Lipkin's Monster ME/CFS Study: Microbes, Immunity & Big Data
The Microbe Discovery Project outlines an ambitious new study by top researchers that has collected patient samples, but needs desperately funds to complete the work.
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. Kati

    Kati Patient in training

    Messages:
    5,451
    Likes:
    19,501
    For our patient group though, you'd hope that the fatty acid oxydation is going on normally, which is not necessarily a given for each and every patients.

    Personally being overweight and having attempted an atkin's type of diet and gained 10 lbs in the first week, I would be stupid to try this. i'm going to wait for more papers to come through and my doctor's advice. So much more research is needed.
     
    MEMum and Marco like this.
  2. dannybex

    dannybex Senior Member

    Messages:
    3,174
    Likes:
    2,112
    Seattle
    I agree, they said no nutritional amino acid deficiencies, but didn't see any discussion of other deficiencies besides proteins. :)
     
    Paintmyturquoise and merylg like this.
  3. lansbergen

    lansbergen Senior Member

    Messages:
    2,478
    Likes:
    2,673
    I do and it works for me.
     
  4. J.G

    J.G

    Messages:
    69
    Likes:
    276
    That's a good discovery. It dovetails nicely with observations that large-scale breakdown of collagen (the body's most abundant structural protein) is occurring in a group of PWME. The skin is home to large collagen stores and stretchy skin, indicating catabolism thereof, is a somewhat common symptom. (See also this thread.)
     
    Last edited: Dec 23, 2016
    sb4, PatJ, MastBCrazy and 4 others like this.
  5. ash0787

    ash0787 Senior Member

    Messages:
    292
    Likes:
    572
    no roller isn't trolling he is just fixated on one particular line of inquiry for some reason,
    I understand his concern but I think if there is a persistent pathogen its likely to be one that doesn't cause a lot of damage / is relatively inactive or localized, otherwise it would be fairly easy to detect and the rituximab patients would become very ill no ?
     
  6. thegodofpleasure

    thegodofpleasure Player in a Greek Tragedy

    Messages:
    197
    Likes:
    353
    Matlock, Derbyshire, Uk
    Dr Karl Morten (Neurosciences Group, Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford) is evidently an expert in these matters:

    Dichloroacetate stabilizes the mutant E1α subunit in pyruvate dehydrogenase deficiency

    http://www.neurology.org/content/53/3/612

    I know that Dr Sarah Myhill's research colleague, Dr Norman Booth (Dept of Physics, Oxford) has encouraged him to get involved in ME/cfs research.

    He gave a talk to the Oxford ME Support Group earlier this year (introduced by @charles shepherd)

    His opinion on these findings would be of considerable value.
    To have him replicate them would be even better.
     
    Advocate, natasa778, MEMum and 10 others like this.
  7. bel canto

    bel canto Senior Member

    Messages:
    239
    Likes:
    465
    How would this be likely to show up on a Nutreval test if at all? Would the pyruvate levels (urine) be increased if it's not being converted into acetal CoA?
     
  8. lansbergen

    lansbergen Senior Member

    Messages:
    2,478
    Likes:
    2,673
    But seems not to know parasites party when the host is under stress from for example an infecction.
     
  9. Deepwater

    Deepwater Senior Member

    Messages:
    135
    Likes:
    715
    I can't lose weight on Atkins either, but lost a lot of weight on the Dukan diet, which is Atkins minus fat. As soon as I added a moderate amount of fat and carbs and into my diet the weight went straight back on.
     
  10. roller

    roller wiggle jiggle

    Messages:
    451
    Likes:
    214
    ..or a vaccination...

    or PPIs ... etc etc
     
  11. Barry53

    Barry53 Senior Member

    Messages:
    2,277
    Likes:
    13,689
    UK
    Yes, if closed loop control mechanisms have gone awry, and you unwittingly mess directly with a badly controlled variable rather than fix the underlying problem in the closed loop regulation itself, then you may just force its bad regulation to do even weirder things. Especially if there happen to be several interdependent control loops in play, possibly with several of them faulty.
     
  12. alex3619

    alex3619 Senior Member

    Messages:
    12,413
    Likes:
    34,775
    Logan, Queensland, Australia
    Which is my suspicion.
     
    merylg, Barry53, JaimeS and 3 others like this.
  13. ash0787

    ash0787 Senior Member

    Messages:
    292
    Likes:
    572
    so a bit like some of the computer viruses you sometimes get, you think you have found the main files of the virus and you delete it, only for it to reappear later because another part of the virus elsewhere in the system is monitoring what you did
     
    MEMum, JaimeS, Comet and 1 other person like this.
  14. Marky90

    Marky90 Science breeds knowledge, opinion breeds ignorance

    Messages:
    1,167
    Likes:
    4,253
    Maybe we are programmed to be sick :nervous: #Westworld #reference

    I have skimmed through the paper, not carefully read it, as I lack the sufficient understanding of metabolomics anyway. It gets me thinking that we probably do not know a whole lot about the whole picture when it comes to how the body can work, but obviously this is a conclusion that`s very easy to come to when you know jack all about the particular subject anyway.

    I`m starting to be doubtful that antibodies are the main culprit for the majority, mainly because very few seemingly get fully recovered by rituximab and cyclo (based on the trials, and the cyclo patent). Is it because in a majority long lived plasma cells are hard to reach? Might there be some pathological immunological "castle" somewhere, like in sarcoidosis? May other immunological processes not yet known of, "mimic", what seemingly seems like a case of autoimmunity?

    I`m asking, because there are other severely debilitating diseases like e.g sclerodermia, which looks like autoimmunity, but dont respond properly to the treatment of it. Even autologous stem-cell transplantation does not always impact the level of functioning in these patients.

    I feel that the fact that cultured muscle cells react to being exposed with ME-blood is a big lead, perhaps more than the concrete metabolic findings. At the very least it is a reason for the researchers to be completely open minded about what may be causing the metabolic abnormalities, and the cause might even be due to processes unknown of.
     
    Advocate, hixxy, MEMum and 10 others like this.
  15. caledonia

    caledonia

    Messages:
    4,203
    Likes:
    3,220
    Cincinnati, OH, USA
    This is basic biochemistry - a deficiency of vitamin B1 and also the presence of mercury and/or arsenic inhibit the pyruvate metabolism.

    https://www.ncbi.nlm.nih.gov/books/NBK22340/
     
    Last edited: Jan 28, 2017
    sb4, Advocate, Helen and 3 others like this.
  16. Hip

    Hip Senior Member

    Messages:
    9,137
    Likes:
    14,052
    Yes, dichloroacetate (DCA) will up-regulate the pyruvate dehydrogenase complex. Detailed in this post.

    Someone a few years ago on this forum tried DCA — see this thread — and got some positive results.



    Dichloroacetate (DCA) boosts pyruvate dehydrogenase function specifically by inhibiting the pyruvate dehydrogenase kinases (PDK), and DCA does this by the same mechanism that pyruvate inhibits PDK. See here.

    So DCA would seem like a good drug to try in order to boost pyruvate dehydrogenase function in ME/CFS.



    DCA is sold online as an alternative/experimental cancer treatment. If you Google search on "dichloroacetate cancer buy" you will find some suppliers. It is a little expensive, but not prohibitively so (it would be worth the money if it works).


    The anti-cancer effect of DCA is thought to be due to its ability to:
    "reactivate suppressed mitochondria in some types of oxygen-starved tumor cells, and thus promotes apoptosis.

    DCA is known to be relatively safe, available, and inexpensive, and it can be taken by mouth as a pill."
    Ref: 1
     
    Last edited: Dec 23, 2016
    sb4, Advocate, WendyM and 5 others like this.
  17. SherDa

    SherDa

    Messages:
    18
    Likes:
    26
    I'm excited to try a ketogenic diet. Providing ketones would bypass PDH, right? Ketones could maybe then provide an energy source and spare proteins. I've been considering trying it anyway.
     
    JaimeS likes this.
  18. deleder2k

    deleder2k Senior Member

    Messages:
    1,104
    Likes:
    4,744
  19. Forbin

    Forbin Senior Member

    Messages:
    929
    Likes:
    3,906
    Is the idea that autoantibodies are attacking PDH? This is apparently part of the etiology of primary biliary cirrhosis (PBC). According to the Wikipedia article on PBC, the disease is "strongly associated" with the presence of a bacterium that is "cross reactive" with liver cell mitochondria. Also...
    I'm guessing that means that, in going after the bacteria, the immune system starts going after PDH enzyme as well [but I could be wrong].
    If the immune system were going after PDH, might cells down-regulate the production of PDH as a defensive countermeasure?

    [I could be misinterpreting the above, but, if this is going on, I wonder if other bacteria, say, from "leaky gut," could trigger a similar process. It seems as though "leaky gut" itself might be triggered by an altered microbiome, which, in turn, might be the result of a variety of strong immune responses to viruses, toxins, physical injury, etc... This might explain the multiple triggers, in that they funnel down to one cause, i.e. bacterial translocation from GI tract.]
     
    Last edited: Dec 23, 2016
    sb4, Advocate, MEMum and 9 others like this.
  20. lansbergen

    lansbergen Senior Member

    Messages:
    2,478
    Likes:
    2,673
    http://m.worldpapercat.com/1766/Article3360782.htm

    Regulation of Pyruvate Dehydrogenase Activity In Rat Fat Pads And Isolated Hepatocytes by Levamisole

    . Levamisole at 1.5 mM and 2.0 mM were as potent as insulin (1.0 mU/ml) in adipose tissue and as dichloroacetate (2.0 mM) in isolated hepatocytes, respectively, in increasing the catalytic activity of the PDH complex.
     

See more popular forum discussions.

Share This Page