Vernon, Suzanne D, Rond, Candace, Sun, Yifei et al. · Frontiers in neurology · 2025 · DOI
This study tested whether a compound called oxaloacetate (OAA) could help people with ME/CFS feel less fatigued and think more clearly. Over 90 days, people taking OAA showed better cognitive improvement and slightly more ability to stay upright compared to those taking a placebo. The results suggest that fatigue and thinking problems are closely linked in ME/CFS, and treating one may help improve the other.
This study is important because it examines how fatigue, cognitive dysfunction, and physical activity interconnect in ME/CFS—three hallmark symptoms that profoundly impact quality of life. By testing a metabolic intervention and demonstrating differential treatment responses, the research supports the exploration of targeted metabolic approaches and highlights the need for multidimensional outcome measures in future ME/CFS trials.
This study does not prove that oxaloacetate is an effective treatment for ME/CFS, as the responder rate differences did not achieve statistical significance and effect sizes were modest. It also does not establish mechanisms by which OAA may work or whether the observed fatigue-cognition coupling is causal versus correlational. The small sample size and short 90-day duration limit generalizability and long-term conclusions.
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
Vernon, Suzanne D, Rond, Candace, Sun, Yifei, Roundy, Shad, Bell, Jennifer, Rond, Bella, et al. (2025). Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome.. Frontiers in neurology. https://doi.org/10.3389/fneur.2025.1691147
BibTeX
@article{mecfsatlas-vernon-2025-relationships-between,
author = {Vernon, Suzanne D and Rond, Candace and Sun, Yifei and Roundy, Shad and Bell, Jennifer and Rond, Bella and Kaufman, David L and Cash, Alan B and Yellman, Brayden and Bateman, Lucinda},
title = {Relationships between fatigue, cognitive function, and upright activity in a randomized trial of oxaloacetate for myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Frontiers in neurology},
year = {2025},
doi = {10.3389/fneur.2025.1691147},
note = {PubMed: 41132887},
url = {https://www.mecfsatlas.com/evidence/vernon-2025-relationships-between},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/vernon-2025-relationships-between
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