The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
Discuss the article on the Forums.

Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy/CFS

Discussion in 'Latest ME/CFS Research' started by deleder2k, Dec 22, 2016.

  1. M Paine

    M Paine Senior Member

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    The psuedo-science is strong in this one.
     
  2. ash0787

    ash0787 Senior Member

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    I heard something recently that seems to be relevant to CFS, I think it was an assessment of military performance, the metabolism of women is different in such a way that they turn extra energy into fat whereas men keep more in the form of temporary energy reserves.

    Not knowing much about these tests I wonder as to how accurate they are, I am afraid that we might see a contradictory result from a different source later on ... I have heard of upregulation before so I presume it is a standard procedure. Aside from that little doubt though it does actually feel like we are getting somewhere with this one.

    So maybe if they can find the chain of command they can find that a single chemical in the blood is ultimately controlling this particular effect and inject something to counteract it and see what happens ?
     
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  3. AndyPR

    AndyPR I'm a DAD, I Donate, Advocate and Demonstrate

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    :rofl::rofl::rofl:
     
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  4. Riley

    Riley Senior Member

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    Edit:I'm trying to quote what AndyPR quoted but can't figure it out on mobile :p.
    "Poe's law is an Internet adage that states that, without a clear indicator of the author's intent, it is impossible to create a parody of extreme views so obviously exaggerated that it cannot be mistaken by some readers or viewers as a sincere expression of the parodied views."

    I've never seen true trolling on these forums which leads me to believe that this person is sincere.
     
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  5. Snow Leopard

    Snow Leopard Hibernating

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    Wait, did someone mention PPAR-delta and PDK4?

    *dusts off my old hypothesis involving CD36 and fatty acid metabolism dysregulation*

    "The pivotal role of pyruvate dehydrogenase kinases in metabolic flexibility."
    https://www.ncbi.nlm.nih.gov/pubmed/24520982

    "CD36-dependent regulation of muscle FoxO1 and PDK4 in the PPAR delta/beta-mediated adaptation to metabolic stress."
    https://www.ncbi.nlm.nih.gov/pubmed/18308721/

    By the way, the above study is by @znahle and I first read it before Zaher was hired by the Solve ME/CFS Initiative...

    I would be very interested to hear what Zaher has to say about this study.
     
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  6. eljefe19

    eljefe19

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    ELI5 please
     
  7. Snow Leopard

    Snow Leopard Hibernating

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  8. alex3619

    alex3619 Senior Member

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    This might explain why SSRIs are so badly tolerated in ME. SSRIs raise Sirtuin 4, which suppresses PDH. See for example:

    http://www.cell.com/cell/abstract/S0092-8674(06)01020-8?_returnURL=http://linkinghub.elsevier.com/retrieve/pii/S0092867406010208?showall=true&cc=y=

    This research needs to be pursued and some of the implications ruled out because it suggests SSRIs might lead to early death. Its only suggestive however. It might already have been investigated too, this is not my area of expertise.
     
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  9. alex3619

    alex3619 Senior Member

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    Good questions. I think the argument they are providing is that this is the cause of the low energy, though perhaps not other issues. Indeed they hypothesize an immune mediated process, and this will have other impacts. In other words, we may have to fix the immune problems to fix this. However if we can restore PDH function we would still probably be sick but we would also have restored energy ... which in my view is a huge plus.

    Now there is a lot of anecdotal evidence that ME patients do better on higher protein diets. A PDH problem would explain that.

    What we do not know are the feedback loops. Its possible that doing things to try to restore PDH, outside of an experimental setting, might make the signals shutting down PDH increase in intensity. We just don't know.

    I suspect from the anecdotal data that there is at least a large subset with ME who do better on higher protein. I was aware in the 90s that many docs in Australia found that higher protein was better, and together arrived at a decision that 1.5g/kg of body weight was about ideal. I don't know if this was ever published as it was based on informal investigation. I also cannot determine if this figure is reliable.

    If restoring PDH function can lead to a cure or remission then we might find treating ME is even easier than we thought, but first we have to find the correct protocol.

    PS I am currently reading the full paper.
     
  10. roller

    roller wiggle jiggle

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    @Ben Howell so, you dont believe...?

    Naviaux findings point pretty strongly at parasites.
    his findings are common in certain parasitic infections.
    dont you think they should be ruled them out after those results?

    so, which ones did he check the participants for?

    which parasitic infections did he rule out?

    can we have this list, please?
     
  11. roller

    roller wiggle jiggle

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    i absolutely disagree.

    that is exactly the problem with "medicine".
    it DOES matter what the trigger is.

    otherwise we are having band aids that just shift the whole mess.
    it may go well for some time then symptoms change and mostly worsen.

    we need to know the triggers and treat them.

    it seems quite wrong to bomb (interfere with) the immune system as a solution.
     
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  12. roller

    roller wiggle jiggle

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    we know that glycolyis, fatty acid metabolism go wrong.
    pyruvate dehydrogenase dysfunction has been found in other diseases (alzheimers, parkinson and what not) as well.

    iits old news.
    it leads to nothing. zilch.

    they may be just desperate in explaining their rituximab.

    they have no clue and dont know what they are doing.
    such sort of "research" just underlines that.
    its aweful. scaring. horror. for us.
     
  13. TiredSam

    TiredSam The wise nematode hibernates

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    Here's an anecdote based on a sample of 1 - about 3 months ago I decided it was time to lose weight (6 kg so far, thanks for asking). So I switched from spreading the usual jams, peanut butter, cheese spreads etc on my bread in the evening to just putting slices of lean meat on them, or tuna, and eating more boiled eggs. In the same time period I have noticed a significant improvement in my ME symptoms and am now dangerously well (ie my biggest problem now is to stop myself from doing more because I feel ok. I still have my limits and will still crash, but it's getting harder to remember that because I don't have a headache all the time to remind me).

    I thought the correlation between my change in diet and ME improvement could be due to just losing a bit of weight and generally eating more healthily, but now it looks like it may be due to my increased protein intake over the last 3 months?

    Meat and red wine - I will continue experimenting with the Gout Diet and report back.
     
    Last edited: Dec 23, 2016
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  14. Kati

    Kati Patient in training

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    The paper specifically mentions that there is no nutritional deficiencies present in either patient or control groups, it is simply how the body utilizes the amino acid that is the difference. The experiment of introducing ME plasma to healthy muscle cells shows that that the muscle cells behave differently is most interesting and hopefully it will pique the curiosity of many more scientists.

    I do not believe that the study said that male subjects were breaking down proteins any faster. The opposite actually, as all of these experiments yielded significant results for women but not in men, with the suggestion that the number of men was not sufficient enough to provide statistical power.

    So take home message: eat well, eat varied and fund research.
     
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  15. Countrygirl

    Countrygirl ME is not MUS

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    http://www.kon.org/urc/v10/rahim.ht

    The above was posted elsewhere by our very own in-house God of Pleasure, but I don't think he has posted it anywhere here.

    It is useful for those of us who don't have a spare PhD in biochemistry lying around.


     
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  16. Marco

    Marco Grrrrrrr!

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    Although some (congenital) PDH deficiency disorders respond to thiamine supplementation and to a lesser extent a ketogenic diet.
     
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  17. dannybex

    dannybex Senior Member

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    Perhaps I missed it (eyes are wiped out) but I couldn't find where it 'specifically' mentioned there were 'no nutritional deficiencies' between the two groups, especially of those that help may help improve mitochondrial function. Could you quote where they ruled out any specific nutritional deficiencies?

    It's worth noting they didn't mention (that I could see) what might be interfering w/PDH, like heavy metals or other environmental toxins, not to mention toxic byproducts from bacterial, viral, fungal infections like acetaldehyde, just as one example. For some people oxalates can be a problem, and oxalate impairs both pyruvate kinase and pyruvate dehydrogenase.

    Quoting: "Concentrations of 3-methylhistidine (3-MHis), a marker of endogenous protein catabolism (e.g., muscle atrophy) (28, 29), were significantly higher in men with ME/CFS compared with healthy men."

    Which unfortunately I can relate to. And the high lactate.
     
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  18. dannybex

    dannybex Senior Member

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  19. Snow Leopard

    Snow Leopard Hibernating

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    I agree with most of what you said, and agree that these findings are unlikely to be due to nutritional deficiencies.

    But the authors did explicitly find increased signs of muscle breakdown:
    "Concentrations of 3-methylhistidine (3-MHis), a marker of endogenous protein catabolism (e.g., muscle atrophy) (28, 29), were significantly higher in men with ME/CFS compared with healthy men (P = 0.003 by t test, Cohen’s d = 0.80), while there was no corresponding difference in 3-MHis between female ME/CFS patients and healthy women (Table 2 and Figure 2, I and J)."
     
  20. Kati

    Kati Patient in training

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    Sorry I can't copy and paste on my ipad, it was in the 'discussion' if I remember well, and they said that there was no nutritional amino acid deficiencies, meaning it's not caused by a protein-poor diet. Moreover they tested patients of all body weights (BMI) and they could see the differences across all body sizes in women.
     
    Last edited: Dec 27, 2016
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