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Dysregulated Provision of Oxidisable Substrates to the Mitochondria in ME/CFS Lymphoblasts, 2021, Missailidis et al

Discussion in 'BioMedical ME/CFS Research' started by John Mac, Feb 19, 2021.

  1. John Mac

    John Mac Senior Member (Voting Rights)

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    https://www.mdpi.com/1422-0067/22/4/2046
     
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  2. borko2100

    borko2100 Established Member (Voting Rights)

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    That's how I experience it. When I do aerobic activities I feel lactate build up, this feeling comes up extremely quick, like my body immediately switches to some inefficient energy burning mode.

    I think this is the second or third paper these researchers have published about Complex V problems, has anyone besides them found problems with Complex V? Seems to me like a good lead.
     
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  3. Creekside

    Creekside Senior Member (Voting Rights)

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    I was suspicious of Complex V long before I knew about ME. I thought I had some problem with kynurenine production, which involved superoxide and Complex V. There were some other factors, now forgotten, that kept me suspicious. Now I've become sensitive to proline, which reduces activity of cytochrome c oxidase (complex IV). Since proline gives me symptoms seemingly identical to PEM, this might indicate that PEM involves mitochondrial dysfunction.
     
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  4. Trish

    Trish Moderator Staff Member

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    I'm curious about how anyone would find out they were sensitive to proline, since it is an amino acid prevalent in a wide range of foods.
     
  5. Aslaug

    Aslaug Moderator Staff Member

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    What do you mean by "sensitive to proline", sensitive to the amount we get from a regular diet or some supplement?
     
  6. strategist

    strategist Senior Member (Voting Rights)

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  7. Aslaug

    Aslaug Moderator Staff Member

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    Glutamine and glutamate can be drastically altered by dietary changes in otherwise healthy humans (I've seen around 1.5 fold increase in glutamine, with a similar reduction in glutamate, by changing diet alone), and reduced glutamine with increased glutamate is seen in many conditions.
     
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  8. borko2100

    borko2100 Established Member (Voting Rights)

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    I get insomnia and some neuro symptoms from MSG, so glutamine / glutamate definately affects me in some way.
     
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  9. Cheesus

    Cheesus Established Member (Voting Rights)

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    How do you measure that? What does the diet entail?
     
  10. Hutan

    Hutan Moderator Staff Member

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    @DMissa, nice to see another paper out. What is up next for you and the team? Do you have funding?
     
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  11. Hutan

    Hutan Moderator Staff Member

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    A really nice background - it can be hard to get it right, but this one nails it, I think.
    Background
    Page 3 typo
     
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  12. Milo

    Milo Senior Member (Voting Rights)

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    I think the mistake many people make is translating what scientific experiments, at the cellular level, means or implies for their functioning as owners of a complex machine.

    Remember that no diet and no supplements so far have worked for patients with ME including the one clinical trial for mito support from a couple years ago, and remember that the authors are not implying that changes in diets will change anything. Science is not there yet.

    (That is when people add: but i feel better on x,y and z...)
     
  13. Aslaug

    Aslaug Moderator Staff Member

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    A bloodsample. In this case, it was a change from a "standard" diet to a diet following that country's specific dietary guidelines (these are pretty much the same all over the world: increase intake of whole foods, fiber-rich foods such as fruits/vegetables/legumes/grains, eat high quality protein and fats). But as I said, this was otherwise healthy humans, it might be different once someone has a disease. The reason for the change glutamine/glutamate values may also be different.

    But I feel better... ;)

    Diet as a treatment in other disease is also for the most part in the "science is not there yet", except in the cases of nutrient deficiency diseases and celiac disease. There are cool results for inflammatory bowel disease, where certain dietary approaches can induce remission of inflammation in the gut, but I guess that's about it. Or, low-FODMAP or IBS might be included here, even if there are some questions about how it works.

    There's impairment of the integrity of the intestinal wall ("leaky gut") and changes in gut microbiome composition in several diseases, and we know certain foods/dietary approaches (and other lifestyle approaches) that can improve things, but if that influences the state of the disease is more uncertain. In the case of the gut microbiome we don't know what the ideal microbiome should look like for anyone. That said, for any disease not meeting your nutrient requirements is an unnecessary strain on your body that has enough to deal with already.

    Edit: Forgot inborn errors of metabolism.
     
    Last edited: Feb 21, 2021
  14. Hutan

    Hutan Moderator Staff Member

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    So, if those differences are there between ME/CFS and controls, in both non-immortalised PBMCs and lymphoblasts, what does that tell us about what is causing the differences? The lymphoblasts will have been frozen, and presumably washed, and cultured, and treated with the EBV, umm, treatment that immortalises them. And presumably new cells are being made by the lymphoblasts, with the new cells also showing the differences. So, what is perpetuating the difference from controls, in the lymphocytes taken from the patients all the way through to new generations of lymphoblast cells?

    Is it epigenetic changes? Could it be bits of virus?
    (Sorry, I've run out of energy, so haven't read much of the last bit of the paper.)


    There are quite big differences between patient lymphoblasts and control lymphoblasts in gender (88% female vs 45% female) and age (53 years vs 30 years). No significant effect of age or gender was found, but it's less than ideal. I guess Covid may have made blood collection difficult in 2020 - but perhaps Emerge could help with control recruitment, to try to get better matched control samples going forward?
     
    Last edited: Feb 20, 2021
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  15. strategist

    strategist Senior Member (Voting Rights)

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    The glutamine caught my attention because my mother says she needs to take glutamine before going to sleep or she will wake up from hypoglycemia or epilepsy (the two are connected). She has suffered from mystery illness for many years and also had postinfectious ME/CFS for a while and I suspect that there is a large overlap between our illnesses.
     
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  16. butter.

    butter. Senior Member (Voting Rights)

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  17. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    Thanks for the interesting comments and background. What about diabetes, obesity, heart disease: is there reliable evidence that diet works there as a treatment?
     
  18. Michiel Tack

    Michiel Tack Senior Member (Voting Rights)

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    The methods and various pathways are a bit too complex for me to understand but this seems to be the main conclusion/hypothesis behind it:
     
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  19. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    Very happy to see @DMissa and team collaborating with other researchers. I also appreciate that Sweetman and co in NZ have been attempting to replicate some of their previous work with small cohorts.
     
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  20. strategist

    strategist Senior Member (Voting Rights)

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    My interpretation is: in a previous study, their main finding was a mitochondrial complex V inefficiency, in cells that had been immortalized. Immortalization of cells is an invasive technique and they need to be sure that this complex V inefficiency is due to ME/CFS and not the immortalization. This study looks like an attempt to collect more data with different methods to show that this inefficiency is due to ME/CFS. The data appears to be consistent with this.
     
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