A chemical signature for chronic fatigue syndrome

Chronic fatigue syndrome (CFS) is a mysterious and debilitating condition with no known cause, cure or diagnostic test. With its symptoms common to many other diseases, patients may spend thousands of dollars and several years trying to get a correct diagnosis. Now, US researchers have identified a characteristic chemical signature that they believe will improve CFS diagnosis and provide clinical targets for personalised care.

Scientists at the University of California San Diego School of Medicine, led by Professor Robert K Naviaux, studied 84 subjects: 45 men and women who met the diagnostic criteria for CFS and 39 matched controls. They targeted 612 metabolites (substances produced by the processes of metabolism) from 63 biochemical pathways in blood plasma by hydrophilic interaction liquid chromatography, electrospray ionisation and tandem mass spectrometry in a single-injection method. The results were published in the journal Proceedings of the National Academy of Sciences.

The scientists found that individuals with CFS showed abnormalities in 20 metabolic pathways. 80% of the diagnostic metabolites measured were decreased, making them similar to the state of dauer — a type of stasis in the development in some invertebrates that is prompted by harsh environmental conditions — and other hypometabolic syndromes like caloric restriction, diapause and hibernation. The diagnostic accuracy rate exceeded 90%.

“Despite the heterogeneity of CFS, [and] the diversity of factors that lead to this condition, our findings show that the cellular metabolic response is the same in patients,” said Professor Naviaux. “And interestingly, it’s chemically similar to the dauer state you see in some organisms, which kicks in when environmental stresses trigger a slowdown in metabolism to permit survival under conditions that might otherwise cause cell death. In CFS, this slowdown comes at the cost of long-term pain and disability.”

Professor Naviaux said the findings show that CFS possesses an objectively identifiable chemical signature in both men and women and that targeted metabolomics, which provide direct small molecule information, can provide actionable treatment information. Only 25% of the metabolite disturbances found in each person were needed for the diagnosis of CFS. Roughly 75% of abnormalities were unique to each individual, which Professor Naviaux said will be useful in guiding personalised treatment.

Commenting on the study, Professor Andrew McIntosh from the University of Edinburgh noted that “it is difficult to know whether the changes reported are a cause or an effect of CFS” and that there is “a lot more to be done before there can be any clinical or diagnostic impact from this relatively new technology”.

“Further genomic and metabolic studies, independent replications and much larger samples will be needed to address these and other issues before any assessment of clinical impact can be made,” Professor McIntosh said. “Nevertheless, this is a promising start to a young and rapidly growing area of research with broad application to a number of common diseases.”