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

[frozenborderline]

Thanks for posting that.

I wonder if coconut / MCT oil and triheptanoin oil help replenish the Krebs cycle intermediates by virtue of the fact that they provide an energy input to the mitochondrial Krebs cycle (when converted into acetyl-CoA)?

When these oils supply energy to the mitochondrial Krebs cycle, that may mean that it takes some of the energy demands off pyruvate, which is the other energy input to the mitochondrial Krebs cycle (when converted into acetyl-CoA); if there is less demand on pyruvate to supply energy, then more of the pyruvate can be used to supply new intermediates to the Krebs cycle, rather than providing energy to the Krebs cycle.

Remember that pyruvate has a dual role in the Krebs cycle: it can either supply energy to the Krebs cycle (by being converted to acetyl-CoA), or can supply new Krebs cycle intermediates (by being converted into either oxaloacetate or alpha-ketoglutarate — see this post).



In the Myhill, Booth and McLaren-Howard studies, they found that Group A2 ME/CFS patients appear to be short in Krebs cycle substrates — see this post.

I have also been wondering about triheptanoin. One of the things it's given for is pyruvate decarboxylate deficiency. However, the deficiency in ME/CFS is a pyruvate dehydrogenase deficiency. I actually mixed these two up and got overly excited thinking that triheptanoin would be a cure. However, if it's safe, i'll probably try it anyway, as I plan on trying anything that can affect the kreb's cycle and is shown to be reasonably safe. e.g. no injecting atp lol ...

 

[frozenborderline]

I have also been wondering about triheptanoin. One of the things it's given for is pyruvate decarboxylate deficiency. However, the deficiency in ME/CFS is a pyruvate dehydrogenase deficiency. I actually mixed these two up and got overly excited thinking that triheptanoin would be a cure. However, if it's safe, i'll probably try it anyway, as I plan on trying anything that can affect the kreb's cycle and is shown to be reasonably safe. e.g. no injecting atp lol ...

oh wait... but pyruvate decarboyxlase could be relevant, since it is involved in converting pyruvate to oxoloacetic acid. better put my thinking cap on.

 

[frozenborderline]

as for the safety: http://www.g1dfoundation.org/wp-content/uploads/2013/09/Triheptanoin-FAQ-final.pdf

 

[Hip]

I have also been wondering about triheptanoin.

I looked at triheptanoin, but unfortunately it's difficult to get hold of: see this post.

 

[frozenborderline]

I looked at triheptanoin, but unfortunately it's difficult to get hold of: see this post.

has anyone tried these guys? first hit on google: https://us.lgcstandards.com/US/en/Triheptanoin/p/LA 33-0700-9

 

[frozenborderline]

the person who recommended this to me worked for the glut 1 foundation at some point. may be able to get me some triheptanoin. I would want to use food grade i guess, it is used in cosmetics

 

[scisolver]

I've been wondering about this ATP profile test from the UK lab as well. I wonder what Ron Davis at Stanford thinks of this. He said he developed a cheap microchip test for ME/CFS that measure mitochonrdial function, but it isn't released. Shouldn't Ron Davis know about this ATP test since he is working on a test and biomarkers?

He also said that whatever it is that is causing the problem is a high molecular weight and is in the serum. They were able to filter it out. Also, if you put the ME/CFS serum on control patient cells then their mitochondria fail, and if you put control serum on ME/CFS cells then the ME/CFS cells work perfectly fine.

 

[Deepwater]

I've been wondering about this ATP profile test from the UK lab as well. I wonder what Ron Davis at Stanford thinks of this. He said he developed a cheap microchip test for ME/CFS that measure mitochonrdial function, but it isn't released. Shouldn't Ron Davis know about this ATP test since he is working on a test and biomarkers?

He also said that whatever it is that is causing the problem is a high molecular weight and is in the serum. They were able to filter it out. Also, if you put the ME/CFS serum on control patient cells then their mitochondria fail, and if you put control serum on ME/CFS cells then the ME/CFS cells work perfectly fine.

I believe the McLaren test which Dr. Myhill uses involves testing in serum, and also fresh (never been frozen), and both of those things are reckoned to be critical to getting a good result, but don't quote me.
However, I feel duty bound to warn that if the test is being ordered to convince hostile UK doctors, then the fact that the central test, for mitochondrial function, hasn't yet been verified by anyone else could be a problem; some work on comparing the result to those of conventional muscle tests is ongoing but we don't know the results.

There are other uncontroversial tests in the panel, for deficiencies in things like CoQ10, L carnetine and cell free DNA, which should indicate serious problems to the doctor if abnormal, which they usually are in pwME, but doctors working in the NHS can be remarkably dumb. The cell free DNA is often several times the normal level so a clear indication that the body is under attack.

The Department of Work and Pensions (DWP) and the companies such as ATOS whom they employ to weed out scroungers do accept these test results, and now there is work ongoing to verify the central ATP test doctors might be reluctant to section or force GET on someone who has abnormal results from these tests. But I should warn that, despite having them accepted by the DWP, I had my results roundly rejected by the consultant at one of England's CFS clinics, although this was at the time when Dr. Myhill was suspended, a fact of which this doctor was gloatingly aware. He simply slammed them to the corner of his desk with an explanation of 'not recognised here'.

Professor Newton's research was funded by UK taxpayer and found mitochondrial defects using more conventional muscle biopsies, so she might be an alternative, but she doesn't offer a testing service and is based in the far NE so unless the biopsies could be taken locally and sent up to her that would be a very difficult option with such a sick child.

 

[frozenborderline]

I can't understand the mechanism of how pyruvate supplementation might help in ischemia, because you need oxygen in order to burn pyruvate in the Krebs cycle in the mitochondria. And in ME/CFS, if there are mitochondrial defects, additional pyruvate may not be of much help, since pyruvate is burnt in the mitochondria.

Although in the paper you linked to, I think they are looking more at reperfusion after ischemia. They say that pyruvate dehydrogenase (the mitochondrial enzyme that processes pyruvate) becomes dysfunctional during ischemia-reperfusion, and they speculate that ethyl pyruvate might help fix this. But they also speculate on several other mechanisms of how ethyl pyruvate might maintain ATP levels; so they don't really know for sure how it works.

https://www.ncbi.nlm.nih.gov/pmc/?term=ethyl+pyruvate

Ethyl pyruvate seems to have a very broad range of protective effects, interesting stuff

 

[pattismith]

I have AMP deaminase deficiency (genetic). My endurance sucked all my life, and my recovery time from exercise was always longer, even as a child, but I never had PEM or any other ME symptoms. I guess if things had gone differently this common genetic disorder would have been completely unimportant, but in light of my illness I wonder if exploring AMP metabolism might be worthwhile. Sorry to dump on your thread Hip but I was wondering if you think there is a "best" metabolic test out there at the moment that would cover many of the bases surrounding AMP metabolism.

AMP deaminase deficiency is a new one for me, but according to Wikipedia, AMP deaminase is an enzyme that converts AMP to inosine monophosphate (IMP). Since conversion of AMP to IMP forms part of the pathway by which AMP is flushed from the body, leading to PEM according to the theory (see this post), my first thought is that if you had the usual virally-triggered ME, you might actually be less prone to getting PEM.

Looking at the Wikipedia article, AMP deaminase deficiency seems quite complicated and not very well understood, so it is hard to suggest anything. The article does say that one of the issues is loss of ribose and fumarate, so you might want to try taking D-ribose and fumarate, if you are not already. Also it says that low levels of nitric oxide may be an issue, so some NO boosting supplements like arginine and dietary nitrates (eg beetroot juice) might help.

The last study by Levine/Hanson found low IMP in patient, so it would be relevant that some ME/CFS patients have an impaired AMP deaminase activity.


It would fit with my case, as I have found that the potential activation of the salvage pathway (hypoxanthine to IMP) is solving my symptoms completely for some hours.


I explained it here:

https://forums.phoenixrising.me/ind...ease-symptomatology.62445/page-2#post-1019944


;;;;

 

[frozenborderline]

I can't understand the mechanism of how pyruvate supplementation might help in ischemia, because you need oxygen in order to burn pyruvate in the Krebs cycle in the mitochondria. And in ME/CFS, if there are mitochondrial defects, additional pyruvate may not be of much help, since pyruvate is burnt in the mitochondria.

Although in the paper you linked to, I think they are looking more at reperfusion after ischemia. They say that pyruvate dehydrogenase (the mitochondrial enzyme that processes pyruvate) becomes dysfunctional during ischemia-reperfusion, and they speculate that ethyl pyruvate might help fix this. But they also speculate on several other mechanisms of how ethyl pyruvate might maintain ATP levels; so they don't really know for sure how it works.

theres some discussion of ethyl pyruvate and pdh In this thread
https://raypeatforum.com/community/threads/pyrucet-liquid-ethyl-pyruvate-aceatoacetate-mix.27487/

 

[frozenborderline]

Looks interesting, but ethyl pyruvate does not seem to be available as a supplement. I have in the past tried calcium pyruvate, but did not notice much benefit.

Pyruvate is created by glycolysis, and when the mitochondria are working properly, this pyruvate is transported into the mitochondria, where more energy is extracted from it, by burning the pyruvate with oxygen. But if the mitochondria cannot accept pyruvate, then the pyruvate from glycolysis gets converted to lactic acid, which leads to a lactic acid build up.

There have been some suggestions recently by Fluge and Mella that there may be a defect in ME/CFS patients' mitochondrial pyruvate uptake (because of problems with the pyruvate dehydrogenase enzyme).

Looks interesting, but ethyl pyruvate does not seem to be available as a supplement. I have in the past tried calcium pyruvate, but did not notice much benefit.

Pyruvate is created by glycolysis, and when the mitochondria are working properly, this pyruvate is transported into the mitochondria, where more energy is extracted from it, by burning the pyruvate with oxygen. But if the mitochondria cannot accept pyruvate, then the pyruvate from glycolysis gets converted to lactic acid, which leads to a lactic acid build up.

There have been some suggestions recently by Fluge and Mella that there may be a defect in ME/CFS patients' mitochondrial pyruvate uptake (because of problems with the pyruvate dehydrogenase enzyme).

Ethyl pyruvate now available as a supplement here http://www.idealabsdc.com/ , although it’s mixed w acetoacetate (and called pyrucet)

 

[kangaSue]

Ethyl pyruvate now available as a supplement here http://www.idealabsdc.com/ , although it’s mixed w acetoacetate (and called pyrucet)

Good find, I'll have to check this out.

 

[frozenborderline]

Good find, I'll have to check this out.

The site is a little weird to navigate. When you click on the products it links you to a forum where it explains a lot about them and what they are. But to buy them it’s a separate click. Haven’t tried the pyrucet yet but I’ve had some products from them that are pretty good

 

[kangaSue]

Haven’t tried the pyrucet yet but I’ve had some products from them that are pretty good

Thanks, that's good to know.

The site is a little weird to navigate. When you click on the products it links you to a forum where it explains a lot about them and what they are. But to buy them it’s a separate click.

You're not wrong there and I've been umming and ahhing over trying their products for that reason. I did manage to find my way to the shop in the end though but still debating with myself whether or not to give this a shot.

Let me know here if you try this one, and I'll do likewise.

 

[tiredowl]

*
I have ordered from them recently (The pyruvate product). It is a bit messy to navigate the site, but overall the process was simple. They used to accept PayPal but I couldn't find that option anymore.
I am not sure if I can just apply it to the skin, or do I have to consume it. I applied the MitoLipin to my skin before.

Going to try it soon when it arrives. However now I seem to be having some success with C60. It is a bit early to tell, (Don't wanna get my hopes up too much) but it gives me some energy and I am sleeping better!

Sorry edited, quite a few typos haha.

 

[frozenborderline]

*
I have ordered from them recently (The pyruvate product). It is a bit messy to navigate the site, but overall the process was simple. They used to accept PayPal but I couldn't find that option anymore.
I am not sure if I can just apply it to the skin, or do I have to consume it. I applied the MitoLipin to my skin before.

Going to try it soon when it arrives. However now I seem to be having some success with C60. It is a bit early to tell, (Don't wanna get my hopes up too much) but it gives me some energy and I am sleeping better!

Sorry edited, quite a few typos haha.

What c60 source are u using. The theory sounds solid but I’ve heard differing things about products available. Another weird antioxidant that I’d like to try is hydrogen but seems tricky and scammy in practice

 

[kangaSue]

I am not sure if I can just apply it to the skin, or do I have to consume it.

The gist I got from that forum is that they are only promoting things as cosmetic ingredients due to regulatory laws and can only reccomend applying it to the skin but they say it's food grade too, the inference being that it is so safe to ingest as well.

 

[tiredowl]

What c60 source are u using. The theory sounds solid but I’ve heard differing things about products available. Another weird antioxidant that I’d like to try is hydrogen but seems tricky and scammy in practice

I am using the GoodandCheap brand as it was reccommended to me here and it had mostly good reviews on Amazon.
And I am still not sure what C60 does exactly, maybe it just works as a really good antioxidant? but there are plenty of testimonials of people having improvement in their health from it, such as more vivid dreams and energy. Even hair-regrowth. I was skeptical as well.

Regarding hydrogen, I saw someone reccommend eating an apple before taking C60 to increase it's effect. Haven't tried that. But how does it work exactly?

Here is the link to their site:
https://www.goodandcheapc60oo.com/

 

[tiredowl]

Yes, that makes sense as to why they have to label the products 'Not for ingestion'.

I feel like I am almost using myself as guinea pig!