Question about niacin and niacinamide

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  • #3776 Reply



    I have a question about niacin and niacinamide.

    Reading the info on this web site I learned that niacin of even small intakes quenches methylation. Important info to those of us on methylation protocols. It is also my understanding that in vivo, niacin can convert to niacinamide but the reverse is not the case (at least at an effective rate in most people).

    Doing some research online, I found that niacinamide is converted to 1-methylnictonamide via Nictonamide N-methyltranferase with the reactions S-adenosyl-L-methionine + nicotinamide = S-adenosyl-L-homocysteine + 1-methylnicotinamide.

    So is the quenching actions of methylation by niacin, indirect, in that it is first converted to niacinamide and then SAMe is converted to SAH?

    Does this mean in fact that supplementation with niacinamide is just as likely to reduce methylation?

    I ask since one of my doctors put me on 500 mg of niacinamide a day supposedly for Krebs cycle support among other things. In the past, attempts by other doctors to put me on high dose niacin (on order of 1.5-2 grams / day in divided doses) devastated me even ignoring the awful flushes.

    I suspect we all need some B3 supplementation, so what is your suggestions? Just a small amount? Does it matter which type?

    Thanks ahead of time :)

    #3782 Reply


    Hi David,

    I also am trying to work out dosage for my son who has mental health problems and is an overmethylator.  In all the books by Dr Carl Phfeifer, Eve  Edleman, (an excellant book on Natural Healing for  Schizophrenia) Title of book.   Plus Dr Abam Hoffer, they are all advocating taking Niacin and or niacinamide for people who are overmethylators, which means their histamins levels are low. On page 27 of Eve Eddelmans Book,  she says B3 is important in Histapenia, pyroluria, and other disorders, deficiency has been associated with irritablity, apprehension, sensitivity to light, hyperacute sense of smell and auditory and visual hallucinations.  and suggests taking 25-1500,mg, 2x/day. Along of course with other nutrients.

    Dr Ben in his formula for B complex Plus, has 200mg of niacinamide in the formula.

    On the other hand this web-site is saying dont take too much as it mops up methylation,  but if a person is over-methylated surely they need B3 for this very reason.  Confusing, can someone enlighten us?

    Have you tested for Histamine, Daivd. This seems to be a large factor in whether ou should take it?

    #3785 Reply


    Hi Grace.

    It is pretty hard to my knowledge to directly test for histamine as a serum level is not necessarily indicative of what is stored in tissues, etc. The exception being histadelia but those are usually under-methylators. Histapenia is low histamine and presumably over-methylation. Over-methylation usually means no or little MTHFR defects (not sure but seems to make sense). I have read the works of Pfeiffer et al and Hoffer et al. and there seems to be some interesting ideas but also some conflicting ideas as well. The main one being they claim that histadelics should not touch folates but I think that is before better understanding of the folate and methylation cycles. I think histadelics (high histamine) are under-methylators. I think they may have stumbled onto the issues some people with severe low methylation have with folic acid which can lead to big problems. But back then the supplements with the L-5MTHF were not available.

    What I do know is if I take even 50-100 mg Niacin (not niacinamide) with no food, I flush. I even tried a high dose niacin regime in 2011, and flushed like crazy to the point I had a bad enough crisis I ended up in the ER having benadryl pumped into me via IV. Since then I have noticed that taking the occasional anti-histamine reduces some of my abdominal and torso / back pains. But I am already on a massively restricted gluten-free, corn-free, soy-free, dairy-free, chocolate-free, grain-free, (you get the idea), diet. So sometimes I will run into foods like strawberries or even fish / fish oil, that I am not allergic to (verified IgE, IgG, IgA negative) and I will have a minor flush like even. Why? The aforementioned cause histamine release from mast cell degranulation.

    Given my experience with niacin, I switched to niacinamide under the assumption it would not cause flushes. But the reaction to anti-histamines has me thinking that I am harming my current methylation protocol in some fashion. Since one of the tasks of methylation cycle is to deactivate histamine (think of histamine as an excitatory neurotransmitter), maybe my high-ish histamine (which exacerbates some of my pain symptoms via self-testing with anti-histamines) and high-normal MCV (mean corpuscular volume) are due to still insufficient methylation capacity.

    So maybe that is the niacinamide or I need more methylfolate.

    So I am hoping Dr Ben can shed some insight since I don’t want to make a wrong step here.


    #3788 Reply


    Hi Paul,

    I have got the results of my sons, Mthfr results today, he is homozygous for  677 . same as me. but he is also histapenia,(according to his low histamine blood test) so according to Dr Ben, he should start with hydroxycobalamin, instead of methycoblamin., then Methyfolate.  Then other nutrients I guess.     I just presumed he would need niacin as well, its a shame the Dr we see dont seem to know much about this, hence our inquiries I suppose.

    Have you done the Mthfr gene test yet?


    #3790 Reply


    Trying to get my doctor to order it. My brother is heterozygote on both genes. But my symptoms are much worse than his.

    Sorry to hear your son is homozygous. But if he is histapenia (low histamine) then isn’t he an over-methylators?

    #3792 Reply


    Yes he is an overmethylator, so surely he would need Niacin to “mop up” the overmethylation?

    #3901 Reply


    How do we know if we are overmethylators or undermethylators? Do you go by symptoms, genetic mutations, or just blood work? I’m homozygous for 2 different COMT mutations. Plus homozygous for CBS and heterozygous for C677t.  (several others but those are the main ones) I’m guessing that I might be an overmethylator because of the COMT mutations and feel better taking hydroxyb12 instead of methyl b12.

    David, just wondering how you feel taking the niacinamide? Did you start it?



    #3907 Reply


    Hi MaryS,

    If you get a blood histamine test done,   Low histamine, overmethylator,    High histamine, low methylator, and according to Dr William Walsh, different nurients for both types.  42% of people with schizophrenia are overmethylated, 28% are undermethylated, plus other biotypes, pyroluria,thyroid deficency etc.  Of course this is for mental health problems and autism, I had my histamine levels done and they were in the normal range.

    Dr Walsh, also studies the genetics,  he come to Australia once a year to teach Drs to go down this path rather than just use drugs for people with these conditions.  Wonderful, just hard finding Drs, who understand this.  Anyone in Aust. can go to to find a Dr.

    Still trying to find how much niacin to give someone who is overmethylated???     Grace


    #3941 Reply


    I have relatively low normal serum histamine but I respond very positively to antihistamines in terms of reduction of muscle pain in my torso. Also on niacin without food I flush like crazy. So technically I would be an under-methylator which correlates also with my high MCV.  My doctor in California tells me that serum histamine is not by itself a reliable indicator. I also am heterozygous COMT which means my catecholamine metabolism is reduced 2-3x. For me niaciniamide gives me energy but hard to tell is it from Krebs cycle or reducing methylation so norepinephrine hangs around longer. Norepinephrine is the kiss of death for me since I have a very,very nasty autoimmune disease that I have to take mineral and corticosteroids plus many other meds / supplements to even remotely contain.

    It is possible that in lowering my niacinamide, I have improved effective methylation but at the same time increased inflammation somehow. Not a happy thought. My pain is worse on niacinamide at 250 mg than at 500 mg for sure. So yeah I am confused right now.

    I also started taking my 800 mcg folinic acid and 800 mcg 5MTHF in morning away from food and vitamin C so again that may have increased effective methylation.  I am pretty sure that niacin / niacinamide also stimulate the production of both serotonin and dopamine.  In terms of methyl b12 I take 5000 mcg a day. Supposedly sublinguals are about 20% absorbed. I find when I increase to 7500 mcg I have good aspects in terms of energy and mood, but more pain again. So many mysteries.

    I am awaiting my gene tests before I make any changes.  I will probably go back on 500 mg niacinamide until the results come back. If I am simply heterozygous (like my brother) then I am probably in the ballpark. But if I am homozygous then I need to make some big changes. I also have the dairy antibodies which I have yet to understand how they factor into all of this.

    #4415 Reply


    Hi David,

    I’m not an expert at all — but just in the last few days have been reading more of Dr. Ben’s blog, and remembered that he said that too much methylfolate may cause increased pain, among other things. (I tried to post the link, but it wouldn’t let me, so a google search of “methylfolate side effects” should pull up the page.

    So perhaps lowering the amount of methylfolate would help? He doesn’t seem to mention b12 as having that problem — at least not that I’ve seen.

    For me, I can’t seem to tolerate niacinamide. I’m guessing it’s because perhaps I’m still too low on methyl donors, which it ‘soaks up’, according to the doctor, and also helps preserve serotonin levels. Serotonin (or at least tryptophan) constricts blood vessels, and in my case this seems to always lead to bad circulation, and increased pain.

    Just my two cents.


    #5168 Reply



    You propose an interesting theory regarding possibly too much methylfolate. I actually only recently determined I am heterozygote A1298C. Something that supports your theory also is that I take high vitamin C during the day to bowel tolerance (about 10 grams per day). For a long time I took my first 2 grams of the day with food with methylfolate and folinic acid in the morning. Then reading this site, I took the methylfolate and folinic acid with water on an empty stomach and waited 20-30 minutes every morning … and ironically there was more pain within a couple of days. I stopped doing the ‘waiting protocol’ after a couple of weeks recently. Hmmm have to re-evaluate this a bit methinks.

    Btw niacin is a vasodilator, niacinamide is neither a constrictor nor dilator and serotonin is both
    depending on which tissue we are talking and which 5HT receptor is dominant. Also depends on if vessels are healthy or damaged.

    Excess serotonin can cause significant problems in the periphery especially the gut, but so does too little.
    Personally I tend to have low brain levels of serotonin, since I have a nasty CNS autoimmune disease, so I find 5HTP supplementation to be critical (200 mg at night) to help with sleep and at least with coping with pain. Hard to explain.

    #8094 Reply

    Kelly Richards

    Hi all thought I’d join in to this conversation. I am hetro COMP and have trouble with the methyl folate too. With my research I have found suggestions by Bill Walsh and Doc Ben to take Niacin if you have your methyl folate and you feel bad (pain, irritability). I often take 1/4 tablet so I don’t flush but I try to do so while I am really hydrated. I have reduced my methyl folate which helps but I still take niacin every couple of days. I read the methylation process is fairly touchy and you can easily go from under to over methylating. It’s good to have niacin on hand I find for this reason, but only a little is required, well in my case anyway.

    #223878 Reply


    I was also wondering if niacinamide uses up methyl groups as much as niacin. I’ve been having a lot of issues with joint and muscle pain, worsening allergies, some rashes, tendonitis in 2 different places, and headaches. and my doctor recommended 500 mg niacinamide 3 x a day. He did not seem to think it would use up too many methyl groups “as long as I’m taking my multivitamin” with 1 mg methyl folate. I also recently started an adrenal support with methyl B12 so I think I was over methylated anyway. I’m ++COMT (2 of them) among others. Well today I took the niacinamide and I feel so much better in many ways. I felt stronger today, less fatigued, and really no muscle or joint pain! I even seemed a bit more into my job today with less brain fog. My sciatica symptoms are even gone! It is actually quite amazing. I’m also recovering from an MCL injury in my knee and even that feels a lot better today. However, around lunch I started sneezing like crazy. And now have a stuffed up nose. The eczema on my hands is itchy too. Did I switch from over to under methylation?

    I’m not sure what to make of this. How can sinus issues be a symptom of over and under methylation? The improvements were so significant that I don’t want to stop taking it. Any thoughts?


    #376784 Reply


    I was just looking online for an answer to this question, and I came upon this thread on this forum. I noticed that Dr. Lynch has not responded. Does he usually respond to questions on this forum?

    #377090 Reply


    Mary it sounds like you are histamine intolerant, perhaps there is some gut dysbiosis occuring and you may want to look in to reducing foods high in histamine

    #383885 Reply


    I just found this study that suggests that both niacin and niacinamide can increase ‘methyl consumption’. doses of nicotinic acid produced a dose-dependent increase in the plasma levels of N(1)-methylnicotinamide and hydrogen peroxide, which was associated with a decrease in liver and skeletal muscle glycogen levels. At the same dosage (2 g/kg), in comparison with nicotinamide, nicotinic acid was weaker in raising plasma N(1)-methylnicotinamide levels (0.7 ± 0.11 µg/mL vs. 4.69 ± 0.24 µg/mL, P < 0.001), but stronger in increasing plasma hydrogen peroxide levels (1.88 ± 0.07 µmol/L vs. 1.55 ± 0.05 µmol/L, P < 0.001). Moreover, nicotinamide, unlike nicotinic acid, did not reduce liver glycogen levels.DISCUSSION AND CONCLUSION:This study suggested that excessive nicotinic acid, like nicotinamide, might induce methyl consumption, oxidative stress and insulin resistance. Long-term consumption high niacin may increase the risk of type 2 diabetes.  

    #383886 Reply


    Sorry for the lack of paragraph breaks in my last post.  Not sure why that happened.

    #384010 Reply


    Just realized that link doesn’t work.  Here’s a corrected one:

    #550005 Reply

    Sue F

    I want to take niaciamide spread throughout the day as suggested by some for arthritis. This would lead to quite a high dose. Is this dangerous if I am homozygous for c677t? Can I counter with more methylated supplements? Do I need SAMe? I don’t know enough. Who can help ?

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