Introducing Chris Masterjohn Lite

Many people use niacin supplements to reduce their methylation rate. Some use it regularly because they are “overmethylators” and some use it intermittently when they experience symptoms they associate with overmethylation.

In this episode, I describe why I don’t recommend using niacin in this way. Doing so is using niacin as a drug, not a nutrient. Our goal should be instead to supply glycine in nutritionally adequate amounts to make the methylation system run smoothly like a well-oiled machine.

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43 Comments

  1. Update – I have posted here several times regarding my success in using niacin (350 mg 2x daily along with supporting nutrients to balance things out). As mentioned, eventually I became intolerant of the niacin flushing for some reason, and also concerned because niacin was causing big spikes in blood sugar and chronic low grade hypoglycemia (or that is surely what it felt like). Also concern over the unnaturalness of taking such a high dose over long term. Nothing else would seem to work. Glycine for a few weeks seemed to be working, but when under stress it could not keep the over-reaction down. Finally I believe I have gotten on to a more natural way to control the effects of overmethylation.
    I did a Dutch complete test and my ND found that my aromatase was too active along with the expected hormonal consequences. Went on some anti-aromatase supplements (I can provide dosages if anyone is interested). Well, that gradually yielded some improvements, including a lowering of anxiety, much greater calmness, very muted reaction to stressors (compared to before). I tried going off of niacin, and low and behold its been over 2 months and I have taken very little supplemental niacin and have maintained this level of ‘normal’ reaction to stimulation. I also got interested in neurotransmitters responsible for over excitement and started to take serious steps to avoid activities that stimulate dopamine during this same time period. – more good results.
    Interestingly, after all that, I drilled into the results of a DNA ancestry test I had done several years ago, and sure enough turns out I have slow COMT meaning that I am slow to get rid of dopamine, nor-epinephrine, and epinephrine (adrenaline) [and also estrogen by the way]. That means that all those NTs and hormones tend to be high. This compounded by the fact that I also have very slow MAO (both A and B are slow), which also leads to elevated dopamine and other stimulatory NTs. Bingo. Now I understand. So while niacin does speed clearance of adrenaline, and others excitatory NTs, a more natural approach is to support my slow COMT and MAO (mainly by avoiding certain foods) and minimizing activities that create excess dopamine (like writing this blog post…) – as well as giving some support to GABA via theanine (250mg daily) and glycine (350 mg daily) supplementation. So far this has worked very well in keeping the effects we call overmethylation under control.
    We are all different, but maybe this can help someone else.

    1. I sound just like you except that I don’t tolerate glycine over time (it accumulates and starts to cause insomnia, wired tired stuff)… I wish I could as it would help with Glyphosate toxicity which is a guarantee with my situation. I’d love to know more of what you are taking daily/practices (if more than what you mention) as there is definitely something screwy when it comes to neurotransmitters, BH4 pathway and a lot in the dopamine dept. Symptom wise I’ve sorted that sny methyl-including betaine hcl, anything that raises serotonin ( likely MAO related or compounded pathway issue, high glutamate tendencies (also pathway related in my genetic interpretation)make me insane, severe insomnia that horse tranquillizers couldn’t knock me down (or high high THC dosing or very high Liposomal melatonin, glutamate scavanger etc).Food wise, having been on so many diets since birth (still on), I’m not a fan of cutting foods but no dairy or gluten for sure but I do love foods on the “no” list for slowing COMT.

  2. Dear Dr,
    I am struggling with histamine issues affecting sleeping with insomina.
    l-glutamine is for me kriptonite for insomina, horrible. Also, whey and hydrolyzed collagen.
    I match the profile of an overmethylator according to my character.
    I tried with methyl-cobalamine and more anxiety.
    Quercetine, and Mg glicinate also nervousness and (low) insomia.
    Some (folate rich?) foods are also an issue: rootbeet, cheakpeas, tomatoes, sweet potatoes, brocoli. These triggering a kind of groaning while sleeping.
    Inositol and taurine negative effects. Good only at the beginning.

    I wonder if controlling overmethylation I could get more results than controlling histamine rich foods.

    Could be vitamin B3 a way to try?
    Folic acid ?

    Thanks a lot.
    Pedro

    1. Pedro,

      I have the same problem, or had the same problem. If you get more anxiety with methyl-cobalamin, then try slowly adding folinic acid or methylfolate. Slowly increase both over time and you’ll feel calmer, your anxiety WILL go down. I guarantee it.

      It took me years to figure that out because I had a bad reaction at first — so I stopped both. That was a mistake. I am finally doing better, but you must take both in order for methylation to work. Also riboflavin will help.

      1. Thank you a lot for your kind help!!
        Methylfolate will not provide further methyl groups?
        Folic acid could also be valid? It has a bad reputation on Internet….
        God bless you

    2. Hello Pedro. Sorry you are having to deal with methylation problems. I too have been diagnosed as an overmethylator. The only thing that works consistently for me is Niacin (B3). For me, it has to be the kind that causes flushing (nicotinic acid). The other forms do not work well at all for me. It appears that the flushing part is beneficial for me, as flushing is mediated by histamine and repeated flushing tends to deplete histamine levels. I know that overmethylators are supposed to have already too low histamine (and indeed my own blood tests comfirm as much) – and I do not suffer with seasonal or environmental allergies. Yet in other ways I have the symptoms of too much histamine (constantly swollen nasal passages for example). A diet of high histamine foods will sometimes precipitate a migraine headache. A low histamine diet does make me feel better and more calm. But the niacin is by far the most effective thing for me. I went to a professional who was trained in the Walsh Protocol, as it is probably not healthy to take high doses of niacin without balancing it with other nutrients. In my case, I was prescribed 500mg of niacin twice daily, plus B12, folate (or folic acid), B6, C, E, and zinc. Its a complicated business. When I tried niacin, I started low (50 mg) to see how it served me. The flush can be very intense and scary if you’ve never taken niacin before, but I came to like it as it left me calm and relaxed. I later learned that taking 1/2 an aspirin 30 mins before the niacin with greatly reduce or eliminate the flushing. However, doing that prevents histamine from being expended as well. Eventually I had to back off of the niacin because I was getting lethargic, and finally settled on 350 mg twice a day. Before I paid for expert advice, I tried niacin and found that it did work well, then I went to the Walsh practitioner to get expert advice on what other supplements I needed to take so as to not get my nutrients out of balance. That was expensive, but a good investment. I hope you can get some relief.

  3. https://pubmed.ncbi.nlm.nih.gov/9184125/#:~:text=Glycine%20is%20an%20inhibitory%20neurotransmitter,in%20organotypic%20hippocampal%20slice%20cultures.

    I had a strong reaction to glycine once, where I had an extreme panic attack and hyperexcitability. This was even on a small dose of glycine. I felt almost as if I was about to have a seizure, and I am not epileptic. It was pretty bad. I counteracted this hyperexcitation with Gotu Kola which was effective and calmed my brain in about 30m to 1hr.

    Chris, have you ever heard of this before? And if so, do you have any explanation or advice? Thanks.

  4. I am an overmethylator and tried Dr Walsh’s approach, unfortunately it did not work for me, because one of the main supplements (folic acid) of the program raises serotonin (which is already elevated in overmethylators). Folic acid helped to reduce dopamine though, but serotonin remained elevated.

    I am now trying just Niacin, but i will give glycine a go.

    Thanks

    1. For me niacin works the best of anything. However high dose niacin needs to be balanced with other nutrients or a relative imbalance can occur. I sought expert advice because the relationships are rather complicated. Nicotinic acid (the type of niacin that causes flushing ) works the very best for me, but eventually it began to irritate my stomach, and the frequent flushing, which I actually did not mind, we came associated with some other problems. Niacinamide does for dose not work as well for me, but it does work.
      Surprised that folic acid raises your serotonin. The theory is that while it does raise serotonin briefly, it primarily acts as a serotonin reuptake promoter, which has a net effect of lowering serotonin. While my feeling is that it worked that way for me, it’s really hard to know for sure since both high and low neurotransmitter symptoms can be quite similar.
      Then again we are all different. I wish the experts would be willing to admit that despite all the research, we still only know a very little about how our complex body operates.

  5. Hey Chris,

    Would you agree that it is plausible that SAM -e and methionine can act as sert transporter inhibitors?

  6. Chris, very informative. Thanks so much for sharing your insight. I am very intrigued by the possibility of tamping down methylation without niacin. I had for many years knownn I produce too much adrenaline, but did not know why or what to do about it. Eventually came in contact with a person familiar with William Walsh protocols. Tested very low for histamine, therefore diagnosis of overmethylation. Niacin works wonders, brings me to what I always thought should be normal. Even at 500mg 2x per day, it took many weeks to start to feel draggy (undermethylation I am guessing) at which I would back off on dosage a few days till I felt over stimulated again. I finally titered my dose to 350mg 2x daily, and that works well long term, with occasional extra needed during times of increased stress. But, I have developed some visual problems that I think is related to long term niacin supplementation. (several cases of macular edema and maculopathy have been reported.) Plus, that high of a dose is very unnatural and bound to have some long term adverse consequences – but nothing else could substitute for niacin. Till now maybe. The use of glycine seems much closer to a truly natural solution.
    Any idea on how much glycine it would take to have the same effect as 700mg of niacin daily?
    Thanks again for such a helpful article!

    1. Well, I’ve answered my own question – maybe. I did a short taper off niacin about 3 weeks ago and have been doing glycine at about 500mg to 1.5 grams per day. Some straight glycine, sometimes as magnesium glycinate (which is 86% glycine), and sometimes as collagen. I’ve had to take a little niacin sporadically, but overall the effects are pretty good. Not quite as good a niacin for calming, but acceptably well.

      1. Update
        The glycine didn’t work so well after all. Back to niacin. The visual problems I finally figured out – my blood sugar shoots up for a while after meals when I regularly take niacin. Temporary, as it is back to normal (less than 90) before the next meal. Still not good. Vigorous exercise brings the glucose down quickest for me in that situation.
        So far, no good substitute for niacin, at least for me.

  7. Is it possible to Tajke sodium Citrate instead of salt to get my sodium. And would it be better tolerated in my stomach.. Salt is pukey for me..

  8. Does this also apply to NR and NMN? I’ve been thinking about starting one or the other for the purported longevity benefits.

      1. There’s a gentleman named Ken Lassesen who has gone into remission from ME/CFS three times over the last forty or so years. He runs a blog called CFSRemission.com.

        Although his main focus altering the microbiome, he also takes 500 milligrams of nicotinic acid every day, and to my knowledge has never taken B12 or other forms of folate or methionine to balance the niacin.

        I guess the question is, according to the methyl-group depletion hypothesis, why wouldn’t he be dead by now?

        And why wouldn’t the millions of others who take high dose niacin every day?

        Thanks Chris.

  9. Very informative and fascinating research! Thank you! I have a few questions for you if you can help. I plan on getting some genetic testing done, as I am curious to see if I can determine whether I am under or overmethylating or in between. I had positive responses to SSRI and SNRI in the past, but recently it’s been adverse. I honestly suspect overmethylation for me. In the recent past I had positive responses to niacinamide, niacin, & lithium orotate. However, I may have went overboard with dosages and swing into under. Would magnesium glycinate be a sufficient source of glycine if I take the highest dosage that’s safe? What if I take some niacin as well with glycine? I’m only considering adding some niacin to my stack because of “anecdotal” praise of benefits for anxiety and depression etc. I take probiotics, 2g of C, 1000mcg of methyl B12 everyday. I feel good after eating a large amount of spinach (folate). Fish oils and cod liver make me feel worse. Another question I had is, do you have any thoughts on phosphatidylserine affecting methylation? I’ve just started taking it, 200mg a day, and wondering if if could benifit one side of the methylation spectrum more than the other?

    1. Please read through this page in its entirety on methylation in general and on testing approaches:

      https://chrismasterjohnphd.com/methylation

      On the supplements see here:

      https://chrismasterjohnphd.com/balancing-methionine-and-glycine-in-foods-the-database/

      In addition to these sources, there is some glycine in certain mineral supplements. For example, 300 milligrams of calcium from calcium glycinate provides just over 1 gram of glycine, and 300 milligrams of magnesium from magnesium glycinate contains almost 2 grams of glycine. It is best to use these when you have a specific reason for supplementing with the mineral that is attached to the glycine.

      I don’t know anything about phosphatidylserine and methylation.

    2. I did just this, because I saw this post and the glycine caused a horrible gallbladder attack since I shifted my bile acid content to higher glycine which is more hydrophobic than taurine. No good bueno, I almost had to have surgery. And I saw no benefits. Been studying this for 10 years. I have 0 basophils. I’ll stick to niacinamide thanks.

      1. Glycine didn’t work as well for me either. Niacinamide also does not work for me. Not sure why. Can I ask how much you take? I need 750 mg daily or more of nicotinic acid to keep things in control.

  10. Hello Chris
    It would be tremendously helpful if you could help me find an answer to a question I‘ve been battling with for the last couple of days.
    I have been taking Sarcosine for a while as an antidepressant and a cognitive enhancer for the negative symptoms of what I suspect as a prodromal schizophrenia. The cognitive effect was so strong that my negative symptoms completely disappeared.
    About 10 days ago I started megadosing Niacin for a few days after a recommendation from a friend, which was the only change I made in this time period, and ever since Sarcosine stopped working. Any idea what the reason could be? Could it be that I am so undermethylated that Sarcosine gives up its methyl group before doing its magic on the NMDAR? Or could it be that Niacin caused a desensetization of the NMDAR? I would greatly appreciate any possible explanation how it happened / advice to make Sarcosine work again.
    Thanks for any help,
    Liad

    1. If sarcosine is activated NMDA receptors then it is definitely giving up its methyl group first because glycine is the coagonist for the NMDA receptor. Sarcosine is a methyl donor within the mitochondria. Niacin depletes methyl groups. So your story is not at all surprising.

  11. Hello Chris, thank you for all the information. I understand you are not a doctor, I just want your educated opinion.

    I have been in troubles with intestinal issues, constipation, very low stomach acid, anxiety and insomnia at night, fatigue and sleepy during the day. Enzimes and HCL Beatine help, 5htp and GABA not so much, and recently I have been trying with B3 and I truly feel a difference for my sleep, but I start to have undermethylation symptoms.

    It’s like I’m unable to have a balance. That’s why your post made a match with my situation. I am a little bit lost, everything has been self education for me. Could a disbalance on these processes end up generating Low Stomach Acid? Do you think these symptoms could probably be methylation issues? Where whould you recommend me going or trying or reading from here?

    TY!

    1. Overmethylation could cause low stomach acid because stomach acid is made in response to histamine.

  12. Very interesting post, and it makes sense considering known research regarding methionine and glycine balance. I come back to this subject occasionally so I was glad to find this post. Although there is a lot of published research on this subject already, the transcript above presents the issue in a concise and comprehensible manner. (Thanks for offering transcripts by the way, I lack the time and patience for videos and podcasts, which have a low rate of information transfer compared to reading.)

    One problem that some people will run into with glycine supplementation is that it’s a direct NMDAR (NMDA receptor) agonist. I noted another comment in this thread about insomnia following glycine supplementation. Your response primarily mentioned electrolytes but this issue is much more complex. NMDARs are involved in long-term memory and learning. Some people have internalized negative experiences that are associated with elevated NMDAR activity and this can lead to a stress response that seemingly has no explanation. This gets into the whole calcium overload, glutamate excess (GABA deficient), overstimulation, excitotoxicity battle that is well documented elsewhere.

    One issue that I find with virtually all supplements is that the typical dosages (even in a single tablet or capsule) are too high and tend to throw things off balance. I would strongly recommend that anyone experimenting with glycine supplementation should slowly ramp up their intake and potentially supplement with magnesium to avoid excessive NMDAR activity. For me personally, niacin is easier to tolerate than glycine for the reasons mentioned above, though I do get some benefits from glycine (in moderation) as well.

    Supplementing with either niacin or glycine after taking a methyl donor supplement (methionine, TMG, folate, MTHF) quite clearly demonstrates how well both compounds are at clearing methyl groups, but apart from that, both compounds have a wide range of other physiological effects that should be carefully considered.

    1. I think it is misleading to call glycine a direct NMDAr agonist. It’s a permissive co-agonist at non-synaptic NMDA receptors where ambient glycine sets the tone of the kinetics of glutamate activation. It doesn’t activate them by itself, doesn’t activate them at all as a synaptic neurotransmitter, and probably doesn’t even act as a permissive co-agonist at synapses, where D-serine fulfills the analogous role instead. It’s probably mainly or only relevant to long-term depression (the opposite of long-term potentiation), and it’s not clear that taking glycine would lead to a change in ambient glycine levels in those places, though it certainly could if glycine were running deficient.

  13. What happens to the methylated glycine? Does it float around waiting to act as a methyl doner like SAMe or does it get excreted? I tend to have a lot of exercise fatigue and am begging to think it is hypomethylation related. If methylated glycine sticks around, would boosting it act as a buffer and become a doner during and after exercise?

    1. It gets recycled in the mitochondria by giving folate a carbon from the methyl group, but if there isn’t enough unmethylated folate in the mitochondria, it gets lost in the urine.

  14. Hi Chris, Me again. Going back and forwards between your material and William Walsh’s book. It seems to me that the terms undermethylation and overmethylation may be the cause of the supposed differences.
    From my reading of the Walsh information the emphasis is on the effects on the enzymes that have opposing epigenetic effects on histone acetylation versus methylation. E.g. Folic acid/folates enhance histone DEmethylation, and reducing dietary folates can increase methylation at histone tails and DNA sites. Methyl and folate have opposite epigenetic impacts on neurotransmitter reuptake at synapses….. The genetic expression of transporters is inhibited by methylation and enhance by acetylation…. The net result is that activities of serotonin, dopamine, and other neurotransmitters are strongly influenced by the methy/folate ratio. Folates increase methyl levels in tissues and the bloodstream, but they reduce methylation at certain histones that regulate gene expression…. So in an interesting paradox even though the Walsh Approach is trying to increase Methylation doing so by using methylfolate has a negative impact on the methyl/folate ratio. My understanding is that your work is focused on the general methylation cycle in tissues. The Walsh institute has 10s of thousands of clients biochemical records suffering from mental health issues (Depression, Schizophrenia, Autism, ADHD,….) that confirm a strong correlation with blood histamine levels and (high – termed undermethyaltion, low – termed overmethylation) and which treatment protocols work to assist. A depressed SAMe/SAH ratio also correlates. Those that have high levels of whole blood histamines (above a certain range are classed as undermethylators) respond well to supplementation of methionine, SAMe, B6, B2, Magnesium … and avoidance of Folate, B3, Choline, DMAE and B5 as they increase chromatin acetylation and SERT levels. On the other hand Folates/Folic Acid/Folinic Acid, B-12, and B3, Choline, DMAE…. is recommended for those with a low level of whole blood histamine. Vitamin B3 (niacinamide) inhibits sirtuins, a class of proteins that effectively remove acetyl groups from histones and promotes methylation. Attachment or removal of methyl and acetyl at histone tails is dominated by enzymes called methylases, acetylases, demethylases, and deacteylases – NOT by the amounts of methyl and acetyl present…..A good example is niacinamide (vitamin B3) that reduces the activity of sirtuin, an important deactylase enzyme. So from my understanding it’s not about buffering and mopping up methyl it’s about having a direct effect on histones.
    The Walsh Approach works and has assisted many, many thousands of people suffering from mental health issues.
    I would also suggest that the way you use Vitamin A could also be termed as ‘using it as a drug’. It’s all about addressing challenging genetics amd epigenetics.
    Now whether their approach can be sidestepped to achieve the same level of mental health improvements, by balancing the methylation cycle the way you suggest – provide all of the nutrients that support healthy methylation – is the big question. I am open to the fact that your approach, possibly coupled with upstream healing of digestion and detoxification systems and supporting mitochondrial health, may achieve the same result. But individual genetics, just as they do with your use of therapeutic doses of Vitamin A, may very well require the Walsh Approach.
    Either way using whole blood histamine levels (and SAMe/SAG ratios) and the resulting protocols have long term demonstrated benefits for those addressing mental health issues. You may be doing people a disservice by putting them off the use of the Walsh Approach.
    I think you could develop a more nuanced interpretation and approach by delving deeply into the whole Walsh Protocol and drawing the best from both perspectives.
    Happy to be corrected.

    1. The reason I focus on the methylation of neurotransmitters, phosphatidylcholine, and creatine is because everything I have read about the kinetics of the system and the sensitivity of the various enzymes to concentrations of methyl groups overwhelmingly suggests that in all but the most extreme conditions the methylation of DNA is going to be entirely dictated by factors specific to the regulation of those genes and be completely independent of the methylation cycle.

      I will have to read his book at some point to see what research he is relying on but I just really doubt the mechanisms you are describing are under most conditions meaningfully impacted by variations in folate intake.

      Is “Nutrient Power” the best thing for me to read?

      1. Nutrient Power is a good starting point to get a full overview of his thinking and approach. Lots of references. As per mentioned earlier my children both reacted very badly to methylfolate supplementation – became very brittle, withdrawn, and depressed. They were already down. They had hit the wall to a certain extent 12 to 18 months after their mother died, but the dial got turned up majorly within a very short time after starting folate supplementation – several days. Teachers contacted me very concerned as well. I found Nutrient Power at this time and it was a life saver. They matched perfectly statements from the book such as “Nearly all low-serotonin depressives tend to be deficient in methionine and SAMe and react adversely to folic acid”.

  15. Something about glycine is excitatory for me – if I take it at night, I don’t sleep. I have tried plain glycine and mag glycinate. I do consume it during the day via gelatin. However, if I take niacinamide at night, I sleep markedly better – it somehow affects that 3 AM wake up that can happen, and instead I sleep soundly all night. I am an “overmethylator”, I have no idea if this has anything to do with the effects of glycine or niacinamide.

    1. Glycine and GABA are both excitatory if you have impaired potassium and chloride transport that causes higher than normal intracellular chloride within your neurons. I suspect your primary problem is energy metabolism and the niacin might be helping with that. Also improving your electrolyte intake, particularly salt and potassium, might help.

      1. Thanks Chris! That’s very good information, and I think its spot on. I do have to eat a lot of salt and potassium, as I have low serum sodium levels. I am borderline CFS (at about 70% of “normal” since I’ve been sick).

        Any idea why this cellular issue develops with high chloride? Do the bicarbonate forms of sodium and potassium swing the balance favorably?

        Your kung fu is the best. 🙂

        1. It can be tissue damage, and direct damage to neurological tissues is beyond my skills.

          But it could just be lack of energy. Think insulin resistance, thyroid disorders, magnesium, or any of the other vitamins and minerals involved in energy metabolism — there are many.

          It could also be electrolytes. If you don’t get enough salt, or enough potassium, you aren’t going to be able to properly balance these ions across your neuronal membranes.

          I favor using table salt and potassium citrate.

  16. Some people take glycine for better sleep. What’s the likelihood that they are an overmethylator? How does overmethylation affect sleep?

    1. Glycine itself helps sleep by lowering core body temperature and acting as an inhibitory neurotransmitter.

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