Hara, Yurie, Kume, Satoshi, Kataoka, Yosky et al. · Heliyon · 2021 · DOI
This study tested whether citric acid (a compound found in citrus fruits) changes the levels of energy-related chemicals in the blood of rats. Researchers found that giving citric acid increased levels of several metabolites involved in energy production—the opposite pattern seen in ME/CFS patients. This suggests citric acid might help restore normal energy metabolism, which could explain why some people report feeling less fatigued after consuming it.
ME/CFS is characterized by abnormal TCA cycle metabolism, and this study provides a potential biochemical explanation for why citric acid supplementation might help restore normal energy production pathways. Understanding how dietary interventions affect the metabolic defects in ME/CFS could lead to evidence-based nutritional strategies to manage fatigue.
This rat study does not prove that citric acid improves fatigue or energy in ME/CFS patients. The correction of plasma metabolite levels in healthy rats may not translate to clinical benefit in humans with ME/CFS, and the study does not directly test whether these metabolic changes reduce fatigue symptoms or improve exercise tolerance.
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
Hara, Yurie, Kume, Satoshi, Kataoka, Yosky, & Watanabe, Nakamichi (2021). Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats.. Heliyon. https://doi.org/10.1016/j.heliyon.2021.e08501
BibTeX
@article{mecfsatlas-hara-2021-changes-tca,
author = {Hara, Yurie and Kume, Satoshi and Kataoka, Yosky and Watanabe, Nakamichi},
title = {Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats.},
journal = {Heliyon},
year = {2021},
doi = {10.1016/j.heliyon.2021.e08501},
note = {PubMed: 34934832},
url = {https://www.mecfsatlas.com/evidence/hara-2021-changes-tca},
}Atlas snapshot reference
ME/CFS Atlas. Generator v1 / Scanner v1.4 / policy v0.1. Accessed 2026-05-30. https://www.mecfsatlas.com/evidence/hara-2021-changes-tca
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