EFR 791: Why Aging is Not a Disease, Debunking Longevity Claims, SIRT 2 and SIRTUINS, the Benefits of NAD, and "Podcast Disease" with Dr. Charles Brenner

00:00 - Speaker 1 The following is an Operation Podcast production. What is the difference between longevity and anti-aging? Is aging a disease? Do you view those two? Things differently at all.

00:09 - Speaker 2 No, no, aging is not a disease. Humans are very good agers. It is a fundamental feature of life. I don't think there's any evidence that there's a technology that's going to allow people to extend maximal human lifespan, but I do think that there are things that we can do that will allow us to age better. Resveratrol is probably the you know the biggest stench. It's garbage.

00:36 Are there examples in mammalian biology where single genes can extend lifespan? Yes, would you want to have those genes. Would you want to have your growth hormone pathway inactivated? No, you would not. So SIRT2 is like the founding member of a gene family called SIRT2ins. They are not longevity genes.

00:56 - Speaker 1 We could summarize our conversation and boil it down to one statement about NAD. What would it be?

01:04 - Speaker 2 NADs. This is Dr Charles Brenner. I'm a professor at City of Hope in Duarte, california, and it was super fun to be here on Ever.

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03:08 Hey, what's up everybody? Welcome back to Ever Forward Radio. I am so grateful you are here. Thank you for tuning in If you have not yet done so on your podcast platform of choice, tapping that follow button or subscribe if you're watching tuning in on YouTube. It does a couple things. One, it really really does support the show in a big, big way. It helps us grow. It helps us expand production. It helps us get even more amazing guests, like today with Dr Charles Brenner. It also, too, is going to make sure that you never miss another amazing episode If you are interested in learning how to move forward in key areas of your life, your wellness, learn how to move ever forward, then this is the podcast for you.

03:46 Dr Brenner is a professor at City of Hope in Duarte, california. He sat down with me in studio here, so if you want to check out the video, I'll have it linked for you down at the bottom. You can always find us on YouTube. Just search Ever Forward Radio or post it at everforwardradiocom. And this conversation. It was a lot of fun.

04:03 He pushed back a little bit. I was challenged in terms of some concepts that I have heard and I'd be willing to bet you have too on a lot of other platforms podcasts and this is the cool thing about science is that we always need to be challenging it, we need to be testing it, we need to be retesting it, because what we might find to be true air quote here true now, a year, 10 years down the road, might not still be the case. Always do your own research. N equals one is a concept I drive home hard today, but we're going to be exploring the nuances between longevity and anti-aging and whether aging itself should be classified as a disease or not.

04:44 Charles is going to share his expert perspective on the fundamental aspects of aging as an inherent feature of animal life, even debunking common misconceptions around our ability to extend a maximal human lifespan, but also he's going to shift our focus towards maintaining our capacities physical, mental and emotional throughout our adult lives. Whatever you can do, whatever you can do consistently, is really what matters most. We're going to be hitting on the controversial topic of resveratrol, talking about growth hormone pathways and sirtuins, and even what's all the buzz around NAD in the realm of longevity wellness optimization. All this and more is waiting for you in today's episode. Charlie, great to have you here. Thank you so much. Yeah, my pleasure. What is the difference between longevity and anti-aging? Is aging a disease? Do you view those two things differently at all?

05:37 - Speaker 2 No, no, aging is not a disease. Aging is a fundamental feature of animal life. But as far as mammals are concerned, you know particular mammalian species, all have a distribution, a normal distribution, in which we get to sexual maturity and then some animals are able to maintain their capacity as adults for a long period of time. Some animals basically reproduce once, one and done right and really don't have a whole lot of longevity. Humans are very good agers. Aging isn't a disease, it is a fundamental feature of life. I mean, I consider the part of life between fertilization of an egg and through our puberty and reaching sexual maturity. I consider that a component of aging. And then what we're trying to do is we're trying to maintain our capacity for as long as possible, be able to provide for others, be able to run, you know, a mile and get up stairs and think hard problems and do hard things. And we do lose capacity as we age beyond our sexual maturation.

07:01 - Speaker 1 When you say capacity, what exactly are you referring to? In the human experience, we're trying to maintain our capacity. What is?

07:07 - Speaker 2 that, you know it means that you're not going to um. Your 70 year old self is not going to, you know, will beat your seven-year-old self at a game of chess, right.

07:35 But there are, you know, there's capacities, right, there's abilities physical, mental, and so we mature physically, we mature mentally and emotionally Right, different rates and then, basically, when we're adults, we're trying to maintain our functions Right. So we're trying to maintain our physical functions, we're trying to retain our mental capacity, and so that's what healthy aging is, and so I'm very interested in, you know, in longevity, as, as as most most people are, I don't think there's any evidence that there's a technology that's going to allow people to extend maximal human lifespan. I don't either consider aging a disease, but I do think that there are things that we can do that will allow us to age better.

08:34 - Speaker 1 And we're going to get there, absolutely. But while we're still on the topic of longevity and anti-aging when do we start aging and is there an age or age period that is the ideal time to begin adopting anti-aging habits?

08:51 - Speaker 2 you think okay, so I'm not fully comfortable with the word anti-aging, um, because I don't quite know what you mean by it. Um, I'm do any of us really know what you mean by it.

09:05 - Speaker 1 Do any of us really know what we mean by it? The reason I bring it up is because it is so top of mind. Did I even say trendy right now? And I'll be totally honest, I think about the concept of anti-aging pretty often. It's very much a part of my personal and professional world, so please enlighten us.

09:22 - Speaker 2 If it's maintaining repair capacity and maintaining our power and our function, then I'm all for it.

09:30 - Speaker 1 Right If it's a counterfactual narrative that we don't have to age you know, this is probably under the belief that some people have, or some people claim that aging is in fact a disease, but your stance is that aging is not a disease.

09:52 - Speaker 4 So therefore, anti-aging is not really what we think it is Well the, the.

09:54 - Speaker 2 The first of all, anti-aging is um. It's just a sort of a hazardous term and it means a lot of different things, right? So um, anti-aging is kind of like a. Um is a is a marketing term for cosmetics and for um. You know procedures in a, in a, in a in a skincare clinic or med spa that um don't fundamentally change very much, right? So you can take, you know, botulinum toxin, right, botox, right, and you can take an injection into a neuromuscular junction, right, and you can get a forehead so that it doesn't show wrinkles. Right, and?

10:49 - Speaker 1 so you can improve people's, and people think that as anti-aging.

10:51 - Speaker 2 Right. I mean that is an anti-aging treatment, right. It certainly doesn't affect a root cause of aging. The anti-aging category is such a big thing, so in part it includes things like that that are superficial right. In part it includes things that are totally counterfactual right. What would be an example of that in your opinion?

11:25 - Speaker 1 Resveratrol is probably the biggest stench out there. Open that up for us a little bit, please, because I remember about 20 years ago, when I was starting my 20, 21 years ago, starting my personal wellness journey, resveratrol was the shit. It was the biggest keyword. It was popping in all the key supplements and the brands that I was looking at, and it was this promise that we have cracked the aging code. It is going to I I might be paraphrasing some stuff here, but I even think, like you know, increasing telomere length and increasing the quality of like everything at the cellular level, reducing aging, adding quality and quantity years to your life. How'd that turn out? Well, now we see we have the science right. Well, like 10, 15, 20 years later, it's really, it's kind of falling flat it's garbage, okay, wow, so.

12:09 - Speaker 2 So I mean, all right. So resveratrol was a known natural product for for a very long time, right, um? By the way, it's not only in, you know, red wine, it's it's in peanuts, peanuts, no it Peanuts, no, it's in a lot of plants.

12:27 It's a phytonutrient, okay, and you know it's a polyphenolic compound. It has some mild antioxidant properties. It's related to a lot of other compounds and, um, and certainly you know it's in red wine, right, um and so, um, it was described in, I think, a 2003, if I have the the year right paper yeah, nature paper as an activator of a particular enzyme. Okay, there's a yeast enzyme called SIRT2. There's a human version called SIRT1, s-i-r-t-1. And the report was that resveratrol, as well as a number of other molecules, increased the activity of this enzyme. It was a biochemical assay, okay, it didn't actually increase the activity of the SIRT2 enzyme, didn't actually increase the activity of the SIRT1 enzyme, and even increasing the activity of the SIR2 enzyme only extends lifespan for one out of five million yeast cells. How interested in that are you? Hold up so?

13:52 - Speaker 1 how can this be? Is this only because now we have years to look at the data? How can we go from something that is discovered and is so widely accepted to bullshit? In one word hype. It was all, all hype. You're saying. There was no scientific data.

14:07 - Speaker 2 So so some of it was honest mistakes, um, but um, the the fact that it was so it's called a biochemical artifact, right, which means that um, let's say, um, let's say we identify, you know, a drug target. You know, you told me that you know one of your most popular, you know episodes was about nitric oxide.

14:36 Nitric oxide- synthase Shout out to Dr Liu Right, okay, let's say, somebody wants to inhibit nitric oxide synthase or somebody wants to activate nitric oxide synthase right, for you know something about, you know erections or something about cancer, whatever it is that they want to do, right. So they identify a particular enzyme and they say, okay, so we want drugs to whatever they decide to do. They want to inhibit the enzyme, they want to activate the enzyme Okay, so they're going to set up a biochemical experiment in which they want to see whether these small molecules interact. Right, and you know, you, you can't see enzymes under a microscope. They're too small.

15:29 Okay, so you have to link them to something that generates a fluorescent signal, an optical signal. We're going to do something where the enzyme does something, and then yada, yada, yada, you get a fluorescent signal. Okay, and then you have to do controls. Okay, you have to make sure that the drug candidate, in this case resveratrol, which was reported to be a SIRT2 activator you have to do controls to make sure that it wasn't just affecting the assay. There's something happens at the level of the enzyme, then there's yada, yada, yada and then you get a fluorescent signal. Okay, by within one year of the Nature paper that reported that resveratrol is an activator of SIRT2 and SIRT1,. It was already reported by two different groups that it was a fluorescent artifact.

16:40 So in one year it basically fell Within one year biochemists already knew that resveratrol was not hitting its target, that it was disturbing the fluorescent assay that was being used to measure the enzyme activity.

16:55 - Speaker 1 I feel like this is the fall of the biochemical Roman Empire. There was so much hype around, even still now.

17:02 - Speaker 2 No, but even still, that's the problem, right so? So biochemists knew that the result was wrong. Okay, um, similar at the same time. Okay, there was this. The SIR2 gene is a dominantly acting monogenic longevity gene in everything from yeast to people.

17:32 - Speaker 1 Okay, in layman's terms, okay.

17:35 - Speaker 2 That's a lot of vocabulary there. So longevity is basically how long an organism lives right and like. Worms live for, let's say, three weeks and flies may live for two months and mice live for, you know, two, three years and people live on average 80 some years, with maximum credible data saying that somebody lived to 122, right, and very few people live into 100, 110. And so there are, as we were saying before we started, there are some rare genes in mice where you inactivate a single gene and you get a very long-lived mouse but it inactivates genes in growth factor pathways, right Pituitary pathways.

18:35 - Speaker 1 And these mice Meaning. The physical maturation of the animal is limited.

18:40 - Speaker 2 Yeah, if you disrupt growth factor or growth factor receptor, you can get tiny mice that cannot do thermoregulation, they can't keep themselves warm, they can't compete for food and they don't sexually mature, but they do live twice as long. If you separate them and you give them adopted sisters to keep them warm and you make sure they have enough food, they can live twice as long as normal mice. So that's what's called a monogenic longevity gene. Okay, okay that you inactivate a single gene, both copies, actually you inactivate both copies, you can get a very long lived mouse. Is that a way to live, by the way?

19:28 - Speaker 1 Absolutely, I feel. I feel sorry for the mouse. I mean, yeah, well, two, three more years of life, but at what cost?

19:34 - Speaker 2 Right, I mean, and there are actually people with mutations in this pathway. There it's called Laron syndrome.

19:42 - Speaker 1 They're very small and they don't dwarfism yeah, it's a type of even smaller than that no, it's a type of uh, these are called dwarf mice because this was the uh, the study that I was pulling up. Actually, I found, um this work by dr david sinclair talking about this and it really made me pause to think to your point. Yeah, you found this mutation.

20:06 - Speaker 2 These and these dwarf mice are able to snip it okay, but then they live longer but, okay, so we're doing. We're doing nuance. Now, right, are we doing nuance?

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23:04 - Speaker 2 Yeah. So is it true that there are some genes in a mouse that will extend its lifespan? Yes, okay, is it, and it's cancer free, so in some ways looks good. But does it involve healthy function? No, they can't thermoregulate, they don't sexually mature, they can't compete for food. The people with this mutation don't actually live longer. Right, so it's so.

23:38 Are there examples in you know, from from mammalian biology, where single genes can extend lifespan? Yes, would you want to have those genes? Would you want to have your growth hormone pathway inactivated? No, you would not, right, because you would not have muscle mass, you would not have sexually matured, you would not be able to compete for food, you would not be, you know, married to a very capable nurse practitioner, as you've told me, right, yes, she is, and so all of those things right. So, on the other hand, you know, if there were single genes that were really beneficial for life, that were dominantly acting, right, we would all want those genes, right. So for about 25 years we've been told that a class of genes called sirtuins are those genes right? And the initial report came out of the 1990s, right, in a very productive, you know, yeast molecular biology lab that showed that extra copies of a gene called SIR2 extended one type of lifespan in yeast right.

25:10 - Speaker 1 What do you mean? One type of lifespan.

25:12 - Speaker 2 Okay, so the yeast is baker's yeast, right? Just before driving down here to Santa Monica, I put together the you know the dough for tonight's dinner, right? So the same organism, saccharomyces cerevisiae, baker's yeast. And so you can monitor aging of yeast in two different ways. One of them is basically under a microscope, where you take a new cell and you see how many times it can divide and produce what are called daughter cells. So you're looking at, you know you? Basically you have to kind of install a graduate student or a postdoc in front of a microscope for two weeks, right? And every first they array these yeast cells, single cell. It's like it's not an animal, okay.

26:16 It's a single cell fungus, even as far as fungi are concerned, it's a very simplistic model, okay, and I don't have anything against yeast. I actually started my career doing yeast molecular biology, so that's why I understand these models so well, and we've done them in our own lab as well. We just don't over-interpret the results. So you are following the number of times you know a single cell will divide, right, and the observation was that if you give them extra copies of this SIR2 gene, that rather than dividing about 21 times, they will divide around 25 or 26 times. Okay, so that's, that's good, but that's only for the oldest mothers in the culture, because if you go back to the culture, right, so think about you know, a flask of yeast, right? Or the yeast that is growing in the pizza dough that is sitting on my countertop right now. 50% of the cells are new cells that have never been a mother.

27:38 - Speaker 1 I see Right. I see Right 50% of them are new cells.

27:41 - Speaker 2 Yeah, 25% of the cells have divided one time. Right One out of eight of the cells have divided two times.

27:53 - Speaker 1 Insert that Galifianakis hangover math scene here Right, right.

27:58 - Speaker 2 So it turns out the advantage of having extra copies of SIRT2 advantages one out of five million cells and you can regenerate the culture from any one cell. So it's what we call, not a selected trade, okay, so it's interesting that sir 2 does something for that yeast, old mother yeast cell that it can divide four or five more times when it's produced a lot of daughters, wow, but it's totally irrelevant. Wow for animal life totally irrelevant, okay.

28:38 So what I'm hearing in this is, I think, a huge sir 2 is not even a good target, right, right, even a good target for what you would want, what you care about in terms of animal aging. What matters in animal aging is tens of thousands of thousands, if not tens of thousands, of different genes interacting with each other, not the SIRT1 gene. And when people initially said, okay, let's see if SIRT2-related genes are important in worms and flies, they initially reported that extra copies of the worm and fly SIRT gene extends lifespan in worm and flies, which is mind-blowing to me. That a yeast gene that's not even important until there's millions of offspring, that that somehow anticipates the causes of aging in animals, that would be mind-blowing to me. Yeah, and guess what? It's not true. Wow.

29:46 And so, just as the resveratrol thing was not reproducible and was an artifact, the idea that cert one homologues and worms and flies extend lifespan is non-reproducible. And when, literally something like 10 years later, after the initial reports that SIRT genes extend lifespan in worms and flies, when that was repeated by a group of investigators that carefully looked at the strain backgrounds, the effect went away, went away, went away. So that means anybody that is writing books into you know, 2019, or is on podcasts in 2023, or is on Instagram in 2024. That is telling you that sirtuins are longevity genes and that resveratrol is an activator of longevity genes, is intentionally obfuscating and spreading debunked information.

31:01 - Speaker 1 A few of those come to mind. A few of those people come to mind.

31:04 - Speaker 2 That's the problem here, because those people have a massive amount of influence and their ideas are essentially non-falsifiable.

31:15 - Speaker 1 Okay, Well, couldn't you say that at the time and the few that come to mind that we talked about, off air anybody who's interested in longevity? You could probably just research and figure out um, the bigger names out there Did. Were they not just going off of the best data, the best science that they had at the time and coming to the best conclusion, and unbeknownst to them, a year, several years later? This really isn't holding the same weight. So like what fault can we place on them? Or is it just a matter of science needs to out science, old science kind of thing? We just got to wait it out.

31:51 - Speaker 2 It's. It's a brutally difficult problem to solve right now because there are like in late 2022,. I wrote a comprehensive review of this topic entitled Sirtuins are not conserved longevity genes, and I went all the way back through the original data and I described how the SIRT2 gene was discovered in 1975, actually Really, yeah. But from the mid-1970s and the work of Jasper Rhein and Ira Herskowitz, it was known that the SIR2 gene regulates mating type in yeast. Okay, you probably didn't know this. Um, you know yeast has. Yeast is really interesting. Um, it sounds like yeast is cool, it's cool.

32:53 It's not relevant to human aging. Actually it is relevant to to human cell cycle and cancer biology that we use for bread, beer, wine. People have been carrying it around in, you know, in clay pots for thousands of years. Right Ur, where you know, the father of the Abrahamic religions, right, abraham was from, you know, mesopotamia, modern-day Iraq, between the Tigris and Euphrates rivers.

33:34 - Speaker 1 The Fertile Crescent baby.

33:35 - Speaker 2 Right, that's right. He was from a city called Ur Okay, and you can find artwork from Ur where there are basically crocks and people are drinking some type of fermented beverage I don't know if it was more like a beer or more like a wine.

33:52 - Speaker 1 Oh, my money's on Koukian. Have you read the immortality key? That's a whole nother tangent, but you familiar with it. If I say Koukian, do you know what I'm talking about? No, I don't. All right, I got a book for you.

34:06 - Speaker 2 Okay, I got a book for you. Okay, everybody check out the immortality, but but basically we've been carrying around yeast and you know, in in in pottery for thousands of years, right, we've been cultivating yeast and yeast helped cultivate and civilize us, just as, in the same way that you know growing grains and growing rice and figuring out agriculture and figuring out, you know transportation led to, you know, advanced civilization, right, and you're saying even so.

34:31 - Speaker 1 So we've had times this was present and aware of and people were actually making sure to have it on them People had.

34:38 - Speaker 2 they didn't know how it worked, but so yeast is cool. Yeast is cool. So so so. So there's there's a diploid phase of yeast, there's a haploid phase of yeast and the SIR2 gene was discovered in the 1970s. Sir2, it actually stands for silent information, regulator Okay, regulator, okay, and it basically the SIR2 gene has a role in turning off a particular gene.

35:14 - Speaker 1 So that a haploid cell can mate. It's actually from my own understanding, and maybe the audience. When we say SIR2 and SIR2N, are these the same things?

35:21 - Speaker 2 SIR2N is like a family of related genes.

35:24 - Speaker 1 Okay, right, because that was the term for me and they're involved in epigenetic regulation. Are these the same things? Sirtuin is like a family of related genes.

35:28 - Speaker 2 Okay, right, because that was the term for me, and they're involved in epigenetic regulation.

35:30 - Speaker 1 Okay, so, but it's not the same thing, but similar.

35:33 - Speaker 2 No, so Sirtuin is, like the founding, member of a gene family called Sirtuins. Okay, right, okay, okay, they are not longevity genes. That doesn't mean that they're not interesting. Like I'm saying, they're involved in gene regulation, but they don't do magical things in all of our cells. They don't promote longevity in animals. Resveratrol doesn't activate them. They don't mediate the beneficial effects of NAD boosting.

36:06 - Speaker 1 You know, they're there, sounds like a lot of what I've heard them described to do Right, right Interesting. Today's episode is brought to you by Blokes, modern Men's Health and their Complete Hormone Panel. For less than $100, guys, you can analyze 44 key biomarkers to your health, aging, metabolism, sex drive and so much more. Simply put, it all comes down to our hormones, and the Complete Hormone Lab Panel provides a comprehensive examination of 44 key markers. You'll get insights into why you may be functioning at a lower level than normal and where to go from there. It's extremely convenient. Some cities they can even schedule a phlebotomist to come to your house. It takes a matter of minutes. I've done it myself multiple times. Or you can go to a convenient location in your city. Then, really just a few days later, you're gonna get your results, gonna go over it with a healthcare provider. You're gonna get an accurate and optimal interpretation of where you land. Your results are your results. They're gonna help you figure out what exactly they mean and how optimizing them can fit into your lifestyle or recommend key supplementation.

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38:03 - Speaker 2 A lot of you know, what I've had to do in the last few years is to try to, you know, set the record straight. I mean, nad is important because NAD is the central catalyst of metabolism and metabolism is converting everything that we eat into everything that we do and everything that we are. And NAD is a carrier of high energy electrons that allow us to generate ATP and allow us to make nucleotides and lipids and repair ourselves.

38:39 - Speaker 1 And we're here. Yeah, can we please? I wanted to transition definitely into NAD and since we're already here before, I kind of let you finish that train of thought, excuse the interruption. Can we define NAD? What is it? Why should we care about it?

38:54 - Speaker 2 adenine dinucleotide. Okay, it's actually four different coenzymes. These are small molecules. They're not proteins, they're not nucleic acids, they're not lipids, but they're. They're coenzymes that are required to make all of those things Okay. So what they do is it's a dinucleotide, so it contains something that's related to ATP, and then it contains something related to nicotinamide, which is a vitamin. Okay, related to nicotinamide, which is a vitamin. Okay, one of the cycles of life is that we all living now I'm going to embrace all living things bacteria and and plants and and fungi and animals all living things need a source of energy, right? Most of the living things that we're familiar with are what are called autotrophic or, I'm sorry, are heterotrophic, which means that we get energy from outside, right?

40:21 - Speaker 1 So we, we don't autonomously create the energy necessary for capacity for life.

40:34 - Speaker 2 Right, that's right. So we have to consume food, so, so, so here's, here's my, my intro to biology. Okay, okay, my intro to biology is that if we were to step outside of the studio, we would see the sun. Okay, 93 million miles away, right, the sun is sending photons to this planet Earth, right, and the photons are captured by plants. Plants are using that solar energy and carbon dioxide as a carbon source Right, and they're growing plant matter Right, plant protein, plant fat and plant carbohydrate. Then animals come along and eat the plant matter, ok, and we come along and we either eat the plants directly or we eat the animals that eat the plants, and so we're heterotrophs. We're taking in energy, right, that's the circle, because we have to.

41:34 Basically, we have to deal with the fact, the facts of physics right, and physics tells us, the second law of thermodynamics tells us that there is a tendency towards entropy in the universe, and entropy is Entropy, is disorder, billiard table right today. And then we come back after there's time and temperature added to the system, those, those balls, are not going to be where we. They started, right, they're going to be jiggled away. They may be jiggled away a little, they may be jiggled away a lot. That's actually how you can measure time in some sense. Okay, all right, all right.

42:24 - Speaker 1 If I can, not to derail this part too much, but I'm just thinking. Sure that might make sense and I might just be thinking too literal here, but if, if that happened like in a house, someone might say like okay, like vibrations coming in and out of living, yeah, if we took that exact same billiard table, Um in a vacuum.

42:47 - Speaker 2 So I'm not a physicist.

42:49 - Speaker 1 In a suspended place, are we saying that entropy, the natural tendency of entropy, will still exist?

42:55 - Speaker 2 Um. Entropy exists and the only thing that opposes it is an influx of energy. Okay, Okay.

43:04 Okay. So the thing is so living, and people come up to me and they say, well, doesn't a growing, you know animal violate the second law? And the answer is no, it doesn't violate the second law. Like a dividing oocyte going from the one cell stage to the two cell stage, to the 14, 16, as the 4, 16, etc. Stage is actually increasing in complexity and a in a baby is growing and increasing in complexity, right, but all of that requires energy input. Growing things can increase their complexity, right, and we can keep our S together. Right, and we can only self-repair right and keep our S together by the homeostatic forces of life and taking in energy. So we have a complex gene set and we have metabolism that allows us to repair ourselves.

44:17 Okay, nad coenzymes all four NAD coenzymes are the key connection between taking in energy and converting it to biological power in the form of ATP and conforming it to biological materials, the proteins and fats and carbohydrates that build our cells and build our organs and all of our capacity. So NAD coenzymes are the critical wiring of life that carries high energy electrons, that allows life to be possible. And then the connection between NAD and aging is that as we go through life. Our NAD system comes under attack in many different ways. What would be an?

45:16 - Speaker 1 example of that.

45:17 - Speaker 2 So alcohol, you know, being almost the most obvious one. That's something that was known before our lab got into NAD.

45:28 - Speaker 1 How does alcohol affect NAD.

45:30 - Speaker 2 So alcohol metabolism primarily occurs in the liver and ethanol gets converted to acetaldehyde, which is toxic, and then acetaldehyde gets converted into acetate, which is pretty much non-toxic. But in the course of converting ethanol to acetate, nad accepts electrons from the ethanol over two different cycles, over two different cycles, and NAD plus gets converted to NADH and it basically puts the liver into a more lipogenic state. It puts the liver into a state in which it's less able to accept fuel and convert it into energy and it is more capable of converting fuel into fat.

46:34 - Speaker 1 So is this? Am I understanding correctly? Is this fatty liver disease? Is this kind of what happens besides cirrhosis?

46:41 - Speaker 2 So yeah, the initiation of fatty liver is from what's called de novo lipogenesis in hepatocytes, where hepatocytes are taking in fuel right and converting. So there are different things that the hepatocyte can do. Right, the hepatocyte can take in fuels and convert to atp. Right, the hepatocytes can take in fuels and um, like overnight, for example, um there's fatty acids that are being released, that hepatocytes are taking up and to some degree, and the liver is actually trying to make glucose. Overnight the liver is trying to make a primary energy source, one of right, so so.

47:45 So the liver can, can store glucose as glycogen. It can take glycogenic and gluconeogenic precursors. It can produce glucose for the bloodstream. It can produce glycogen that it's stored. It can do all of its biosynthetic processes. It can make and store lipids. It can make and export cholesterol right. It can make, you know, steroid hormones to some degree, um but um, fatty liver, you know a function of overnutrition, right, and also a function of alcohol intake, you know involves a disturbance to the NAD system. That we're very interested in.

48:43 - Speaker 1 So I'm going to do my best to boil that down in a very simple way, my best to boil that down in a very simple way Drinking alcohol directly limits the function of our NAD system in your liver and our liver, which I think most people would kind of like. Yeah, I'm already kind of aware of that, but the direct correlation to NAD dysfunction is immediate in any amount of alcohol.

49:12 - Speaker 2 Oh, you know, I don't want to pathologize life, right, so I you know I'm not going to pathologize aging, right, and I'm not going. I mean, we can go through the list of things that disturb the NAD system. And then we can decide which ones we want to pathologize.

49:35 - Speaker 1 Yeah, let me reign it in. This is where my brain wants to go off.

49:39 - Speaker 2 So? But overnutrition, okay, which is eating too much, yeah, let's bring it back to NAD. So overnutrition disturbs the NAD system. We showed that.

49:48 - Speaker 1 Overnutrition meaning consuming too many calories than necessary.

49:51 - Speaker 2 Yep, so, um, so we? A number of years ago we put mice on on a high fat diet. Um, we gave them obesity. Basically, we pushed them into a mouse model of type two diabetes. We saw their liver NAD system under attack. Okay, in the case of alcoholism, some of that work predated us, but then we showed in humans with alcoholic liver disease, their NAD system in their liver is disturbed. It's been shown that sunlight, you know, our skin is exposed to ultraviolet radiation that damages DNA In that process. You know, nad is used to repair DNA. Okay, I don't want to pathologize sunlight, but ultraviolet radiation is a way to accelerate the aging of the skin. Use sunscreen. Okay, I think there are people on podcasts that have pathologized sunscreen. I think that is not okay.

51:03 I think that's not okay. Sun exposure without sunscreen is responsible for skin cancer and premature aging of skin. There's no question about that.

51:16 - Speaker 1 But you're saying all sun exposure, isn't it? Here's what I've been led to believe. I will say this what I look at in podcasts and influencers and research even is certain times and duration. And research even is certain times and duration. So if I'm outside under the sun between 11 am to 4 pm, we'll say for a long period of time, consistently, day after day, week after week, month after month, boom, potentially skin cancer. And I actually have melanoma in my family. So it's very top of mind for me. Compared to that with or without sunscreen you're saying it's going to top of mind for me. Compared to that with or without sunscreen, you're saying it's going to go one way or the other.

51:51 - Speaker 2 Um well, absolutely during. You know peak sun exposure and you know um that's when it's most important. But if you go to, if you talk to, you know.

52:21 I I've been to been fortunate enough to go to um three times in the last couple of years where there's a huge amount of concern for skin aging, in fact, nr. I'm a co-founder of a company called Juvenis that's based in Seoul that has been able to formulate NR into skin products and physical barriers. Like you know, umbrellas or whatever is the most important. First thing that you do, you know, to take care of your skin is to, you know, protect it from ultraviolet exposure.

52:58 - Speaker 1 And so that's also the best thing for the quality and health of our NAD.

53:22 - Speaker 2 So that's probably an overstatement. That's probably an overstatement. I mean, we know that NAD is crucially important for DNA repair, you know, and that ultraviolet, you know, exposure, you done that topical NR really works and actually improves skin elasticity. When people applied the stuff to their skin for four and eight weeks two times a day, there was a strongly measurable improvement in skin elasticity. But I don't like to get you know, way out over my skis and, you know, say things that are not evidence-based. But you know, NAD is crucially important for, you know, for repair, Okay, and that's really the use case for it. So you know.

54:03 So I'm not one of these people that will tell you, you know, take NR and then you don't have to age. That will tell you, you know, take NR and then you don't have to age. We are all aging. What we want to do is we want to age better, we want to age with strong repair capacity, we want to maintain our you know, our strength and our mental acuity. That's why there have been something like 80 registered clinical trials of NR in various diseases and conditions, including Parkinson's, in which there's a positive signal, I think. In mild cognitive impairment, there's a positive signal. Seven trials showed an anti-inflammatory effect of NR, so we think that you can age better. There's a use case for NR in aging better.

54:50 - Speaker 1 When I think aging better, I also think of a fundamental concept. I think of mitochondria. Mitochondria is the popular kid on campus right now, I think in the last couple of years, at least in my world and I think we have a lot of things coming out now bringing, in my opinion, good research, but also potentially bringing misinformation around. What is good functioning mitochondria mean? What does it mean to improve or increase the quantity and quality of mitochondria? Are we focusing, maybe, on the wrong thing? Should we be focusing on the quality and quantity of mitochondria or NAD? Do the two serve each other? What is the correlation?

55:25 - Speaker 2 between the two. They serve each other. I mean there's a little bit of podcast disease in this topic. Oh, I know I know, you know what I'm talking about right and what podcast disease is is a lot of highly specific mechanistic recommendations.

55:40 - Speaker 1 For people to know. It's like I heard it on a podcast, right, but if you say you heard it on Everford Radio, I allow it.

55:45 - Speaker 3 That's right. I'll allow it. That's right. This podcast is the exception, right? Please continue.

55:51 - Speaker 2 But people will dive into these rabbit holes and they emerge with very, you know, obsessive diet culture. Basically, they will, you know, pathologize carbohydrates, for example, or they will say that, um fixate on one thing and they'll fixate on it or fixate on on on a whole bunch of different things. Um like, um, you know, physical activity is, is is great, and and and. Sunlight is great and circadian biology is great, but, no, you don't need to take a walk when the sun is at a particular angle. Is that a particular angle?

56:49 - Speaker 1 Habits is running rampant right now, and one of them that I see a lot of is get your walk in in the morning because it's the right amount of like red light right, and then at night you got to walk because it's the right amount of like blue light.

57:03 - Speaker 2 I might have them backwards. It's whatever is sustainable for a person.

57:08 - Speaker 1 Sure, I agree, I agree you understand this.

57:11 - Speaker 2 People have kids, people have jobs, people have their own individual practices.

57:17 - Speaker 1 If we take that aside, if you want to Take that aside.

57:20 - Speaker 2 No, I'm not willing to take it aside, because the thing that is going to help people the most is what they can sustain in their life. Of course, right, of course, and if somebody wants to, if somebody. First of all, I seriously doubt that large percentages of people are functioning better without breakfast than with breakfast.

57:50 - Speaker 1 There may be some people intermittent fasting.

57:53 - Speaker 2 If there may be some people that for for whom, it's great. But if, like, I'm a competitive person, okay, I'm a. You know, when you know, my, my, my, my wife ran like a 320-something marathon, right, oh, wow. And so I don't like being the, you know, the second fastest person in my family, right, because I ran cross country in high school and you know this is not cool. You know, I can't run a four-hour marathon, right, and there's somebody in my family who can run a three, 27 or whatever she did in Chicago. So so, um, that's really good.

58:33 And, and I compete in science and I, you know, compete in in other things. And so if, if all of my competitors want to like go without breakfast, um, that's great for me. You know, it's like I'm going to have breakfast because I'm going to get up in the morning, I'm going to have my coffee right away, I'm going to have my breakfast and I'm going to be productive, I'm going to be able to exercise, I'm going to be able to think, I'm going to be able to do my work.

59:00 - Speaker 1 I'm wholeheartedly with you.

59:02 - Speaker 2 So I'm personally on team breakfast. There's nothing an influencer could say to me that would change my feeling about breakfast, because I've lived with breakfast. I live without breakfast. I function better on breakfast. Okay, I can work out better, you know, with a certain amount. I can work out worse with a ton of food in my system.

59:25 - Speaker 1 Right, but let me go back and ask ask directly just to for clarification for the listener and the viewer here. Our lifestyle allows us to do this. We'll just say this right, and we choose to make it happen and we're able to make it consistently happen. Is there no value, no biological longevity, circadian rhythm value to walking to be exposed to the sun, ie certain wavelengths of light at certain times over the others?

59:58 - Speaker 2 I think it's massively overstated, okay, okay, massively overstated. Interesting I don't think you'd be able to pick up a signal in a properly done clinical trial and and and I barely know anyone that that thinks that you, you could and there certainly aren't data in all.

01:00:18 - Speaker 1 Here's the data. There are not the super charismatic nucleus getting triggered to then, 14 to 16 hours later, begin to trigger you're talking about mechanisms okay, so the, the and that's basically podcast disease.

01:00:32 - Speaker 2 Podcast disease is when someone says, podcast disease is when someone starts talking about their autophagy. They start talking about their mitochondria. They start talking about their autophagy, they start talking about their super chiasmatic nucleus. Okay, so they're. They're talking about deep mechanisms and they're not talking about their performance. I'm talking to you about my performance. Right that if I try to go to the gym and do the same things, or if I'm in a chess match and I try against the same type of opponent, or if I'm trying to solve a problem in metabolism and I try to do those things fed or fasted, I am going to perform better fed than fasted. Now, there may be some things that I would do better, and you know that through your own personal trial and error.

01:01:33 - Speaker 1 Huge point, yeah, I mean. I advocate that all day long. The thing is N equals one every day.

01:01:39 - Speaker 2 But then you do. You can't then use your own experience to advocate what kind of diet or what kind of walk another person?

01:01:47 - Speaker 1 should take.

01:01:48 - Speaker 2 Because the kind of diet or the kind of walk the other person should take is the one that is sustainable for them. Okay, now we understand enough about these diets. So, first of all, you know, whatever you know, you and I are doing with our dietary and lifestyle practices basically working right. So I'm 62. I'm jealous of somebody that can run a 325 marathon, but I'm doing, okay, right, you know, and I'm competing with myself. Right, I'm competing with my former mile time. Right, and I'm competing with my, you know, I want to be able to ski as well this year, or better than I skied last year. Right, I want to be able to be provide enough support and, and you know, to everyone else around me, as I this decade, as I did last decade, I want to maintain my capacity, right?

01:02:52 - Speaker 1 And cure all the podcast disease too.

01:02:54 - Speaker 2 Right, but um, but um. If I told you, first of all, I don't know what percent of my macronutrients come from protein, fat and carbohydrate, but even if I did know what percentages they were for me, I wouldn't tell someone else that they have to be those percentages, Sure, Sure.

01:03:18 - Speaker 4 Sure, I do Sure, I do Sure, I do Sure, I do Sure, I do Sure, I do Sure, I do.

01:03:55 - Speaker 2 I do, I do, I do, I do, I do, I do, I do, I do, I do, I do, I do, I do, I do. And a diet is, is is probably the most important thing that there is in managing that you there. There are, there are quality data showing that you can't get to where you want to be by increasing physical activity alone, because increasing physical activity will actually increase your hunger and your demand for food. And so what we know from the GLP-1, you know experience of the last you know three, four, four years is that these are drugs that work on the brain right To reestablish satiety, right, and they lower energy intake, right, it's so interesting because Meaning everybody.

01:04:30 - Speaker 1 we feel fuller more often and therefore want to eat less.

01:04:34 - Speaker 2 People eat less when they take, you know, semaglutide, right yeah? Or terzapetide and olotrizepetide and olotrizepetide and olotrizepetide and olotrizepetide and olotrizepetide and olotrizepetide and olotrizepetide and olotrizepetide and olotrizep, and all those which are the keto bros out on the internet. You know that are pathologizing carbohydrates. They would say that a drug that increases your insulin would prevent you from losing weight. But those drugs actually do increase your secretion of insulin. That's not the primary mechanism of weight loss. The primary mechanism of weight loss is that they also act on the brain and they get people to push away from the, from the table and and eat less. So, basically, any diet that works for people that basically results in, you know, in weight loss, is is putting a person into a calorie deficit. And and so the people that swear by ketogenic diet um, it's the, the ketogenic diet, or a time restricted feeding, or a low fat diet, you know, whatever it is that worked if, if it worked, it put them into a calorie deficit.

01:06:09 - Speaker 1 That's what we understand what are the best things we can do to help the quality, the quantity, the efficiency of our NAD Exercise.

01:06:21 - Speaker 2 Yeah, the number one thing that you can do is to be active, while I, you know, I just said that you, you can't use exercise alone, for you know significant, you know weight, weight loss. It's incredibly important for life, it's incredibly important for everyone.

01:06:42 - Speaker 1 Why, specifically, is exercise good for NAD? Well, what's going on?

01:06:46 - Speaker 2 there I mean, first of all, exercise is essential for everything right, and physical activity improves people's mood, improves people's mental function, improves people's balance and resistance to falls and coordination.

01:07:14 - Speaker 1 Produces all-cause mortality, chronic disease, inflammation.

01:07:17 - Speaker 2 It also increases NAD synthesis. I think that there actually are some data coming along that show that inactivity depresses NAD synthesis.

01:07:42 - Speaker 1 There are certainly data that I've seen that show mechanisms by which activity increases NAD synthesis. So it's not enough that if we're not exercising we're not getting better NAD or helping the health of our NAD, but actually being inactive.

01:07:54 - Speaker 2 It may depress the NAD system. In fact, yeah, Certainly overnutrition does. Certainly, you know, overfeeding alcohol does.

01:08:04 - Speaker 1 Is fasting a better approach in terms of nutrition or eating habits and timing for benefiting NAD?

01:08:10 - Speaker 2 So you know what I'm about to tell you. I got to ask the question I got to ask. I'm not, I'm not, so I'm basically I'm not going to contribute to podcast disease, okay, and I'm not going to advocate fasting, obviously. Neither am I going to advocate you sleepwalking, right.

01:08:30 - Speaker 1 So so so let's say I choose to fast, I choose to intermittent fast and I only eat my eating window. I'm not saying this is true, I'm just this is hypothetical. I eat between 11 am and 7 pm. Am I having better nad or not?

01:08:45 - Speaker 2 there's no human data for that.

01:08:48 - Speaker 1 Um you know, um know um so um, but it could be personal. For me, Like I, the N equals one. I could just find that I function better, I feel better that you function better and that that's a sustainable practice.

01:09:02 - Speaker 2 No, that doesn't necessarily mean that you have better NAD, and I think that to to, to start, you know saying, oh yeah, you're optimizing your autophagy or you're optimizing your NAD I think it's basically sort of non-falsifiable talking points. I don't find it very interesting, I don't? You know, people have to do what is sustainable for them, right? So if you want to do hard things, right, and then you want to see what allows you to do hard things, right, and so you want to have some sweat in your life, right, so you want to have some. You want to have some sweat in your life, right? So you want to have some heavy, heavy weight in your life. You want to have some some fast movement in your life.

01:09:56 I recently read a study that was remarkable, that was looking at the effectiveness of, you know, antidepressants and a bunch of different lifestyle practices on mood right, and antidepressants were effective, but not super effective, and activity was actually really effective. And then the most amazing thing to me was that, of all the activities, they tried to subclassify different activities and they actually found dancing was the best damn thing it probably has a huge emotional connection there as well by different activities, and they actually found dancing was the best really thing.

01:10:30 - Speaker 1 Oh, it probably, probably has a huge emotional connection there as well, because most people when you think, most people, I think will accept the fact that exercise is good for the human experience. Now, um, are we all going to enjoy doing it? Having joy in your life, exactly, is really important, exactly.

01:10:47 - Speaker 2 Okay. So doing things that make you miserable, right? First of all, it's not going to be sustainable, Right, and second of all, it's not going to give you the whole body, whole brain, whole somatic joy that dancing or sex is going to have, yeah Right, joy that dancing or sex is going to have, yeah Right. So some of the things, if we want to circle back to, to, to longevity, you know some of the best things are, you know, joy, um and um. You know physical activity and mental activity and social engagement. I think dancing is amazing. I think being outside.

01:11:35 - Speaker 3 I'm no good at it, but I do it all the time.

01:11:36 - Speaker 2 Yeah, I'm terrible at it. If you want me to get prescriptive, the most prescriptive thing that I will say is you know, be really active, sweat, do some hard things, do some fun things. Do some fun things that are hard, like you know climbing trails, challenge yourself, have a pet, hang around with people of different ages, chase around young people. But you know I'm not going to make a prescription for for fasting. You know I don't think that eating super late night dinners is is great for me.

01:12:21 So that means that I have a fast built into my 24 hour cycle. If I'm done eating by you know 7pm or something and I, you know, eat at the next 7am, then there's 12 hours in which my glucagon is running and my liver is doing you know, I've tracked it if I eat after 9pm via my whoop right here.

01:12:46 - Speaker 1 If I eat after 9 PM, I has the same negative effect on my recovery, my sleep, my HRV and a couple other biometrics as if I have one serving of alcohol.

01:12:57 It's pretty interesting it's pretty interesting Me personally again, n equals one study of one. I do want to ask a couple other quick questions around NAD before we kind of begin to get to the end. I'm thoroughly enjoying this conversation. Thank you, we want to take it exogenously there are a lot of different ways to do that now and a lot of people in the biohacking optimization space and I'm one of them choose to. What are some of the best ways? What are the best ways to take NAD? How can we take it?

01:13:26 - Speaker 2 IV intranasal injectable take it um iv intranasal injectable capsule. Walk us through that, okay. So a while ago we were talking about the cycle of life, right that? Um, we're eating plants, right, or we're eating the animals that eat the plants and we're getting our protein, fat and carbohydrate, right? Uh, those plants and animals are also running metabolism. They also have NAD as the central catalyst of their metabolism. So when we eat food whole food with a small W and a small F, we're getting not only macronutrients like protein, fat and carbohydrate, we're also getting micronutrients. We're getting NAD coenzymes in our food.

01:14:08 Nad is the cycle of life. It's going to be broken down into vitamin forms, right. The biggest piece of NAD that can get into a cell is called nicotinamide riboside, nr. In 2004, so 20 years ago Bionofsky and Brenner started coming out of my lab. We discovered the vitamin activity of NR. We discovered that cells can not only make NAD from nicotinic acid or nicotinamide, which have been basically in the food supply since the 1940s. They can also make NAD from NR.

01:14:50 Okay, for about the last 10 years, or even more, nr has been commercialized by Chromadex, for whom I'm the chief scientific advisor. It's safety tested. It's orally available. It's the way your body is expecting to get nad precursors right, because normally we're eating food, we're breaking down the nad into nr or something even smaller than nr, and then those vitamins are going into our cells and they're going into these pathways. When we exercise we're ramping up the gene expression of the enzymes that are making NAD. Oh wow, so it's actually synergistic between dietary NR and boosting your NR. So you're going to get a boost of NR from taking a precursor orally.

01:15:45 - Speaker 1 Now I've also read that NAD has a short lifespan and as we age we begin to create less of it anyway. So is it, does it behoove the general public to take NAD?

01:16:00 - Speaker 2 exotically In aging better, you know, in promoting DNA repair. Seven clinical studies showed anti-inflammatory effects of NR. Human trials Human trials, we're not talking mice here. There's hundreds and hundreds of mouse studies. You know there's mouse studies in which it you know, mouse lifespan. But I don't make those kinds of claims because you can't really do the human trial that would measure that.

01:16:41 But the use case for NR is promoting repair, muscle tissue Like after a workout, yeah, tissue Like after a workout, yeah. So in promoting workout recovery, anti-inflammation, you know, one of the things that we did in our lab is we showed that a coronavirus infection disturbs the NAD system Makes sense and that, like, there's five different enzymes that get activated as part of the innate immune response to the virus that degrade cellular NAD supply. Really, people looked at that study and they registered clinical trials and there were positive results showing that NR, combined with other over-the-counter ingredients, accelerated time to recovery from COVID. Wow. And there are other trials in long COVID and COVID-related kidney disease that are looking at NR as well. So I'm pretty excited about that.

01:17:42 - Speaker 1 That's fantastic.

01:17:43 - Speaker 2 Yeah, so the use cases are you know, there's athletes that are 20 years old that take NR because they're in a contact sport.

01:17:53 - Speaker 1 So they're taking exogenous NR preferred over taking exogenous NAD.

01:17:59 - Speaker 2 So because NR is the biggest piece of NAD that can enter cells, you know it's orally available right as a supplement and it's safety tested as a supplement. You know Nige and NR is the stuff that went through all of the safety testing. There are people that take oral NMN. Nmn is going to be converted to NR. Also, you don't really know what you're getting if you take NMN. Nmn is going to be converted to NR. Also, you don't really know what you're getting if you take NMN, because it's actually been sort of banned by the FDA because NMN is being tested as a drug.

01:18:41 - Speaker 1 What about injectable NAD? I've done that a lot at home.

01:18:44 - Speaker 2 Have you done it?

01:18:44 Yeah, so I have not, and I love the way it makes me feel what may be happening in NAD injections is that the body is interpreting intact NAD as some type of a lytic process, like an inflammatory process. Because that's how you know, like intact mitochondria and ATP and NAD get extracellularized in an infection, cells basically blow up Right, right, and then I think that part of the painful effect of NAD is that there's kind of an, but it's not really going to benefit your cells until it breaks down to N, into NR. Any company that I'm associated with is going to do safety testing, you know, and it's going to have some data behind it before something is introduced. And so I would, in terms of injectables, I would wait until there's some data and some safety and you sort of know what you're injecting.

01:19:49 - Speaker 1 So what about the new kid on the block? I know there's one now. You can do NAD intranasally and like a spray.

01:19:53 - Speaker 2 I don't. I don't like new kids on the block, because I'm not talking about the, the the group from the nineties, but but I need to see safety data and I don't think that those kinds of companies do do safety?

01:20:10 - Speaker 1 Do you think that delivery mechanism um has potential?

01:20:14 - Speaker 2 I'd like to see data, you know. So, um, I'd like to see safety first, basically, and um, so you know, and I mean, the clinical doses of of niagen are like a gram a day, right. The thing is that, um, it's orally available and it's safe, and that's where the safety dossier is, and the clinical dossier is for sort of a higher dose and are like a gram a day. And you know, that's kind of what pro athletes do and what you know. Clinical trialists that are looking at anti-inflammatory effects or effects in fatty liver or skin repair are going to be looking at a gram a day.

01:20:58 - Speaker 1 Well, I would like to ask one more question before my final question. Sure, and again, this has been a fantastic interview. I feel like we've got another one coming. Like I was sharing with you earlier my episode with Dr Lou Ignaro, who discovered nitric oxide in the human body, has been getting a lot of new attention, especially on the YouTube channel, which you guys need to subscribe like comment.

01:21:19 All the things boil it down to one statement about NAD that you would want everybody to walk away with having the highest level of understanding, but also like a tool or a concept to actually apply it in their life. What would it be?

01:21:43 - Speaker 2 NAD is the central catalyst of metabolism. It comes under attack in conditions of metabolic stress. You can boost and maintain your cellular NAD with oral NR Niagen being the safety-tested gold standard material. And don't be too prescriptive about your lifestyle. You want to have the most active lifestyle that you can have that brings joy to you and that you can do consistently throughout your life.

01:22:19 - Speaker 1 Love that, love that. Thank you so much. So my last question I ask every guest the whole point of Ever Forward Radio is to bring on topics and guests and have conversations around unique areas of our wellbeing. We are multifaceted creatures and there's a lot of different ways to skin the cat here physical, mental, emotional, spiritual wellbeing. How would you define those two words ever forward, to live a life ever forward? What does that mean to you? And, kind of through your expertise and your life experience, what does that look like, feel like to you?

01:22:50 - Speaker 2 Part of it is questioning received wisdom right, asking questions and realizing that there are questions that haven't been asked before, that there are things that we assume to be true that haven't actually been tested or challenged. And the other is to, you know, to love one another and to you know, care about other people, to seek the truth but to seek to help people, and you know, to not be selfish and to not be overly prescriptive not be overly prescriptive and to not extend the life of podcast disease.

01:23:35 - Speaker 1 All right, let's nip that in the bud. I hope I'm not contributing to that. You know I I've been doing this for seven years. I have to take myself out of the equation. Well, you know, people tell me.

01:23:43 - Speaker 2 the people that make the defense of podcasts will say well, you know, I put my earbuds on and I take the dog for a walk, or something like that, so you know if it's, if it's, you know, people are learning right, people are educating themselves by listening to expert views and they're also, you know, climbing the San Gabriel mountains or something. At the same time, then it sounds great. If they're going into little rabbit holes where they are falling in love with science-y sounding mechanisms and coming away with the idea that they need to have very prescriptive dietary habits or lifestyle practices that they can't actually achieve because they have childcare and other things, then it's not helpful.

01:24:38 - Speaker 1 So, yeah, I love that. Well, charlie, thank you so much. All right, my pleasure. For more information on everything you just heard, make sure to check this episode's show notes or head to everforwardradio.com