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Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by adreno, Jun 19, 2012.

  1. adreno

    adreno 3% neanderthal

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    I found the following study interesting. It describes how the balance of B3 and methyl groups ultimately determine health status and aging.

    An illustration from the study:
    [​IMG]
    I must admit that I really don't have the knowledge to understand the implications of the article in depth. I'm hoping someone more knowledgeable than me will chime in.

    But as I understand it, both under- or overdosing B3 and methyl groups will lead to serious health problems. The question is, how do we find the right balance? From the full text:

    So what does this tell the many of us who are essentially megadosing on B vitamins and methyl donors? Is it safe at all? Or should we not supplement them? Are the problems related to ratio, dose or both? How would supplementing NAD or NADH change the picture?

    If I seem confused, it's because I am.
     
    alex3619 and Sidereal like this.
  2. adreno

    adreno 3% neanderthal

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    Here is another study showing that high NNMT activity is linked with Parkinson's:

     
  3. adreno

    adreno 3% neanderthal

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    Certainly, B3 deficiency is problematic. This article argues that pellagrins (patients with B3 deficiency) suffer from a myriad of infections, because pathogens apparently supply NAD. PWCs are often found to have multiple infections, and are low in NADPH, which could point in that direction. Oversupplying methyl groups would then further deplete B3. Is this why so many of us feel rotten on high doses of methylcobalamin and methylfolate?

     
    Gondwanaland likes this.
  4. adreno

    adreno 3% neanderthal

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    This study found that NAD deficiency leads to excess DNA methylation of the BDNF promoter:

    Nicotinamide adenine dinucleotide (NAD)-regulated DNA methylation alters CCCTC-binding factor (CTCF)/cohesin binding and transcription at the BDNF locus.
    This is obviously not a good thing. Decreased BDNF expression is associated with dementia, depression, bipolar disorder and suicidal behaviour.
     
    nanonug likes this.
  5. bertiedog

    bertiedog Senior Member

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    I do terribly on high dose MB12 and methylfolates but do very well when taken daily but only in relatively low amounts such as in 3 Thorne's Basic Nutrients (500 and 400 respectively). I have added in about 33 mg B3 and 20 mg B2, 100 mg B2 plus extra minerals like manganese, moly and selenium without any problems at all. Its the high dose MB12 and high dose methylfolates that are the problem my brain doesn't like it at all and sends me completely hyper.

    Pam
     
  6. learner2life

    learner2life David Pain

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    Hi Adreno,
    My Dad has been reading a book called "Niacin, the real story" which he has been trying to get me to read. From what I read and what he tells me (coming from the book) is that people should be taking 3 gms per day. I do plan on taking it when I feel like I can tolerate a change. It goes into alot of mental disorders, schizophrenia as well as helping people live longer. I really haven't read but only a few pages but it seems very interesting. Just some thoughts.
    David
     
  7. Lynn_M

    Lynn_M Senior Member

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    Niacin eats up methyl groups. It's recommended for people who are experiencing hyper effects from too much methylfolate and/or methylcobalamin.
     
  8. adreno

    adreno 3% neanderthal

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    Yes, I believe psychosis and mania have been associated with hypermethylation, so B3 might help in those cases. There is a danger of liver damage though, when taking high doses of niacin. Perhaps a lower dose of regular B3 combined with NAD would work better.
     
  9. adreno

    adreno 3% neanderthal

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    Yes, and maybe this is the reason Christine is concerned that methyl supps can deplete B2. Excess methyl groups would deplete NAD, and B2 is needed to synthesize NAD.
     
  10. place

    place Be Strong!

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    I know I am behind the 8 ball but what are the "methyl groups"? Amino Acids, the B's???
     
  11. adreno

    adreno 3% neanderthal

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    Methyl groups are the chemicals that methyl donors donate to other compounds. Methyl groups are transferred to other compounds during methylation. It is the "methyl" part of methylcobalamin and methylfolate. Other methyl donors include choline, TMG and SAM-e. All of them donate methyl groups to other compounds.
     
  12. Lynn_M

    Lynn_M Senior Member

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    A methyl group is a carbon with three hydrogens attached.
     
  13. bertiedog

    bertiedog Senior Member

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    I forgot to say that I have become very well since I was diagnosed with very poor oxygen saturation in my tissues and was advised to breathe oxygen for up to 4 hours daily. In order for me to be very well I have to continue to take physiological doses of steroid so that I am able to tolerate some dessicated thyroid and of course the low dose supplements to aid methylation and essential fatty acids plus lots of antioxidants.

    I would never have believed the energy my body now has. I believe it is an enterovirus that has caused all this damage as per Dr Chia's explanation and so a week ago I started on Equilibrant. Time will tell but meanwhile my life has turned around completely and at 64 that is wonderful.

    Pam
     
  14. Martial

    Martial Senior Member

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    Interesting studies thanks for sharing Adreno, one thing that did pique my interest before is from Dr. Lynch. He described the issue of compounding methyl donors and their implications on the rest of the b vitamins, alongside other vitamins and minerals. He mentioned that high dose methyl b12 on its own does not drastically increase methylation but the added methyl folate in higher doses alongside with it.

    When they are added together in very high doses then depletion of the other b vitamins gets diminished fairly quickly at first. After the increased demand is met then there is a sort of maintenance phase to upkeep with the extra demand. Here is a quote from him when I asked about adding additional vitamins to the methyl folate/methyl b12 combo. directly.

    " B12 and methylfolate increase methylation which puts 'burden' on cells - dividing, replicating, increased mitochondrial function, etc - so in that sense, having sufficient B vitamins, minerals on board - along with fatty acid balance and glutathione, electrolytes - are key. I've learned this the hard way and now I lecture about it ALL the time. Must support all indirect and direct pathways prior to supporting methylation - or some traffic jams will occur ie symptoms/side effects." - Dr. Ben Lynch
     
  15. adreno

    adreno 3% neanderthal

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    Yes, the golden question is of course what are the correct ratios. Seems hard to find, IME.
     
  16. Martial

    Martial Senior Member

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    The only thing I have gathered so far was that other b vitamins should be in a balanced range between 5-20 mg based on each persons response, though this is a pretty broad range as it stands. Not too minimal as to cause deficiency of other groups and or too high to burden an overload. There are multiple disorders that would require more specific attention to certain co factors though. Pyroluria for one will cause a severe b 6 and zinc deficiency also affecting biotin, magnesium, manganese, and a changing effect on fatty acid ratios.

    Seems there are a lot of unique situations for each person that could have a different response to all of this though. This is all only touching the basics as well. From what else I have seen there is also the need for additional Sam E for some, reduction or higher doses of taurine, the removal of certain sulfates as to prevent blockages for CBS up regulation, changes to methylation protocol based on specific SNPs for each person. Keeping in mind of course the changes for each genetic expression results seems highly theoretical right now.
     
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  17. alex3619

    alex3619 Senior Member

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    ... and how stable are those ratios over time and between patients? My ratio might not be your ratio, and my ratio today might not be my ratio in a year from now.
     
  18. Martial

    Martial Senior Member

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    That's the part that is really hard to say, there isn't enough known about all of this to give a good estimate. Most researchers right now are trying to formulate exactly that based on individual SNPs and symptoms that appear before, during, and after any treatment. I would hope myself that keeping things in very moderate amounts, having balance would lead to less repercussions. For the most part b vitamins are water soluble after all, the risk of running deficient is mitigated with small to moderate added supplementation. No real toxicities aside from b 6 and perhaps b 3 in mega dosing, keeping other vitamin and mineral levels in balance would solve the other issues. In this sense it seems there is some degree of leeway when it comes to it all.
     
  19. alex3619

    alex3619 Senior Member

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    The first protocol I designed back in the late 90s was highly successful until rising side effects and cost put the kibosh on it. It was essentially a broad approach, with low doses of everything that might help and was available, with a strong emphasis on B vitamins ... but at the time I was using folic acid, doh. I concur that lower doses and balanced dosage might reduce risk, especially in the long term. A corollary for that though is that lower and broader doses can exert multiple beneficial effects using multiple pathways, and so prevent an excess of a single pathway which will raise the risk of side effects.
     
  20. Little Bluestem

    Little Bluestem Senescent on the Illinois prairie, USA

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    @bertiedog, are you still around? How was your poor tissue oxygen saturation diagnosed?
     

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