Choline on the Brain? A Guide to Choline in Chronic Fatigue Syndrome
http://phoenixrising.me/research-2/the-brain-in-chronic-fatigue-syndrome-mecfs/choline-on-the-brain-a-guide-to-choline-in-chronic-fatigue-syndrome-by-cort-johnson-aug-2005
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In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

Discussion in 'Latest ME/CFS Research' started by A.B., Apr 8, 2015.

  1. A.B.

    A.B. Senior Member

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    A theoretical paper from the Institute for Condensed Matter Physics, Technische Universität Darmstadt, Germany. Authors: Nicor Lengert, Barbara Drossel.

    Abstract
    Post-exertional malaise is commonly observed in patients with myalgic encephalomyelitis/chronic fatigue syndrome, but its mechanism is not yet well understood. A reduced capacity for mitochondrial ATP synthesis is associated with the pathogenesis of CFS and is suspected to be a major contribution to exercise intolerance in CFS patients. To demonstrate the connection between a reduced mitochondrial capacity and exercise intolerance, we present a model which simulates metabolite dynamics in skeletal muscles during exercise and recovery. CFS simulations exhibit critically low levels of ATP, where an increased rate of cell death would be expected. To stabilize the energy supply at low ATP concentrations the total adenine nucleotide pool is reduced substantially causing a prolonged recovery time even without consideration of other factors, such as immunological dysregulations and oxidative stress. Repeated exercises worsen this situation considerably. Furthermore, CFS simulations exhibited an increased acidosis and lactate accumulation consistent with experimental observations.

    http://www.sciencedirect.com/science/article/pii/S0301462215000630

    @alex3619 might be interested in this.
     
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  2. Helen

    Helen Senior Member

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    Thanks @A.B. It would be interesting to read the full article but I guess it´s only available behind the pay-wall.
     
  3. drob31

    drob31 Senior Member

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    This probably why baking soda helps some people.

    So, supplement list:

    MitoQ or PQQ
    and baking soda
     
  4. Sidereal

    Sidereal Senior Member

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    According to their model

    This is in line with our own experiences of prolonged overexertion leading to cumulative PEM damage, sometimes permanent.
     
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  5. Sidereal

    Sidereal Senior Member

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    If I understand this right, when we try to exercise we're ripping through our protein in order to survive.

     
  6. alex3619

    alex3619 Senior Member

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    This appears (without reading the full paper) to be plausible, but is only formally restating what is already in the literature, and then modelling it. It requires real world validation. However its good to see such models. I think they are important steps forward, and give us predictions that can be tested.

    I do not recall reading the term "in silico" before. It seems appropriate.
     
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  7. Snow Leopard

    Snow Leopard Hibernating

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  8. leokitten

    leokitten Senior Member

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    Attached is the full PDF article
     

    Attached Files:

    Helen likes this.
  9. alex3619

    alex3619 Senior Member

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    My biochem degree is now 13 years old, and it does not appear in most of the papers I read.
     
  10. Bob

    Bob

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    I think I've come across it once before but I'd completely forgotten what it meant until you pointed it out. I remember thinking it was quite a clever turn of phrase when i first saw it.
     
  11. jimells

    jimells Senior Member

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    What's this pool, and is there any way to fill it faster?
     
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  12. Bob

    Bob

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    Turn the tap on? (Sorry, I couldn't resist.)

    I'm trying to get my head around all these metabolic pathways, but they're really complicated. I think it might be referring to the mix of certain metabolites that incorporate adenine, and I've seen it specifically being used to refer to ATP+ADP+AMP. I'm not sure if it can also refer to other nucleotides that incorporate adenine such as NAD (nicotinamide adenine dinucleotide).
     
    Last edited: Apr 8, 2015
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  13. corni

    corni

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    Darmstadt, Germany
    I'm the author of this article. I am happy to see it being discussed already here. If you are interested, the full text is available for free from here:
    http://authors.elsevier.com/a/1QuQW14YsaFG8s until June,8 (after that just write me a mail).

    The paper about EBV inducing CFS has a really interesting approach. Does anyone know the percentage of CFS patients with preceding EBV infection (I am one of those)?

    I agree that most of the qualitative predictions can be made from the already available literature, but still, the paper leads to a better understanding on a biochemical level and to quantitative statements. E.g. it shows that the reaction 2 ADP->ATP+AMP does not contribute much to the energy supply (as often stated) but it mainly stabilizes the free Gibbs energy gained from ATP hydrolysis. Also, it can make predictions about the recovery time, which hopefully will be compared to experimental data some day.

    Well, it was shown that ribose leads to a slightly faster recovery. On the other hand, permanent high ribose level might be harmful because of glycation of proteins. So I would take it only during PEM or before any higher energy demand. The problem is that the low mitochondrial capacity may be the cause of PEM but itself is probably caused by immunological dysfunctions like an upregulated RNase L pathway or a dysfunction in the memory cells to EBV. So supplementing with ribose, Q10, carnitine etc. can improve the symptoms a bit but does not remove the underlying cause.
     
    Last edited: May 2, 2015
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  14. rosie26

    rosie26 Senior Member

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    Welcome to PR, great to have you here! Thanks for your for your cautious guide on taking ribose. I will feel more comfortable taking ribose that way from now on. It does help to take some rough edges off PEM for me.
     
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  15. adreno

    adreno PR activist

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    The problem with ribose for me is that there is a crash when it wears off, that is making me feel even worse than before I took it.
     
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  16. alex3619

    alex3619 Senior Member

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    This is why I like it. It makes specific testable predictions. That is what science should be, even if its later shown to be wrong.
     
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  17. Battery Muncher

    Battery Muncher Senior Member

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    Welcome @corni ! It's always a pleasure to have a researcher appear on our boards.

    Thank you for drawing our attention to the free availability of this paper, I look forward to reading it when I have the time.
     
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  18. corni

    corni

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    Thank you for the warm welcome. :)
    I think with ribose it is the same as with many other supplements, which sound very promising in theory, but in practice you can't really tell how well they work since there are so many other factors like sleep, hormones etc.
     
    Last edited: May 2, 2015
  19. Gijs

    Gijs Senior Member

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    Great report Corni. I know a lot of patients who have used D-Ribose. Some experienced an improvement (not strong) but many supplements provide one improvement in ME patients. Even though they are not signifcant improvements still I wonder why patients respond so strongly to supplementation. Much more interesting for me is what causes 'mitochondrial dysfunction' or reduced energy metabolisme, could it be due to low bloodflow or gut problems... it is very complicated.
     
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  20. jimells

    jimells Senior Member

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    Thank you for joining the discussion of your paper. We are always hungry for new papers, and they always get a thorough, but fair, examination. Personally, I can barely understand most of this stuff. But I always enjoy following the discussion (as best I can) among some of the smartest folks in the world. :thumbsup:
     

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