Fluge, Øystein, Tronstad, Karl J, Mella, Olav · The Journal of clinical investigation · 2021 · DOI
This review article examines what we know about how ME/CFS damages the body and discusses possible treatments. Researchers looked at existing scientific evidence to understand the disease mechanisms—the biological processes that cause ME/CFS symptoms—and evaluated various interventions that might help patients. The goal was to create a comprehensive overview of current scientific understanding to guide future research and treatment development.
This review is important because ME/CFS pathophysiology remains poorly understood, and patients lack effective evidence-based treatments. By consolidating what is known about disease mechanisms and evaluating existing interventions, this work can help researchers prioritize which biological pathways to investigate and inform clinical decision-making about potential therapies.
This review does not prove that any particular intervention is effective in clinical practice—it synthesizes existing evidence rather than conducting new trials. Systematic reviews identify correlations and associations but cannot establish causation without high-quality experimental evidence. The conclusions are limited by the quality and quantity of underlying primary research on ME/CFS.
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 →
The first block is for the primary paper and is the citation you should use in research work. The atlas-snapshot line only applies if you are specifically referring to this atlas’s reading of the paper on the date shown.
Primary citation
Fluge, Øystein, Tronstad, Karl J, & Mella, Olav (2021). Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).. The Journal of clinical investigation. https://doi.org/10.1172/JCI150377
BibTeX
@article{mecfsatlas-fluge-2021-pathomechanisms-possible,
author = {Fluge, Øystein and Tronstad, Karl J and Mella, Olav},
title = {Pathomechanisms and possible interventions in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).},
journal = {The Journal of clinical investigation},
year = {2021},
doi = {10.1172/JCI150377},
note = {PubMed: 34263741},
url = {https://www.mecfsatlas.com/evidence/fluge-2021-pathomechanisms-possible},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/fluge-2021-pathomechanisms-possible
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