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Substrate utilisation of cultured skeletal muscle cells in patients with CFS, Tomas et al, 2020

Discussion in 'ME/CFS research' started by John Mac, Oct 26, 2020.

  1. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I think Ron Davis has said that there was some evidence that Whitney had been cannibalising his muscle - there's a particular excretion product which is increased in these circumstances.
    Not sure if Ron has introduced these amino acids as a means of increasing Whitney's nutrition.

    Chris Armstrong (OMF) is returning to Melbourne - he's focusing on nitrogen metabolism; which I assume is all of this protein stuff.

    Fluge and Mella published their PDH paper in December 2016 - why does it take so long to move these things along? Money/competing priorities I guess but still frustrating.
     
    Last edited: Nov 8, 2020
  2. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    If it's yet to be explained, and there seems to be evidence of utilising certain amino acids, then is diet unreasonable? Also I think Ron Davis and Chris Armstrong may have considered diet supplementation.
     
  3. Kitty

    Kitty Senior Member (Voting Rights)

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    Yes, I don't think what's being researched is the same as a diet deficiency. Some or all of us may be consuming more of a resource than normal; if that's shown to be the case it makes sense to take in a bit more of it, as long as it's not going to cause problems elsewhere.

    (Although one of the questions is going to be whether eating more of X can actually increase the body's reserves of it, of course; it's not always that simple.)
     
  4. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    https://www.nature.com/articles/srep34990

    This is just one of the studies that found problems in the general area of the TCA and urea cycle.

    Data from the UK Biobank also suggested that the gene for the ornithine transporter 1 was associated with ME/CFS (ornithine plays a role in the urea cycle).
     
    Last edited: Nov 7, 2020
  5. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Milo "The dysfunction in glucose oxidation [muscle cells] is similar to what has previously been shown in blood cells from CFS patients." This seems to indicate that PBMCs would be a substitute i.e. for muscle cells.

    However, @Jonathan Edwards suggestion, re MR Spectroscopy, would be much more interesting i.e. if the sensitivity of MR Spectroscopy is adequate.
     
  6. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I suspect you're correct i.e. if you're consuming more of X (certain amino acids for energy production) then supplementing your diet with X may not lead to an improvement in your health/functioning.

    I wonder if a blood test (PMBCs) could identify people who have this problem and then a genetic test could be used to identify genes (gene expression) that are relevant?
     
  7. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    Amino acids are definitely absorbed in the gut.;)
     
    Amw66 and Kitty like this.
  8. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    I recall that Ron Tompkins (OMF) was planning to do work on muscle cells i.e. with UK researchers - any news of that?

    Anyone with links to OMF on this forum?

    @Giada Da Ros
     
    Kitty and cfsandmore like this.
  9. FMMM1

    FMMM1 Senior Member (Voting Rights)

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    Hi @strategist hope you don't mind me pointing out @alicec explanation of how amino acids etc. are utilised for energy, there also info re diet supplementation,

    https://www.s4me.info/threads/amino-acids-and-energy-production.1262/#post-21189

    perhaps alicec could link it to this thread.

    Also, here's a quote from alicec's post
    "They [Fluge & Mella] then showed that the pyruvate dehydrogenase complex (PDH), which catalyses the pyruvate to acetylCoA conversion, is inhibited in ME/CFS.

    This was a result of upregulation of genes coding for several enzymes which inhibit PDH, viz SIRT4, members of the PDH kinase family of enzymes (PDK) and the transcription factor PPRD."


    I was just wondering if the levels of SIRT4 etc. would be a biomarker for ME i.e. inhibition of PDH? Sure someone has thought of that and discounted it.

    Fluge and Mella thought the metabolic changes were reversible; however, Cara et al propose that they are not reversible - transferred to next generation of cells.

    Someone mentioned the UK Biobank turned up a possible link to Ornithine Transporter?

    Quite a bit of interesting information.
     
  10. Andy

    Andy Committee Member

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    Simon M, sebaaa, Fizzlou and 5 others like this.
  11. leokitten

    leokitten Senior Member (Voting Rights)

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    Have they, or anyone else, examined cells collected from the muscle biopsies and tried to confirm or refute the Prusty hypothesis that the reduced OXPHOS they are seeing is due to mitochondrial fragmentation?
     
    Last edited: Jan 11, 2021
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  12. DMissa

    DMissa Established Member (Voting Rights)

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    Not sure, but if somebody does visually inspect ME/CFS mitochondria specifically in muscle one would hope for a comparison against sedentary controls. Muscle mitochondria from people who can't undertake exercise, or can only undertake reduced exercise (due to disease burden) would probably look different from a more active person's given that muscle mitochondrial biogenesis is stimulated by exercise. This would have to be dismissed as a potential confounding variable.
     
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