Maughan, David, Toth, Michael · Biology · 2014 · DOI
This review examines why fatigue happens in chronic diseases like ME/CFS, multiple sclerosis, and heart failure. The authors point out that fatigue comes from a mix of problems in how the body uses energy, how the nervous system works, and how muscles function. They emphasize that inactivity and loss of fitness may contribute significantly to fatigue, and this is often overlooked when researchers only focus on the disease itself.
For ME/CFS patients and researchers, this paper highlights a critical gap in fatigue research: distinguishing what symptoms come directly from the disease versus what develops from reduced activity and deconditioning. This distinction is essential because it affects rehabilitation strategies—if some fatigue is due to deconditioning, appropriately designed exercise might help, whereas if it's primarily disease-driven, different approaches may be needed.
This is a commentary review, not a primary research study with new data. It does not prove cause-and-effect relationships or provide new experimental evidence about which factors most strongly drive fatigue in ME/CFS specifically. It also does not demonstrate that exercise rehabilitation is universally safe or effective for all ME/CFS patients, only that understanding the source of muscle changes is necessary to evaluate rehabilitation utility.
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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Primary citation
Maughan, David & Toth, Michael (2014). Discerning primary and secondary factors responsible for clinical fatigue in multisystem diseases.. Biology. https://doi.org/10.3390/biology3030606
BibTeX
@article{mecfsatlas-maughan-2014-discerning-primary,
author = {Maughan, David and Toth, Michael},
title = {Discerning primary and secondary factors responsible for clinical fatigue in multisystem diseases.},
journal = {Biology},
year = {2014},
doi = {10.3390/biology3030606},
note = {PubMed: 25247274},
url = {https://www.mecfsatlas.com/evidence/maughan-2014-discerning-primary},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/maughan-2014-discerning-primary
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