The 12th Invest in ME Conference, Part 1
OverTheHills presents the first article in a series of three about the recent 12th Invest In ME international Conference (IIMEC12) in London.
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. Murph

    Murph :)

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    @Sasha @CFS_for_19_years Thanks for the welcome!

    As for questions about whether whey is meant to spur ketosis, I don't think so, but I admit I don't remember everything the doctor said when he recommended it. (The recommendation came before I'd read about *why* it might work, so I lacked a framework to integrate what he was saying. Much of the technical detail went, sadly, in one ear and out the other!)

    One thing I do recall is he said to take it after my daily activities, (which is presumably a point where glycogen stores are diminished) where it might work as a PEM preventer.

    It is whey protein isolate, hydrolysed, made with "cross-flow microfiltration." The brand is Dymatize ISO 100. I've bought whey only once, but I'd be surprised if there were not other types that are the same. As for dose, I'm taking one 31g scoop per diem, in water, but I will experiment over time.

    (My sole objection to the whey is the size of the tub it comes in - it barely fits on the shelf. Perhaps that appeals to body builders on some subconscious level.)

    The doc also recommended digestive enzymes, which I bought at the same time. They are still unopened - I'm trying to minimise the number of simultaneous changes for the sake of untangling cause and effect.
     
    Last edited: Dec 30, 2016
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  2. ash0787

    ash0787 Senior Member

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    Yes trace the chain of causation using the knowledge that the offending agent is carried within the blood and can seemingly act on the cells of different people regardless of genetic differences, this seems to be a winning strategy, they said they can use filtration techniques either mechanical or otherwise to reduce it to certain types or groups.
    Apparently there is a lot of different things in the blood though so it might take a while. Perhaps one form of that 'filtration' could be 'degradation', see how pervasive the agent is after being applied to live cells repeatedly, or vulnerable to heat / radiation damage, once you have that experiment that gives very interesting results theres lots of interesting things you can do with it.
     
  3. Hip

    Hip Senior Member

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    I am not really offering a hypothesis as such. I am just saying I am not really clear on how processing the lactic acid from exercise via liver Cori cycle could worsen PEM, or have much affect on ME/CFS, which what they propose in the Myhill, Booth and McLaren-Howard Papers.

    Though possibly the acidosis due to lactic acid might play a role in ME/CFS. In the MBM 2012 paper they mention something along these lines:
    ETC = electron transport chain (found within the mitochondria).

    So what they may be saying in this paper (if I understood it correctly) is that because it takes a lot of energy to convert lactate back to pyruvate in the Cori cycle in the liver, and because ME/CFS patients are short of energy, the lactic acid created from exercise will be hanging around for a longer time than usual in the body, because the Cori cycle may be running slow due to poor energy supplies.

    So ME/CFS patients may not only be creating more lactic acid from exercise (because their defect mitochondria may force them to use anaerobic glycolysis); but in addition, it may take them longer to clear this lactic acid, due to a slow Cori cycle.

    Which means the lactic acid will be hanging around f or a long time, causing acidosis and cellular damage, according to the MBM 2012 paper.
     
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  4. duncan

    duncan Senior Member

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    Something is missing here. Not sure this covers all the bases. What about PEM triggered by concentration?

    Exchange exertion for exercise - it will not be the same, and I think it needs to be.

    Same holds true for strident emotions, except this more readily and overtly involves muscle extremes. But intellectual exertion PEM? How does that fit? Or the simple act of focusing too long or too hard?
     
    Last edited: Dec 30, 2016
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  5. PennyIA

    PennyIA Senior Member

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    Agreed. I'd also read stuff about issues with the KREB cycle and we know some of us have issues with Methylation (which by itself has been ruled out from being an issue for everyone.

    I'm betting that any one person can survive and handle ONE of the cycles not working at par. Add stressor or toxin or virus load and introduce damage to another metabolism pathway or to more than one and I'm betting it's a combination factor that leads to a point where people start seeing serious issues.

    While I'm with everyone's eagerness to try to find something ANYTHING that can help us... I think we're just looking at the tip of the ice burg and we still have a lot to learn. The exciting bit is that I'm thinking we've finally found an ice burg instead of a bunch of false leads. This feels like it can lead somewhere real.
     
  6. Kati

    Kati Patient in training

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    Intellectual work requires more glucose to the brain. It's a work out for the brain.
     
  7. Hip

    Hip Senior Member

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    Post-exertional malaise from mental exertion could be explained by the same hypothesized mechanism for PEM that Myhill, Booth and McLaren-Howard (MBM) propose — a mechanism which is described in this post.

    In brief, the mechanism MBM propose is that a temporary loss of ATP molecules, which results from putting a defective cellular energy metabolism under strain, is the cause of PEM. You only get over PEM once these lost ATP molecules are remanufactured from scratch (via de novo synthesis, which can take several days — hence why PEM can last several days).

    Quite possibly this loss of ATP molecules could also occur in brain cells when there is significant mental exertion, thereby causing worsened cognitive and neuropsychological symptoms afterwards.
     
    Last edited: Dec 30, 2016
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  8. Marco

    Marco Grrrrrrr!

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    It's early days for this line of research but it would have been preferable if they had used additional control groups - e.g. sedentary controls or controls with metabolic syndrome (where reduced PDH complex activity/increased PDK expression is also found).

    Nevertheless, studies of muscle fibre characteristics in ME/CFS by Lane et al may argue against mere deconditioning :

    http://jnnp.bmj.com/content/64/3/362.full

    * Note : Only 37% of the cohort displayed an abnormal lactate response to exercise (Oxford criteria - ahem!).
     
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  9. Sasha

    Sasha Fine, thank you

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    Interesting experience - sorry to hear that the benefit didn't keep up.

    I know I tried whey powder at some point years ago but I can't even remember if I was already ill then or taking it for another reason!
     
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  10. Sasha

    Sasha Fine, thank you

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    Thanks, Murph - that's very helpful. I see that particular brand always comes flavoured (vanilla, chocolate, banana, etc.) which might cause migraines for me so I'll have to see if there's a nonflavoured brand with a similar amino acid profile. (I'm a bit worried that any of the amino acid products are going to give me migraines any, because tyramine seems to trigger migraines for me, as well as strong flavours, but all I can do is give it a go!)
     
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  11. TrixieStix

    TrixieStix Senior Member

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    I just saw a gastroenterologist for the specific purpose of ruling out Primary Biliary Cirrhosis as it is one of few diseases other than ME/CFS that are known to cause post exertional malaise, plus I have a lot of itching, I have an enlarged spleen, and have been more jaundiced than usual (i have a hereditary blood disease that causes me to always be jaundiced). Plus my mother died of liver failure in her early 50's and I do not know details of why. So I wanted to be certain to rule PBC out.

    The blood tests came back last week and thankfully I do not have PBC.

    If you really are worried you may have PBC you should be evaluated immediately as the sooner treatment is begun the less likely a liver transplant will be needed in the future and better chance of a normal life span. Sadly a large % of those with PBC have no symptoms until the disease has already caused significant damage to the liver.
     
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  12. TrixieStix

    TrixieStix Senior Member

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    Dr. Fluge and Dr. Mella stated this last year.... "Older ME / CFS patients have shown increased risk of B-cell lymphoma (2), especially a type (marginal zone) associated with chronic infections or with autoimmunity."

    http://www.healthrising.org/forums/...us-disorder-deserves-serious-treatments.2011/
     
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  13. Sasha

    Sasha Fine, thank you

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  14. NexusOwl

    NexusOwl Spanish advocate

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    I've been increasing my aa and protein intake for some days now and I have felt that urge to increase meals too. The hunger is unbearable. At first I thought there might be some bacterial/candida infection going on, but maybe I'm experiencing what you did.
     
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  15. alicec

    alicec Senior Member

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    There was a little discussion about this on another thread.

    Here and here are some relevant considerations.
     
  16. JaimeS

    JaimeS Senior Member

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    Whey protein improved my symptoms dramatically, but I dropped it when I dropped milk products. I'm encouraged to hear that casein is what bothers a lot of people, but I'm not certain that's the case for me.
     
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  17. knackers323

    knackers323 Senior Member

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    Same thing happens to me. Think its pretty standard when carbs are cut out. Veggies just dont keep you full for long and the body seems to process them much quicker
     
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  18. JaimeS

    JaimeS Senior Member

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    I felt this way when I first went off of carbs. It didn't last long though -- maybe a week?
     
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  19. NexusOwl

    NexusOwl Spanish advocate

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    I'm not out of carbs tho.

    Just increasing aminoacids and protein intake dramatically.

    My carbs intake hasn't even been reduced to its half, and it was my main meal source.
     
  20. JaimeS

    JaimeS Senior Member

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    You've increased protein intake and amino acids but not decreased any other food intake and you're very, very hungry? That's baffling! :confused:
     
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