Oxaloacetate Treatment For Mental And Physical Fatigue In (ME/CFS) and Long-COVID fatigue patients, 2022, Cash and Kaufman

This is channel 16 in Asheville, NC. 16 is constant Christian stuff and weird vitamins. I’ve not watched his show, but being on that channel is a red flag.

 

Another paper claiming effect when there is none at all

 

I was a patient of Kaufman from 2015-2017 and his fees were much much lower than cited above at that time. It seems after cci (both Jen and Jeff were his patients) his waiting lists got much longer and his fees much higher. I find the situation very sad.

 

Hi,
I haven't read this full thread, but I wanted to chime in as someone who participated in the study, here are my notes, apologies if some of the points have already been covered:

1. I was in the ME/CFS arm of the study. I dropped out due to an adverse event. Neither my dropping out or the adverse event were reported in the paper. I emailed the paper authors about this and was told this was a mistake. Somehow my data accidentally got dropped. They said this wouldn't have changed the overall results (likely true), but it is concerning and indicates a lack of carefulness. Also, I would argue, that it is a significant omission if the difference is 0 vs 1 adverse event w/ such a small sample size.

2. Alan Cash, who owns the company selling oxaloacetate was apparently the only one doing data analysis. This raises huge red flags for me.

3. To be accepted into the study, you had to fill out various questionnaires. In order to determine who to accept, they put a cutoff score.
This raises a couple of issues for me:
- First, it increases the odds of accepting someone into the study that is in a temporary flare when they fill out the first questionnaire, which will resolve on its own without oxaloacetate supplementation
- Second, Oxaloacetate is expensive. If, someone wanted to try it, but wasn't sure if they would meet the cutoff for the study, there is an incentive to maybe inflate the scores a little bit on this first questionnaire, just to make sure they get in. This incentive is removed after you have been accepted into the study for the two follow up questionnaires, hence creating an automatic improvement in symptom scores.

These are reasons why you need a proper control group. I don't have a good idea of the magnitude of these effects, but I imagine they could be quite large.

4. I'm not sure / don't remember what time periods all of the questionnaires were asking about? In some studies, I've seen, one questionnaire asks about 2 weeks of symptoms whereas another asks about 6 weeks of symptoms, making them not comparable (yet the study does, directly compare them). Can someone confirm if there is evidence that they did *not* do this? I wouldn't be surprised if the first questionnaire asked about 4 weeks of symptoms whereas the second two each asked about 2 weeks of symptoms, which again, could given an easy improvement (more likely to experience any symptom given 4 weeks vs with 2 weeks).

5. https://psblab.org/?p=618 - Interesting read, claiming oxaloacetate can't work the way it is claimed to work. Would be interested to hear someone w/ knowledge of this kind of thing chime in on accuracy.

 

Oxaloacetate is super acidic.
To do this properly, I imagine you would also need to use a super acidic placebo.
Although maybe most people wouldn't notice?
Agree though that they really need a proper placebo control.

 

So they never ran a panel of tests to determine if pwME oxaloacetate levels were low and retest to see if it increased or changed with this supplement?

 

They did not. I think someone else conclude pwME are low previously, but this study was entirely based on questionnaires no blood tests.

 

@zippymouse

A simple urine test before and after would have been sufficient. Mine was at -33%- the lowest on my OAT. I took oxaloacetate years ago, made on difference.

 

It seems to me that oxaloacetate is aimed at raising the rate of production of ATP via the citric acid cycle. Yet it probably is not a critical treatment point that I can see. Other things might be better. It certainly is not working as an energy source, the only value is to increase substrate in the cycle, which is then modified by other factors. That might have an impact but its hard to be sure without lots more research than I have seen.

In any study of this kind I want to see objective outcome markers. I am increasingly of the view that questionnaires should be used strictly for secondary (and subjective) outcome markers.

Why oxaloacetate is low in some patients is also critical. It might signal a mitochondrial problem at some earlier point. In other words, its after the block. Given suspected problems with complex V, and potential hypoxia, this looks like a potentially irrelevant treatment. Which means that any study needs to be even more careful, and pay attention to objective results.

If there is some other reason why it is low, not due to a citric acid cycle problem, then it needs to be identified. Where is that study?

 

Difference in the test or actually feeling better?

 

https://www.youtube.com/watch?v=WlUPaImRZts

 

That looks a fairly good account of why oxaloacetate isn't going to do anything.
It also looks like fairly good account of why this is almost certainly a scam.

 

I’ve always thought there were red flags around Kauffman. On PR, patients of his would report on treatment protocols that seemed very heavy handed for ME patients — I remember one being advised to do both IVIG and rituximab at once. As far as I recall he also relied on iGenex Lyme disease tests that are known to be hyper sensitive and have false positives.

 

I have sent a mail to Prof Francesco Marincola, Editor-in-Chief of the Journal of Translational Medicine, to alert him about two errors:

1) the claim that the trial was controlled even though it was not, which is explicitly acknowledged by the authors in the paper and was reaffirmed by Dr Kaufman at the 2022 IACFS/ME conference

2) the historical placebo group from the RCT of fluoxetine and graded exercise (Wearden 1998) did not improve by 5.9% at 26 weeks as claimed in the paper but by 7.9%, so the reported effectiveness of oxaloacetate supplementation was artificially inflated.

Edit: I have sent the same mail to Dr Monica Panelli, editor of the section Illnesses of Unknown Etiology in which the paper was published.

 

thank you @cassava7 I wish that there was more discussion at IACFSME surrounding this presentation but also others in regards to the limitations of their study. Kaufman reported no conflict of interest, it was a question that was asked in the Q&A. Beyond COI though, I wish it had been pointed out to him that this was not a controlled trial, there was no placebo and therefore this is not a strong clinical trial.

I would say as a research community, the experts lack clinical trial training and experience but I am willing to be wrong on this. Compare this field to the fields that have medical specialties dedicated to the disease they serve, and having funded drug trials left and right, I do sense that there is a low bar for success and for clinical trial standards with ME. Of course it doesn't help that we are still relying on self-report outcome measures and the possibility of all kinds of bias, from the patients, from the study design and from the researcher/sponsor point of view.

edit to add: I am sorry, I was venting. it is so frustrating to witness how slow it is to find what's wrong and how to fix it.

 

Post on the ME Association Facebook page.

"Oxaloacetate - a new treatment for ME/CFS and Long Covid?
I have been at the annual IACFS conference in (virtual) America for the past three days
One of the presentations in a Treatment session on Saturday afternoon came from Dr David Kaufman - who described the non-randomised clinical trial that he and Dr Alan Cash have carried out into the use of a nutritional supplement called oxaloacetate
The results that have been published - reductions in both physical and mental fatigue - are clearly interesting but have to be regarded as very preliminary at this stage
We will need more information from further clinical trials before any conclusions about the use of this supplement can be made
If anyone has tried using an oxaloacetate supplement please let us know
Dr Charles Shepherd - MEA"

https://www.facebook.com/meassociat...4tAmFpiFNHxJsaCKcg3bxDfQaVgVKGKoUxMo5vsWyx76l

I posted a link to this thread in the comments.

 

Could it have been the prohibitive cost? Were the long-covid patients required to purchase it?
Would allegiance to your doctor matters when it comes to participating in a study like this? Long-Covid patients would not have such allegiance or connection with the doctor.