Cash, Alan, Vernon, Suzanne D, Rond, Candace et al. · Frontiers in neurology · 2024 · DOI
This study tested whether a supplement called oxaloacetate could help reduce fatigue in ME/CFS patients. Eighty-two people with ME/CFS took either 2,000 mg of oxaloacetate or a placebo daily for three months. The oxaloacetate group experienced a significant 25% reduction in fatigue, while the placebo group only improved by 10%, and the supplement was well tolerated with no safety concerns.
Fatigue is the hallmark and most disabling symptom of ME/CFS, and existing treatments are limited. This study provides evidence that targeting a specific metabolic deficiency—low oxaloacetate—may be a viable therapeutic approach, offering potential relief to a patient population with few effective options. The high proportion of "enhanced responders" suggests oxaloacetate could benefit a substantial subset of ME/CFS patients.
This study does not prove that oxaloacetate deficiency is the root cause of ME/CFS fatigue—only that supplementation improves symptoms. It also does not establish optimal dosing, duration of treatment, long-term safety, or whether benefits persist after supplementation stops. The study's 3-month timeframe limits conclusions about sustainability of improvement.
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
Cash, Alan, Vernon, Suzanne D, Rond, Candace, Bateman, Lucinda, Abbaszadeh, Saeed, Bell, Jennifer, et al. (2024). RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome.. Frontiers in neurology. https://doi.org/10.3389/fneur.2024.1483876
BibTeX
@article{mecfsatlas-cash-2024-restore-rct,
author = {Cash, Alan and Vernon, Suzanne D and Rond, Candace and Bateman, Lucinda and Abbaszadeh, Saeed and Bell, Jennifer and Yellman, Brayden and Kaufman, David L},
title = {RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome.},
journal = {Frontiers in neurology},
year = {2024},
doi = {10.3389/fneur.2024.1483876},
note = {PubMed: 39664752},
url = {https://www.mecfsatlas.com/evidence/cash-2024-restore-rct},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-29. https://www.mecfsatlas.com/evidence/cash-2024-restore-rct
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