Cash, Alan, Kaufman, David Lyons · Journal of translational medicine · 2022 · DOI
This study tested whether a supplement called oxaloacetate could help reduce fatigue in ME/CFS and Long COVID patients. Over 6 weeks, patients taking oxaloacetate showed significant improvements in both mental and physical fatigue—with ME/CFS patients improving by 22–33% depending on dose, and Long COVID patients improving by up to 47%—compared to expected placebo improvements of about 6%.
With no FDA-approved treatments for ME/CFS fatigue and millions suffering from persistent post-COVID fatigue, this study offers preliminary evidence for a potential low-risk nutritional intervention. The dose-dependent response pattern and improvements substantially exceeding historical placebo suggest oxaloacetate warrants further rigorous investigation in this severely understudied patient population.
This study does not prove oxaloacetate is effective because it lacks a concurrent randomized control group receiving placebo in parallel—relying instead on historical placebo data introduces bias and cannot control for concurrent environmental or temporal factors. The open-label design is subject to placebo response and expectancy effects, and the study cannot establish whether oxaloacetate specifically alleviates fatigue through a biological mechanism or through other unmeasured factors.
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 & Kaufman, David Lyons (2022). Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial.. Journal of translational medicine. https://doi.org/10.1186/s12967-022-03488-3
BibTeX
@article{mecfsatlas-cash-2022-oxaloacetate-treatment,
author = {Cash, Alan and Kaufman, David Lyons},
title = {Oxaloacetate Treatment For Mental And Physical Fatigue In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long-COVID fatigue patients: a non-randomized controlled clinical trial.},
journal = {Journal of translational medicine},
year = {2022},
doi = {10.1186/s12967-022-03488-3},
note = {PubMed: 35764955},
url = {https://www.mecfsatlas.com/evidence/cash-2022-oxaloacetate-treatment},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-28. https://www.mecfsatlas.com/evidence/cash-2022-oxaloacetate-treatment
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