ME and CFS Medical Abnormalities – Metabolic Issues


Following is a list of articles about abnormalities in metabolism in ME and CFS.

Links to the more than 1,000 peer-reviewed journal articles are listed on the ME and CFS Medical Abnormalities page of this website.


Yamano E, Kataoka Y. New Diagnostic Biomarkers for Chronic Fatigue Syndrome. Brain Nerve. 2018 Jan;70(1):27-34. PMID: 29348372

The authors performed comprehensive metabolomic analyses of blood samples obtained from patients with CFS and healthy controls to establish an objective diagnosis of CFS. They review previous findings concerning the immune, endocrine, and metabolic system in animal models for CFS and the patients, and present our results which may contribute to the development of a diagnostic biomarker for CFS.


Dunstan RH, Sparkes DL, Dascombe BJ, Stevens CJ, Murphy GR, Macdonald MM, Gottfries J, Gottfries CG, Roberts TK. Sex differences in amino acids lost via sweating could lead to differential susceptibilities to disturbances in nitrogen balance and collagen turnover. Amino Acids. 2017 Aug;49(8):1337-1345. PMID: 28474126

Fluid collected during sweating is enriched with amino acids derived from the skin’s natural moisturising factors and has been termed “faux” sweat. Faux sweat collected by healthy adults after exercise, and at rest by chronic fatigue patients, was analysed for amino acid composition. Females reporting chronic fatigue had higher levels of methionine in faux sweat than healthy females. Males reporting chronic fatigue had higher levels of numerous amino acids in faux sweat compared to healthy males. Higher amino acid loss in faux sweat associated with chronic fatigue could contribute to a hypometabolic state.


Germain A, Ruppert D, Levine SM, Hanson MR. Metabolic profiling of a myalgic encephalomyelitis/chronic fatigue syndrome discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol Biosyst. 2017 Jan 31;13(2):371-379. PMID: 28059425

In this pilot study, the researchers compare plasma metabolic signatures in a discovery cohort, 17 ME/CFS patients and 15 matched controls, and explore potential metabolic perturbations as the aftermath of the complex interactions between genes, transcripts and proteins. This approach to examine the complex array of symptoms and underlying foundation of ME/CFS revealed 74 differentially accumulating metabolites, out of 361. The list includes several essential energy-related compounds which could theoretically be linked to the general lack of energy observed in ME/CFS patients.


Fluge Ø, Mella O, Bruland O, Risa K, Dyrstad SE, Alme K, Rekeland IG, Sapkota D, Røsland GV, Fosså A, Ktoridou-Valen I, Lunde S, Sørland K, Lien K, Herder I, Thürmer H, Gotaas ME, Baranowska KA, Bohnen LM, Schäfer C, McCann A, Sommerfelt K, Helgeland L, Ueland PM, Dahl O, Tronstad KJ. Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/chronic fatigue syndrome. JCI Insight. 2016 Dec 22;1(21):e89376. PMID: 28018972

Analysis in 200 ME/CFS patients and 102 healthy individuals showed a specific reduction of amino acids that fuel oxidative metabolism via the TCA cycle, mainly in female ME/CFS patients. Serum 3-methylhistidine, a marker of endogenous protein catabolism, was significantly increased in male patients. The amino acid pattern suggested functional impairment of pyruvate dehydrogenase (PDH), supported by increased mRNA expression of the inhibitory PDH kinases 1, 2, and 4; sirtuin 4; and PPARδ in peripheral blood mononuclear cells from both sexes. Myoblasts grown in presence of serum from patients with severe ME/CFS showed metabolic adaptations, including increased mitochondrial respiration and excessive lactate secretion.


Naviaux RK, Naviaux JC, Li K, Bright AT, Alaynick WA, Wang L, Baxter A, Nathan N, Anderson W, Gordon E. Metabolic features of chronic fatigue syndrome. Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):E5472-80. PMID: 27573827

Patients with CFS showed abnormalities in 20 metabolic pathways. Eighty percent of the diagnostic metabolites were decreased, consistent with a hypometabolic syndrome. Pathway abnormalities included sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism. Data show that despite the heterogeneity of factors leading to CFS, the cellular metabolic response in patients was homogeneous, statistically robust, and chemically similar to the evolutionarily conserved persistence response to environmental stress known as dauer.


Links on this page are in orange (no underlining).