Mitochondrial and Energy Metabolism Dysfunction in ME/CFS — Myhill, Booth and McLaren-Howard Papers

[Learner1]

@Hip and @sb4 @Learner1 --curious about what you think about the first post in this thread: https://raypeatforum.com/community/threads/pyrucet-liquid-ethyl-pyruvate-aceatoacetate-mix.27487/

It seems like haidut dumps a dizzying amount of links validating ethyl pyruvate , which is fine, but it's an excessive amount. I trust ethyl pyruvate. All the links serve to do is distract from the relative lack of links supporting safety and efficacy of ethyl acetoacetate , which is the more unknown variable. I dont know if its unsafe but I'm also just eternally annoyed by haiduts very grandstanding, manic ideas to constantly combine novel things when one product would be good enough. Like just giving people consumer grade ethyl pyruvate would be a huge improvement on the status quo , why add this ethyl acetoacetate that had like no study on it? Just to have a mad scientist feeling of validation of "combining cool shit "?

To be clear I've taken this a lot and not noticed any specific negative effects . I think it helps me a bit. But I could rest easier taking higher doses if there was just a simpler product with ethyl pyruvate.
@rpapen77 have you noticed any of the studies in that thread validating the safety of the doses of acetoacetate being used with this product ? @sb4 has anyone questioned haidut on this specifically.

Thanks for sharing the link. From what I understand, Pyrucet and it's constituents would help decrease FAO and increase use of glucose. My testing indicates I need the opposite, more FAO and less glucose usage as my issues with aerobic exercise seem to be related to burning up glycogen faster than I can replenish it and not having enough glucose to use, while FAO is idle.

Good luck with your experiments. I'd want to be sure I was solving a problem I actually had....

 

[sb4]

I just did a quick search and I asked hadiut about ethyl acetoactate here https://raypeatforum.com/community/...ethyl-pyruvate-aceatoacetate-mix.27487/page-8

but it is from the perspective of taking it at high doses to stimulate a ketogenic type effect so not sure if thats any use to you. It seems I came up with 15g ethyl acetoacetate being safe presumably due to rat LD50s but I wouldn't rely on that info.

How high of a dose are you intending to try?

 

[frozenborderline]

Thanks for sharing the link. From what I understand, Pyrucet and it's constituents would help decrease FAO and increase use of glucose. My testing indicates I need the opposite, more FAO and less glucose usage as my issues with aerobic exercise seem to be related to burning up glycogen faster than I can replenish it and not having enough glucose to use, while FAO is idle.

Good luck with your experiments. I'd want to be sure I was solving a problem I actually had....

Thanks for your input. I'm sure I have issues that ethyl pyruvate would address, my concern is merely over ethyl acetoacetate safety. Given that I haven't fully recovered from surgery and reading at length is hard, it has been hard to pick through those threads to find the studies that would suggest either way

 

[frozenborderline]

15g ethyl acetoacetate being safe presumably due to rat LD50s but I wouldn't rely on that info.

So 15 g is the equivalent of rat LD50s, or 15 g is safe bc it's well under the equivalent of rat ld50s? Bc ld50, as you know, isn't maximum safe dose, its dose at which 50 percent of population die

I'm looking at doses a bit under that. Stated dose is 500 mg. I often went up to 1500 or 1.5 g. Didnt notice issues but you said there may be significant amounts of alcohol when its broken down? I'm trying to avoid alcohol except in tiny amounts like under 1 standard drunk.

 

[sb4]

@frozenborderline TBH I can't remember much about this as it was 2 years ago. I have just looked at a data sheet for LD50 in rats and its 4g/kg.
4 * 100kg = 400g convert to human / 7.4 = 54g.
Wouldn't trust these calculations as I don't really know what I am talking about.

I think I was also trying to factor in taking a similar dose of ethyl pyruvate which my lower the LD50.

Either way it would be easier if you could just find a way to buy from one of those companies that only sells to labs. Trick them some how into selling it to you maybe.

 

[Learner1]

Thanks for your input. I'm sure I have issues that ethyl pyruvate would address, my concern is merely over ethyl acetoacetate safety. Given that I haven't fully recovered from surgery and reading at length is hard, it has been hard to pick through those threads to find the studies that would suggest either way

Just curious. How are you so sure you need it if you can't find the research that supports it? And, have you done any testing that would support your belief? I'm certainly not trying to attack you, but just point out that many people around here are taking things based on a belief that it will help when there is no evidence to support that it will, and they run the risk that it might be extremely counterproductive.

Hope it helps.

 

[frozenborderline]

Just curious. How are you so sure you need it if you can't find the research that supports it?

I can find the research that supports it. Ethyl pyruvate is what I want to take , and theres ample research to support its use in conditions like mine. I cannot find much research to support ethyl acetoacetate on the other hand. This may be the source of the confusion. Ethyl acetoacetate is combined with ethyl pyruvate in this product, which is the only commercially available supplement that has ethyl pyruvate in it. So, to get ethyl pyruvate, you have to get ethyl acetoacetate basically. That's the problem I am looking for research on--ethyl acetoacetate, not ethyl pyruvate.

I'm certainly not trying to attack you, but just point out that many people around here are taking things based on a belief that it will help when there is no evidence to support that it will, and they run the risk that it might be extremely counterproductive.

That is true. I'm willing to bet all of us, in this thread, take some things that aren't based on any evidence. But the point is not 0perfection, it's to try and collectively experiment. Refine theories of etiology, and use the theory/praxis loop to smooth out any issues in ones theory. That is what I have been doing since I got here .

 

[frozenborderline]

Either way it would be easier if you could just find a way to buy from one of those companies that only sells to labs. Trick them some how into selling it to you maybe.

Still recovering from pneumonia post surgery so its not exactly the best time for doing in depth haggling with some chemical company .

Maybe this isnt that bad of an issue if I just stick to doses I've used before. Or I could make a new account and ask haidut (was banned for saying covid is real and bad)

 

[Learner1]

and theres ample research to support its use in conditions like mine.

I've found that taking something based on one's condition can lead to disaster. One's genetics and labs can indicate something very different is needed. What lab suggests you need it?

That is what I have been doing since I got here .

Experimenting based on research can definitely lead to improvement. However, I've found it's better to lab test my bunches based on the research I read, as I've had some real surprises along the way that have led to different paths altogether ...

 

[frozenborderline]

I've found that taking something based on one's condition can lead to disaster. One's genetics and labs can indicate something very different is needed. What lab suggests you need it?

There are some personalized lab tests that may matter, like I pay attention to my igg levels, infectious tests, and more... but a lot of snps and the metabolite tests that you have talked about I just dont find convincing evidence for. I'm somewhere in the middle wrt treating based on the disease in general versus based on personalized tests. Some tests dont give useful info that a trial of a relatively safe drug wouldn't. For example my doctor for ME/CFS explained david bell's blood volume research and said I probably have low blood volume so let's try saline. I asked about testing for that and she said there is a complicated radioactive tracer cell test that we could do but a trial of saline would tell us as much in context. I agree with her and the saline helped.

There are some personalized tests beyond just knowing about having ME/CFS, or mcas, etc that are important for treatment, but I dont think there are any consumer grade metabolic panels that are at all useful. Maybe if I managed to see a mito disease specialist at some top hospital but I haven't done that.

I'm personally testing for HAT, which I think would be useful to know, have tested for neuropathy, and for CVID and cci and tc , and come back positive for all of these, so I'm not against all personalized testing but I haven't seen convincing evidence that metabolic tests that are consumer grade are going to help one navigate whether or not they need metabolic supplements, especially in context of a disease where the metabolic problem could be in the cells, it could be downstream of the major issue, it might only show up under PEM, etc ...

 

[frozenborderline]

One's genetics and labs can indicate something very different is needed

Again there are a few consumer available genetic tests that might be useful, validated by NIH, like for connective tissue disorders, or the hereditary alpha tryptasemia, but I dont see how the snps in anything like 23andme are very useful at all, everything I've seen from a source that is unbiased suggests that its just a small part of the genome and we dont know much about how meaningful these parts are, and that its waste of money.

 

[Learner1]

Again there are a few consumer available genetic tests that might be useful, validated by NIH, like for connective tissue disorders, or the hereditary alpha tryptasemia, but I dont see how the snps in anything like 23andme are very useful at all, everything I've seen from a source that is unbiased suggests that its just a small part of the genome and we dont know much about how meaningful these parts are, and that its waste of money.

23and me found my hemachromatosis, celiac disease, Factor 2. Comprehensive WES and mtDNA testing also found a significant cancer gene which may explain my early cancer.

As for comprehensive metabolomic testing, there are the Metabolon, Great Plains OAT, and Genova Diagnostics NutrEval or Metabolomix+. I haven't done the first, but I've done the others and have corroborated the results with LabCorp and Quest Diagnostics tests (the 2 major US labs) as well as a couple of major hospital labs and found them to be useful. They have highlighted a number of issues that have led to effective treatment over the past few years, that there is medical research behind.

 

[frozenborderline]

I've found that taking something based on one's condition can lead to disaster.

With ME/CFS, if by disaster you mean crashing , basically anything could lead to it. Following naturopaths orders that were highly recommended by people in the community , or taking meds or herbs personalized for me by various doctors, all ended up making me crash. Anyway , some of my experiments made me crash. One of them was the best treatment I've ever done. It was something no doctor or naturopath would have ever told me to do as far as I know , besides a single person in NH who has personal experience with it (but 1 out of 1000s of ME/CFS literate docs is not good odds, and he recommends it based on his experience not based on his medical knowledge ).

Re ethyl pyruvate, I have prior experience with it , it's fairly helpful and I think benign, again, my point in posting in this thread was to get an idea about Ethyl acetoacetate, which is unfortunately bundled with EP. It's as if you wanted only b12 and didnt want emodin bc you dont know much about emodin, but the only b12 supplement on the market had emodin

 

[frozenborderline]

As for comprehensive metabolomic testing, there are the Metabolon, Great Plains OAT, and Genova Diagnostics NutrEval or Metabolomix+. I haven't done the first, but I've done the others and have corroborated the results with LabCorp and Quest Diagnostics tests (the 2 major US labs) as well as a couple of major hospital labs and found them to be useful.

So you're saying the private labs found the same things as lab Corp and quest ? My ME/CFS docs have run lots of metabolic labs thru labcorp but I I suppose they could've missed something a private lab would pick up. I'm not against all private labs but there seems to be a lack of validation and regulation of them in many cases. Like igenex are just total frauds when it comes to lyme testing. And great plains urine mycotoxin testing is totally invalidated and meaningless. This doesn't mean they couldn't be right about o6her 6things but if I was going to spend lots of money on labs I'd want to see how they show that their results mean something compared to healthy controls. Like igenex gives false positives to tons of healthy people.

 

[frozenborderline]

@sb4 what I'm still wondering about is the whole issue with ethyl acetoacetate and ethyl pyruvate turning into alcohol ??? How did u get that.

So wow, haidut is actually formally studying this supplement? In hamsters ? But he's, as usual being sloppy by studying 20 things at once. Well in this case, two supplements ar once , but each contains more than one ingredient each.

https://www.journaljpri.com/index.php/JPRI/article/view/31248

This is just bad science to the extent I didn't read the rest of the paper but maybe theres some interesting stuff in there in terms of safety data. You can learn things from bad studies too.

"Haidut" on ray peatforum, which made the supplement pyrucet, is Georgi Dinkov I believe

 

[sb4]

turning into alcohol ??? How did u get that.

Can't remember now. Just quickly googled it and this came up https://www.quora.com/When-ethyl-ac...etonic-hydrolysis-what-is-the-ketone-obtained

 

[frozenborderline]

Can't remember now. Just quickly googled it and this came up https://www.quora.com/When-ethyl-ac...etonic-hydrolysis-what-is-the-ketone-obtained

According to that it turns into ethanol and acetone whoa

 

[frozenborderline]

You got a link to that reddit thread? Any idea the doses he was taking and if it helped long term?

Yes! Found one of them at least:

https://www.reddit.com/r/Nootropics/comments/5ip31u

 

[Methyl90]

Has anyone here had any experiences with methylene blue and SKQ1?

 

[Wendi C]

Has anyone here had any experiences with methylene blue and SKQ1?

My doc ordered MB for me and I'm taking my 1st dose now. He said he's seen great improvements in others like me but now I'm hearing from a researcher I follow that it breaks DNA strands. 🤦 I guess at this point risk/reward!?

Don't know what SKQ1 is.