Joseph, Phillip, Pari, Rosa, Miller, Sarah et al. · Chest · 2022 · DOI
This study tested whether a medication called pyridostigmine could help people with ME/CFS exercise better by improving blood flow and heart function. Researchers gave 45 ME/CFS patients either pyridostigmine or a placebo, then measured their exercise capacity twice using specialized heart and lung tests. The group taking pyridostigmine showed improved oxygen uptake and better heart function during exercise, while the placebo group actually got worse, suggesting the medication may help counteract some of the body's dysfunctional responses to exercise in ME/CFS.
This study provides mechanistic evidence that neurovascular dysregulation—a treatable condition—may underlie exercise intolerance in ME/CFS, offering hope for a potential targeted therapeutic approach. If confirmed in larger trials, pyridostigmine or similar agents could provide symptom relief for patients with postexertional malaise and orthostatic intolerance, two hallmark and disabling features of ME/CFS.
This study does not prove that pyridostigmine is an effective long-term treatment for ME/CFS—it only shows acute effects in a single exercise session. It does not establish that neurovascular dysregulation is the sole cause of ME/CFS, only that it may contribute to acute exercise intolerance. The study cannot determine whether these improvements would persist with repeated dosing or benefit all ME/CFS patients, as responders and non-responders were not distinguished.
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
Joseph, Phillip, Pari, Rosa, Miller, Sarah, Warren, Arabella, Stovall, Mary Catherine, Squires, Johanna, et al. (2022). Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.. Chest. https://doi.org/10.1016/j.chest.2022.04.146
BibTeX
@article{mecfsatlas-joseph-2022-neurovascular-dysregulation,
author = {Joseph, Phillip and Pari, Rosa and Miller, Sarah and Warren, Arabella and Stovall, Mary Catherine and Squires, Johanna and Chang, Chia-Jung and Xiao, Wenzhong and Waxman, Aaron B and Systrom, David M},
title = {Neurovascular Dysregulation and Acute Exercise Intolerance in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Randomized, Placebo-Controlled Trial of Pyridostigmine.},
journal = {Chest},
year = {2022},
doi = {10.1016/j.chest.2022.04.146},
note = {PubMed: 35526605},
url = {https://www.mecfsatlas.com/evidence/joseph-2022-neurovascular-dysregulation},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-26. https://www.mecfsatlas.com/evidence/joseph-2022-neurovascular-dysregulation
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