Nicotinamide Riboside

“It's blowing up already. So here's the question. And then we'll go right back to what we were saying before. There's been so much interest in NAD, NMN and NR to upregulate NAD. NAD is a pro longevity. NAD for, you know, one of these things that drops over the lifespan.”

“NAD boosters such as NMN, NR, hydration, electrolytes, and more. So all that said, I think we'll get into it with talking about family history. So we've talked about family”

“including obesity, insulin resistance, peripheral artery disease, and age-related cognitive decline. We also talk a little bit about the surprising implications of nicotinamide riboside and NAD for exercise recovery. We discuss how inflammation profoundly taxes the NAD system”

“particularly the rationale behind why taking nicotinamide riboside in the morning is important to align with circadian biology. We discuss the emerging data indicating nicotinamide riboside's potential benefits for fertility, improved maternal lactation, and notably enhanced developmental outcomes in offspring, everything from lean muscle mass to cognitive function.”

“their soluble precursor form. So NAD breaks down to NR, nicotinamide, nicotinic acid goes back into cells. Cells rebuild the NAD stores. Coenzyme A breaks down to pantothenate.”

“kind of like a top line failure in the sense that the first trial that reported that NR is anti-inflammatory set out to determine whether NR could improve old men's grip strength in like two or three weeks.”

“outcomes. And they found it was NR was strongly anti-inflammatory, like greatly lowering IL-6, IL-10 and other markers of inflammation. In fact, it was so strong that the people that had the NR first followed by placebo still had lower anti-inflammatory results after three weeks on placebo.”

“an NAD precursor. supplement like a nicotinamide riboside. And you do see that, as you mentioned, that you'll see the NAD levels go up, like very high in the blood. What does that tell us about levels in the brain? Can we assume, I mean, I don't know that we can, or can we assume that the levels are going to go up in the brain or in the muscle?”

“when they were on NR, there's an improvement that was not seen in the placebo group. Did anyone look at whether or not that improvement correlated with inflammatory status? So baseline inflammatory status being higher and that being reduced?”

“That if you can, you know, either reduce that inflammation, obviously through lifestyle and diet, that would be ideal. And or if you take the nicotinamide riboside, you know, to help replenish some of that NAD to help with the inflammation, that you would affect, you know, some of the functional outputs as well.”

“And we had mice that were on high-fat diets, plus or minus nicotinamide riboside. And we simply didn't get enough fat mice to be pregnant. And go to term with their baby mice in the fat group.”

“Which is, we had perfect fertility. We had mice that were, whose moms were either supplemented with NR or not. And we were able to follow their offspring.”

“And we were able to follow their offspring. And what we found is that the offspring of supplemented. Their mothers had better lean mass at the time of weaning that they were able to maintain for their whole lives.”

“Why do I have to take this precursor, like nicotinamide riboside? So, maybe you could talk about why that is and also maybe just touch on nicotinamide riboside versus nicotinamide mononucleotide. That's another precursor. Yeah, yeah.”

“Yeah. Yeah. And so... So, nicotinamide... Nicotinamide riboside is probably the kind of premium NAD precursor in the sense that the NR kinase pathway gets upregulated in a lot of conditions of metabolic stress.”

“So, it's not that it's necessarily easier for nicotinamide riboside to get there. Oh, well, you asked about NAD and NMN, right? Well, yeah. NAD... So, NAD is not even getting inside of cells, essentially.”

“Because NAD can't get into cells. Neither can NMN get into cells. So, these compounds break down into NR or something smaller. Right. So, NAD is breaking down into... Probably breaks down into NMN first and then to NR.”

“Probably breaks down into NMN first and then to NR. And then... NR can get into cells. Nicotinamide can get into cells. Nicotinic acid can get into cells. So, this is the mechanism for the NAD drips that we're talking about, right? Yeah, yeah, yeah. Right. There's actually now a Niagen Plus, which is like a drip-grade nicotinamide riboside, which is not painful.”

“Than IV. Yeah. That said, there are some mouse experiments where intravenous NR goes further into different tissues than oral NR.”

“That's pharmacokinetics. You can get higher levels through IV. You potentially can deliver more NR to the heart. Or to other tissues through IV. So, I think that in the future, we're going to have more disease-relevant data from IV delivery.”

“So, I'm happy that there is clinical-grade intravenous NR. But there's much more data today in January of 2026 on oral NR.”

“I mean, half of the molecular weight or 40 or some percent of the molecular weight. The total molecular weight of NAD is NR. So, it's going to break down into, you know... So, it'll be digested and deliver, presumably deliver some small fraction of the total molecular weight as an NAD booster.”

“You can argue whether it's a precursor. It's sort of... It's sort of a precursor of NR, which is a precursor to cellular NAD. But again, NMN breaks down to NR and then that gets into cells and becomes NMN and NAD again.”

“Okay. NMN has a phosphate on it. But that... So, it's a funny thing. Like, why, as a chemist, would you put a phosphate onto NR to produce NMN? Why? When NMN has to be degraded down to NR in order to get into cells.”

“Meet the label claims. Some people... So, some people that are listening are familiar with both NR and NMN. Some people, this is the first time they're, like, hearing about all this. But they do know about NAD. You know, when... I know a lot of people, the way they think about it is they think, well, NMN is one step closer to producing NAD.”

“So, it's a direct precursor of NAD. The NR can get into cells. It can get decorated with the phosphates and converted into its final nucleotide form. NMN can't because NMN already has a phosphate.”

“But if you could find a safe form of NMN and take it orally, that NMN is being converted back to NR before it gets into cells. Right. That was the long-winded way of answering the question, which is essentially that you actually... It's being converted back into NR. Yeah. So, then why not just take the NR? Well, NR is the most safety-tested NAD booster on the market.”

“Yeah, yeah. How is that? Is the gut bacteria in our guts playing a role in the conversion of NR, NMN into... Brand new paper out of Nestle in Switzerland says that the gut microbiome plays a role in human conversion.”

“You can see gravitational effects of matter in cases where you can't see the matter itself. So, once someone takes or a mouse takes nicotinamide riboside orally, you can see effects in the cardiac tissue.”

“You're extracellularizing, to use a technical term. You're releasing enzymes that break down the NR artifactually. So, there are things that are difficult to observe in clinical testing.”

“For the gut bacteria. Interesting. So this was a human study? Yeah, it was a human study. Okay, I'll have to look at that. So talking now, getting into some of these conditions and supplementation, right? Now we're talking NAD precursors mostly, and nicotinamide riboside, NR, is a major one that's used in animal studies, as you mentioned, in clinical studies as well.”

“to hear your speculation on this, which is, I know the immune system is a major consumer of energy, right? I mean, it's a major consumer. If you're sick, that is a huge, obviously, sink for NAD. Do you think that supplementing with NR could help with any other immune-related benefits like fighting off infections, autoimmune disease, like you're having someone that's chronically having an”

“And in McDermott et al., and I believe that she's the top peripheral artery disease clinical trialist in the country, she's at Northwestern, did a three-arm clinical trial, placebo versus nicotinamide riboside versus NR plus resveratrol, and found that the NR arm improved their six-minute walk test.”

“And the placebo arm, as well as the NR plus resveratrol arm, degraded their six-minute walk test. So the resveratrol not only was not helpful, but it actually blocked some of the benefit of supplementing with NR.”

“So, yeah, that resveratrol thing, as you know well, is just kind of science fiction. But the NR result was really quite striking. And I believe it was N of 40 or 75.”

“In a lot of people's aging, then you could say that eight randomized clinical trials showing beneficial effects of NR in lowering inflammation could be broadly useful for human aging.”

“This is the first clinical trial, like, ever. And, look, the way I see it is, like, this is how you often find things, too. Well, right, right. So, the first trial can maybe teach you how to do the trial. But the problem is that NR is so remarkable in mice that, you know, I can induce obesity and type 2 diabetes in a mouse in a couple of months, and I can treat it in a couple of months, right?”

“You guys ought to... So I think if we randomize people that all had fatty liver disease... Yeah. And then also we did some exercise, plus minus NR could be positive in fatty liver. Did you guys look at... Look, within that group, within the NR group, just going back to this inflammation thing, because it seems like that's such a powerful lever that NR is affecting, that, like, within the people”

“They should be randomized for liver fat, right? Right. Probably they should be on either GLP-1 or exercise or something to try to mobilize fat and then see the beneficial effect of NR and talk about that.”

“If you are making the lifestyle changes, that's the most important thing. Yep. Right? If you can add this on in addition to that, like you said, like, weight loss, expecting someone to take nicotinamide riboside and lose weight in 13 weeks is... I mean, you have to do something in...”

“is a substantive amount of NR to take. The safety and the source of the NR is very important. And this material has been safety tested up to three grams per day in certain populations.”

“When it comes to taking nicotinamide riboside, these NAD precursors, you mentioned stacking it with resveratrol, which is a type of polyphenol, that it's sort of negated some of the benefits.”

“Yeah, I think that, you know, for the, the general public, you know, we're, we're, we think NR is safe. Um, there's a registry at FDA. So as you know, the F in FDA stands for food and, um, nutritional supplements are in under the F in FDA.”

“or clinical trial observations that are linked to NR, there's a file on them, you know, that we're aware of. And so far the safety data look really good.”

“Yeah. The liver can make NAD from tryptophan, nicotinamide riboside, nicotinamide and nicotinic acid. So any precursor, they can make NAD and they...”