How Chronic Fatigue Syndrome Affects Your Metabolism

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A new study links the disease to depressed levels of metabolites, the waste products of ordinary cell function.

By Nathan Collins

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(Photo: Peter Macdiarmid/Getty Images)

There are somewhere around one or two million Americans with chronic fatigue syndrome (CFS), a disease that often leaves sufferers barely able to move or think. But after decades in the dark, researchers have finally taken a step toward better understanding CFS: Among other things, the disease is correlated with a substantial decline in metabolites, the waste products our cells produce as part of their normal function.

It’s been a strange couple of years for people with CFS, also known as myalgic encephalomyelitis (ME), and for researchers working toward a better understanding of it. In that time, doctors and epidemiologists have discovered new tests for ME/CFS and strong hints that it could be a disorder of the immune system. Meanwhile, the National Institutes of Health announced it was in the planning phase of a major new study aimed at understanding the causes and mechanisms behind the disease.

That’s the good news. Now the bad news: The belief that chronic fatigue syndrome is essentially a psychological disorder persists, even among researchers. In particular, a British study known as the PACE trial claimed to have found evidence that special exercise regimens and cognitive behavioral therapy could make for an effective treatment. Though the PACE study has come under heavy fire for methodological problems, the belief remains that ME/CFS exists purely in sufferers’ minds.

Perhaps the new study will put that notion to rest: Not only do ME/CFS patients show signs of lowered metabolism, the severity of their disease is tied to the degree by which a person’s metabolism is below normal. Robert Naviaux and his colleagues at the University of California–San Diego and Gordon Medical Associates targeted metabolites, the waste products of chemical reactions inside cells. That’s in part because there are relatively few metabolites compared to, say, the number of base pairs in our DNA (around two thousand compared to six billion). Metabolites can also reflect environmental stresses, such as exposure to bacteria, viruses, and mold— factors that are thought to be crucial to the development of ME/CFS.

The belief that chronic fatigue syndrome is essentially a psychological disorder persists, even among researchers.

Naviaux and his team therefore measured the levels of 612 different metabolites in blood plasma samples from 45 people with ME/CFS and 39 healthy controls. Two classes of metabolites, both associated with nerve cell walls, stood out and accounted for the bulk of metabolic disruption in both men and women. However, many more were suppressed. Out of the 25 metabolites the team identified as most associated with ME/CFS, four were increased and 21 were decreased in patients compared to healthy controls, “consistent with the notion that CFS is a coordinated hypometabolic [low metabolism] state,” the authors write.

Perhaps most important, in the near term at least, is what the results mean for diagnosis. The team could correctly identify ME/CFS patients about 95 percent of the time using just a small sample of metabolites—13 in women and eight in men—meaning a lab test for ME/CFS based on metabolic function could be within reach. Right now, diagnoses are made on the basis of a series of symptoms, such as severe post-exercising fatigue, all of which must persist for at least six months—criteria that are relatively subjective and vastly more time consuming than a blood test.

“The study of larger cohorts from diverse geographical areas, and comparison with related medical disorders like depression and post-traumatic stress disorder, will be needed to validate the universality and specificity of these findings,” the researchers write, but finding clear chemical signs in ME/CFS “helps to remove diagnostic uncertainty, will help clinicians monitor individualized responses to treatment, and will facilitate multicenter clinical trials.”

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