Andrew Huberman· PhD
the doses that they give mice in the studies where they're testing the efficacy — are typically on the order of 500 to 1,000 milligrams per kilogram
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The headline is broadly defensible, but the qualifications matter. Effect sizes vary by population, the strongest claims rest on shorter trials, and credible voices push back on how it's typically framed.
the doses that they give mice in the studies where they're testing the efficacy — are typically on the order of 500 to 1,000 milligrams per kilogram
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And so not particularly, like, wholly different than what we saw in the NR cases with the mice. - Right, a little bit better than that, but certainly those mice are healthier and more active and are more youthful.
So with the clinical studies, you know, I've seen a couple with nicotinamide riboside, but I guess the, you know, the question is with the nicotinamide riboside, there's been a little confusion about like, you know, whether or not nicotinamide riboside's even really getting converted into NAD inside cells and different organs other than the liver. This was this NAD flux paper that was done by Rabinowitz? [David]: Rabinowitz? [Rhonda]: Rabinowitz. Thank you. Yes, that study he recently published just a few months ago looking at nicotinamide riboside and how orally, at a dose half of what typically is used in all the other nicotinamide riboside animal studies. So typically, they do 400 milligrams per kilogram body weight per day. I don't remember how long, the duration they were doing it. But in the NAD flux study, he did 200 milligrams per kilogram body weight, which is significantly less than what all of these other studies like the one you mentioned with Alzheimer's disease and other studies that have shown improvements in mitochondrial function in mitochondrial mutator mice, and also muscular dystrophy, and all that. So... [David]: Yeah, we use double that dose for a while. [Rhonda]: Yeah, so maybe, you know, this NAD flux study that showed nicotinamide riboside given orally didn't form NAD in the muscle, but it did in the liver could have been a dose-dependent thing? [David]: It would make sense because we've done a lot of this in mice and now in humans, and that there's a threshold that you need to cross, you need to take a certain amount to get over probably the body's clearance mechanisms and then you get up to a level that plateaus after about nine days. And they may have just been under that threshold, so the body was just clearing it out. But you have to seemingly overwhelm that clear-out system, so that's why we do at least 400 mgs per kilogram in mice. [Rhonda]: And that's with nicotinamide riboside. The question is, I mean, that's like if you talk about a human equivalent dose for like a 180-pound man, that's like over two grams a day. And it kind of leads me to my next question, which was the most recent clinical study with nicotinamide riboside where they actually used a much higher dose than the original study that was done with Basis, the Elysium that had pterostilbene in it. This dose was like 1,000 milligrams a day and they looked at a variety of endpoints in addition to...I mean, they looked at endurance, looked at... [David]: Right. It was Doug Seals' study. [Rhonda]: Yes. And there was no statistical significance in anything. It raised NAD levels, but there was no statistical significance. There was trending improvement in the vascular system, but there was no effect on endurance. And I'm wondering again, well, if we go back to the human equivalent dose, what was given to the animals, that was still less than half. I mean, so the question becomes, is it not even making NAD in the muscle tissue at that dose or, you know, so...which brings me to the nicotinamide mononucleotide. You know, like now those studies have been done in animals at a much lower dose than 400 milligrams.
The oral dose that was used in the long term aging study used a dose range on the low end the dose was a hundred milligrams per kilogram body weight which is a human equivalent dose of around 8 milligrams per kilogram body weight so for an hundred and eighty pound person that translates to about six hundred and fifty three milligrams of nicotine amide mononucleotide which seems pretty doable of course the mitigation of age associated physiological decline was much more robust at the high dose of 300 milligrams per kilogram body weight which is a human equivalent dose of 24 milligrams per kilogram body weight or approximately 2 grams of nicotinamide mononucleotide per day for a hundred and eighty pound person again that's a pretty high dose
the nicotinamide mononucleotide animal studies the majority of them all used very high dose about 500 milligrams per kilogram body weight and typically it was injected into the abdominal region of animals which makes it quite difficult to translate findings to humans