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

[frozenborderline]

Maybe.. it is really confusing. But I'm guessing most of the people who have tried this on the Raypeat forum don't have ME. And If this metabolic switch theory is correct, tampering with it sounds kind of scary. Ron Davis did urge caution about experimenting with this pathway.

Hope it works, I'll post my experiences if I try it. I guess applying it topically should work as well

I mean, I’m pretty sure Ethyl pyruvate is just a form of pyruvate that is normally bioavailable, and according to Ron davis, he also added pyruvate in the nanochip test with the result of helping the cells have better electrical impedance. @Hip might know this but I’m pretty sure Ethyl pyruvate is just a way of getting pyruvate into the cell.

I haven’t seen any studies showing adverse effects from this. It seems to be fairly antiinflammatory and help with organ damage in a very broad selection of diseases. Phairs theory seems to contradict a lot of the literature on IDO2 , but at the same time ido1 inhibitors do cause fatigue and side effects like he says.

 

[Hip]

@Hip might know this but I’m pretty sure Ethyl pyruvate is just a way of getting pyruvate into the cell.

I imagine that's the case. Although ethyl pyruvate probably does have properties unique to itself. In any case, ethyl pyruvate is considered safe enough to be used as a flavoring food additive. There's also methyl pyruvate.

You guys might want to create a new thread on your ethyl pyruvate experiments, to make other members aware of it. It will just get lost and largely unnoticed within this thread.

 

[frozenborderline]

You might want to check your insurance requirements for IVIG...if you qualify under any of the categories (as I remember, you well might) any doctor can order it. (Of course, you'd want it ordered with proper support meds, which might include steroids, NSAIDS, and benadryl, to reduce side effects.) You could start on an immunodeficient dose, then as you get to the doctor who understands autoimmunity, he/she could up your dose.

My pcp didn’t feel comfortable doing ivig without Susan Levine’s recommendation. I may try going to an integrative medicine place in Massachusetts that seems enthusiastic about SCIG.

 

[frozenborderline]

You guys might want to create a new thread on your ethyl pyruvate experiments, to make other members aware of it. It will just get lost and largely unnoticed within this thread.

I will do this soon. I’m sort of getting over an acute flu like illness on top of my normal level of debility so brain not work so good.

Found this : https://www.ingentaconnect.com/content/ben/cdt/2007/00000008/00000004/art00005

Ethyl pyruvate as novel treatment for sepsis.

The reason this excites me is that I’m sort of a fan of David Bells “slow sepsis” theory of ME. The orthostatic intolerance, lactic acidosis , widespread inflammation—-all perhaps after infection, seem to be like sepsis in many ways. And some of the same treatments seem to help—thiamine megadose, saline, etc. at least on some level. There seems to be a lot of promising literature on ethyl pyruvate but I’m going to keep experimenting before saying more about results

 

[ljimbo423]

The reason this excites me is that I’m sort of a fan of David Bells “slow sepsis” theory of ME.

Chris Armstrong has the same basic theory of ME/CFS. The sepsis-like condition in ME/CFS is causing the mitochondria to go into glycolysis and burn amino acids and fats for fuel, instead of glucose.

Armstrong speculated that an infection or autoimmune process may have triggered a sepsis-like condition which then lead to a state of chronic starvation. During sepsis immune cells rely entirely upon glycolysis to proliferate wildly.

They are so energy hungry during this process that they can deplete the system of essential cofactors perhaps leading to a state of chronic cellular starvation.
In starvation amino acids and fats are preferentially used to feed the TCA or Krebs cycle instead of glucose.

Likewise, in anorexia the mitochondria switch to amino acids and lipids to fuel ATP production. The Aussie team believes the inability to use glucose properly may be contributing to a kind of low-level chronic starvation of mitochondria.

https://www.healthrising.org/blog/2...hronic-fatigue-syndrome-starvation-australia/

 

[frozenborderline]

https://link.springer.com/article/10.1007/s00134-003-1966-x this study suggests a dosage range that may be quite higher than what I was using , but I don’t know how to extrapolate from rats, and additionally if ethyl acetoacetate would be likely to cause any toxicity, @sb4 did you look into that at all?

 

[kangaSue]

this study suggests a dosage range that may be quite higher than what I was using , but I don’t know how to extrapolate from rats

See table 1 in this paper;
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804402/

 

[sb4]

If I remember right from the ray peat thread, I found LD50 for rats and converted it to HID of 40g ethyl-acetoacetate, which to me seemed pretty low.

Considering that it gets hydrolysed into ethanol and acetoacetate, that would be something like 10g ethanol and 30g acetoacetate. Now people drink way way more ethanol than 10g so that can't be it.

As for acetoacetate, it can transform to beta hydroxybutyrate, and if you look at the dosages of BHB esters being sold in supplements, it's around 25g per serving. I doubt they would be going so close to a lethal dose if that where the case. If you look at the promotional websites they claim that this amount of BHB gets you to 3-5mmol/L BHB. Ketoacidosis is 7+. So there is a possibility that in some rats they could be scraping into ketoacidosis from that range but even that shouldn't kill them.

I would have to assume it's the ethyl-acetoacetate before getting hydrolysed that is the problem. I think it is lipothilic and it obviously has other actions based on Hiadut's thread. Perhaps it knocks GSH down to zero and keeps it down there causing massive problems?

I know Haidut said that the dosages he is using shouldn't cause GSH to drop to zero but I think in one or two of the studies he linked it said it would. Either way I have been consuming 60 drops, 1.5g ethyl-AA, 1.5g ethyl-Pyruvate, and so far I am not feeling any worse, perhaps better (more hungry). I intend to try ethyl-AA soon and slowly build the dose up.

 

[ebethc]

Chris Armstrong has the same basic theory of ME/CFS. The sepsis-like condition in ME/CFS is causing the mitochondria to go into glycolysis and burn amino acids and fats for fuel, instead of glucose.

https://www.healthrising.org/blog/2...hronic-fatigue-syndrome-starvation-australia/

I've tried BCAA's and they made me sleepy - which is weird. I'm going to go back to amino acids and this time try a broad range of aminos, like this one:
https://www.amazon.com/gp/product/B00RKDHXQY/ref=ox_sc_act_title_4?smid=A2EJCTH67GJMT3&psc=1

It claims to have a "natural ratio" which might be helpful...

Do CFS'ers need large doses of aminos?

 

[Learner1]

Fluge and Mella's study show that ME/CFS patients burn aminos for fuel, especially women.

The product you are looking at I wouldn't buy because:

• It's not pure aminos and has ingredients that you may or may not need, in the wrong doses
• The doses are ridiculously low
• It contains arginine which can promote EBV etc.
• It contains tryptophan

Might be useful to figure out why BCAAs make you sleepy, they should help mitos.

Best to figure out what your needs are and dose based on that. I take 1-6g of most aminos and typically need larger doses of BCAAs, tyrosine, glycine, ornithine aspartate, citrulline, asparagine, and methionine, in that order, than most people.

 

[ebethc]

Fluge and Mella's study show that ME/CFS patients burn aminos for fuel, especially women.

The product you are looking at I wouldn't buy because:

• It's not pure aminos and has ingredients that you may or may not need, in the wrong doses
• The doses are ridiculously low
• It contains arginine which can promote EBV etc.
• It contains tryptophan

thanks!

Might be useful to figure out why BCAAs make you sleepy, they should help mitos.

Right, but how?

Best to figure out what your needs are and dose based on that.

Right, but how?

I take 1-6g of most aminos and typically need larger doses of BCAAs, tyrosine, glycine, ornithine aspartate, citrulline, asparagine, and methionine, in that order, than most people.

thanks for the guidelines

 

[ljimbo423]

I've tried BCAA's and they made me sleepy - which is weird. I'm going to go back to amino acids and this time try a broad range of aminos, like this one:

That is odd that BCAA's make you sleepy but I've heard of other people having side effects too. So maybe not so odd. It does seem like we would benefit with a good amino acid supplement of some kind. Some people just use protein powder and have good results.

Do CFS'ers need large doses of aminos?

As learner1 said, Fluge and Mella found that people with CFS use more aminos than usual. Because we are using it for fuel in the krebs cycle instead of glucose.

This is a diagram from the Fluge and Mella study. The aminos in the pink box are the ones they found to be used the most. They are Isoleucine, Leucine, Lysine, Phenylalanine, Tryptophan and Tyrosine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/

 

[ebethc]

It does seem like we would benefit with a good amino acid supplement of some kind. Some people just use protein powder and have good results.

agreed.
re protein powder, I tried that last year or the year before w no luck... This year, I've been on a higher protein diet, and that seems to be too hard for my digestion, so I figured I'd adjust to moderate protein + aminos...

As learner1 said, Fluge and Mella found that people with CFS use more aminos than usual. Because we are using it for fuel in the krebs cycle instead of glucose.

This is a diagram from the Fluge and Mella study. The aminos in the pink box are the ones they found to be used the most. They are Isoleucine, Leucine, Lysine, Phenylalanine, Tryptophan and Tyrosine.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5161229/

Interesting, and helpful to know which ones to keep an eye on w CFS b/c there are so many in general

Isoleucine and leucine are BCAAs, so that's interesting.

@Learner1 what's your beef w tryptophan?

I just dug out some citrulline malate (2:1, "Bulk Supplements" brand) from my closet and took 3 grams.... I do feel better, more relaxed (my joints are cracking, which is a good sign that energy is moving), but I don't know how much of the result is due to malate, though, which I know my body loves... stay tuned..

thanks

 

[Learner1]

Tryptophan seems to be high in cells in Phair's IDO2 metabolomic trap theory. I have a couple of the IDO2 SNPs and was put on 5-HTP for over a year for sleep. Not sure if it promoted my ME/CFS, which came on gradually, but I'm not going to supplement it..

Citrulline works in the urea cycle, helps to get rid of ammonia.

LabCorp has an amino acid panel that can help you determine your needs.

 

[ebethc]

wow...$250
https://www.healthlabs.com/amino-acid-profile-blood-testing

 

[Learner1]

Well, if you do a Genova NutrEval, you get a lot more info, and their Prepay is $179.

 

[ebethc]

Well, if you do a Genova NutrEval, you get a lot more info, and their Prepay is $179.

that's better, although still out of my range... plus, the first test is a baseline that you try to improve, and to know that you're improving/failing/maintaining, you need to re-test and then change your plan accordingly... So, you really have to do a minimum of 3 tests to make sure you're succeeding... all in all, more like $540... ugh.. I don't have $540, but if I did, I'd buy lottery tickets because that would be a better investment .. ha

 

[frozenborderline]

If I remember right from the ray peat thread, I found LD50 for rats and converted it to HID of 40g ethyl-acetoacetate, which to me seemed pretty low.

Considering that it gets hydrolysed into ethanol and acetoacetate, that would be something like 10g ethanol and 30g acetoacetate. Now people drink way way more ethanol than 10g so that can't be it.

As for acetoacetate, it can transform to beta hydroxybutyrate, and if you look at the dosages of BHB esters being sold in supplements, it's around 25g per serving. I doubt they would be going so close to a lethal dose if that where the case. If you look at the promotional websites they claim that this amount of BHB gets you to 3-5mmol/L BHB. Ketoacidosis is 7+. So there is a possibility that in some rats they could be scraping into ketoacidosis from that range but even that shouldn't kill them.

I would have to assume it's the ethyl-acetoacetate before getting hydrolysed that is the problem. I think it is lipothilic and it obviously has other actions based on Hiadut's thread. Perhaps it knocks GSH down to zero and keeps it down there causing massive problems?

I know Haidut said that the dosages he is using shouldn't cause GSH to drop to zero but I think in one or two of the studies he linked it said it would. Either way I have been consuming 60 drops, 1.5g ethyl-AA, 1.5g ethyl-Pyruvate, and so far I am not feeling any worse, perhaps better (more hungry). I intend to try ethyl-AA soon and slowly build the dose up.

I have gotten transient but noticeable good effects from this product however I think pdh dysfunction is downstream of some other issues in my case so it hasn’t been miraculous. However I am continuing to take it as I think It’s most likely harmless in these doses and since I can’t get myself out of possible biotoxin exposure atm this treatment should help And be protective. I haven’t worked out the max safe doses of EA or EP yet but I think they are many times higher than me and @sb4 have been dosing most likely. I am pretty soon just going to stop buying supplements though and try getting out of my moldy house and then reevaluate all of these supplements. I have a suspicion that many of the things I’ve tried will work 10x better when I figure out the root problem and treat that. I think ethyl pyruvate could probably be beneficial for anyone here who is somewhat recovered from this illness but still not 100%

 

[frozenborderline]

Tryptophan seems to be high in cells in Phair's IDO2 metabolomic trap theory. I have a couple of the IDO2 SNPs and was put on 5-HTP for over a year for sleep. Not sure if it promoted my ME/CFS, which came on gradually, but I'm not going to supplement it..

Citrulline works in the urea cycle, helps to get rid of ammonia.

LabCorp has an amino acid panel that can help you determine your needs.

It’s also worth noting that a lot of muscle meat eating gives one tryptophan and that eating gelatin as traditional cultures did would give more bcaas and proline ans glycine I believe

 

[frozenborderline]

Tryptophan is far from benign even if you don’t have this particular illness. Dose makes the poison applies to everything but I think tryptophan is more harmful than many of the other amino acids, at a lower dose.