Bohne, Victoria J Berdikova, Bohne, Øyvind · Medical hypotheses · 2019 · DOI
This paper proposes that ME/CFS might result from a problem in how the body converts fuel into energy, specifically involving a protein complex called the pyruvate dehydrogenase complex. The researchers suggest that when this complex isn't working properly, it causes lactate (a byproduct of metabolism) to build up suddenly in the body, which could explain the exhaustion and post-exertional malaise (worsening after activity) that patients experience. They propose that the body isn't efficiently recycling important molecules needed for energy production, leading to low energy and fatigue.
Understanding the cellular mechanisms behind ME/CFS is crucial for developing targeted treatments, as current therapies remain ineffective for most patients. If PDC dysfunction is confirmed as central to disease pathology, it could guide development of novel interventions targeting lactate metabolism and energy production. This hypothesis also offers a potential explanation for why standard fatigue treatments fail and why activity can worsen symptoms so dramatically.
This is a theoretical hypothesis paper with no experimental data, clinical measurements, or patient samples presented—it does not prove that PDC dysfunction causes ME/CFS in humans. The proposed mechanism connecting lactate fluctuations to symptoms is speculative and requires empirical validation through controlled studies. The paper does not establish whether any observed lactate elevations are a cause or consequence of the disease process.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
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