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

[Hip]

So if I'm reading that correctly, it's useless.

At this point I am not sure, but it does place a question mark over the Acumen Lab test.

 

[nandixon]

At this point I am not sure, but it does place a question mark over the Acumen Lab test.

Yes, I would really like to see blinded samples of patients and healthy controls sent to the Acumen people to see if they can correctly discriminate between the two just to make sure there's not some hidden little detail that Acumen does that Karl Morten's group isn't aware of that actually makes the Acumen test work right and be valid. The Acumen people should be making that offer if they stand behind their test.

 

[boolybooly]

Dr Myhill has previously responded.

FYI

https://drmyhill.co.uk/wiki/Response_to_the_paper_'Assessing_cellular_energy_dysfunction_in_CFS/ME_using_a_commercially_available_laboratory_test'_by_Cara_Tomas_et_al

Why does the Tomas Paper fail to replicate our findings?
Dr Norman Booth suggested that before the Tomas group proceeded with their test, they should do paired samples to compare with the Acumen test. The idea was that Dr Myhill would take blood from one patient and send samples to both laboratories to be tested on the next day. Dr Myhill offered to fund the cost of such a comparison. This offer was never taken up. What this means is that we can have little confidence in the ability of the Tomas group to replicate the Acumen test.

 

[nandixon]

"The idea was that Dr Myhill would take blood from one patient and send samples to both laboratories to be tested on the next day. Dr Myhill offered to fund the cost of such a comparison."

A single patient analyzed by the two groups is not good enough. Blinded amples need to come from multiple patients and multiple healthy controls and Myhill needs to show that the Acumen test can differentiate between the patients and healthy controls without knowing which is which.

 

[grapes]

Just for everyone's reference, the mitochondria dysfunction ME/CFS patient subtypes that Myhill et al discovered are these:

ME/CFS Patient Mitochondria Dysfunction Subtype Groups:

Group A Patients — oxidative phosphorylation running normally. Group A then divides into two subgroups:

• Group A1 Patients ('no HIs') — These are Group A patients who have normal or sub-normal TL IN values (and 87% of these patients also have sub-normal TL OUT values).
• Group A2 Patients ('HI TL IN') — Group A patients who have super-normal TL IN value.

Group B Patients ('HI Blk') — oxidative phosphorylation partially blocked and running at low efficiency.

• All of the Group B patients were found have sub-normal TL IN values (ie, they have reduced translocator protein transfer of ATP from mitochondria to the cytosol of the cell). And 78% of the Group B patients have sub-normal values of TL OUT (decreased translocator protein ferrying of ADP from the cell to the mitochondria).

Group A patients try to compensate for the mitochondrial ATP shortage by increasing glycolysis to make ATP.

Group B patients try to compensate for the shortfall in mitochondrial ATP most likely by using the adenylate kinase reaction to make ATP.

Does TL refer to the translocator protein transfer of ATP from mitochondria to the cytosol of the cell?

 

[Hip]

Does TL refer to the translocator protein transfer of ATP from mitochondria to the cytosol of the cell?

The translocator protein (TL) has two functions and is a two-way street: it carries fresh ATP from the mitochondria into the rest of the cell (this Myhill calls TL IN), and also carries the spent ATP (it becomes ADP once spent) back out from the cell into the mitochondria for recycling (TL OUT).

Note that Myhill et al use the term "translocator protein" to refer to the adenine nucleotide translocator (ANT).

 

[grapes]

The Lactic Acid Build-Up Problem in PEM

PEM is compounded and exacerbated by the problem of lactic acid build-up in the muscles, in ME/CFS patients who rely on anaerobic glycolysis to make up for the shortfall of energy (a shortfall originally resulting from dysfunctional mitochondria). This because anaerobic glycolysis produces lactic acid as a by-product.

This lactic acid build-up then further compounds the energy shortage problem of PEM, because to clear lactic acid by converting it back to glucose, it requires considerably more energy than was originally gained from the conversion of glucose to lactic acid.

Hip, in my process of reading everything, I haven't yet found this. Do problems in ANY of the five energy processes excess high lactic acid? Because the lactic acid issues seems to be mentioned more in (3) Oxidative Phosphorylation.

 

[Hip]

Hip, in my process of reading everything, I haven't yet found this. Do problems in ANY of the five energy processes excess high lactic acid? Because the lactic acid issues seems to be mentioned more in (3) Oxidative Phosphorylation.

According to the Myhill theory, lactic acid build up is a problem in Group A patients. It's not such an issue in the Group B patients (Group B have more severe ME/CFS than Group A).

 

[godlovesatrier]

It would be brilliant if someone could be funded to do a genetic mapping (WGS) and ATP test as these studies did, replicate the ATP tests and then perform the genetic mapping to single out high incidence of gene mutations correlated as a trend in the same way the ATP mitochondrial performance correlates depending on severity of symptoms. That would at least rule out genetic issues, including genes we may not even have fully understood yet.

 

[frozenborderline]

It appears I have gotten increased hunger from Pyrucet though too early to tell yet. I do intend to try significantly increased doses soon.

I'd like to resolve this , I want to know what the safe dose for Pyrucet is. It seems like ethyl pyruvate on its own might be more effective and safe than with ethyl acetoacetate but haidut is very willful.

There are just so many studies where ethyl pyruvate is very helpful for sepsis or inflammation and energy and I found a very intriguing anecdote on reddit by someone who had CFS and used to find old brand of energy shots containing ethyl pyruvate which really helped him.
Also when I was focused on pyruvate and the Krebs cycle but also the precursors and glycolysis and oxidation of Pyruvate or reduction of pyruvate to lactate... All of which seemed important to me/cfs

Now even though my focus has shifted to things upstream of metabolism , I need to remember how metabolism and inflammation and shutdown of metabolism in protective ways can influence even the upstream factors

Anyway back to Pyrucet. We probably can't find a cheap ready made source of solely ethyl pyruvate which complicated the safe dose. While haidut is often an ideologically driven guy with a blind spot caused by his arrogance and single mindedness , I'm not sure how unsafe this other ingredient, ethyl acetoacetate, is. It may be ineffective andnit tastes bad but its Hopefully not vary toxic ... Bc they're mixed together in the product Pyrucet and higher doses of ethyl pyruvate than the dose on the label are probably warranted based on my research.


Ahh... Hey all, I had found stuff on dosing beforehand but can't now. This is a nightmare. But it seems helpful in sepsis which is related to me/cfs. If u can tease out proper doses from any of the full texts... Most are rats, if u can extrapolate to humans or find one of the few human studies theyve done ... Would be amazing , https://scholar.google.com/scholar?hl=en&as_sdt=0,31&q=ethyl+pyruvate+sepsis&btnG=


And them there's this, one of these studies should tell us the true safety level of EA https://pubmed.ncbi.nlm.nih.gov/?term=Ethyl+acetoacetate

@sb4 @Hip what are your thoughts

https://raypeatforum.com/community/threads/pyrucet-liquid-ethyl-pyruvate-aceatoacetate-mix.27487/

This is the ray peat forum thread on this, though I am banned from the ray peat forum ...

 

[sb4]

@frozenborderline If I remember correctly, the Pyrucet acted quite like thiamine in the sense that I had a noticable positive reaction (in this case increased hunger) that vanished after a few days. Think I took high doses.
I remember looking up the LD50s of ethyl pyruvate and acetate and trying to find the max dose I could reasonably take without running into too much issues but can't remember if I put it into action.

I managed to get hold of some ethyl acetate but ethyl pyruvate I couldn't get any, other than Pyrucet.

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

Why did you get banned from RayPeatForum?

 

[frozenborderline]

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

I just had surgery. Been offline for awhile. Reminding myself to try and find that.

I want to know if theres any negative interactions btwn my meds and surgical healing and pyrucet. It's such a niche product of supplement that I doubt theres much info I may be flying blind. But I need something for metabolism and inflammation that will help my overtaxed wounded muscles heal.

 

[sb4]

I just had surgery.

Neck related surgery?

 

[frozenborderline]

Neck related surgery?

Yes

 

[frozenborderline]

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

No, I cant find it even searching Google which would have deleted threads, should've archived it. He was unaffiliated w ray peat forum so less biased. Said there used to be gas station energy shot w that that was helpful for cfs.

 

[frozenborderline]

Heres posts I and another user made about the reddit post awhile ago but no link.

Ethyl pyruvate has been on my radar since last year. Someone on reddit (presumably healthy) posted that they took a supplement which had Ethyl pyruvate as the main ingredient and got amazing cognitive improvements from it. Sadly that supplement is no longer available, and the only other sources I can find are research suppliers.

I'd also like to try a non-calcium based source of regular pyruvate (doesn't have to be ethyl), just because whilst I do well with pyruvate, I don't do well with calcium, and all the pyruvate supplements seem to be calcium pyruvate. Pyruvate is one of the few mito boosters that actually does what it says on the tin.

I saw the reddit post haha! they said that there used to be an energy drink with ethyl pyruvate in it. I'm gonna wait and maybe try it with doctor supervision though. Some of these supplements are more mild and have a lot more anecdotal evidence of safety, but I learned my lesson with taking a high dose of pregnenolone.

 

[sb4]

Did you say you tried Haiduts Pyrucet? If not why not try a small dose and titrate up?

 

[frozenborderline]

Did you say you tried Haiduts Pyrucet? If not why not try a small dose and titrate up?

I do but that doesn't replace having safety data on ethyl acetoacetate. Unfortunately that limits me. Ethyl pyruvate seems safe at high doses in studies, could potentially do 5 g or more , but its combined w this unknown. I wish someone would sell EP on its own

 

[frozenborderline]

As Hamilton Morris has pointed out, there are potent neurotoxins that dont "feel" like they're doing anything bad to you, you cant always rely on intuition with these things

 

[frozenborderline]

@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.