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Post-Exertional Malaise Is Associated with Hypermetabolism, Hypoacetylation and Purine Metabolism Deregulation in ME/CFS Cases, 2019, McGregor et al

Discussion in 'ME/CFS research' started by Andy, Jul 4, 2019.

  1. obeat

    obeat Senior Member (Voting Rights)

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    @Wonko Could you pm me also? Thanks
     
  2. Andy

    Andy Committee Member

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  3. Hutan

    Hutan Moderator Staff Member

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    I agree. I'd have expected, in metabolites that might tell us something about PEM, that either the level in the controls would be high, the level in the people with ME/CFS who reported a low level of PEM symptoms in the last seven days would be lower and the level in the people with ME/CFS who reported a high level of PEM symptoms would be lower still. Or vice versa.

    Instead, it's the people with ME/CFS with low recent PEM who look most different to the controls. Of the 12 serum and urine metabolites reported in Table 2, only one, phenylalanine, follows the expected pattern. I've charted the figures here:

    Screen Shot 2019-07-08 at 4.12.34 PM.png

    With results like that, I'm wondering how useful the two categories of people with ME/CFS are; whether the criteria for the categories really do distinguish between people still showing the effects of PEM; or whether these metabolites have anything to do with PEM.

    Later in the paper there's a suggestion of a physical process associated with PEM that might be confounding metabolite levels:

    The figures given for urine acetate and urine urea were:

    I'm not really sure if they have something here or not. I need to read the paper again. There were quite a lot of metabolites tested and then they did a lot of different things with the figures; absolute levels, percentage of metabolites, ratios, correlation with the 7 day PEM score (in both whole group and just the ME/CFS group) and with the 12 month frequency of PEM score.

    To be fair to the authors, they aren't claiming to be sure if they have something here or not either. Just that it's worth looking at some of these things some more.
     
  4. Milo

    Milo Senior Member (Voting Rights)

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    i wonder whether there would be a difference between PEM self-report and provoked PEM-with timely blood collection. And of course it would involve much effort in going through ethic reviews and performing the exercise tests. That would be a much different study design, but it would control the self-report aspect which is always problematic in my view.

    It seems to me that it can be hard to tell sometime whether you are in PEM or not if you push yourself every day and end up having symptoms every day.

    My 2 cents.
     
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  5. Midnattsol

    Midnattsol Moderator Staff Member

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    But since people experience PEM at different times after exertion, you would probably have people at different stages of PEM if you had blood collections at specific time points.
     
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  6. Sarah94

    Sarah94 Senior Member (Voting Rights)

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    Would 'hypermetabolism' explain why I am really hungry during PEM?
     
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  7. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    I have the same reaction. Eating seems to compensate a little bit.

    My mental model of this was hypometabolism in the sense of lacking energy and trying to compensate for it, but it could also be thought of as hypermetabolism.

    Anyway the idea that there are changes in metabolism seem to be consistent with what is happening in reality.
     
    Last edited: Jul 8, 2019
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  8. Midnattsol

    Midnattsol Moderator Staff Member

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    I don't always get very hungry when I have PEM, but often. To me it makes sense, if the body has an increased need for certain nutrients (and energy) then starting up some hunger-signalling pathways seems like a good idea.
     
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  9. Denise

    Denise Senior Member (Voting Rights)

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    And yet anecdotally some (I have no idea how many) patients barely have the energy to eat during PEM.
     
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  10. Mij

    Mij Senior Member (Voting Rights)

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    I'm normally a very good eater, but in PEM I lose my appetite.

    Doesn't our digestive system require a lot of ATP to process and digest food? Something I have less of in PEM.
     
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  11. Hoopoe

    Hoopoe Senior Member (Voting Rights)

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    Maybe in some patients the body reacts by trying to compensate with increased nutrient intake, in others maybe it reacts by reducing energy expenditure to a minimum.
     
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  12. Mithriel

    Mithriel Senior Member (Voting Rights)

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    Sometimes I think our results are normal because they are so wrong! For instance I tend not to fall over during a romberg test (closing your eyes) because I am so bad I fall over when I blink so I have trained myself to feel the ground through my feet.

    Relevant to these results this way. Healthy controls have a certain level of substance A in their blood because the body produces it and then gets rid of it in the normal way. Patients who are in low PEM produce substance A but do not have the resources to mop it up so their levels are high. Patients in bad PEM do not have the resources to produce substance A so their figures match the healthy controls yet they are the most sick.
     
  13. wigglethemouse

    wigglethemouse Senior Member (Voting Rights)

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    @mariovitali I watched the recent Hardvard OMF talk by Mike VanElzakker. In the brain in PEM both Glutamate and Glutamine are reduced vs baseline scan (small sample size, unpublished data) as well as reduced blood flow in certain areas (blood flow on previous slide, sample 2 people, duplicating others work but in much greater detail with newer technology)

    Talk :

    https://www.youtube.com/watch?v=bJ3UxSZ6MII




    Slide at 17m:19s
    upload_2019-7-8_8-50-29.png
     
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  14. mariovitali

    mariovitali Senior Member (Voting Rights)

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    @wigglethemouse

    Thank you, i am adding hypoperfusion to the software system to see what i am getting (currently 10K abstracts) and see what kind of connections occur with other known concepts of interest.

    I looked for some papers and found the following figure. Many concepts there we've seen before :

    Link : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5094314/figure/fig1-0271678X16666846/

    [​IMG]

    Lower glutamine / glutamate levels are a result of hypoperfusion from what i understand. I will have to read more about this.
     
    Last edited: Jul 8, 2019
  15. Ravn

    Ravn Senior Member (Voting Rights)

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    I've also been trying to get my head around this seeming contradiction. Wondering if there could be a kind of compensation mechanism at play?

    An example of such a mechanism would be my experience of OI, which I've seen other people describe, too.
    • When my ME was mild I had problems with fainting due to my BP dropping on standing. So my BP was very different from a healthy person's.
    • Once I got more severe I began to have compensatory tachycardia, at least that's how I interpret it, and that compensatory tachycardia kept my BP up. So now my BP looks perfectly normal (even though my HR doesn't).
    So if you only look at my BP I looked ill while mild but healthy while severe.

    Not saying that something equivalent in PEM is a likely mechanism to explain the more normal results with PEM than without PEM in this paper, only that it's the only mechanism I could think of apart from the results simply being random coincidences. @Mithriel added another angle. Can anyone add more possible explanations?
     
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  16. Subtropical Island

    Subtropical Island Senior Member (Voting Rights)

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    I’d make a distinction between hunger and ability to eat and digest.
    In the sense of:
    The first is a motivation, a signal given by whatever it is the body does to make desires and compulsions etc.
    The second is a response to the action that results.

    E.g. I can be (feel) ravenous, driven to eat etc. But also really struggle to digest the food my body seemed to want. Or perhaps for some, even struggle with the eating part (bite, chew, swallow).

    ETA: have not read this thread yet, just a few comments so let me know if this is OT.
     
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  17. mariovitali

    mariovitali Senior Member (Voting Rights)

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    Well, i can definitely say that this day has a lot of positive vibes. Both Dr Phair and Dr Bergquist replied back today saying that they will look at some associations that the Information Extraction tool has found with excitotoxicity, kynurenine, glutamate and the paper cited above mentioning hypoxanthine in Cerebrospinal Fluid (CSF). Dr Bergquist's response was very positive i would say regarding Hypoxanthine and CSF in the sense that such finding sounds very interesting .

    I am finding connections in both hypoxanthine (Dr McGregor) and hypoperfusion (Dr VanElzakker). I will post as soon as i have the results in the Machine Learning thread so as to not be OT here.
     
  18. JemPD

    JemPD Senior Member (Voting Rights)

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    No comments on this study @Jonathan Edwards?
    I'd be interested in your thoughts as well as other people's, particularly as it's rather beyond me & i don't want to waste my energy learning about 'Hypoacetylation and Purine Metabolism' if it looks like it could be a blind alley.
     
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  19. hinterland

    hinterland Senior Member (Voting Rights)

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    Could it be both the controls and high PEM patients have been active; whereas low PEM patients have been resting? So the metabolites measured correlate with activity levels, not necessarily disability.
     
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  20. hinterland

    hinterland Senior Member (Voting Rights)

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    Does anyone else keep needing to pee when on the verge of crashing? What could this mean?!
     

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