Oxaloacetate improves Cognition in ME/CFS and Long COVID
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In a newly published article in “Frontiers in Neurology”, a double-blinded, randomized, controlled clinical trial at the Bateman Horne Center, an ME/CFS Center of Excellence, found that a metabolite, “Oxaloacetate,” significantly increased cognition over the control group (p=0.034) in ME/CFS patients. Interestingly, in the oxaloacetate group, perceived fatigue and cognition were coupled (p< 0.0001) but the coupling was non-significant in the control group.
This provides further evidence that oxaloacetate, which has been shown to enhance neuronal functioning https://pubmed.ncbi.nlm.nih.gov/26811028/ may be able to reduce perceived physical fatigue via treating metabolic issues in the central nervous system. The 82 adults in the study took either 2,000 mg/day of oxaloacetate or 2,000 mg/day of rice flour for 90 days in the study.
In a previous publication in “Frontiers in Neurology”, another double-blinded, randomized, controlled clinical trial at the Bateman Horne Center found that oxaloacetate significantly increased cognition in Long COVID patients. https://pubmed.ncbi.nlm.nih.gov/40757370/ Total cognitive efficiency was highly significant over control (p<0.0001), indicating overall improvement in cognitive performance across visits. The 69 adults in the study also took either 2,000 mg/day of oxaloacetate or 2,000 mg/day of rice flour for 42 days.
“Emerging research has implicated mitochondrial dysfunction (Szögi et al., 2025), altered redox homeostasis (Vlaming-van Eijk et al., 2024), and altered metabolism (Saito et al., 2024) as potential contributors to the persistence of symptoms in long COVID patients. Oxaloacetate, a key intermediate of the citric acid cycle, has demonstrated the potential to modulate cellular metabolism, enhance mitochondrial biogenesis, and reduce neuroinflammation in preclinical models (Wilkins et al., 2014).”
- Vernon, et al 2025
“Cognitive function, or “Brain Fog”, is a hallmark and highly disabling feature of both ME/CFS and Long COVID. At least 57% of individuals with long COVID reported experiencing cognitive symptoms daily and may continue to experience chronic cognitive symptoms for months or years.”
- Vernon, et al 2025
Like Long COVID, ME/CFS patients also experience cognitive disfunction, or “Brain Fog”. Brain Fog can affect everyday life by making it difficult to focus, remember things and perform daily tasks, which can negatively impact work, social life and relationships. Brain Fog may also put others at risk, as the number of impacted ME/CFS and Long COVID patients that are driving on the roads may number in the millions. Reduced reaction time certainly increases risk in driving.
Oxaloacetate CFS, the medical food used in the studies, is now commercially available for ME/CFS patients and Long COVID patients that have transitioned to ME/CFS. In the clinical trials, patients in the treatment group took 2 500 mg capsules of oxaloacetate with breakfast and 2 500 mg capsules of oxaloacetate with lunch each day.