NAD

“But from a purity standpoint, I mean, we're getting the awards now. You're the most pure in the NAD, most pure in CMOS, one of the highest trust factors in the entire industry for the whole supplement space.”

“I'm going to throw a basketball to Gary and I'm going to put all these nutrients in there. You talked about our NAD formula. You know, we have 300 milligrams of NAD. We have a gram, a thousand milligrams of trimethylglycine. We have apigenin in there. We have our Lutemax trademark in there, zeaxanthins.”

“Today, we're going to separate the facts from the fiction on NAD, because some of what you've heard is absolutely true, and some of it is complete nonsense. NAD, nicotinamide adenine dinucleotide, is in every single cell in your body, and it has two jobs. The first job is energy. The second job is how that NAD gets used.”

“NAD and Resveratrol, new discoveries. Before we get into that, though, what discoveries have excited you most since 2019? Gee, a lot. I'm very lucky to have a lab where there's up to 40 people running around making discoveries.”

“There's a molecule called NAD that a lot of your listeners and viewers would know about. This enzyme responds to NAD levels. But long story short is when you're in adversity mode, your body switches from growth and reproduction into survival mode.”

“We'll see what they say. What was the controversy? Because I know since the last time we spoke, there's been some furore around resveratrol, some more furor around NAD, maybe NMN as well. Yeah. Can you explain what happened? Yeah, sure. These are all typhoons in a teacup or whatever it is.”

“Unless you want to complain about atomic theory, you know, we're done here. Okay. And what happened with NAD, NMN? So, yeah, let's bring everyone up to spear on what NAD is. So CERT1 also can be activated by giving it fuel, which is NAD. CERT1 chomps with NAD. And in fact, this is not often known. The chemical that it takes off the epigenome structures is donated to NAD.”

“just my lab, that raising NAD levels above normal baseline is very good for humans. Okay, I can give you examples. Shelly Basin, you could look up in PubMed, he's got a couple of really good papers giving NMN, which is the precursor to NAD, to people that are either obese or have pre-diabetes or even super fit ones.”

“So raising NAD, I think most people would say that it's good for humans and animals. Okay. And again, we're going to publish that it's good for longevity too. Where the debate that came up, I think you're talking about the one that was maybe a few months ago.”

“Somebody showed that human blood levels in white blood cells, the white blood cells don't have less NAD as you get older. So some people who love to make a living of being naysayers, especially towards my career, jumped on that and said the whole theory is wrong.”

“whole theory is wrong. If white blood cell NAD levels don't go down with aging, then the whole theory must be incorrect, which, as you can tell, is complete BS. In fact, we've known for probably a decade that that was true.”

“What's the status? I'd looked at something to do with it. It was a pharmaceutical, then it was a supplement, and now I don't know what the level of access is with NAD and stuff at the moment. How's that classified? Yeah. Oh, just a final thought.”

“or they had metabolic syndrome. Anyway, we could check it out, but there is some good correlations between NAD levels and age-related conditions. Want to be accurate? All right. So the FDA thing.”

“If you don't find the deficiency, nothing else matters, which is why your sister took NAD and she felt like a rock star and you took NAD and felt nothing. This is why resveratrol cleared up the skin of a friend of yours and you take resveratrol and nothing happens.”

“I'm a huge fan of NAD. Delivering it through the gut requires a liposome, right? Or else it's destroyed in something called first-pass metabolism. Or you can inject it or you can do it in a patch, or you may be able to do it sublingually. But if you're going to put NAD into the body and get it through the stomach, you need this liposome. By the way, I don't sell liposomal NAD.”

“Now it has to go into the mitochondria and then it exerts its effect in the electron transport chain and the Krebs cycle. But the amount of cofactors that are needed to target direct that NAD, things like phosphatidylcholine, trimethylglycine, if you don't have those cofactors, you've gotten NAD through the gut and you've dropped it into the gut.”

“It's not as hard on your gut, but it's harder on your mitochondria. Yeah. And so then I just, I started supplementing with high dose vitamin B2 and taking more mitochondria support, like CoQ10, PQQ, NAD+. And my energy, Gary went from a six out of 10 to a 10 out of 10.”

“And the question that they know you personally lean on lifestyle interventions. But the biohacking community is very interested in compounds like methylene blue, urethylene A, and NAD plus boosters. In your opinion, what does the sort of...”

“To the electron transport chain. So the mitochondria can flow those electrons with low resistance. So if you're depleted of NAD, that's going to cause increased resistance for electrons to flow through this metabolic circuit. So NAD plus seems to calm things down a little bit in terms of energy processing.”

“And it makes people... Feel more energetic. Is that in pill form? Like, how do people take NAD plus? Because I know there was some like drips one time that some guy gave me. Yes. I think there's oral supplements that are precursors to NAD. If you eat NAD directly, it doesn't... The bioavailability, it's called, it doesn't get into, you know, your cells very well.”

“Yeah. And so the term mitochondrial dysfunction is, I think, a little misleading. Like there was a lot of hype about NAD. There was a lot of hype about coenzyme Q, CoQ10. There was a lot of hype about all sorts of things, anti-inflammatory, you know, berries and antioxidants was a big thing 10, 20 years ago. Turned out not to be so useful.”

“I actually really like NAD. I use another company. I have, it has something called Urolithin A A in it”

“vitamin D. I take MNN or NAD, and then glutathione. My dad was always a massive glutathione guy. There's a lot of real health benefits to glutathione.”

“So I'll take iron, but not on a consistent basis. And I'm hoping the new one is, this is an area of controversy, NAD. This is the, you know, it's a precursor for a main enzyme that's highly involved in metabolism. There's been evidence to suggest it goes down with aging. So my eye is closely on that, to see if that's going to be something to come up in the play.”

“disorders, brain fog, fatigue problem, etc. You could do all the NAD you want to do. You could do all this analytics and all these different things. But if you have an unresolved issue cellularly in dealing with toxicity, you cannot biohack yourself out of that.”

“regenerate what is that uh regenerate is uh uh like and and what is it nad or something like that okay yeah stuff like that and so it's nmn so it's like a precursor to nad yeah the ufc can find that stuff ufc provides it yeah okay so that means”

“two two fights ago and yeah i feel great i guess it's like nad like some kind of anti-aging or yes yeah It basically lengthens your telomeres, and it sort of brings your body back to, like, a level of recovery that it had when it was younger, allegedly.”

“There's a lot of people that take IV, NAD, and they take NAD, and, you know, you can get it in the subcutaneous, under the fat injections.”

“Subcutaneous injections, they do it that way, too. Yeah. Yeah, but— But I think some of the best ways is actually NMN, that stuff, because what it does is it's like a precursor, and your body just makes more NAD that way. Yeah.”

“So some of this stuff, I don't even know what it does, and I'm just like, oh, it's for recovery. I'll do it, you know? Hyperbaric works. And it works in the same way that NAD and NMN work. Mm-hmm. Mm-hmm. Mm-hmm. It strengthens your telomeres. Like, they did this study out of a university in Israel, I believe it was, where they put”

“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”

“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.”

“things NAD with Dr. Charles Brenner. Welcome back to the podcast, everyone. I'm very excited to be here with Dr. Charles Brenner, who is a professor and chair in the Department of Diabetes and Cancer Metabolism at the City of Hope.”

“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?”