The effect of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) severity on cellular bioenergetic function, by Cara Tomas, Joanna L Elson, Victoria Strassheim, Julia L Newton, Mark Walker in PLoS One vol 15, #4, e0231136, April 10, 2020


Research abstract:

Myalgic encephalomyelitis/ Chronic fatigue syndrome (ME/CFS) has been associated with abnormalities in mitochondrial function. In this study we have analysed previous bioenergetics data in peripheral blood mononuclear cells (PBMCs) using new techniques in order to further elucidate differences between ME/CFS and healthy control cohorts.

We stratified our ME/CFS cohort into two individual cohorts representing moderately and severely affected patients in order to determine if disease severity is associated with bioenergetic function in PBMCs.

Both  ME/CFS cohorts showed reduced mitochondrial function when compared to a healthy control cohort. This shows that disease severity does not correlate with mitochondrial function and even those with a moderate form of the disease show evidence of mitochondrial dysfunction.

Equations devised by another research group have enabled us to calculate ATP-linked respiration rates and glycolytic parameters. Parameters of glycolytic function were  calculated by taking into account respiratory acidification. This revealed severely affected ME/CFS patients to have higher rates of respiratory acidification and showed the importance of accounting for respiratory acidification when calculating parameters of glycolytic function. Analysis of previously published glycolysis data, after taking into account respiratory acidification, showed severely affected patients have reduced glycolysis compared to moderately affected patients and healthy controls. Rates of ATP-linked respiration were also calculated and shown to be lower in both ME/CFS cohorts.

This study shows that severely affected patients have mitochondrial and glycolytic impairments, which sets them apart from moderately affected patients who only have mitochondrial impairment. This may explain why these patients present with a more severe phenotype.

ME Research UK explains:

In this latest study, the authors reanalysed some of the findings from their previous work, separating the ME/CFS patients into two groups: moderately affected (housebound) and severely affected (bedbound)…

In their previous study, the authors had found no difference in glycolysis between controls and ME/CFS patients. However, by separating out the patients into the two groups by disease severity, we can now see that the most severely affected patients do actually appear to have reduced glycolysis levels, while moderately affected patients do not…

The study also highlights the importance of conducting research into the most severely affected ME/CFS patients, where possible…

Potential next steps would be to test these methods in other diseases with symptoms of severe fatigue, to determine if the findings are a result of the symptoms (fatigue) or the underlying disease (ME/CFS).

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