How to Safely Take Nicotinamide Riboside for Anti-Aging | Chris Masterjohn Lite #132

How to Safely Take Nicotinamide Riboside for Anti-Aging | Chris Masterjohn Lite #132

Nicotinamide riboside. Here’s the safest way to take it for anti-aging. Hi. I’m Dr. Chris Masterjohn of And this is Chris Masterjohn Lite, where the name of the game is “Details? Shmeetails. Just tell me what works!” And today we’re going to talk about the safest way to take nicotinamide riboside for anti-aging. I’ve done a couple of previous episodes that are relevant, and I’ll link to them in the description of this one. In the last two episodes, I talked about why at the present time I would not use injectable NAD for this purpose, and I talked about why I think nicotinamide riboside is the best supplement to take as a precursor to NAD. In a long ago episode, I talked about some safety concerns about taking nicotinamide riboside, and I’ll summarize them here so I can use that as a lead-in to talk about how to avoid the safety problems and how to maximize the efficacy of the nicotinamide riboside. So, here’s the main safety problem. When you take nicotinamide riboside or any other form of niacin, your body has a choice. Either it’s going to make NAD with it, which is what we want, or it’s going to methylate it and pee it into the urine. If you don’t know what methylation is, see for some background. So, every time we methylate it, we lose it and we also lose the methyl group. We’re losing methyl groups that we could be putting towards other important purposes. Chief among them are the synthesis of creatine, which is needed for athletic performance and for muscular power, but it’s also needed for many other things including digestion and mental health. We also, after we lose control of our creatine synthesis, the next most sensitive thing is we’re going to lose control over our dopamine levels. When we can’t properly regulate dopamine, we run the risk of becoming too mentally rigid, and that can lead us to ruminate for example on anxiety or depression-producing thoughts, and that can lead to its own set of mental problems alongside the sapping of the creatine supply. And we know from the studies published on nicotinamide riboside that it absolutely saps methyl groups because it causes a very large increase in the methylated niacin metabolites detected in the blood and the urine. So, in the way that it’s being dosed, it’s absolutely sapping the methyl supply. Word on the street is that ChromaDex will at some point soon publish a study showing it doesn’t effect homocysteine in the blood and it doesn’t effect levels of S-adenosylmethionine in the blood either. But I’m not too concerned about those. I’m concerned about decreasing creatine synthesis, and I’m concerned about losing control over dopamine. And if you were to assume that most of a dose of nicotinamide riboside is actually going to be sapped into the methylation pathway and peed out in the urine, then what you would expect from that is that for every 1,000 milligrams of nicotinamide riboside you take, you’re decreasing your creatine synthesis by 25%. So if you take 2,000 milligrams of nicotinamide riboside, if most of that is methylated and peed out in the urine, you’re cutting your creatine synthesis in half. And if you cut your creatine synthesis in half, that can cause negative responses in your muscular power, in your digestion, in your mental health, and so on. So how do we make sure that the nicotinamide riboside is number one, not methylated and instead goes into making NAD, which is the positive response we’re looking for, and then number two, to the degree it is methylated, how can we make up for that and make sure that it’s not hurting our creatine synthesis or our regulation of dopamine? This is what I would do. Number one, always take it with meals. Why? Because even though you can absorb niacin in any form fine without a meal, your meal is going to boost your energy levels, and your energy levels in the form of ATP are going to help drive that niicotinamide riboside into synthesizing NAD. The better you do that, the less you’re going to methylate out. The second thing that I would do is spread it evenly across meals. And the reason is that with any given dose at one meal, there’s only a limited amount that you’re going to be able to retain as NAD. And we don’t know exactly what that amount is, but we know from the studies that publish, that have been published using the dosing regimens that have been published, we know that we are losing a lot of it as methylated metabolites, so our best defense against that is to divide it evenly across meals. Finally the third thing is we’re going to assume that there’s going to be some portion that we’re going to lose in the urine as methylated metabolites, and there’s nothing we can do about that, but we can replace the methyl groups. So I would take trimethylglycine, or TMG, in a dose that is 100 milligrams of TMG for every 200 milligrams of nicotinamide riboside. This episode is brought to you by Ancestral Supplements living collagen. Our Native American ancestors believed that eating the organs from a healthy animal would support the health of the corresponding organ of the individual. Ancestral Supplements has a nose-to-tail product line of grass-fed liver, organs, living collagen, bone marrow, and more. All in the convenience of a capsule. For more information or to buy any of their products, go to This episode is brought to by Ample. Ample is a meal in a bottle that takes a total of two minutes to prepare, consume, and clean up. It provides a balance of fat, protein, and carbs, plus all the vitamins and minerals you need in a single meal. All from a blend of natural ingredients. It’s available in original, vegan, and keto versions portioned as either 400 or 600 calories per meal. I’m an advisor to Ample, and I use it to save time when I’m working on major projects on a tight schedule. It keeps my brain going while I power through the day, never letting food prep get in the way of my productivity. Head to and enter the promo code: CHRIS15 at checkout for a 15% discount off your first order. For ad-free versions of these episodes with transcripts that you can read and getting early access to the episodes often weeks or maybe even months ahead of time, you can sign up for the CMJ Masterpass at and use the code: LITE10 to get 10% lifetime discount. The audio of this episode was enhanced and post-processed by Bob Davodian of Taurean Mixing. You can find more of his work at All right, I hope you found this useful. Signing off, this is Chris Masterjohn of This has been Chris Masterjohn Lite. And I will see you in the next episode.



  • Green Eggs and Ham

    Very helpful. I've been taking what now seem to be large doses of TMG ~3000mg [level teaspoon] with my NAM at 300mg, two or three times a day. I don't think there's a danger with that much TMG?? I also take creatine ~2g twice a day. Also a high strength B-complex as I remember reading somthing about NA/NAM messing with …something ?? maybe homocystene?? …that is put right with one of the B vits in my complex [can't remember which] ??

    Twice a week I've just started taking NA in the mornings on an empty stomach, repeat dosing after an hour and again after an hour to supress FFA in the blood and stimulate GH ready for resistance training in a fasted state [there's research to back that up]. I've included TMG with those doses.

    Any thoughts welcome.

  • Green Eggs and Ham

    I wonder if the case for taking CoQ10 increases with up-regulated NAD+ ?? [I need some persuasion to take it as it's pricey for me]

  • Ross UK

    Thanks Doc. Because of your last vid on the dangers of niacin and my own experience I was led to discover TMG which I respond really well too. I think I had what you described – an initial lowering of histamine but then an increase in homocysteine. Now I try and get by through a balance of the two. Maybe I'm MTHFR? I plan on taking a test soon…

  • Aragon Guillard

    Wouldn't be better to take creatine together?

  • Anemic Goal Hop

    Is TMG preferable to straight glycine? I realize there are methyl groups attached to the TMG, and if you're losing methyl groups by taking NR you want to replace them, but isn't the purpose of taking it to get the glycine rather than the methyl groups? You can get more methyl groups by eating more protein. It's the glycine that's important here, right?

  • Rone

    I find that sublingual pure NAD+ has the most pronounced effect in my testing 🙂

  • WeDon’tExist

    Hey Doc,
    Was just wondering what the effects of mixing NR and Resveratrol are. Would it have any effect on how much NR is made into NAD and how much of it is urinated?

  • obeysteve

    Can you recommend a TMG supplier? All of the manufacturers on Amazon make 500mg-1g capsules, which is massive overkill if I'm taking 300mg of NR and following your protocol (which would be 150mg of TMG).

  • Mandy Beddoes

    please help Chris …can creatine help with hairloss ? age 52 women hair fell out

  • MonteSanoMTBer


  • Rose Heindel Howsden

    Too bad it’s so expensive. Is there a certain age you should be taking this by to get maximum benefit? Can I just wait until I’m that age and still get the effect?

  • dannybex

    Chris, does this form of niacin increase histamine? I react poorly to the other forms…

  • Outlaw

    Very useful and important info, thanks Chris!

  • Jesus Alvarez

    So after researching these types of videos I went to Amazon, and I looked up some NR suppliments, and came across Thorne ReservaCel. It seems to have 150 mg of nicotinamide riboside chloride 75mg of resveratrol and 25 mg of trimethyglycine per pill. The instructions recommend to take 2 pills one or more times per day, but based on these vids that seems like overkill. I prefer to take one pill 2 times a day. Are these good ratios? Is it too much, or too little? I'm feeling good by the way. No side effects yet one month in.

  • Todd Skelton

    What do you recommend for people only consuming one meal a day? Right now, I'm taking 150 mg in the morning on an empty stomach and 150 mg with my meal.

  • Jason Voss

    Ironic if the anti aging benefits of NR were negated by the financial stress of paying for it haha. Doh!

  • My Healthobs

    Q) I’m taking niacin (in the hope of reducing lp(a) as well as 250mg NR .
    Can I take Methyl Folate instead of TMG ?

  • Georgia37890

    I take my NR immediately after breakfast every other day with a dose of only 150 mg. I assume that the low dose of NR and taking it after breakfast will minimize those metabolic pathways which might divert the NR from converting into metabolic products other than NAD. I hold a B.S. in Biochemistry.

  • Andrew James

    Very helpful. In terms of the danger mitigation techniques you describe, would you recommend the same things for NMN taken sublingually? Including taking with meals? And do you have a recommended dose of TR. Tru Niagen's version comes in 150 millgrams capsules. So if I have three Paleo-ish meals in a day, I should take one TR pill for each meal? Plus 75 mg of TMG with each meal,I guess.

  • jim dee

    the whole methionine that is made into Sam-E and half of that is used to make creatine … I don't understand why mental health doctors don't suggest, take CREATINE directly instead of expensive Sam-E or cheaper precursor l-methionine

  • KiwiM3P

    Is Niacinamide a cheaper alternative or is it totally ineffective?

  • MrEspirit91

    Hi Chris. I am wondering does the mitochondria need FADH2 (flavin adenine dinucleotide) together with NADH (Nicotinamide adenine dinucleotide) do make ATP (in the electron transport chain)? Or does the NADH donate electrons separetely to make ATP from the FADH2?

  • Informed Consent

    About a year ago I took nicotinamide riboside for a short period of time and absolutely hated it. It was tanking my workouts. Whether I was running or doing resistance workouts, muscle fatigue was coming on quicker, performance was going down and I felt like I was dying during the workout. Thank you Chris for explaining what was going on. Metabolizing the nicotinamide was causing me a methylation deficit and a creatine deficiency.

  • Charles Brenner

    As people pointed out already, you get methyl groups from virtually everything you eat. The fact that there is methyl group deposition on nicotinamide is not equivalent to a safety concern. There have been no adverse events reported in any clinical testing of NR. We have tested 8 weeks of NR at 3 doses and looked for depressed 1-carbon metabolism using exactly the assay that was used for nicotinic acid and nicotinamide. Whereas single doses of nicotinic acid and nicotinamide increase plasma homocysteine at 300 mg, we saw NO CHANGE after 8 weeks at 3 different doses of NR. Moreover, the idea that you would get "sticky brain" from any form of niacin is inconsistent with DECADES of use of gram levels of nicotinic acid. Abram Hoffer is literally in the Orthomolecular Medicine Hall of Fame for advocating high dose niacin for psychiatric conditions. It's not clear that it works for all-comers but it does not produce sticky brain and it's not unsafe. There's a danger to people saying there's a danger when you don't have the data….

  • wayne terry

    You recommended taking 100 mg of TMG for every 200 mg of NR. If you split the 2 pills of Tru Niagen over 2 meals each table has 150 mgs.
    So that would be 75 mg's of TMG, I couldn't find any products with anything close to that, all much higher? Any advice?

  • Tony Gordon

    I have been taking niagen for four years. Currently taking 2 tablets of Elysium which is 250mg of NR-E (Crystaline Nicotinamide Riboside) and 50mg of Pterostbene(similar to Reversatol). I do it on an empty stomach. Is that bad? It seems to work. Also How much TMG and Creatine should I be taking?

  • Brian Hickey

    Stack it with betaine problem solved

  • Robert Hoffmann

    Thanks for the information ! Gonna get some TMG…
    Would you say this:
    Which contains: Inositol Hexinicatinate / Riboflavin similar to NR, or has absolutely no similarity ? I'm asking because this seems cheaper, and since Niacin/Riboflavin seem to be the actual precusors to NAD production. OR maybe even just stacking Niacin with Riboflavin ?
    Thanks !

  • Lisa A

    Excellent detailed info explained simply. Thank you

  • Maximus L. Satherozian

    Can it be taken with antipsychotics like latuda ?

  • Boondock Saint

    No news to me. I take one with breakfast and one with dinner. Don't take too much

  • frank brown

    i've been taking NR on empty stomach–300 mg (2 pills) and then an hour later still on empty stomach 300 mg more. believe this has increased yoverall energy level quite a bit. I work out 1.5 hrs. day and take a slew of other supplements at age 72. After this Masterjohn vid i will make another effort to see if there's more info re when and how much to take, but i do notice that David Sinclair takes nmn on empty stomach and the Resveratrol mixed with a little Yogurt.


    I was taking niacinamide.. to sleep but I could never wake up the day after I’d be way too groggy 🥴 …xoxo

  • Nmethyltransferase

    Is it actually worth the money?

  • Corey Tman

    Nican gives me too much engergy mental

  • Eric Klein

    Chris can you please comment? (New from PubMed)

    The manufacturers of TrueNiacin claim no methylation dysfunction as per proxy of no HCY elevation. Can you please review and comment? (Hypothesis: NR differs from older well established studies of "generic B3" supplementation)

    Sci Rep. 2019 Jul 5;9(1):9772. doi: 10.1038/s41598-019-46120-z.
    Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults.

    … NR and plasma homocysteine

    Nicotinamide N-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine (SAM) to NAM, generating to MeNAM and S-adenosylhomocysteine49–51. S-adenosylhomocysteine is then subsequently cleaved to homocysteine (HCY) and adenosine. It has been reported that single 300 mg oral doses of NA and NAM increase plasma HCY levels23, indicating a potential shortage of methyl groups that could be needed for formation of molecules such as dopamine and creatine. Moreover, increased plasma HCY is an independent risk factor for the development of vascular disease57–59. To determine whether prolonged ingestion of NR increases plasma HCY levels, a post hoc analysis was conducted using sodium citrate-treated plasma samples collected during the study. Compared to baseline or the placebo-treated group, NR ingestion had no effect on plasma HCY levels (Fig. 4).

  • hoishey

    Can a 77 yr old man take it?

  • Harold Dean

    I take niacin and NR as well as TMG. Will taking TMG at the same time with niacin or NR change their effectiveness or bio-availability?

  • The Void

    Then what about CR and fasting ? that increases NAD production

  • hanig11

    Another expensive supplement that promises life ,but only empty’s your wallet.Just exercise and eat healthy and hope you don’t get run over by a bus .Save your money for vacations on the beach .

  • Eric Philo

    all visitors please READ THIS new transporter found "Slc12a8 is a nicotinamide mononucleotide transporter" at nature site. going to avoid links cause comments end up a lot of times in MY cache ONLY. here is another "What’s the Deal with Oral NAD+ and NAD+ Precursors? A Bioavailability Report" . i went for sublingual absorbtion of NR but now its not on my radar. researchers are homing in maybe on another pathway that i think was something involving NRdisulfide which could pan out. Brenner comments below and him, Sinclair, and Dr. Leonard Guarente were involved in research and production and are some smart guys imo. all of us together are moving this forward AS THINGS CHANGE and i appreciate everyone here. i have 50+ bookmarks on topics involving 1. SIRT mods(started resvera in 2007 and then the recession aged me like a dog) 2. NAD precursors 3. AMPK mods 4. Senylitics 5. Mitophagics . i've goofed with all in various modes off and on. mitophagics(ya thats probably not a word) is a new area of interest and right now i'm pounding down pomegranite juice and pomegranite powder and probiotics hoping i've got the bacteria to convert ellagic acid into urilithin a. i have felt various positive effects from all of these however there is evidence of downregulation to liver toxicity and others depending on the compound/dose/route so sometimes and mostly because of finances i fall back on Fisetin, berberine, healthy foods and just more sleep. all of our interest in these and parabiosis and Liz Parish for example is on private companies radar and some serious shiaht is in trials. as things continue to evolve it will be on our radar and have immediate meaning due to our early participation. probably at some point the storm clears= FDA classifies aging as a disease, personalized medicine and clinics flush,reprogram and reseed our meat machines with the help of A.I. drivin inference to great effect. these videos,participants in low hanging fruits, and pessimists are all pioneers and it is nice to have ya.
    more -i used the term "aged like a dog" above so maybe see this Dog Aging Project: Dr. Creevy on utubee (rapamycin clinical trial research) and Anti-Aging Pill For Dogs Is A Reality.

  • mims c

    Thank you for this video and all your videos. I had an adverse effect with Tru Niagen. Bad muscle cramps, insomnia, anxiety, and I was going to the bathroom a lot and was very fatigued. I’m MTHFR positive (from one parent). Once I stopped taking it, all my symptoms went away!!!

  • Tom Yum

    Nicotinamide mononucleotide, does anyone take them instead?

  • Dzo Vancica

    Is it ok to take niacin 250mg as in pakeg in pharmacy?! asking for dementia.

  • IJustHitTheFan

    Wouldn't taking TMG block the beneficial effect of NR?
    The whole reason behind taking NR (or NMN) supplements is to demethylate the DNA. But if NR can easily bind to methyl groups from the TMG instead of forcing them out of DNA, would it even be effective?

  • UHFStation1

    How about safely taking Nicotinamide mononucleotide (NMN)?

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