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Does methyl-absorbing niacin neutralise methyl supplements?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by Creachur, Oct 9, 2017.

  1. Creachur

    Creachur

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    I want to take niacin to help improve energy (in the Electron Transport Chain) in the mitochondria.

    However, I believe that niacin absorbs methyl groups.

    I understand some of the basic about methylation but not the details. I have a problem with lack of energy and find supplements like methylfolate and B12 are very helpful. These supplements could be doing other useful things than provide methyl groups but I have the general impression that more methyl is better for me.

    Would a daily dose of 250 or 500mg niacin counteract many of the benefit of other supplements which might be providing useful methyl groups?
     
  2. ljimbo423

    ljimbo423 Senior Member

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    Hi @Creachur -

    Yes it most likely would. However, in the form of niacinamide (non-flush b-3) instead of Niacin (nicotinic acid) it would not be a problem. Niacinamide does not use up methyl groups like nicotinic acid does.

    If I take 50mg a day of nicotinic acid, it wipes me out. I feel tired, heavy, and have significant brain fog. The same dose of niacinamide, I have no problem with.

    Jim
     
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  3. Mary

    Mary Senior Member

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    @ljimbo423 - I didn't know that about niacinamide vs. niacin, that's good information.

    @Creachur - I do take niacin at night before bed and in the middle of the night for sleep - it's quite helpful for sleep and it doesn't make me tired during the day. However, if I take niacin during the day (which I don't any more), it does make me tired. So I'm getting a good dose of niacin (500 mg before bed and 400 mg middle of the night) but it doesn't seem to be negatively affecting my energy.

    Other supplements which have increased my energy (in addition to methylfolate and MB12) are B1 and P-5-P (B6). Both made a noticeable improvement. d-ribose helps me with energy also. I take 15 grams a day in two divided doses.
     
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  4. ljimbo423

    ljimbo423 Senior Member

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    I sometimes will take a small dose of niacin at night to help me sleep, maybe 25-30mg. I'm assuming it helps me sleep because it slows methylation and that makes me more tired.

    Jim
     
  5. Mary

    Mary Senior Member

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    That may be part of it, but niacin and niacinamide do something to GABA receptors - I think they sensitize or stimulate them, which I think is the main help with sleep. I take niacin together with l-theanine (and bunch of other stuff!) and it seems to be a good combo.
     
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  6. alicec

    alicec Senior Member

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    Niacinamide (aka nicotinamide), not niacin (aka nicotinic acid), is directly methylated by the enzyme nicotinamide N methyltransferase (NNMT). Here is the wikipedia entry.

    The enzyme catalyses the methylation of nicotinamide using SAMe as methyl donor.

    Here is a more detailed review of the enzyme or if you don't want to wade through the detail, here is just the abstract and figures.

    If you look at box 2, or the fig 2nd from right on the abstract page, you will see that it is nicotinamide, not niacin, that is directly cleared by the methylation pathway.

    Of course niacin may be indirectly converted to nicotinamide, so could ultimately be cleared by this pathway also, but only after it has participated in metabolism via NAD+/NADH.

    NNMT is a minor activity in liver where most methylation occurs and the paper concludes, after discussing various studies in cells and whole animals,

    So large doses of nicotinamide might reduce the SAMe/SAH ratio and so affect methylation, but it depends on many other things as well. I doubt that niacin would do it and if it did have any effect, it would take time.
     
  7. Creachur

    Creachur

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    Thank you to everyone (Jim, Mary, Alice) who has replied. I appreciate it.


    So it seems niacin (nicotinic acid) would not affect methyl groups. Also, it would probably need large doses of nicotinamide to affect SAMe enough to affect methylation.

    If you recall my original message, I am particularly interested in taking niacin or niacinamide to help improve the function of my Electron Transport Chain and I believe it is in fact this part of metabolism which you are referring to when you wrote "NAD+/NADH" above. Unfortunately my biochemistry is a bit weak, so am I right in reading your post as saying that nicotinic acid takes part in metabolism via NAD+/NADH but not niacinamide?

    In other words, I should take niacinamide because (a) it does not affect methylation and (b) it helps the Electron Transport Chain. Is this understanding correct?

    Thank you for any further clarification.
    Regards,
    Creachur


    PS: As background, this interest in niacin started for me when I was told by someone that "Niacin is able to increase NAD+, and therefore works to increase NAD-levels in cells similar to nicotinamide riboside".
     
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  8. Learner1

    Learner1 Professional Patient

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    Niacinamide (nicotinamide) may indeed impact methylation as stated above.

    My doctor told me to up my niacinamide if I felt overmethylated.

    As for having more energy, I think we're individuals and what will work for each of us may differ. I have tried nicotinamide riboside in high doses to no effect, but Enada sublingual NADH gives me more energy either 15 minutes. There are studies out there that will tell you that nicotinamide riboside increased energy in athletes.

    Also, you'll want to ensure adequate supplies of other mitochondrial nutrients, such as CoQ10 and carnitine to encourage optimum ATP production. And ensure health of mitochondrial membranes through NT Factor. And remove toxins from mitochondria with ALA or PolyMVA.
     
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  9. ljimbo423

    ljimbo423 Senior Member

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    Hi @Creachur - This is an email exchange between Dr. Ben Lynch and a client that gave him permission to post this. Dr. Lynch is a leading expert in methylation.

    Dr. Lynch-
    http://mthfr.net/overmethylation-and-undermethylation-case-study/2012/06/27/

    Dr. Lynch makes it very clear that niacin is a "methyl sponge". If you go to his site he also makes it clear that niacinamide does not use up methyl groups the way niacin does. I have had the very same experience as Dr. Lynch's client above, dozens of times over the last few years treating overmethylation with niacin.


    Both niacin (nicotonic acid) and niacinamide are converted to NAD/NADH, however, niacin uses up a lot of methyl groups and niacinamide does not.


    Yes. Niacinamide will be converted to NAD and NADH so that it can be used in the Electron Transport Chain and not have a negative effect on methylation.

    Hope this is helpful.:)

    Jim
     
    Last edited: Oct 10, 2017
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  10. alicec

    alicec Senior Member

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    No, both niacin and niacinamide can be converted to NAD+/NADH and so be used in the ETC.

    See for example the simplified diagram in Fig 2 in this article. It doesn't show all pathways, eg the methylation of niacinamide, but does show how niacin and niacinamide are both converted to NAD (and of course NADP) and used in redox reactions such as the ETC.

    No, niacinamide may affect methyl groups, it is much more likely to do so than niacin. Whether it does with you is something you would have to determine empirically.

    All I can suggest is that you try both niacin (be careful of the flushing effect - start low and increase slowly) and niacinamide and see what effect they have in your system.

    Both of them have separate effects independent of their action in the ETC and these could influence your response to the supplements.
     
  11. alicec

    alicec Senior Member

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    Yes I have read Lynch's claims about methyl sponges, along with those that proliferate on the internet offering advice about methylation.

    I simply say what is the mechanism?

    It is niacinamide that is cleared by methylation via the enzyme NNMT.

    If you look at sites detailing niacin and niacinamide metabolism, there is no enzyme listed that methylates niacin.

    See for example the entry in KEGG pathways. If you look in the top left hand section you will see niacinamide being converted to N-methyl nicotinamide via the enzyme NNMT, as I described above.

    If you look immediately below niacinamide, you will see nicotinate (aka niacin). It is taken in several directions as part of different metabolic pathways and only one which is terminal or a clearance reaction. This is the conversion to nicotinurate.

    I didn't canvas this in my previous post because I didn't want to overcomplicate things. This clearance reaction involves the addition of glycine - ie one of the phase II detox pathways which occur predominantly in the liver and which help the body excrete excess or unwanted metabolic products or exogenous substances.

    So excess niacin is glycinated, excess niacinamide is methylated.

    So I repeat, if Lynch and others claim that niacin is methylated, how does it happen?

    I have no doubt the Lynch is knowledgeable about many things and has been helpful to at least some patients, but on this issue he is wrong.
     
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  12. ljimbo423

    ljimbo423 Senior Member

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    Hi @alicec- Niacin works for over-methylation at doses as low as 50mg. I have been using it for a few years like this, very successfully.

    It works and it works fast, usually within 30-45 minutes. There are many posts here at Phoenix Rising of people that have had the very same results and niacinamide just don't work.

    So I respectfully disagree.

    Jim
     
    Last edited: Oct 10, 2017
  13. ljimbo423

    ljimbo423 Senior Member

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    Hi again @alicec - I just thought of something. A reason why niacin might work for overmethylation other than using methyl groups. It's my understanding that increasing methylation increases neurotransmitters.

    Could it be that niacin somehow lowers neurotransmitters like dopamine or epinephrine. Thereby stopping over-methylation symptoms without using methyl groups?

    Jim
     
  14. alicec

    alicec Senior Member

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    You find niacin helpful but you don't know that it is doing so by reducing over-methylation. You believe that because Lynch or someone else has told you so.

    Again I repeat there is no known mechanism for this reaction - niacin is not methylated.

    I find niacinamide helpful - it has a calming effect and helps sleep. Some might say this is because it is reducing over-methylation (not that I think I am overmethylated). It could just as easily be because of its effects on GABA, or for some other reason.

    I don't really know why niacinamide rather than niacin suits me, nor I suggest do you know why niacin is better for you.

    Both substances affect many different systems and the ultimate effect of a relatively large dose will depend on the individual balance of those pathways in any individual.

    I doubt it would be an effect on neurotransmitters if as you say the effect happens quickly. Possibly it could have something to do with vasodilation and increased blood flow via effects on the niacin receptor.
     
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  15. pattismith

    pattismith Senior Member

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    I have not fully understood why, but it seems that Electron transport chain works better when the ratio NAD/NADH is high... NADH is an inhibitor for some enzymes like Pyruvate Dehydrogenase or Glycine cleavage system, so maybe a start of an explanation?


    I wonder if taking directly NAD would help instead of Niacin or Nicotinamide, but couldn't find the answer.

    Here what selfhacked says about it:

    "8) Nicotinamide Riboside
    Nicotinamide riboside (NR) is the best supplement to increase NAD+.

    Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with positive effects on energy metabolism and neuroprotection. These work by increasing NAD+ (R).

    In a study published in Nature, human blood NAD+ can rise as much as 2.7-fold with a single oral dose of Nicotinamide Riboside in a pilot study of one individual (R).

    The study also mentioned that there’s a “distinct and superior” effect compared to nicotinic acid and nicotinamide (R).

    Mice that consume NR also have elevated liver NAD+ levels (R).

    Doses of 100, 300 and 1,000 mg of NR produce dose-dependent increases in blood NAD+ "

    https://selfhacked.com/blog/nad-important-increase/#8Nicotinamide_Riboside
     
  16. Creachur

    Creachur

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    Hello Pattismith. I found that Nicotinamide Riboside is far too expensive, so I turned to niacin as a second best.

    One research team which looked into Nicotinamide Riboside had told me that "niacin is able to increase NAD+, and therefore works to increase NAD-levels in cells similar to nicotinamide riboside".

    Then I found some types of niacin might reduce methyl groups, so I posted this thread.


    .
     
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  17. pamojja

    pamojja Senior Member

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  18. pattismith

    pattismith Senior Member

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    if you look at the link I put in my previous post (from selfhacked), you will find a long list of things to improve your NAD level.:thumbsup:

    Fasting and fructose are on the list.

    Strangely after I had my first major crash, i was eating very little (I went from 52 to 46 kilos between 2002 to 2007, for 1m69), and honey was a big part of my "diet"....And my condition did improve in some aspects but not all of them.

    You should have a look at this page, if I had known it before, I bet it would have helped me...:)
     
    Last edited: Oct 12, 2017
  19. Creachur

    Creachur

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    @pattismith
    I took a look at the site you mentioned and the author seems very enthusiastic! He quotes so many studies that I have difficulty assessing which of the study results are reliable and which need to be confirmed. Nevertheless he brings up a lot of topics which give a lot of food for thought.
     
    Last edited: Oct 13, 2017
  20. pattismith

    pattismith Senior Member

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    Today I start a trial with Nicotinamide Riboside!


    Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3

    Abstract
    "Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD+/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early‐ and late‐stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD+ levels are a promising treatment strategy for mitochondrial myopathy."

    @BeautifulDay @Learner1

    Full text available, http://embomolmed.embopress.org/content/6/6/721

    Another paper about NAD+ supplementation to treat MitoD:

    NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease

    NAD+ is a substrate activator of Sirtuin 1, a key player of mitochondrial biogenesis


    Parp1 inhibitors and nicotinamide riboside increase the NAD+ content in tissues


    These compounds improve the phenotype of a mitochondrial disease mouse model


    These are potential therapies for human mitochondrial disorders

    Summary
    Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation of mitochondrial biogenesis has been proposed as an effective means to correct the biochemical defects and ameliorate the clinical phenotype in these severely disabling, often fatal, disorders. Pathways related to mitochondrial biogenesis are targets of Sirtuin1, a NAD+-dependent protein deacetylase. As NAD+ boosts the activity of Sirtuin1 and other sirtuins, intracellular levels of NAD+ play a key role in the homeostatic control of mitochondrial function by the metabolic status of the cell. We show here that supplementation with nicotinamide riboside, a natural NAD+ precursor, or reduction of NAD+ consumption by inhibiting the poly(ADP-ribose) polymerases, leads to marked improvement of the respiratory chain defect and exercise intolerance of the Sco2 knockout/knockin mouse, a mitochondrial disease model characterized by impaired cytochrome c oxidase biogenesis. This strategy is potentially translatable into therapy of mitochondrial disorders in humans.

    full text available
    http://www.sciencedirect.com/science/article/pii/S1550413114001648

     
    Last edited: Oct 16, 2017

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