9 months ago
“Today, my guest is Dr. Charles Brenner, who is a distinguished biochemist who made the groundbreaking discovery of nicotinamide riboside. This is a potent vitamin precursor to NAD. This is a molecule that is fundamental to cellular energy, DNA repair, gene regulation, and also immunity.”
“things NAD. In this episode, Dr. Brenner and I discuss why nicotinamide riboside is uniquely positioned among NAD precursors for effectively boosting NAD levels. It has robust clinical evidence supporting anti-inflammatory benefits at doses between 500 to 1,000 milligrams a day.”
“riboside and NAD for exercise recovery. We discuss how inflammation profoundly taxes the NAD system across a variety of different tissues. It's not merely just the blood, but also other organs as well, highlighting really the necessity of addressing all of these underlying lifestyle factors that affect inflammation.”
“very critical evaluation of intravenous NAD therapies versus oral supplementation. We get through the myths, we talk about realities, we talk about evidence-based data, bioavailability, how these precursors and whether NAD can enter our cells, and we talk about clinical efficacy.”
“can affect how we actually can benefit from supplementation. All this is to say, you're going to learn a lot about all things NAD and how to boost NAD levels in an evidence-based, way in this episode. But before we dive in, I have a couple of quick announcements.”
“of the Department of Diabetes and Cancer Metabolism at the City of Hope. And I think what Dr. Brenner is going to be talking about today is not just in the scientific community, but in the broader health community in general, is his contribution to understanding NAD biology. He had discovered a precursor for NAD nicotinamide riboside, which has been made into a supplement.”
“Yeah, yeah, yeah. No, I know. But you're talking generally speaking. Right, generally speaking. So when people say NAD levels decline in age, I don't think that there's evidence that human blood NAD declines in age. I think that the likelihood that a number of human tissue NAD pools decline or a disturbed age is incontrovertibly true.”
“Because I've seen a lot of human blood NAD metabolomes. And essentially, there's three types of data that we get. We get normal people, male and female, who have 20 micromolar NAD plus calculated on a volumetric basis in their blood.”
“mitochondrial myopathy, right, are walking around with low blood NAD, right? Generally, we don't see people having low blood NAD.”
“that have noise-induced hearing loss, I would bet a fair amount of money that their cochlear NAD is damaged. Okay, so we're talking about blood NAD versus tissue NAD. And I think the question I'm generally asking you is a more broader question, not blood NAD.”
“we'll get into this, do play a role in lowering NAD levels in the blood in other organs? So the question... More broadly, yeah. But even in the blood, I'm curious, like, if someone, if you're saying I've got normal people and we looked at them, does that mean normal, like, they don't have any diseases?”
“mean they don't have mitochondrial disease? Because, like, does someone who's obese have lower blood NAD levels than someone who is not? You know, clinical trials always have our, you know, inclusion criterion, right? So the clinical trials that looked at people that were simply older and probably were not on, you know, 12 medications saw largely normal blood NAD.”
“medications saw largely normal blood NAD. So it could be that if we look into people that have a lot of disease and conditions and have polypharmacy, we may see abnormally low blood NAD in aging people much more than I've seen. So that's a really good point.”
“disease and conditions in which the NAD system is disturbed. In not just the blood, but in every organ. So one of the things that we found in 2020, you know, so remember, we all remember where we were in March 2020, right?”
“done NAD metabolomics on it. And we had kind of a shocking result. So, we were actually able to stay in the lab. And we published a paper in 2020 on the effect of coronavirus infection, not just on mouse liver, but on human lung samples that we're able to get from war, from morgues, and from databases where they had COVID infection.”
“activated by coronavirus infection. Wow. So, were they consuming NAD? Yeah. You know what I think it is, is double-stranded RNA, right, is seen as an invader of the virus.”
“some of the drivers of NAD loss. Maybe that's a better way to put it. Yeah. When you're talking about measuring NAD levels in the blood, how much of that is really just reflective of your diet? Let's say you're getting a lot of B3 nicotine, gas, or whatever, like you're getting a lot of tryptophan.”
“gas, or whatever, like you're getting a lot of tryptophan. Is there somewhat of this like artifactual thing where NAD levels look normal or elevated because they're taking in the precursors and we're measuring it like in the blood? Well, when people take substantive amounts of NAD precursor vitamins into the 300 milligram plus,”
“you can see a substantive change in people's circulating NAD metabolome. Probably the foods that have the most NAD precursors are the same foods that have the most micronutrients of all kinds, right?”
“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.”
“you know, perhaps there is more of an age-related decline in NAD in other tissues that we're not able to see in the blood. I think there are very substantive age-related declines in NAD in tissues.”
“and conditions, the NAD system really comes under attack. So heart failure, the NAD system comes under attack. And central and peripheral neurodegeneration comes under attack. Sun exposure comes under attack.”
“illness, but like, how do those, you know, conditions put stress on the NAD system? So like obesity, the chronic inflammation, and then... So we talked about... You talked about acute inflammation.”
“We pushed them all the way into type 2 diabetes. Their liver NAD system was disturbed. And the pH was the center of that. So their ability to detoxify reactive oxygen species was degraded by being fat and being insulin resistant.”
“that has looked at how that taxes the NAD system? I don't think there is, to my knowledge. And to some... I mean, fat is an accessible tissue.”
“Okay, great. So you were going to mention sleep disturbance and chronic inflammation and how both of these sort of very common human conditions sort of tax the NAD system. Right. So chronobiology... First. So sleep, I'm not sure a study has been done exactly on sleep. But for sure in mice,”
“kind of losing their synchrony. And the NAD system becomes disturbed. There's a lot of time of day cues that go into NAD synthesis and NAD dependent...”
“assured to disturb the NAD system. Well, I'm going to circle back and go a little more in depth than that, because I have some more questions on that. And then what about the chronic inflammation? I mean, this is, to me, it makes sense knowing what I know about NAD biology.”
“disturb the NAD system, but we've been able to show that in human beings and randomized control trials that nicotinamide riboside at like a gram a day type doses is anti-inflammatory. So that's now common.”
“their lifestyle within the next two to three months, like what would have the biggest bang for their buck in terms of supporting their NAD? And it really sounds like the thing that's causing the inflammation, the chronic inflammation might be a big driver. So if it's obesity, you know, weight loss, right?”
“probably moving their bodies more is going to be, you know. Right, right. I want to get back to this, this idea of why, you know, the blood NAD isn't necessarily indicative of your, what's going on in your muscle and your brain.”
“And, and specifically, I want to get into the, you know, let's say you're taking this, 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.”
“that we can, or can we assume that the levels are going to go up in the brain or in the muscle? Yeah, there are, there are imaging experiments that show that oral NAD precursors increase, brain NAD. There are small clinical studies that show that oral nicotinamide riboside improves cerebral blood flow in people with mild cognitive impairment.”
“some of that NAD to help with the inflammation, that you would affect, you know, some of the functional outputs as well. So how would, you know, and that kind of gets to this thing, you know, and a lot of people are taking, there's a lot of people that are taking NAD boosting supplements.”
“kind of like, like, like the fitness improvements, right? Let's say they are working out and they take the NAD, like, should they be measuring their grip strength or their, you know, Okay, so let me, let me cover my COI right here, right? Yes, let's do that. So, so, so, so it was initially my technology that turned into the nicotinamide riboside, and NAD boosting industry.”
“and NAD boosting industry. So I'm chief scientific advisor of Niagen, which makes this Niagen pill, right? I'm also chief scientific advisor of NADMED, which is an NAD testing company. Do I think there's a use case for Niagen in people in healthy aging?”
“a value of NAD testing in people? Definitely in clinical trials, right? So this company, NADMED provides, you know, kits and reagents for clinical trial observations. People, some individual people buy the kits.”
“their NAD is higher. Like, do you, do you go to, if you take an aspirin, do you need to do a mass spec to see whether you ingested an aspirin? I don't, I don't see the use case for that.”
“I agree. You have to choose your battles, otherwise you're going to drive yourself nuts. And like I said, we're going to get a little bit more into the NAD precursors. I kind of want to wrap up this lifestyle, diet lifestyle, you know, factors that are supporting NAD. We talked about that are consuming, but I want to talk a little bit about the supporting systems for NAD. And”
“How does exercise affect NAD, and what type of exercise would be better for increasing NAD? Would it be aerobic? Would it be, you know, strength training, resistance training, both?”
“the gene expression of NAD biosynthetic enzymes. So I recently published that with a group in Germany, and I can't remember what kind of exercise that they did. But yeah, there's evidence that people that exercise, you're boosting a lot of transcription pathways and gene expression pathways that are, you know, I hate the word rejuvenating, but it's that are associated with youth and...”
“but when it's true, it's true, right? It's true, it's true. Does... Yeah. Does mitochondrial biogenesis play a role in some of the NAD increases as well? If you're making more mitochondria, is it like an adaptation where the body's like, we need more of this, you know, NAD around?”
“you know, you make more mitochondria, you have better beta-oxidation. How does NAD play a role in exercise recovery? Like, recovering? Recovering from, and now, I mean, like, that's part of the repair, right? Right. So you imagine it helps, but...”
“Yeah, and not just recovery, but in performance. I mean, you'd think if you're taxing the NADs that you're consuming more NAD, your muscles are working harder, and like you said, the adaptation is that you're increasing transcription. Prescription, you're going to, you know, whatever these genes or enzymes are important for making more NAD are going to be increased, so you're going to make more”
“How does that affect the NAD system? Does it know? I'm not sure that we have hard data on it. Because I don't, I mean, there probably are accessible mouse experiments.”
“I don't know how much you would value them, because you can do things, you know, with mice where you change the lighting around in the room or give them food in weird times per day, and you could potentially measure changes in the NAD system.”
“for the mammary biosynthetic lactation, biosynthetic program, it's also distributing NAD precursors. So, the mammary NAD in NR supplemented mothers was greatly increased.”
“or if they're just experiencing it because they're traveling in a different time zone. What do you think would be some good strategies to help them mitigate the effects on NAD system? Yeah. I mean, would supplementation come in there or would it be, you know, bright light exposure?”
“You just brought up a really interesting question in my brain. And that is, and the next thing we're getting into is the NAD supplementation and all of that. But before we get there, you said you were talking about taking nicotinoid riboside perhaps in the morning.”
“But also, let's say, like, let's say you are, you know, a shift worker or you are changing time zones and your NAD system is disrupted. Lots of things are disrupted.”
“You know, is that, is that really going to, is that going to affect your energy? Like, the NAD being down, one way to presume it would, you would feel lower energy, like, cognitively. And is that something that you think could be replenished through supplementation? I know I'm asking you to speculate, which is hard for you.”
“Okay. Let's get into this. I mean, hopefully, by now, everyone's convinced. They know what NAD is. They're convinced it's important, at the very least, for energy, right? If not more, repair, regulating genes, a lot of things, right? But I think energy stands out to a lot of people.”
“Phosphates don't get into cells. So, the biggest piece of NAD that can get into a cell is nicotinamide riboside. It gets into cells, nicotinamide riboside kinase, then phosphorylates it, puts a phosphate group on it.”
“Like, in the heart failure experiments, nicotinamide can't actually boost the NAD in the failing heart. Because in the failing heart, it's overexpressing a gene called NMRK2, nicotinamide riboside kinase 2.”
“So, the failing heart is sort of looking for the whole nucleus side in order to boost its NAD system. So, it's not that it's necessarily easier for nicotinamide riboside to get there.”
“Because NAD can't get into cells. Neither can NMN get into cells. So, these compounds break down into NR or something smaller. Right.”
“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.”
“Okay. Well, just for people that are listening here, just summarize. Because I know that you can actually go online and buy an NAD oral supplement. That is not going to work, right?”
“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.”
“Got it. Okay. So, it's not... But NAD itself, you know, I... Technically, NMN is... You can argue whether it's a precursor. It's sort of...”
“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.”
“Yeah. So, then why not just take the NR? Well, NR is the most safety-tested NAD booster on the market. Well, this is good. At least people have an idea now. So, I think I want to get to some of these health outcomes.”
“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”
“which is generally not a good thing for people. So, for people that are interested in just boosting their NAD, not necessary. No, not necessary. Okay, good. So the safety issues that I kind of wanted to touch on have to do with a reason I stopped taking NAD precursors many years ago.”
“to do with cancer risk. So obviously NAD is important for all of our cells. Our cells need to make energy. There's a variety of, you know, other processes that you described that are very important biosynthesis of molecules.”
“the classic NAD booster nicotinamide, um, lowers cancer risk at the population level. So it's not like if, if there was a signal that said that higher NAD status would, um, cause more, you know, small tumors to appear, you would have seen that in, you know, the clinical data.”
“um, you know. It looks like some tumors could potentially be limited by NAD supply, um, NAD is not really a fuel.”
“Um, but overall the clinical data say that NAD boosting is preventative for cancer and that Niagen is safe. Did you see this study?”
“Which isn't too surprising. I mean, if you already have a bunch of tumors and then you're giving, you know, a bunch of, whether it's folate or NAD or something, you might expect, um, rapid cancer growth, but who knows? So I think, I think that's kind of what shut me down for a little bit on, on taking the NAD precursors and back to taking them.”
“And so you can see what we're up to in the laboratory. Amazing. All right. Well, thank you for, you know, this evidence-based discussion on NAD, boosting NAD. It's very, I think, informative. And it's good to have this out there because it definitely is a popular… topic right now.”
“Dr. Charles Brenner. You've obviously studied NAD for decades. So can you tell me, you know, what were some of the early observations in your career that convinced you, this is an important molecule?”
“NAD synthetase from yeast. And he showed that it required glutamine, and no one had ever explained why the yeast and the human NAD synthetases needed or could use glutamine to provide that ammonia group.”
“So I thought, given the importance of NAD as the central catalyst in metabolism, I really need to work on this enzyme. And I loved that enzyme because it had two active sites, it had the glutaminase active site.”
“from one active site to the other active site where it's going to form NAD+. And so I decided I was going to work on that enzyme. And in the course of working on that enzyme, I realized how many people were drawing diagrams of NAD synthetase.”
“of NAD synthetase. So folks at MIT Harvard. Washington University and a lot of places were drawing these cartoon diagrams of how NAD is made.”
“And I realized. And I realized that if I knocked out the gene that I was working on in yeast, according to prediction, there's no other way to make NAD. And I thought there might be another way to make NAD through a nucleoside, nicotinamide riboside. And I essentially set up the experiment to test whether there might be an NR pathway.”
“And I knew that view. Wow. Yeah. Okay. Well, when most people hear the word NAD, they think of energy or they'll think anti-aging buzzwords. So maybe you could explain to people in sort of more simple, understandable terms, like why is NAD so important to biology?”
“You can, or maybe you could talk a little bit about what... Let's talk about maybe the two most important roles of NAD in the body. What would you say? Well, first, I'd like to expand. I just called out two NAD coenzymes, NAD plus and NADH, right?”
“And the maintenance of all of the things that we are and do, right? So one of the really amazing things that NAD coenzymes can do is they can take the high energy electrons on NAD, which is NADH, and get those high energy electrons put onto NADP, forming NADPH.”
“So you talked a little bit about this mitochondrial energy production. Right. How does NAD play a role in the repair process and all of that? And also in the gene regulation process? These are like some other important aspects of NAD.”
“mutation to occur. So... What about the role of NAD in repairing DNA damage, though? I think about, for example, PARP. Yeah. So PARP1 is incredibly important. It's a huge NAD consumer.”
“And this is the first time I use the word consumer this morning. So in the classic NAD coenzyme function, high-energy electrons are being basically transferred onto NAD, forming NADH.”
“that do that... Yeah. ...consume NAD. We have other enzymes that are involved in regulating our genes, right, making sure they're active or not active, and, you know, so that's another role of NAD.”
“Do you want to touch on that for a minute? Yeah. Yeah. And then I have another follow-up question. Yeah, yeah. So in this area of NAD-consuming enzymes, there's PARPs. PARP 1 was kind of the first one that was described.”
“ADP ribose, but they modify proteins with ADP ribose, so they cut NAD, and they add an ADP ribose unit on something to do a signaling reaction.”
“There's enzymes called sirtuins that use NAD. Yeah. Yeah. Yeah. And then they have a small modification on protein lysines, so acetyl modifications on lysines, acyl groups on lysines, succinyl groups on lysines.”
“There's also things like ADP-ribosyl cyclase. There's enzymes that can take NAD and kick off the nicotinamide group and then cyclize the ADP ribose.”
“So the question is, you know, if all these really important functions are, NAD is central to them, right? What happens if there's a limiting amount of NAD? Like how does the body triage or does the body triage?”
“Like how does the body triage or does the body triage? Who gets the NAD pool? How do we know if we're able to make enough NAD? Like where, like what's the bottleneck here?”
“Yeah. The liver can make NAD from tryptophan, nicotinamide riboside, nicotinamide and nicotinic acid. So any precursor, they can make NAD and they...”
“Where if they don't have a pathway to make NAD from tryptophan, and they generally don't have a pathway to make NAD from nicotinic acid, then what happens in a neuron that has high bioenergetic requirements, if it starts losing expression of one or the other pathways?”
“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.”
“Yeah. The liver can make NAD from tryptophan, nicotinamide riboside, nicotinamide and nicotinic acid. So any precursor, they can make NAD and they...”
“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.”
“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. You're taking it orally. There's a funny thing where people started injecting, right?”
“I thought NR got broken down to NMN. Well, no. NR gets phosphorylated, gets converted up to NMN. 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?”
“There are some reports that 17 out of 20 products labeled as NMN don't have NMN in it or don't meet... Meet the label claims.”
“Yeah, it doesn't work that way, though. Why doesn't it work that way? Well, it doesn't work because the NMN has a phosphate group that precludes its transport into the cell. So, in the 1980s, there were people that were developing nucleosides and bases as anti-cancer and anti-viral drugs.”
“That phosphate has to be put on inside of cells. So, if someone is able to find a safe purification... A pure form of NMN, which if you're at a drug company that is making and testing NMN, you could have access to that.”
“Right? If it just has the same chemical name, like if it's, you've read some study about NMN being done in a hospital in Boston or Tokyo or something like that, and then you go on Amazon and you buy NMN, you're probably not using the same material that was tested in that hospital. Right? And there's really no telling what's in it. Right?”
“They already had, they had pancreatic cancer and they gave them nicotinamide mononucleotide and it accelerated tumor growth. Is that ringing a bell? Um, no, but you know, there are, there are a lot of trials that you can do, things”
“study. It might've been out of Japan. Um, but it was definitely NMN given orally, no, no, actually it was given by, it might've been injected to mice with pancreatic cancer and it accelerated cancer growth.”
“you know, GLP-1 medications, that in conjunction with resistance training can really improve people's health. So for people that have overweight and obesity, that's probably, you know, number one.”
“you know, number one. There's a lot of options now to lose weight. People that, people that are, are drinking GLP-1 actually helps some of those people. But, you know, people that are drinking or are, you know, sitting, you know, in front of a screen too many hours a day and are not moving their bodies, probably moving their bodies more is going to be, you know.”
“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.”
“You can find some of these NAD boosters with other combinations, Pterostilbene being one.”
“Like, should they be mixed? There's no use case for resveratrol or pterostilbene in my view. Both of those compounds were thought to be SIRT1 activators.”
“pterostilbene and resveratrol don't. They don't actually increase the activity of SIRT1 anyway. And as you said, pterostilbene shows a dose-dependent increase in LDL cholesterol, which is generally not a good thing for people.”
“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.”
“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.”
“You know, when you're talking about measuring NAD levels in the blood, like how much of that is really just reflective of your diet? Like, you know, like, let's say you're getting a lot of, you know, B3, nicotinic acid, whatever, like you're getting a lot of tryptophan.”
“That said, there's some... There's some cardiologists that recommend it for lipid regulation, and so it has a long, you know, human experience. Nicotinamide has been in the food supply for a long time, usually pretty low dose.”
“trials are the. The top of the, of, of the hierarchy. Right. And so we know from the Australian nicotinamide trials that supplementing with, you know, the classic NAD booster nicotinamide, um, lowers cancer risk at the population level.”
“We don't get injected with a million MCF seven cells. Good. So it sounds, I think that that evidence with the nicotinamide that was given to people in Australia. Yeah. That, that not only didn't increase cancer risk, it lowers the risk of melanoma.”
“Amazing. Okay. And I think it's worth a try. Well, full disclosure here, I have been taking Tru Niagen for about, I mean, since August, and I too have a lot of other things, but my recovery is great.”
“But if there's someone like myself, you know, so I'm taking 1,000 milligrams a day of tru niagen, nicotinamide riboside. Does that seem like a reasonable dose in your opinion?”
“So I think that that person would probably have coffee and Niagen at that beginning of their work cycle. To me, that's the most logical way of doing it.”
“I mean, would supplementation come in there or would it be bright light exposure? The things that we've heard of from the chronobiologists, like melatonin, getting bright light exposure, trying to time-restricted eating if you're a shift worker, trying to not eat all throughout the day, like things like that.”
“the F in FDA. And so. So because Niagen went through the process of being a, uh, compound that is generally regarded as safe and as a new dietary ingredient, if there are any complaints or observations or clinical trial observations that are linked to NR, there's a file on them, you know, that we're aware of.”
Also filed under Nicotinamide Riboside
As referenced on air, with the quote and the moment. Reported, not evaluated.
“There was a recent study, I think in the last month or two, it's Wu et al. And I think it's Lancet e-med, clinical medicine or something like that. I'm a co-author on the paper that shows that there's within group improvement”
“We published this, I think, in 2019. So, we had this idea that if we had really overweight female mice”
“Dr. Gehrman and a number of other folks at UC Davis are some of the biggest experts in lactation in the world. And they started planning some large animal trials as well as human trials.”
“Australia, you know, where there's a very high incidence of skin cancer, right? So high that you can do a prospective preventative clinical trial to see whether nicotinamide supplementation lowers the risk of skin cancer.”
“Brand new paper out of Nestle in Switzerland says that the gut microbiome plays a role in human conversion.”
“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.”
“So, there was a trial that was done, I think it was Dollar Up et al., 2018, and I'm a co-author on the first paper, in which the hypothesis to be tested was that NR was going to improve weight loss and insulin sensitivity in 13 weeks.”
“It wasn't until around 2019 that Al-Hassan et al., in another, you know, top-line failure trial... said, wow. The inflammation is much lower.”
“And so we know from the Australian nicotinamide trials that supplementing with, you know, the classic NAD booster nicotinamide, um, lowers cancer risk at the population level.”