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Biological Chemistry

Metabolite abnormalities pinpointed in chronic fatigue syndrome

Blood plasma study reveals chemical signature associated with lowered metabolic activity

by Stu Borman
September 12, 2016 | A version of this story appeared in Volume 94, Issue 36

Chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis, is a complex disorder characterized by malaise, sleep problems, and pain. The cause of the condition is unclear and difficult to diagnose and treat.

A metabolomics study now reveals a characteristic chemical signature of the condition in the blood plasma of people with CFS. The work could lead to a diagnostic test for CFS and aid the understanding of its underlying biology and cause.

“The finding of an objective chemical signature in CFS helps remove diagnostic uncertainty, will help clinicians monitor individualized responses to treatment, and will facilitate multicenter clinical trials,” writes Robert K. Naviaux of the University of California San Diego School of Medicine and coworkers, who carried out the study (Proc. Natl. Acad. Sci. USA 2016, DOI: 10.1073/pnas.1607571113).

The researchers used liquid chromatography-mass spectrometry to analyze 612 metabolites from 63 biological pathways in blood plasma from 84 men and women, 45 of whom have CFS. Of the 63 pathways, 20 were distinctly perturbed in the CFS subjects relative to non-CFS subjects. Nine of these pathway abnormalities were common to CFS-diagnosed men and women, whereas 11 showed gender differences. The greatest variations in CFS-related metabolites were widespread decreases in concentrations of sphingolipids and glycosphingolipids. Most of the reductions were similar to decreases in metabolite concentrations that occur in dauer, a well-studied worm response to environmental stress.

Industrial analytical chemist Mark Camenzind of San Ramon, Calif., who is a parent of a university student disabled by the condition and an advocate of CFS research, calls the study “one of the most important papers in three decades.”

Naviaux and coworkers caution that the study of larger cohorts from diverse areas and comparison with conditions such as depression and post-traumatic stress disorder will be needed to validate the findings.

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