Characteristic Chemical Signature Identified for Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS) is a multisystem disease that causes long-term pain and disability and it is difficult to diagnose because of its protean symptoms and the lack of a diagnostic laboratory test.

The disease is characterized by profound fatigue and disability lasting for at least six months, episodes of cognitive dysfunction, sleep disturbance, autonomic abnormalities, chronic or intermittent pain syndromes, microbiome abnormalities, cerebral cytokine dysregulation, natural killer cell dysfunction, and other symptoms that are made worse by exertion of any kind.


Scientists at the University Of California San Diego School Of Medicine (San Diego, CA, USA) recruited prospectively patients and controls to their study over a one-year period. Healthy controls were age- and sex-matched volunteers without CFS. The total number of subjects analyzed in this study was 84. This included 23 females and 22 males with CFS and 18 male and 21 female controls.

Targeted, broad-spectrum, chemometric analysis was performed for 612 metabolites from 63 biochemical pathways by hydrophilic interaction liquid chromatography, electrospray ionization, and tandem mass spectrometry in a single-injection method. Samples were analyzed on an AB SCIEX QTRAP 5500 triple quadrupole mass spectrometer (AB SCIEX, Framingham, MA, USA) equipped with a Turbo V electrospray ionization (ESI) source, Shimadzu LC-20A UHPLC system (Shimadzu Corporation, Kyoto, Japan), and a PAL CTC autosampler (CTC Analytics AG, Lake Elmo, MN, USA).

Patients with CFS showed abnormalities in 20 metabolic pathways with 80% 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. The diagnostic accuracy rate exceeded 90%. Area under the receiver operator characteristic curve analysis showed diagnostic accuracies of 94% in males using eight metabolites and 96% in females using 13 metabolites.

Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology and first author of the study said, “CFS is a very challenging disease. It affects multiple systems of the body. Symptoms vary and are common to many other diseases. There is no diagnostic laboratory test. Patients may spend tens of thousands of dollars and years trying to get a correct diagnosis. Despite the heterogeneity of CFS, the diversity of factors that lead to this condition, our findings show that the cellular metabolic response is the same in patients.” The study was published on August 29, 2016, in the journal Proceedings of the National Academy of Sciences of the United States of America.

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University Of California San Diego
AB SCIEX
Shimadzu
CTC Analytics