Low cell metabolism plagues ME/CFS sufferers

Myalgic encephalomyelitis, commonly known as chronic fatigue syndrome or ME/CFS, is a disease of many mysteries. Even the most fundamental questions remain unanswered: how does ME/CFS develop, and how can patients recover?

Researchers across the globe are addressing different aspects of this enigma. They seek to uncover a fundamental disruption that underlies the array of symptoms – or at least to identify an exclusive test result, or biomarker, that a general practitioner could use in making a diagnosis. Some labs focus on immune function, others on the gut microbiome, aerobic energy, or brain inflammation, among others.

Promising results are common, but two recent studies of cell metabolism have garnered special attention for their potential in both aiding diagnoses and explaining what goes wrong.

These two studies measured the same thing: cell metabolites. These are molecules that cells produce as part of their myriad activities. Different activities produce different metabolites. So the level of each metabolite in the blood provides a strong clue as to which processes cells are undertaking and how intensely. Sampling blood and cataloguing these molecules to interpret cells’ activity is called metabolomics.

Despite a similar focus, these two studies employed different equipment and searched for different, but overlapping, sets of metabolites. The first work came from the lab of Robert Naviaux at the University of California, San Diego, and was published last month in the Proceedings of the National Academy of Sciences. Studying the levels of 612 metabolites in the blood of 45 ME/CFS patients and 39 controls, Naviaux’s team found that:

• Most metabolites were lower in ME/CFS patients’ blood than in that of controls, but four were higher.
• The levels of a relatively few metabolites, considered together, could serve as a biomarker to distinguish ME/CFS sufferers from healthy controls in more than 90 percent of cases.
• The list of key metabolites differed between women and men, although there was some overlap.
• The pattern for ME/CFS was the opposite of that found during a healthy response to infection or in metabolic syndrome.

This work suggests that metabolic signatures could provide a straightforward biomarker for ME/CFS. Naviaux’s lab currently is engaged in a larger project to solidify this conclusion.

In explaining these results, Naviaux suggests that a hypometabolic state – or low activity – in cells is the central problem in ME/CFS. He notes that ME/CFS sufferers do not share a single type of triggering event, such as the same kind of infection. Instead, different stresses hit different people, and their bodies respond in the same way. They permanently enter a mode that resembles, metabolically at least, hibernation. Naviaux specifically argues that the metabolic pattern found in ME/CFS evokes that of dauer, a type of hibernation among nematodes.

The problem is that humans don’t hibernate.

A second, as-yet-unpublished study led by Maureen Hanson at Cornell University found the same overall patterns in metabolites – that is, a hypometabolic state. However, the details differed – such as the specific metabolites that were found to be most key. In a recent webinar, Hanson noted that these divergences might be due to differences in the study design or populations involved.

Subsequent research, such Naviaux’s larger follow-up project, might yield a more complex set of divisions among ME/CFS sufferers, beyond gender. Until then, these two studies have been hailed for their dual promise: to identify a potential biomarker and to explain a, or the, basic disruption that ME/CFS sufferers need to rectify.