lactic acid bacteria may be of therapeutic value. Logan AC, Venket Rao A, Irani D. Toronto, Canada. Med Hypotheses. 2003 Jun;60(6):915-23