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Declining NAD+ Induces a Pseudohypoxic State Disrupting Nuclear-Mitochondrial Communication...

Discussion in 'Other Health News and Research' started by anne_likes_red, Jan 1, 2014.

  1. Star-Anise

    Star-Anise Senior Member

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    @Radio Awesome! Thanks so much. I have some reading to do... S:thumbsup:
     
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  2. pemone

    pemone Senior Member

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    Just to play devil's advocate here:

    1) It is not necessarily that we have a failure to convert Tryptophan. We might have a dietary insufficiency, or alternatively we might have an absorption issue. People with fructose malabsorption have low levels of tryptophan in the blood, and fructose malabsorption affects one THIRD of all white people of European descent!! The tryptophan levels should be easy to test using any of the good nutritional eval tests? It's very worth noting that fructose malabsorption also affects folic acid levels!! Interesting that so many CFS patients have both the NAD+ production problem (maybe from tryptophan deficiency) but also have folic acid deficiencies. Interesting that those two symptoms get tied together here.

    2) Do we really want to be supplementing large doses of tryptophan? Some of that converts to serotonin and would strongly affect many other systems not just NAD+ production? Also, if we have a failure to convert tryptophan, how would supplying more tryptophan fix that?

    3) NADH is probably the one supplement you would NEVER want to take, The whole point of this paper was that the NADH is piling up in your body and is not able to convert back to NAD. As a result, the mitochondria are processing it in some very bad way that creates lots of free radicals. It would not only not solve the NAD+ problem to take NADH, but you would actually be making the damage to your body significantly worse, by increasing free radical production.

    4) The recommendation for R-lipoic acid makes great sense. This will help to process the backlog of NADH to NAD+. But the question is dosing. How much do we take, and how often do we take it? Is there any objective testing we can do for that?

    As some approximation for dosing, what kind of intravenous doses do the Europeans give of R-lipoic as a treatment for diabetic neuropathy? This might be used both to establish an upper limit for toxicity, as well as to help establish a range of effective oral doses.

    5) It seems to me the key recommendation should be for niacinimide, NMN (used in David Sinclair's mouse study), or Niagen / Nicotinamide Riboside (NR). I have read that NMN and NR may promote cancer so you use them at your own risk. What about niacinimide? I read one source that claimed studies show it is not only safer, but generates 20%+ more NAD+ conversion? I have yet to locate the original sources on this claim.

    And - the difficult question - what doses would be therapeutic? How often would we need to take it?

    6) Can you explain the riboflavin recommendation? I don't see how the MOA enzymes here would be deficient or needed.

    Point number 5) deserves its own thread. I can't believe this is not being discussed every day on this site. To me this looks like something very close to a potential cure.
     
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  3. dannybex

    dannybex Senior Member

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    Seattle
    Hi @pemone -- interesting observations. I was told I should take an NADH supplement about 2 years ago, and believe it made me a lot worse, but not certain because I was taking other things as well, BUT, the NADH was the only new thing I had added.

    About a month or so later I switched to flush-free niacin, and the next month (March 2014) there was no mention of any horrific effects.

    I'm the guy who had high levels of quinolinic acid on my OAT test, mentioned earlier in this thread, which I believe is a toxic byproduct of tryptophan metabolism to NAD(?), so it makes sense to me that supplementing with tryptophan would be a mistake (as you noted in your original post), but I'm curious -- do you think that by taking NADH, that I was not only not addressing the quinolinic issue, but was making things worse?

    And does it make sense that supplying more niacin (in forms other than NADH) would help gradually reduce elevated quinolinic?

    Thanks in advance,

    Dan

    p.s. I believe that since this thread was started 2 years ago, there are indeed more threads on the importance of niacin, although it's still not talked about 'every day'. :)
     
  4. pemone

    pemone Senior Member

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    I made myself significantly more ill by taking B vitamins. They sped up my metabolism, felt bad, and they sent my pituitary hormones skyrocketing. I don't really supplement very much now.

    The title of this thread is about NAD+ and its association to a pseudohypoxic state. That makes sense since NAD+ is a marker for functioning of the electron transport chain that works with aerobic metabolism. In a hypoxic state the ETC ramps down and NAD+ is not getting created.

    I would not be looking at niacin or any supplement to create NAD+. You might want to look at oxidative therapies, particularly ozone, since those supposedly result in a cascade of NAD+
     
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  5. Justin30

    Justin30 Senior Member

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    A little tid bit of information regarding all this info, Lipopolysacharides/LPS have been implicated in blocking the conversion of Tryptophan to serotonin and other critical neurotrasmitters as per one of the top specialists.

    Im might not have this completely correct but this info seems very relevant in large proportion of ME/CFS cases. Screws up brain and mitochondris production via endo and neurotoxins.
     
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  6. Justin30

    Justin30 Senior Member

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    KYNURENIC ACID is what I have just been tested for so something definately going on with this thread and what the top specialist believes. I am going to ask him about.
     
  7. rippe

    rippe

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    germany
    Hi,
    maybe it is important to look where all the NADH : NAD+ ratio is actually coming from? Yes it comes from Complex I but as far as I know Complex IV is supposed to regenerate NAD+ by using oxygen. So it would be important to look at Complex IV which needs sufficient copper! I mention this because in my own experience I got mitochondrial disfunction and lactic acid mainly from a long term copper deficiency which resultes in low Cytochrome-c-oxidase / Complex IV function and low NAD+ regeneration which then will be regenerated by Lactate Dehydrogenase by sacrificing Pyruvate into Lactate. I assume the body then has to use more tryptophan to build NAD and tryptophan is then missing for serotonin and melatonin production? So for me it is comprehensible why muscle pain and sleep problems often come in pairs. So I think helping out with some NR supplementation along with fixing any possible copper and/or Ubiquinol deficiencies for Complex IV might be a reasonable trial? I know there is more then just this but i rarely hear about this connection/dependency between Complex I and IV (copper) which results in high NADH : NAD+ Ratio.



     
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