Introducing Chris Masterjohn Lite

Are you using niacin or nicotinamide riboside? If so, watch this video! These supplements can help you age more gracefully and give you more energy, but they can also hurt your liver, mess with your neurotransmitters and your mood, and even sap your energy.

In this video I discuss using a powder for better control over the dose, and how to match your niacin dose to a corresponding dose of trimethylglycine (TMG).

The nicotinamide riboside powder can be found at

The TMG can be found at

If you use my affiliate link for the TMG, I will get a small commission at no extra cost to you, which will help support the free work

How to watch it:

How to share it and show it love:

This episode is brought to you by Testing Nutritional Status: The Ultimate Cheat Sheet. Everything you could ever need to know to optimize your nutrition, all in one place. Easier to find and use than ever before. Get your copy at Use the code LITE5 to get $5 off.

Want a Transcript?

CMJ Masterpass holders can access the transcript here.

Transcripts make it easier to use the information. You may just prefer to read. But having transcripts and video or audio can massively increase your productivity. For example, you can listen while you are washing the dishes, commuting to work, or doing other menial tasks, getting familiar with the material and scanning for things you want to learn more about. Then you can come back and keyword-search the transcript for the exact things you want to master in more detail.

To get these episodes free of ads, with transcripts, and weeks or sometimes even months before they are released to the public, along with access to monthly live Q&A sessions, sign up for the CMJ Masterpass at Use the code LITE10 to get 10% off. To make it easier to get the discount, use this link, which has the coupon already activated:

You may also like


  1. What about NAM? (B3 niacinamide) Is there any real compelling reason to take this newere more expensive stuff over the good old Niacinamide?

  2. Hi Dr. Masterjohn,

    I recently tried NMN from what seems to be a reputable company in Europe (powder form in approx 250mg dose, keeping in the mouth for a few minutes before swallowing), and within 5-10 minutes suffered a quite severe panic attack (calming down after 1-1.5 hours and even feeling a “high”/euphoria at times, though with occasional dizziness and a sense of being out of control).

    I woke the next day feeling slightly strange but much more normal/stable. I speculated from multiple sources that I may have required methylation support, so sampled an extremely small dose of TMG purchased from the same company (at most a few tiny granules on its own, with no NMN taken alongside it). Shortly thereafter I had a similar but more minor panic attack and a return of the same mental instability (periods of very high energy, followed by what I imagine depression to feel like), dizziness and occasional surges of unprompted anxiety until I went for a walk late in the day.

    Several days later I am still having periods of dizziness, scrambled thinking and the occasional racing heart, especially after drinking coffee – it’s only when I get out and walk that I feel better/back to normal.

    FYI I had no history of panic attacks prior to taking the NMN, apart from a similar reaction to Magnesium L-Threonate about 1 month ago (no obvious issues to-date with other forms of Magnesium).

    For context, I have been on keto/carnivore with a controlled 20-25% calorie deficit for about 4 months (very low calcium and vitamin C during the carnivore portion) and have taken a range of supplements over that time (including D3, K2, Magnesium, liquid iodine – which I stopped awhile back – Selenium Methionine, and most recently methyl folate). I have tried eating at calorie maintenance/surplus since (assuming there’s a cortisol connection), but not sure what impact that’s having.

    I want to understand why I’m reacting this way, as I’d like to be able to use NMN in the future – is it potentially high cortisol/low DHEA from the calorie restriction, a methylation issue, or some other pattern/combination of factors you can see that might explain it?

    1. Yes, probably high cortisol which can be checked with a 24 hour salivary cortisol test. If you’re cutting back on carbs and in calorie deficit, then that’s almost a guarantee as cortisol will go high to raise blood sugar. But in the process it’s breaking down your muscle to make that glucose.

      I HIGHLY doubt your ‘extremely small dose of TMG’ is responsible for anything, considering methylation is essential 24/7, and hundreds of thousands take betaine HCL (which is trimethylglycine + chloride) every day for hypochlorhydia. You may need more methylfolate or methylcobalamin if you’re getting too much NMN. And plain ol’ niacin or niacinamide works just as well and is a HELL of a lot cheaper.

      1. I so agree with you on the niacin working just as well. I take it everyday and get a huge boost in energy, and rarely have any flush reaction. I study found that niacin boosted NAD levels in muscle in humans by 8 fold. I take the 2 g of betaine every day and 400 mcg of methylfolate, and methyl B12 with no side effects or noticeable reactions. Just get good energy from niacin. I didn’t notice as much benefit from niacinamide. I read it boosted NAD in one study but not by as much as niacin. It uses the salvage pathway which is possibly less direct or efficient

    2. Also — why the low calcium? If you don’t get enough calcium, it’s pulled from your bones, causing bone spurs. If you’re eating high amounts of meat, that will INCREASE your need for calcium and other minerals.

  3. I started Niagen a week ago. I am feeling very irritable with low energy and my search brought me here. Thank you for this information. I am stopping the supplement. $45 a month to feel like crap isn’t worth it.

  4. Hello. Very glad to find this site. I will post again in a month, around end of 1/20, when I have more experience. I am 82 and have spinal stenosis. I have been taking NMN, pill form daily , for 16 days. My spinal stenosis has gotten worse and I am guessing my nerves are more sensitive. My eye soreness, when too long on the computer screen, seems slightly lessened. So now I’ll take a 3-day break and then resume but this time powder sublingually, 125mg morning and 125 mg evening. Will see what happens.
    A lot of people have been influenced by David Sinclair taking 1 gr of NMN daily (noted in his book but other places it’s 500 mg, which dose his 80 year old father takes.) But even 500 mg seems to be 100 times more than we get in food. Also, why has Sinclair become the rock star of anti-aging with NO human research? Mice are not humans. Is it so difficult or costly to do a few human trials, which could stimulate other trials? With Harvard’s prestige the money would come in. Or is there some fear human trials would be negative? I understand MNM cannot be patented so its sellers are not that interested in sponsoring, but isn’t this what universities are for? Lots of questions: is sublingual better? ; as months go by is there a decline in effectiveness; what is optimal dose.? I suggest Sinclair stop giving so many interviews and organize some human trials.

    1. I was getting spinal stenosis and read an article that it was from eating to much protein at one meal. When the excess protein left it took calcium with it. Then when calcium was available I did not have enough MAGNESIUM to tell the calcium where to go so it ended up as bone spurs or stenosis. I started 400-800 mg of several magnesiums and the stenosis and spurs went away. They no longer even show up on scans. Hope my story helps you.

  5. People who take NR or other NAD+ activators need to study mitochondrial fission/fusion balance and supplement-recycling. Don’t take NAD+ precursors everyday. Cycle it. Something like this (this has been discussed in detail in longecity)

    Week Set
    3x Days

    NR (fasting / morning) + strength straining after 1 hour
    No anti-oxidants
    Vit D3 + trace-minerals (except zinc may be) are OK to take

    3x days

    Anti-oxidants and mito-protective nutrients like CoQ10/PQQ/B-Vits/Methylating supps etc.
    HIIT Cardio


    BP / VO2Max / Kidney-Liver function test

    Repeat Weekly set x N

    Slowly you should see an improvement.

  6. I may have missed it but I don’t see any discussion of David Sinclair and some of his suggestions. Would be very curious on any thoughts about the combination of Resveratrol and NMN supplementation. He seems to be basing his dosage on mice studies. I suggest a podcast with Chris, David Sinclair and Peter Attila to help sort all of this out.

  7. This is a very informative endeavor by Chris. Thank you for providing this platform.
    Well… I had similar problems with NMN.
    I am a healthy male, age 45, loosely follow the pattern of intermittent fasting (2 meals a day with no snaking – 16:8 regimen and it has worked fantastic for me since I started in 2017) and exercise 2 to 3 times a week.
    So with in a week of taking 30 mg of NMN daily (I have never ever tolerated any mitochondrial enhancer –NMN/Co10/Carnosine etc– in more than a 50 mg dose).
    With NMN I would feel the same bad psychological effects that people have described above. To cut the long story short…
    I started testing and created my own protocol which goes like this…

    200 mg of Tyrosine /50 mg of 5HTP / 200 mg of Alpha GPC (Daily)
    500 mg of Vitamin C (Morning and evening daily)
    25 mg of B complex (Daily)
    50 mg of TMG (2 to 3 times a week)
    1 gram of EPA & DHA combined (700/300 – 2 to 3 times a week)
    500 mg of Spirulina (1 Tablet only- just threw in the mix for the heck of it)
    Indole-3-carbinol 100 mg (Every other day)
    Dr. Tobias Adult Multivitamin (2 tabs-Every other day)
    30 mg of NMN (4 to 5 times a week)

    I take all of this with my brunch. My brain and body has been in stable TIP TOP condition and I have not experienced any shitty side effects since I have started this “Khalid Protocol” 15 months ago. I think I covered most of the shit storm of depletion that NMN creates 🙂
    I hope this might help some people.

  8. 56 years old, have been taking NAD+ (Niagen) 250mg 1x/day (sometimes skip a day or two here & there just because… life) for about a year now and do definitely notice a bit more energy and focusRecently reading more about NAD+ and NMN I learned about the methyl-depletion possibility, so I have added taking TMG 500mg 1 or 2x/week. I feel there has been a very slight uptick in energy levels from that as well. I’m pretty sold on NAD+ at this point as having some value in potential health-span extension. As a side note also take CoQ10 with PQQ, AMPK Activator, Glucosamine Sulfate, European Milk Thistle and a multivitamin (LEF formula) and some Omega3 fish oil – also mostly daily. These I have been taking for nearly eight years now – but the big noticeable difference seems to be with the NAD+ supplementation. The Omega3 oil also seems to make a difference. YMMV as they say, but this seems to be a good combo for me so far.

  9. Hi,

    Interesting discussion. I have been taking NR for about 3 years with great results. Although I don’t get a “kick” like caffeine, I have noticed a general overall increase in stamina. For example, I have skied regularly since I was 8 years old and now at 56 I believe I am skiing with more vigor than when in my 20s & 30s. In fact, I often ski with my son and his friends who are in their 20s/30s and outlast them…..they often ask how I can do it and I tell them I believe it is NR! So yes, I am a believer.

    My blood tests have also shown a great improvement, with my LDL/HDL ratios improving dramatically. One thing I have also noticed however is my Red Blood Cell Distribution Width (RDW) has trended up and now stands at 14.1% which is close to the upper limit. According to much research, that is not a good thing as it is an early indicator of possible cardiac problems and other disease. The higher the RDW the higher the risk. High RDW also is linked to low levels of Folate/B12! So, this got me to thinking that perhaps my increase in RDW is linked to NR due to methylation?

    I just recently started taking Thorne TMG as you suggested……it will be interesting to see if my RDW falls….will let you know!

    1. Just got my lab report back and my RDW fell back to 13.1%…now in the mid-range of normal. Needless to say, I will continue to take the Thorne TMG! Looks like it may be helping….

  10. The problem here is that the NMN doses used in the mouse study with the impressive anti-aging results was 500mg/kg/day (Li et al, Science 355:1315+,2017). Human metabolism is an order of magnitude lower than a mouse and also qualitatively different than that of a mouse, so much smaller doses would be likely safer and effective, if they work at all in humans. Even considering this, doses of 25mg/day are unlikely to be effective…a rough metabolic
    calculation in humans would be more like 500mg-1 gram per day of NMN. While the mouse studies are very impressive
    I wouldn’t recommend the higher doses, but would suggest further research in humans and primates, and keep an open
    mind that a larger dose may be necessary. The methylated problems could be real as well, but I wouldn’t base that on anecdotal evidence, but should be addressed with laboratory studies.

  11. I’ve recently begun taking a Nicotinamide riboside product. The manufacturer suggests a 300mg per day dose. I asked the company about the methylation issues that you posed and they replied that they were familiar with your concerns and responded with the following:

    ” There is currently no evidence from human or animal studies to suggest that NR depletes methyl donors (molecules needed for methylation) enough to contribute to any metabolic or physiological problems. Methylation is a particularly important process in the liver. As such, markers of liver health can be used to monitor whether or not methyl donor depletion is causing problems in the body. Published clinical studies have administered NR in doses up to 2,000 mg/day (eight times our daily recommended serving) without changing circulating levels of the liver enzyme ALT (increased levels of ALT in circulation are a sign of liver damage).”

    I’d appreciate your feedback on their response.

    Thank you.

  12. I too felt pretty bad a few days after taking 500 mg of niacin, with a toxic, tired, fuzzy headed feeling. I also tried taking TMG, methylfolate and methylcobalamin at the same time to increase methylation, but then it seemed that it shut down certain gene transcription for growth factors involved in wound healing. Tiny abrasions on my fingers from work related activities then became deep, irritated cuts within a day of taking TMG. This has repeated itself with cessation followed by resuming it again. The wounds would literally not heal until I stopped TMG. Methylation is known to silence many genes and I think some are involved in growth or angiogenesis, or other cellular processes. I reason now that it is too difficult a fine tuned balancing act to know how much of niacin, niagen, and TMG or other methylations factors to consume to achieve the right balance for good health. I now only take 25 mg of niacin but feel i’m missing out on the antiaging benefits of NAD+ upregulation. However, so many anti-aging strategies seem to fall short. Fisetin, a senolytic has been shown to shorten telomeres in non-oxidative stress environments for example. So you get attrition of senescent cells and possible phenotype rejuvenation but then lose telomeres in the process? Is that worth the price?

    1. I don’t know whether this is your problem, but I’d like to propose another possibility. A large percentage of people have a gut microbiome containing bacteria that metabolize TMG (AKA betadine, for those who saw both terms used in other posts but didn’t know they’re the same thing) producing TMA. Normal liver metabolism converts it to TMAO, which is extremely proinflammatory, especially for cardiovascular tissues. TMAO has recently been identified as a smoking gun for heart disease, and probably contributes to a bunch of other undesirable effects. Oral consumption of trimethylglycine (TMG/betaine) should be avoided. I recommend sublingual or buccal doses followed by rinse-and-spit, instead. Anyone on a high protein diet should be particularly wary, because dietary carnitine and choline also elevate TMAO in individuals with those bacteria in their guts, and probably increase their population relative to other genuses. Geni? Anyway…

      1. TMG isn’t ‘betadine’, it’s betaine. And that study you reference was highly flawed.

        Google is your friend. Also spell-check.

      2. Does this mean we should avoid TMG containing foods too? Beets are a very rich source of TMG yet are also rich in other healthy food factors such as anthocyanins (anti-inflammatory) and naturally occuring nitrates – good for heart health based on nitric oxide synthesis. Also legumes and peanuts are rich in choline, not just eggs which they advise against consumption, but these are also rich in antioxidants and phytocompound which might be anti-inflammatory. I only noticed the skin inflammation problem with supplemental TMG but not with beets or any of these other foods including eggs (choline).

        1. I have to say in my browsing of countless forums and websites and observing many knee jerk reactions and responses of the general public to several stimuli, the general consensus is too jump to conclusions about new research or new tech. I include myself and know all too well the easy trap of the ideological echo chamber. (And by the way Google is definitely not your friend! ) Search encrypt, Ecosia and Duck Duck Go are! Facebook and Amazon are not but Signal and Ethical Consumer and Ethical Internet are! But an advert or an advocation for any particular companies or organisation. I merely share information that I find has helped me become discerning and a cutter or of BS. And Big Corp and Big Pharma are all part of the Military Industrial Complex, the power construct that excerts it’s Dominion over all humanity! I bet you smirking to yourself reading this right now? Just another impulsive reaction that is born out of fear of what none of us fully comprehends about the nature and intent of this murderous power construct! Phew! Okay now that that’s out the way: I’ve found in my browsing and observations of the world and it’s people’s that polarisation and the duality of life is rampant and very deeply embedded within human culture since the beginning of our existence so it is very difficult and one of life’s greatest challenges to overcome this duality that is and always has been intrinsically embedded within our very DNA. That being said it is up to us to accept this duality because it is a paradox that can never be overcome. The very act of attempting to overcome duality is in fact duality itself so you see my argument in the end is that we shouldn’t try to pigeon whole or categorise or sever one thing from another. The minute we try to say this is good and that is bad we have already missed another opportunity for lifting the veil a little more towards peace and Nirvana. What I’m saying is limiting yourselves to certain doses of substances and completely abolishing certain others is a completely flawed premise for optimum health. I’m starting to understand that experience and existence is super multi dimensional not 1 single flat dimension. If we continue to observe life on one dimension we will observe and act ourselves out of existence, literally! What I’m saying Brien is try to maintain a balance of everything. A good dose of common sense though goes a long way. We know that smoking and drinking large doses of alcohol will eventually kill you, especially if you have a compromised immune system. I believe a healthy balanced nutritious organic home grown diet with a reasonable amount of non pasteurised properly fermented foods incorporated, not too acidic, not too Alkaline and an amount of fasting that feels right to you is an adequate approach. Trust your gut literally. If you are in tune with it you will know exactly what you do and don’t need. I think this whole supplement shenanigans is a farce! If you get the natural balance of minerals, vitamins and nutrients correct for you, you won’t need to take anything extra except maybe vitamin D3 if you live in the Northern hemisphere where for a majority of the year the days are short and even more so if throughout the year your are inclined to working indoors rather than outside. I may be wrong? Maybe one day when I’m older I may find that I haven’t been getting all the nutrients my body required but I accept that responsibility because I was too lazy to educate myself about nutrition earlier on in life! I’m definitely paying attention now and I’m definitely making a concerted effort to maximise on balancing my bodies systems which like all life are interconnected and inter dependent!I hope this long tangent of my mad ramblings has given you some food for thought? Namaste

          1. I nearly forgot to mention, almost all of humanity are severely dehydrated because the quality of water we drink even if we drink a lot is very very poor all around the globe! The poor water quality effects the ability of our entire body to transport and process throughout digestion, all the other metabolic processes and final ejection of water as well from our systems. For decades people, some, have been aware of this and have tried to replicate natural water living water instead of stagnant, dead water from reservoirs. Many snake oil sellers jumped on the band wagon proffering all manner of structured water devices preying on people’s vulnerability! This is now for me a life long learning process and water despite the centuries of research, remains a highly mysterious molecule/substance? I’ve come to the conclusion (which could change as I educate myself more) that due to many discerning citizens that decided that it was a good idea to drink water filtered with reverse osmosis devices failed to observe that although the human is almost like a car battery we are definitely far more multi dimensionally complex and therefore continuously topping up with now wonderfully distilled water from a reverse osmosis filter is in fact highly detrimental to the human body.
            With water being the very strange and mysterious substance that it is it is also extremely hungry so if you remove all these substances (during the reverse osmosis process which strips everything not just the harmful substances) it will latch onto minerals present in our bodies! Many people now who have been drinking reverse osmosis filtered water for a number of years have actually developed osteoporosis and or osteo arthritis as a result for to the filtered water actually talking calcium out of their bones! Literally! And that’s just one element! So in this case of you are someone that drinks reverse osmosis filtered water I highly recommend that you educate yourself about all of the minerals and their quantities and that are naturally present in water before reverse osmosis and then remineralising the water again before consumption. There are kits available for this procedure though I couldn’t begin to recommend any. Do your research, Search Encrypt and Startpage are your friends as they don’t track one iota of your browsing nor collect or mine your personal details like Chrome, Google, opera, Bing, Yahoo and several others do! All I can say is do your research, educate educate educate! happy drinking natural clean living water in optimum quantities, whatever feels right for you. Peace to you all, Namaste

    2. You might be taking the wrong supplement. Many (and I would say the majority of) people feel bad taking high dose niacin. Niacin releases histamine and many stress response growth factors from mast cells, and invariably causes flushing and itching in most people, and abdominal stress and diarrhea many, and in some cases internal bleeding (including strokes!) . Carefully prescribed higher dose niacin may have beneficial effects on cholesterol in those with hypercholesterolemia, and may have a “small” and poorly studid anti-aging affect in animals as well. NMN-beta and niagen are related but different compounds than niacin and are the ones with the significant anti-aging effects in animal studies. Neither NMN-beta nor niagen cause significant flushing or ill feeling to my knowledge and not in my case anecdotally. NMN-beta is quite bitter from some suppliers, and I am not sure if that is a contaminant or some suppliers are using an additive to cover up a naturally bitter taste.

  13. Hi, how about nicotinamide (NA) as a precursor for NAD+? It seems it boosts NAD+ production on the one hand but inhibits SIRT on the other. I have about 1.5Kgs of this stuff and I would really like to know if it’s recommended or not antiaging wise.

  14. We’ve used NR for the last few years with relatively good results, however since the evolution of the NMN and NAD supplements results have been incredible!

    1. I agree there is not just one ingredient that works. Science is advancing all the time. Also you want to address other factors of aging like lipofuscin, glycation, senescent cells, telomeres and more.

  15. Well, after experimenting with Niagen(NR) I’m gonna go ahead an call it confirmed…at least by me; NR is a Bad Idea for MTHFR folks. I was taking 4 a day for 3 days then 1 a day for 2 more. It was kind of a perfect storm scenario though so I can’t blame it entirely on NR…On the 4th day wound up very hypoglycemic and cut the nr back to the aformentioned 1 a day. Sidenote: I take 2x daily thorne Methyl guard plus and 2 x daily AOR Advanced B…so I get about 3 mg of B12 daily plus the other Methyl items. 5th day took a Rabaprazole (sp?) an antacid that also depletes b12, as I was going to be drinking…woke up after the party with the worst ever hangover (only drank about 6-7 drinks) super hypo glycemic and continued to repeatedly go hypo glycemic (very rare for me on my keto diet) repeatedly over the next 5 days with severe debilitating anxiety, dizziness, thinking issues, other weird brain stuff, breathlessness, super tired etc etc. On the verge of going to the hospital several times…when someone suggested look at my b12 (I wasnt’ thinking I was low given what I supplement) I decided to try a few megadoses of b12 with some TMG…one hour later, blood sugar corrected, dizzyness 90% reduced as where other symptoms…3 days later after much b12 supplementation and me feeling much better, (because I am stupid), I decide to see what an NR will do to me… pill later:right back into hell with the aformentioned symptoms!!! Anyways…just wanted to confirm that people SHOULD absolutly be cautious with this nutrient despite the attractive benefits. Thanks to you Chris for being a light in the dark for this issue.

    1. Sounds like you’re overdoing everything. Why do you need to supplement so heavily? Go easy. Just take the recommended 250 mg of NR per day (or half that if you’re young (cause you don’t need it much then)). Also take a small to moderate amount of TMR or beatine.

  16. I am 84 years old and in good health. I take no prescription medications or over the counter medications (except caprylic acid as further discussed). Brain glucose absorption declines in the elderly, but ketone, the alternative energy source for the brain, does not decline with age. The medium chain fatty acids caprylic acid (C8) and capric acid (C10) which comprise about 15% of coconut oil are an excellent source of ketones. I now take 60 ml (4 tablespoons) of caprylic acid daily in four doses between early morning and late night in hopes of maintaining brain health.

    Use of ketones in lieu of glucose results in increased NAD+ because when ketones metabolized by NAD they reduce 64% less NAD+ compared to glucose metabolism. This fact is now considered to be the main mechanism behind the many observed benefits of ketones. I have not seen any studies that compare the increase in NAD+ brought about by ketones compared to that brought about by NR.

    Because ketones provide an alternative energy source for the aging brain while NR does not, it seems to me that the elderly would benefit from increasing NAD+ with ketones rather than NR. What is your opinion?

  17. BTW…based upon your recommendation, I am ordering TMG, especially since it seems very cost-effective! Thanks!

  18. I am 66 years old. Aside from osteoarthritis, I’m in good health. I have been taking NADH+ (25-50 mg sublingually) for 6 months. NR (300mg/day) for 4 months. Pterostillbene (150mg/day) for 5 months. Fisetin (1gr – 2 consec days, for 2 consec months – to reduce senescent cells). Quercetin (39mg/day) for 1 month. I have suffered from severe degenerative arthritis for over 30 years, having been on 300mg of tramadol, plus other anti-inflammatories for over 20 years. In the past month, I have stopped my anti-inflammatories completely, and I have, so far, cut my tramadol, by 1/3 (some slight withdrawal symptoms). My arthritis-related pain levels have been reduced and I am hopeful to continue cutting back on my tramadol, slowly.

    Of course, I realize that I am self-experimenting, but I am JD-level educated (law, not in sciences! lol) and feel that I am trying to do my due diligence. MY QUESTION: On my next bloodwork, what should I be looking for? Any other thoughts? Thanks for your work and commitment, Chris!

  19. Why do the leading researchers (who have no financial incentive) use doses in clinical trials that far exceed 35 mg (for NR and NMN)? And have there not been any negative side effects associated with these higher doses?

      1. Chris, I think, has suggested that taking daily doses of TMG (Trimethylglycine) will reduce or eliminate this issue. I have been taking 1gr per day, with no side effects. I am having updated blood tests in 2 weeks and I will update my comments with relevant results!

  20. Hi Chris,

    Thanks for the video, I appreciate getting this kind of information from someone with your academic background, and balanced tone.

    Thorne sells a supplement containing both Niagen and betaine in a single pill (link below), which seems more convenient. A single pill contains 150mg niagen and 25mg betaine. Given the information in your video, does this by itself strike you as a good balance?


  21. Hello chris,

    i have experienced the trouble you are describing, by taking NR 250 mg a day, i was becoming very anxious, and very anxious, to a point having panic attack for nearly nothing. I have to take ISRS (seroplex) and i have stopped to take any complement, at that time i did not know that NR could have this effect, i tried again NR 6 months later (always not knowing this issue), and they day after day (about 10 days) i was becoming very anxious again, so i search NR anxiety and found your article .. i stop NR and anxiety vanish .. so i am pretty sure that the problem came from NR (without TMG i am assuming)
    My question is why it happens on me, and some other, but FDA authorised NR (so i assume they have tested it !) , and many users does not experiment such problem ?
    best regards

      1. Chris, I hope you see this as it is valuable information/insight. I am someone who has struggled with pain off and on in the past (depending on my stress levels / how much sleep I am getting, etc). Niagen started increasing my pain a few days after taking it. Typically it only hurts if I press down on certain bones on my face (I have TMJ) but after taking Niagen I noticed it was hurting if I pushed on various muscles as well. I took your methyl group advice and started taking 1g TMG (I took extra to be sure I was covered) and it resolved the issue at first but then a few weeks later I developed full blown fibromyalgia where many of my muscles were permanently aching even at rest. This on a dose of 125mg/day Niagen. This went on for days then I stopped taking Niagen and quickly reverted back to my normal self (thank god) that only has pain if I press down on my TMJ points (so I just don’t touch them and it’s 0 impact on my life!). Also I am VERY sensitive to dopamine changes and can definitely confirm what you said about Niagen affecting dopamine levels. When I first start taking it (I have run a few trials) it makes me hyperstimulated and wake up earlier in the morning but tolerance to those effects did develop for me after a few weeks. I am sure this is involved with why many people “wake up earlier than usual but alert” when they are on Niagen — unlike them, I don’t see this as necessarily a good thing. I think the dopamine provides the alertness but that getting less rest is a red flag as I do not believe the niagen is magically making the body work more efficiently and “need less sleep” causing them to wake up earlier. I know NAD+ is involved in sleep wake cycles and dopamine and I think this waking up early is a worrisome side effect not a added benefit, and will contribute to burn out eventually. Note that I have every COMT defect listed on the MHTFR sites (all but one are homozygous) and I am MTHFR C667T double. Just wanted to let you know that, unfortunately, the extra methyl groups are a patch for the niagen issues but don’t seem to address the root cause whatever that may be (and don’t work for everyone either!). This makes me worry about other subtle effects Niagen is having on the body that we can’t see. My morbid curiosity might lead me to try your other suggestion of only taking 30mg Niagen just to see what happens with the widespread pain. Also I have my suspicions about Niagen possibly having side effects similar to taking 150%+ RDA of certain antioxidants (such as C, E, NAC, and many others I am sure) which are proven to suppress the exercise adaptation of increased VO2Max and who knows what else. I know the study they did on mice used INSANE dosages of Niagen and caused them to be able to exercise less, but I don’t know what else has been looked at (such as VO2Max). High dose antioxidants can also speed tumor/cancer growth. I also have my suspicions about most of Niagen’s benefits being similar or the same as exercising or intermittent fasting and that we should 100% NOT be taking Niagen but doing those instead.. and if you already do one of those things (intermittent fasting or exercise) I have a feeling that Niagen is not just redundant but an an unwise addition. Of course caution is implicated for fasting of any kind as it can raise stress hormones AND some people (such as chronic fatigue people) don’t make ATP very well without constantly eating and could have their conditions worsened by fasting.
        Anyway, hope this helps in some way, I am FULLY in support of what you are doing and I am on a similar mission.. hopefully one day we can get this information out on a mass scale. You are exposing everything that I have been dying to tell the world and just the fact that you exist has given me hope for this planet. Thank you! I would love to be more involved so if there is anything you can send me or invite me to I would greatly appreciate it and would love to have the ability to feed you information that I deem vital and important to mankind (not spam — more along the lines of the most important things to helping on a mass scale — similar to my input on this topic, or genius ideas such as the choline calculator). Good luck!

      2. Chris,

        A simple question:

        If niacin caused such serious depletion of methyl groups, wouldn’t we have seen hundreds, if not thousands of reports of problems in people who take high-dose niacin on a daily basis?

  22. If i take 125 mg of NR and a cap of Thorne Methyl-Guard at the same time, will i hinder the effect of NR??

    Thanks Chris

  23. The link to the product show that it comes in capsules / fixed dose. (Picture 2). Is it powder and just a typo?
    Is there a place that is reputable that sells powder for less money? I believe money will be the biggest barrier to using this product.

    1. Maybe you clicked on the TMG. The NR powder link goes to a powder. I don’t know of a cheaper one.

  24. “Or maybe she’s starting to have lower creatine levels”. Are you insinuating that one excretes their creatine with overconsumption of niacin ( all forms)?

    1. No, I’m not “insinuating” anything at all, but I am arguing that since niacin depletes methyl groups, 45% of methylation is used to synthesize creatine, and creatine synthesis is by far and away the most acutely sensitive process to the methyl group supply, that her creatine synthesis would drop.

    “So far there is no evidence from human or animal studies that nicotinamide riboside reduces methyl donors enough to contribute to any metabolic or other physiological problems.” …” In fact, preclinical models of liver dysfunction16-18 and a recent clinical study9 all point toward nicotinamide riboside’s potential to support rather than harm liver health, which is an important physiological marker for the state of our methyl donor system.”

    1. Therefore, something that one-to-one steals methyl groups on a molar basis, should not be regarded as having *any* potential to cause problems in *anyone* because the statistical *means* in studies show it is ok, and the easy pairing with a methyl donor should be disregarded as a means of mitigating the potential issue?

      1. I have haemochromatosis and have just started taking 250mg of NIAGEN® (nicotinamide riboside chloride) per day. Is this a bad idea?

      2. Hi Chris, I noticed you responded to the reference for the article, but I’m still a bit confused. Is your stance that NR is not as different as Nicotinamide or Niacin as suggested? “Nicotinamide riboside has a much larger molecular weight than the other B3 vitamins, which means that their milligram doses are not directly comparable. Two grams of niacin or nicotinamide is not equivalent to two grams of nicotinamide riboside. These doses deliver very different numbers of molecules, and this matters because it’s the total number of molecules and not their overall weight that determines how many methyl donors get used. To get the same number of molecules found in two grams of niacin—and thus put a similar strain on your methyl donor system—you would need to ingest nearly five grams of nicotinamide riboside. The highest dose clinical trial of NR to date (2 grams per day for 12 weeks) actually showed trends toward improved liver health.” While I firmly believe in bioindividuality and unique factors for each person, I’m currently researching the effects of Niagen supplementation for stem cell injections, and with the exception of methylation (which as noted has varying views), I’ve yet to see many contraindications for NR. Would you be able to expand or speak to this in more detail on another video? Appreciate you!

        1. I don’t remember the original context here. Nicotinamide riboside is approximately twice as heavy as TMG, so you need half the amount of TMG. TMG generally is found in doses of 500 mg, so you’d have to take 1 gram of NR to need more than one capsule of TMG. I was recommending using doses starting as low as 35 mg and titrating up. If you were using niacinamide, the molecule is about half as heavy as NR and similarly as heavy as TMG, so you’d need equivalent doses. But if you were operating at the doses I recommended it wouldn’t matter because you’d be way under the TMG requirement that you get from a single capsule. At higher doses you do in fact need to take the different weight into consideration.

          1. Will TMG protect my liver from the niacin or NR? I think it’s have a negative effect

      3. the human organism is complex – genetics, epigenetics, hormones, signalling, microorganisms all influencing our metabolism. The observations made using Niacin and derivatives could be valid and as you propose for a large group of men independent of MTHFR polymorphism or other genetic traits. But the hypothesis that this is due to consumption of methyl groups should be examined closer:

        what is the daily nutritional need of methyl groups on a molar basis? Suppose you take 250 or 500 mg of Niacin daily and all of it will be methylated and excreted. What part of the daily nutritional need of methyl groups does this correspond to? 1%. 10%, 50% more? Are we talking about a relevant quanity.

        Did anyone who took Niacin and experienced loss of energy after the initial phase take methyl-group donors (MSM, DMSO, methyl donating aminoacids, …) to counteract the hypothesized consumption of methyl groups by Niacin? This exercise could give some hints confirming/disproving the quantitative aspect of your methyl group deficiency hypothesis.

        Should the quantitative aspect concerning whole body methyl group homeostasis turn out to be improbable, there could still be a local effect for instance in liver methyl group metabolism.

        This is a late reply to an old post. Do you have new insights that could be sharde or aded to the main body (link to newer article, …?)

    1. The abstract of this study kinda implies that there is no bioavailability to oral administration or NR. This is in contrast to many, many other studies that conclude just the opposite. We may all just be living in a delusion but most of the people who regularly take NR orally would also respectfully disagree with Mr Rabinowitz.

  26. I was advised to take 500 mg Nicotinamide twice daily for multiple basal cells. I’m concerned now about the side effects mentioned here.

  27. I’d been under the impression that the main reason to take NR is that it solves the problem of flushing that high doses of niacin can cause. At this low of a dose, why not just take niacin?

  28. Have you heard of anyone having trouble stopping nicotinamide riboside (Niacel)? Ive been taking 250 mg about 6 months, probably 2 to 3 days in a row then resting. I went down to 125 and after 3 days it almost feels like ive cut a benzodiazepine in half. I don’t understand why am i feeling so terrible coming off of a supplement like this?

  29. Hi Dr. Masterjohn,
    Thanks for the excellent information. I’m in my mid sixties and already take a vitamin supplement that contains 20 mg of Niacin. Can I take 25 mg of Nicotinamide Riboside in powder form, as well, or is it better to take a smaller dose? Also, is it safe to give a minute amount, i.e. a tiny “pinch” in dog food, to an older dog? I greatly appreciate your wisdom. -Beth

    1. Hello,
      I have been giving my elderly small dog (10 lb) about 10mg for the past few months on occasion. She seems to have no difficulty and I will be administering it more regularly now. I have read where a guy has been giving his (older)70lb dog around 300mg per day. I won’t be giving much more until I read more about it.

  30. I’m in my mid sixties and already take a vitamin supplement that contains 20 mg of Niacin. Can I take 25 mg of Nicotinamide Riboside as well, or is it better to take a smaller dose? Also is it safe to give a minute amount to an older dog? Thanks.

  31. hi thank you for all those precious informations. NMN makes me jittery after3days.
    I hesitate to add TMG because TMG taken alone can also make me feel anxious, But maybe it is a matter of balancing one with the other?
    should i take the same amount of TMG and NMN ? sublingually both? at day or night pre or post work out ?
    ps: i noticed by chance that folic acid at no less than 15mg a day makes me feel so better

    1. I would try them in equal amounts. I don’t know how to explain why you’d need such large doses of folic acid.

        1. I will check that, thank you Chris, but I know i have some MTHFR genes by dna analysis.
          another subject :
          Do you think that take nicotinamide/TMG not every other day but let’s say every 3 days could be better for anti aging purpose, and avoiding back effect rather than take it continuously?

  32. Hi Chris,

    Great article!

    I’m an Overmethylator. Activated B-Vitamins (Thorne Research) often make me feel a little ‘high’ for a few hours after taking them, and then I start to feel a bit titchy, anxious, kinda stressed, and moody. I feel like the ‘juice is drained from my brain’, it’s hard to explain.

    I then take one tablet of Nicotinamide 250mg, and I feel better within 15mins; and you’re right, I also feel a little flat afterwards, and dare I say a tiny bit disassociated for a few hours..?

    I realise now that I was taking too much Nicotinamide, and would be better off taking maybe 30-50mg…

    After watching your video on ‘Glycine over Niacin’, I quickly bought a Glycine Supplement (Thorne).

    My questions:

    1.) Is Glycine sufficient, or does it have to be trimethylglycine?

    2.) I’ve had Eczema my whole Life (35yr old male), and after I started taking Activated Bs relatively recently, my Eczema broke out.

    I read somewhere that because my Body & [Mutated] Genes are now receiving what they need to properly detoxify, this is now what is occurring, and for me, my dominant pathway is my skin. Have you heard of this before?

    P.S. For any Eczema / Dermatitis Sufferers reading this, you have my sympathy. Buy some Quercetin. Research it. Quercetin & Bromelain is UNBELIEVABLE!


    1. You want glycine for this purpose NOT trimethylglycine. Treat them as two completely different things.

      The eczema — maybe, I don’t know.

    2. You want glycine for this purpose NOT trimethylglycine. Treat them as two completely different things.

      I don’t know about the eczema.

  33. Why not just take an additional creatine and choline supplement along with the dosage recommended if there are issues? Most people exercising will be doing this anyway.

    1. Creatine lowers the methyl demand but it doesn’t supply methyl groups. Choline, yes, but I recommended betaine on the basis that it is easier to get the needed amount and the betaine goes into the pathway more directly.

  34. Started NR about Feb this year. 250mg daily. Great results for 4-6 months then effect wore off.

    Started taking 1000mg TMG along with b6 and b12 and folic acid (homocysteine modulators). Combined this with 250mg NR. I felt improvements from TMG almost immediately (including helping with allergies) and the benefits of NR previously had seem to return over a week or two.

    I might not be using ideal dosage cause it’s what is available to me at the moment but TMG definitely helps with NR in my experience.

  35. I’m curious if you have any thoughts on supplement timing wrt methyl-donors and B3.

    While practicing intermittent fasting, I usually take Methyl-folate + Methyl-B12 with TMG when I wake up, then have breakfast in the mid to late afternoon.

    I’m curious if it would make more sense to add Nicotinamide Riboside to the fasted B vitamin routine, or take the B’s with my first protein-rich meal, or do something like NR in the evening.

  36. Have to disagree with you on the niacin issue. I’ve been taking 3 grams of regular niacin daily with food, for decades, with no adverse effects of any kind. My liver enzymes and urine have always come back within normal limits. HDL within 70, LDL under 80, TGC under 60. I eat whatever I want. Worse side effect is a niacin flush that dissipates after just a few minutes. Results may vary; do your blood labs regularly.

    1. I agree with you. I took NR for almost 2 years. I elevated my dose up to 750 over time. I noticed very little, except how much money it cost. For well over a year now I’ve be taking 3 grams of Niacin a day. I would love to see some studies where NR is compared to normal Niacin. I believe Niacin would prove to be better on many levels, as long as its tested at a therapeutic dose…

      1. Niacin is one vitamin that many knowledgeable doctors love, if one takes enough of it. I’ve been taking straight Niacin for decades, 3 grams with my one meal of the day, then I fast for the next 18+ hours until my next meal. I do not take NR, yet this has worked great for more than 30 years, plus I can eat whatever I want. No kidney or liver issues, and lipids are ideal. Two baby aspirin with the meal (uncoated) tame the temporary flushing.

    1. Because one methyl group is used per molecule of TMG and the dosing is therefore easy. Methylfolate and Methylcobalamin are not primarily methyl donors, since virtually all the methyl groups they will supply will come from serine. The dose cannot be computed, and they cannot possibly supply the number of methyl groups needed in any case.

  37. FINDING:
    Over-expression of the NAMPT (NAD+) pathway can increase the cancer cell proliferation and survival rate in glioblastoma ( a type of brain cancer) and make those cells more resistant to cancer treatments and natural apoptosis.

    Does supplementing with Niacel Nocotinamide Riboside OR with more generic Niacinamide make it more likely to : 1) get glioblastoma 2) die from glioblastoma, if one gets it?

    1. The comment below is incorrect with regards to the kinetics of the NAD biosynthesis. Raising your NAD+ levels is neuroprotective. NR is not the solution and should NOT be used a supplement.

      NMN is the only precursor one should take. Just make sure it’s a 100% natural source.

      The bottom line is, we are aging due to an accumulation of DNA damage in our cells.

      NR is a synthetic compound the body may not recognize and has been shown to trigger an inflammatory response. I would stay away from Niagen and Basis (Chromadex and Elysium) products which have Nicotinamide Riboside. NR has to first be converted to NMN in the cells anyway.

      Why use a synthetic molecule that has an extra conversion step??? Also, how can you trust Chromadex – who adds a bulking aging to their Niagen NR powder to make more money?

      NMN is a more direct precursor shown to safely increase systemic NAD+ levels even in large doses. Dr. David Sinclair, professor of Genetics at Harvard personally takes 750 mg of NMN every day.

      NMN used sublingually is the best way to eliminate any worry, as it’s not being degraded. NMN IMPROVES YOUR METHYLATION RATE.

      Again, taking NMN sublingually avoids over-expression of NAMPT.

      1. I ran a search for the differences between NR ans NMN and it revealed the following…
        It is true that NR must convert to NMN inside the cell before being converted to NAD. However it is also true that NMN is too big to enter a cell. It needs to be converted to NR before it can enter the cell. Then it is converted to NMN and then NAD.
        So NR requires 2 steps to become NAD while NMN requires a 3 step conversion.

      2. David Sinclair doesn’t recommend on NAD precursor over another in his book. He said there is currently not enough research on NMN to recommend it over NR. Though NMN is what he and his family take. None of the NMN supplements out there, that I can find, have the dosage that he takes, so you would at least need to double up on the dosage, which gets a bit expensive. So far I haven’t found a good one so I will stick with Thorne Research’s ResveraCel for now. Other recommendations are welcome.

  38. I cleared up my actinic keratosis (AK) with the recommended daily dose of 1500mg of niacinamide + daily doses of aspirin so I am reluctant to stop what is working …

    1. Boy did your comment get my attention.
      Did you have AK over your scalp for a long time?
      Did you try 500 mg of Nicotinamide (what I’m about to try) before you went to 1500 and aspirin (what strength)?
      How long did you use 1500 and aspirin before the AK cleared? Do you mean the red scales are actually gone?
      I am looking forward to seeing your comments, I assure you.

      1. The AK was on my forearms and the aspirin + niacinamide caused the entire appearance of the skin to look better in just weeks.

  39. NAD levels decline with age. NR is suppose to increase NAD levels in older people and is considered worthless for younger people. Do you think that the negative issues you are discussing are true for both young and old?
    I’m 69. Two years ago I started taking 250mg of NR daily and also started exercising for 1 hour, 3X per week. I’ve significantly improved my breathing, stamina and mental clarity. I’ve put on some muscle and lost 8 pounds. I thought I was doing myself a good thing but now you’ve got me wondering what’s what. Is it the NR or just the fact that I’m exercising regularly.

      1. Hi Chett, so how is it going on with your TMG-NR ? Do you feel a difference in energy, aging,or anything more than exercise alone?

        PS/I take metformin for anti aging purpose(non diabetic) . & currently I am also trying to figure if Nicotinamide works better taken every other day, or just every three days.

        1. Hi Robin,
          I took 500 mg of TMG daily for about a month. I take my 250mg NR in the morning and decided to take the TMG a couple of hours later to avoid any interactions. I did not notice any differences at all with my mood or stamina. Out of respect for Dr. Masterjohn’s analysis and combined with the fact that I’ve still got this big bottle of pills, I continue to take a 500mg TMG dose a couple of times a week. I’m still a big believer in NR.
          I have been exploring with interest the use of the metformin/rapamycin anti aging protocol. I’ve known about rapamycin anti-aging effects for years now and have been following a few companies that are working on various “rapalogs” to overcome rapamycin’s diabetic side effects. Recently I became aware of a Dr. Green who has been sucessfully using low dose rapamycin on an intermittent basis (weekly). I’d be curious to hear about your experience with metformin.

  40. Aside from low Creatine, are there any blood markers that would indicate one is undermethylating due to too much Niacin?

  41. Does nicotinamide riboside have the same deleterious effect on insulin sensitivity as niacin? Is there anyway to counteract this?

  42. I’m so happy you published this info about niacin. I’ve used it for 6 years for mood issues. Several lab results in the last 3 years have shown slightly elevated alt. I think I will try tmg.
    I was using a lot of betaine hcl for digestion but digestion is better so I have decreased that.

    I also was using 5k iu d3 for about 6 years. I’ve cut that dose down and added more k2 and vitamin a. The current enthusiasm for high d3 levels is troubling and I’m glad you addressed it and clarified the calcium involvement on blood tests that are used for d3 “deficiency. “

    Also, I tried Cronometer based on your recommendation and was quite surprised at how many nutrients were not even reaching rda.

    I’m planning to get the ultimate cheat sheet soon.

    I don’t want to get too lengthy but I’m grateful for all the work you do and effective way you present it to lay people like me.

Leave a Reply

Your email address will not be published.