Trial Report Relationships Between Fatigue, Cognitive Function, and Upright Activity in a Randomized Trial of Oxaloacetate for [ME/CFS], 2025, Vernon et al

forestglip

forestglip

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Now published, see post #6
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Relationships Between Fatigue, Cognitive Function, and Upright Activity in a Randomized Trial of Oxaloacetate for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Suzanne D Vernon, Candace Rond, Yifei Sun, Shad Roundy, Jennifer Bell, Bella Rond, David Kaufman, Alan Brian Cash, Brayden Yellman, Lucinda Bateman

[Line breaks added]

Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating condition characterized by fatigue, cognitive impairment, and reduced physical function.

Oxaloacetate (OAA), a metabolic compound with potential mitochondrial and neuroprotective effects, has shown promise in reducing fatigue symptoms in ME/CFS. However, the interrelationships between fatigue, cognitive performance, and physical activity and their responsiveness to treatment remain poorly understood in ME/CFS.

Methods
This 90-day randomized, double-blind, controlled trial evaluated the effects of 2,000 mg/day OAA or a control of 2,000 mg rice flour in 82 adults with ME/CFS. Self-reported fatigue (Chalder Fatigue Questionnaire), cognitive function (DANA Brain Vital), and upright activity time (UP Time) were assessed at baseline and three follow-up visits.

Linear mixed-effects models examined associations between fatigue severity and cognitive/physical function, with treatment group interactions. Responder status at the last visit (Visit 4) was classified based on ≥15% fatigue reduction and/or ≥10% cognitive improvement.

Results
The OAA group showed greater cognitive improvement over time, with a significant between-group difference at Visit 3, 60 days into the trial, (p = 0.034) and trends at other visits. Higher fatigue was significantly associated with reduced cognitive gains in the OAA group (β = –0.34, p < 0.0001), but not in controls.

UP Time increased modestly in the OAA group, reaching significance at Visit 2, day 30 (p = 0.044), though fatigue was not a strong predictor of UP Time in either group. At Visit 4, day 90, Global and Fatigue Only Responders were more frequent in the OAA group, while Cognitive Only Responders were more frequent in controls, though group differences did not reach statistical significance (p = 0.10).

Conclusions
OAA supplementation was associated with improved cognitive performance and small improvement in UP Time in ME/CFS participants receiving OAA. Fatigue– cognition coupling was particularly strong in OAA-treated participants, suggesting a potentially targetable phenotype.

These findings underscore the importance of multidimensional outcome measures in ME/CFS clinical trials and support the need for more research and trials of metabolic interventions in ME/CFS.

Web | Frontiers in Neurology | Abstract only ahead of publication
 
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:unsure:For what its worth a mid section MRI with report currently costs $4000.00 in nz.
Naltrexone in minute,liquid suspension,dosage cost $98 per month plus script , plus pharmacist fee (and from what I understand here thats a relatively easily accessed medication).
While I hear you, !, costs worldwide are on the rise … its frightening to me what a simple meal now costs in NZ.
Just saying.
 
ChronicallyOverIt said:
I am very skeptical of this one. Anyways 2,000mg a day is $600 USD for 22.5 days; so $2,400 for the 90 day course. This is an outrageous price for such cherry-picked data. It is unfortunate they are selling this to sick people.
Click to expand...
see above… re costs… sorry, tough week.
 
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Five of the Krebs cycle reactions convert the glutamate metabolite α-ketoglutarate into oxaloacetate. My a-ketoglutarate is at 1 (ref range 5-80) so it's not going to make the conversion.

The conversion of α-ketoglutarate to succinyl-CoA is the next step after α-ketoglutarate is formed, which then continues to become oxaloacetate through a series of reactions: oxidation of succinyl-CoA to succinate and then the oxidation of malate to oxaloacetate. This entire process of converting α-ketoglutarate back to oxaloacetate is the final part of the citric acid cycle.

My CAC is low.
 
I tried it. No effect. I have genetic variants in OGDH which is essential to the Krebs cycle (I also have possible high impact variants in SLC25A5/ATAD3A)
 
I’d love for someone to mass spec the supplements themselves… I wonder how much that would cost. As we all know supplements are not regulated by the FDA. I wonder if it’s even oxaloacetate.
 
One of the authors from the paper re: Alan Cash

https://psblab.org/?p=618

So where’s the evidence?

As is often the case with the murky waters of poorly-regulated dietary supplements are a number of shortcomings with the actual underlying scientific evidence for OAA’s effects. Most of the hype appears to hinge on this 2009 paper in Aging Cell, claiming that addition of 8 mM (!) OAA to growth media enhances lifespan in the nematode C. elegans. A notable feature of this paper is that it was published in September 2009 and contains no conflict of interest statement.

Compare and contrast with an October 2009 review article (Submitted April that year) in the OA journal Open Longevity Science (which no longer exists), in which author Alan B. Cash lists a conflict of interest – namely being an officer of a company that sells OAA supplements (that would be Terra Biological, founded in 2006).

So, Dr. Cash (and the lead author on the Aging Cell paper David Williams) appear to have seen fit to disclose this rather massive COI in an OA review article, but not in an Aging Cell primary research paper. Another notable find is that Cash submitted a patent application on OAA as a CR mimetic in 2005 – a full 4 years before the paper was published. You might think such an event would require disclosure?

Back to the science, Cash’s glorious PowerPoint deck from 2014 includes claims that studies in mice were underway in 2011, in collaboration with Steve Spindler at UC Riverside. A quick PubMed search indicates that nothing was ever published on this. Similarly, claims are made about lifespan extension in flies, but again there’s nothing published.

For brain cancer, there are a couple of papers showing alleged effects of OAA in mice, but the data are just not very believable, and the dose used – 2 grams per kg (that’s not a typo) equating to 150 grams in a human – is ridiculous!

So, that leaves just about the entirety of the medical claims about OAA based on a single published paper about worms, a shady pay-to-play OA review article by the CEO of the company, and a bunch of unsubstantiated and unpublished claims in PowerPoint slides. Despite this, some people saw fit to convince the FDA to allow clinical trials – one for Parkinson’s, which failed, and another for Alzheimer’s which is ongoing (wanna bet how it’ll turn out?)

Someone needs to go read a biochemistry text book.
 
Bateman hornes “deep dive” feels misleading:

batemanhornecenter.org

Deep Dive: Oxaloacetate for Fatigue Reduction

A new clinical trial led by researchers at the Bateman Horne Center (BHC) offers encouraging evidence that targeting metabolism may help improve both brain function and daily activity in people with…
batemanhornecenter.org batemanhornecenter.org

The deep dive was spurred by seemingly more misleading page:

batemanhornecenter.org

Understanding the Potential of Oxaloacetate for Long COVID and ME/CFS

The REGAIN study, published in Frontiers in Neuroscience, explored the effects of oxaloacetate (OAA), a naturally occurring compound, on individuals living with Long COVID. Conducted as a randomized…
batemanhornecenter.org batemanhornecenter.org
 
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