Trial Report REGAIN: A Randomized Controlled Clinical Trial of Oxaloacetate for Improving the Symptoms of Long COVID, 2025, Vernon et al

[forestglip]

REGAIN: A Randomized Controlled Clinical Trial of Oxaloacetate for Improving the Symptoms of Long COVID

Suzanne D Vernon, Candace Rond, Jennifer Bell, Brindisi Butler, Sara Isolampi, Annaleah Otteson, Pearl Phalwane, Samantha Mower, Shad Roundy, David Kaufman, Alan Brian Cash, Lucinda Bateman

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.

Link (Frontiers in Neuroscience) [Provisionally accepted, currently only abstract]

 

[V.R.T.]

Why is any study that acknowledges ME/CFS as a physiological illness using the Chalder Fatigue Questionare at all, let alone as a primary outcome?

 

[NelliePledge]

They mentioned time upright as a measure but unlike the other measures didn’t say anything about the results. Surely time upright is going to be an important factor on cognitive performance for those affected by OI so should be considered in any judgment of improvement.

 

[Utsikt]

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.

«Significant», but no mention of «clinical significant». Might just be a low p-value for a small change.

 

[Mij]

Did they test their oxaloacetate levels to see if they were low to begin with?

 

[jnmaciuch]

I wonder if this study is also sponsored by the supplement company. I sure hope that if they do have any responders in this trial, they do the honest thing and let them know that malic acid is cheaply available and will almost certainly do the exact same thing.

 

[Mij]

https://benagene.com/pages/faqs

https://oxaloacetatecfs.com/pages/doctors
"CFS patients have low oxaloacetate levels"

True, mine were the lowest level on my OAT results. I took the supplement two decades ago and felt zero difference.

 

[InitialConditions]

on my OAT results

Are these tests actually legit? I never know whether they're just pure pseudoscience or not.

 

[Mij]

I had my test done through a biomedical center which included panels testing for antioxidants, iron metabolism, amino acids, fatty acids et. I think the tests are legit, but making up 'custom formula' to correct the imbalances is a scam. It did nothing for me.

 

[JES]

https://benagene.com/pages/faqs

https://oxaloacetatecfs.com/pages/doctors
"CFS patients have low oxaloacetate levels"

True, mine were the lowest level on my OAT results. I took the supplement two decades ago and felt zero difference.

The benaGene one? My understanding is they have some kind of patent for stabilizing it with vitamin C and that's why they can sell it for ridiculously expensive, but it may also work better than other oxaloacetate supplements if such have been on the market.

 

[Mij]

No, I didn't take the BeneGene brand. I don't remember which one I took or what dosage it was.

 

[jnmaciuch]

The benaGene one? My understanding is they have some kind of patent for stabilizing it with vitamin C and that's why they can sell it for ridiculously expensive, but it may also work better than other oxaloacetate supplements if such have been on the market.

Oxoaloacetate has to be converted into malate/malic acid first anyways, so stabilizing with vitamin C would not make any difference since it's going to get lobbed off before it does anything. I've been taking regular malic acid for months and can testify that it is absorbed perfectly fine, which is the only thing that vitamin C stabilization might help with. I suspect it's a situation where a drug company puts a completely irrelevant spin on an existing formula solely for the purposes of keeping the patent going for longer. You only need to show a tiny margin of benefit to qualify for the new patent.