REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID

BackgroundLong 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.MethodsA total of 69 partici...

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Main Authors: Suzanne D. Vernon, Candace Rond, Jennifer Bell, Brindisi Butler, Sara Isolampi, Annaleah Otteson, Pearl Phalwane, Samantha Mower, Shad Roundy, David L. Kaufman, Alan B. Cash, Lucinda Bateman
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Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2025.1627462/full
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author Suzanne D. Vernon
Candace Rond
Jennifer Bell
Brindisi Butler
Sara Isolampi
Annaleah Otteson
Pearl Phalwane
Samantha Mower
Shad Roundy
David L. Kaufman
Alan B. Cash
Lucinda Bateman
author_facet Suzanne D. Vernon
Candace Rond
Jennifer Bell
Brindisi Butler
Sara Isolampi
Annaleah Otteson
Pearl Phalwane
Samantha Mower
Shad Roundy
David L. Kaufman
Alan B. Cash
Lucinda Bateman
author_sort Suzanne D. Vernon
collection DOAJ
description BackgroundLong 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.MethodsA total of 69 participants were randomized to receive either 2,000 mg/day of OAA or the control for 42 days. The primary outcome was fatigue reduction, measured by the Chalder Fatigue Questionnaire (CFQ). The secondary and exploratory outcomes included the DePaul Symptom Questionnaire Short Form (DSQ-SF), health-related quality of life (RAND-36), cognitive function (Defense Automated Neurobehavioral Assessment (DANA) Brain Vital), and time upright (UP Time).ResultsNo significant difference in the CFQ-measured fatigue reduction was observed between the groups. However, the OAA group showed significantly greater improvements in the DSQ-SF-measured fatigue and total symptom burden at day 21 of the trial. Cognitive performance improved significantly in the OAA group, with strong correlations between symptom response and cognitive gains. OAA was well tolerated.ConclusionOAA may contribute to earlier improvements in symptom burden and cognitive function in individuals with long COVID. Further studies are warranted.
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spelling doaj-art-8a6317a514b248ec9d14018ff809a7852025-08-20T03:28:01ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2025-07-011910.3389/fnins.2025.16274621627462REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVIDSuzanne D. Vernon0Candace Rond1Jennifer Bell2Brindisi Butler3Sara Isolampi4Annaleah Otteson5Pearl Phalwane6Samantha Mower7Shad Roundy8David L. Kaufman9Alan B. Cash10Lucinda Bateman11Bateman Horne Center, Salt Lake City, UT, United StatesBateman Horne Center, Salt Lake City, UT, United StatesBateman Horne Center, Salt Lake City, UT, United StatesBateman Horne Center, Salt Lake City, UT, United StatesBateman Horne Center, Salt Lake City, UT, United StatesBateman Horne Center, Salt Lake City, UT, United StatesBateman Horne Center, Salt Lake City, UT, United StatesDepartment of Mechanical Engineering, University of Utah, Salt Lake City, UT, United StatesDepartment of Mechanical Engineering, University of Utah, Salt Lake City, UT, United StatesCenter for Complex Diseases, Seattle, WA, United StatesTerra Biological LLC, San Diego, CA, United StatesBateman Horne Center, Salt Lake City, UT, United StatesBackgroundLong 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.MethodsA total of 69 participants were randomized to receive either 2,000 mg/day of OAA or the control for 42 days. The primary outcome was fatigue reduction, measured by the Chalder Fatigue Questionnaire (CFQ). The secondary and exploratory outcomes included the DePaul Symptom Questionnaire Short Form (DSQ-SF), health-related quality of life (RAND-36), cognitive function (Defense Automated Neurobehavioral Assessment (DANA) Brain Vital), and time upright (UP Time).ResultsNo significant difference in the CFQ-measured fatigue reduction was observed between the groups. However, the OAA group showed significantly greater improvements in the DSQ-SF-measured fatigue and total symptom burden at day 21 of the trial. Cognitive performance improved significantly in the OAA group, with strong correlations between symptom response and cognitive gains. OAA was well tolerated.ConclusionOAA may contribute to earlier improvements in symptom burden and cognitive function in individuals with long COVID. Further studies are warranted.https://www.frontiersin.org/articles/10.3389/fnins.2025.1627462/fulloxaloacetatelong COVIDfatiguecognitive impaimentrandomized clinical trial
spellingShingle Suzanne D. Vernon
Candace Rond
Jennifer Bell
Brindisi Butler
Sara Isolampi
Annaleah Otteson
Pearl Phalwane
Samantha Mower
Shad Roundy
David L. Kaufman
Alan B. Cash
Lucinda Bateman
REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID
Frontiers in Neuroscience
oxaloacetate
long COVID
fatigue
cognitive impaiment
randomized clinical trial
title REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID
title_full REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID
title_fullStr REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID
title_full_unstemmed REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID
title_short REGAIN: a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long COVID
title_sort regain a randomized controlled clinical trial of oxaloacetate for improving the symptoms of long covid
topic oxaloacetate
long COVID
fatigue
cognitive impaiment
randomized clinical trial
url https://www.frontiersin.org/articles/10.3389/fnins.2025.1627462/full
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