How To Boost NAD Levels To Fight Inflammation, Improve Recovery, and Slow Aging

When most people hear the word NAD, When most people hear the word NAD, they'll think anti-aging buzzword. So they'll think anti-aging buzzword. So they'll think anti-aging buzzword. So the question is why is NAD so important the question is why is NAD so important the question is why is NAD so important to biology? to biology? to biology? >> So converting fuel, building stuff, and >> So converting fuel, building stuff, and >> So converting fuel, building stuff, and repairing stuff. Those are the buckets repairing stuff. Those are the buckets repairing stuff. Those are the buckets in which NAD co-enzymes are critical. in which NAD co-enzymes are critical. in which NAD co-enzymes are critical. >> So NAD levels do decline with age. >> So NAD levels do decline with age. >> So NAD levels do decline with age. There's a lot of people that are taking There's a lot of people that are taking There's a lot of people that are taking NAD boosting supplements. It was NAD boosting supplements. It was NAD boosting supplements. It was initially my technology that turned into initially my technology that turned into initially my technology that turned into the nicotenoid ribocide and NAD boosting the nicotenoid ribocide and NAD boosting the nicotenoid ribocide and NAD boosting industry and we published a paper in industry and we published a paper in industry and we published a paper in 2020. We had kind of a shocking result. 2020. We had kind of a shocking result. 2020. We had kind of a shocking result. >> How does NAD play a role in exercise >> How does NAD play a role in exercise >> How does NAD play a role in exercise recovery? recovery? recovery? >> Sports trainers and athletic programs >> Sports trainers and athletic programs >> Sports trainers and athletic programs swear by this. It's well known that the swear by this. It's well known that the swear by this. It's well known that the Patriots took Niagen for many years. Can Patriots took Niagen for many years. Can Patriots took Niagen for many years. Can you please tell people the question I you please tell people the question I you please tell people the question I know that's in their minds, which is why know that's in their minds, which is why know that's in their minds, which is why can't I just supplement with NAD? Why do can't I just supplement with NAD? Why do can't I just supplement with NAD? Why do I have to take this precursor? I have to take this precursor? I have to take this precursor? >> The the thing that your listeners need >> The the thing that your listeners need >> The the thing that your listeners need to know is that to know is that to know is that >> Welcome back to the podcast everyone. >> Welcome back to the podcast everyone. >> Welcome back to the podcast everyone. I'm very excited to be here with Dr. I'm very excited to be here with Dr. I'm very excited to be here with Dr. Charles Brener who is a professor and Charles Brener who is a professor and Charles Brener who is a professor and chair in the department of diabetes and chair in the department of diabetes and chair in the department of diabetes and cancer metabolism at the city of hope. cancer metabolism at the city of hope. cancer metabolism at the city of hope. But I think what Dr. Brener is probably But I think what Dr. Brener is probably But I think what Dr. Brener is probably more well known for in not only in the more well known for in not only in the more well known for in not only in the scientific community but in the comm scientific community but in the comm scientific community but in the comm broader health community in general is broader health community in general is broader health community in general is his contribution to understanding NAD his contribution to understanding NAD his contribution to understanding NAD biology. He had discovered a precursor biology. He had discovered a precursor biology. He had discovered a precursor for NAD nicotenomide ribocide which has for NAD nicotenomide ribocide which has for NAD nicotenomide ribocide which has been made into a supplement. It's a a been made into a supplement. It's a a been made into a supplement. It's a a NAD boosting supplement that a lot of NAD boosting supplement that a lot of NAD boosting supplement that a lot of you are familiar with. We're going to you are familiar with. We're going to you are familiar with. We're going to get into all that today. Um Dr. Brener get into all that today. Um Dr. Brener get into all that today. Um Dr. Brener is very evidence-based and so I'm very is very evidence-based and so I'm very is very evidence-based and so I'm very excited to have this conversation with excited to have this conversation with excited to have this conversation with you today on all things NAD and we're you today on all things NAD and we're you today on all things NAD and we're going to talk about what that is and why going to talk about what that is and why going to talk about what that is and why it's important. So, thank you for it's important. So, thank you for it's important. So, thank you for joining me on the show. joining me on the show. joining me on the show. >> I'm really happy to be here. >> I'm really happy to be here. >> I'm really happy to be here. >> Well, this is a perfect segue into what >> Well, this is a perfect segue into what >> Well, this is a perfect segue into what I am very I think excited to talk about I am very I think excited to talk about I am very I think excited to talk about with you and that really is you know NAD with you and that really is you know NAD with you and that really is you know NAD levels with age, right? So, levels with age, right? So, levels with age, right? So, >> NAD levels do decline with age. Now, can >> NAD levels do decline with age. Now, can >> NAD levels do decline with age. Now, can you explain the leading theories why you explain the leading theories why you explain the leading theories why that happens in humans? So, like what do that happens in humans? So, like what do that happens in humans? So, like what do you think the strongest evidence is? Is you think the strongest evidence is? Is you think the strongest evidence is? Is it, you know, diseases, lifestyle that, it, you know, diseases, lifestyle that, it, you know, diseases, lifestyle that, you know, changes that happen as we get you know, changes that happen as we get you know, changes that happen as we get older? older? older? >> Why why is it that it, you know, can you >> Why why is it that it, you know, can you >> Why why is it that it, you know, can you just talk a little bit about what your just talk a little bit about what your just talk a little bit about what your thoughts on that? Well, thoughts on that? Well, thoughts on that? Well, I'm not super comfortable accepting I'm not super comfortable accepting I'm not super comfortable accepting every premise that you, you know, can every premise that you, you know, can every premise that you, you know, can pull from from Instagram, right? And so, pull from from Instagram, right? And so, pull from from Instagram, right? And so, so, um, so, um, so, um, >> I didn't pull anything. >> I didn't pull anything. >> I didn't pull anything. >> Yeah. Yeah. No, I know. >> Yeah. Yeah. No, I know. >> Yeah. Yeah. No, I know. >> But you're talking generally speaking, >> But you're talking generally speaking, >> But you're talking generally speaking, >> right? Generally speaking, so when >> right? Generally speaking, so when >> right? Generally speaking, so when people say NAD levels decline in age, I people say NAD levels decline in age, I people say NAD levels decline in age, I don't think that there's evidence that don't think that there's evidence that don't think that there's evidence that human blood NAD declines in in age. I human blood NAD declines in in age. I human blood NAD declines in in age. I think that the likelihood that a number think that the likelihood that a number think that the likelihood that a number of human tissue NAD pools decline or are of human tissue NAD pools decline or are of human tissue NAD pools decline or are disturbed in age is incontrovertibly disturbed in age is incontrovertibly disturbed in age is incontrovertibly true. But I think that the idea that true. But I think that the idea that true. But I think that the idea that every human systems NAD declines in age every human systems NAD declines in age every human systems NAD declines in age is probably overstated because I've seen is probably overstated because I've seen is probably overstated because I've seen a lot of human blood NAD metaboloms and a lot of human blood NAD metaboloms and a lot of human blood NAD metaboloms and essentially there's three types of data essentially there's three types of data essentially there's three types of data that we get. We get normal people male that we get. We get normal people male that we get. We get normal people male and female who have 20 microar and female who have 20 microar and female who have 20 microar NAD plus calculated on a volutric basis NAD plus calculated on a volutric basis NAD plus calculated on a volutric basis in their blood. You have people that in their blood. You have people that in their blood. You have people that supplement that are maybe twice that and supplement that are maybe twice that and supplement that are maybe twice that and you have people with mitochondrial you have people with mitochondrial you have people with mitochondrial disease that are lower. disease that are lower. disease that are lower. >> Okay. So we like we discovered in in in >> Okay. So we like we discovered in in in >> Okay. So we like we discovered in in in collaboration with University of of collaboration with University of of collaboration with University of of Helsinki a number of years ago that Helsinki a number of years ago that Helsinki a number of years ago that people with mitochondrial disease that people with mitochondrial disease that people with mitochondrial disease that were thought to primarily have muscle were thought to primarily have muscle were thought to primarily have muscle mitochondrial myopathy right are walking mitochondrial myopathy right are walking mitochondrial myopathy right are walking around with low blood NAD. around with low blood NAD. around with low blood NAD. >> Okay. >> Okay. >> Okay. >> Right. >> Right. >> Right. Generally we don't see people have low Generally we don't see people have low Generally we don't see people have low blood NAD. We don't see older people blood NAD. We don't see older people blood NAD. We don't see older people having low blood NAD, but when we've having low blood NAD, but when we've having low blood NAD, but when we've looked at alcoholics, we see disturbed looked at alcoholics, we see disturbed looked at alcoholics, we see disturbed NAD in their liver. NAD in their liver. NAD in their liver. When um you have a population of people When um you have a population of people When um you have a population of people that have noise induced hearing loss, I that have noise induced hearing loss, I that have noise induced hearing loss, I would bet a fair amount of money that would bet a fair amount of money that would bet a fair amount of money that their cocklear NAD is damaged. Okay. So, their cocklear NAD is damaged. Okay. So, their cocklear NAD is damaged. Okay. So, we're talking about blood NAD versus we're talking about blood NAD versus we're talking about blood NAD versus tissue NAD. Um, and I think the question tissue NAD. Um, and I think the question tissue NAD. Um, and I think the question I'm generally asking you is a more I'm generally asking you is a more I'm generally asking you is a more broader question, not blood NAD. I'm broader question, not blood NAD. I'm broader question, not blood NAD. I'm talking about, you know, as humans age, talking about, you know, as humans age, talking about, you know, as humans age, unfortunately, they become more unfortunately, they become more unfortunately, they become more sedentary. They become more overweight, sedentary. They become more overweight, sedentary. They become more overweight, more obese. They they have things like more obese. They they have things like more obese. They they have things like diabetes and metabolic syndrome and all diabetes and metabolic syndrome and all diabetes and metabolic syndrome and all these disease states that do occur with these disease states that do occur with these disease states that do occur with age. Right. Right. So the question that age. Right. Right. So the question that age. Right. Right. So the question that I'm I'm asking you is you know basically I'm I'm asking you is you know basically I'm I'm asking you is you know basically like do is there evidence that some of like do is there evidence that some of like do is there evidence that some of these these disease states and I guess these these disease states and I guess these these disease states and I guess we'll get into this do play a role in we'll get into this do play a role in we'll get into this do play a role in lowering NAD levels in the blood in lowering NAD levels in the blood in lowering NAD levels in the blood in other organs. So, so the question other organs. So, so the question other organs. So, so the question >> broad more broadly. Yeah. >> broad more broadly. Yeah. >> broad more broadly. Yeah. >> But even in the blood, I'm curious like >> But even in the blood, I'm curious like >> But even in the blood, I'm curious like if someone if if you're saying I've got if someone if if you're saying I've got if someone if if you're saying I've got normal people and we looked at them, normal people and we looked at them, normal people and we looked at them, does that mean normal like they don't does that mean normal like they don't does that mean normal like they don't have any diseases or does it mean they have any diseases or does it mean they have any diseases or does it mean they don't have mitochondrial disease? don't have mitochondrial disease? don't have mitochondrial disease? Because like does someone who's obese Because like does someone who's obese Because like does someone who's obese have lower blood NAD levels than someone have lower blood NAD levels than someone have lower blood NAD levels than someone who does not? who does not? who does not? >> You know, clinical trials always have a, >> You know, clinical trials always have a, >> You know, clinical trials always have a, you know, inclusion criterion, right? you know, inclusion criterion, right? you know, inclusion criterion, right? So, um, the clinical trials that looked So, um, the clinical trials that looked So, um, the clinical trials that looked at people that were simply older and at people that were simply older and at people that were simply older and probably were not on, you know, 12 probably were not on, you know, 12 probably were not on, you know, 12 medications medications medications saw largely normal blood NAD. Um so it saw largely normal blood NAD. Um so it saw largely normal blood NAD. Um so it could be that if we look into people could be that if we look into people could be that if we look into people that have a lot of diseasing conditions that have a lot of diseasing conditions that have a lot of diseasing conditions and have polyfarm pharmacy we may see um and have polyfarm pharmacy we may see um and have polyfarm pharmacy we may see um abnormally low blood NAD in in aging abnormally low blood NAD in in aging abnormally low blood NAD in in aging people much more than than I than I than people much more than than I than I than people much more than than I than I than I've seen. So that's a really um good I've seen. So that's a really um good I've seen. So that's a really um good point. Um but um I think that um point. Um but um I think that um point. Um but um I think that um inflammatory processes are probably at inflammatory processes are probably at inflammatory processes are probably at work in many of the diseasing conditions work in many of the diseasing conditions work in many of the diseasing conditions in which the NAD system is disturbed in which the NAD system is disturbed in which the NAD system is disturbed >> in in in not just the blood but in >> in in in not just the blood but in >> in in in not just the blood but in >> but in every organ. So, so one of one of >> but in every organ. So, so one of one of >> but in every organ. So, so one of one of the things that that we found in 2020, the things that that we found in 2020, the things that that we found in 2020, um, you know, so remember we all um, you know, so remember we all um, you know, so remember we all remember where we were in March 2020, remember where we were in March 2020, remember where we were in March 2020, right? So I was a I was a department um right? So I was a I was a department um right? So I was a I was a department um head at University of Iowa and you know head at University of Iowa and you know head at University of Iowa and you know I got an email from either the the dean I got an email from either the the dean I got an email from either the the dean of the college of medicine or the of the college of medicine or the of the college of medicine or the president of the university saying president of the university saying president of the university saying everybody needs to to go home. tell the everybody needs to to go home. tell the everybody needs to to go home. tell the people in your department that um we're people in your department that um we're people in your department that um we're going to be teaching from home, we're going to be teaching from home, we're going to be teaching from home, we're going to be learning from home and we're going to be learning from home and we're going to be learning from home and we're not going to be going into the lab. The not going to be going into the lab. The not going to be going into the lab. The exception is if you're doing something exception is if you're doing something exception is if you're doing something related to corona viruses, you can stay related to corona viruses, you can stay related to corona viruses, you can stay in the lab. in the lab. in the lab. So, um, turns out fourth floor of the So, um, turns out fourth floor of the So, um, turns out fourth floor of the BSB building where I was working was one BSB building where I was working was one BSB building where I was working was one flight above Stanley Pearl Pearlman's flight above Stanley Pearl Pearlman's flight above Stanley Pearl Pearlman's lab who was probably one of the five lab who was probably one of the five lab who was probably one of the five most expert people on corona viruses in most expert people on corona viruses in most expert people on corona viruses in the world and uh he had been working on the world and uh he had been working on the world and uh he had been working on corona viruses when no one cared about corona viruses when no one cared about corona viruses when no one cared about them and actually had given us samples them and actually had given us samples them and actually had given us samples of um corona virus infected mice of um corona virus infected mice of um corona virus infected mice and uh we had done NAD metabolomics on and uh we had done NAD metabolomics on and uh we had done NAD metabolomics on it and we had kind of a shocking result. it and we had kind of a shocking result. it and we had kind of a shocking result. So we were actually able to stay in the So we were actually able to stay in the So we were actually able to stay in the lab and we published a paper in 2020 on lab and we published a paper in 2020 on lab and we published a paper in 2020 on the effect of corona virus infection not the effect of corona virus infection not the effect of corona virus infection not just on mouse liver but on human lung just on mouse liver but on human lung just on mouse liver but on human lung samples that we're able to get from from samples that we're able to get from from samples that we're able to get from from morgs from morgs and from like databases morgs from morgs and from like databases morgs from morgs and from like databases where they had COVID infection. And just where they had COVID infection. And just where they had COVID infection. And just to to to come back to the PARP question, to to to come back to the PARP question, to to to come back to the PARP question, we found five different members of the we found five different members of the we found five different members of the PARP super family that were PARP super family that were PARP super family that were transcriptionally activated by uh corona transcriptionally activated by uh corona transcriptionally activated by uh corona virus infection. virus infection. virus infection. >> Wow. Yeah. So they're that were they >> Wow. Yeah. So they're that were they >> Wow. Yeah. So they're that were they consuming the NAD? consuming the NAD? consuming the NAD? >> Yeah. You know what I think it is is >> Yeah. You know what I think it is is >> Yeah. You know what I think it is is doublestranded RNA, right, is seen as an doublestranded RNA, right, is seen as an doublestranded RNA, right, is seen as an invader by the innate immune system. So invader by the innate immune system. So invader by the innate immune system. So um just to bring everybody up to the the um just to bring everybody up to the the um just to bring everybody up to the the same speed um your your immune system same speed um your your immune system same speed um your your immune system has two parts. One is your innate immune has two parts. One is your innate immune has two parts. One is your innate immune system that can tell that doublestranded system that can tell that doublestranded system that can tell that doublestranded RNA is a problem because the human body RNA is a problem because the human body RNA is a problem because the human body just gen generally doesn't make just gen generally doesn't make just gen generally doesn't make doublestranded RNA right and the human doublestranded RNA right and the human doublestranded RNA right and the human body doesn't make endotoxin. body doesn't make endotoxin. body doesn't make endotoxin. So cells don't have to wait for So cells don't have to wait for So cells don't have to wait for antibodies to come along that are very antibodies to come along that are very antibodies to come along that are very specific for doublestranded RNA or specific for doublestranded RNA or specific for doublestranded RNA or endotoxin. They recognize doublest endotoxin. They recognize doublest endotoxin. They recognize doublest stranded RNA and endotoxin as a foreign stranded RNA and endotoxin as a foreign stranded RNA and endotoxin as a foreign invader and they do something immediate invader and they do something immediate invader and they do something immediate early to um to respond. And it turns out early to um to respond. And it turns out early to um to respond. And it turns out that one of the things that our cells that one of the things that our cells that one of the things that our cells are programmed to do is turn on five are programmed to do is turn on five are programmed to do is turn on five members of the PARP super family. So members of the PARP super family. So members of the PARP super family. So that infection and turns out this is a that infection and turns out this is a that infection and turns out this is a common response not just to COVID but to common response not just to COVID but to common response not just to COVID but to a lot of things is that we turn on these a lot of things is that we turn on these a lot of things is that we turn on these PARPs. PARPs. PARPs. >> So you think that that may be something >> So you think that that may be something >> So you think that that may be something that happens with you know respiratory that happens with you know respiratory that happens with you know respiratory illness or illness or illness or >> Yeah. >> Yeah. >> Yeah. >> Interesting. Um that brings me back to >> Interesting. Um that brings me back to >> Interesting. Um that brings me back to this question you know and I do want to this question you know and I do want to this question you know and I do want to talk about you know some of the drivers talk about you know some of the drivers talk about you know some of the drivers of NAD loss. Maybe that's a better way of NAD loss. Maybe that's a better way of NAD loss. Maybe that's a better way to put it. um you know what we're to put it. um you know what we're to put it. um you know what we're talking when you're talking about talking when you're talking about talking when you're talking about measuring NAD levels in the blood like measuring NAD levels in the blood like measuring NAD levels in the blood like how much of that is really just how much of that is really just how much of that is really just reflective of your diet like you know reflective of your diet like you know reflective of your diet like you know like let's say you're you're getting a like let's say you're you're getting a like let's say you're you're getting a lot of you know B3 nicotinic acid lot of you know B3 nicotinic acid lot of you know B3 nicotinic acid whatever like you're getting a lot of whatever like you're getting a lot of whatever like you're getting a lot of tryptophan um is there is there somewhat tryptophan um is there is there somewhat tryptophan um is there is there somewhat of this like artifactual thing where of this like artifactual thing where of this like artifactual thing where okay NAD levels look normal or elevated okay NAD levels look normal or elevated okay NAD levels look normal or elevated because they're taking in the precursors because they're taking in the precursors because they're taking in the precursors and we're measuring it like in blood and we're measuring it like in blood and we're measuring it like in blood >> well when people you know when people >> well when people you know when people >> well when people you know when people take substantive amounts of um NAD take substantive amounts of um NAD take substantive amounts of um NAD precursor vitamins into the 300 mgram precursor vitamins into the 300 mgram precursor vitamins into the 300 mgram plus you can see a substantive change in plus you can see a substantive change in plus you can see a substantive change in people's people's people's um circulating NAD metabolom um circulating NAD metabolom um circulating NAD metabolom um um probably the foods that have the um um probably the foods that have the um um probably the foods that have the most NAD precursors are the same foods most NAD precursors are the same foods most NAD precursors are the same foods that have the most micronutrients of all that have the most micronutrients of all that have the most micronutrients of all kinds. Right? People always talk about kinds. Right? People always talk about kinds. Right? People always talk about liver, spinach, right? Spinach source of liver, spinach, right? Spinach source of liver, spinach, right? Spinach source of iron and micronutrients. iron and micronutrients. iron and micronutrients. Um liver a source of iron and Um liver a source of iron and Um liver a source of iron and micronutrients. That's because they're micronutrients. That's because they're micronutrients. That's because they're chalk full of mitochondria, right? And chalk full of mitochondria, right? And chalk full of mitochondria, right? And chloroplast in the case of of plants chloroplast in the case of of plants chloroplast in the case of of plants that contain all of these co-enzymes, that contain all of these co-enzymes, that contain all of these co-enzymes, right? And the co-enzymes you you know right? And the co-enzymes you you know right? And the co-enzymes you you know this the co-enzymes break down to this the co-enzymes break down to this the co-enzymes break down to their soluble precursor form. So NAD their soluble precursor form. So NAD their soluble precursor form. So NAD breaks down to NR nicotenomide nicotenic breaks down to NR nicotenomide nicotenic breaks down to NR nicotenomide nicotenic acid goes back into cells. Cells acid goes back into cells. Cells acid goes back into cells. Cells rebuilds the NAD stores. Co-enzyme A rebuilds the NAD stores. Co-enzyme A rebuilds the NAD stores. Co-enzyme A breaks down to pantaththenate. breaks down to pantaththenate. breaks down to pantaththenate. Pantaththnate gets into cells. Cells Pantaththnate gets into cells. Cells Pantaththnate gets into cells. Cells make up their own pantaththenate. make up their own pantaththenate. make up their own pantaththenate. So, So, So, >> so then you know and this h how much do >> so then you know and this h how much do >> so then you know and this h how much do you do you think measuring blood levels you do you think measuring blood levels you do you think measuring blood levels of NAD really is indicative of what's of NAD really is indicative of what's of NAD really is indicative of what's going on in the whole system and you going on in the whole system and you going on in the whole system and you know perhaps there is more of an age know perhaps there is more of an age know perhaps there is more of an age related decline in NAD in other tissues related decline in NAD in other tissues related decline in NAD in other tissues that we're not able to see in the blood. that we're not able to see in the blood. that we're not able to see in the blood. I think that there I think there are I think that there I think there are I think that there I think there are very substantive age related declines in very substantive age related declines in very substantive age related declines in NAD in tissues and disease and NAD in tissues and disease and NAD in tissues and disease and conditiondriven conditiondriven conditiondriven declines in NAD tissues and people are declines in NAD tissues and people are declines in NAD tissues and people are not you know there's no reason for you not you know there's no reason for you not you know there's no reason for you to volunteer a piece of your brain or to volunteer a piece of your brain or to volunteer a piece of your brain or your liver to to measure that. Right. your liver to to measure that. Right. your liver to to measure that. Right. >> What about animal studies? Do you think >> What about animal studies? Do you think >> What about animal studies? Do you think >> animal studies we we have a lot of data >> animal studies we we have a lot of data >> animal studies we we have a lot of data on that in in animals? Yeah. on that in in animals? Yeah. on that in in animals? Yeah. >> And and what have those shown? I mean, >> And and what have those shown? I mean, >> And and what have those shown? I mean, are we seeing declines in the muscle and are we seeing declines in the muscle and are we seeing declines in the muscle and the liver and the brain? Is that the liver and the brain? Is that the liver and the brain? Is that something you think translates to something you think translates to something you think translates to humans? humans? humans? >> Um, I think it it probably translates to >> Um, I think it it probably translates to >> Um, I think it it probably translates to humans. I think in the liver it's humans. I think in the liver it's humans. I think in the liver it's related to inflammation and the related to inflammation and the related to inflammation and the microbiome. It kind of varies from microbiome. It kind of varies from microbiome. It kind of varies from university to university in terms of university to university in terms of university to university in terms of where their mice are kept and what kind where their mice are kept and what kind where their mice are kept and what kind of, of, of, >> you know, um, microbiome there is in in >> you know, um, microbiome there is in in >> you know, um, microbiome there is in in those facilities. But um for sure in a those facilities. But um for sure in a those facilities. But um for sure in a lot of disease and conditions the NAD lot of disease and conditions the NAD lot of disease and conditions the NAD system really comes under attack. So in system really comes under attack. So in system really comes under attack. So in heart failure the NAD system comes under heart failure the NAD system comes under heart failure the NAD system comes under attack in central and peripheral attack in central and peripheral attack in central and peripheral neurodeeneration comes under attack. Sun neurodeeneration comes under attack. Sun neurodeeneration comes under attack. Sun exposure it comes under attack. exposure it comes under attack. exposure it comes under attack. >> Okay. So let's talk about some of this. >> Okay. So let's talk about some of this. >> Okay. So let's talk about some of this. I mean, um, if we're talking about three I mean, um, if we're talking about three I mean, um, if we're talking about three really common conditions in humans, really common conditions in humans, really common conditions in humans, obesity, insulin resistance at the top, obesity, insulin resistance at the top, obesity, insulin resistance at the top, right? We have chronic inflammation, right? We have chronic inflammation, right? We have chronic inflammation, which is the driver of heart disease, of which is the driver of heart disease, of which is the driver of heart disease, of Alzheimer's disease, right? Alzheimer's disease, right? Alzheimer's disease, right? >> Um, chronic sleep deprivation. >> Um, chronic sleep deprivation. >> Um, chronic sleep deprivation. >> Like of those three conditions, >> Like of those three conditions, >> Like of those three conditions, >> how you kind of described a little bit >> how you kind of described a little bit >> how you kind of described a little bit of the illness, but like how do those, of the illness, but like how do those, of the illness, but like how do those, you know, conditions put stress on the you know, conditions put stress on the you know, conditions put stress on the NAD system? So like obesity, NAD system? So like obesity, NAD system? So like obesity, >> the inflam chronic inflammation and then >> the inflam chronic inflammation and then >> the inflam chronic inflammation and then so we talked about you talked about so we talked about you talked about so we talked about you talked about acute inflammation. I'm talking about acute inflammation. I'm talking about acute inflammation. I'm talking about chronic chronic chronic >> and then also sleep deprivation. >> and then also sleep deprivation. >> and then also sleep deprivation. >> Yeah. Well, I would say um we actually >> Yeah. Well, I would say um we actually >> Yeah. Well, I would say um we actually have data from our lab for I think those have data from our lab for I think those have data from our lab for I think those those three. So um from 2016, one of our those three. So um from 2016, one of our those three. So um from 2016, one of our first mouse experiments was overfeeding first mouse experiments was overfeeding first mouse experiments was overfeeding mice. We gave them a highfat diet. We mice. We gave them a highfat diet. We mice. We gave them a highfat diet. We pushed them all the way into type 2 pushed them all the way into type 2 pushed them all the way into type 2 diabetes. their liver NAD system was diabetes. their liver NAD system was diabetes. their liver NAD system was disturbed and the pH was the center of disturbed and the pH was the center of disturbed and the pH was the center of that. So their ability to detoxify uh that. So their ability to detoxify uh that. So their ability to detoxify uh reactive oxygen species was degraded by reactive oxygen species was degraded by reactive oxygen species was degraded by being fat and being insulin uh being fat and being insulin uh being fat and being insulin uh resistant. Um sleep deprivation. resistant. Um sleep deprivation. resistant. Um sleep deprivation. >> So are they consuming more NAD? Is that >> So are they consuming more NAD? Is that >> So are they consuming more NAD? Is that like the driver? like the driver? like the driver? >> I think that they're facing a kind of >> I think that they're facing a kind of >> I think that they're facing a kind of raw storm that is consuming NADPH is raw storm that is consuming NADPH is raw storm that is consuming NADPH is churning NADPH. churning NADPH. churning NADPH. >> So, it's not like they can't make the >> So, it's not like they can't make the >> So, it's not like they can't make the NAD. It's that they're just they can't NAD. It's that they're just they can't NAD. It's that they're just they can't get enough of it because of all the get enough of it because of all the get enough of it because of all the >> and there could be more than one >> and there could be more than one >> and there could be more than one mechanism, right? Okay. mechanism, right? Okay. mechanism, right? Okay. >> Yeah. Yeah. And then um sleep >> Yeah. Yeah. And then um sleep >> Yeah. Yeah. And then um sleep disturbance. Um, we know, disturbance. Um, we know, disturbance. Um, we know, >> sorry, before you go to sleep, can I go >> sorry, before you go to sleep, can I go >> sorry, before you go to sleep, can I go back to the obesity because you back to the obesity because you back to the obesity because you mentioned the animal data? Yeah. mentioned the animal data? Yeah. mentioned the animal data? Yeah. >> What do we know from humans in terms of >> What do we know from humans in terms of >> What do we know from humans in terms of like has there has there been any like has there has there been any like has there has there been any research looking at obesity andor research looking at obesity andor research looking at obesity andor metabolic syndrome? I'm kind of glum metabolic syndrome? I'm kind of glum metabolic syndrome? I'm kind of glum gathering them in the same group here. gathering them in the same group here. gathering them in the same group here. Um, do we know any is there any human Um, do we know any is there any human Um, do we know any is there any human data that has looked at how that taxes data that has looked at how that taxes data that has looked at how that taxes the NAD system? the NAD system? the NAD system? >> There is to my knowledge. Um, >> There is to my knowledge. Um, >> There is to my knowledge. Um, and to some I mean fat is an accessible and to some I mean fat is an accessible and to some I mean fat is an accessible tissue tissue tissue um people remove fat you know from um people remove fat you know from um people remove fat you know from people that have more than they want and people that have more than they want and people that have more than they want and so it is something that could be so it is something that could be so it is something that could be determined in the atapost tissue. um determined in the atapost tissue. um determined in the atapost tissue. um we'd be very interested in knowing we'd be very interested in knowing we'd be very interested in knowing what's happening in the liver and I what's happening in the liver and I what's happening in the liver and I think I know of a resource in Europe think I know of a resource in Europe think I know of a resource in Europe where they have um liver from people where they have um liver from people where they have um liver from people that were undergoing beriatric surgery. that were undergoing beriatric surgery. that were undergoing beriatric surgery. So I think it'll be a good thing that we So I think it'll be a good thing that we So I think it'll be a good thing that we can look into in the future. can look into in the future. can look into in the future. >> Okay, great. So um you you were going to >> Okay, great. So um you you were going to >> Okay, great. So um you you were going to mention sleep disturbance and chronic mention sleep disturbance and chronic mention sleep disturbance and chronic inflammation and how both of these sort inflammation and how both of these sort inflammation and how both of these sort of very common human conditions sort of of very common human conditions sort of of very common human conditions sort of tax the NAD system, tax the NAD system, tax the NAD system, >> right? So chronobiology first. So sleep, >> right? So chronobiology first. So sleep, >> right? So chronobiology first. So sleep, I'm not sure a study has been done I'm not sure a study has been done I'm not sure a study has been done exactly on sleep, but um for sure in exactly on sleep, but um for sure in exactly on sleep, but um for sure in mice mice mice um we've looked at, you know, young mice um we've looked at, you know, young mice um we've looked at, you know, young mice that have really good um chrono that have really good um chrono that have really good um chrono synchrony and older mice that are kind synchrony and older mice that are kind synchrony and older mice that are kind of losing their synchrony and the NAD of losing their synchrony and the NAD of losing their synchrony and the NAD system becomes disturbed. There's a lot system becomes disturbed. There's a lot system becomes disturbed. There's a lot of time of day cues that go into NAD of time of day cues that go into NAD of time of day cues that go into NAD synthesis and NAD dependent metabolic synthesis and NAD dependent metabolic synthesis and NAD dependent metabolic processes. So I think that lack of sleep processes. So I think that lack of sleep processes. So I think that lack of sleep or time zone disruption is um or time zone disruption is um or time zone disruption is um essentially assured to disturb the NAD essentially assured to disturb the NAD essentially assured to disturb the NAD system. system. system. >> Well, I'm going to circle back and go a >> Well, I'm going to circle back and go a >> Well, I'm going to circle back and go a little more in depth than that because I little more in depth than that because I little more in depth than that because I have some more questions on that. have some more questions on that. have some more questions on that. >> Um and then what about the chronic >> Um and then what about the chronic >> Um and then what about the chronic inflammation? I mean, and this is to me inflammation? I mean, and this is to me inflammation? I mean, and this is to me it makes sense knowing what I know about it makes sense knowing what I know about it makes sense knowing what I know about biology. And here's where I can really biology. And here's where I can really biology. And here's where I can really claim some benefit in human which is claim some benefit in human which is claim some benefit in human which is which is amazingly satisfying that um which is amazingly satisfying that um which is amazingly satisfying that um we've not only have we shown that we've not only have we shown that we've not only have we shown that inflammatory inflammatory inflammatory stimuli stimuli stimuli like corona viruses disturb the NAD like corona viruses disturb the NAD like corona viruses disturb the NAD system but we've been able to show that system but we've been able to show that system but we've been able to show that in human beings and randomized control in human beings and randomized control in human beings and randomized control trials that nicotenomide ribos side at trials that nicotenomide ribos side at trials that nicotenomide ribos side at like a gram a day type type doses is like a gram a day type type doses is like a gram a day type type doses is anti-inflammatory. anti-inflammatory. anti-inflammatory. So that's now a that's now a proven So that's now a that's now a proven So that's now a that's now a proven fact. And um it was initially um you fact. And um it was initially um you fact. And um it was initially um you know a result that came out of trials know a result that came out of trials know a result that came out of trials where it was kind of like a topline where it was kind of like a topline where it was kind of like a topline failure in the sense that the first failure in the sense that the first failure in the sense that the first trial that reported that NR is trial that reported that NR is trial that reported that NR is anti-inflammatory anti-inflammatory anti-inflammatory set out to determine whether NR could set out to determine whether NR could set out to determine whether NR could improve old men's grip strength in like improve old men's grip strength in like improve old men's grip strength in like 2 or 3 weeks. Well, it's kind of a dumb 2 or 3 weeks. Well, it's kind of a dumb 2 or 3 weeks. Well, it's kind of a dumb trial, Rhonda. Okay. Because if you want trial, Rhonda. Okay. Because if you want trial, Rhonda. Okay. Because if you want to get stronger, you have to exercise. to get stronger, you have to exercise. to get stronger, you have to exercise. Yeah. Yeah. Yeah. >> Right. Not take a pill. >> Right. Not take a pill. >> Right. Not take a pill. >> So, so the the premise of the trial was >> So, so the the premise of the trial was >> So, so the the premise of the trial was kind of unreasonable. It was the magical kind of unreasonable. It was the magical kind of unreasonable. It was the magical thing. thing. thing. >> There's no exercise involved in the >> There's no exercise involved in the >> There's no exercise involved in the >> No, there's no exercise. >> No, there's no exercise. >> No, there's no exercise. >> There needs to be exercise plus the NA. >> There needs to be exercise plus the NA. >> There needs to be exercise plus the NA. >> Yeah. Yeah. You do exercise as standard >> Yeah. Yeah. You do exercise as standard >> Yeah. Yeah. You do exercise as standard of care and then you can see whether and of care and then you can see whether and of care and then you can see whether and Exactly. Exactly. Exactly. >> Yeah. And we even have a um you know >> Yeah. And we even have a um you know >> Yeah. And we even have a um you know like a review article saying exercise like a review article saying exercise like a review article saying exercise should be the standard of care and then should be the standard of care and then should be the standard of care and then you look for beneficial effects of NR you look for beneficial effects of NR you look for beneficial effects of NR and other things beyond that. But um and other things beyond that. But um and other things beyond that. But um what they did is they took older men and what they did is they took older men and what they did is they took older men and they did muscle biopsies and it was they did muscle biopsies and it was they did muscle biopsies and it was placeboc controlled crossover design placeboc controlled crossover design placeboc controlled crossover design actually. So some had the NR first and actually. So some had the NR first and actually. So some had the NR first and then they got placebo. Some had placebo then they got placebo. Some had placebo then they got placebo. Some had placebo first and then they they got NR. and um first and then they they got NR. and um first and then they they got NR. and um nobody's grip strength got better and nobody's grip strength got better and nobody's grip strength got better and then they went to the secondary outcomes then they went to the secondary outcomes then they went to the secondary outcomes and they found it was NR was strongly and they found it was NR was strongly and they found it was NR was strongly anti-inflammatory anti-inflammatory anti-inflammatory like greatly lowering IL6 IL 10 and like greatly lowering IL6 IL 10 and like greatly lowering IL6 IL 10 and other markers of inflammation. In fact, other markers of inflammation. In fact, other markers of inflammation. In fact, it was so strong that the people that it was so strong that the people that it was so strong that the people that had the NR first followed by placebo had the NR first followed by placebo had the NR first followed by placebo still had lower anti-inflammatory still had lower anti-inflammatory still had lower anti-inflammatory results after 3 weeks on placebo. Yeah. results after 3 weeks on placebo. Yeah. results after 3 weeks on placebo. Yeah. >> But the effect was strongest right after >> But the effect was strongest right after >> But the effect was strongest right after NR. Right. So then you worry a little NR. Right. So then you worry a little NR. Right. So then you worry a little bit, right? Because and I had to learn bit, right? Because and I had to learn bit, right? Because and I had to learn about clinical research because I'm a about clinical research because I'm a about clinical research because I'm a bench guy, right? that started out with bench guy, right? that started out with bench guy, right? that started out with enzymes and now has mice and so forth enzymes and now has mice and so forth enzymes and now has mice and so forth and so on. And the thing that clinical and so on. And the thing that clinical and so on. And the thing that clinical researchers will tell you is that your researchers will tell you is that your researchers will tell you is that your pre-specified endpoint is the most pre-specified endpoint is the most pre-specified endpoint is the most valuable thing, right? because because valuable thing, right? because because valuable thing, right? because because their their criticism of this their their criticism of this their their criticism of this anti-inflammatory result could be that anti-inflammatory result could be that anti-inflammatory result could be that well you set out to test whether NR well you set out to test whether NR well you set out to test whether NR would improve grip strength and then you would improve grip strength and then you would improve grip strength and then you measured anti-inflammation measured anti-inflammation measured anti-inflammation but for every 20 things that you measure but for every 20 things that you measure but for every 20 things that you measure you might find one thing that achieves you might find one thing that achieves you might find one thing that achieves this statistical significance at P.05. this statistical significance at P.05. this statistical significance at P.05. So if you measure 100 things you might So if you measure 100 things you might So if you measure 100 things you might find five positive results. it's maybe find five positive results. it's maybe find five positive results. it's maybe not that interesting, right? So, you not that interesting, right? So, you not that interesting, right? So, you have to worry when you get a result as a have to worry when you get a result as a have to worry when you get a result as a as a non- primary endpoint, but by this as a non- primary endpoint, but by this as a non- primary endpoint, but by this time there are eight trials showing time there are eight trials showing time there are eight trials showing anti-inflammatory activity in in human anti-inflammatory activity in in human anti-inflammatory activity in in human RCTs, including RCTs, RCTs, including RCTs, RCTs, including RCTs, one that I just read the other day in one that I just read the other day in one that I just read the other day in which that was the primary endpoint. The which that was the primary endpoint. The which that was the primary endpoint. The patient population all had COPD, so patient population all had COPD, so patient population all had COPD, so they're all very inflammatory. they're all very inflammatory. they're all very inflammatory. They're looking at inflammatory markers They're looking at inflammatory markers They're looking at inflammatory markers in sputum. So it's really disease re in sputum. So it's really disease re in sputum. So it's really disease re relevant for this, you know, people with relevant for this, you know, people with relevant for this, you know, people with a respiratory condition. NR lowers those a respiratory condition. NR lowers those a respiratory condition. NR lowers those inflammatory markers. Placebo doesn't. inflammatory markers. Placebo doesn't. inflammatory markers. Placebo doesn't. So we know as for a fact. So, so what So we know as for a fact. So, so what So we know as for a fact. So, so what what I think it's doing is it's what I think it's doing is it's what I think it's doing is it's rebuilding NAD in a system in which the rebuilding NAD in a system in which the rebuilding NAD in a system in which the NAD systems come under attack, NAD systems come under attack, NAD systems come under attack, rebuilding those supplies so that rebuilding those supplies so that rebuilding those supplies so that uh free radical species can be uh free radical species can be uh free radical species can be detoxified detoxified detoxified and the anabolic processes and the and the anabolic processes and the and the anabolic processes and the repair processes can can work better. repair processes can can work better. repair processes can can work better. >> Well, I think you kind of answered, you >> Well, I think you kind of answered, you >> Well, I think you kind of answered, you know, my question. And I was kind of know, my question. And I was kind of know, my question. And I was kind of going to ask you, you know, with respect going to ask you, you know, with respect going to ask you, you know, with respect to these these chronic conditions that to these these chronic conditions that to these these chronic conditions that are very common in, you know, US and are very common in, you know, US and are very common in, you know, US and also just a lot of developed countries, also just a lot of developed countries, also just a lot of developed countries, you know, what if someone could change you know, what if someone could change you know, what if someone could change only one aspect of their their lifestyle only one aspect of their their lifestyle only one aspect of their their lifestyle within the next 2 to 3 months? Like what within the next 2 to 3 months? Like what within the next 2 to 3 months? Like what would have the biggest bang for their would have the biggest bang for their would have the biggest bang for their buck in terms of supporting their NAD? buck in terms of supporting their NAD? buck in terms of supporting their NAD? And it really sounds like the thing And it really sounds like the thing And it really sounds like the thing that's causing the inflammation, the that's causing the inflammation, the that's causing the inflammation, the chronic inflammation, chronic inflammation, chronic inflammation, um, might be a big driver. So if it's um, might be a big driver. So if it's um, might be a big driver. So if it's obesity, you know, weight loss, right? obesity, you know, weight loss, right? obesity, you know, weight loss, right? If it's the if it's the the um you know, If it's the if it's the the um you know, If it's the if it's the the um you know, the sleep. So whether or not you're the sleep. So whether or not you're the sleep. So whether or not you're we're talking about, like I said, we're we're talking about, like I said, we're we're talking about, like I said, we're going to dive into this, but like if going to dive into this, but like if going to dive into this, but like if you're if your circadian rhythms you're if your circadian rhythms you're if your circadian rhythms disrupted, I mean, trying to fix fix disrupted, I mean, trying to fix fix disrupted, I mean, trying to fix fix that or obviously supplementation, we're that or obviously supplementation, we're that or obviously supplementation, we're going to get into that as well. And for going to get into that as well. And for going to get into that as well. And for people wondering what NR is, again, people wondering what NR is, again, people wondering what NR is, again, nicotine, my ribboside, we're going to nicotine, my ribboside, we're going to nicotine, my ribboside, we're going to get into all that very very soon. Um get into all that very very soon. Um get into all that very very soon. Um whether or not it's stress, stress whether or not it's stress, stress whether or not it's stress, stress causes inflammation, right? causes inflammation, right? causes inflammation, right? >> It could be drinking though. I mean, it >> It could be drinking though. I mean, it >> It could be drinking though. I mean, it could be drinking, could be drug use, could be drinking, could be drug use, could be drinking, could be drug use, >> right? A lot of things cause >> right? A lot of things cause >> right? A lot of things cause inflammation. inflammation. inflammation. >> Yeah. Yeah. Um, and >> Yeah. Yeah. Um, and >> Yeah. Yeah. Um, and >> and the thing is, the thing that's >> and the thing is, the thing that's >> and the thing is, the thing that's important and I think that that's that's important and I think that that's that's important and I think that that's that's good about about your show is that, you good about about your show is that, you good about about your show is that, you know, there aren't oneizefits all know, there aren't oneizefits all know, there aren't oneizefits all recommendations for people, right? So, recommendations for people, right? So, recommendations for people, right? So, you know, I don't understand why someone you know, I don't understand why someone you know, I don't understand why someone would tell large podcast audiences that would tell large podcast audiences that would tell large podcast audiences that everybody should be fasting or doing everybody should be fasting or doing everybody should be fasting or doing timerestricted feeding because then timerestricted feeding because then timerestricted feeding because then you're going to get the people that have you're going to get the people that have you're going to get the people that have the most OCD, the most OCD, the most OCD, right? Um that have the most problematic right? Um that have the most problematic right? Um that have the most problematic relationship with their food to worry relationship with their food to worry relationship with their food to worry about time of day eating and counting about time of day eating and counting about time of day eating and counting calories. and they may be perfectly calories. and they may be perfectly calories. and they may be perfectly lean, right? So, I don't think that lean, right? So, I don't think that lean, right? So, I don't think that everybody needs to be fasting, right? everybody needs to be fasting, right? everybody needs to be fasting, right? But people with overweight actually now But people with overweight actually now But people with overweight actually now have medical options that work, right? have medical options that work, right? have medical options that work, right? And um including oral, you know, GLP-1 And um including oral, you know, GLP-1 And um including oral, you know, GLP-1 medications that in conjunction with medications that in conjunction with medications that in conjunction with resistance training can really improve resistance training can really improve resistance training can really improve people's health. So for people that have people's health. So for people that have people's health. So for people that have overweight and obesity, that's probably, overweight and obesity, that's probably, overweight and obesity, that's probably, you know, number one. you know, number one. you know, number one. >> There's a lot of options now to lose >> There's a lot of options now to lose >> There's a lot of options now to lose weight. weight. weight. >> People that people that are are >> People that people that are are >> People that people that are are drinking, JLP1 actually helps some of drinking, JLP1 actually helps some of drinking, JLP1 actually helps some of those people. But um you know, people those people. But um you know, people those people. But um you know, people that are drinking or are, you know, that are drinking or are, you know, that are drinking or are, you know, sitting, sitting, sitting, you know, in front of of a screen too you know, in front of of a screen too you know, in front of of a screen too many hours a day and are not moving many hours a day and are not moving many hours a day and are not moving their bodies. probably moving their their bodies. probably moving their their bodies. probably moving their bodies more is is gonna be, you know, bodies more is is gonna be, you know, bodies more is is gonna be, you know, important. important. important. >> Right. Right. Um, I want to get back to >> Right. Right. Um, I want to get back to >> Right. Right. Um, I want to get back to this this idea of why, this this idea of why, this this idea of why, you know, the blood NAD isn't you know, the blood NAD isn't you know, the blood NAD isn't necessarily indicative of your what's necessarily indicative of your what's necessarily indicative of your what's going on your muscle and your brain. Um going on your muscle and your brain. Um going on your muscle and your brain. Um and and specifically I want to get into and and specifically I want to get into and and specifically I want to get into the you know let's say you're taking a the you know let's say you're taking a the you know let's say you're taking a an NAD precursor supplement like a an NAD precursor supplement like a an NAD precursor supplement like a nicotenomide ribocide nicotenomide ribocide nicotenomide ribocide >> and you do see that as you mentioned >> and you do see that as you mentioned >> and you do see that as you mentioned that you'll see the NAD levels go up that you'll see the NAD levels go up that you'll see the NAD levels go up like very high in the blood. like very high in the blood. like very high in the blood. What does that tell us about levels in What does that tell us about levels in What does that tell us about levels in the brain? Can we assume I mean I don't the brain? Can we assume I mean I don't the brain? Can we assume I mean I don't know that we can or can we assume that know that we can or can we assume that know that we can or can we assume that the levels are going to go up in the the levels are going to go up in the the levels are going to go up in the brain or in the muscle? Yeah, there are brain or in the muscle? Yeah, there are brain or in the muscle? Yeah, there are there are imaging um experiments that there are imaging um experiments that there are imaging um experiments that show that oral NAD precursors in show that oral NAD precursors in show that oral NAD precursors in increase brain NAD. Um there are small increase brain NAD. Um there are small increase brain NAD. Um there are small clinical studies that show that oral clinical studies that show that oral clinical studies that show that oral nicotenomide riocide improves cerebral nicotenomide riocide improves cerebral nicotenomide riocide improves cerebral blood flow in people with mild cognitive blood flow in people with mild cognitive blood flow in people with mild cognitive impairment. So, you know, that's a impairment. So, you know, that's a impairment. So, you know, that's a functional um measurement. So, I feel functional um measurement. So, I feel functional um measurement. So, I feel pretty good about that. Does it improve pretty good about that. Does it improve pretty good about that. Does it improve cognition or was not not looked at? cognition or was not not looked at? cognition or was not not looked at? um people have tried you know to see so um people have tried you know to see so um people have tried you know to see so there is a longco study um in which um there is a longco study um in which um there is a longco study um in which um all of the people that are enrolled have all of the people that are enrolled have all of the people that are enrolled have long co so they have complaints about long co so they have complaints about long co so they have complaints about their executive function depression their executive function depression their executive function depression their sleep quality their sleep quality their sleep quality um their mood and um there was a recent um their mood and um there was a recent um their mood and um there was a recent study I think in the last month or two study I think in the last month or two study I think in the last month or two it's woo at all and I think it's Lancet it's woo at all and I think it's Lancet it's woo at all and I think it's Lancet e clinical medicine or something like e clinical medicine or something like e clinical medicine or something like that. I'm a co-author on the paper um that. I'm a co-author on the paper um that. I'm a co-author on the paper um that shows that there's within group that shows that there's within group that shows that there's within group improvements. So again, this is not improvements. So again, this is not improvements. So again, this is not quite the gold standard of placeboc quite the gold standard of placeboc quite the gold standard of placeboc controlled NR group is superior to the controlled NR group is superior to the controlled NR group is superior to the placebo group at the end of the study. placebo group at the end of the study. placebo group at the end of the study. But it's a um within group meaning when But it's a um within group meaning when But it's a um within group meaning when people compared their baseline level of people compared their baseline level of people compared their baseline level of executive function to their executive executive function to their executive executive function to their executive function when they were on NR, function when they were on NR, function when they were on NR, there's an improvement there's an improvement there's an improvement >> that was not seen in the placebo group. >> that was not seen in the placebo group. >> that was not seen in the placebo group. >> Did anyone look at whether or not that >> Did anyone look at whether or not that >> Did anyone look at whether or not that improvement correlated with inflammatory improvement correlated with inflammatory improvement correlated with inflammatory status? So baseline inflammatory status status? So baseline inflammatory status status? So baseline inflammatory status being higher and that being being higher and that being being higher and that being >> No, but that's a beautiful hypothesis >> No, but that's a beautiful hypothesis >> No, but that's a beautiful hypothesis that um Dr. Guzman uh should should look that um Dr. Guzman uh should should look that um Dr. Guzman uh should should look at. If you're listening to this, Dr. at. If you're listening to this, Dr. at. If you're listening to this, Dr. Gooseman, make sure each of you look at Gooseman, make sure each of you look at Gooseman, make sure each of you look at the the inflammatory status. Um, and the the inflammatory status. Um, and the the inflammatory status. Um, and then, you know, because I would think, then, you know, because I would think, then, you know, because I would think, you know, there's lots of evidence now you know, there's lots of evidence now you know, there's lots of evidence now that you can even there's even, you that you can even there's even, you that you can even there's even, you know, human trials where people are know, human trials where people are know, human trials where people are injected with lipopolyaccharide, which injected with lipopolyaccharide, which injected with lipopolyaccharide, which induces inflammation or or a saline induces inflammation or or a saline induces inflammation or or a saline control, and you can affect mood, you control, and you can affect mood, you control, and you can affect mood, you can depress the mood, you can depress can depress the mood, you can depress can depress the mood, you can depress cognitive function because inflammation cognitive function because inflammation cognitive function because inflammation affects brain function. Mhm. affects brain function. Mhm. affects brain function. Mhm. >> So I mean I I feel like it's a pretty I >> So I mean I I feel like it's a pretty I >> So I mean I I feel like it's a pretty I would say I I would feel comfortable would say I I would feel comfortable would say I I would feel comfortable speculating that if you have yeah if you speculating that if you have yeah if you speculating that if you have yeah if you have someone with a you know high have someone with a you know high have someone with a you know high inflammatory status baseline for inflammatory status baseline for inflammatory status baseline for whatever reason alcoholism obesity whatever reason alcoholism obesity whatever reason alcoholism obesity chronic sleep deprivation whatever it is chronic sleep deprivation whatever it is chronic sleep deprivation whatever it is there's many many things that can get there's many many things that can get there's many many things that can get you there right you there right you there right >> that if you can you know either reduce >> that if you can you know either reduce >> that if you can you know either reduce that inflammation obviously through that inflammation obviously through that inflammation obviously through lifestyle and diet that would be ideal lifestyle and diet that would be ideal lifestyle and diet that would be ideal and or if you take the nicotenomide riv and or if you take the nicotenomide riv and or if you take the nicotenomide riv side, you know, to help replenish some side, you know, to help replenish some side, you know, to help replenish some of that NAD to help with the of that NAD to help with the of that NAD to help with the inflammation that you would affect, you inflammation that you would affect, you inflammation that you would affect, you know, some of the functional outputs as know, some of the functional outputs as know, some of the functional outputs as well. well. well. >> So, how would I'm, you know, I and that >> So, how would I'm, you know, I and that >> So, how would I'm, you know, I and that kind of gets to this thing, you know, kind of gets to this thing, you know, kind of gets to this thing, you know, and a lot of people are taking there's a and a lot of people are taking there's a and a lot of people are taking there's a lot of people that are taking NAD lot of people that are taking NAD lot of people that are taking NAD boosting supplements boosting supplements boosting supplements >> and what do you think for them like >> and what do you think for them like >> and what do you think for them like should they go get their NAD blood should they go get their NAD blood should they go get their NAD blood levels measured? Is there any sort of levels measured? Is there any sort of levels measured? Is there any sort of you know functional test that they can you know functional test that they can you know functional test that they can do to really know if it's working or is do to really know if it's working or is do to really know if it's working or is it just kind of like a like like the it just kind of like a like like the it just kind of like a like like the fitness improvements right let's say fitness improvements right let's say fitness improvements right let's say they are working out and they take the they are working out and they take the they are working out and they take the NAD like should they be measuring their NAD like should they be measuring their NAD like should they be measuring their grip strength or their grip strength or their grip strength or their >> you know okay so let me let me cover my >> you know okay so let me let me cover my >> you know okay so let me let me cover my COI right here right COI right here right COI right here right >> yes let's do that yeah so um so it was >> yes let's do that yeah so um so it was >> yes let's do that yeah so um so it was initially my technology that turned into initially my technology that turned into initially my technology that turned into the nicotoni ribocide and NAD boosting the nicotoni ribocide and NAD boosting the nicotoni ribocide and NAD boosting industry so I'm chief scientific ific industry so I'm chief scientific ific industry so I'm chief scientific ific adviser of Niogen which makes this adviser of Niogen which makes this adviser of Niogen which makes this Niogen pill right I'm also chief Niogen pill right I'm also chief Niogen pill right I'm also chief scientific adviser of NadMed which is an scientific adviser of NadMed which is an scientific adviser of NadMed which is an ND testing company do I think there's a ND testing company do I think there's a ND testing company do I think there's a use case for Niogen in people in healthy use case for Niogen in people in healthy use case for Niogen in people in healthy aging yes on the basis of eight aging yes on the basis of eight aging yes on the basis of eight randomized clinical trials showing randomized clinical trials showing randomized clinical trials showing anti-inflammatory benefits in people anti-inflammatory benefits in people anti-inflammatory benefits in people positive trial and peripheral artery positive trial and peripheral artery positive trial and peripheral artery disease and some of these suggestively disease and some of these suggestively disease and some of these suggestively positive trials like long co which which positive trials like long co which which positive trials like long co which which we talked about um do I think that there we talked about um do I think that there we talked about um do I think that there is a value of NAD testing in people is a value of NAD testing in people is a value of NAD testing in people definitely in clinical trials right so definitely in clinical trials right so definitely in clinical trials right so this company NADMED provides you know this company NADMED provides you know this company NADMED provides you know kits and reagents for clinical trial kits and reagents for clinical trial kits and reagents for clinical trial observations observations observations um people some individual people buy the um people some individual people buy the um people some individual people buy the kit kits do I think that there's a use kit kits do I think that there's a use kit kits do I think that there's a use case for it no I don't case for it no I don't case for it no I don't >> okay I'm kind of I'm kind of with you on >> okay I'm kind of I'm kind of with you on >> okay I'm kind of I'm kind of with you on that I feel like it's probably known that I feel like it's probably known that I feel like it's probably known that they're increasing it they're that they're increasing it they're that they're increasing it they're they're um if they're if they're buying they're um if they're if they're buying they're um if they're if they're buying um you know nicotenocide um you know nicotenocide um you know nicotenocide um from niogen it's going to boost their um from niogen it's going to boost their um from niogen it's going to boost their NAD like 6 to 8 hours after ingestion NAD like 6 to 8 hours after ingestion NAD like 6 to 8 hours after ingestion their NAD is higher like do you do you their NAD is higher like do you do you their NAD is higher like do you do you go to when if you take an aspirin do you go to when if you take an aspirin do you go to when if you take an aspirin do you need to do a mass spec to see whether need to do a mass spec to see whether need to do a mass spec to see whether you ingested an aspirin I I don't I you ingested an aspirin I I don't I you ingested an aspirin I I don't I don't see the use case for that don't see the use case for that don't see the use case for that >> um And there's probably some individual >> um And there's probably some individual >> um And there's probably some individual variability right right there. variability right right there. variability right right there. >> So, so but again in the context of a >> So, so but again in the context of a >> So, so but again in the context of a clinical trial, right? If we've enrolled clinical trial, right? If we've enrolled clinical trial, right? If we've enrolled 50 people and we're trying to figure 50 people and we're trying to figure 50 people and we're trying to figure out, you know, we had some responders out, you know, we had some responders out, you know, we had some responders and some non-responders, right? Which is and some non-responders, right? Which is and some non-responders, right? Which is kind of getting into the questions that kind of getting into the questions that kind of getting into the questions that you're you're asking, did it correlate you're you're asking, did it correlate you're you're asking, did it correlate with blah blah blah. So now you in the with blah blah blah. So now you in the with blah blah blah. So now you in the context of a clinical trial, you want to context of a clinical trial, you want to context of a clinical trial, you want to did it correlate with inflammatory did it correlate with inflammatory did it correlate with inflammatory markers? Did it correlate with the way markers? Did it correlate with the way markers? Did it correlate with the way their blood responded? Is there anything their blood responded? Is there anything their blood responded? Is there anything unusual about the way their blood unusual about the way their blood unusual about the way their blood responded? But I think that there's kind responded? But I think that there's kind responded? But I think that there's kind of a lot of overw worrying and over of a lot of overw worrying and over of a lot of overw worrying and over testing in of the worried well and I testing in of the worried well and I testing in of the worried well and I don't think that that's very helpful. don't think that that's very helpful. don't think that that's very helpful. >> Um, I agree. You have to choose your >> Um, I agree. You have to choose your >> Um, I agree. You have to choose your battles otherwise you're going to drive battles otherwise you're going to drive battles otherwise you're going to drive yourself nuts. Um, and like I said, yourself nuts. Um, and like I said, yourself nuts. Um, and like I said, we're going to get a little bit more we're going to get a little bit more we're going to get a little bit more into the NAD precursors. I kind of want into the NAD precursors. I kind of want into the NAD precursors. I kind of want to wrap up this lifestyle diet, to wrap up this lifestyle diet, to wrap up this lifestyle diet, lifestyle, lifestyle, lifestyle, >> you know, factors that are supporting >> you know, factors that are supporting >> you know, factors that are supporting NAD. We talked about that are consuming, NAD. We talked about that are consuming, NAD. We talked about that are consuming, but I want to talk a little bit about but I want to talk a little bit about but I want to talk a little bit about the supporting the supporting the supporting >> systems for NAD. And for me, exercise is >> systems for NAD. And for me, exercise is >> systems for NAD. And for me, exercise is always at the top of everything. So, I'd always at the top of everything. So, I'd always at the top of everything. So, I'd love to start there. love to start there. love to start there. >> Um, how how does exercise affect NAD? >> Um, how how does exercise affect NAD? >> Um, how how does exercise affect NAD? And what type of exercise would be And what type of exercise would be And what type of exercise would be better for increasing NAD? Would it be better for increasing NAD? Would it be better for increasing NAD? Would it be aerobic? Would it be, you know, strength aerobic? Would it be, you know, strength aerobic? Would it be, you know, strength training, resistance training, both? I training, resistance training, both? I training, resistance training, both? I can come up with rationale for why I can come up with rationale for why I can come up with rationale for why I think both would be either or. think both would be either or. think both would be either or. >> But you know that the exercise that you >> But you know that the exercise that you >> But you know that the exercise that you do is infinitely better than the do is infinitely better than the do is infinitely better than the exercise that you plan to do or wish you exercise that you plan to do or wish you exercise that you plan to do or wish you did. Yeah. did. Yeah. did. Yeah. >> Right. >> Right. >> Right. >> Totally. So, anything's better than >> Totally. So, anything's better than >> Totally. So, anything's better than nothing. nothing. nothing. >> Yeah. and and we do have some clinical >> Yeah. and and we do have some clinical >> Yeah. and and we do have some clinical evidence showing that exercise leads to evidence showing that exercise leads to evidence showing that exercise leads to an increase in the gene expression of an increase in the gene expression of an increase in the gene expression of NAD biosynthetic enzymes. So I recently NAD biosynthetic enzymes. So I recently NAD biosynthetic enzymes. So I recently published that with a group in Germany published that with a group in Germany published that with a group in Germany and I can't remember what kind of and I can't remember what kind of and I can't remember what kind of exercise that they did but um yeah exercise that they did but um yeah exercise that they did but um yeah there's there's evidence that people there's there's evidence that people there's there's evidence that people that um exercise you're boosting a lot that um exercise you're boosting a lot that um exercise you're boosting a lot of transcription pathways and gene of transcription pathways and gene of transcription pathways and gene expression p pathways that are you know expression p pathways that are you know expression p pathways that are you know I I hate the word rejuvenating but it's I I hate the word rejuvenating but it's I I hate the word rejuvenating but it's that are associated with youth and that are associated with youth and that are associated with youth and >> I mean mitochondrial biogenesis goes up >> I mean mitochondrial biogenesis goes up >> I mean mitochondrial biogenesis goes up when you exercise that's a rejuvenating when you exercise that's a rejuvenating when you exercise that's a rejuvenating I you you have to kind of there are I you you have to kind of there are I you you have to kind of there are buzzwords that can you you kind of get buzzwords that can you you kind of get buzzwords that can you you kind of get you know they're overplayed but you know they're overplayed but you know they're overplayed but >> but it when it's true it's true right >> but it when it's true it's true right >> but it when it's true it's true right >> it's true true >> it's true true >> it's true true >> um does does mitochondrial biogenesis >> um does does mitochondrial biogenesis >> um does does mitochondrial biogenesis play a role in some of the NAD increases play a role in some of the NAD increases play a role in some of the NAD increases as well if you're making more as well if you're making more as well if you're making more mitochondria is it like an adaptation mitochondria is it like an adaptation mitochondria is it like an adaptation where the body's like we need more of where the body's like we need more of where the body's like we need more of this you know NAD around so like this this you know NAD around so like this this you know NAD around so like this like key transcription factor that like key transcription factor that like key transcription factor that responds to the NAD system and then you responds to the NAD system and then you responds to the NAD system and then you know you make more mitochondria, you know you make more mitochondria, you know you make more mitochondria, you have better beta oxidation. have better beta oxidation. have better beta oxidation. >> How does NAD play a role in exercise >> How does NAD play a role in exercise >> How does NAD play a role in exercise recovery? Like recovering from and now I recovery? Like recovering from and now I recovery? Like recovering from and now I mean like that that's part of the mean like that that's part of the mean like that that's part of the repair, right? repair, right? repair, right? you would imagine it helps. But you would imagine it helps. But you would imagine it helps. But >> so yeah, the the um the sports trainers >> so yeah, the the um the sports trainers >> so yeah, the the um the sports trainers and the heads of, you know, professional and the heads of, you know, professional and the heads of, you know, professional football clubs and and college um football clubs and and college um football clubs and and college um athletic programs that buy, you know, athletic programs that buy, you know, athletic programs that buy, you know, Niogen by the tub swear by this. So Niogen by the tub swear by this. So Niogen by the tub swear by this. So there's not a lot of rigorous placebo there's not a lot of rigorous placebo there's not a lot of rigorous placebo control data on it, but there's train control data on it, but there's train control data on it, but there's train Yeah. Yeah. Yeah. >> An anecdot. >> An anecdot. >> An anecdot. >> Yes. Um there's um you know, and there's >> Yes. Um there's um you know, and there's >> Yes. Um there's um you know, and there's there's like photos of um two advisors there's like photos of um two advisors there's like photos of um two advisors of NIA and myself and and Dr. Rudolph of NIA and myself and and Dr. Rudolph of NIA and myself and and Dr. Rudolph Tanzy who's a professor at Harvard um Tanzy who's a professor at Harvard um Tanzy who's a professor at Harvard um you know with Bill Bich when he was the you know with Bill Bich when he was the you know with Bill Bich when he was the coach of the New England Patriots and coach of the New England Patriots and coach of the New England Patriots and and the coach of of a 40-year-old Tom and the coach of of a 40-year-old Tom and the coach of of a 40-year-old Tom Brady. So it's well known that the Brady. So it's well known that the Brady. So it's well known that the Patriots um took Niagen for for many Patriots um took Niagen for for many Patriots um took Niagen for for many years. I don't actually know whether years. I don't actually know whether years. I don't actually know whether they're still taking it postbell check they're still taking it postbell check they're still taking it postbell check but um it's in a lot of um training but um it's in a lot of um training but um it's in a lot of um training rooms for the reason of recovery. Have rooms for the reason of recovery. Have rooms for the reason of recovery. Have any of the exercise physiology any of the exercise physiology any of the exercise physiology scientists become interested in in scientists become interested in in scientists become interested in in looking at this? looking at this? looking at this? >> Yeah, I think that it's something that >> Yeah, I think that it's something that >> Yeah, I think that it's something that really needs to be studied in, you know, really needs to be studied in, you know, really needs to be studied in, you know, laboratory exercise physiology science laboratory exercise physiology science laboratory exercise physiology science because you can do those kinds of because you can do those kinds of because you can do those kinds of trials, right? Um, you can you can work trials, right? Um, you can you can work trials, right? Um, you can you can work people really hard on a bicycle and you people really hard on a bicycle and you people really hard on a bicycle and you know see whether you can work them as know see whether you can work them as know see whether you can work them as hard the following day, right? hard the following day, right? hard the following day, right? >> Yeah. And al and not just recovery but >> Yeah. And al and not just recovery but >> Yeah. And al and not just recovery but in performance. I mean you'd think if in performance. I mean you'd think if in performance. I mean you'd think if you're taxing the NAD that you're you're taxing the NAD that you're you're taxing the NAD that you're consuming more NAD, your muscles are consuming more NAD, your muscles are consuming more NAD, your muscles are working harder and like you said your ad working harder and like you said your ad working harder and like you said your ad the adaptation is that you're increasing the adaptation is that you're increasing the adaptation is that you're increasing transcription. you're going to, you transcription. you're going to, you transcription. you're going to, you know, whatever these genes or enzymes know, whatever these genes or enzymes know, whatever these genes or enzymes important for making more NAD are going important for making more NAD are going important for making more NAD are going to be increased. So, you're going to to be increased. So, you're going to to be increased. So, you're going to make more NAD because your b because make more NAD because your b because make more NAD because your b because your body knows I'm using more. I need your body knows I'm using more. I need your body knows I'm using more. I need to like respond to that. to like respond to that. to like respond to that. >> Um, it it would be interesting to know >> Um, it it would be interesting to know >> Um, it it would be interesting to know if you supplemented with the precursor if you supplemented with the precursor if you supplemented with the precursor if that also was beneficial. I would if that also was beneficial. I would if that also was beneficial. I would assume assume assume >> it would be, but it would be nice >> it would be, but it would be nice >> it would be, but it would be nice synergistic, right? synergistic, right? synergistic, right? >> Yeah, it would be exactly it would be >> Yeah, it would be exactly it would be >> Yeah, it would be exactly it would be nice for someone to actually prove that. nice for someone to actually prove that. nice for someone to actually prove that. Um, Um, Um, >> we talked a little bit about circadian >> we talked a little bit about circadian >> we talked a little bit about circadian biology and being out of sync with your biology and being out of sync with your biology and being out of sync with your circadian rhythm. I want to kind of get circadian rhythm. I want to kind of get circadian rhythm. I want to kind of get to that, but before getting there, I to that, but before getting there, I to that, but before getting there, I think something that even more people think something that even more people think something that even more people are familiar with is like acute sleep are familiar with is like acute sleep are familiar with is like acute sleep loss. Like you have, let's say you have loss. Like you have, let's say you have loss. Like you have, let's say you have one night, you're out socializing later one night, you're out socializing later one night, you're out socializing later than usual, you get to bed later, you than usual, you get to bed later, you than usual, you get to bed later, you have to wake up at the same time, you have to wake up at the same time, you have to wake up at the same time, you miss sleep, right? miss sleep, right? miss sleep, right? >> How does that affect the NAD system? >> How does that affect the NAD system? >> How does that affect the NAD system? >> Is it known? I'm not sure that we have >> Is it known? I'm not sure that we have >> Is it known? I'm not sure that we have hard data on it because I don't I mean hard data on it because I don't I mean hard data on it because I don't I mean the there probably are accessible mouse the there probably are accessible mouse the there probably are accessible mouse experiments. I don't know how much you experiments. I don't know how much you experiments. I don't know how much you would value them because you can do would value them because you can do would value them because you can do things um you know with mice where you things um you know with mice where you things um you know with mice where you um change the lighting around in the um change the lighting around in the um change the lighting around in the room or give them food in weird times room or give them food in weird times room or give them food in weird times per day. and you could potentially per day. and you could potentially per day. and you could potentially measure changes in the NAD system, but measure changes in the NAD system, but measure changes in the NAD system, but um it would be hard to enroll human um it would be hard to enroll human um it would be hard to enroll human trials like that. trials like that. trials like that. >> Yeah, I guess there's no real it's not >> Yeah, I guess there's no real it's not >> Yeah, I guess there's no real it's not there's not a lot of empirical data on there's not a lot of empirical data on there's not a lot of empirical data on that. If I were to speculate on this and that. If I were to speculate on this and that. If I were to speculate on this and I'm sure you would agree like at least I'm sure you would agree like at least I'm sure you would agree like at least in this certainly with acute you do get in this certainly with acute you do get in this certainly with acute you do get an increase in inflammatory SAS but I an increase in inflammatory SAS but I an increase in inflammatory SAS but I would say more so with chronic sleep would say more so with chronic sleep would say more so with chronic sleep deprivation. Let's say you have a new deprivation. Let's say you have a new deprivation. Let's say you have a new mom or you know like who's just getting mom or you know like who's just getting mom or you know like who's just getting constant fragmented sleep like we do constant fragmented sleep like we do constant fragmented sleep like we do know that inflammatory you know the know that inflammatory you know the know that inflammatory you know the inflammatory status is increased like inflammatory status is increased like inflammatory status is increased like people have more inflammatory biomarkers people have more inflammatory biomarkers people have more inflammatory biomarkers that are elevated that are elevated that are elevated >> with chronic sleep loss. >> with chronic sleep loss. >> with chronic sleep loss. >> Yeah. Well, I do want to tell you about >> Yeah. Well, I do want to tell you about >> Yeah. Well, I do want to tell you about a new mom though a new mom though a new mom though >> cuz I can tell you about um new mother >> cuz I can tell you about um new mother >> cuz I can tell you about um new mother mice and and rats. Um we published this mice and and rats. Um we published this mice and and rats. Um we published this I think in 2019. I think in 2019. I think in 2019. Um so um we had this idea that if we had Um so um we had this idea that if we had Um so um we had this idea that if we had really um overweight female mice really um overweight female mice really um overweight female mice that um they'd be conferring like a that um they'd be conferring like a that um they'd be conferring like a metabolic syndrome to their offspring. metabolic syndrome to their offspring. metabolic syndrome to their offspring. But it was our first time trying to get But it was our first time trying to get But it was our first time trying to get fat mice to be pregnant. Okay. And um so fat mice to be pregnant. Okay. And um so fat mice to be pregnant. Okay. And um so we had mice that were on control diets we had mice that were on control diets we had mice that were on control diets plus or minus nicotenomide ribocide and plus or minus nicotenomide ribocide and plus or minus nicotenomide ribocide and we had mice that were on highfat diets we had mice that were on highfat diets we had mice that were on highfat diets plus or minus nicotenomide ribocide. And plus or minus nicotenomide ribocide. And plus or minus nicotenomide ribocide. And we simply didn't get enough fat mice to we simply didn't get enough fat mice to we simply didn't get enough fat mice to be pregnant and go to term with their be pregnant and go to term with their be pregnant and go to term with their baby mice in the fat group. But in the baby mice in the fat group. But in the baby mice in the fat group. But in the control group, something interesting control group, something interesting control group, something interesting happened, which is we had perfect happened, which is we had perfect happened, which is we had perfect fertility. We had mice that were whose fertility. We had mice that were whose fertility. We had mice that were whose whose moms were either supplemented with whose moms were either supplemented with whose moms were either supplemented with NR or not. And we were able to follow NR or not. And we were able to follow NR or not. And we were able to follow their offspring. And what we found is their offspring. And what we found is their offspring. And what we found is that the offspring of supplemented that the offspring of supplemented that the offspring of supplemented mothers mothers mothers had better lean mass um at the time of had better lean mass um at the time of had better lean mass um at the time of weaning that they were able to maintain weaning that they were able to maintain weaning that they were able to maintain for their whole lives. They had um for their whole lives. They had um for their whole lives. They had um faster uh mechanical physical faster uh mechanical physical faster uh mechanical physical development. So their performance on development. So their performance on development. So their performance on like a balance beam type thing was like a balance beam type thing was like a balance beam type thing was better if the mom was supplemented. Um better if the mom was supplemented. Um better if the mom was supplemented. Um they had lower fear and anxiety to the they had lower fear and anxiety to the they had lower fear and anxiety to the degree to which you can test such things degree to which you can test such things degree to which you can test such things in in mice. Um so they did better on a in in mice. Um so they did better on a in in mice. Um so they did better on a Morris water maze and they even had Morris water maze and they even had Morris water maze and they even had better adult hippocample neurogenesis if better adult hippocample neurogenesis if better adult hippocample neurogenesis if the mom had been supplemented. the mom had been supplemented. the mom had been supplemented. >> This is very interesting. I mean I think >> This is very interesting. I mean I think >> This is very interesting. I mean I think for me in my brain two things are going for me in my brain two things are going for me in my brain two things are going on here. One, we're talking about on here. One, we're talking about on here. One, we're talking about fertility. I'm thinking mitochondrial fertility. I'm thinking mitochondrial fertility. I'm thinking mitochondrial health. I'm thinking all this. And two, health. I'm thinking all this. And two, health. I'm thinking all this. And two, I'm thinking if these if these pregnant I'm thinking if these if these pregnant I'm thinking if these if these pregnant mice were taking nicotine ribbocide mice were taking nicotine ribbocide mice were taking nicotine ribbocide throughout pregnancy, then I'm shifting throughout pregnancy, then I'm shifting throughout pregnancy, then I'm shifting to gene regulation. So, did you guys to gene regulation. So, did you guys to gene regulation. So, did you guys look at any of the look at any of the look at any of the >> So, so the the weight at weaning of a >> So, so the the weight at weaning of a >> So, so the the weight at weaning of a mouse is really important because the mouse is really important because the mouse is really important because the more um you do calorie transfer from the more um you do calorie transfer from the more um you do calorie transfer from the mom from lactation, right? then the more mom from lactation, right? then the more mom from lactation, right? then the more um you know muscle and fat the baby has um you know muscle and fat the baby has um you know muscle and fat the baby has and the kind of the better life course and the kind of the better life course and the kind of the better life course it has. it has. it has. >> So it turns out that the NR supplemented >> So it turns out that the NR supplemented >> So it turns out that the NR supplemented new moms also had better weight new moms also had better weight new moms also had better weight management, right? And it was simply management, right? And it was simply management, right? And it was simply calorie transfer. They produced more calorie transfer. They produced more calorie transfer. They produced more milk. milk. milk. >> The NR supplemented moms produced more >> The NR supplemented moms produced more >> The NR supplemented moms produced more milk than the non-supplemented moms. and milk than the non-supplemented moms. and milk than the non-supplemented moms. and potentially it was higher in bioactives potentially it was higher in bioactives potentially it was higher in bioactives as well. We don't actually know um we as well. We don't actually know um we as well. We don't actually know um we don't have a full characterization of don't have a full characterization of don't have a full characterization of the milk from the supplemented moms the milk from the supplemented moms the milk from the supplemented moms versus the non supplemented moms. So versus the non supplemented moms. So versus the non supplemented moms. So there may have been very specialized there may have been very specialized there may have been very specialized fatty acids or altered microbiome. fatty acids or altered microbiome. fatty acids or altered microbiome. There's a whole bunch of different There's a whole bunch of different There's a whole bunch of different things it could be right. But it was things it could be right. But it was things it could be right. But it was also more bulk calories. So also more bulk calories. So also more bulk calories. So >> interesting. Yeah. um >> interesting. Yeah. um >> interesting. Yeah. um histone deacetylases histone deacetylases histone deacetylases epigenetics. I'm thinking are we is that epigenetics. I'm thinking are we is that epigenetics. I'm thinking are we is that like a possibility as well in terms of like a possibility as well in terms of like a possibility as well in terms of >> um yeah there could be a lot of >> um yeah there could be a lot of >> um yeah there could be a lot of different things going on but one of the different things going on but one of the different things going on but one of the things that we found is that a new things that we found is that a new things that we found is that a new mother's liver not only is it mother's liver not only is it mother's liver not only is it distributing protein fat and distributing protein fat and distributing protein fat and carbohydrate to the mammorary system for carbohydrate to the mammorary system for carbohydrate to the mammorary system for the mammorary biosynthetic lactation the mammorary biosynthetic lactation the mammorary biosynthetic lactation yeah biosynthetic program yeah biosynthetic program yeah biosynthetic program >> it's also distributing NAD precursors so >> it's also distributing NAD precursors so >> it's also distributing NAD precursors so the mammory NAD the mammory NAD the mammory NAD >> in NR our supplemented mothers was >> in NR our supplemented mothers was >> in NR our supplemented mothers was greatly increased. greatly increased. greatly increased. >> Interesting. >> Interesting. >> Interesting. >> And actually the liver NAD system >> And actually the liver NAD system >> And actually the liver NAD system declines in a non-supplemented mother. declines in a non-supplemented mother. declines in a non-supplemented mother. The blood NAD metabolism increases and The blood NAD metabolism increases and The blood NAD metabolism increases and it basically accumulates in the memory it basically accumulates in the memory it basically accumulates in the memory in order to support the mammorary in order to support the mammorary in order to support the mammorary biosynthetic program. biosynthetic program. biosynthetic program. >> I we are going to talk about safety and >> I we are going to talk about safety and >> I we are going to talk about safety and stuff. We're I'm jumping ahead of myself stuff. We're I'm jumping ahead of myself stuff. We're I'm jumping ahead of myself but since we're on this topic. but since we're on this topic. but since we're on this topic. >> Yeah. Do you I mean with pregnancy it's >> Yeah. Do you I mean with pregnancy it's >> Yeah. Do you I mean with pregnancy it's always like it's always my you know rule always like it's always my you know rule always like it's always my you know rule that I like to sort of get off all the that I like to sort of get off all the that I like to sort of get off all the like like like dozens of supplements I'm taking and go dozens of supplements I'm taking and go dozens of supplements I'm taking and go down to the essentials right that we down to the essentials right that we down to the essentials right that we know is safe important know is safe important know is safe important >> um is there any reason to believe that >> um is there any reason to believe that >> um is there any reason to believe that taking nicenide ribocide during taking nicenide ribocide during taking nicenide ribocide during pregnancy would not be safe or is that pregnancy would not be safe or is that pregnancy would not be safe or is that something that something that something that >> there's there's no data um and >> there's there's no data um and >> there's there's no data um and >> aside from the animal study human data >> aside from the animal study human data >> aside from the animal study human data >> there's no human data >> there's no human data >> there's no human data Um however, you know, as soon as um our Um however, you know, as soon as um our Um however, you know, as soon as um our group published this work, we got calls group published this work, we got calls group published this work, we got calls from UC Davis and um the whole group in from UC Davis and um the whole group in from UC Davis and um the whole group in Sacramento that works on human lactation Sacramento that works on human lactation Sacramento that works on human lactation and model system lactation. So um Dr. and model system lactation. So um Dr. and model system lactation. So um Dr. Garman and a number of other folks at at Garman and a number of other folks at at Garman and a number of other folks at at UC Davis are some of the biggest experts UC Davis are some of the biggest experts UC Davis are some of the biggest experts in lactation in the world and they in lactation in the world and they in lactation in the world and they started um planning some large animal started um planning some large animal started um planning some large animal trials as well as human trials. So one trials as well as human trials. So one trials as well as human trials. So one of their ideas was that preeie moms of of their ideas was that preeie moms of of their ideas was that preeie moms of preeis don't generally produce enough preeis don't generally produce enough preeis don't generally produce enough milk because you know this very very milk because you know this very very milk because you know this very very well is that you're the the things that well is that you're the the things that well is that you're the the things that are happening in the new mom's body are are happening in the new mom's body are are happening in the new mom's body are kind of in sync with baby development, kind of in sync with baby development, kind of in sync with baby development, right? And so if baby for some reason right? And so if baby for some reason right? And so if baby for some reason comes out really early, mom's mammorary comes out really early, mom's mammorary comes out really early, mom's mammorary system is not generally ready to produce system is not generally ready to produce system is not generally ready to produce a lot of milk and you have a a new very a lot of milk and you have a a new very a lot of milk and you have a a new very small baby that has major nutritional small baby that has major nutritional small baby that has major nutritional needs. So I believe that they have needs. So I believe that they have needs. So I believe that they have planned a human lactation study with planned a human lactation study with planned a human lactation study with moms of preeis and I think that there moms of preeis and I think that there moms of preeis and I think that there are some other studies that are being are some other studies that are being are some other studies that are being done or being planned at UC Davis. done or being planned at UC Davis. done or being planned at UC Davis. >> Well, at least with the with the >> Well, at least with the with the >> Well, at least with the with the lactation. That's interesting. I always lactation. That's interesting. I always lactation. That's interesting. I always I mean it sounds like for like fertility I mean it sounds like for like fertility I mean it sounds like for like fertility wise it's always you know it might not wise it's always you know it might not wise it's always you know it might not be a bad idea to try the nicotenomide be a bad idea to try the nicotenomide be a bad idea to try the nicotenomide ribocide. I do actually know some ribocide. I do actually know some ribocide. I do actually know some fertility doctors that do recommend true fertility doctors that do recommend true fertility doctors that do recommend true niogen by the way. niogen by the way. niogen by the way. >> Yeah. for fertility. >> Yeah. for fertility. >> Yeah. for fertility. >> We know that it's being done. Um, you >> We know that it's being done. Um, you >> We know that it's being done. Um, you know, this is an this is an area where, know, this is an this is an area where, know, this is an this is an area where, you know, it's a little bit like the you know, it's a little bit like the you know, it's a little bit like the sports trainers being out um ahead of sports trainers being out um ahead of sports trainers being out um ahead of randomized trials. Um the animal results randomized trials. Um the animal results randomized trials. Um the animal results are so strong and that generally the are so strong and that generally the are so strong and that generally the safety data are so you know uh safety data are so you know uh safety data are so you know uh comforting that um there are a lot of comforting that um there are a lot of comforting that um there are a lot of women that are you know presumably women that are you know presumably women that are you know presumably taking 500 milligrams or a gram of taking 500 milligrams or a gram of taking 500 milligrams or a gram of Niogen you know per day during pregnancy Niogen you know per day during pregnancy Niogen you know per day during pregnancy or to get pregnant. or to get pregnant. or to get pregnant. >> Would that be the the human equivalent >> Would that be the the human equivalent >> Would that be the the human equivalent dose from from your animal study? Would dose from from your animal study? Would dose from from your animal study? Would it be something like 500 millig? it be something like 500 millig? it be something like 500 millig? >> The clinical doses are generally around >> The clinical doses are generally around >> The clinical doses are generally around a gram a day. a gram a day. a gram a day. >> A gram. So that would be like two true >> A gram. So that would be like two true >> A gram. So that would be like two true ngen. ngen. ngen. >> There's different >> There's different >> There's different >> different. Okay. But yeah. >> different. Okay. But yeah. >> different. Okay. But yeah. >> Okay. Um fascinating. >> Okay. Um fascinating. >> Okay. Um fascinating. And I would like to kind of just circle And I would like to kind of just circle And I would like to kind of just circle back to the the sleep because um you do back to the the sleep because um you do back to the the sleep because um you do have some at least pre-clinical evidence have some at least pre-clinical evidence have some at least pre-clinical evidence on disrupted circadian rhythms. Yeah. on disrupted circadian rhythms. Yeah. on disrupted circadian rhythms. Yeah. There are many many people in the United There are many many people in the United There are many many people in the United States who are shift workers. We rely States who are shift workers. We rely States who are shift workers. We rely upon them. Thank you for all the work upon them. Thank you for all the work upon them. Thank you for all the work you do. We've got nurses, doctors, you do. We've got nurses, doctors, you do. We've got nurses, doctors, firemen, policemen. I mean, there's just firemen, policemen. I mean, there's just firemen, policemen. I mean, there's just and and there's a ton of other shift and and there's a ton of other shift and and there's a ton of other shift workers, right? They're doing a lot of workers, right? They're doing a lot of workers, right? They're doing a lot of really important work to help our really important work to help our really important work to help our society out society out society out >> at the cost of their own health. >> at the cost of their own health. >> at the cost of their own health. >> And um >> And um >> And um >> you mentioned that that >> you mentioned that that >> you mentioned that that being out of sync with your circadian being out of sync with your circadian being out of sync with your circadian rhythm. So that could be shift work, it rhythm. So that could be shift work, it rhythm. So that could be shift work, it could be traveling to another time zone, could be traveling to another time zone, could be traveling to another time zone, right? Jet lag as we call it. right? Jet lag as we call it. right? Jet lag as we call it. >> For those individuals that are, you >> For those individuals that are, you >> For those individuals that are, you know, either under chronic, you know, know, either under chronic, you know, know, either under chronic, you know, circadian misalignment with their their circadian misalignment with their their circadian misalignment with their their work or if they're just experiencing it work or if they're just experiencing it work or if they're just experiencing it because they're traveling in a different because they're traveling in a different because they're traveling in a different time zone. time zone. time zone. >> Um, what do you think would be some good >> Um, what do you think would be some good >> Um, what do you think would be some good strategies to help them mitigate the strategies to help them mitigate the strategies to help them mitigate the effects on NAD system? I mean, would effects on NAD system? I mean, would effects on NAD system? I mean, would supplementation come in there or would supplementation come in there or would supplementation come in there or would it be, you know, bright light exposure? it be, you know, bright light exposure? it be, you know, bright light exposure? The things that we've heard of from, you The things that we've heard of from, you The things that we've heard of from, you know, the chronobiologists, right? know, the chronobiologists, right? know, the chronobiologists, right? >> Like melatonin, getting bright light >> Like melatonin, getting bright light >> Like melatonin, getting bright light exposure, trying to timerestricted exposure, trying to timerestricted exposure, trying to timerestricted eating if you're a shift worker, trying eating if you're a shift worker, trying eating if you're a shift worker, trying to not eat all throughout the day, like to not eat all throughout the day, like to not eat all throughout the day, like things like that. things like that. things like that. >> Yeah. So, I mean, this is something >> Yeah. So, I mean, this is something >> Yeah. So, I mean, this is something that, you know, clinical and human that, you know, clinical and human that, you know, clinical and human experience is very valuable, right? So experience is very valuable, right? So experience is very valuable, right? So people that do it a lot that have people that do it a lot that have people that do it a lot that have figured out a way to do it will tell you figured out a way to do it will tell you figured out a way to do it will tell you that they set their w if they're going that they set their w if they're going that they set their w if they're going to be taking an international trip, to be taking an international trip, to be taking an international trip, which I'm taking on Monday. Um set your which I'm taking on Monday. Um set your which I'm taking on Monday. Um set your um calendar to where you're going to be. um calendar to where you're going to be. um calendar to where you're going to be. Think about trying to sleep when they're Think about trying to sleep when they're Think about trying to sleep when they're sleeping. sleeping. sleeping. um get bright sunlight at you know 6 or um get bright sunlight at you know 6 or um get bright sunlight at you know 6 or 7 a.m. their time. Um if you I think 7 a.m. their time. Um if you I think 7 a.m. their time. Um if you I think this this is a potential use case for this this is a potential use case for this this is a potential use case for for niogen. So um you know bright for niogen. So um you know bright for niogen. So um you know bright sunlight um and you know potentially sunlight um and you know potentially sunlight um and you know potentially nicotenoid ribocide at that morning nicotenoid ribocide at that morning nicotenoid ribocide at that morning time. Um, so and in particularly if time. Um, so and in particularly if time. Um, so and in particularly if you've been taking Niagen in in the you've been taking Niagen in in the you've been taking Niagen in in the morning, um, you might have a weird day morning, um, you might have a weird day morning, um, you might have a weird day that is only 14 hours or 40 hours that is only 14 hours or 40 hours that is only 14 hours or 40 hours depending on which direction you're depending on which direction you're depending on which direction you're going. And so you're going to have a going. And so you're going to have a going. And so you're going to have a weird day that you have to get through weird day that you have to get through weird day that you have to get through and then you you try to re reset with and then you you try to re reset with and then you you try to re reset with sunlight and activity. you just brought sunlight and activity. you just brought sunlight and activity. you just brought up a really interesting question in my up a really interesting question in my up a really interesting question in my brain and that is and the next thing brain and that is and the next thing brain and that is and the next thing we're getting into is the NAD we're getting into is the NAD we're getting into is the NAD supplementation and all of that. But supplementation and all of that. But supplementation and all of that. But before we get there, um you said you before we get there, um you said you before we get there, um you said you were talking about taking nicotenomide were talking about taking nicotenomide were talking about taking nicotenomide ribbide perhaps in the morning. Does the ribbide perhaps in the morning. Does the ribbide perhaps in the morning. Does the timing of when you take it actually timing of when you take it actually timing of when you take it actually matter? So let's say you you're you know matter? So let's say you you're you know matter? So let's say you you're you know you're Okay, I have two questions. you're Okay, I have two questions. you're Okay, I have two questions. That's one. the timing does the timing That's one. the timing does the timing That's one. the timing does the timing matter because you did mention that that matter because you did mention that that matter because you did mention that that you get this boost in your in your you get this boost in your in your you get this boost in your in your circulation I don't know how many hours circulation I don't know how many hours circulation I don't know how many hours after taking the supplement but also after taking the supplement but also after taking the supplement but also let's say like let's say you are you let's say like let's say you are you let's say like let's say you are you know a shift worker or you are changing know a shift worker or you are changing know a shift worker or you are changing time zones and your NAD system is time zones and your NAD system is time zones and your NAD system is disrupted lots of things are disrupted disrupted lots of things are disrupted disrupted lots of things are disrupted but that's one of many things but that's one of many things but that's one of many things >> you know is that is that really going to >> you know is that is that really going to >> you know is that is that really going to is that going to affect your energy is that going to affect your energy is that going to affect your energy levels like the NAD being down one would levels like the NAD being down one would levels like the NAD being down one would presume it would you would feel lower presume it would you would feel lower presume it would you would feel lower energy like cognitively and is that energy like cognitively and is that energy like cognitively and is that something that you think could be something that you think could be something that you think could be replenished through supplementation? I replenished through supplementation? I replenished through supplementation? I know I'm asking you to speculate, which know I'm asking you to speculate, which know I'm asking you to speculate, which is hard for you. is hard for you. is hard for you. >> I know. Um >> I know. Um >> I know. Um >> like I I try to be evidence-based here. >> like I I try to be evidence-based here. >> like I I try to be evidence-based here. Um what I can tell you is that um NR is Um what I can tell you is that um NR is Um what I can tell you is that um NR is doesn't feel like a stimulant. No. doesn't feel like a stimulant. No. doesn't feel like a stimulant. No. >> Right. Yeah. >> Right. Yeah. >> Right. Yeah. >> Um most people take it in the morning. >> Um most people take it in the morning. >> Um most people take it in the morning. Um there's not a to me it's logical to Um there's not a to me it's logical to Um there's not a to me it's logical to take it in the morning because um the take it in the morning because um the take it in the morning because um the way your body gets micronutrients and way your body gets micronutrients and way your body gets micronutrients and macronutrients is the same, right? Is macronutrients is the same, right? Is macronutrients is the same, right? Is that we if if if you were eating, you that we if if if you were eating, you that we if if if you were eating, you know, a plate of of of liver, you'd be know, a plate of of of liver, you'd be know, a plate of of of liver, you'd be getting protein, fat, um a little bit of getting protein, fat, um a little bit of getting protein, fat, um a little bit of carbohydrate, and micronutrient in the carbohydrate, and micronutrient in the carbohydrate, and micronutrient in the same meal, right? the micronutrients are same meal, right? the micronutrients are same meal, right? the micronutrients are going into your cells to rebuild going into your cells to rebuild going into your cells to rebuild co-enzymes and the macronutrients are co-enzymes and the macronutrients are co-enzymes and the macronutrients are going into your your liver and intestine going into your your liver and intestine going into your your liver and intestine and breaking down and depending upon and breaking down and depending upon and breaking down and depending upon co-enzymes for their conversion to ATP. co-enzymes for their conversion to ATP. co-enzymes for their conversion to ATP. So to me waking up in the morning and So to me waking up in the morning and So to me waking up in the morning and I'm on team breakfast. I'm not a I'm on team breakfast. I'm not a I'm on team breakfast. I'm not a timerestricted guy. Um you know I take timerestricted guy. Um you know I take timerestricted guy. Um you know I take niggen in the morning. I have coffee and niggen in the morning. I have coffee and niggen in the morning. I have coffee and I and I and I work. Um I and I and I work. Um I and I and I work. Um so it could well be valuable for shift so it could well be valuable for shift so it could well be valuable for shift workers. workers. workers. Um, presumably if somebody has night Um, presumably if somebody has night Um, presumably if somebody has night shifts and let's say they start work at shifts and let's say they start work at shifts and let's say they start work at 11:00 p.m. and they wake up at 9:30 p.m. 11:00 p.m. and they wake up at 9:30 p.m. 11:00 p.m. and they wake up at 9:30 p.m. then they're presumably having breakfast then they're presumably having breakfast then they're presumably having breakfast at 1000 a.m. And I would at 1000 a.m. And I would at 1000 a.m. And I would >> 10 p.m. >> 10 p.m. >> 10 p.m. >> think or sorry 1000 p.m. So I think that >> think or sorry 1000 p.m. So I think that >> think or sorry 1000 p.m. So I think that that person would probably have coffee that person would probably have coffee that person would probably have coffee and naggen at that beginning of their and naggen at that beginning of their and naggen at that beginning of their work cycle. To me that's work cycle. To me that's work cycle. To me that's >> the most >> the most >> the most >> logical way of doing it. >> logical way of doing it. >> logical way of doing it. >> Okay. Um let's get into this. I mean >> Okay. Um let's get into this. I mean >> Okay. Um let's get into this. I mean hopefully by now everyone's convinced. hopefully by now everyone's convinced. hopefully by now everyone's convinced. They know what NAD is. They're convinced They know what NAD is. They're convinced They know what NAD is. They're convinced it's important at the very least for it's important at the very least for it's important at the very least for energy, right? If not more repair, energy, right? If not more repair, energy, right? If not more repair, regulating genes. Um I a lot of things, regulating genes. Um I a lot of things, regulating genes. Um I a lot of things, right? But I think energy stands out to right? But I think energy stands out to right? But I think energy stands out to a lot of people. a lot of people. a lot of people. >> Uh can you please tell people and >> Uh can you please tell people and >> Uh can you please tell people and explain to them the question I know explain to them the question I know explain to them the question I know that's in their minds which is why can't that's in their minds which is why can't that's in their minds which is why can't I just supplement with NAD? Why do I I just supplement with NAD? Why do I I just supplement with NAD? Why do I have to take this precursor like have to take this precursor like have to take this precursor like nicotenomide ribocide? So maybe you nicotenomide ribocide? So maybe you nicotenomide ribocide? So maybe you could talk about could talk about could talk about >> why that is and also maybe just touch on >> why that is and also maybe just touch on >> why that is and also maybe just touch on nicotenomide ribocide versus nicotenomide ribocide versus nicotenomide ribocide versus nicotenomide monucleotide. That's nicotenomide monucleotide. That's nicotenomide monucleotide. That's another precursor. another precursor. another precursor. >> Yeah. Yeah. So basically the the issue >> Yeah. Yeah. So basically the the issue >> Yeah. Yeah. So basically the the issue is phosphates. So um you know compounds is phosphates. So um you know compounds is phosphates. So um you know compounds with phosphates don't get into cells. Um with phosphates don't get into cells. Um with phosphates don't get into cells. Um so the biggest piece of NAD that can get so the biggest piece of NAD that can get so the biggest piece of NAD that can get into a cell is nicotenocide. into a cell is nicotenocide. into a cell is nicotenocide. Um it gets into cells nicoten ribocide Um it gets into cells nicoten ribocide Um it gets into cells nicoten ribocide kinase then phosphorolates it puts a kinase then phosphorolates it puts a kinase then phosphorolates it puts a phosphate group on it. Then there's phosphate group on it. Then there's phosphate group on it. Then there's another enzyme that comes along that another enzyme that comes along that another enzyme that comes along that adds what's called an AM group to it. adds what's called an AM group to it. adds what's called an AM group to it. And then it's a ducleotide that has two And then it's a ducleotide that has two And then it's a ducleotide that has two phosphates on it. Um, phosphates on it. Um, phosphates on it. Um, nicotinic acid does not have phosphates. nicotinic acid does not have phosphates. nicotinic acid does not have phosphates. Nicotenomide does not have phosphates. Nicotenomide does not have phosphates. Nicotenomide does not have phosphates. Both of them are considered NAD Both of them are considered NAD Both of them are considered NAD precursor vitamins. Um, problem with precursor vitamins. Um, problem with precursor vitamins. Um, problem with nicotinic acid is high doses of it cause nicotinic acid is high doses of it cause nicotinic acid is high doses of it cause flushing. So, if you're trying to take flushing. So, if you're trying to take flushing. So, if you're trying to take enough nicotinic acid to boost NAD, enough nicotinic acid to boost NAD, enough nicotinic acid to boost NAD, you're probably going to feel kind of an you're probably going to feel kind of an you're probably going to feel kind of an uncomfortable hot flash type experience. uncomfortable hot flash type experience. uncomfortable hot flash type experience. Um, that said, um, there's some Um, that said, um, there's some Um, that said, um, there's some cardiologists that recommend it for cardiologists that recommend it for cardiologists that recommend it for lipid regulation and so it has a long, lipid regulation and so it has a long, lipid regulation and so it has a long, you know, human experience. Nicotinomide you know, human experience. Nicotinomide you know, human experience. Nicotinomide has been in the food supply for a long has been in the food supply for a long has been in the food supply for a long time, usually pretty low dose. It's in time, usually pretty low dose. It's in time, usually pretty low dose. It's in pro probably every multivitamin. pro probably every multivitamin. pro probably every multivitamin. Um, we know it's really safe. We know Um, we know it's really safe. We know Um, we know it's really safe. We know that it's cancer preventative, which is that it's cancer preventative, which is that it's cancer preventative, which is a very good thing about this class of a very good thing about this class of a very good thing about this class of molecules is that they were tested in molecules is that they were tested in molecules is that they were tested in Australia, you know, where there's a Australia, you know, where there's a Australia, you know, where there's a very high incidence of skin cancer, very high incidence of skin cancer, very high incidence of skin cancer, right? so high that you can do a right? so high that you can do a right? so high that you can do a prospective prospective prospective um preventative clinical trial to see um preventative clinical trial to see um preventative clinical trial to see whether nicotinomide supplementation whether nicotinomide supplementation whether nicotinomide supplementation lowers the risk of skin cancer and it lowers the risk of skin cancer and it lowers the risk of skin cancer and it does. Right. So nicotenomide is really does. Right. So nicotenomide is really does. Right. So nicotenomide is really safe. safe. safe. >> Do you think that has to do with DNA >> Do you think that has to do with DNA >> Do you think that has to do with DNA damage repair? damage repair? damage repair? >> Yeah. Yeah. Yeah. And um so so >> Yeah. Yeah. Yeah. And um so so >> Yeah. Yeah. Yeah. And um so so nicotenoid ribocide is probably the kind nicotenoid ribocide is probably the kind nicotenoid ribocide is probably the kind of premium um NAD precursor in the sense of premium um NAD precursor in the sense of premium um NAD precursor in the sense that the NR kinace pathway gets that the NR kinace pathway gets that the NR kinace pathway gets upregulated in a lot of conditions of upregulated in a lot of conditions of upregulated in a lot of conditions of metabolic stress. So in the failing metabolic stress. So in the failing metabolic stress. So in the failing heart in a um damaged neuron heart in a um damaged neuron heart in a um damaged neuron nicotenomide ribocide kynise one and two nicotenomide ribocide kynise one and two nicotenomide ribocide kynise one and two genes get upregulated and so that's why genes get upregulated and so that's why genes get upregulated and so that's why NR you know works in a lot of mouse NR you know works in a lot of mouse NR you know works in a lot of mouse models in which nicotenomide doesn't models in which nicotenomide doesn't models in which nicotenomide doesn't work like in the heart failure work like in the heart failure work like in the heart failure experiments nicotenomide can't actually experiments nicotenomide can't actually experiments nicotenomide can't actually boost the NAD in the failing heart boost the NAD in the failing heart boost the NAD in the failing heart because in the failing heart it's because in the failing heart it's because in the failing heart it's overexpressing a gene called NMRK2 overexpressing a gene called NMRK2 overexpressing a gene called NMRK2 nicotenomide ribosite kynes 2. So the nicotenomide ribosite kynes 2. So the nicotenomide ribosite kynes 2. So the failing heart is sort of looking for the failing heart is sort of looking for the failing heart is sort of looking for the whole nucleus whole nucleus whole nucleus >> in order to boost its NAD system. >> in order to boost its NAD system. >> in order to boost its NAD system. >> Um so it's not that it's necessarily >> Um so it's not that it's necessarily >> Um so it's not that it's necessarily easier for nicotine easier for nicotine easier for nicotine to get there. to get there. to get there. >> Oh well you asked about NAD and NMN, >> Oh well you asked about NAD and NMN, >> Oh well you asked about NAD and NMN, right? right? right? >> Well yeah NAD so NAD is not even getting >> Well yeah NAD so NAD is not even getting >> Well yeah NAD so NAD is not even getting in inside of cells essentially. You're in inside of cells essentially. You're in inside of cells essentially. You're taking it orally. There's a there's a taking it orally. There's a there's a taking it orally. There's a there's a funny thing where people started um funny thing where people started um funny thing where people started um injecting, right? injecting, right? injecting, right? >> Yeah. Let's get to that. NAD NAD IV >> Yeah. Let's get to that. NAD NAD IV >> Yeah. Let's get to that. NAD NAD IV drips. drips. drips. >> Yeah. So, so and then um have you ever >> Yeah. So, so and then um have you ever >> Yeah. So, so and then um have you ever talked to anybody that has done it? Yes. talked to anybody that has done it? Yes. talked to anybody that has done it? Yes. >> Did they tell you how painful it is? >> Did they tell you how painful it is? >> Did they tell you how painful it is? >> No. They talked about how great they >> No. They talked about how great they >> No. They talked about how great they felt and how they had energy. felt and how they had energy. felt and how they had energy. >> Yeah. But it's a it's delivered over a >> Yeah. But it's a it's delivered over a >> Yeah. But it's a it's delivered over a several hour period in which the people several hour period in which the people several hour period in which the people experience an innate immune response experience an innate immune response experience an innate immune response because the NAD can't get into cells. because the NAD can't get into cells. because the NAD can't get into cells. Neither can NMN get into cells. So these Neither can NMN get into cells. So these Neither can NMN get into cells. So these compounds break down into NR or compounds break down into NR or compounds break down into NR or something smaller, right? So NAD is something smaller, right? So NAD is something smaller, right? So NAD is breaking down into breaking down into breaking down into probably breaks down into Nammen first probably breaks down into Nammen first probably breaks down into Nammen first and then to NR and then to NR and then to NR and then NR can get into cells and then NR can get into cells and then NR can get into cells nicotenomide can get into cells nicotenomide can get into cells nicotenomide can get into cells nicotinic acid. nicotinic acid. nicotinic acid. >> So this is the mechanism for the NI NAD >> So this is the mechanism for the NI NAD >> So this is the mechanism for the NI NAD drips that we're talking about. Right. drips that we're talking about. Right. drips that we're talking about. Right. >> Yeah. Yeah. Right. There's actually now >> Yeah. Yeah. Right. There's actually now >> Yeah. Yeah. Right. There's actually now a niogen plus which is like a uh drip a niogen plus which is like a uh drip a niogen plus which is like a uh drip grade nicotenoid ribocide which is not grade nicotenoid ribocide which is not grade nicotenoid ribocide which is not painful but painful but painful but >> that you can do in a drip that you >> that you can do in a drip that you >> that you can do in a drip that you >> can do that in a drip. Um again the >> can do that in a drip. Um again the >> can do that in a drip. Um again the clinical data behind oral niogen is much clinical data behind oral niogen is much clinical data behind oral niogen is much more extensive than IV. That said, that more extensive than IV. That said, that more extensive than IV. That said, that said, there are some, you know, mouse said, there are some, you know, mouse said, there are some, you know, mouse experiments where intravenous NR goes experiments where intravenous NR goes experiments where intravenous NR goes further into different tissues than oral further into different tissues than oral further into different tissues than oral NR. NR. NR. >> Why is that? >> Why is that? >> Why is that? >> So the whole biodistribution, >> So the whole biodistribution, >> So the whole biodistribution, you know, thing is that's you know, thing is that's you know, thing is that's pharmaccoinetics. pharmaccoinetics. pharmaccoinetics. >> You can get higher levels. potentially >> You can get higher levels. potentially >> You can get higher levels. potentially can deliver more NR to the heart or to can deliver more NR to the heart or to can deliver more NR to the heart or to other tissues through IV. So I think other tissues through IV. So I think other tissues through IV. So I think that in the future we're going to have that in the future we're going to have that in the future we're going to have more, you know, disease relevant data more, you know, disease relevant data more, you know, disease relevant data from IV delivery. So I'm happy that from IV delivery. So I'm happy that from IV delivery. So I'm happy that there is, you know, clinical grade there is, you know, clinical grade there is, you know, clinical grade introvenous NR, but there's much more introvenous NR, but there's much more introvenous NR, but there's much more data today in January of 2026 on oral data today in January of 2026 on oral data today in January of 2026 on oral NR. We know it's safe. We know it boosts NR. We know it's safe. We know it boosts NR. We know it's safe. We know it boosts NAD. IV is something that is kind of a, NAD. IV is something that is kind of a, NAD. IV is something that is kind of a, you know, developing product and um but you know, developing product and um but you know, developing product and um but it's now available to the clinical it's now available to the clinical it's now available to the clinical research community as well. research community as well. research community as well. >> Okay. Well, just for people that are >> Okay. Well, just for people that are >> Okay. Well, just for people that are listening here to summarize because I listening here to summarize because I listening here to summarize because I know that you can actually go online and know that you can actually go online and know that you can actually go online and buy an NAD oral supplement. Um, that is buy an NAD oral supplement. Um, that is buy an NAD oral supplement. Um, that is not going to work right. not going to work right. not going to work right. >> Well, it's going to break down. I mean, >> Well, it's going to break down. I mean, >> Well, it's going to break down. I mean, half of the molecular weight or 40 or half of the molecular weight or 40 or half of the molecular weight or 40 or some percent of the molecular weight of some percent of the molecular weight of some percent of the molecular weight of NAD is NR. So it's going to break down NAD is NR. So it's going to break down NAD is NR. So it's going to break down into into into um you know so it'll be digested and um you know so it'll be digested and um you know so it'll be digested and deliver presumably deliver some small deliver presumably deliver some small deliver presumably deliver some small fraction of the total molecular weight fraction of the total molecular weight fraction of the total molecular weight as an NAD booster. as an NAD booster. as an NAD booster. >> Okay. So it's not >> Okay. So it's not >> Okay. So it's not >> NAD itself >> NAD itself >> NAD itself you know I technically you know I technically you know I technically uh NMN is you can argue whether it's a uh NMN is you can argue whether it's a uh NMN is you can argue whether it's a precursor. It's sort of a precursor of precursor. It's sort of a precursor of precursor. It's sort of a precursor of NR, which is a precursor to cellular NR, which is a precursor to cellular NR, which is a precursor to cellular NAD. But again, NMN breaks down to NR NAD. But again, NMN breaks down to NR NAD. But again, NMN breaks down to NR and then that gets into cells and and then that gets into cells and and then that gets into cells and becomes NMN and NAD. Again, becomes NMN and NAD. Again, becomes NMN and NAD. Again, >> I thought NR got broken down to NN. >> I thought NR got broken down to NN. >> I thought NR got broken down to NN. >> Well, no, NR gets um phosphorolated gets >> Well, no, NR gets um phosphorolated gets >> Well, no, NR gets um phosphorolated gets converted up to NMN. Okay. NMN has a converted up to NMN. Okay. NMN has a converted up to NMN. Okay. NMN has a phosphate on it, but that so it's a it's phosphate on it, but that so it's a it's phosphate on it, but that so it's a it's a funny thing like why as a chemist a funny thing like why as a chemist a funny thing like why as a chemist would you put a phosphate on to NR to would you put a phosphate on to NR to would you put a phosphate on to NR to produce NMN when NMN has to be degraded produce NMN when NMN has to be degraded produce NMN when NMN has to be degraded down to NR in order to get into cells down to NR in order to get into cells down to NR in order to get into cells but it's popular right it was but it's popular right it was but it's popular right it was popularized by a number of researchers popularized by a number of researchers popularized by a number of researchers and and and um the question with NMN is whether you um the question with NMN is whether you um the question with NMN is whether you can get um pure safety tested material can get um pure safety tested material can get um pure safety tested material There are some reports that 17 out of 20 There are some reports that 17 out of 20 There are some reports that 17 out of 20 products labeled as NMN don't have NMN products labeled as NMN don't have NMN products labeled as NMN don't have NMN in it or don't meet meet the label in it or don't meet meet the label in it or don't meet meet the label claims. claims. claims. >> Some people So some people that are >> Some people So some people that are >> Some people So some people that are listening are familiar with both NR and listening are familiar with both NR and listening are familiar with both NR and NMN. Some people this is the first time NMN. Some people this is the first time NMN. Some people this is the first time they're like hearing about all this but they're like hearing about all this but they're like hearing about all this but they do know about NAD. they do know about NAD. they do know about NAD. >> Um you know when the I I know I know a >> Um you know when the I I know I know a >> Um you know when the I I know I know a lot of people the way they think about lot of people the way they think about lot of people the way they think about it is they think well NMN is one step it is they think well NMN is one step it is they think well NMN is one step closer to producing NAD. That's closer to producing NAD. That's closer to producing NAD. That's >> in the cell. >> in the cell. >> in the cell. >> Yes, in the cell. That's a general like >> Yes, in the cell. That's a general like >> Yes, in the cell. That's a general like idea that's that's kind of in a lot of idea that's that's kind of in a lot of idea that's that's kind of in a lot of people's minds. So, why wouldn't I just people's minds. So, why wouldn't I just people's minds. So, why wouldn't I just supplement with the closer supplement with the closer supplement with the closer part of this process? part of this process? part of this process? >> Yeah, it doesn't work that way though. >> Yeah, it doesn't work that way though. >> Yeah, it doesn't work that way though. Yeah. Yeah. Yeah. >> Why doesn't it work that way? >> Why doesn't it work that way? >> Why doesn't it work that way? >> Well, it doesn't work because the NMN >> Well, it doesn't work because the NMN >> Well, it doesn't work because the NMN has a phosphate group that precludes its has a phosphate group that precludes its has a phosphate group that precludes its transport into the cell. So in the 1980s transport into the cell. So in the 1980s transport into the cell. So in the 1980s there were people that were developing there were people that were developing there were people that were developing nucleotides nucleotides nucleotides and bases as anti-cancer and antiviral and bases as anti-cancer and antiviral and bases as anti-cancer and antiviral drugs. In fact three of them got a Nobel drugs. In fact three of them got a Nobel drugs. In fact three of them got a Nobel Prize. Gertrude Dion and Hitchens and Prize. Gertrude Dion and Hitchens and Prize. Gertrude Dion and Hitchens and someone else got a Nobel Prize. They someone else got a Nobel Prize. They someone else got a Nobel Prize. They worked at um research park in North worked at um research park in North worked at um research park in North Carolina. And um what they the idea is Carolina. And um what they the idea is Carolina. And um what they the idea is that if you make something that that if you make something that that if you make something that resembles a nucleotide resembles a nucleotide resembles a nucleotide that it can go into cells and be that it can go into cells and be that it can go into cells and be converted into a toxic nucleotide and it converted into a toxic nucleotide and it converted into a toxic nucleotide and it can do things like block viral can do things like block viral can do things like block viral replication. Like you've heard of ACT, replication. Like you've heard of ACT, replication. Like you've heard of ACT, >> right? HIV drug. So act is a nucleioide >> right? HIV drug. So act is a nucleioide >> right? HIV drug. So act is a nucleioide right. right. right. So it's the you make nucleioide it gets So it's the you make nucleioide it gets So it's the you make nucleioide it gets taken up into cells and then inside the taken up into cells and then inside the taken up into cells and then inside the cell act gets converted into a cell act gets converted into a cell act gets converted into a triphosphate triphosphate triphosphate act triphosphate and then that is an act triphosphate and then that is an act triphosphate and then that is an inhibitor reverse transcriptase. Right? inhibitor reverse transcriptase. Right? inhibitor reverse transcriptase. Right? So nicotenomide ribocide is not toxic. So nicotenomide ribocide is not toxic. So nicotenomide ribocide is not toxic. Um it's an NAD booster. So it's a direct Um it's an NAD booster. So it's a direct Um it's an NAD booster. So it's a direct precursor of NAD. The NR can get into precursor of NAD. The NR can get into precursor of NAD. The NR can get into cells. cells. cells. >> It can get decorated with the phosphates >> It can get decorated with the phosphates >> It can get decorated with the phosphates and converted into its final nucleotide and converted into its final nucleotide and converted into its final nucleotide form. NMN can't because NMN already has form. NMN can't because NMN already has form. NMN can't because NMN already has a phosphate. That phosphate has to be a phosphate. That phosphate has to be a phosphate. That phosphate has to be put on inside of cells. So if someone put on inside of cells. So if someone put on inside of cells. So if someone takes if someone is able to find a safe takes if someone is able to find a safe takes if someone is able to find a safe pure form of NMN pure form of NMN pure form of NMN um which you're if you're at a drug um which you're if you're at a drug um which you're if you're at a drug company that is making and testing NMN company that is making and testing NMN company that is making and testing NMN you could have access to that. Most of you could have access to that. Most of you could have access to that. Most of us wouldn't have access to that but if us wouldn't have access to that but if us wouldn't have access to that but if you could find a safe um form of NMN and you could find a safe um form of NMN and you could find a safe um form of NMN and take it orally that NMN is being take it orally that NMN is being take it orally that NMN is being converted back to NR before it gets into converted back to NR before it gets into converted back to NR before it gets into cells. cells. cells. >> Right? That was the long-winded way of >> Right? That was the long-winded way of >> Right? That was the long-winded way of answering the question, which is answering the question, which is answering the question, which is essentially that you actually it's being essentially that you actually it's being essentially that you actually it's being converted back into NR. Yeah. converted back into NR. Yeah. converted back into NR. Yeah. >> So then why not just take the NR? >> So then why not just take the NR? >> So then why not just take the NR? >> Well, um NR is the most, you know, >> Well, um NR is the most, you know, >> Well, um NR is the most, you know, safety tested NAD booster on on the safety tested NAD booster on on the safety tested NAD booster on on the market. So, market. So, market. So, >> well, this is good. At least people have >> well, this is good. At least people have >> well, this is good. At least people have an idea now. So, an idea now. So, an idea now. So, I think um I want to get to some of I think um I want to get to some of I think um I want to get to some of these health outcomes, but before we do these health outcomes, but before we do these health outcomes, but before we do that, you mentioned something that, you mentioned something that, you mentioned something interesting when you were talking about interesting when you were talking about interesting when you were talking about some of these animal studies that kind some of these animal studies that kind some of these animal studies that kind of piqued my curiosity here, which was of piqued my curiosity here, which was of piqued my curiosity here, which was you said gut microbiome you said gut microbiome you said gut microbiome >> and you were talking about different >> and you were talking about different >> and you were talking about different strains of animals and how the gut strains of animals and how the gut strains of animals and how the gut microbiome seem to possibly play a role microbiome seem to possibly play a role microbiome seem to possibly play a role in NAD levels in different tissues in NAD levels in different tissues in NAD levels in different tissues perhaps. perhaps. perhaps. >> Yeah. Um, how is that do they is the gut >> Yeah. Um, how is that do they is the gut >> Yeah. Um, how is that do they is the gut bacteria in our guts playing a role in bacteria in our guts playing a role in bacteria in our guts playing a role in the conversion of NR and amen into the conversion of NR and amen into the conversion of NR and amen into >> brand new paper out of um Nestle in >> brand new paper out of um Nestle in >> brand new paper out of um Nestle in Switzerland says that um the gut Switzerland says that um the gut Switzerland says that um the gut microbiome plays a role in human microbiome plays a role in human microbiome plays a role in human conversion of NR and NMN into NAD conversion of NR and NMN into NAD conversion of NR and NMN into NAD in our tissues. I think that they got in our tissues. I think that they got in our tissues. I think that they got part of the story right. I don't think part of the story right. I don't think part of the story right. I don't think that they got all of it right because that they got all of it right because that they got all of it right because it's very difficult to see NR in human it's very difficult to see NR in human it's very difficult to see NR in human blood. Um we know that um it sort of blood. Um we know that um it sort of blood. Um we know that um it sort of behaves like dark matter, you know. So behaves like dark matter, you know. So behaves like dark matter, you know. So dark matter is stuff that um you can see dark matter is stuff that um you can see dark matter is stuff that um you can see like gravitational effects of of matter like gravitational effects of of matter like gravitational effects of of matter in cases where you can't see the matter in cases where you can't see the matter in cases where you can't see the matter itself. So there's um once someone takes itself. So there's um once someone takes itself. So there's um once someone takes or a mouse takes nicotenide riocide or a mouse takes nicotenide riocide or a mouse takes nicotenide riocide orally, you can see effects in the orally, you can see effects in the orally, you can see effects in the cardiac tissue. You're going to see cardiac tissue. You're going to see cardiac tissue. You're going to see effects in the muscle. You can't always effects in the muscle. You can't always effects in the muscle. You can't always see how it got there. see how it got there. see how it got there. Because when you draw blood, Because when you draw blood, Because when you draw blood, you're breaking half of 1% of the blood you're breaking half of 1% of the blood you're breaking half of 1% of the blood cells cells cells and you're releasing, you're and you're releasing, you're and you're releasing, you're extracellularizing, extracellularizing, extracellularizing, to use a technical term, you're to use a technical term, you're to use a technical term, you're releasing enzymes that break down the NR releasing enzymes that break down the NR releasing enzymes that break down the NR artifactually. So there are things that artifactually. So there are things that artifactually. So there are things that are difficult to observe in clinical are difficult to observe in clinical are difficult to observe in clinical testing. testing. testing. So it's hard to see the effect of NR So it's hard to see the effect of NR So it's hard to see the effect of NR getting into various tissues, but this getting into various tissues, but this getting into various tissues, but this group um at Nestle showed that the um group um at Nestle showed that the um group um at Nestle showed that the um microbiome is altered in a very useful microbiome is altered in a very useful microbiome is altered in a very useful positive way by supplementing with NR. positive way by supplementing with NR. positive way by supplementing with NR. And they suggested that there's some And they suggested that there's some And they suggested that there's some conversion of NR into things like conversion of NR into things like conversion of NR into things like nicotinic acid that could be beneficial nicotinic acid that could be beneficial nicotinic acid that could be beneficial as well as well as well >> for the gut bacteria. Interesting. So So >> for the gut bacteria. Interesting. So So >> for the gut bacteria. Interesting. So So this was a human study. this was a human study. this was a human study. >> Yeah, that was a human study. >> Yeah, that was a human study. >> Yeah, that was a human study. >> Okay. I'll have to look at that. So >> Okay. I'll have to look at that. So >> Okay. I'll have to look at that. So talking now getting into some of these talking now getting into some of these talking now getting into some of these you know conditions and and you know conditions and and you know conditions and and supplementation right now we're talking supplementation right now we're talking supplementation right now we're talking NAD you know precursors mostly and NAD you know precursors mostly and NAD you know precursors mostly and nicotenomide ribocide NR is is a major nicotenomide ribocide NR is is a major nicotenomide ribocide NR is is a major one that's used in animal studies as you one that's used in animal studies as you one that's used in animal studies as you mentioned in clinical studies as well. I mentioned in clinical studies as well. I mentioned in clinical studies as well. I think the you've made a pretty strong think the you've made a pretty strong think the you've made a pretty strong statement with respect to the tried statement with respect to the tried statement with respect to the tried andrue andrue andrue function of at least something that we function of at least something that we function of at least something that we can mostly expect if someone's going to can mostly expect if someone's going to can mostly expect if someone's going to supplement with the right dose being 500 supplement with the right dose being 500 supplement with the right dose being 500 milligrams to 1,000 milligs of nicotine milligrams to 1,000 milligs of nicotine milligrams to 1,000 milligs of nicotine riide riide riide >> lowering inflammation particularly if >> lowering inflammation particularly if >> lowering inflammation particularly if you have a higher inflammatory status you have a higher inflammatory status you have a higher inflammatory status presumably to like start with. Um do you presumably to like start with. Um do you presumably to like start with. Um do you think there's any other first of all is think there's any other first of all is think there's any other first of all is there any data and if there's not any there any data and if there's not any there any data and if there's not any data I would love to hear your data I would love to hear your data I would love to hear your hypothesis and speculation on this which hypothesis and speculation on this which hypothesis and speculation on this which is um is um is um >> I know the immune system is a major >> I know the immune system is a major >> I know the immune system is a major consumer of energy right I mean it's a consumer of energy right I mean it's a consumer of energy right I mean it's a major consu if you're act if you're if major consu if you're act if you're if major consu if you're act if you're if you're if you're if you're sick like you're if you're if you're sick like you're if you're if you're sick like that is a huge you know obviously sink that is a huge you know obviously sink that is a huge you know obviously sink for for NAD for for NAD for for NAD >> do you think that supplementing with NR >> do you think that supplementing with NR >> do you think that supplementing with NR are could help um with any other immune are could help um with any other immune are could help um with any other immune related benefits like fighting off related benefits like fighting off related benefits like fighting off infections, autoimmune disease like infections, autoimmune disease like infections, autoimmune disease like having someone that's chronically having having someone that's chronically having having someone that's chronically having an activated immune system. You an activated immune system. You an activated immune system. You mentioned long co I don't know how much mentioned long co I don't know how much mentioned long co I don't know how much of an autoimmune component there is to of an autoimmune component there is to of an autoimmune component there is to that perhaps some but I'd love to know that perhaps some but I'd love to know that perhaps some but I'd love to know your thoughts on um yeah on that. So your thoughts on um yeah on that. So your thoughts on um yeah on that. So there are some human data showing that there are some human data showing that there are some human data showing that um NR could be active in conditions in um NR could be active in conditions in um NR could be active in conditions in which the inflammosome which the inflammosome which the inflammosome is activated. Um there for sure there's is activated. Um there for sure there's is activated. Um there for sure there's randomized control trials in in that randomized control trials in in that randomized control trials in in that space. Um my idea after seeing the space. Um my idea after seeing the space. Um my idea after seeing the innate immune response to corona virus innate immune response to corona virus innate immune response to corona virus infection of these parts getting infection of these parts getting infection of these parts getting transcribed is that it was going to transcribed is that it was going to transcribed is that it was going to inhibit infection. So, I wanted to see a inhibit infection. So, I wanted to see a inhibit infection. So, I wanted to see a clinical trial with people that were clinical trial with people that were clinical trial with people that were still going into work during still going into work during still going into work during um COVID, you know, work restrictions um COVID, you know, work restrictions um COVID, you know, work restrictions like um nurses and people that are like um nurses and people that are like um nurses and people that are roommates with delivery drivers and and roommates with delivery drivers and and roommates with delivery drivers and and nurses to see whether in a placebo nurses to see whether in a placebo nurses to see whether in a placebo control trial NR was lowering infection. control trial NR was lowering infection. control trial NR was lowering infection. >> Right? Those trials to my knowledge were >> Right? Those trials to my knowledge were >> Right? Those trials to my knowledge were not done when they could have been done. not done when they could have been done. not done when they could have been done. Um there were trials including Um there were trials including Um there were trials including successful phase 2 three trials that successful phase 2 three trials that successful phase 2 three trials that showed NR in a cocktail of three other showed NR in a cocktail of three other showed NR in a cocktail of three other over-the-counter over-the-counter over-the-counter supplements lowered um time to um supplements lowered um time to um supplements lowered um time to um recovery from from CO. So it it does recovery from from CO. So it it does recovery from from CO. So it it does look like it has use cases in infectious look like it has use cases in infectious look like it has use cases in infectious diseases and and inflammation, diseases and and inflammation, diseases and and inflammation, >> which makes I mean it makes sense. I can >> which makes I mean it makes sense. I can >> which makes I mean it makes sense. I can logically logically logically >> understand why that would be. If you're >> understand why that would be. If you're >> understand why that would be. If you're giving your cells the precursors they giving your cells the precursors they giving your cells the precursors they need to have energy to fight off need to have energy to fight off need to have energy to fight off >> Yeah. >> Yeah. >> Yeah. >> you know, pathogens, then you would >> you know, pathogens, then you would >> you know, pathogens, then you would imagine they would fight them better. imagine they would fight them better. imagine they would fight them better. Yeah. Yeah. Yeah. >> Or it wouldn't take as you'd lower the >> Or it wouldn't take as you'd lower the >> Or it wouldn't take as you'd lower the the severity and or duration of the the severity and or duration of the the severity and or duration of the illness. illness. illness. >> But the thing I'm I'm even more excited >> But the thing I'm I'm even more excited >> But the thing I'm I'm even more excited about is peripheral artery disease about is peripheral artery disease about is peripheral artery disease because because because >> let's talk about that. 10 or 15 >> let's talk about that. 10 or 15 >> let's talk about that. 10 or 15 Americans probably have peripheral Americans probably have peripheral Americans probably have peripheral artery disease. artery disease. artery disease. >> Can you describe what that is? >> Can you describe what that is? >> Can you describe what that is? >> So, a lot of times they're former >> So, a lot of times they're former >> So, a lot of times they're former smokers. Um, they have very limited smokers. Um, they have very limited smokers. Um, they have very limited ability to do exercise. Um, they get ability to do exercise. Um, they get ability to do exercise. Um, they get tired easily, stuff is painful for them. tired easily, stuff is painful for them. tired easily, stuff is painful for them. Um, in extreme cases, they could um be Um, in extreme cases, they could um be Um, in extreme cases, they could um be told that something has to be amputated. told that something has to be amputated. told that something has to be amputated. Right? So this is a serious, you know, Right? So this is a serious, you know, Right? So this is a serious, you know, condition, age related condition. condition, age related condition. condition, age related condition. >> Wow. So is it like a like a pain >> Wow. So is it like a like a pain >> Wow. So is it like a like a pain sensation like that they feel like it's sensation like that they feel like it's sensation like that they feel like it's peripheral? peripheral? peripheral? >> Fatigued. Um they can't um walk fast. >> Fatigued. Um they can't um walk fast. >> Fatigued. Um they can't um walk fast. You do a clinical trial of these people, You do a clinical trial of these people, You do a clinical trial of these people, a six-month clinical trial, and you a six-month clinical trial, and you a six-month clinical trial, and you know, the end of the of clinical trial know, the end of the of clinical trial know, the end of the of clinical trial at at at six months, they might walk, at at at six months, they might walk, at at at six months, they might walk, you know, 8 m fewer than they did at the you know, 8 m fewer than they did at the you know, 8 m fewer than they did at the beginning of the trial. So, they're beginning of the trial. So, they're beginning of the trial. So, they're really in decline. And in uh Mcdermach, really in decline. And in uh Mcdermach, really in decline. And in uh Mcdermach, McDermott at all, and I believe that McDermott at all, and I believe that McDermott at all, and I believe that she's the top peripheral artery disease she's the top peripheral artery disease she's the top peripheral artery disease clinical trialist in the country. She's clinical trialist in the country. She's clinical trialist in the country. She's at Northwestern did a threearm clinical at Northwestern did a threearm clinical at Northwestern did a threearm clinical trial placebo trial placebo trial placebo versus nicotenomide ribocide versus NR versus nicotenomide ribocide versus NR versus nicotenomide ribocide versus NR plus resveratrol plus resveratrol plus resveratrol and found that the NR arm improved their and found that the NR arm improved their and found that the NR arm improved their six-minute walk test and the placebo arm six-minute walk test and the placebo arm six-minute walk test and the placebo arm as well as the NR plus resveratrol arm as well as the NR plus resveratrol arm as well as the NR plus resveratrol arm degraded their six-minute walk test. So degraded their six-minute walk test. So degraded their six-minute walk test. So the resveratrol not only was not helpful the resveratrol not only was not helpful the resveratrol not only was not helpful but it actually blocked some of the but it actually blocked some of the but it actually blocked some of the benefit of supplementing with. So yeah benefit of supplementing with. So yeah benefit of supplementing with. So yeah that reserverrol thing as you as you that reserverrol thing as you as you that reserverrol thing as you as you know well is just kind of science know well is just kind of science know well is just kind of science fiction fiction fiction >> but um but the NR result was really >> but um but the NR result was really >> but um but the NR result was really quite striking and I believe it was N of quite striking and I believe it was N of quite striking and I believe it was N of 40 or 75 people per arm. it was like not 40 or 75 people per arm. it was like not 40 or 75 people per arm. it was like not a super small trial and on the basis of a super small trial and on the basis of a super small trial and on the basis of the positive results McDermad is doing a the positive results McDermad is doing a the positive results McDermad is doing a much larger trial. So um this might be much larger trial. So um this might be much larger trial. So um this might be one of the first real medical one of the first real medical one of the first real medical indications indications indications for niagen in an age related disease for niagen in an age related disease for niagen in an age related disease population. That said, um if you want to population. That said, um if you want to population. That said, um if you want to consider inflammaging, consider inflammaging, consider inflammaging, >> you know, to be an underlying condition >> you know, to be an underlying condition >> you know, to be an underlying condition in a lot of people's aging, then you in a lot of people's aging, then you in a lot of people's aging, then you could say that eight randomized clinical could say that eight randomized clinical could say that eight randomized clinical trials showing beneficial effects of NR trials showing beneficial effects of NR trials showing beneficial effects of NR in lowering inflammation could be in lowering inflammation could be in lowering inflammation could be broadly useful for for human aging. broadly useful for for human aging. broadly useful for for human aging. >> Yeah, neurogenerative disease comes to >> Yeah, neurogenerative disease comes to >> Yeah, neurogenerative disease comes to my mind as well, right? Right. I mean my mind as well, right? Right. I mean my mind as well, right? Right. I mean this is something we know that this is something we know that this is something we know that neuroinflammation is now known to be neuroinflammation is now known to be neuroinflammation is now known to be play a very early causal role in play a very early causal role in play a very early causal role in Alzheimer's disease. I mean the brain Alzheimer's disease. I mean the brain Alzheimer's disease. I mean the brain you know having chronic inflammation in you know having chronic inflammation in you know having chronic inflammation in the brain is is is not good. No the brain is is is not good. No the brain is is is not good. No >> so it would be interesting >> so it would be interesting >> so it would be interesting to know you know whether or not there to know you know whether or not there to know you know whether or not there first of all if there's any biomarker I first of all if there's any biomarker I first of all if there's any biomarker I mean obviously inflammation would be mean obviously inflammation would be mean obviously inflammation would be something to look at but yeah you know something to look at but yeah you know something to look at but yeah you know cognition improvements in people. It's cognition improvements in people. It's cognition improvements in people. It's always harder when you have someone that always harder when you have someone that always harder when you have someone that has Alzheimer's disease, right? You has Alzheimer's disease, right? You has Alzheimer's disease, right? You know, so the the question is, you know, know, so the the question is, you know, know, so the the question is, you know, it it always becomes, well, they're it it always becomes, well, they're it it always becomes, well, they're already so broken, it's hard to fix already so broken, it's hard to fix already so broken, it's hard to fix them. Like you if you and it goes with them. Like you if you and it goes with them. Like you if you and it goes with anything like omega-3 supplements, anything like omega-3 supplements, anything like omega-3 supplements, anything, right? Like anything, right? Like anything, right? Like >> like it's always easier to help prevent >> like it's always easier to help prevent >> like it's always easier to help prevent like like you don't want all the like like you don't want all the like like you don't want all the inflammation to to get to the point inflammation to to get to the point inflammation to to get to the point where you're like already in the disease where you're like already in the disease where you're like already in the disease state, right? state, right? state, right? >> So mild cognitive impairment might be >> So mild cognitive impairment might be >> So mild cognitive impairment might be the disease population, right? And so the disease population, right? And so the disease population, right? And so that's I think I'm I'm on at least one that's I think I'm I'm on at least one that's I think I'm I'm on at least one paper on mild cognitive impairment where paper on mild cognitive impairment where paper on mild cognitive impairment where nicotenoid ribocide is beginning to show nicotenoid ribocide is beginning to show nicotenoid ribocide is beginning to show some you know important signs like some you know important signs like some you know important signs like improving cerebral blood flow you know improving cerebral blood flow you know improving cerebral blood flow you know in this population but you will like in this population but you will like in this population but you will like ultimately to have you know functional ultimately to have you know functional ultimately to have you know functional metrics of like metrics of like metrics of like >> keeping your stuff together. Yeah. >> keeping your stuff together. Yeah. >> keeping your stuff together. Yeah. >> Right. Yeah. I mean improving blood flow >> Right. Yeah. I mean improving blood flow >> Right. Yeah. I mean improving blood flow >> most of the time if you have an increase >> most of the time if you have an increase >> most of the time if you have an increase in blood flow you're going to see a in blood flow you're going to see a in blood flow you're going to see a correlation with improved cognition. correlation with improved cognition. correlation with improved cognition. >> Right. Right. I mean, you're getting >> Right. Right. I mean, you're getting >> Right. Right. I mean, you're getting energy, you're getting glucose, you're energy, you're getting glucose, you're energy, you're getting glucose, you're getting all the goodies to your brain, getting all the goodies to your brain, getting all the goodies to your brain, right? Oxygen. right? Oxygen. right? Oxygen. >> Yeah. So, I mean, one would think that >> Yeah. So, I mean, one would think that >> Yeah. So, I mean, one would think that would that would also play a role. I'm would that would also play a role. I'm would that would also play a role. I'm al I'm also interested in asking you al I'm also interested in asking you al I'm also interested in asking you about the liver about the liver about the liver >> because I mean, the liver is obviously >> because I mean, the liver is obviously >> because I mean, the liver is obviously the first the first the first >> one of like one of the first places that >> one of like one of the first places that >> one of like one of the first places that you know is going to see this these NAD you know is going to see this these NAD you know is going to see this these NAD precursors like nicotenomide ribocide. precursors like nicotenomide ribocide. precursors like nicotenomide ribocide. Um do you is there any evidence that Um do you is there any evidence that Um do you is there any evidence that taking nicotenomide ribocide would have taking nicotenomide ribocide would have taking nicotenomide ribocide would have a positive benefit on some liver a positive benefit on some liver a positive benefit on some liver diseases? diseases? diseases? >> There there is there is in fact there is >> There there is there is in fact there is >> There there is there is in fact there is in fact human data on this. in fact human data on this. in fact human data on this. >> Okay, let's hear about it. >> Okay, let's hear about it. >> Okay, let's hear about it. >> Well, so again it's one of these things >> Well, so again it's one of these things >> Well, so again it's one of these things that's a little bit frustrating for me that's a little bit frustrating for me that's a little bit frustrating for me because um the primary endpoint was an because um the primary endpoint was an because um the primary endpoint was an unreasonable endpoint in in this trial. unreasonable endpoint in in this trial. unreasonable endpoint in in this trial. >> This is a story this is this is like the >> This is a story this is this is like the >> This is a story this is this is like the story of every clinical trial like ever. story of every clinical trial like ever. story of every clinical trial like ever. And look, the way I see it is like this And look, the way I see it is like this And look, the way I see it is like this is how you often find things too well, is how you often find things too well, is how you often find things too well, you know. you know. you know. >> Right. Right. So some the first trial >> Right. Right. So some the first trial >> Right. Right. So some the first trial can maybe teach you how to do the trial. can maybe teach you how to do the trial. can maybe teach you how to do the trial. But the problem is that NR is so But the problem is that NR is so But the problem is that NR is so remarkable in mice that you know I can remarkable in mice that you know I can remarkable in mice that you know I can induce obesity and type 2 diabetes in a induce obesity and type 2 diabetes in a induce obesity and type 2 diabetes in a in a mouse in a couple of months and I in a mouse in a couple of months and I in a mouse in a couple of months and I can treat it in a couple months, right? can treat it in a couple months, right? can treat it in a couple months, right? But um you can't then go to um 60 or But um you can't then go to um 60 or But um you can't then go to um 60 or 70year-old Danish men who are overw 70year-old Danish men who are overw 70year-old Danish men who are overw weightight and type 2 diabetic and weightight and type 2 diabetic and weightight and type 2 diabetic and insulin resistant and expect to see insulin resistant and expect to see insulin resistant and expect to see weight loss and insulin sensitization in weight loss and insulin sensitization in weight loss and insulin sensitization in 13 weeks without 13 weeks without 13 weeks without uh you know because it's not it's not uh you know because it's not it's not uh you know because it's not it's not itself a weight loss drug right it's a itself a weight loss drug right it's a itself a weight loss drug right it's a supplement So if you had supplement So if you had supplement So if you had you know imposed caloric restriction or you know imposed caloric restriction or you know imposed caloric restriction or if you had GLP-1 if you had GLP-1 if you had GLP-1 medication then you could see the uh NR medication then you could see the uh NR medication then you could see the uh NR on top of that right so there was a on top of that right so there was a on top of that right so there was a trial was done I think it was dollar up trial was done I think it was dollar up trial was done I think it was dollar up at all 2018 at all 2018 at all 2018 and I'm a co-author on on the first and I'm a co-author on on the first and I'm a co-author on on the first paper in which the hypothesis to be paper in which the hypothesis to be paper in which the hypothesis to be tested was that NR was going to improve tested was that NR was going to improve tested was that NR was going to improve weight loss and insulin insulin weight loss and insulin insulin weight loss and insulin insulin sensitivity in 13 weeks as a monotherapy sensitivity in 13 weeks as a monotherapy sensitivity in 13 weeks as a monotherapy >> in 70 year old 70-year-old Danish K. >> in 70 year old 70-year-old Danish K. >> in 70 year old 70-year-old Danish K. Okay. And um that's a moonshot. So So Okay. And um that's a moonshot. So So Okay. And um that's a moonshot. So So yeah, it's really a moonshot, right? yeah, it's really a moonshot, right? yeah, it's really a moonshot, right? Because they last played hockey, you Because they last played hockey, you Because they last played hockey, you know, four or five decades ago. Um they know, four or five decades ago. Um they know, four or five decades ago. Um they smoke, they're smoke, they're smoke, they're >> um they don't have a lot of physical >> um they don't have a lot of physical >> um they don't have a lot of physical activity. And so in terms of the topline activity. And so in terms of the topline activity. And so in terms of the topline results, it failed. But then we went in results, it failed. But then we went in results, it failed. But then we went in and we looked at everything else, right? and we looked at everything else, right? and we looked at everything else, right? >> And so we found that um it was about an >> And so we found that um it was about an >> And so we found that um it was about an N of 20 I think in placebo and NR and N of 20 I think in placebo and NR and N of 20 I think in placebo and NR and there was quite a big effect on hypatic there was quite a big effect on hypatic there was quite a big effect on hypatic fat. fat. fat. >> Mhm. >> Mhm. >> Mhm. >> Okay. like a difference of >> Okay. like a difference of >> Okay. like a difference of um something like 21% down to 11% um something like 21% down to 11% um something like 21% down to 11% fat fat in the liver like 10 absolute fat fat in the liver like 10 absolute fat fat in the liver like 10 absolute percent points. percent points. percent points. >> Was this a subgroup analysis like did or >> Was this a subgroup analysis like did or >> Was this a subgroup analysis like did or was this this was was this this was was this this was >> no that's that's the NR group. Now the >> no that's that's the NR group. Now the >> no that's that's the NR group. Now the problem and it it when you calculate a p problem and it it when you calculate a p problem and it it when you calculate a p value it was p.13 which means it value it was p.13 which means it value it was p.13 which means it probably worked. Yeah. Right. P.13 is probably worked. Yeah. Right. P.13 is probably worked. Yeah. Right. P.13 is actually pretty darn close to P.05 actually pretty darn close to P.05 actually pretty darn close to P.05 >> when you do the way that the the math >> when you do the way that the the math >> when you do the way that the the math works out. But the reason is works out. But the reason is works out. But the reason is >> don't get me started on I I feel like >> don't get me started on I I feel like >> don't get me started on I I feel like there's a lot Yeah. There's there's a there's a lot Yeah. There's there's a there's a lot Yeah. There's there's a lot of arbitrary stuff going on there lot of arbitrary stuff going on there lot of arbitrary stuff going on there too. Right. Anyway, but but the problem too. Right. Anyway, but but the problem too. Right. Anyway, but but the problem is they weren't randomized for their is they weren't randomized for their is they weren't randomized for their liver fat. And so there was a lot of liver fat. And so there was a lot of liver fat. And so there was a lot of variability in the liver fat, which is variability in the liver fat, which is variability in the liver fat, which is why even though um on an absolute basis why even though um on an absolute basis why even though um on an absolute basis it was like 10fold better than placebo, it was like 10fold better than placebo, it was like 10fold better than placebo, it didn't reach um statistical it didn't reach um statistical it didn't reach um statistical significance on the liver fat. So I significance on the liver fat. So I significance on the liver fat. So I think if we randomize people that all think if we randomize people that all think if we randomize people that all had fatty liver disease and then also we had fatty liver disease and then also we had fatty liver disease and then also we did some exercise plus minus NR could be did some exercise plus minus NR could be did some exercise plus minus NR could be positive in positive in positive in >> did you did you guys look within that >> did you did you guys look within that >> did you did you guys look within that group um of within the NR group it all group um of within the NR group it all group um of within the NR group it all just going back to this inflammation just going back to this inflammation just going back to this inflammation thing because it seems like that's such thing because it seems like that's such thing because it seems like that's such a powerful lever that NR is affecting a powerful lever that NR is affecting a powerful lever that NR is affecting >> that like within the people that you >> that like within the people that you >> that like within the people that you know obviously there's a lot of them know obviously there's a lot of them know obviously there's a lot of them that have fat liver but like if they that have fat liver but like if they that have fat liver but like if they also had that high inflammatory status also had that high inflammatory status also had that high inflammatory status >> yeah no one had done the inflammatory >> yeah no one had done the inflammatory >> yeah no one had done the inflammatory everything in 2018. It wasn't until everything in 2018. It wasn't until everything in 2018. It wasn't until around 2019 around 2019 around 2019 >> that Alhassan and at all in another, you >> that Alhassan and at all in another, you >> that Alhassan and at all in another, you know, topline failure trial showed, wow, know, topline failure trial showed, wow, know, topline failure trial showed, wow, the inflammation is is much lower. So the inflammation is is much lower. So the inflammation is is much lower. So now, you know, we can design better now, you know, we can design better now, you know, we can design better trials. They should be randomized for trials. They should be randomized for trials. They should be randomized for liver fat, right? probably they should liver fat, right? probably they should liver fat, right? probably they should be on either GLP1 or exercise or be on either GLP1 or exercise or be on either GLP1 or exercise or something to try to mobilize fat and something to try to mobilize fat and something to try to mobilize fat and then see the beneficial effect of NR on then see the beneficial effect of NR on then see the beneficial effect of NR on top of that. top of that. top of that. >> Well, I mean it's encouraging. It sounds >> Well, I mean it's encouraging. It sounds >> Well, I mean it's encouraging. It sounds like there's a there's a nice signal like there's a there's a nice signal like there's a there's a nice signal there to continue to study. Um, I think there to continue to study. Um, I think there to continue to study. Um, I think to me it become it's a little bit for me to me it become it's a little bit for me to me it become it's a little bit for me it's it's becoming clear the pattern it's it's becoming clear the pattern it's it's becoming clear the pattern which is you know there's there is room which is you know there's there is room which is you know there's there is room for improvement particularly in people for improvement particularly in people for improvement particularly in people that are unhealthy whether that's that are unhealthy whether that's that are unhealthy whether that's because they don't exercise a lot or because they don't exercise a lot or because they don't exercise a lot or they're obese or um if you're making the they're obese or um if you're making the they're obese or um if you're making the lifestyle changes that's the most lifestyle changes that's the most lifestyle changes that's the most important thing right if you can add important thing right if you can add important thing right if you can add this on in addition to that like you this on in addition to that like you this on in addition to that like you said like weight loss giving give said like weight loss giving give said like weight loss giving give expecting someone to take nicotine expecting someone to take nicotine expecting someone to take nicotine ribicide and lose weight in 13 weeks is ribicide and lose weight in 13 weeks is ribicide and lose weight in 13 weeks is >> I mean you have to do something in you >> I mean you have to do something in you >> I mean you have to do something in you know in addition to that right know in addition to that right know in addition to that right >> if that's especially if that's helping >> if that's especially if that's helping >> if that's especially if that's helping with the energy and inflammation status with the energy and inflammation status with the energy and inflammation status and things so um and things so um and things so um >> if there's a healthy individual out >> if there's a healthy individual out >> if there's a healthy individual out there right someone who's not overweight there right someone who's not overweight there right someone who's not overweight or obese someone that is physically or obese someone that is physically or obese someone that is physically active active active >> um it and they do want to add a what >> um it and they do want to add a what >> um it and they do want to add a what would you what would you say is the best would you what would you say is the best would you what would you say is the best argument for adding I think I already argument for adding I think I already argument for adding I think I already know your answer but I'm going to ask know your answer but I'm going to ask know your answer but I'm going to ask you anyways the best argument for adding you anyways the best argument for adding you anyways the best argument for adding a NAD precursor like nicotine ribocide a NAD precursor like nicotine ribocide a NAD precursor like nicotine ribocide to their routine and the best argument to their routine and the best argument to their routine and the best argument why they don't need to do that. why they don't need to do that. why they don't need to do that. >> Yeah, I think the best argument is >> Yeah, I think the best argument is >> Yeah, I think the best argument is probably um workout recovery, probably um workout recovery, probably um workout recovery, >> right? Because that it synergizes so >> right? Because that it synergizes so >> right? Because that it synergizes so well, you know, with exercise that and well, you know, with exercise that and well, you know, with exercise that and exercise makes everything else work exercise makes everything else work exercise makes everything else work better. better. better. >> Amazing. Okay. >> Amazing. Okay. >> Amazing. Okay. >> And I think it's worth with a worth a >> And I think it's worth with a worth a >> And I think it's worth with a worth a try. Well, full disclosure here. I have try. Well, full disclosure here. I have try. Well, full disclosure here. I have been taking Triogen for about I mean been taking Triogen for about I mean been taking Triogen for about I mean since August and I too a lot of other since August and I too a lot of other since August and I too a lot of other things but um things but um things but um >> my recovery is great. >> my recovery is great. >> my recovery is great. >> That's why and I work out a lot. >> That's why and I work out a lot. >> That's why and I work out a lot. >> Great. >> Great. >> Great. >> So great recovery and then um I was >> So great recovery and then um I was >> So great recovery and then um I was going to say inflammation as well but going to say inflammation as well but going to say inflammation as well but because even a healthy individual because even a healthy individual because even a healthy individual there's always you know maybe a little there's always you know maybe a little there's always you know maybe a little bit of room for for recovery but I like bit of room for for recovery but I like bit of room for for recovery but I like that I like that answer. I I'd love to that I like that answer. I I'd love to that I like that answer. I I'd love to talk a little bit about you know dosing talk a little bit about you know dosing talk a little bit about you know dosing a little deeper. I know we sort of a little deeper. I know we sort of a little deeper. I know we sort of touched on it a little bit. You talked touched on it a little bit. You talked touched on it a little bit. You talked about some of the clinical trials out about some of the clinical trials out about some of the clinical trials out there there there >> typically using 500 milligrams to 1,000 >> typically using 500 milligrams to 1,000 >> typically using 500 milligrams to 1,000 milligs. milligs. milligs. >> 1,000. Yeah. >> 1,000. Yeah. >> 1,000. Yeah. >> Right. Or a thousand. >> Right. Or a thousand. >> Right. Or a thousand. >> Is there an upper limit? I say this >> Is there an upper limit? I say this >> Is there an upper limit? I say this because there's a lot of people that because there's a lot of people that because there's a lot of people that like to go the extreme and so it's like to go the extreme and so it's like to go the extreme and so it's really important to talk about like I really important to talk about like I really important to talk about like I think I've seen even a 2,000 milligram think I've seen even a 2,000 milligram think I've seen even a 2,000 milligram study out there for nictimide rigide. So study out there for nictimide rigide. So study out there for nictimide rigide. So I'd love to know your thoughts like in I'd love to know your thoughts like in I'd love to know your thoughts like in terms of you know obviously there terms of you know obviously there terms of you know obviously there there's the evidence and we can talk you there's the evidence and we can talk you there's the evidence and we can talk you know you can mention I don't know the know you can mention I don't know the know you can mention I don't know the 2,000 milligram a day what the end 2,000 milligram a day what the end 2,000 milligram a day what the end points were but if if there's someone points were but if if there's someone points were but if if there's someone like myself you know so I'm taking 1,000 like myself you know so I'm taking 1,000 like myself you know so I'm taking 1,000 milligrams a day of true ngen nicotine milligrams a day of true ngen nicotine milligrams a day of true ngen nicotine my ribbocide does that seem like a my ribbocide does that seem like a my ribbocide does that seem like a reasonable dose in your opinion I know reasonable dose in your opinion I know reasonable dose in your opinion I know this this this >> well so I'm not your doctor and I based >> well so I'm not your doctor and I based >> well so I'm not your doctor and I based on the evidence of mice Um, and um, I I on the evidence of mice Um, and um, I I on the evidence of mice Um, and um, I I think that um, you know, for for for think that um, you know, for for for think that um, you know, for for for most people, you know, 500 milligrams to most people, you know, 500 milligrams to most people, you know, 500 milligrams to 1,000 milligrams is a is a substantive 1,000 milligrams is a is a substantive 1,000 milligrams is a is a substantive amount of of NR to take. The safety and amount of of NR to take. The safety and amount of of NR to take. The safety and the source of the NR is very important. the source of the NR is very important. the source of the NR is very important. Um Um Um this material has been safety tested up this material has been safety tested up this material has been safety tested up to um 3 g per day in certain to um 3 g per day in certain to um 3 g per day in certain populations. Um I don't think that populations. Um I don't think that populations. Um I don't think that people should really um go beyond that. people should really um go beyond that. people should really um go beyond that. You know I don't think and and also you You know I don't think and and also you You know I don't think and and also you know in certain you know diseases and know in certain you know diseases and know in certain you know diseases and conditions we always say ask your conditions we always say ask your conditions we always say ask your doctor. um your doctor may or may not doctor. um your doctor may or may not doctor. um your doctor may or may not have a background and and be able to um have a background and and be able to um have a background and and be able to um address it, but if somebody has some address it, but if somebody has some address it, but if somebody has some weird condition, you know, they could weird condition, you know, they could weird condition, you know, they could potentially get a weird result, right? potentially get a weird result, right? potentially get a weird result, right? >> Yeah, for sure. And I do want to get >> Yeah, for sure. And I do want to get >> Yeah, for sure. And I do want to get into some more safety um precautions in into some more safety um precautions in into some more safety um precautions in in a little bit. in a little bit. in a little bit. When it comes to taking nicotenomide When it comes to taking nicotenomide When it comes to taking nicotenomide ribocide, these NAD precursors, you ribocide, these NAD precursors, you ribocide, these NAD precursors, you mentioned stacking it with rveratrol, mentioned stacking it with rveratrol, mentioned stacking it with rveratrol, which is a type of polyphenol which is a type of polyphenol which is a type of polyphenol that um it sort of negated some of the that um it sort of negated some of the that um it sort of negated some of the bene benefits at least in peripheral bene benefits at least in peripheral bene benefits at least in peripheral artery disease, right? artery disease, right? artery disease, right? >> Um there are you can find some of these >> Um there are you can find some of these >> Um there are you can find some of these NAD boosters with other combinations. NAD boosters with other combinations. NAD boosters with other combinations. Teroselbean being one. I think the Teroselbean being one. I think the Teroselbean being one. I think the rationale behind that was that it rationale behind that was that it rationale behind that was that it increased the bioavailability or increased the bioavailability or increased the bioavailability or something like that. that I remember something like that. that I remember something like that. that I remember reading. Maybe you can maybe you can reading. Maybe you can maybe you can reading. Maybe you can maybe you can correct me on that. But um it also correct me on that. But um it also correct me on that. But um it also perhaps could potentially raise LDL. I perhaps could potentially raise LDL. I perhaps could potentially raise LDL. I think terrace still at least to some think terrace still at least to some think terrace still at least to some degree. I don't know that that matters degree. I don't know that that matters degree. I don't know that that matters unless you're already someone that has unless you're already someone that has unless you're already someone that has high LDL cholesterol because it wasn't high LDL cholesterol because it wasn't high LDL cholesterol because it wasn't like a huge huge amount. But I'd love to like a huge huge amount. But I'd love to like a huge huge amount. But I'd love to know your thoughts on um can they be know your thoughts on um can they be know your thoughts on um can they be mixed like should they be mixed like should they be mixed like should they be >> there's there's no use case for >> there's there's no use case for >> there's there's no use case for resveratrol or terrace still in in in my resveratrol or terrace still in in in my resveratrol or terrace still in in in my view um both of those compounds were view um both of those compounds were view um both of those compounds were thought to be cert one activators thought to be cert one activators thought to be cert one activators um I don't think that there's a evidence um I don't think that there's a evidence um I don't think that there's a evidence basis for saying that cert one is a basis for saying that cert one is a basis for saying that cert one is a longevity gene um terrace still and longevity gene um terrace still and longevity gene um terrace still and resveratrol don't actually increase the resveratrol don't actually increase the resveratrol don't actually increase the activity of certain one anyway and and activity of certain one anyway and and activity of certain one anyway and and as you said terrace shows a dose as you said terrace shows a dose as you said terrace shows a dose dependent increase in LDL cholesterol dependent increase in LDL cholesterol dependent increase in LDL cholesterol which is generally not a good thing for which is generally not a good thing for which is generally not a good thing for people. people. people. >> So for people that are interested in >> So for people that are interested in >> So for people that are interested in just boosting their NAD just boosting their NAD just boosting their NAD >> this is no not necessary. >> this is no not necessary. >> this is no not necessary. >> Okay. Um good. So the safety issues that >> Okay. Um good. So the safety issues that >> Okay. Um good. So the safety issues that I I kind of wanted to touch on um have I I kind of wanted to touch on um have I I kind of wanted to touch on um have to do with a reason I stopped taking NAD to do with a reason I stopped taking NAD to do with a reason I stopped taking NAD precursors many years ago when I had precursors many years ago when I had precursors many years ago when I had started taking them. started taking them. started taking them. >> So for let's start with the top safety >> So for let's start with the top safety >> So for let's start with the top safety questions like what do you think are the questions like what do you think are the questions like what do you think are the most safe important safety questions most safe important safety questions most safe important safety questions right now when it comes to taking an NAD right now when it comes to taking an NAD right now when it comes to taking an NAD precursor? Well, sourcing is probably precursor? Well, sourcing is probably precursor? Well, sourcing is probably the biggest safety issue, right? Because the biggest safety issue, right? Because the biggest safety issue, right? Because if the material is the same material if the material is the same material if the material is the same material that has been clinically tested, then that has been clinically tested, then that has been clinically tested, then you have some, you know, basis for you have some, you know, basis for you have some, you know, basis for feeling that you can take it as a as a feeling that you can take it as a as a feeling that you can take it as a as a human, right? Um, if it just has the human, right? Um, if it just has the human, right? Um, if it just has the same chemical name, like if it's you same chemical name, like if it's you same chemical name, like if it's you read some study about NMN being done in read some study about NMN being done in read some study about NMN being done in a hospital in Boston or Tokyo or a hospital in Boston or Tokyo or a hospital in Boston or Tokyo or something like that and then you go on something like that and then you go on something like that and then you go on Amazon and you buy NN, you're probably Amazon and you buy NN, you're probably Amazon and you buy NN, you're probably not using the same material that was not using the same material that was not using the same material that was tested in that hospital, right? And tested in that hospital, right? And tested in that hospital, right? And there's really no telling what's in it. there's really no telling what's in it. there's really no telling what's in it. So I think that um the source is really So I think that um the source is really So I think that um the source is really really important in terms of what people really important in terms of what people really important in terms of what people are taking. are taking. are taking. >> And just for people listening I mean >> And just for people listening I mean >> And just for people listening I mean this is not specific to NAD precursors. this is not specific to NAD precursors. this is not specific to NAD precursors. This is a systemic problem in This is a systemic problem in This is a systemic problem in neutrauticals in the supplement neutrauticals in the supplement neutrauticals in the supplement industry. There have now been many many industry. There have now been many many industry. There have now been many many published studies showing that quite a published studies showing that quite a published studies showing that quite a large large range of a variety of large large range of a variety of large large range of a variety of supplements that you can pull off the supplements that you can pull off the supplements that you can pull off the shelf at any store that most people shop shelf at any store that most people shop shelf at any store that most people shop at or off the shelf of Amazon warehouse at or off the shelf of Amazon warehouse at or off the shelf of Amazon warehouse shelf. Um oftent times don't contain shelf. Um oftent times don't contain shelf. Um oftent times don't contain much of the active ingredient and even much of the active ingredient and even much of the active ingredient and even more concerning often contain more concerning often contain more concerning often contain contaminants that could be harmful to contaminants that could be harmful to contaminants that could be harmful to ingest as well particularly if you're ingest as well particularly if you're ingest as well particularly if you're ingesting large doses. And so my ingesting large doses. And so my ingesting large doses. And so my recommendation always is to get recommendation always is to get recommendation always is to get third-party tested uh supplement brands third-party tested uh supplement brands third-party tested uh supplement brands that have been thirdparty tested that that have been thirdparty tested that that have been thirdparty tested that you can look at the data NSF you can look at the data NSF you can look at the data NSF certification which also is very certification which also is very certification which also is very rigorous and they're testing for rigorous and they're testing for rigorous and they're testing for potential contaminants as well um with potential contaminants as well um with potential contaminants as well um with any supplement because it's it's really any supplement because it's it's really any supplement because it's it's really a big problem in the entire industry. So a big problem in the entire industry. So a big problem in the entire industry. So I think that is definitely a a good I think that is definitely a a good I think that is definitely a a good thing to point out. thing to point out. thing to point out. >> Yeah. Um let me ask you specifically >> Yeah. Um let me ask you specifically >> Yeah. Um let me ask you specifically about a concern that I have had over the about a concern that I have had over the about a concern that I have had over the years and this has to do with cancer years and this has to do with cancer years and this has to do with cancer risk. risk. risk. >> So obviously NAD is important for all of >> So obviously NAD is important for all of >> So obviously NAD is important for all of our cells. Our cells need to make our cells. Our cells need to make our cells. Our cells need to make energy. There's a variety of you know energy. There's a variety of you know energy. There's a variety of you know other processes that you described that other processes that you described that other processes that you described that are very important. Biosyn synthesis of are very important. Biosyn synthesis of are very important. Biosyn synthesis of molecules. molecules. molecules. >> These are also things that cells that >> These are also things that cells that >> These are also things that cells that are mutated and potentially are are mutated and potentially are are mutated and potentially are cancerous also like they need energy. cancerous also like they need energy. cancerous also like they need energy. They need to build more cancer cells. They need to build more cancer cells. They need to build more cancer cells. Right? tumor wants to grow. Right? tumor wants to grow. Right? tumor wants to grow. And so I'd love to know your thoughts on And so I'd love to know your thoughts on And so I'd love to know your thoughts on the role of taking an NAD precursor with the role of taking an NAD precursor with the role of taking an NAD precursor with respect to cancer risk. Obviously, respect to cancer risk. Obviously, respect to cancer risk. Obviously, someone already has cancer currently or someone already has cancer currently or someone already has cancer currently or had previously had cancer in those had previously had cancer in those had previously had cancer in those context as well. context as well. context as well. >> Yeah. So um there's a hierarchy of >> Yeah. So um there's a hierarchy of >> Yeah. So um there's a hierarchy of evidence right in which um large evidence right in which um large evidence right in which um large randomized placebo control trials are randomized placebo control trials are randomized placebo control trials are the the top of the of of the hierarchy the the top of the of of the hierarchy the the top of the of of the hierarchy right and so we know from the Australian right and so we know from the Australian right and so we know from the Australian nicotenomide trials that supplementing nicotenomide trials that supplementing nicotenomide trials that supplementing with you know the classic NAD booster with you know the classic NAD booster with you know the classic NAD booster nicotenomide um lowers cancer risk at nicotenomide um lowers cancer risk at nicotenomide um lowers cancer risk at the population level. So it's not like the population level. So it's not like the population level. So it's not like if if there was a signal that said that if if there was a signal that said that if if there was a signal that said that higher NAD status would um cause more higher NAD status would um cause more higher NAD status would um cause more you know small tumors to appear. You you know small tumors to appear. You you know small tumors to appear. You would have seen that in you know the would have seen that in you know the would have seen that in you know the clinical data. So that's we can be clinical data. So that's we can be clinical data. So that's we can be grounded with that as kind of um you grounded with that as kind of um you grounded with that as kind of um you know foundational information. know foundational information. know foundational information. >> It's clearly not causing cancer. >> It's clearly not causing cancer. >> It's clearly not causing cancer. >> Yeah. Not causing cancer. Right. Um now >> Yeah. Not causing cancer. Right. Um now >> Yeah. Not causing cancer. Right. Um now um there are things that you can do with um there are things that you can do with um there are things that you can do with cell lines and in mice cell lines and in mice cell lines and in mice um where um you know it looks like some um where um you know it looks like some um where um you know it looks like some tumors could potentially be limited by tumors could potentially be limited by tumors could potentially be limited by NAD supply. Um NAD is not really a fuel. NAD supply. Um NAD is not really a fuel. NAD supply. Um NAD is not really a fuel. Like I said it's more the wiring of um Like I said it's more the wiring of um Like I said it's more the wiring of um between the fuel and ATP production. So between the fuel and ATP production. So between the fuel and ATP production. So I think at the population level it's not I think at the population level it's not I think at the population level it's not really you know a risk. That said, um we really you know a risk. That said, um we really you know a risk. That said, um we do say, you know, ask your doctor and if do say, you know, ask your doctor and if do say, you know, ask your doctor and if you have a disease or condition, you you have a disease or condition, you you have a disease or condition, you know, if there's some type of cancer know, if there's some type of cancer know, if there's some type of cancer chemotherapy a person is undergoing, chemotherapy a person is undergoing, chemotherapy a person is undergoing, um, you know, it could be um, you know, it could be um, you know, it could be contraindicated potentially. And so I contraindicated potentially. And so I contraindicated potentially. And so I don't have the knowledge to, you know, don't have the knowledge to, you know, don't have the knowledge to, you know, to reassure every possible situation. Um to reassure every possible situation. Um to reassure every possible situation. Um but overall the clinical data say that but overall the clinical data say that but overall the clinical data say that NAD boosting is preventative for cancer NAD boosting is preventative for cancer NAD boosting is preventative for cancer and that niggen is safe. and that niggen is safe. and that niggen is safe. >> Did you see the study the animal study >> Did you see the study the animal study >> Did you see the study the animal study that that that gave mice that had I believe it was gave mice that had I believe it was gave mice that had I believe it was pancreatic cancer they already had they pancreatic cancer they already had they pancreatic cancer they already had they had pancreatic cancer and they gave them had pancreatic cancer and they gave them had pancreatic cancer and they gave them nicotenomide monucleotide and it nicotenomide monucleotide and it nicotenomide monucleotide and it accelerated tumor growth. Is that accelerated tumor growth. Is that accelerated tumor growth. Is that ringing a bell? Um, no. But you know, ringing a bell? Um, no. But you know, ringing a bell? Um, no. But you know, there are there are a lot of trials that there are there are a lot of trials that there are there are a lot of trials that you can do, things that you can do in in you can do, things that you can do in in you can do, things that you can do in in mice that are very prone to to cancer or mice that are very prone to to cancer or mice that are very prone to to cancer or where you're injecting them with, you where you're injecting them with, you where you're injecting them with, you know, a literally 10 to the 6th, you know, a literally 10 to the 6th, you know, a literally 10 to the 6th, you know, MCF7 cells or something like that know, MCF7 cells or something like that know, MCF7 cells or something like that where they're all going to get tumors. where they're all going to get tumors. where they're all going to get tumors. And I just don't know how important And I just don't know how important And I just don't know how important those are for the human condition. And those are for the human condition. And those are for the human condition. And that's not the way you know human that's not the way you know human that's not the way you know human cancers develop. We don't get injected cancers develop. We don't get injected cancers develop. We don't get injected with a million MCF7 cells. with a million MCF7 cells. with a million MCF7 cells. >> Good. So it sound I think that that >> Good. So it sound I think that that >> Good. So it sound I think that that evidence with the nicotenomide that was evidence with the nicotenomide that was evidence with the nicotenomide that was given to pe to people in Australia. given to pe to people in Australia. given to pe to people in Australia. Yeah. Yeah. Yeah. >> And it actually not only didn't increase >> And it actually not only didn't increase >> And it actually not only didn't increase cancer risk, it lowered cancer risk, it lowered cancer risk, it lowered >> lowers the risk risk of of melanoma. >> lowers the risk risk of of melanoma. >> lowers the risk risk of of melanoma. >> Yep. Yeah. >> Yep. Yeah. >> Yep. Yeah. >> Of uh I think it might have been >> Of uh I think it might have been >> Of uh I think it might have been non-melanoma skin cancer like the most non-melanoma skin cancer like the most non-melanoma skin cancer like the most common. common. common. >> Okay. Got it. Um that's very reassuring >> Okay. Got it. Um that's very reassuring >> Okay. Got it. Um that's very reassuring um particularly for me because I had um particularly for me because I had um particularly for me because I had seen this this Japan I don't if it was seen this this Japan I don't if it was seen this this Japan I don't if it was Japanese said it might have been out of Japanese said it might have been out of Japanese said it might have been out of Japan um but it was definitely en given Japan um but it was definitely en given Japan um but it was definitely en given orally no actually it was given by it orally no actually it was given by it orally no actually it was given by it might have been injected might have been injected might have been injected >> to mice with pancreatic cancer and it >> to mice with pancreatic cancer and it >> to mice with pancreatic cancer and it accelerated cancer growth which isn't accelerated cancer growth which isn't accelerated cancer growth which isn't too surprising I mean if you already too surprising I mean if you already too surprising I mean if you already have a bunch of tumors and then you're have a bunch of tumors and then you're have a bunch of tumors and then you're giving you know a bunch of whether it's giving you know a bunch of whether it's giving you know a bunch of whether it's folate or NAD or something you might folate or NAD or something you might folate or NAD or something you might expect um rapid cancer growth but who expect um rapid cancer growth but who expect um rapid cancer growth but who knows knows knows >> so I think I I think that's kind of what >> so I think I I think that's kind of what >> so I think I I think that's kind of what shut me down for a little bit on on shut me down for a little bit on on shut me down for a little bit on on taking the NAD precursors. I'm back to taking the NAD precursors. I'm back to taking the NAD precursors. I'm back to taking them, taking them, taking them, >> but um I guess it's always a concern if >> but um I guess it's always a concern if >> but um I guess it's always a concern if you already if you actually have cancer, you already if you actually have cancer, you already if you actually have cancer, you probably probably not going to want you probably probably not going to want you probably probably not going to want to take a bunch of supplements in to take a bunch of supplements in to take a bunch of supplements in general. Um anyway, so um I do want to general. Um anyway, so um I do want to general. Um anyway, so um I do want to ask you, is that something that you kind ask you, is that something that you kind ask you, is that something that you kind of agree on? Is that what you're kind of of agree on? Is that what you're kind of of agree on? Is that what you're kind of getting at? What? Yeah, I think that, getting at? What? Yeah, I think that, getting at? What? Yeah, I think that, you know, for the the general public, you know, for the the general public, you know, for the the general public, you know, we're we're we think an R is you know, we're we're we think an R is you know, we're we're we think an R is safe. Um there's a registry at FDA. So, safe. Um there's a registry at FDA. So, safe. Um there's a registry at FDA. So, as you know, the F in FDA stands for as you know, the F in FDA stands for as you know, the F in FDA stands for food. And um nutritional supplements are food. And um nutritional supplements are food. And um nutritional supplements are in under the F in FDA. And so because in under the F in FDA. And so because in under the F in FDA. And so because Nigen went through the process of being Nigen went through the process of being Nigen went through the process of being a uh compound that is generally regarded a uh compound that is generally regarded a uh compound that is generally regarded as safe and as a new dietary ingredient, as safe and as a new dietary ingredient, as safe and as a new dietary ingredient, if there are any complaints or if there are any complaints or if there are any complaints or observations or clinical trial observations or clinical trial observations or clinical trial observations that are linked to NR, observations that are linked to NR, observations that are linked to NR, there's a file on them, you know, that there's a file on them, you know, that there's a file on them, you know, that we're aware of. And so far the safety we're aware of. And so far the safety we're aware of. And so far the safety data look really good. data look really good. data look really good. >> So if there were I'm going to ask you >> So if there were I'm going to ask you >> So if there were I'm going to ask you this like final question. If a listener this like final question. If a listener this like final question. If a listener does come up to you and say, "Dr. does come up to you and say, "Dr. does come up to you and say, "Dr. Brener, I mean, do you think that it'd Brener, I mean, do you think that it'd Brener, I mean, do you think that it'd be worthwhile, worth my my time to start be worthwhile, worth my my time to start be worthwhile, worth my my time to start supplementing with nicotenomide supplementing with nicotenomide supplementing with nicotenomide ribocide? Um, in addition to the other ribocide? Um, in addition to the other ribocide? Um, in addition to the other healthy lifestyle factors and diet and healthy lifestyle factors and diet and healthy lifestyle factors and diet and lifestyle factors that I'm adopting to lifestyle factors that I'm adopting to lifestyle factors that I'm adopting to improve my health, like what would be improve my health, like what would be improve my health, like what would be the most honest answer you would tell the most honest answer you would tell the most honest answer you would tell them?" Yeah, I think that there's them?" Yeah, I think that there's them?" Yeah, I think that there's there's use cases for people and I don't there's use cases for people and I don't there's use cases for people and I don't I don't think that it's strictly age I don't think that it's strictly age I don't think that it's strictly age related, right? Because, you know, related, right? Because, you know, related, right? Because, you know, 20-year-old football players that are in 20-year-old football players that are in 20-year-old football players that are in a you know, collision sport on Sunday a you know, collision sport on Sunday a you know, collision sport on Sunday and have to be back on the practice and have to be back on the practice and have to be back on the practice field on Tuesday have a have a benefit field on Tuesday have a have a benefit field on Tuesday have a have a benefit from from Niogen supplementation. from from Niogen supplementation. from from Niogen supplementation. um people that are busy and people are um people that are busy and people are um people that are busy and people are doing, you know, intense workout doing, you know, intense workout doing, you know, intense workout schedules. Um people that um go into schedules. Um people that um go into schedules. Um people that um go into crowded rooms where 5% of the people crowded rooms where 5% of the people crowded rooms where 5% of the people might have the flu or 2% of the people might have the flu or 2% of the people might have the flu or 2% of the people might have COVID infection. There's might have COVID infection. There's might have COVID infection. There's probably a use case in not getting sick probably a use case in not getting sick probably a use case in not getting sick all the time. So, I think it's, you all the time. So, I think it's, you all the time. So, I think it's, you know, I'm I'm happy, I'm kind of proud know, I'm I'm happy, I'm kind of proud know, I'm I'm happy, I'm kind of proud that we developed something that is that we developed something that is that we developed something that is useful to to people and is safe and that useful to to people and is safe and that useful to to people and is safe and that with future trials of peripheral artery with future trials of peripheral artery with future trials of peripheral artery disease and potentially the fatty liver disease and potentially the fatty liver disease and potentially the fatty liver trial that that we talked about trial that that we talked about trial that that we talked about >> um fertility, you know, there could be >> um fertility, you know, there could be >> um fertility, you know, there could be really multiple use cases for this really multiple use cases for this really multiple use cases for this compound. compound. compound. >> Wonderful. Wonderful. Well, thanks. >> Wonderful. Wonderful. Well, thanks. >> Wonderful. Wonderful. Well, thanks. >> Thank you so much, Dr. Brener, for >> Thank you so much, Dr. Brener, for >> Thank you so much, Dr. Brener, for joining me on this podcast. I know that joining me on this podcast. I know that joining me on this podcast. I know that you're very active on X. you're very active on X. you're very active on X. >> You want to tell people your your >> You want to tell people your your >> You want to tell people your your >> Yeah. So, it's Charles M. Brener. Um >> Yeah. So, it's Charles M. Brener. Um >> Yeah. So, it's Charles M. Brener. Um people can ask me questions there. I do people can ask me questions there. I do people can ask me questions there. I do my best to um to respond and reply. my best to um to respond and reply. my best to um to respond and reply. >> Is there anywhere else you want to >> Is there anywhere else you want to >> Is there anywhere else you want to direct people to that they can direct people to that they can direct people to that they can >> Yeah, my my lab website is brenerlab.net >> Yeah, my my lab website is brenerlab.net >> Yeah, my my lab website is brenerlab.net and so you can see what we're up to in and so you can see what we're up to in and so you can see what we're up to in the laboratory. the laboratory. the laboratory. >> Amazing. All right. Well, thank you for, >> Amazing. All right. Well, thank you for, >> Amazing. All right. Well, thank you for, you know, this evidence-based discussion you know, this evidence-based discussion you know, this evidence-based discussion on NAD, boosting NAD. Um, I it's it's on NAD, boosting NAD. Um, I it's it's on NAD, boosting NAD. Um, I it's it's very, I think, informative and it's good very, I think, informative and it's good very, I think, informative and it's good to have this out there because it to have this out there because it to have this out there because it definitely is a a popular topic right definitely is a a popular topic right definitely is a a popular topic right now. now. now. >> Great. Thank you so much. >> Great. Thank you so much. >> Great. Thank you so much. >> Thank you for joining me today in this >> Thank you for joining me today in this >> Thank you for joining me today in this fascinating conversation with Dr. fascinating conversation with Dr. fascinating conversation with Dr. Charles Brener exploring the science of Charles Brener exploring the science of Charles Brener exploring the science of NAD, aging, and inflammation. For those NAD, aging, and inflammation. For those NAD, aging, and inflammation. For those who love to dive deeper, be sure to stay who love to dive deeper, be sure to stay who love to dive deeper, be sure to stay tuned for an exclusive bonus segment at tuned for an exclusive bonus segment at tuned for an exclusive bonus segment at the end of this episode. Dr. Brunner the end of this episode. Dr. Brunner the end of this episode. Dr. Brunner shares the fascinating biochemical shares the fascinating biochemical shares the fascinating biochemical journey behind his discovery of journey behind his discovery of journey behind his discovery of nicotenomide ribocide, uncovering an NAD nicotenomide ribocide, uncovering an NAD nicotenomide ribocide, uncovering an NAD pathway that was previously unknown to pathway that was previously unknown to pathway that was previously unknown to science. You've obviously studied NAD science. You've obviously studied NAD science. You've obviously studied NAD for decades. for decades. for decades. >> So, can you tell me, you know, what were >> So, can you tell me, you know, what were >> So, can you tell me, you know, what were some of the early observations in your some of the early observations in your some of the early observations in your career that convinced you this is an career that convinced you this is an career that convinced you this is an important molecule? this isn't just some important molecule? this isn't just some important molecule? this isn't just some biochemistry, you know, metabolite. Like biochemistry, you know, metabolite. Like biochemistry, you know, metabolite. Like this is like this is something to pay this is like this is something to pay this is like this is something to pay attention to. attention to. attention to. >> Well, I I can't get behind um >> Well, I I can't get behind um >> Well, I I can't get behind um downgrading the interest of biochemical downgrading the interest of biochemical downgrading the interest of biochemical metabolites because I'm that kind of metabolites because I'm that kind of metabolites because I'm that kind of nerd, right? So, I really grew up as an nerd, right? So, I really grew up as an nerd, right? So, I really grew up as an enzyologist enzyologist enzyologist and I did my posttock and discovered a and I did my posttock and discovered a and I did my posttock and discovered a super family of nucleotide binding super family of nucleotide binding super family of nucleotide binding proteins. So, I was just really proteins. So, I was just really proteins. So, I was just really interested in enzymes and proteins that interested in enzymes and proteins that interested in enzymes and proteins that bind and interact with nucleotides. And bind and interact with nucleotides. And bind and interact with nucleotides. And sometime around 2003, sometime around 2003, sometime around 2003, I ran across an amino acid sequence that I ran across an amino acid sequence that I ran across an amino acid sequence that really really interested me. And um really really interested me. And um really really interested me. And um essentially it was um found in yeast and essentially it was um found in yeast and essentially it was um found in yeast and it was found in human. and it clearly it was found in human. and it clearly it was found in human. and it clearly had a so-called NAD synthetase domain. had a so-called NAD synthetase domain. had a so-called NAD synthetase domain. This is not actually nicotenomide This is not actually nicotenomide This is not actually nicotenomide ribocide or nicotenomide ribocide. This ribocide or nicotenomide ribocide. This ribocide or nicotenomide ribocide. This is an enzyme that converts a a wacky is an enzyme that converts a a wacky is an enzyme that converts a a wacky metabolite called nicotinic acid adine metabolite called nicotinic acid adine metabolite called nicotinic acid adine ducleotide ducleotide ducleotide NAD. NAD. NAD. I didn't stutter. It's N A um converts N I didn't stutter. It's N A um converts N I didn't stutter. It's N A um converts N A into NAD. It has an piece on it that A into NAD. It has an piece on it that A into NAD. It has an piece on it that basically puts an amino group on basically puts an amino group on basically puts an amino group on nicotinic acid adding ducleide to form nicotinic acid adding ducleide to form nicotinic acid adding ducleide to form NAD, right? And the the interesting NAD, right? And the the interesting NAD, right? And the the interesting thing to me was that all of the thing to me was that all of the thing to me was that all of the ukareotic ones, the ones in yeast and ukareotic ones, the ones in yeast and ukareotic ones, the ones in yeast and human and flies, etc., etc., human and flies, etc., etc., human and flies, etc., etc., had what was what I could see was a had what was what I could see was a had what was what I could see was a glutaminase domain, an enzyme that will glutaminase domain, an enzyme that will glutaminase domain, an enzyme that will take an am a vitam amino acid glutamine take an am a vitam amino acid glutamine take an am a vitam amino acid glutamine and convert it to glutamate liberating and convert it to glutamate liberating and convert it to glutamate liberating an ammonia group, a nitrogen group. an ammonia group, a nitrogen group. an ammonia group, a nitrogen group. So that seems pretty obscure, but in So that seems pretty obscure, but in So that seems pretty obscure, but in 1958, I'm a I'm a kind of master of 1958, I'm a I'm a kind of master of 1958, I'm a I'm a kind of master of knowing literature. 1958, knowing literature. 1958, knowing literature. 1958, somebody named Jack Priest of Priest and somebody named Jack Priest of Priest and somebody named Jack Priest of Priest and Handler fame had purified this enzyme Handler fame had purified this enzyme Handler fame had purified this enzyme NAD synthetase from yeast and he showed NAD synthetase from yeast and he showed NAD synthetase from yeast and he showed that it required glutamine and no one that it required glutamine and no one that it required glutamine and no one had ever explained why the yeast and the had ever explained why the yeast and the had ever explained why the yeast and the human NADases human NADases human NADases needed or could use glutamine to provide needed or could use glutamine to provide needed or could use glutamine to provide that ammonia group. So I thought given that ammonia group. So I thought given that ammonia group. So I thought given the importance of NAD as the central the importance of NAD as the central the importance of NAD as the central catalyst in metabolism, I really need to catalyst in metabolism, I really need to catalyst in metabolism, I really need to work on this enzyme. And I loved that work on this enzyme. And I loved that work on this enzyme. And I loved that enzyme um because it had two active enzyme um because it had two active enzyme um because it had two active sites. It had the glutaminase active sites. It had the glutaminase active sites. It had the glutaminase active site that interacts with this amino acid site that interacts with this amino acid site that interacts with this amino acid and then it's liberating an ammonia and then it's liberating an ammonia and then it's liberating an ammonia group and somehow it's shuttling the group and somehow it's shuttling the group and somehow it's shuttling the ammonia group from one active site to ammonia group from one active site to ammonia group from one active site to the other active site where it's going the other active site where it's going the other active site where it's going to form NAD+. to form NAD+. to form NAD+. And so I decided I was going to work on And so I decided I was going to work on And so I decided I was going to work on that enzyme. And in the course of that enzyme. And in the course of that enzyme. And in the course of working on that enzyme, I realized how working on that enzyme, I realized how working on that enzyme, I realized how many people were drawing diagrams of NAD many people were drawing diagrams of NAD many people were drawing diagrams of NAD synthetists. So folks at MIT, Harvard, synthetists. So folks at MIT, Harvard, synthetists. So folks at MIT, Harvard, um, Washington University and and a lot um, Washington University and and a lot um, Washington University and and a lot of places were drawing these cartoon of places were drawing these cartoon of places were drawing these cartoon diagrams of how NAD is made. diagrams of how NAD is made. diagrams of how NAD is made. So they had a pathway that came from So they had a pathway that came from So they had a pathway that came from tryptophan tryptophan tryptophan that went through this NAD synthetase that went through this NAD synthetase that went through this NAD synthetase enzyme that I was working on. They had a enzyme that I was working on. They had a enzyme that I was working on. They had a pathway through nicotinic acid niacin pathway through nicotinic acid niacin pathway through nicotinic acid niacin that was discovered uh 1938 that was discovered uh 1938 that was discovered uh 1938 and they had a pathway from nicotinomide and they had a pathway from nicotinomide and they had a pathway from nicotinomide and uh I realized that if I knocked out and uh I realized that if I knocked out and uh I realized that if I knocked out the gene that I was working on in yeast the gene that I was working on in yeast the gene that I was working on in yeast according to prediction there's no other according to prediction there's no other according to prediction there's no other way to make NAD and I thought there way to make NAD and I thought there way to make NAD and I thought there might be another way to make NAD through might be another way to make NAD through might be another way to make NAD through a nucleioide nicotenoid ribocide and I a nucleioide nicotenoid ribocide and I a nucleioide nicotenoid ribocide and I essentially set up the experiment to essentially set up the experiment to essentially set up the experiment to test whether there might be an NR test whether there might be an NR test whether there might be an NR pathway. So basically started working on pathway. So basically started working on pathway. So basically started working on on an enzyme and ended up working on the on an enzyme and ended up working on the on an enzyme and ended up working on the whole pathway because at the end of the whole pathway because at the end of the whole pathway because at the end of the pathway is the central catalyst of pathway is the central catalyst of pathway is the central catalyst of metabolism and I knew that view. metabolism and I knew that view. metabolism and I knew that view. >> Wow. >> Wow. >> Wow. >> Yeah. >> Yeah. >> Yeah. >> Okay. Well, when most people hear the >> Okay. Well, when most people hear the >> Okay. Well, when most people hear the word NAD, they think of energy or word NAD, they think of energy or word NAD, they think of energy or they'll think anti-aging buzzword. So they'll think anti-aging buzzword. So they'll think anti-aging buzzword. So maybe you could explain to people in maybe you could explain to people in maybe you could explain to people in sort of you know more simple sort of you know more simple sort of you know more simple understandable terms like why is NAD understandable terms like why is NAD understandable terms like why is NAD >> okay >> okay >> okay >> so important to biology. >> so important to biology. >> so important to biology. >> So my wife just dropped me off in an >> So my wife just dropped me off in an >> So my wife just dropped me off in an electric vehicle right there's a big electric vehicle right there's a big electric vehicle right there's a big battery in it and the battery has copper battery in it and the battery has copper battery in it and the battery has copper wires going to the front drivetrain and wires going to the front drivetrain and wires going to the front drivetrain and the rear drivetrain. This is a big um the rear drivetrain. This is a big um the rear drivetrain. This is a big um Ford F-150 Lightning. They're they're Ford F-150 Lightning. They're they're Ford F-150 Lightning. They're they're not a sponsor of the podcast as far as I not a sponsor of the podcast as far as I not a sponsor of the podcast as far as I know, but um so two two drivetrains know, but um so two two drivetrains know, but um so two two drivetrains front and back. There's windshield front and back. There's windshield front and back. There's windshield wipers that run on electricity. There's wipers that run on electricity. There's wipers that run on electricity. There's air conditioning and heating that runs air conditioning and heating that runs air conditioning and heating that runs on electricity. So there's a lot of on electricity. So there's a lot of on electricity. So there's a lot of copper wires going to a lot of different copper wires going to a lot of different copper wires going to a lot of different places, right? And the um the the places, right? And the um the the places, right? And the um the the battery is storing battery is storing battery is storing uh high energy electrons and then copper uh high energy electrons and then copper uh high energy electrons and then copper wires are distributing those high energy wires are distributing those high energy wires are distributing those high energy electrons to all of the moving parts. electrons to all of the moving parts. electrons to all of the moving parts. The the thing that your listeners need The the thing that your listeners need The the thing that your listeners need to know or watchers need to know is that to know or watchers need to know is that to know or watchers need to know is that high energy electrons run us as well. high energy electrons run us as well. high energy electrons run us as well. They run living things as well. And the They run living things as well. And the They run living things as well. And the wiring for the high energy electrons are wiring for the high energy electrons are wiring for the high energy electrons are basically NAD co-enzymes. So NAD basically NAD co-enzymes. So NAD basically NAD co-enzymes. So NAD co-enzymes NAD+ co-enzymes NAD+ co-enzymes NAD+ captures high energy electrons from our captures high energy electrons from our captures high energy electrons from our food protein, fat and carbohydrate food protein, fat and carbohydrate food protein, fat and carbohydrate and it collects those high energy and it collects those high energy and it collects those high energy electrons as a hydide group. That's a electrons as a hydide group. That's a electrons as a hydide group. That's a proton with two high energy electrons proton with two high energy electrons proton with two high energy electrons forming NADH. forming NADH. forming NADH. you're being very patient that because you're being very patient that because you're being very patient that because you you learned this in first year of you you learned this in first year of you you learned this in first year of college, right? Um but um NAD+ collects college, right? Um but um NAD+ collects college, right? Um but um NAD+ collects the high energy electrons from food. the high energy electrons from food. the high energy electrons from food. It's now NADH It's now NADH It's now NADH and then it passes on those electrons and then it passes on those electrons and then it passes on those electrons along things like the electron transfer along things like the electron transfer along things like the electron transfer chain. And every time the high energy chain. And every time the high energy chain. And every time the high energy electrons get passed on to a lower electrons get passed on to a lower electrons get passed on to a lower energy carrier, right? Because things energy carrier, right? Because things energy carrier, right? Because things flow downhill, water flows downhill, flow downhill, water flows downhill, flow downhill, water flows downhill, right? You don't see waterfalls that go right? You don't see waterfalls that go right? You don't see waterfalls that go up. You only see waterfalls that go up. You only see waterfalls that go up. You only see waterfalls that go down. So when electrons get passed to down. So when electrons get passed to down. So when electrons get passed to carriers at a lower energy state, work carriers at a lower energy state, work carriers at a lower energy state, work can be done, right? So we can do things can be done, right? So we can do things can be done, right? So we can do things like we can pump protons across like we can pump protons across like we can pump protons across membranes and you can use the return of membranes and you can use the return of membranes and you can use the return of those protons to drive ATP synthesis. those protons to drive ATP synthesis. those protons to drive ATP synthesis. Right? So, so when you say your your Right? So, so when you say your your Right? So, so when you say your your typical um listener thinks about NAD+ typical um listener thinks about NAD+ typical um listener thinks about NAD+ as energy, this is the way that that as energy, this is the way that that as energy, this is the way that that that transaction works is that NAD+ is that transaction works is that NAD+ is that transaction works is that NAD+ is taking taking taking um high energy electrons from food. um high energy electrons from food. um high energy electrons from food. Um, it's not. So, the the amazing thing Um, it's not. So, the the amazing thing Um, it's not. So, the the amazing thing about biological fuel oxidation that's about biological fuel oxidation that's about biological fuel oxidation that's different than if we were to we could different than if we were to we could different than if we were to we could take my breakfast, right? And we could take my breakfast, right? And we could take my breakfast, right? And we could light it with a match light it with a match light it with a match and its calorie content would be and its calorie content would be and its calorie content would be essentially what its calorie content is essentially what its calorie content is essentially what its calorie content is for me in my body. But the the problem for me in my body. But the the problem for me in my body. But the the problem is that when we light it on fire to is that when we light it on fire to is that when we light it on fire to generate heat, the high energy electrons generate heat, the high energy electrons generate heat, the high energy electrons go up in smoke, right? The water vapor go up in smoke, right? The water vapor go up in smoke, right? The water vapor goes up in smoke, right? We can't we goes up in smoke, right? We can't we goes up in smoke, right? We can't we don't have a way to um direct that don't have a way to um direct that don't have a way to um direct that energy energy energy into our muscle function, our memory into our muscle function, our memory into our muscle function, our memory formation, and our heart beating and formation, and our heart beating and formation, and our heart beating and pumping and all the other things that we pumping and all the other things that we pumping and all the other things that we want to do, right? So the way living want to do, right? So the way living want to do, right? So the way living things work is they couple all of the things work is they couple all of the things work is they couple all of the energy transfers energy transfers energy transfers to reactions that need to be run and we to reactions that need to be run and we to reactions that need to be run and we don't let the high energy electrons go don't let the high energy electrons go don't let the high energy electrons go up in smoke. up in smoke. up in smoke. >> Well, so for everyone that was uh >> Well, so for everyone that was uh >> Well, so for everyone that was uh following that hopefully definitely following that hopefully definitely following that hopefully definitely important for energy. I think that you important for energy. I think that you important for energy. I think that you get anything out of this. get anything out of this. get anything out of this. >> But but do you want me to do a couple >> But but do you want me to do a couple >> But but do you want me to do a couple more? Um you can or maybe you could talk more? Um you can or maybe you could talk more? Um you can or maybe you could talk a little bit about you know what like a little bit about you know what like a little bit about you know what like let's talk about maybe like the two mo let's talk about maybe like the two mo let's talk about maybe like the two mo most important roles of NAD in the body. most important roles of NAD in the body. most important roles of NAD in the body. Okay. What would you say? Okay. What would you say? Okay. What would you say? >> But well first can I'd like to expand I >> But well first can I'd like to expand I >> But well first can I'd like to expand I I I just called out two NAD co-enzymes. I I just called out two NAD co-enzymes. I I just called out two NAD co-enzymes. Okay. NAD+ and NADH. Right. Okay. NAD+ and NADH. Right. Okay. NAD+ and NADH. Right. So let's call out the other two which So let's call out the other two which So let's call out the other two which are NADP++ are NADP++ are NADP++ and NADPH and NADPH and NADPH which is which are really really which is which are really really which is which are really really important for anabolism anabolism right important for anabolism anabolism right important for anabolism anabolism right making stuff right so we like to say making stuff right so we like to say making stuff right so we like to say that metabolism that metabolism that metabolism is the set of processes by which we is the set of processes by which we is the set of processes by which we convert everything that we eat into convert everything that we eat into convert everything that we eat into everything that we are and everything everything that we are and everything everything that we are and everything that we do and the maintenance of all of that we do and the maintenance of all of that we do and the maintenance of all of the things that we are and and do, the things that we are and and do, the things that we are and and do, right? right? right? >> So, one of the really amazing things >> So, one of the really amazing things >> So, one of the really amazing things that NAD co-enzymes can do is they can that NAD co-enzymes can do is they can that NAD co-enzymes can do is they can um take the high energy electrons on um take the high energy electrons on um take the high energy electrons on NAD, which is NADH, and get those high NAD, which is NADH, and get those high NAD, which is NADH, and get those high energy electrons put onto NADP energy electrons put onto NADP energy electrons put onto NADP forming NADPH. And then NADPH can forming NADPH. And then NADPH can forming NADPH. And then NADPH can distribute those high energy or direct distribute those high energy or direct distribute those high energy or direct those high energy electrons to do things those high energy electrons to do things those high energy electrons to do things like form carboncarbon bonds, convert like form carboncarbon bonds, convert like form carboncarbon bonds, convert riboucleotides into deoxy riboucleotides into deoxy riboucleotides into deoxy ribboucleotides, ribboucleotides, ribboucleotides, right? So then because we have to make right? So then because we have to make right? So then because we have to make all of our own RNA, we have to make all all of our own RNA, we have to make all all of our own RNA, we have to make all of our own DNA. We have to make all of of our own DNA. We have to make all of of our own DNA. We have to make all of our own lipids. We have to make all of our own lipids. We have to make all of our own lipids. We have to make all of our own proteins, right? We have to make our own proteins, right? We have to make our own proteins, right? We have to make everything in all of our cells and we everything in all of our cells and we everything in all of our cells and we have to repair all of those processes. have to repair all of those processes. have to repair all of those processes. Right? So in in the biggest buckets that Right? So in in the biggest buckets that Right? So in in the biggest buckets that I can describe to to not get into the I can describe to to not get into the I can describe to to not get into the specificity initially, the biggest specificity initially, the biggest specificity initially, the biggest buckets are converting fuel into ATP, buckets are converting fuel into ATP, buckets are converting fuel into ATP, right? Um building stuff right? Um building stuff right? Um building stuff and repairing stuff. Those are the three and repairing stuff. Those are the three and repairing stuff. Those are the three biggest buckets in which NAD co-enzymes biggest buckets in which NAD co-enzymes biggest buckets in which NAD co-enzymes are critical. I think that's a pretty are critical. I think that's a pretty are critical. I think that's a pretty good explanation and hopefully um that good explanation and hopefully um that good explanation and hopefully um that makes sense to people. I think you know makes sense to people. I think you know makes sense to people. I think you know we're about to get into the NAD biology we're about to get into the NAD biology we're about to get into the NAD biology and you've described it as this and you've described it as this and you've described it as this rechargeable molecule. Um I think I rechargeable molecule. Um I think I rechargeable molecule. Um I think I think that a lot of people have heard of think that a lot of people have heard of think that a lot of people have heard of energy production, mitochondrial energy energy production, mitochondrial energy energy production, mitochondrial energy production, DNA repair, gene regulation. production, DNA repair, gene regulation. production, DNA repair, gene regulation. So you talked a little bit about this So you talked a little bit about this So you talked a little bit about this mitochondrial energy production, mitochondrial energy production, mitochondrial energy production, >> right? How does NAD play a role in the >> right? How does NAD play a role in the >> right? How does NAD play a role in the repair process and also in the gene repair process and also in the gene repair process and also in the gene regulation process? These are like some regulation process? These are like some regulation process? These are like some other important aspects of NAD. other important aspects of NAD. other important aspects of NAD. >> Well, um, repair is a really big bucket, >> Well, um, repair is a really big bucket, >> Well, um, repair is a really big bucket, right? And so part of repair is right? And so part of repair is right? And so part of repair is reynthesis, reynthesis, reynthesis, right? So part of repair like if if if I right? So part of repair like if if if I right? So part of repair like if if if I were to cut myself then um or I I don't were to cut myself then um or I I don't were to cut myself then um or I I don't cut myself but if I were to but I cut myself but if I were to but I cut myself but if I were to but I constantly get into cuts and and and constantly get into cuts and and and constantly get into cuts and and and scrapes and um we all we all do and um scrapes and um we all we all do and um scrapes and um we all we all do and um so we have to make make more lipids. We so we have to make make more lipids. We so we have to make make more lipids. We have to make more nucleic acids and so have to make more nucleic acids and so have to make more nucleic acids and so that depends on NADPH. that depends on NADPH. that depends on NADPH. So that's an example where we take fuel So that's an example where we take fuel So that's an example where we take fuel oxidation oxidation oxidation and then we put the high energy and then we put the high energy and then we put the high energy electrons onto NADP forming NADPH and we electrons onto NADP forming NADPH and we electrons onto NADP forming NADPH and we can make more lipids. So you can make can make more lipids. So you can make can make more lipids. So you can make more cell membranes and you can make more cell membranes and you can make more cell membranes and you can make more nucleic acids and you can basically more nucleic acids and you can basically more nucleic acids and you can basically make more cells. Um but in addition make more cells. Um but in addition make more cells. Um but in addition because we live in an oxygen environment because we live in an oxygen environment because we live in an oxygen environment um there's always reactive oxygen um there's always reactive oxygen um there's always reactive oxygen species being made and the species being made and the species being made and the detoxification detoxification detoxification of react reactive oxygen species also of react reactive oxygen species also of react reactive oxygen species also depends on entity pH depends on entity pH depends on entity pH >> and what about so you know you're >> and what about so you know you're >> and what about so you know you're talking about oxidation oxidation's also talking about oxidation oxidation's also talking about oxidation oxidation's also formed as a byproduct of metabolism formed as a byproduct of metabolism formed as a byproduct of metabolism right as well right as well right as well >> and um you know a lot of these oxidation >> and um you know a lot of these oxidation >> and um you know a lot of these oxidation products can damage mitochondria, which products can damage mitochondria, which products can damage mitochondria, which have to be repaired, but they can also have to be repaired, but they can also have to be repaired, but they can also damage our DNA. Y and as people that damage our DNA. Y and as people that damage our DNA. Y and as people that have listened to this podcast before have listened to this podcast before have listened to this podcast before know, DNA damage can be a precursor to know, DNA damage can be a precursor to know, DNA damage can be a precursor to encogenic mutations that cause cancer, encogenic mutations that cause cancer, encogenic mutations that cause cancer, particularly if they're double stranded particularly if they're double stranded particularly if they're double stranded breaks, particularly if the double breaks, particularly if the double breaks, particularly if the double stranded breaks occur in parts of the stranded breaks occur in parts of the stranded breaks occur in parts of the genome that allow for an encogenic genome that allow for an encogenic genome that allow for an encogenic mutation to occur. mutation to occur. mutation to occur. >> So what about the role of NAD in >> So what about the role of NAD in >> So what about the role of NAD in repairing DNA damage? So I think about repairing DNA damage? So I think about repairing DNA damage? So I think about for example PARP. Yeah. So part one is for example PARP. Yeah. So part one is for example PARP. Yeah. So part one is incredibly important. It's a huge NAD incredibly important. It's a huge NAD incredibly important. It's a huge NAD consumer and this is the first time I consumer and this is the first time I consumer and this is the first time I word used the word consumer this word used the word consumer this word used the word consumer this morning. So in in in the N in the morning. So in in in the N in the morning. So in in in the N in the classic NAD co-enzyme function high classic NAD co-enzyme function high classic NAD co-enzyme function high energy electrons are being basically energy electrons are being basically energy electrons are being basically transferred onto NAD forming NADH. NADH transferred onto NAD forming NADH. NADH transferred onto NAD forming NADH. NADH can become can basically distribute can become can basically distribute can become can basically distribute those electrons again which reoxidizes those electrons again which reoxidizes those electrons again which reoxidizes it to NAD+. The same thing happens with it to NAD+. The same thing happens with it to NAD+. The same thing happens with NADP+ and NADPH. NADP+ and NADPH. NADP+ and NADPH. But when an enzyme, an NAD dependent But when an enzyme, an NAD dependent But when an enzyme, an NAD dependent enzyme called PARP one sees DNA damage, enzyme called PARP one sees DNA damage, enzyme called PARP one sees DNA damage, it basically gets excited if enzymes get it basically gets excited if enzymes get it basically gets excited if enzymes get excited and um it actually starts excited and um it actually starts excited and um it actually starts churning NAD and forming a polymer. churning NAD and forming a polymer. churning NAD and forming a polymer. It's kind of a weird ribboucleic acid It's kind of a weird ribboucleic acid It's kind of a weird ribboucleic acid polymer that consists of ADP ribos that polymer that consists of ADP ribos that polymer that consists of ADP ribos that is polymerized. It can form a polyadp is polymerized. It can form a polyadp is polymerized. It can form a polyadp ribos polymer um that is linked to ribos polymer um that is linked to ribos polymer um that is linked to protein. It can form a poly ADP ribos protein. It can form a poly ADP ribos protein. It can form a poly ADP ribos primer just in the nucleus. primer just in the nucleus. primer just in the nucleus. And that's a signal that assembles a And that's a signal that assembles a And that's a signal that assembles a bunch of DNA repair enzymes to localize bunch of DNA repair enzymes to localize bunch of DNA repair enzymes to localize at a particular point and get that DNA at a particular point and get that DNA at a particular point and get that DNA repaired. and and then there's a point repaired. and and then there's a point repaired. and and then there's a point at which DNA repair sort of can't be at which DNA repair sort of can't be at which DNA repair sort of can't be done and then some of these signaling done and then some of these signaling done and then some of these signaling processes can essentially induce cell processes can essentially induce cell processes can essentially induce cell death in order to eliminate the cell death in order to eliminate the cell death in order to eliminate the cell because in a big organism like like us because in a big organism like like us because in a big organism like like us with 37 trillion cells or however many with 37 trillion cells or however many with 37 trillion cells or however many we have um we can it's better for us to we have um we can it's better for us to we have um we can it's better for us to lose some cells than to try to repair lose some cells than to try to repair lose some cells than to try to repair everything, Right. So, you already everything, Right. So, you already everything, Right. So, you already described, you know, a a few very, very described, you know, a a few very, very described, you know, a a few very, very important, you know, biological important, you know, biological important, you know, biological processes in our bodies that I think processes in our bodies that I think processes in our bodies that I think people can kind of gravitate to. We're people can kind of gravitate to. We're people can kind of gravitate to. We're talking about energy production talking about energy production talking about energy production >> is essential for everything. >> is essential for everything. >> is essential for everything. >> Yeah. >> Yeah. >> Yeah. >> You're talking about repairing, you >> You're talking about repairing, you >> You're talking about repairing, you know, damage at the cellular level, know, damage at the cellular level, know, damage at the cellular level, being able to like make new cells, but being able to like make new cells, but being able to like make new cells, but also repairing damage to DNA and how also repairing damage to DNA and how also repairing damage to DNA and how these very important enzymes that do these very important enzymes that do these very important enzymes that do that consume NAD. we have other enzymes that consume NAD. we have other enzymes that consume NAD. we have other enzymes that are involved in regulating our that are involved in regulating our that are involved in regulating our genes, right? Making sure they're active genes, right? Making sure they're active genes, right? Making sure they're active or not active and you know, so that's or not active and you know, so that's or not active and you know, so that's another role of NAD. Do you want to another role of NAD. Do you want to another role of NAD. Do you want to touch on that for a minute and then I touch on that for a minute and then I touch on that for a minute and then I have another follow-up question? have another follow-up question? have another follow-up question? >> Yeah. Yeah. So, so in in this in this um >> Yeah. Yeah. So, so in in this in this um >> Yeah. Yeah. So, so in in this in this um area of NAD consuming enzymes, there's area of NAD consuming enzymes, there's area of NAD consuming enzymes, there's PARPs. PARP one was kind of the first PARPs. PARP one was kind of the first PARPs. PARP one was kind of the first one that was described, but there one that was described, but there one that was described, but there another 15 or 16 members of the PARP another 15 or 16 members of the PARP another 15 or 16 members of the PARP super family. Many of them don't super family. Many of them don't super family. Many of them don't polymerize ADP ribos, but they modify polymerize ADP ribos, but they modify polymerize ADP ribos, but they modify proteins with ADP ribos. So they they proteins with ADP ribos. So they they proteins with ADP ribos. So they they they cut NAD and they add an ADP ribos they cut NAD and they add an ADP ribos they cut NAD and they add an ADP ribos unit on something to do a signaling unit on something to do a signaling unit on something to do a signaling reaction. Um there's enzymes called reaction. Um there's enzymes called reaction. Um there's enzymes called certuins that use NAD. certuins that use NAD. certuins that use NAD. Um they very often remove a small Um they very often remove a small Um they very often remove a small modification on protein lysines. So modification on protein lysines. So modification on protein lysines. So acetil modifications on lysines, asil acetil modifications on lysines, asil acetil modifications on lysines, asil groups on lysines, suanil groups on groups on lysines, suanil groups on groups on lysines, suanil groups on lysines. That's usually something to do lysines. That's usually something to do lysines. That's usually something to do with enzyme regulation, gene regulation. with enzyme regulation, gene regulation. with enzyme regulation, gene regulation. As you said, classically, there's a lot As you said, classically, there's a lot As you said, classically, there's a lot of gene silencing that is done with with of gene silencing that is done with with of gene silencing that is done with with uh this this reaction. Um there's also uh this this reaction. Um there's also uh this this reaction. Um there's also things like ADP ribosyes. things like ADP ribosyes. things like ADP ribosyes. There's a there's enzymes that can take There's a there's enzymes that can take There's a there's enzymes that can take NAD and kick off the nicotenomide group NAD and kick off the nicotenomide group NAD and kick off the nicotenomide group and then cyize the ADP ribos. And and then cyize the ADP ribos. And and then cyize the ADP ribos. And usually what that is doing is releasing usually what that is doing is releasing usually what that is doing is releasing calcium from an intracellular store like calcium from an intracellular store like calcium from an intracellular store like the endopplasmic reticulum in order to the endopplasmic reticulum in order to the endopplasmic reticulum in order to do some kind of a signaling reaction. do some kind of a signaling reaction. do some kind of a signaling reaction. >> So the question is you know if all these >> So the question is you know if all these >> So the question is you know if all these really important functions are NAD is really important functions are NAD is really important functions are NAD is central to them. central to them. central to them. >> Yes. >> Yes. >> Yes. >> Right. >> Right. >> Right. What happens if there's a limiting What happens if there's a limiting What happens if there's a limiting amount of NAD? Like how does the body amount of NAD? Like how does the body amount of NAD? Like how does the body triage or does the body triage? Who gets triage or does the body triage? Who gets triage or does the body triage? Who gets the NAD pool? How do we know if we're the NAD pool? How do we know if we're the NAD pool? How do we know if we're able to make enough NAD? Like where able to make enough NAD? Like where able to make enough NAD? Like where where like what's the bottleneck here? where like what's the bottleneck here? where like what's the bottleneck here? So um you know the full systems analysis So um you know the full systems analysis So um you know the full systems analysis of it is not fully understood right and of it is not fully understood right and of it is not fully understood right and I'm not the type of person that is going I'm not the type of person that is going I'm not the type of person that is going to claim to know things that are that to claim to know things that are that to claim to know things that are that are not known. So what is generally are not known. So what is generally are not known. So what is generally understood understood understood which is easy to determine from gene which is easy to determine from gene which is easy to determine from gene expression patterns is that certain expression patterns is that certain expression patterns is that certain tissues like the liver can make NAD from tissues like the liver can make NAD from tissues like the liver can make NAD from tryptophan tryptophan tryptophan nicotenomide ribocide nicotenomide and nicotenomide ribocide nicotenomide and nicotenomide ribocide nicotenomide and nicotinic acid. So any precursor nicotinic acid. So any precursor nicotinic acid. So any precursor they can make NAD and they um there are they can make NAD and they um there are they can make NAD and they um there are processes in the aging liver that processes in the aging liver that processes in the aging liver that disturb that system. Alcoholism can disturb that system. Alcoholism can disturb that system. Alcoholism can disturb that system. Over nutrition can disturb that system. Over nutrition can disturb that system. Over nutrition can disturb that system. But it's actually a disturb that system. But it's actually a disturb that system. But it's actually a fairly robust system. And and that liver fairly robust system. And and that liver fairly robust system. And and that liver tends to be a very generous organ. it tends to be a very generous organ. it tends to be a very generous organ. it actually distributes things for other actually distributes things for other actually distributes things for other tissues. tissues. tissues. But um the more concerning thing is in But um the more concerning thing is in But um the more concerning thing is in cells like neurons right where if they cells like neurons right where if they cells like neurons right where if they don't have a pathway to make NAD from don't have a pathway to make NAD from don't have a pathway to make NAD from tryptophan tryptophan tryptophan and they generally don't have a pathway and they generally don't have a pathway and they generally don't have a pathway to make NAD from nicotinic acid then to make NAD from nicotinic acid then to make NAD from nicotinic acid then what happens in a neuron that has high what happens in a neuron that has high what happens in a neuron that has high bioenergetic requirements if it starts bioenergetic requirements if it starts bioenergetic requirements if it starts losing expression of one or the other losing expression of one or the other losing expression of one or the other pathways and you get a lot of, you know, pathways and you get a lot of, you know, pathways and you get a lot of, you know, cell and tissue dysfunction in those cell and tissue dysfunction in those cell and tissue dysfunction in those conditions. There's a lot of disease conditions. There's a lot of disease conditions. There's a lot of disease processes that disturb the NAD system. processes that disturb the NAD system. processes that disturb the NAD system. Well, this is