The research, published recently in the Proceedings of the National Academy of Sciences, focuses on the devastating condition known as myalgic encephalomyelitis, more popularly known as chronic fatigue syndrome. CFS is one of the biggest mysteries of modern medicine and is characterized by severe fatigue and related issues such as headaches and memory problems. According to conservative estimates, 2.5 million people in the United States suffer from it, but no cause has ever been pinpointed. That has made some doctors so skeptical of the diagnosis that many patients complain that they have sought help, only to be told the symptoms are in their heads.

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The PNAS study, led by University of California at San Diego researcher Robert K. Naviaux, looked at metabolites in the bodies of people with CFS and those without the condition. The number of participants was small — just 84 people, 45 with CFS symptoms and 39 who served as a control.

Naviaux looked at 612 different metabolites, which are intermediate substances such as glucose produced by cells as they break down larger molecules and produce energy. They found that 80 percent of the metabolites were lower in those with CFS. They also found what they described as “abnormalities” in 20 of the metabolic pathways.

All this suggests that the metabolism of people with CFS is markedly slowed down.

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The researchers said it appears to be similar to the “dauer state” in nematode worms when they are faced with starvation, overcrowding or other toxic environments. The dauer state involves a massive slowdown of the metabolism — an ability that has been of great interest to researchers for years because it is adaptive and is essentially a “non-aging” state when no cell death occurs. Cynthia Kenyon, a University of California at San Francisco scientist who now works for Google’s Calico start-up, gained fame for doubling the life span of a worm by altering a single gene that regulates the dauer state.

When it comes to CFS, this theory appears to explain some of the mysteries of the condition, such as why many people seem to come down with it after a trigger event such as an infection or exposure to chemicals.

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In a Q&A to the CFS community, Naviaux described this theory of humans having a cell-danger response in more depth: “Historical changes in the seasonal availability of calories, microbial pathogens, water stress and other environmental stresses have ensured that we all have inherited hundreds to thousands of genes that our ancestors used to survive all of these conditions.”

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When faced with adversity, cells go into defensive mode, he explained. “In most cases, this strategy is effective and normal metabolism is restored after a few days or weeks of illness, and recovery is complete after a few weeks or months.” But with CFS, it’s that possible the body got “stuck” in that state.

He said that although he does not believe that CFS is actually hibernation and although humans do not, in fact, hibernate, he said the “metabolic signature” is similar to that of animals in hibernation.

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Stanford Professor Ronald Davis called the work — if it can be replicated and validated — a “game-changer” for people with CFS. For the first time, it presents a possible biomarker for diagnosing the condition and provides a target for possible treatments.

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“What they found is that there may be an ancient pathway, and maybe in humans it’s not working very well. Or maybe people have gotten themselves too far down into the state and can’t get back out,” Davis said in an interview.

If that were the case, he explained, curing people of CFS may be akin to waking the body up. Davis said it’s possible that the treatment may not be anything radical; it might involve putting the body back in balance with the right mix of diet and supplements.

But even Davis cautioned that however alluring the paper’s implications are, “it is only a hypothesis.”

Davis, a professor of biochemistry and genetics, who was not involved in the original study, is collaborating with other scientists on a larger study to try to replicate the PNAS findings.

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