Agents for Change: The 10th Invest in ME International ME Conference, 2015 - Part 1
The 10th Invest in ME International ME Conference (IIMEC10) was held, as usual, in the Lecture Theatre at 1 Birdcage Walk in Westminster on May 29th, 2015.
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'Adding Pyruvate makes ME cells normal' - What questions does this prompt?

Discussion in 'General Treatment' started by AdamS, Apr 11, 2017.

  1. Jesse2233

    Jesse2233 Senior Member

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    @Hip don't want to derail this thread, but I got test results today showing high levels of pyruvate and low levels of lactate, would those findings then validate Fluge/Mella and not Ron?
     
  2. Hip

    Hip Senior Member

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    I wouldn't know how to interpret lactate and pyruvate level test results, and what the results entail. There is some info on the lactate/pyruvate ratio test here, but I am not sure how this would connect to Fluge & Mella's and Ron Davis's hypotheses.
     
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  3. adreno

    adreno Learned helplessness

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    I also showed high pyruvate on a urine amino acids test. So I doubt adding more would help.
     
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  4. AdamS

    AdamS

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    Yeah from what i've read, the signs seem to point towards an inability to utilise pyruvate properly rather than a shortage of it. Your reply is quite timely actually because I was just reading @Jesse2233 's thread HERE which shows high levels of pyruvate from Genova CardioION test results. This would certainly suggest to me that pyruvate is being produced, but it is accumulating rather than being utilised.

    I'd be interested to know what % or ratio of pyruvate is accumulating in the cytosol vs in the mitochondrion. If it was all or mostly accumulating in the cytosol, one could assume that there could be a problem with the transport protein pyruvate translocase which facilitates the transport of pyruvate into the mitochondria. I'm not sure if this is the case though, the reason it came to mind was because of the action of 'adding' pyruvate described by Davis, if the pyruvate can't be 'added' or moved at a regular rate of flow into the mitochondria then I guess it can't be utilised or could in fact down-tune the cell, something we see in the hypometabolic state.

    [​IMG]
     
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  5. Hip

    Hip Senior Member

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    Nice image, AdamS. It's good to have a clear diagram to refer to when trying to understand these things through the veil of brain fog.

    I was looking at how pyruvate gets transported into the mitochondria when I was trying to learn about all this stuff a few months ago.

    I understand that pyruvate diffuses across the outer mitochondrial membrane just on its own, but pyruvate requires a dedicated transporter protein to ferry it across the inner mitochondrial membrane. The name I learnt for that transporter protein is the mitochondrial pyruvate carrier (MPC), but I think pyruvate translocase may just be another name for the MPC (though I am not entirely sure — the MPC phrase seems to be more commonly used).



    That's an interesting question. I wonder if there is any easy way to determine that ratio experimentally.

    There may of course be different subsets of ME/CFS patients, with each subset having a different sort of blockage in their energy metabolism.

    This is what they found in the Myhill, Booth and McLaren-Howard (MBM) studies on ME/CFS energy metabolism: the MBM studies discovered that there were different patient subsets, with blockages in different areas of energy metabolism.

    In MBM, the main blockage points were in: the mitochondrial translocator protein (aka ATP-ADP translocator, or the adenine nucleotide translocator), which is the mitochondrial membrane protein that transports the ATP generated in the mitochondria into the cytosol of the cell, as well as having the job of transporting the ADP (= the spent ATP) out of the cytosol and back into the mitochondria for recycling; and there were also blockages in oxidative phosphorylation itself (the mitochondrial process that recycles ADP back to ATP).
     
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  6. AdamS

    AdamS

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    From Wikipedia:

    'PDK1 shunts Pyruvate away from the citric acid cycle to keep hypoxic cells alive' - I found this very interesting, it would explain the accumulation of un-used Pyruvate and also the low power state which keeps cells alive but leaves us functioning extremely poorly.

    From Fluge & Mella's paper:

    AMPK: We know that AMPK activation is abnormal in ME/CFS patients. AMPK is activated in response to stresses that deplete cellular ATP supplies such as low glucose, hypoxia, ischemia, and heat shock.

    HIF-1 - Can we target this and inhibit it? Would doing so downregulate/inhibit PDK1 and thus allow PDH to function more normally, resulting in more pyruvate getting into the citric acid cycle?

    From Cort's recent Stanford Paradox article on Health Rising:

    I'm piecing stuff together here, but it seems like hypoxia/low oxygen is pretty key here.
     
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  7. Jesse2233

    Jesse2233 Senior Member

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    Reminds of Dr Bell's findings on low blood volume. Tissues aren't getting enough oxygen because there's not enough blood. His solution was daily IV saline treatments for a year. Brought one woman from being bedridden back to work
     
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  8. melihtas

    melihtas

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  9. ljimbo423

    ljimbo423 Senior Member

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    Bacterial Lipopolysaccharides (LPS), like from a leaky gut, can cause an increase in HIF1, a decrease in oxygen consumption, an increase in PDK1 and therefore an inhibition of PDH.

    LINK
     
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  10. AdamS

    AdamS

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    @ljimbo423 Interesting stuff, i've always wondered whether my gut has been responsible for ME all along. LPS certainly could be a factor!
     
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  11. ljimbo423

    ljimbo423 Senior Member

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    I think the gut is where it starts, but that's just the beginning. After 10 years of reading and research, I think the immune activation and oxidative stress from the LPS causes a domino effect. The results of which are, neuro-inflammation, mitochondrial dysfunction, methylation dysfunction, immune dysfunction and more.

    Treating the gut though, can be, and often is extremely difficult and complicated. Having said that, I feel better than I have in years, by treating my gut.
     
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  12. AdamS

    AdamS

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    Glad to hear that you're feeling better than you have done in years! Yeah I wouldn't really know where to start with the gut, it does seem like a complex puzzle to crack. I tried eating lots of Sauerkraut and a range of expensive probiotics to begin with but noticed little difference in overall energy/functioning.
     
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  13. ljimbo423

    ljimbo423 Senior Member

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    You have to have the tenacity of pit-bull holding onto the last bone on earth!:D It really has been and is, a huge ongoing commitment.
     
  14. *GG*

    *GG* Senior Member

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    What are you referring to? Seems like my gut has gotten better, not sure why. Been on LDN since 2009, until relatively recently. Did raw milk years ago, that seemed to help some. Was taking Creon (script) because of diarrhea. Rarely have diarrhea now!

    GG
     
  15. alex3619

    alex3619 Senior Member

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    Do we have details of the pyruvate experiment? Two cautions come to mind without those details:

    1. Supra-physiological doses were used, and directly absorbed. No matter a patient's blood test its not relevant. The dose (concentration) used was far higher than the human body reaches. Ron is not planning to use this clinically, I think that says what we need to know.

    2. The outcome measure might not mean the cells are normal, just normal on that one measure.
     
  16. Murph

    Murph :)

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    https://www.ncbi.nlm.nih.gov/pubmed/19364913

    When you talk hypoxia and ATP you're also straying into the vascular areas that can provide that involve the endothelium and can provide that POTS-ME/CFS linkage.

    http://www.sciencedirect.com/science/article/pii/S2211383512001669
    https://www.ncbi.nlm.nih.gov/pubmed/19364913

    For example:

    Autoimmunity/genetic problems -> endothelial problems -> Low vascular responsiveness -> Low ratio of blood volume to circulatory system volume -> low oxygen absorption -> failure to maintain homeostasis -> immune response including signalling molecules that start hypometabolism

    is just one of many possible linkage chains. Such chains may coexist and will interlink. It's going to be a network of cycles, not a one way street, of course.
     

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