Following is a list of articles about trials of therapies other than prescription drugs in ME and CFS sufferers.
Links to the more than 1,000 peer-reviewed journal articles are listed on the ME and CFS Medical Abnormalities page of this website.
Roman P, Carrillo-Trabalón F, Sánchez-Labraca N, Cañadas F, Estévez AF, Cardona D. Are probiotic treatments useful on fibromyalgia syndrome or chronic fatigue syndrome patients? A systematic review. Benef Microbes. 2018 Jun 15;9(4):603-611. PMID: 29695180
This study systematically reviewed the reported effect of probiotic treatments in patients diagnosed with FMS or CFS. The administration of Lactobacillus casei strain Shirota in CFS patients, over the course of 8 weeks, reduced anxiety scores. Additionally, the treatment with Bifidobacterium infantis 35624 in CFS patients, during the same period, reduced inflammatory biomarkers. The evidence about the usefulness of probiotics in CFS and FMS patients remains limited.
Scheibenbogen C, Loebel M, Freitag H, Krueger A, Bauer S, Antelmann M, Doehner W, Scherbakov N, Heidecke H, Reinke P, Volk HD, Grabowski P. Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME. PLoS One. 2018 Mar 15;13(3):e0193672. PMID: 29543914
Ten patients with post-infectious CFS/ME and elevated ß2 autoantibodies were treated with immunoadsorption with an IgG-binding column for 5 days. The researchers concluded that immunoadsorption can remove autoantibodies against ß2 adrenergic receptor and lead to clinical improvement. B cell phenotyping provides evidence for an effect of IA on memory B cell development.
Corbitt M, Campagnolo N, Staines D, Marshall-Gradisnik S. A Systematic Review of Probiotic Interventions for Gastrointestinal Symptoms and Irritable Bowel Syndrome in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). Probiotics Antimicrob Proteins. 2018 Sep;10(3):466-477. PMID: 29464501
The aim of this study was to conduct a systematic literature review of gastrointestinal and irritable bowel symptoms in CFS/ME, along with any evidence for probiotics as treatment. The authors concluded that there is currently insufficient evidence for the use of probiotics in CFS/ME patients, despite probiotic interventions being useful in IBS.
Wallis A, Ball M, Butt H, Lewis DP, McKechnie S, Paull P, Jaa-Kwee A, Bruck D. Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons. J Transl Med. 2018 Feb 6;16(1):24. PMID: 29409505
Participants in this study included 44 adult ME/CFS patients (27 females) from one specialist medical clinic with Streptococcus viable counts above 3.00 × 105 cfu/g (wet weight of faeces). The 4-week treatment protocol included alternate weeks of Erythromycin twice daily and probiotic (D-lactate free multistrain probiotic, 5 × 1010cfu twice daily). Large treatment effects were observed for the intention-to-treat sample with a reduction in Streptococcus viable count and improvement on several clinical outcomes including total symptoms, some sleep (less awakenings, greater efficiency and quality) and cognitive symptoms (attention, processing speed, cognitive flexibility, story memory and verbal fluency). This study’s results support the notion that specific microorganisms interact with some ME/CFS symptoms and offer promise for the therapeutic potential of targeting gut dysbiosis in this population.
Rowe PC, Marden CL, Heinlein S, Edwards CC 2nd. Improvement of severe myalgic encephalomyelitis/chronic fatigue syndrome symptoms following surgical treatment of cervical spinal stenosis. J Transl Med. 2018 Feb 2;16(1):21. PMID: 29391028
The authors describe three consecutive patients with severe ME/CFS whose symptoms improved after recognition and surgical management of their cervical spinal stenosis. The prompt post-surgical restoration of more normal function suggests that cervical spine stenosis contributed to the pathogenesis of refractory ME/CFS and orthostatic symptoms.
Gunn SR, Gunn GG, Mueller FW. Reversal of Refractory Ulcerative Colitis and Severe Chronic Fatigue SyndromeSymptoms Arising from Immune Disturbance in an HLA-DR/DQ Genetically Susceptible Individual with Multiple Biotoxin Exposures. Am J Case Rep. 2016 May 11;17:320-5. PMID: 27165859
A 25-year-old previously healthy male with new-onset refractory ulcerative colitis (RUC) and chronic fatigue syndrome (CFS) tested negative for autoimmune disease biomarkers. However, urine mycotoxin panel testing was positive for trichothecene group and air filter testing from the patient’s water-damaged rental house identified the toxic mold Stachybotrys chartarum. HLA-DR/DQ testing revealed a multisusceptible haplotype for development of chronic inflammation, and serum chronic inflammatory response syndrome (CIRS) biomarker testing was positive for highly elevated TGF-beta and a clinically undetectable level of vasoactive intestinal peptide (VIP). Following elimination of biotoxin exposures, VIP replacement therapy, dental extractions, and implementation of a mind body intervention-relaxation response (MBI-RR) program, the patient’s symptoms resolved. He is off medications, back to work, and resuming normal exercise.
Alegre J, Rosés JM, Javierre C, Ruiz-Baqués A, Segundo MJ, de Sevilla TF. Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome. Rev Clin Esp. 2010 Jun;210(6):284-8. PMID: 20447621
Administration of oral NADH was associated to a decrease in anxiety and maximum heart rate, after a stress test in patients with CFS.
Rao AV, Bested AC, Beaulne TM, Katzman MA, Iorio C, Berardi JM, Logan AC. A randomized, double-blind, placebo-controlled pilot study of a probiotic in emotional symptoms of chronic fatigue syndrome. Gut Pathog. 2009 Mar 19;1(1):6. PMID: 19338686
CFS patients who received 24 billion colony forming units of Lactobacillus casei strain Shirota (LcS) daily for two months had a decrease in anxiety symptoms.
Sullivan A, Nord CE, Evengård B. Effect of supplement with lactic-acid producing bacteria on fatigue and physical activity in patients with chronic fatigue syndrome. Nutr J. 2009 Jan 26;8:4. PMID: 19171024
Severely ill CFS patients were given the probiotics Lactobacillus paracasei ssp. paracasei F19, Lactobacillus acidophilus NCFB 1748 and Bifidobacterium lactis Bb12. The study reported neurocognitive functioning improvements, but no changes in fatigue or physical activity.
Teitelbaum JE, Johnson C, St Cyr J. The use of D-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study. J Altern Complement Med. 2006 Nov;12(9):857-62. PMID: 17109576
D-ribose was effective at improving CFS patients’ energy, sleep, mental clarity, pain intensity and overall feelings of well-being.
Kodama M, Kodama T. The clinical course of interstitial pneumonia alias chronic fatigue syndrome under the control of megadose vitamin C infusion system with dehydroepiandrosterone-cortisol annex. Int J Mol Med. 2005 Jan;15(1):109-16. PMID: 15583836
A combination of high-dose intravenous Vitamin C and DHEA was effective at treating both CFS and interstitial pneumonia.
Vermeulen RC, Scholte HR. Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome. Psychosom Med. 2004 MarApr;66(2):276-82. PMID: 15039515
The authors compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.
Santaella ML, Font I, Disdier OM. Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. P R Health Sci J. 2004 Jun;23(2):89-93. PMID: 15377055
NADH was effective in CFS for three months, but the positive results faded after that.
Puri BK, Holmes J, Hamilton G. Eicosapentaenoic acid-rich essential fatty acid supplementation in chronic fatigue syndrome associated with symptom remission and structural brain changes. Int J Clin Pract. 2004 Mar;58(3):297-9. PMID: 15117099
Supplementation of an essential fatty acid rid in eicosapentaenoic acid (EPA) was followed by marked improvement in clinical condition after six weeks. Accurate quantification of the lateral ventricular volumes in the baseline and 16-week follow-up registered images of high-resolution magnetic resonance imaging structural scans showed that the treatment was accompanied by a marked reduction in the lateral ventricular volume during this period.
Puri BK. The use of eicosapentaenoic acid in the treatment of chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids. 2004 Apr;70(4):399-401. PMID: 15041033
A series of patients with chronic fatigue syndrome were treated solely with a higheicosapentaenoic acid-containing essential fatty acid supplement. All showed improvement in their symptomatology within eight to 12 weeks.
Cleare AJ, O’Keane V, Miell JP. Levels of DHEA and DHEAS and responses to CRH stimulation and hydrocortisone treatment in chronic fatigue syndrome. Psychoneuroendocrinology. 2004 Jul;29(6):724-32. PMID: 15110921
DHEA levels are raised in CFS and correlate with the degree of self-reported disability. Hydrocortisone therapy leads to a reduction in these levels towards normal, and an increased DHEA response to CRH, most marked in those who show a clinical response to this therapy.
Cleare AJ, Miell J, Heap E, Sookdeo S, Young L, Malhi GS, O’Keane V. Hypothalamopituitary-adrenal axis dysfunction in chronic fatigue syndrome, and the effects of low-dose hydrocortisone therapy. J Clin Endocrinol Metab. 2001 Aug;86(8):3545-54. PMID: 11502777
The authors treat 32 patients with low-dose hydrocortisone and conclude that the improvement in fatigue seen in some patients with CFS during treatment is accompanied by a reversal of the blunted cortisol responses to human CRH.
Forsyth LM, Preuss HG, MacDowell AL, Chiazze L Jr, Birkmayer GD, Bellanti JA. Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome. Ann Allergy Asthma Immunol. 1999 Feb;82(2):185-91. PMID: 10071523
31% of a group of CFS patients responded favorably to NADH, compared to 8% to a placebo.
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 Feb;99(2):112-6. PMID: 10071170
Treatment with an essential fatty acid product (Efamol Marine) did not result in benefits compared to a placebo for CFS patients.
Dykman KD, Tone C, Ford C, Dykman RA. The effects of nutritional supplements on the symptoms of fibromyalgia and chronic fatigue syndrome. Integr Physiol Behav Sci. 1998 Jan-Mar;33(1):61-71. PMID: 9594356
Nutritional supplements resulted in a reduction in initial symptom severity, with continued improvement in the period between initial assessment and the follow-up, in a group of CFS sufferers.
See DM, Cimoch P, Chou S, Chang J, Tilles J. The in vitro immunomodulatory effects of glyconutrients on peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Integr Physiol Behav Sci. 1998 Jul-Sep;33(3):280-7. PMID: 9829439
Addition of glyconutrient homogenate to PBMC from patients with CFS stimulated with phytohemagglutinin significantly increased the expression of each glycoprotein. The glyconutrient preparation significantly enhanced NK cell activity versus human herpes virus 6 (HHV-6)-infected H9 cells in an 8 h 51Cr release assay compared to placebo for PBMC from patients with CFS (p< .01). Finally, apoptosis was significantly higher in patients with CFS. The percentage of apoptotic cells was significantly decreased in PBMC from patients with CFS that had been incubated for 48 h with glyconutrients.
Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology. 1997;35(1):16-23. PMID: 9018019
In a group of 30 CFS patients, l-carnitine demonstrated significant improvements within 4-8 weeks. Amantadine, used to treat fatigue in MS, was poorly tolerated by CFS patients.
De Vinci C, Levine PH, Pizza G, Fudenberg HH, Orens P, Pearson G, Viza D. Lessons from a pilot study of transfer factor in chronic fatigue syndrome. Biotherapy. 1996;9(1- 3):87-90. PMID: 8993764
Of the 20 patients in the placebo-controlled trial of transfer factor, improvement was observed in 12 patients, generally within 3-6 weeks of beginning treatment.
Ablashi DV, Levine PH, De Vinci C, Whitman JE Jr, Pizza G, Viza D. Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports. Biotherapy. 1996;9(1-3):81-6. PMID: 8993763
Specific Human Herpes virus-6 (HHV-6) transfer factor (TF) preparation, administered to two chronic fatigue syndrome patients, inhibited the HHV-6 infection. Prior to treatment, both patients exhibited an activated HHV-6 infection. TF treatment significantly improved the clinical manifestations of CFS in one patient who resumed normal duties within weeks, whereas no clinical improvement was observed in the second patient.
Cox IM, Campbell MJ, Dowson D. Red blood cell magnesium and chronic fatigue syndrome. Lancet. 1991 Mar 30;337(8744):757-60. PMID: 1672392
A clinical trial showed that magnesium supplementation may be helpful in CFS.
Behan PO, Behan WM, Horrobin D. Effect of high doses of essential fatty acids on the postviral fatigue syndrome. Acta Neurol Scand. 1990 Sep;82(3):209-16. PMID: 2270749
High doses of essential fatty acids containing linolenic, gamma-linolenic, eicosapentaenoic and docosahexaenoic acidswere helpful in CFS.
Additional small older studies looking at treatments for chronic fatigue syndrome are listed on another page of this website.
Links on this page are in orange (no underlining).