Trial Report RESTORE ME: A RCT of Oxaloacetate for Improving Fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2024, Cash et al

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RESTORE ME: A RCT of Oxaloacetate for Improving Fatigue in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Alan B. Cash, Suzanne D. Vernon, Candace Rond, Saeed Abbaszadeh, Jen Bell, Brayden Yellman, David Kaufman

*[Provisionally accepted, full text not yet available]*

Abstract
The energy metabolite oxaloacetate is significantly lower in the blood plasma of ME/CFS subjects. A previous open-label trial with oxaloacetate supplementation significantly reduced ME/CFS fatigue.

In a follow-on trial, 82 ME/CFS subjects were enrolled in a 3-month randomized double blinded controlled trial using 2,000 mg oxaloacetate or control/day. The primary endpoints were safety and a reduction in fatigue from baseline. Secondary and exploratory endpoints reviewed functional capacity, and general health status.

Results: Anhydrous enol-oxaloacetate (oxaloacetate) was well tolerated at the doses tested. Oxaloacetate significantly lowered fatigue from baseline by >25%, whereas the control group was not significant at ~10% reduction. Intergroup analysis of oxaloacetate and control measured shifted fatigue to lower levels in the oxaloacetate group (P= 0.0039), but with no significant shift in the control group. The oxaloacetate group had a higher percentage of subjects achieve a > 25% reduction in fatigue compared to the control group (P< 0.05). A subset of subjects that comprised 40.5% of the oxaloacetate group were "Enhanced Responders" with a 63% average fatigue reduction.

Both physical and mental fatigue were improved by oxaloacetate. Oxaloacetate is well-tolerated and helps to reduce fatigue in ME/CFS.

Link (Frontiers in Neurology)
 
I posted my results on the other thread. My levels were very low. They are referring to the supplement as 'medical food grade'. What does that mean exactly?

Here we have clinical trials using Anhydrous Enol-oxaloacetate for brain function fatigue in cancer patients. I'm pretty sure they're not experiencing delayed PEM.

LINK
 
Mij said:
They are referring to the supplement as 'medical food grade'. What does that mean exactly?



LINK
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The term medical food, as defined in section 5(b) of the Orphan Drug Act (21 U.S.C. 360ee (b) (3)) is "a food which is formulated to be consumed or administered enterally under the supervision of a physician and which is intended for the specific dietary management of a disease or condition for which distinctive nutritional requirements, based on recognized scientific principles, are established by medical evaluation."
https://www.fda.gov/food/guidance-d...ods-guidance-documents-regulatory-information​
 
Given this trial was conducted at the Bateman Horne Centre, it is perhaps surprising to not see Lucinda Bateman's name on the study, as I assume she would have been the lead clinician assessing patients, and that usually warrants an authorship.

There were a lot of problems with the initial study, and the journal has now put a note on that study, discussed on the relevant thread, but copied here:
Note on initial study by two of the same authors said:
Editors' Note: Readers are advised that concerns have been raised regarding the methodology and reporting of this clinical trial and an incomplete declaration of competing interests, which are currently being investigated by the Editor-in-Chief. Further editorial action will be taken as appropriate once the investigation into the concerns is complete and all parties have been given an opportunity to respond in full.
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It is hard to know what to make of this new study given the conflicts of interest of a number of the authors is so strong i.e. the study serves as a marketing tool for a very expensive supplement.

If people are considering this treatment, it's worth reading the various threads we have on it e.g Oxaloacetate. Click on the 'oxaloacetate' tag on the top left of the thread for the full list.
 
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There area number of unclear aspects to the abstract text that worry me. We should be getting a straight report of a predefined primary endpoint. It is very unclear what the p value of 0.0039 refers to. If the study is robust it is important so why not write a clear abstract?
 
[Now published]

RESTORE ME: a RCT of oxaloacetate for improving fatigue in patients with myalgic encephalomyelitis/chronic fatigue syndrome

Alan Cash, Suzanne D. Vernon, Candace Rond, Lucinda Bateman, Saeed Abbaszadeh, Jennifer Bell, Brayden Yellman, David L. Kaufman

Background: The energy metabolite oxaloacetate is significantly lower in the blood plasma of ME/CFS subjects. A previous open-label trial with oxaloacetate supplementation demonstrated a significant reduction in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-related fatigue.

Methods: In this follow-up trial, 82 ME/CFS subjects were enrolled in a 3-month randomized, double-blinded, controlled study, receiving either 2,000 mg of oxaloacetate or control per day. The primary endpoints were safety and reduction in fatigue from baseline. Secondary and exploratory endpoints included functional capacity and general health status.

Results: Anhydrous enol-oxaloacetate (oxaloacetate) was well tolerated at the tested doses. Oxaloacetate significantly reduced fatigue by more than 25% from baseline, while the control group showed a non-significant reduction of approximately 10%. Intergroup analysis showed a significant decrease in fatigue levels in the oxaloacetate group (p = 0.0039) with no notable change in the control group. A greater proportion of subjects in the oxaloacetate group achieved a reduction in fatigue greater than 25% compared to the control group (p < 0.05). Additionally, 40.5% of the oxaloacetate group were classified as “enhanced responders,” with an average fatigue reduction of 63%. Both physical and mental fatigue improved with oxaloacetate supplementation.

Conclusion: Oxaloacetate is well tolerated and effectively helps reduce fatigue in ME/CFS patients.

----

Funding
The authors declare that financial support was received for the research, authorship, and/or publication of this article. This study was funded by Terra Biological LLC, who provided blinded active and control products for the trial. An officer of Terra Biological participated with all other authors in the group study design and review of the written article. The funder was not involved in study recruiting, data collection, data/sample storage, initial data analysis, or the decision to submit it for publication.

Conflict of interest
Lead author AC is an officer in the funding company Terra Biological LLC, which is commercializing oxaloacetate to treat fatigue.

The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Link | PDF (Frontiers in Neurology) [Open Access]
 
Kitty said:
If fatigue were the problem, it might be worthwhile for some.

It's not, though, a fact that seems to have escaped the authors.
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I don't know. It's hard to imagine my fatigue significantly improving without PEM changing. Since fatigue is kind of a consequence of PEM, I'd assume it's likely I'm not crashing as bad if my fatigue score is better.

And even if fatigue is literally the only thing that improves, I'll take what I can get. (Well maybe not for $500/month or whatever wild price this is.)
 
Kitty said:
That's the point, really. What if fatigue did lift, without PEM improving? You'd likely crash more because some of the warning signs were suppressed.
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Sure, just in me personally, it's hard to imagine myself reporting that one improved but not the other. If I feel less fatigued, I'll do more, then crash more, then feel more fatigued again. They feel very intertwined in me.

But it is a little odd that they only mention PEM once, and not in relation to the participants in the study, and they don't list any required specific ME/CFS criteria for inclusion, other than "diagnosed with ME/CFS with a stable state of illness in the preceding 3 months and self-reported upright activity between 2 and 6 h per day."

It might be possible it's useful for fatigue in general, but not ME/CFS specifically.
 
I don't like to read the twaddle. Straight to the graphs. According to this the treatment was non-significant. The graph on the right looks like manipulating data to get something nicer looking. i.e. if you cherry pick people who responded you get a significant result.
upload_2024-11-27_9-28-49.png

Now look at the table. Since the treatment is meant to be an energy enhancer I looked at the Energy/Fatigue row. Virtually no difference between patient and control. Well within the noise limits I think. Physical functioning had no difference.

upload_2024-11-27_9-30-19.png

We are never going to get anywhere with research like this. This paper is awful (Disclaimer : this is my take, and only my take, only having read the abstract and looked at key data quickly.]
 
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