Chronic fatigue syndrome (CFS) is a debilitating and complex disorder that causes severe fatigue that is worsened by physical or mental activity and not improved by bed rest. While there is no cure or known cause for the debilitating ailment, researchers at the University of California San Diego School of Medicine have identified a characteristic chemical signature.

The researchers used a variety of techniques to identify and assess targeted metabolites in blood plasma that have brought to light an unexpected underlying biology, that is similar to the state of dauer (German word for persistence or long-lived), and other hypometabolic syndromes like caloric restriction, diapause and hibernation. Dauer is a type of period that involves inactivity in the development in some invertebrates that is prompted by harsh environmental conditions. The latest findings were published in Monday's issue of Proceedings of the National Academy of Sciences (PNAS).

"CFS is a very challenging disease," Robert K. Naviaux, MD, PhD, professor of medicine, pediatrics and pathology and director of the Mitochondrial and Metabolic Disease Center at UC San Diego School of Medicine said. "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."

According to estimates, as many as 2.5 million Americans are believed to have CFS, which mostly affects women in their 30s to 50s. CFA has eight official signs and symptoms, including the central symptom of severe fatigue.

  • Loss of memory or concentration
  • Sore throat
  • Enlarged lymph nodes in your neck or armpits
  • Unexplained muscle pain
  • Pain that moves from one joint to another without swelling or redness
  • Headache of a new type, pattern or severity
  • Unrefreshing sleep
  • Extreme exhaustion lasting more than 24 hours after physical or mental exercise

Naviaux and his colleagues studied 84 subjects, which include 45 men and women who met the diagnostic criteria for CFS and 39 matched controls. The researchers targeted 612 metabolites (substances produced by the processes of metabolism) from 63 biochemical pathways in blood plasma to conduct the study. Researchers found that individuals with CFS showed abnormalities in 20 metabolic pathways. According to the report, the diagnostic accuracy rate exceeded 90 percent.

"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," Naviaux said. "And interestingly, it's chemically similar to the dauer state you see in some organisms, which kicks in when environmental stresses trigger a slow-down in metabolism to permit survival under conditions that might otherwise cause cell death. In CFS, this slow-down comes at the cost of long-term pain and disability."

Possible complications of chronic fatigue syndrome include:

  • Depression
  • Social isolation
  • Lifestyle restrictions
  • Increased work absences

According to the first author, 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. The diagnosis of CFS required only 25 percent of the metabolite disturbances found in each person were needed for. Naviaux said that roughly 75 percent of abnormalities were unique to each individual, something that is useful in guiding personalized treatment.

"This work opens a fresh path to both understanding the biology of CFS and, more importantly to patients, a robust, rational way to develop new therapeutics for a disease sorely in need of them," Naviaux added.

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