Metabolomics and Chronic Fatigue Syndrome

A ground breaking study took blood samples from a group of 84 clearly defined CFS patients and performed an analysis of 612 metabolites from 63 biochemical pathways.1 Such an analysis is called metabolomics. The metabolites measured were those part of normal biochemical pathways such as steroids, fatty acids, amino acids, vitamins and those related to methylation, mitochondria, microbiome, etc.

Of the 63 biochemical pathways studied CFS patients showed abnormalities in 20. This clearly indicates a state of disordered biochemistry in multiple areas. Pathways showing abnormalities included the following:

Sphingolipid, phospholipid, purine, cholesterol, microbiome, pyrroline-5-carboxylate, riboflavin, branch chain amino acid, peroxisomal, and mitochondrial metabolism.

Of the abnormal pathways 80% showed a decreased level of metabolites which suggests a hypometabolic syndrome. There is a general down-regulation of these biochemical pathways. The abnormalities found were distinctly different to those found in metabolic syndrome and the classic metabolic pattern found in infection, inflammation and environmental stress. The pattern in CFS was highly similar to that found in Dauer, a long term state of decreased metabolism induced in order to survive an environmental stressor.

“These facts suggest that CFS is an evolutionarily conserved, genetically regulated, hypometabolic state similar to dauer that permits survival and persistence under conditions of environmental stress but at the cost of severely curtailed function and quality of life.”

Furthermore a computer model was able to predict CFS vs. controls in 94% of cases in males and 96% of cases in females. This is striking and occurred despite highly variable initial illness triggers. Varied triggers appear to result in similar disordered biochemistry. This may result in a diagnostic test for CFS, something which has been sought after since the 1980s. Since this time CFS has remained a syndrome and a diagnosis of exclusion resulting in significant stigma. This study suggests CFS is a hypometabolic state which can be defined by metabolomics analysis.


  1. 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 Aug 29. pii: 201607571.

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