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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Pyruvate Dehydrogenase Deficiencies and Cures?

Discussion in 'General ME/CFS Discussion' started by debored13, Nov 2, 2017.

  1. debored13

    debored13 Senior Member

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    so... I recall Ron Davis saying that the conversion of pyruvate into acetylCoA was somehow blocked in CFS patients. then there's the fluge/mella study showing lower levels of pyruvate dehydrogenase, the enzyme that catalyzes that reaction.
    So then I looked at what is a treatment for pyruvate dehydrogenase complex deficiency, and also symptoms of that disease. That disease seems more severe in some ways than CFS, but I wonder if that is simply because it comes on earlier... or is a more complete deficiency in pyruvate dehydrogenase than CFS is. One of the main problems seems to be the buildup of lactic acid, which people with CFS also have.
    One of the treatments is a ketogenic diet. One of the other treatments being investigated is phenylbutyrate therapy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102924/

    Has anyone here tried keto or phenylbutyrate therapy with any success?
     
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  2. debored13

    debored13 Senior Member

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  3. debored13

    debored13 Senior Member

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    I also wonder if there's any benefit in triheptanoin. It is in trials to treat pyruvate carboxylase deficiency, huntingtons, ALS
     
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  4. Learner1

    Learner1 Forum Support Assistant

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    If you search here, you'll find several discussions on ketogenic diets. Many of us are on low carb, ketogenic diets.

    There's also a lot of discussion of pyruvate dehydrogenase.:)
     
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  5. debored13

    debored13 Senior Member

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    yeah I have found that... i'm too exhausted to go see which threads are active and which aren't. it seems like some of the more science-minded posters have made pretty good summaries of the research on this stuff. after watching ron davis' update on ME/CFS, I am thinking "ok, there’s no fucking way I’m going to figure out what in the blood is causing this to happen, so is there a cruder way to compensate for this, like supplementing something that can increase pyruvate dehydrogenase?" or supplementing various intermediates in the kreb's cycle?
     
  6. debored13

    debored13 Senior Member

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    my problem with keto is simply I don't have great digestive enzymes and have been a vegetarian for most of my life
     
  7. Learner1

    Learner1 Forum Support Assistant

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    Well, many of us take digestive enzymes.;)

    As for being vegetarian, I know you probably don't want to hear this, but it may not be serving you well. In the metabalomics studies, ME/CFS patients were found to be deficient in amino acids, B12, and lipids which comprise cell and mitochondrial membranes.

    My mom was a vegan for 5 years and I used to be mostly vegetarian, but we learned the hard way that humans were meant to be omnivores. We need to feed our bodies the nutrients to properly run our biochemistry.

    Something to consider, though I know it likely doesn't come easy.
     
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  8. Learner1

    Learner1 Forum Support Assistant

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    All good thoughts.

    While we're all looking for the magic pill, the incinvenent truth is that our bodies have complex biochemistry and a small handful of interventions isn't likely to fix us.

    Until the scientists come up with something better, many of us have concluded that if PDH isn't working, then we're best off feeding with fats and protein, and not depending on carbs.

    For each step in the Krebs cycle, there are cofactors that help get to the next step, along with things that inhibit each step. These can be manipulated.

    But there's more to it than that. Mitochondria need methylation working properly. They need lipids for membrane health, and they need carnitine, CoQ10, B3, etc.

    You really need to look at all the nutrients the body requires, amino acids, lipids, B vitamins, antioxidants, minerals, phytochemicals, etc. And to ensure you're getting enough of all of them.

    You might also look into Robert Naviaux's Cell Danger Response paper where he lays out a number of biochemical pathways and maps them from bad to good - when cells sense danger, their chemistry changes, and becoming healthy is a matter of moving from the threatened state to the healthy state. You can manipulate them and ideally, you'll begin to improve.

    There's a lot to all of this, and no one has all the answers yet...but we all keep asking and thinking and trying...
     

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  9. debored13

    debored13 Senior Member

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    I have no attachment to vegetarianism. at the urging of my nutritionist, i'm introducing meat... i was already a sort of pescetarian but didn't eat fish enough to be used to it. My problem is I don't know if i'm ready to do keto until i get better at digesting meat/protein. I know I'm low in a specific digestive enzyme from testing (i forget which) which bears out how I have a hard time digesting heavy food and a lot of upset stomach. So I guess I want to work on my digestion before I just go straight to doing keto. Does keto just bypass pyruvate oxidation altogether?
     
  10. pattismith

    pattismith Senior Member

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    very interesting! phenylbutyrate is worth a try, it is also a treatment for ammonia detox.

    The first treatment to try for PDH impairment is Thiamine, co-factor of PDH:

    this study is about babies under 2 years diagnosed with PDH deficiency:

    [Thiamine-Responsive and Non-responsive Patients with PDHC-E1 Deficiency: A Retrospective Assessment
    Seventeen patients received thiamine treatment: eight did not respond, four showed sustained response and the others responded temporarily/questionably. Sustained response was noted at thiamine doses >400 mg/day. ........ However, this distinction is equivocal and treatment with thiamine (>400 mg/day) should be commenced on all patients suspected of having PDHC deficiency.]

    As you notice, the dose of thiamine is very high,if you compare it to the small weight of a baby.

    Some ME patients here seems to respond well to high Thiamine dose.

    I do myself benefit from high Benfothiamine doses, but sometimes have thiamine injections when it is not enought, and also supplement with B12 injections (hydroxo B12).

    Keto diet has been tryed for PDH deficiency with some successes and some ME patients are doing well on it, (although pancreatitis can be a side effect in some cases)

    If you have poor enzymes, maybe a enzyme supplementation could help?
     
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  11. debored13

    debored13 Senior Member

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    i have been taking a b stack but may try megadosing thiamine,
    can i get thiamine injections?

    I have used up a lot of spoons but i feel a lot closer to understanding this disease than i did a few weeks ago, so i'm feeling hyped/manic even tho i'm tired
     
  12. debored13

    debored13 Senior Member

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    is there any way we can do a megathread on cellular respiration? it seems like it's becoming the most likely etiology of CFS, therefore it seems really like a good idea to do a megathread to post studies AND anecdotal evidence. bioassaying different substances that look like they should work is after all sort of how shulgin discovered the activity of a lot of drugs. It's all we got at this point, I think we should try it
     
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  13. pattismith

    pattismith Senior Member

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    yes it's vast task that could be done, but it is beyond my strength for now. :lol:
     
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  14. debored13

    debored13 Senior Member

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    I guess what I mean is a thread that gets pinned... that's a question for a mod. I know other people have started threads on the same topic, which is why i think they should all be merged... I'm not the most scientific minded person but there are posters on this forum who have not only distilled the gist of Davis' research/most recent update, but made theories combining his findings with Naviaux's theories on purinergic signalling... we should have a megathread for this shit. the fact is, we are all making little discoveries, but are spoonies, so we can't do all of it alone... but if we combine all our efforts I sincerely believe we can get a clear picture of the etiology of CFS, and then do some bioassays and test the most likely things
     
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  15. echobravo

    echobravo Keep searching, the answer is out there

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    True. I was a vegetarian for almost 15 years, and had to give it up because of increasing health issues - pain, headaches, fatigue, colds. Then in 1996 B12 deficiency. This was only the beginning..
     
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  16. echobravo

    echobravo Keep searching, the answer is out there

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    Check @alethea s recent postings on taking active forms of thiamine and co-factors.

    Yes, fatty acids convert to Acetyl-CoA not relying on PDH enzyme complex. However, Fluge Mella indicate that ME patients have inhibited fatty acid metabolism as well, but they don’t go into detail. Keto has not given me more energy or less PEM so far, but might have to to with digestion and low enzymes and bile.
     
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  17. pattismith

    pattismith Senior Member

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    what you are looking for is a synthesis. Someone already started a thread on an unified theory here.:thumbsup:
     
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  18. rodgergrummidge

    rodgergrummidge Senior Member

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    A very nice summary @debored13 and great insight. There has been much discussion in these forums on the possibility that CFS is due (in part) to reduced PDH leading to reduced respiration and lactic acidosis. There has also been much discussion about the use of ketogenic diets to bypass PDH blocks. But I dont think I've seen any one person hit so many "PDH nails" on the 'CFS-head' in one go........ nice work @debored13 . you read the science well!

    The short answer is yes.
    When carbohydrates are abundant, glucose enters the glycolytic pathway to produce pyruvate and lactate. However, if PDH is defective, pyruvate is not converted to AcetylCoA. Instead pyruvate is converted to lactate which (in some cases) lead to lactic acidosis.
    The keto diet is very low carbs and so very little glucose is available for glycolysis. With reduced glycolysis, only very low levels of pyruvate and lactate are produced and so the potential for lactic acidosis is reduced. In addition, because the keto diet results in reduced glycolytic energy production, cells compensate by utilizing alternate fuel sources derived from fatty acids and amino acids. Because these alternate fuel sources enter the TCA 'after PDH', they are not affected by PDH deficiencies. Thus on a keto diet, oxidation of fatty acids and amino acids (not all) provide the fuel for ATP production in the mitochondria. In extreme PDH deficiencies (eg. new borns with genetic deficiencies) where pyruvate cannot be converted to AcetylCoA, patients can be 'treated' (managed) with a keto diet.

    I did some quick searches of these forums, but did not find many clear success stories where CFS patients had significant and sustained recoveries with keto diets. But just in case I missed some posts, I'll raise the question again:

    Has anyone with ME/CFS had significant and sustained recoveries with keto diets?

    If so:

    • what was the % calories composed by carbs in the keto diet?
    • how long before the keto diet gave significant improvements
    • what CFS symptoms did the keto diet improve?
    • were blood/urine ketones measured to confirm ketosis?
    • How much improvement in CFS symptoms was obtained?
    • any other comments?
    great stuff

    Rodger
     
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  19. rodgergrummidge

    rodgergrummidge Senior Member

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    great idea @debored13 !!
     
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  20. Learner1

    Learner1 Forum Support Assistant

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    I haven't had a full recovery as there are other factors beyond lack of pyruvate making me ill, but keto definitely reduced my symptoms:
    • what was the % calories composed by carbs in the keto diet?
    About 10%
    • how long before the keto diet gave significant improvements
    Within 2 weeks
    • what CFS symptoms did the keto diet improve?
    Brain fog, cognitive dysfunction, fatigue
    • were blood/urine ketones measured to confirm ketosis?
    They were measured multiple times on lab tests as well as using keto strips from Wal-Mart
    • How much improvement in CFS symptoms was obtained?
    Enough to keep me on the diet for several months
    • any other comments?
    I did it using C8 oil and endogenous ketones. I've switched to low carb Paleo and don't obsess about ketosis and have maintained what I gained.

    But, like I said, this isn't the one magic bullet, I also have infectious and immune issues that are contributing greatly to my illness, do I need to use multiple strategies and not just this diet.
     
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