Scheibenbogen, Carmen, Wirth, Klaus J · Journal of cachexia, sarcopenia and muscle · 2025 · DOI
This review brings together recent research showing that ME/CFS involves problems in the muscles themselves, particularly damage to mitochondria (the energy-producing structures inside cells) and an imbalance of salt and calcium in muscle tissue. When muscles don't get enough oxygen, they switch to a less efficient way of making energy, which causes sodium (salt) to build up inside cells, triggering calcium overload that damages mitochondria. This cascade of damage may explain why patients experience severe fatigue and feel much worse after exercise.
This synthesis of recent muscle pathology research provides the strongest evidence to date for a specific biological mechanism underlying ME/CFS symptoms, moving beyond speculation toward targetable dysfunction. Understanding that the problem resides in muscle tissue rather than systemic immune dysfunction opens new treatment avenues and validates the reality of the disease for patients and clinicians. This work also helps explain why only some post-COVID patients progress to ME/CFS, identifying specific risk factors and mechanisms.
This review does not prove causation—elevated sodium and mitochondrial damage are correlated with disease but the temporal sequence and whether they are primary or secondary to other processes remains incompletely established. The review also does not establish why hypoperfusion occurs in ME/CFS muscle tissue, only that its consequences fit observed pathology. Additionally, findings from small biopsy studies in selected patients may not represent all ME/CFS patients or all muscle groups.
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 →
Contribute
Private, reviewed by a human. Not a public comment thread.