CLINICAL TRIAL article
Front. Neurosci.
Sec. Autonomic Neuroscience
Volume 19 - 2025 | doi: 10.3389/fnins.2025.1627462
This article is part of the Research TopicExploring Chronic Fatigue: Neural Correlates, Mechanisms, and Therapeutic StrategiesView all 10 articles
REGAIN: A Randomized Controlled Clinical Trial of Oxaloacetate for Improving the Symptoms of Long COVID
Provisionally accepted
Suzanne D Vernon1*
Candace Rond1
Jennifer Bell1Brindisi Butler1Sara Isolampi1Annaleah Otteson1Pearl Phalwane1Samantha Mower2Shad Roundy2
David Kaufman3
Alan Brian Cash4
Lucinda Bateman1- 1Bateman Horne Center, Salt Lake City, United States
- 2University of Utah, Salt Lake City, United States
- 3Center for Complex Diseases, Seattle, United States
- 4Terra Biological LLC, San Diego, United States
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Background: Long COVID is characterized by fatigue, cognitive dysfunction, and other persistent symptoms. This randomized, double-blind, controlled trial evaluated the efficacy of oral oxaloacetate (OAA) in improving fatigue and cognitive function in adults with Long COVID.Methods: Sixty-nine participants were randomized to receive either 2,000 mg/day of OAA or control for 42 days. Primary outcome was fatigue reduction measured by the Chalder Fatigue Questionnaire (CFQ). Secondary and exploratory outcomes included the DePaul Symptom Questionnaire Short Form (DSQ-SF), health-related quality of life (RAND-36), cognitive function (DANA Brain Vital), and time upright (UP Time).Results: No significant difference in CFQ fatigue reduction was observed between groups. However, the OAA group showed significantly greater improvements in DSQ-SF fatigue and total symptom burden 21 days into the trial. Cognitive performance improved significantly in the OAA group, with strong correlations between symptom response and cognitive gains. OAA was well tolerated.Conclusions: OAA may contribute to earlier improvements in symptom burden and cognitive function in individuals with Long COVID. Further studies are warranted.
Keywords: Oxaloacetate, Long Covid, Fatigue, cognitive impaiment, Randomized Clinical Trial
Received: 12 May 2025; Accepted: 25 Jun 2025.
Copyright: © 2025 Vernon, Rond, Bell, Butler, Isolampi, Otteson, Phalwane, Mower, Roundy, Kaufman, Cash and Bateman. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Suzanne D Vernon, Bateman Horne Center, Salt Lake City, United States
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.