Research published in the Journal of Translational Medicine, Frontiers in Neurology and Frontiers in Neuroscience journals finds oxaloacetate improves ME/CFS and Long COVID symptoms including physical fatigue, mental fatigue, cognition, symptom burden and upright activity.

San Diego, CA August 18, 2026 –(PR.com)– Terra Biological today highlighted the substantial and growing body of clinical evidence supporting Oxaloacetate CFS™, a medical food formulated for the specific dietary management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

The body of clinical research of Oxaloacetate CFS now includes four peer-reviewed clinical publications examining anhydrous enol-oxaloacetate in people with ME/CFS and Long COVID. Together, the studies evaluate outcomes including physical and mental fatigue, cognitive performance, total symptom burden and real-world upright activity.

The publications draw on clinical trials enrolling approximately 270 participants. The research program includes a controlled dose-ranging study, two randomized double-blind controlled trials and an additional analysis examining the relationships among fatigue, cognition and physical function.

Unlike evidence based on a single study or outcome measure, this body of research examines oxaloacetate across different patient populations, trial durations, study designs and measures of clinical response.

Four Peer-Reviewed Clinical Study Publications

1. Oxaloacetate Treatment for Mental and Physical Fatigue in ME/CFS and Long COVID
The first clinical study, published in the Journal of Translational Medicine, evaluated six weeks of oral anhydrous enol-oxaloacetate using a dose-escalating methodology.
The study included 76 patients with ME/CFS and 43 patients with Long COVID. Participants with ME/CFS were diagnosed for an average of 8.9 years and Long COVID participants had experienced symptoms for at least six months.
Researchers reported that fatigue reduction among ME/CFS participants was dose-dependent, ranging from 21.7% at the lowest dosage to 33.3% at the highest dosage after six weeks. Long COVID participants experienced fatigue reductions of up to 46.8%.
Both physical and mental fatigue improved significantly compared with both baseline and historical controls.
2. RESTORE ME Randomized Controlled Trial
The RESTORE ME clinical trial is an 82-person, randomized, double-blind controlled study conducted at the Bateman Horne Center in Salt Lake City, Utah, a center of excellence for ME/CFS treatment.
Participants received either 2,000 mg of oxaloacetate or a control daily for 90 days. Oxaloacetate significantly reduced fatigue by more than 25% from baseline, compared with a non-significant reduction in the control group. The difference between groups was statistically significant.
Researchers found that 40.5% of participants receiving oxaloacetate were “enhanced responders,” with an average fatigue reduction of 63%. Improvements were observed in both physical and mental fatigue.
Of additional interest is that the oxaloacetate group saw reduced/eliminated “crashes” as measured by the Chalder Fatigue Scale, whereas the control group continued to have a sizable population that experienced energy crashes.
The study further reported that oxaloacetate was well-tolerated at the tested dosage.
3. REGAIN Randomized Controlled Trial for Long COVID
The REGAIN study was a randomized, double-blind controlled clinical trial evaluating oral oxaloacetate in 69 adults with Long COVID.
Participants received either 2,000 mg of oxaloacetate or a control daily for 42 days. The oxaloacetate group experienced significantly greater improvements in fatigue and total symptom burden measured by the DePaul Symptom Questionnaire Short Form at day 21.
Cognitive performance also improved significantly in the oxaloacetate group, with strong correlations between symptom response and cognitive gains. Oxaloacetate was well tolerated.
The researchers concluded that oxaloacetate may contribute to earlier improvements in symptom burden and cognitive function among people with Long COVID.
4. Relationships Between Fatigue, Cognitive Function and Upright Activity in ME/CFS
A subsequent Frontiers in Neurology analysis examined cognitive performance and upright activity data collected during the 90-day RESTORE ME randomized trial.
Participants receiving oxaloacetate demonstrated greater cognitive improvement over time than the control group, reaching a statistically significant between-group difference at day 60. The oxaloacetate group also experienced an increase in upright activity, with a statistically significant difference at day 30.
The analysis found a strong relationship between fatigue severity and cognitive performance among oxaloacetate-treated participants. Researchers concluded that oxaloacetate supplementation was associated with improved cognitive performance and improvement in upright activity among participants with ME/CFS.

Evidence Across Multiple Dimensions of Chronic Fatigue
Collectively, the four publications investigate oxaloacetate’s effects across several of the most disabling aspects of ME/CFS and Long COVID:

Physical fatigue
Mental fatigue
Cognitive performance and brain fog
Total symptom burden
Functional capacity
Time spent upright
Individual and enhanced responder patterns
Safety and tolerability

The studies were published in peer-reviewed journals including the Journal of Translational Medicine, Frontiers in Neurology and Frontiers in Neuroscience.

“Amelioration of fatigue to this degree can be life changing for ME/CFS patients,” said Alan Cash, founder and Chief Science Officer of Terra Biological LLC.

The expanding research program reflects Terra Biological’s commitment to advancing evidence-based nutritional therapies for people living with ME/CFS and Long COVID—patient communities that have historically had few treatment options and limited resources.

Additional study summaries, full publications and clinical trial information are available through the Oxaloacetate CFS clinical studies library.

Oxaloacetate CFS is a medical food intended to be used under the supervision of a qualified healthcare professional. The information provided in this release is educational and should not be interpreted as individual medical advice.

Terra Biological LLC is a family-owned biotechnology research and development company established in San Diego in 2006. Its patented, thermally stabilized oxaloacetate products were developed from research into the molecular metabolic pathways associated with cellular energy production.

Terra Biological works closely with researchers, healthcare professionals and patient communities to investigate oxaloacetate-based nutritional therapies supporting a range of health needs.

Contact Information:
Terra Biological LLC
Devon Lantry
858-947-5722
Contact via Email
terrabiologicalllc.com

Read the full story here: https://www.pr.com/press-release/976782

Press Release Distributed by PR.com

Media gallery

About The Author
Terra Biological LLC