63. Charles Brenner: NAD, Energy, and Longevity: The Secret Nobody Told You About

What if the reason you're tired, inflamed, or not recovering the way you used to has nothing to do with aging, and everything to do with your NAD system being under attack? In this episode of Extend, I'm joined by Dr. Charles Brenner, the scientist who discovered nicotinamide riboside (NR) and one of the leading experts on NAD metabolism. We unpack why NAD is so critical for energy, repair, and resilience, and why simply "taking NAD" isn't the solution most people think it is. We also break down the key lifestyle factors quietly draining your NAD levels, the real difference between NMN, NR, niacin, and IV NAD, and why NR may be the safest and most effective way to support your body's natural repair systems. Dr. Brenner also shares the science behind NAD's role in inflammation, immunity, and recovery, and why placebo-controlled research is the missing piece in so many longevity conversations. Dr. Charles Brenner is the Alfred E. Mann Family Foundation Chair in Diabetes and Cancer Metabolism at City of Hope and a leading authority on NAD metabolism. His work bridges fundamental science with real-world application. We Also Discuss: Why NAD Is the Missing Link in Energy, Repair, and Longevity The Truth About NAD Decline—and What's Really Draining Your Levels NR vs. NMN: The NAD Debate That Actually Matters Is Oral NR Better Than IV NAD? Here's What the Research Says How NAD Impacts Inflammation, Immunity, and Recovery The Gaps in NAD Science and Why They Matter Thank You to Our Sponsors: TruNiagen: Whether you are looking to stay sharp, feel more energized or simple age better, go to https://www.truniagen.com/IFit: If you are looking to elevate your home gym fitness experience with the best in fitness tech, choose IFIT. Go to https://www.ifit.com/NextHealth: Your destination for cutting-edge health optimization—from IV therapy to hormone balancing. Explore at https://www.next-health.com/Vitaboom: For supplements you can trust and wellness solutions tailored to your health, visit https://vitaboom.com/ Learn more about Dr. Shah: Website: https://www.drshah.com/ Clinic: https://www.next-health.com/ Instagram: https://www.instagram.com/darshanshahmd/ Learn more about Dr. Charles Brenner: Website: brennerlab.net https://brennerlab.netInstagram: @charlesmbrenner https://www.instagram.com/charlesmbrenner/

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:03Dr. Darshan Shah?

  Welcome to Extend with me, Dr. Darshan Shah, a podcast dedicated to cutting-edge science, research, tools, and protocols designed to help you extend your health span. Having become one of the youngest doctors in the country at the age of 21, and trained and board-certified at the Mayo Clinic, I've accumulated three decades of practice as a board-certified surgeon and longevity expert. Over that time, I've discovered that a mere 20% of health knowledge yields 80% of the results when it comes to your health span. We're living in a new era where we are creating a new healthcare system, no longer focused on disease management, but achieving optimal health and vitality. Join me as I interview world-renowned experts, offering you a step-by-step guide to proactively avoid disease, and most importantly, extend your health span.

• 0:49Dr. Darshan Shah?

  What if this secret to aging well, improving resilience, and supporting your health at the cellular level wasn't about doing more, but about replenishing one critical molecule that every cell in your body depends on to function properly? In today's episode of Extend, I'm joined by Dr. Charles Brenner. He is a world-renowned biochemist. He's a chief scientific advisor of Chromadex, and the scientist who discovered nicotinamide riboside NR, one of the most researched NAD precursors available today. We're going to dive deep into the science of NAD, what it is, why it matters for almost every cellular process, your energy levels, your parasympathetic system, your immune function, longevity,

• 1:31Dr. Darshan Shah?

  and why so many of us are walking around with depleted levels of NAD. We break down the biggest misconceptions about the molecules, NAD, NR, NMN, and niacin, and explain why and how and what you supplement matters more than you think. We're also going to discuss where the research really stands today, including what's hype, what's hope, and what's actually proven. At Next Health, we do a ton of NAD infusions and NR infusions. We're also doing lots of supplementation with NR, and this is a very commonly asked about topic in our clinic. Why? Well, because we know that these molecules actually do work. For most people, and also a lot of people are seeking resolution to some of these problems

• 2:15Dr. Darshan Shah?

  with energy levels and sleep and also their immune function. So if you're one of these people that's curious about NAD and whether it's worth the investment to do these infusions or to buy the supplement, or if you're just confused by the growing list of options on the market, this conversation will clear up all the noise for you and get to the truth. And we're going to show you the science that proves it. Dr. Charles Brenner is the Alfred E. Mann Family Foundation Chair in Diabetes and Cancer Metabolism at the City of Hope Hospital, and he's a leading authority on NAD metabolism. We're really lucky to have him here at the podcast today. His work actually bridges the fundamental science of NAD at the cellular level with the real world application of how we can use it to improve our lives every single day.

• 2:59Dr. Darshan Shah?

  Let's dive into the research with Dr. Charles Brenner.

• 3:07Dr. Darshan Shah?

  Dr. Brenner, thank you for joining me today.

• 3:08Speaker 01

  My pleasure.

• 3:09Dr. Darshan Shah?

  Yeah, I'm really excited about this conversation because, man, there's this huge world of NAD that everyone is talking about. Seems like the topic of conversation and the longevity space, I'm doing air quotes, longevity, but also just health span in general, a lot of people are talking about it. And I feel like a lot of it started with you.

• 3:32Speaker 01

  Yeah, I guess so. I mean, NAD has been a thing in biochemistry for 100 years or more. It's the central electron carrier in biology, right? So I was just explaining to my to my stepsons, you know, how how does the biological stuff work, right? You know, are humans like perpetual motion machines? Do we violate the second law of thermodynamics? And the answer is no, we don't violate the second law. The second law says that in a closed system, things become more chaotic, right? Everything falls apart, right? And like when you break an egg, it's broken and you can't get it back together. Humpty Dumpty problem, right?

• 4:17Speaker 01

  But then you can go look out in nature and You can see a squirrel in your yard and you know, you saw it when it was a tiny little squirrel.

• 4:25Dr. Darshan Shah?

  That's true.

• 4:26Speaker 01

  And let's say it had, you know, a hundred thousand brain connections and then it becomes a full grown squirrel. And it's like four times as big and it has a million times as many brain connections. So it seems like it's going in the direction of becoming more orderly, right?

• 4:41Dr. Darshan Shah?

  Right.

• 4:41Speaker 01

  So how is it possible?

• 4:42Dr. Darshan Shah?

  Right.

• 4:42Speaker 01

  And the reason it's possible is that there's a sun ninety three million miles away and the sun is hitting the the earth and making green plants. And then the squirrel and and we are either eating those plants.

• 4:55Dr. Darshan Shah?

  Sure.

• 4:56Speaker 01

  Or we're eating the squirrel that's ate those plants, right?

• 4:59Dr. Darshan Shah?

  Yes.

• 4:59Speaker 01

  We're taking energy into our bodies.

• 5:02Dr. Darshan Shah?

  Yes.

• 5:02Speaker 01

  And then the carrier of the high energy electrons.

• 5:06Dr. Darshan Shah?

  Yes.

• 5:06Speaker 01

  Are NAD coenzymes. And that's that allows us to keep our S together.

• 5:11Dr. Darshan Shah?

  Yeah.

• 5:12Speaker 01

  Keep our stuff together.

• 5:13Dr. Darshan Shah?

  Right.

• 5:13Speaker 01

  And oppose all of the chaos and oppose the the disorder of the universe and you know, be healthy and and live our lives.

• 5:22Dr. Darshan Shah?

  I mean, there's such a beautiful explanation of it because you know, life is basically transfer of energy from the sun to biological beings, squirrels, humans. And the carrier of that energy is NAD.

• 5:37Speaker 01

  Yeah.

• 5:38Dr. Darshan Shah?

  In biological systems.

• 5:39Speaker 01

  Carrier of the high energy electrons, yeah.

• 5:41Dr. Darshan Shah?

  Right, exactly. And so the high energy electrons is what is fueling growth, repair. Every biological process basically is fueled by these high energy electrons. So NAD on a biochemistry level is what's carrying those electrons from place to place to place where they need to go, right?

• 6:00Speaker 01

  Yeah.

• 6:00Dr. Darshan Shah?

  And much of this process occurs in an organelle called the mitochondria.

• 6:06Speaker 01

  Yeah.

• 6:07Dr. Darshan Shah?

  Right?

• 6:07Speaker 01

  Yeah.

• 6:08Dr. Darshan Shah?

  So how does this all fit together? What is, how does NAD kind of carry these electrons through the mitochondrial process?

• 6:14Speaker 01

  Yeah, so when all of your cells take in fuel, right? So they're taking in protein, fat or carbohydrate, right? Those are the three things that have calories. That's the stuff that fuels our body.

• 6:28Dr. Darshan Shah?

  Right.

• 6:28Speaker 01

  We have some micronutrients. Well, NAD is a micronutrient. But it's protein, fat and carbohydrate are the energy containing components of our food. And carbohydrate, and you know, I'm not anti carbohydrate. I'm married to a runner. And you know, we have five millimolar glucose in our body, right?

• 6:54Dr. Darshan Shah?

  Sure.

• 6:54Speaker 01

  And even if you don't even, if you don't eat carbohydrate, your body is going to make it. Right? And, and you can healthily eat carbohydrate. But when the carbohydrate oxidation occurs in what's called the cytoplasm.

• 7:09Dr. Darshan Shah?

  Right, the inside of the cell.

• 7:10Speaker 01

  And, yeah. But the high energy electrons have to be transferred into the mitochondria to make ATP. But then some of the high energy electrons get put on to a molecule called NADP, forming NADPH. And that's how you make lipids. That's how you make nucleotides, right? And so we have to make all of our own DNA and RNA. We have to repair all of our nucleic acids. When you cut yourself, you know, you have to make more cells. You have to make lipids.

• 7:41Dr. Darshan Shah?

  Yeah.

• 7:41Speaker 01

  That depends on NADPH. So these high energy electron carriers are really the central catalyst of life.

• 7:49Dr. Darshan Shah?

  Yeah. And so moving these electrons around to where they need to go is the function of basically NAD, NADP, NADH, right? And once they get into the mitochondria, your mitochondria puts them through a process to make ATP. And ATP is the energy molecule that fuels basically everything else.

• 8:09Speaker 01

  So, so there, yeah, there's, there's this exchange system where you can use higher energy. And now we would need a whiteboard, right? To do the whole, because there's proton pumping and there's multiple electron carriers. But the key is that the highest energy electron carrier is NAD, forming NADH. And then it initiates what's called the electron transfer chain. The end result of which is production of ATP. And then. All of then you can flex your muscles and you can record a an event and create a memory and do all the things that you need to do.

• 8:49Dr. Darshan Shah?

  Yeah, exactly. And so my point of this is all is really just the importance of NAD in our biological systems. I think it's an understatement to say that without NAD we couldn't live, obviously, but everything depends on NAD. And how did we come from? I mean, we've known about NAD, like you said, for decades.

• 9:08Speaker 01

  Yeah.

• 9:08Dr. Darshan Shah?

  How do we come from just this, you know, something being taught in biology class at high school to where we are now, where, you know, NAD is really being looked at as something that people can take, right, as a supplement, is being looked at in many disease states as as a problem if you don't have enough NAD.

• 9:28Speaker 01

  Right.

• 9:28Dr. Darshan Shah?

  And in many other branches of science, where we're looking at NAD to to improve performance, improve, you know, athletic performance, etc. Like, what happened?

• 9:37Speaker 01

  Right, yeah, right. And and the fact that there's a mechanism requiring NAD, that's important.

• 9:44Dr. Darshan Shah?

  Yeah.

• 9:44Speaker 01

  But that doesn't necessitate NAD as a supplement. What you really what really necessitates NAD precursors as supplements is the fact that the NAD system comes under attack, right? So, for example, you know, I could explain to you that neurons firing require sodium, but that doesn't mean that we need more salt in our diet.

• 10:05Dr. Darshan Shah?

  Right, exactly.

• 10:06Speaker 01

  I mean, there are people that will sell you more salt in your diet, but I don't think they should, right? I mean, we're gonna have a we're gonna have a blood pressure problem if everybody adds a gram of sodium chloride to their diet.

• 10:17Dr. Darshan Shah?

  You know, people are selling packets of electrolytes every morning.

• 10:21Speaker 01

  You and I are not among them. But so just because there's a mechanism involving NAD, that's not the use case for for the supplement. What we found when we started looking at the NAD system is that there's many conditions in of metabolic stress in which the NAD system comes under attack, right? So, for example, we found when we made mice fat. So we call it overnutrition, right? It's a nutritional problem by having too much food.

• 10:53Dr. Darshan Shah?

  Right.

• 10:54Speaker 01

  And so you put mice in, you know, small cages with a high-fat diet, and they become really fat, and you can push them over into type 2 diabetes.

• 11:03Dr. Darshan Shah?

  Okay.

• 11:04Speaker 01

  And their liver NAD system goes into decline. We looked at, that's a mouse result. But then we looked at humans with alcoholic liver disease, and their NAD system is under attack. When you and I were just outside in the oxygen and the sunlight, both of which are lovely, we can't live without oxygen, and it's not pleasant to live without sunlight. And ultraviolet, you know, rays will, you know, hit our, our DNA, and will cross-link thiomodines and create, you know, a type of DNA damage. And when that DNA damage is repaired, you use NAD.

• 11:45Dr. Darshan Shah?

  Right.

• 11:45Speaker 01

  So in oxidative stress, you churn NADPH. In DNA repair, you use NAD. When our bodies come across, um, things that are recognized in the innate immune system like viruses.

• 12:00Dr. Darshan Shah?

  Yeah.

• 12:00Speaker 01

  Right? Are, we have some enzymes called PARPs, and the PARPs get angry and activated, and they start churning NAD. So it turns out that inflammation and virus exposure causes use of NAD.

• 12:15Dr. Darshan Shah?

  Right.

• 12:16Speaker 01

  And cell division, you require NADPH. So there's many conditions of metabolism, and then disease processes. Like in heart failure, there's a specific attack on the NAD system. In different kinds of central and peripheral neurodegeneration, there's an attack on the NAD system. So it turns out that NR, and to some degree, the other NAD precursors like niacin or nicotinamide, can support NAD metabolism and support resiliency in face of metabolic stress.

• 12:48Dr. Darshan Shah?

  Got it.

• 12:49Speaker 01

  So I kind of wish that the clinical trialing thing didn't start out with the presumption of like... Lifespan because you can't actually measure that.

• 13:00Dr. Darshan Shah?

  Right.

• 13:00Speaker 01

  Right. So you can measure some biomarkers, but I don't think it's that interesting.

• 13:05Dr. Darshan Shah?

  Right.

• 13:05Speaker 01

  But when you look at, like, there's now eight completed randomized clinical trials that show that NR lowers inflammation.

• 13:14Dr. Darshan Shah?

  That's amazing.

• 13:15Speaker 01

  And inflammation is one of those fundamental components.

• 13:18Dr. Darshan Shah?

  Absolutely.

• 13:19Speaker 01

  Of, you know, disease processes. It's related to the lack of capacity that we we get to in our dotage as we age.

• 13:29Dr. Darshan Shah?

  Right.

• 13:30Speaker 01

  Right. And so you want anti-inflammatory. So I prefer that we do the clinical trials for those really clear endpoints.

• 13:37Dr. Darshan Shah?

  Sure.

• 13:38Speaker 01

  Right.

• 13:38Dr. Darshan Shah?

  Right. We can measure.

• 13:39Speaker 01

  Prove it.

• 13:39Dr. Darshan Shah?

  Yes.

• 13:40Speaker 01

  Right. And then there's a, there's a positive one for peripheral artery disease. Right.

• 13:46Dr. Darshan Shah?

  Okay.

• 13:46Speaker 01

  Where if you take care of people with peripheral artery disease, you do a three or six month trial, their walking speed is going to be less, demonstrably less at the end of the trial.

• 13:57Dr. Darshan Shah?

  Right.

• 13:57Speaker 01

  If they're in a placebo arm.

• 13:58Dr. Darshan Shah?

  Right.

• 13:58Speaker 01

  And, and there was a completed trial.

• 14:00Dr. Darshan Shah?

  Yeah.

• 14:01Speaker 01

  University of Florida and Northwestern University. I was not involved in it. And it showed that the people on a gram of NR a day had improved walking speed.

• 14:11Dr. Darshan Shah?

  That's incredible.

• 14:12Speaker 01

  And placebo was degraded walking speed.

• 14:15Dr. Darshan Shah?

  So it did degrade with the placebo?

• 14:17Speaker 01

  It degraded with placebo because they have peripheral artery disease.

• 14:20Dr. Darshan Shah?

  Exactly.

• 14:21Speaker 01

  And, um, you know, it was a strong enough result that they're going to do, I think, a phase three, you know, to really, I mean, these are establishing use cases for NR.

• 14:32Dr. Darshan Shah?

  Right.

• 14:33Speaker 01

  Right. So generally, I think probably your, your patients are taking it in the context of wellness, right?

• 14:38Dr. Darshan Shah?

  Mm-hmm.

• 14:39Speaker 01

  Disease prevention, wellness, and it says on the bottle, you know, not to, you know.

• 14:44Dr. Darshan Shah?

  Not to treat any disease because you have to say that.

• 14:47Speaker 01

  Yeah. But, um, the use case is that it actually controls inflammation.

• 14:52Dr. Darshan Shah?

  Right.

• 14:52Speaker 01

  And it supports resiliency because, you know, whether or not we have alcaloga liver disease or suffer from, you know, overnutrition with you and I don't, we are exposed to viruses. We are exposed to things that challenge our. NAD system.

• 15:08Dr. Darshan Shah?

  Yeah. So when you say the NAD system is under attack, it's being forced to work harder than our human biology has ever needed to work for overnutrition, for

• 15:19Speaker 01

  I don't know.

• 15:19Dr. Darshan Shah?

  Toxic exposure or

• 15:21Speaker 01

  Humans are amazing at aging.

• 15:23Dr. Darshan Shah?

  Yeah.

• 15:23Speaker 01

  Right? Humans, like gorillas are bigger than than humans.

• 15:27Dr. Darshan Shah?

  Right.

• 15:27Speaker 01

  And generally longevity scales with animal size.

• 15:31Dr. Darshan Shah?

  Uh huh.

• 15:32Speaker 01

  Right?

• 15:32Dr. Darshan Shah?

  Right.

• 15:32Speaker 01

  And like whales and sharks are live a super long time. I mean, not the smallest sharks, the biggest sharks do. But gorillas are bigger than humans.

• 15:41Dr. Darshan Shah?

  They are, yeah.

• 15:41Speaker 01

  But, you know, they live maybe, you know, four decades or something like that. And we live eight, nine decades.

• 15:47Dr. Darshan Shah?

  Right.

• 15:47Speaker 01

  Some people, 10, 11 decades.

• 15:49Dr. Darshan Shah?

  Right.

• 15:50Speaker 01

  Right? So humans are really good at aging. If you don't have the accidents and you don't have polypharmacy and you don't do all the the bad things, humans can live a long time. So but you can just observe that when somebody who is 10 falls off their bike, right? And get some scrapes, they repair really rapidly.

• 16:16Dr. Darshan Shah?

  Right.

• 16:16Speaker 01

  When somebody who is in their seventh or eighth decade, if they're still riding a bike, that's great. But when they fall off their bike, when they're 80 years old, you know, there's those scrapes don't, don't heal very, very rapidly, right?

• 16:31Dr. Darshan Shah?

  Right, right.

• 16:32Speaker 01

  So we want to support that healing process. That's actually another clinical trial I'd like to see done is the wound healing as a function of age, right?

• 16:42Dr. Darshan Shah?

  Or surgical, pre

• 16:43Speaker 01

  Yeah.

• 16:44Dr. Darshan Shah?

  pre-surgical and post-surgical NAD. Yeah, that's a great clinical trial. In my previous life, I did surgery and so anything that you could do to accelerate wound healing is monumentally important. So that's a great idea for a clinical trial, for sure.

• 16:58Speaker 01

  Yeah.

• 16:59Dr. Darshan Shah?

  So you found this molecule NR.

• 17:03Speaker 01

  Yeah.

• 17:03Dr. Darshan Shah?

  Nicotinamide riboside.

• 17:05Speaker 01

  Yeah.

• 17:05Dr. Darshan Shah?

  And since then, there's been other permutations of these that have been talked about. NAD, NMN.

• 17:12Speaker 01

  Yeah.

• 17:12Dr. Darshan Shah?

  Right? Then we also have niacin.

• 17:14Speaker 01

  Yeah.

• 17:14Dr. Darshan Shah?

  Right? Can you kind of tell us the difference between all this whole world of molecules that people hear about?

• 17:20Speaker 01

  Yeah. So NAD, NADH, NAP, and NPH have two or three phosphates on them.

• 17:27Dr. Darshan Shah?

  Right.

• 17:28Speaker 01

  Which are two or three phosphates too many to get into any cell.

• 17:32Dr. Darshan Shah?

  Right.

• 17:32Speaker 01

  Right. So, you know, like if there are docs out there that treat cancer patients or docs that prescribe antivirals, there are cancer drugs and antivirals that are in the class of molecules called nucleosides. They're all active as nucleotides. And the difference between a nucleoside and nucleotide is phosphates.

• 17:56Dr. Darshan Shah?

  Right.

• 17:57Speaker 01

  Right. So, like, there used to be a compound for AIDS, HIV, called AZT.

• 18:04Dr. Darshan Shah?

  Right.

• 18:04Speaker 01

  And you give AZT, and then it would get into cells, and then inside the cells it would turn into AZT triphosphate.

• 18:13Dr. Darshan Shah?

  Uh huh.

• 18:14Speaker 01

  Okay. So, NAD is the great stuff, but if you inject it, or if you eat it, and it's in food, right?

• 18:22Dr. Darshan Shah?

  Right.

• 18:22Speaker 01

  Because, you know, the squirrel that's eating the plant matter, or us that's eating the squirrel or the cow, we're eating cellular stuff, and so all that cellular stuff has NAD in it, right? But in the digestive process, the phosphates basically get taken off.

• 18:39Dr. Darshan Shah?

  Right.

• 18:39Speaker 01

  The biggest piece of NAD that can get into cells is NR, right? This is the thing that we discovered in 2004. We discovered nicotinamide riboside as a vitamin precursor of NAD.

• 18:51Dr. Darshan Shah?

  Can I just add one thing to that? So, the phosphates, the reason NAD connected to a phosphate does not get into a cell is because every cell has a phospholipid bilayer, and so phosphates bang up against phosphates, and they can't get through, right? It's like basically a wall against a wall.

• 19:08Speaker 01

  What a repulsive explanation that you just gave, Dr. Shaw. But that's exactly right. I mean, yeah, there's like negative charges, and there's a negative charge on the membrane, and it doesn't work that way.

• 19:18Dr. Darshan Shah?

  Right. So, the NR can get in because there's no phosphate on it.

• 19:21Speaker 01

  Right. It's not charged.

• 19:23Dr. Darshan Shah?

  Right. And to bring this a practicality, you feel this when you're doing IVNAD versus IV nicotinamide riboside, because IVNAD hangs out in your bloodstream for such a long time. Has to break down. It just feels... Miserable. It takes a long time to get to do these.

• 19:41Speaker 01

  You know why it feels miserable? I think it feels miserable because there's an innate immune reaction to NAD. NAD is supposed to be an intracellular molecule. Just like mitochondria are supposed to be inside cells.

• 19:57Dr. Darshan Shah?

  Right.

• 19:58Speaker 01

  Long chromosomal DNA is supposed to be inside of cells. When cells burst open, there's long chromosomal DNA, mitochondria, NAD itself, and ATP, and all of those things will activate the innate immune system.

• 20:17Dr. Darshan Shah?

  Got it.

• 20:17Speaker 01

  You get an inflammatory reaction. So people feel hot, right?

• 20:20Dr. Darshan Shah?

  Right, right.

• 20:21Speaker 01

  Yeah.

• 20:21Dr. Darshan Shah?

  Yeah.

• 20:22Speaker 01

  And so when people are doing an intravenous NAD injection, and I learned that that was a thing from watching Billions. Yeah. Like a few years ago, they were.

• 20:33Dr. Darshan Shah?

  The show.

• 20:34Speaker 01

  Yeah, they were, they were showing Billions and, you know, people would like the stockbrokers or whatever, or have a long night of drinking and doing drugs or, and they would call up a nurse and they would get IV drip, right? And so people have been doing this for decades.

• 20:51Dr. Darshan Shah?

  Right.

• 20:52Speaker 01

  As it turns out, and, and saying, well, I feel great at the end of this, but miserable during it, and that's what you're, you're talking about.

• 20:59Dr. Darshan Shah?

  Yeah.

• 21:00Speaker 01

  So then, um, yeah, when I, I literally had this conversation with, you know, with the, the CEO of Chromadex.

• 21:07Dr. Darshan Shah?

  Mm-hmm.

• 21:07Speaker 01

  And, you know, he asked, well, you know, could you deliver nicotinamide riboside?

• 21:13Dr. Darshan Shah?

  Mm-hmm.

• 21:13Speaker 01

  And what would be the expectation?

• 21:15Dr. Darshan Shah?

  Mm-hmm.

• 21:16Speaker 01

  And I said, well, the expectation is that it would not be painful.

• 21:20Dr. Darshan Shah?

  Right.

• 21:21Speaker 01

  And it could probably be delivered more rapidly. That's now been demonstrated in people. So that's a, that's a great thing. Now, what's the use case exactly for, you know, IV NR rather than oral NR? I'm going to be honest with you and say, it's not really been demonstrated. You have people at the, at the leading edge, right?

• 21:41Dr. Darshan Shah?

  Yeah.

• 21:42Speaker 01

  That are like performance oriented people, athletes and so forth. They're saying, you know, for. Recovery, they feel great when they do an IV NR. But it's only now that there is clinical grade material. Right. From which you can do clinical trials. Right. With NR, the clinical grade oral NR was available now for more than 10 years. Right. Right? Mm-hmm. Which is why we can now say that, yeah, it's active in anti-inflammation. It's active in peripheral artery disease. So I'm hoping that, you know, in the future, that there will be placebo-controlled trials that will test some of the things that people are claiming about IV NR. Right.

• 22:26Speaker 01

  Like potentially lowering their urge for drugs. Like I've, I've heard that. Yes. That it may have activity in opioid. There's a lot of recovery centers using it, yeah, absolutely, yeah. And so when I've suggested to, to people that are running those recovery centers that they do a trial, they, even a crossover trial, where people, a crossover trial means you enroll everybody. Right. Some people are taking placebo, some people are taking the so-called active, and then they cross over. Right. So if they start out on NR or NAD, they would end up on placebo. If they start out on placebo, they're gonna end up on the, on the active that you're,

• 23:10Speaker 01

  that you're testing. And the people were sort of like true believers and they said, oh no, it wouldn't be ethical to do that trial from my point of view. It's not ethical to do it as a non-placebo-controlled trial. You're never gonna change medicine if you don't do it as a placebo-controlled trial. Because if the person has to lay out like $10,000 to do a treatment and they have a very caring nurse, you know, and treatment team, they may believe that this had value to them. Right. But you need to demonstrate that scientifically. Yeah. Right? So, but to get back to your, your earlier question.

• 23:49Dr. Darshan Shah?

  It's a really good point, though, by the way. I mean, I think a lot of people talk about IV, NR and NAD for drug recovery.

• 23:57Speaker 01

  Yeah.

• 23:57Dr. Darshan Shah?

  But there has not been a placebo-controlled trial. So it's, it's hard to say 100% certain this is working. Anecdotally, however, a lot of people use this all the time.

• 24:07Speaker 01

  Yeah.

• 24:08Dr. Darshan Shah?

  I live in Malibu. There's like a recovery center. Every other house is a recovery center.

• 24:12Speaker 01

  Wow.

• 24:12Dr. Darshan Shah?

  It's a massive use of IV to help people get off alcohol.

• 24:16Speaker 01

  Yeah.

• 24:17Dr. Darshan Shah?

  Opiates, all of it.

• 24:18Speaker 01

  Yeah, yeah. So, so we, you and I both hope that those trials are done.

• 24:23Dr. Darshan Shah?

  Right, they need to be done.

• 24:24Speaker 01

  Yeah.

• 24:24Dr. Darshan Shah?

  Yep.

• 24:24Speaker 01

  But then what about niacin? What about nicotinamide? What about NMN, right?

• 24:28Dr. Darshan Shah?

  Hmm.

• 24:29Speaker 01

  So, NAD itself and NVP have too many phosphates. NMN has too many, has, has a phosphate.

• 24:36Dr. Darshan Shah?

  NMN does have a phosphate group on it, okay?

• 24:38Speaker 01

  So, so it doesn't go into cells.

• 24:39Dr. Darshan Shah?

  Yeah.

• 24:39Speaker 01

  And, and you know, there was a, a claim that a particular molecule is an NMN transporter. It's not an NMN transporter. It's a sodium transporter. We've done the experiments and NMN has to be degraded back to NR before it can get into cells. Then it gets converted into NMN and NAD inside the cells.

• 25:00Dr. Darshan Shah?

  Hmm.

• 25:00Speaker 01

  So, like a chemist has to go to the trouble of putting the phosphate group on.

• 25:05Dr. Darshan Shah?

  Uh huh.

• 25:05Speaker 01

  Then someone takes it orally, the phosphate group comes off. So it sort of doesn't make any sense.

• 25:11Dr. Darshan Shah?

  Right.

• 25:11Speaker 01

  The other problem with it is that there's something called the DASHA Act. D S H E A. DS stands for dietary supplement.

• 25:22Dr. Darshan Shah?

  Okay.

• 25:22Speaker 01

  Right? And the DASHA Act basically said that if something is a food or supplement and it's, enters the food supply as a new dietary ingredient, yes, you can test it as a drug.

• 25:36Dr. Darshan Shah?

  Okay.

• 25:37Speaker 01

  Right? So niacin, you know, has been in the food supply since the 1940s. In the 1970s or something, people started testing it as a drug. Like high dose niacin.

• 25:48Dr. Darshan Shah?

  Wow, okay.

• 25:48Speaker 01

  For lipids, right?

• 25:49Dr. Darshan Shah?

  Right.

• 25:50Speaker 01

  That's legal.

• 25:51Dr. Darshan Shah?

  Mm hmm.

• 25:51Speaker 01

  Still available as a, as a supplement.

• 25:54Dr. Darshan Shah?

  Sure.

• 25:54Speaker 01

  Still in food. But if something is introduced and tested as a drug, you can't sell it as a supplement. Right? Because otherwise you'd be busting everybody's patents.

• 26:06Dr. Darshan Shah?

  Yes.

• 26:07Speaker 01

  And also you'd be taste, taking things that don't go through the safety process that drugs need to go through. Plus, most drugs, ninety-nine percent of drug candidates fail.

• 26:19Dr. Darshan Shah?

  Right.

• 26:20Speaker 01

  Right?

• 26:20Dr. Darshan Shah?

  Right.

• 26:21Speaker 01

  Okay. So what happened with NMN, right? So what happened with NMN is that NR is, you know, discovered as a vitamin, and then there's a number of remarkable things done with, with mice, and then it's introduced as a human dietary ingredient. Chromadex, you know, makes a business out of it. And full disclosure, I'm their chief scientific advisor. NMN comes along, right? And it basically becomes popularized.

• 26:52Dr. Darshan Shah?

  Right.

• 26:52Speaker 01

  And people say, oh yeah, you could take NR or you could take NMN. The most widely read book on longevity in the world, right? There's a particular page number where the person says, oh, I take NMN, I take rapamycin, I take metformin, I take a bunch of other things that don't really make any sense. So there's a market suddenly for NMN, right? But the problem is that a company already started testing it as a drug. So that basically means that anybody that is still selling NMN as a drug isn't going through the safety testing.

• 27:31Dr. Darshan Shah?

  Uh huh.

• 27:32Speaker 01

  You know, it's not legal in the US.

• 27:34Dr. Darshan Shah?

  Uh huh.

• 27:34Speaker 01

  But it also doesn't really make biological sense because again, the phosphate has to come off. So I kind of wish the science communicators would have just, would just say, look, if there is a use case for NAD boosting, which we just explained what it is, anti-inflammation, there's actually a safety-tested form of NAD boosting, which is NR.

• 27:55Dr. Darshan Shah?

  Right.

• 27:55Speaker 01

  In addition, there's nicotinamide, which is available.

• 27:57Dr. Darshan Shah?

  Right, right.

• 27:58Speaker 01

  There's nicotinic acid, which is available. It causes flushing.

• 28:02Dr. Darshan Shah?

  Flushing is a problem, right?

• 28:03Speaker 01

  Causes flushing. Nicotinamide-

• 28:06Speaker 01

  And nicotinic acid don't have quite the advantage of NR. Because, and we were talking about this before the podcast. There's many of these conditions of metabolic stress. Where the NAD system comes under attack. And the NR kinase genes, or the genes that convert NR into NAD. They get upregulated.

• 28:28Dr. Darshan Shah?

  Okay.

• 28:29Speaker 01

  Right? So if you're taking regular nicotinamide.

• 28:32Dr. Darshan Shah?

  Right.

• 28:33Speaker 01

  Or nicotinic acid, they don't go through that pathway. Not every single cell in the body can convert nicotinic acid into NAD.

• 28:42Dr. Darshan Shah?

  Got it.

• 28:42Speaker 01

  As far as we can tell, every cell can convert nicotinamide. And every cell can convert NR into NAD. And the NR has the advantage of fewer different steps.

• 28:57Dr. Darshan Shah?

  Right.

• 28:57Speaker 01

  To making all the way to NAD. And the pathway gets boosted up.

• 29:01Dr. Darshan Shah?

  Right.

• 29:01Speaker 01

  In a number of conditions. So like.

• 29:03Dr. Darshan Shah?

  What you want.

• 29:03Speaker 01

  Failure, yeah. Like in a mouse model of heart failure. Nicotinamide doesn't work. Whereas NR does. Because it's the NR genes that are, the NR responsive genes are getting upregulated. And so it's the failing heart is looking for NR.

• 29:21Dr. Darshan Shah?

  Right.

• 29:22Speaker 01

  So I would say if somebody is going to the trouble to boost their NAD. NR is kind of the more high value.

• 29:28Dr. Darshan Shah?

  Yeah.

• 29:29Speaker 01

  You know, precursor.

• 29:30Dr. Darshan Shah?

  Right.

• 29:30Speaker 01

  NMN is going through the same pathway, actually.

• 29:33Dr. Darshan Shah?

  Right.

• 29:33Speaker 01

  Because the phosphate has to come off and then it's NR.

• 29:36Dr. Darshan Shah?

  Right, exactly.

• 29:37Speaker 01

  The problem is that nine out of 10 products that are sold as NMN are not NMN.

• 29:43Dr. Darshan Shah?

  For sure. That's the other problem.

• 29:45Speaker 01

  And it's, it's been revealed that many of them contain endotoxin and

• 29:50Dr. Darshan Shah?

  Yeah.

• 29:51Speaker 01

  Other things that are not safe. So.

• 29:53Dr. Darshan Shah?

  Right.

• 29:53Speaker 01

  You know, it's better to.

• 29:59Dr. Darshan Shah?

  I've been dissecting the science of NAD for over three years now, and I want to tell you what I use for optimizing my own mitochondrial health. If you want to support healthy aging at a cellular level, True Niagen's NR is scientifically proven to increase NAD plus levels, a critical coenzyme for energy production and overall cellular health. It's my favorite supplement for boosting NAD plus, improving how your body handles stress, optimizing your recovery and supporting longevity. Whether you're looking to stay sharp, feel more energized, or simply age better, True Niagen NR is my go-to solution.

• 30:38Dr. Darshan Shah?

  If you're looking for the best in fitness equipment on the market, I've found it for you. I've recently joined IFIT as their chief science advisor, and I want to tell you why. Their commitment to science and research is commendable, and I see them doing more to incorporate it into their devices than any other brand out there. So whether you're aiming to crush your cardio goals or build serious strength, IFIT's cutting-edge treadmills, bikes, and strength machines are designed to bring the gym to you. With world-class trainers and interactive workouts built into every machine, IFIT doesn't just keep you moving, it keeps you motivated. So if you're looking to elevate your home gym experience with the best in fitness tech, choose IFIT.

• 31:18Dr. Darshan Shah?

  So that's interesting. Okay, so I think the supplement-to-drug versus drug-to-supplement problem is, it seems like it's an arbitrary way to define what's a drug and what's a supplement, right? In the case of NAD boosters especially. And so NMN, was it Metro Biosciences that was testing it as a drug? Is that the?

• 31:37Speaker 01

  Metrobiotech has a patent on a crystal form of NMN.

• 31:43Dr. Darshan Shah?

  Got it.

• 31:43Speaker 01

  And potentially some use patents of like, trying to treat a disease with NMN and so forth. So they started doing their investigational new drug testing. And then the FDA learned that they can't approve NMN as a dietary ingredient because it's already being tested as a drug.

• 32:07Dr. Darshan Shah?

  Right, right. So everyone had to stop selling it online and...

• 32:10Speaker 01

  And if they're, if they didn't stop, then it means that they're willing to do a type of business where their stuff is not being, you know, tested. Yeah. So it's

• 32:23Dr. Darshan Shah?

  And this is the wild west of the supplement market is, you know, you have, like you said, you're selling the supplement, it's not being tested, just because you want to stay under the radar anyway. And then there's endotoxin, there's sawdust in the bottle. You don't know what's in the bottle, right? And so that's, that's the problem. Whereas regular supplements, like, let's just use vitamin D3K2 as an example. The companies that make this legitimately are doing third-party testing. And they are, they rely on their reputation and, and the third-party testing to sell us these supplements. I'm a physician, and so I, basically, I recommend, prescribe these supplements to my patients from certain companies I know that are third-party

• 33:05Dr. Darshan Shah?

  testing and doing this in a legitimate fashion. But you can't have that with N M N because everyone's doing it under the radar.

• 33:11Speaker 01

  Right, right. So, so for your clients, your, your patients, for N A D boosting, it's, it's got to be Niagen, right?

• 33:19Dr. Darshan Shah?

  Right, right. We use Niagen because, number one, the testing and the research behind it is solid. And so, you know, that's why I wanted to have you on because you, you created the product, basically. And I wanted to talk to you more about that. But I think it's really important to clarify these points with people because, you know, when you tell, when you talk about N A D, you talk about N A D. Then you look up N A D, and then you see N R, you see niacin, you see, you see all, the whole menu, and then no one knows what to choose. And these are the reasons I wanted to have you on, so people understand why I make the choice of choosing N R for my patients. Now, there's also N A D that people can take, right? And some of this has been tested, but also with these products

• 34:02Dr. Darshan Shah?

  too, they, they have that phosphate group, which makes them less available inside the cell where they're needed, right? Absorption is slow, there's less of it in the cell. And, you know, the research that's been done by Chromadex is pretty, pretty convincing that the intracellular amount of A T P and N A D is much higher by taking N R, right?

• 34:21Speaker 01

  Yeah, yeah.

• 34:22Dr. Darshan Shah?

  So that, so, so these are all the reasons why, well, let's, let's separate oral versus IV. I think that's as important too. So orally, it seems like taking oral nicotinamide riboside would be the most bang for your buck, right?

• 34:36Speaker 01

  Yeah, I mean, that's actually where most of the of the research is. So the original consumer dose of Nijin NR was 300 milligrams.

• 34:46Dr. Darshan Shah?

  Right.

• 34:47Speaker 01

  But clinical trials have been largely done from one to two grams per day.

• 34:51Dr. Darshan Shah?

  Right.

• 34:52Speaker 01

  Right. And so I think that when the New England Patriots started, you know, taking NR, I mean, they're guys in their twenties, although there was a quarterback who was 40, right?

• 35:03Dr. Darshan Shah?

  Yeah.

• 35:03Speaker 01

  And, um, you know, they're they're taking a gram a day, right? So people that are looking for those types of results of, you know, preserving walking speed for peripheral artery disease or anti-inflammation, probably were taking like three, three pills or something. So at this point, there's like a

• 35:20Dr. Darshan Shah?

  Clinical dose.

• 35:21Speaker 01

  Pro or something that's that is a gram dose.

• 35:25Dr. Darshan Shah?

  Right, right. I use a gram dose myself personally, but what I've found is starting with a lower dose for some people is better because, I mean, there's so much effect that some people, they feel really amped up or they can't sleep. And so there's a little bit of, I have to meter it in on certain, certain people.

• 35:44Speaker 01

  Interesting.

• 35:44Dr. Darshan Shah?

  Yeah, so the bigger the person, I start a little bit higher, but

• 35:49Speaker 01

  Yeah.

• 35:49Dr. Darshan Shah?

  Sometimes I do use a 300-milligram dose if they're a little, a smaller person.

• 35:54Speaker 01

  Yeah. For me, it's not a stimulant, like, uh, it's

• 35:58Dr. Darshan Shah?

  Absolutely.

• 35:59Speaker 01

  You know, and the thing that almost everybody notices is that their fingernails and hair grow

• 36:06Dr. Darshan Shah?

  Grow faster, right?

• 36:07Speaker 01

  Right. So that's a little bit of an anabolic piece of it. That's not been clinically proven, but I think that that would be demonstrable, you know, in a, in a clinical trial. It's like a very obvious

• 36:19Dr. Darshan Shah?

  Yeah, something that that needs to be studied as well.

• 36:22Speaker 01

  Yeah.

• 36:22Dr. Darshan Shah?

  You know, we keep talking about the need to be studied here.

• 36:24Speaker 01

  Yeah.

• 36:24Dr. Darshan Shah?

  And I think it's important to discuss why all of this hasn't been studied. And I think it's because there's not a billion-dollar pharmaceutical company at the back end of this funding massive studies, right?

• 36:35Speaker 01

  Right.

• 36:36Dr. Darshan Shah?

  And so a lot of these studies are being done onesie twosies by curious scientists, right?

• 36:42Speaker 01

  Yeah, yeah.

• 36:43Dr. Darshan Shah?

  And I'm, I'm so glad that there are scientists willing to do studies such as The peripheral artery disease study. I mean, that's fantastic, right? I've seen a lot of studies with nicotinamide riboside, or maybe their case reports around COVID. I've seen some.

• 36:58Speaker 01

  Yeah.

• 36:58Dr. Darshan Shah?

  And I'd love to talk about the efficacy of these molecules in infectious diseases.

• 37:04Speaker 01

  Yeah, yeah. So in 2000, March 2000, you know, I was teaching my biochemistry class and, you know, everybody's reading the, the, the news and, you know, I started giving a couple of lectures online because people didn't want to be in the lecture hall. And then, of course, the, you know, governor of the state of Iowa, where I was at the time, said, you know, don't, don't go to class anymore. And I'm sure the, you know, the same thing happened here. But we were able to keep on working in the lab because we wanted to see what was the effect on the NAD system of coronavirus infection.

• 37:42Dr. Darshan Shah?

  Right.

• 37:43Speaker 01

  And in fact, we were on the, the fourth floor of a particular building on the University of Iowa campus, where one of the world's experts on coronavirus is one that was on the third floor.

• 37:54Dr. Darshan Shah?

  Oh, that's fantastic.

• 37:54Speaker 01

  And we had actually done an experiment a couple of years earlier with a mouse coronavirus. And we had the data, you know, in our notebooks and we had the samples in our freezer. Wow. And we kind of reanalyzed those samples and we said, guess what? You know, double-stranded RNA viruses attacked the NAD system.

• 38:14Dr. Darshan Shah?

  Interesting.

• 38:15Speaker 01

  And then we looked at the, at the gene expression consequences of that. And it turns out that they activate these enzymes called PARPs. And they cause an innate immune response. So the same kind of innate immune response against intact mitochondria or NAD, there's an innate immune response against double-stranded RNA because it's considered like a foreign substance, right? And so the PARPs get activated, NAD goes down. And then we did an experiment to see whether NR would protect against infection. We got a very strong result.

• 38:53Dr. Darshan Shah?

  Interesting.

• 38:53Speaker 01

  And we published a, you know, that paper in the, the end of, of 2020. And then since then, There are a number of groups that tested NR as either a monotherapy or as a combination therapy with like three other over the counter molecules. And essentially, all of these studies have shown that NR accelerates time to recovery from COVID. So we predicted that it would help resist infection. And then others showed clinically that in combination with other non-toxic molecules, it accelerates recovery.

• 39:30Dr. Darshan Shah?

  Right.

• 39:30Speaker 01

  So there's some long COVID studies, I think, that are going to be coming out. And there's some kind of renal protection, kidney protection studies are going to be coming out. So, you know, it has some value in that space.

• 39:42Dr. Darshan Shah?

  Yeah, I totally agree. And, you know, now whenever someone calls me, Dr. Shaw, you know, I think I'm coming down with something, the first thing I do is have them start taking some NR supplementation because I think it really, like you said, it cuts down on their time that they're feeling not so well.

• 39:59Speaker 01

  Mm hmm.

• 40:00Dr. Darshan Shah?

  Let's talk about cognitive disease and also enhancing mental performance and using nicotinamide riboside. Have there been any studies around that?

• 40:10Speaker 01

  There's no real data on, you know, improving mental. I mean, there's, I think that there's a signal for improved cerebral blood flow in mild cognitive impairment. And there seemed to be some improvement in a Parkinson's study.

• 40:30Dr. Darshan Shah?

  Okay.

• 40:30Speaker 01

  And the results in Parkinson's were done in Norway in a small study. And they were strong enough that the Norwegian government, you know, funded a much larger study, which I think is going to be completing and unblinded sometime later in this calendar year of 2025. So we're looking forward to more data. But, I mean, I don't, I don't like to like bullshit people and say it's great for everything, you know, but, but, I mean, the, the thing about NIDRA and NR is that we know it's safe. And so, you know, the clinical trials are being done.

• 41:06Dr. Darshan Shah?

  Yeah, I appreciate you saying that because one thing I know about you, you're not a BSer. So I love, I love that you have data behind everything that you say. But I will say, these are relatively simple studies I would think to be done, especially for mental performance. You can just do a, you know, double blinded study where you give someone placebo versus NR and do a cognitive assessment test, right? And so hopefully someone does those studies. But I'm hopeful because I find myself, for example, podcasting is very mentally demanding, right? And so I definitely feel a difference on the days that I do my NAD or NR versus not, you know? And I say NAD versus NR, it just depends on what's available because I like to do it IV.

• 41:49Dr. Darshan Shah?

  And sometimes IV NAD has been available for a while. IV nicotinamide riboside just came out a few months ago. And I've been super impressed with the ease that we can do that. Specifically because it does absorb quicker, there's less side effect during the absorption process. And it's a good time to touch on this, by the way, about the different delivery mechanisms, right? Because we've touched on oral, which we know there's, there's a benefit to taking oral nicotinamide riboside, better absorption. IV as well, right? Between NAD and NR orally, IV.

• 42:27Speaker 01

  So there, there are some mouse studies that show that there's some improved tissue availability, IV. As I said earlier, you know, the failing heart benefits from oral nicotinamide riboside.

• 42:43Dr. Darshan Shah?

  Right.

• 42:44Speaker 01

  There, there are groups that claim that oral nicotinamide riboside is totally disassembled in the liver. But I don't know how they explain the results that have been obtained where oral NR was available, both to the cardiac tissue as well as to skeletal muscle. So, you know, there's a, I don't know what is the absolute percentage of oral NR that is available to cardiac and skeletal muscle. But it is, you know, qualitatively available.

• 43:17Dr. Darshan Shah?

  Right.

• 43:17Speaker 01

  Can it be optimized potentially with intravenous? Yes, potentially. But that's something, that's an area where it's going to be, you know, clinical trials that will be required to demonstrate.

• 43:28Dr. Darshan Shah?

  Exactly. And just for people listening, when you take something orally, obviously it goes into your gut. It gets absorbed through your gut into your liver. Your liver processes it and whatever is left is what's available. And that's why IV therapy is considered bypasses that whole mechanism, right?

• 43:43Speaker 01

  Yeah.

• 43:44Dr. Darshan Shah?

  What about giving it intramuscularly?

• 43:47Speaker 01

  I think people have done it.

• 43:49Dr. Darshan Shah?

  Yeah.

• 43:49Speaker 01

  But I don't know of, you know, clinical data. I don't know of the ultimate data on that.

• 43:56Dr. Darshan Shah?

  Yeah, yeah. And then finally, there's transdermal patches now too.

• 44:01Speaker 01

  That I don't know anything about. Yeah.

• 44:04Dr. Darshan Shah?

  So, so, you know, I think in the world of supplementation, there's lots of ways that people are trying to sell this stuff to people. And to your point, there's not a lot of data around what is actually bioavailable and what's happening. The studies, the only studies I've seen are oral and IV.

• 44:24Dr. Darshan Shah?

  It's very interesting. Any other potential uses of NR that you see or that you're hopeful could work out in the data in the future?

• 44:32Speaker 01

  Yeah, so I'd, I'd love to see wound healing trial.

• 44:36Dr. Darshan Shah?

  Yes.

• 44:36Speaker 01

  I would love to see a fatty liver trial. There was a little bit of a signal for that. I have to admit that early on, some of the clinical trialists were kind of high on hopium. Right? Of, of thinking that, oh, NR is going to improve, you know, insulin sensitivity and cause weight loss in 12 weeks with no lifestyle modification. And you know that that trial is going to fail, right? If, if you take, if you take 70-year-olds, obese, type 2 diabetic Norwegian, were they Norwegian or were they from Denmark? I think they were from Denmark.

• 45:20Speaker 01

  You were 70 year old obese type 2 diabetic men in Denmark, right? They basically, they haven't played hockey in 30, 40 years, right? They smoke, they overeat, they don't get terribly much exercise. And you just give them a supplement for 12 or 13 weeks? You're not going to improve their insulin sensitivity, right? They're not, they're not gonna, they're not gonna lose weight. It's not magic, right? Well, GLP-1, yeah, you might get a signal in 12 weeks. You're certainly going to get a signal in 26 weeks. But GLP-1, you know, injections cause people to eat less.

• 45:58Dr. Darshan Shah?

  Yes.

• 45:58Speaker 01

  Right? So that, that is the, the, the equivalent of calorie restriction.

• 46:04Dr. Darshan Shah?

  Right.

• 46:04Speaker 01

  It's a, you know, it's a pharmaceutical, you know, imposed way to get a person to follow through on their intention to eat less, right?

• 46:15Dr. Darshan Shah?

  Yeah, it's creating a lifestyle change by force.

• 46:18Speaker 01

  Yeah, I mean, while also doing other things to like slow gastric release and, and other things. So that, that will, that will cause weight loss. But taking vitamins, so, but if you look at that trial, that original trial that was done in Denmark, and you look at the data on the fatty liver, the, the men that had the fattiest liver that were on NR had a reduction in their liver fat. Now, the problem is it wasn't randomized for that, right? So it wasn't randomized for that, so it got to like a P of .13, which means probably was not by chance. It was probably a real result.

• 46:59Speaker 01

  But if you, but you really have to take the people in and say, this is intentionally a fatty liver trial.

• 47:06Dr. Darshan Shah?

  Right.

• 47:06Speaker 01

  They're all starting out at, let's say, .2 or 20%.

• 47:12Speaker 01

  You know, liver fat. And you're going to do it for 26 weeks, which is the way a pharma company would do it. And then you're going to follow that as a primary endpoint.

• 47:21Dr. Darshan Shah?

  Right.

• 47:22Speaker 01

  Because the problem is if you do these exploratory endpoints.

• 47:25Dr. Darshan Shah?

  Right.

• 47:25Speaker 01

  Right? For every 20 exploratory endpoints, you might get lucky.

• 47:30Dr. Darshan Shah?

  Yeah.

• 47:30Speaker 01

  And have a P. 0.05 result.

• 47:32Dr. Darshan Shah?

  Right.

• 47:33Speaker 01

  But if you pre-s specify your primary endpoints, you can't cheat.

• 47:36Dr. Darshan Shah?

  You can't cheat on it.

• 47:37Speaker 01

  You either made your endpoint or you didn't make your endpoint.

• 47:39Dr. Darshan Shah?

  Yeah.

• 47:40Speaker 01

  So now we're getting smarter about trials. And we want to encourage people to do trials where NR can actually work. Plus, exercise should probably be a standard of care.

• 47:52Dr. Darshan Shah?

  Right.

• 47:53Speaker 01

  Right?

• 47:53Dr. Darshan Shah?

  Absolutely.

• 47:53Speaker 01

  If people have overweight and fatty liver, then something like exercise or GLP-1 is probably the standard of care now.

• 48:00Dr. Darshan Shah?

  Right.

• 48:00Speaker 01

  Then you can see, does NR, you know, improve on top of that?

• 48:04Dr. Darshan Shah?

  Sure.

• 48:05Speaker 01

  Right?

• 48:05Dr. Darshan Shah?

  Yeah, you add the standard of care in as well.

• 48:07Speaker 01

  Yeah.

• 48:07Dr. Darshan Shah?

  Right, absolutely. Is there a use for NR in, you mentioned fatty liver disease. I think there's, like you said, there's a signal there.

• 48:17Speaker 01

  Yeah.

• 48:17Dr. Darshan Shah?

  What about for, in cancer, for example? How do you think about NR usage in patients that have diagnosed cancer?

• 48:24Speaker 01

  So, the original idea was that it may protect people against chemotherapeutic neuropathy.

• 48:33Dr. Darshan Shah?

  Okay.

• 48:34Speaker 01

  Because chemoneuropathy specifically attacks the NAD system. And so as a collateral effect of like vincristin type.

• 48:42Dr. Darshan Shah?

  Yes.

• 48:43Speaker 01

  Things which attack the microtubules.

• 48:45Dr. Darshan Shah?

  Right.

• 48:46Speaker 01

  The longest cells in our, in our body are cells that kind of start at the sciatic nerve.

• 48:51Dr. Darshan Shah?

  Okay.

• 48:52Speaker 01

  And go to the tips of your, your fingertips or the tips of your toes.

• 48:55Dr. Darshan Shah?

  Toes, right.

• 48:56Speaker 01

  So the people that have chemotherapeutic neuropathy have kind of a, you know, stocking and glove neuropathy. Right? So the idea is that NR might protect them from neuropathy. To my knowledge, the trials have not been completed that, that have set out to test that. NR has been very active in animal models of chemotherapeutic neuropathy and has not.

• 49:22Speaker 01

  Simultaneously like driven the cancer, right?

• 49:25Dr. Darshan Shah?

  Got it.

• 49:26Speaker 01

  What you would predict is that NR would help with DNA repair. And so, for example, nicotinamide is cancer preventative in a large Australian trial of of skin cancer prevention.

• 49:40Dr. Darshan Shah?

  Really? Okay.

• 49:41Speaker 01

  And so, you know, of course, it's an ask your doctor situation.

• 49:45Dr. Darshan Shah?

  Sure.

• 49:46Speaker 01

  Right? So I don't think it's going to be used as like a cancer treatment, but it could be used as an adjuvant to protect against chemo brain or chemo neuropathy.

• 49:55Dr. Darshan Shah?

  Wow, that's fantastic.

• 50:02Dr. Darshan Shah?

  This episode was brought to you by Next Health, a health optimization and longevity clinic located in Los Angeles, Manhattan, and soon to be opening in Montecito, Nashville, Miami, and many other cities in the United States and Canada. Next Health is the Apple Store of wellness, where you can optimize your health span and lifespan using cutting edge technology. I actually founded Next Health eight years ago to give my patients a place to go get extensive biomarker testing done and provide them with all the tools that I use to get my health in order. The longevity circuit in Next Health using hyperbaric oxygen, sauna, cryotherapy, and LED light is a game changer. In addition, the doctors at Next Health measure thousands of biomarkers and put into place

• 50:46Dr. Darshan Shah?

  a longevity optimization plan using advanced tools like ozone, plasma exchange, and peptides. Go to www Nex dot health to check it out.

• 51:01Dr. Darshan Shah?

  This episode was also brought to you by Vitaboom. Vitaboom is a revolutionary company that sends you a custom supplement protocol based on your needs using blood-based biomarkers. You could either send them your latest blood test or they will send you a finger stick test for blood analysis. Vitaboom then curates and ships you an extremely convenient monthly box of daily supplement packs that have your custom protocol in them. What's great is that they also provide all the best brands like Timeline, TruNiagen, and many others for your custom daily packs. I love mine especially for travel, since I don't have to bring 10 bottles of supplements with me and just open up a daily pack for every day

• 51:45Dr. Darshan Shah?

  that I'm taking my vitamins and supplements. Go to vitaboom.com and check it out.

• 51:53Dr. Darshan Shah?

  We talked about cardiac disease, we talked about heart failure, but what about in cases of just prevention for heart disease in the future?

• 52:03Speaker 01

  Yeah, I think that's a that's a big thing. There's a group in at University of Washington that has been doing the heart failure stuff. But almost every kind of heart disturbance disturbs the cardiac NED system. And so it's, you know, probably a very heart healthy and liver healthy supplement.

• 52:24Dr. Darshan Shah?

  Yeah, so I think with all these varied effects, potential varied effects and some proven effects, I use it as more of a foundational type of supplement with my patients. And so, I mean, you know, with every patient, they're all in N of one as far as their tolerance to supplementation. Some say no supplements at all. I want to get it all from diet and I respect that choice. Some say, you know, I'll take a few, but only the foundational ones. And then some will say, I want to take a few more. I'll take some things that might help, as long as they don't harm me. And then there's people that are like, give me everything that Brian Johnson and, you know, every single person.

• 53:01Speaker 01

  Right, which is polypharmacy and probably stressing their liver and kidney, right?

• 53:07Dr. Darshan Shah?

  Exactly, exactly. So, you know, I try to get people to be somewhere in the middle, you know? And then I take a look at all the supplements out there and I say, where would I put this in those four categories, right? And so I think NR supplementation is definitely coming more towards, for me clinically as a physician, talking to patients about what supplements to take. This seems one that because it's safe, because there's so many varied effects, I put it more in that bucket of more foundational, right? So if someone's going to take their, they have low vitamin D levels, I give them vitamin D3K2, an omega supplement, and then this is one that I put in that bucket of those supplements. Creatine is also one that I'm a big fan of. So that's just how I use it.

• 53:50Dr. Darshan Shah?

  I don't think, you know, that necessarily applies to everybody and not many physicians might disagree with me, but what I've seen treating thousands of people, I feel that that's where I put it in, especially if someone is, you know, ill at this moment with a viral or even bacterial, going through surgery, for example. Those are all use cases that I find helpful. Speaking of side effects, you've seen all the studies. What are some of the reported side effects of NR?

• 54:19Speaker 01

  I've heard of people that feel agitated or something like that, but it's not come up in the peer-reviewed literature. So when you do placebo-controlled trials and you record adverse events, right? You know, somebody has a bellyache or a headache or something like that, and it's recorded, but then when you add up all of the data, you either see an excess in the NR group or you don't. And to my awareness, I haven't seen NR-dependent adverse events in any of the trials. It's been essentially perfectly safe.

• 55:02Dr. Darshan Shah?

  Right. And that's my...

• 55:04Speaker 01

  But there may be, you know, a person out there for whom it causes some type of agitation. Don't do it, but it's not come up. It's not come up in the literature, to my knowledge.

• 55:16Dr. Darshan Shah?

  That's fantastic. Well, great. I mean, I think this is a great review of the whole NAD NR system, potential uses. There's a lot of science that needs to be done, as we both talked about. And I'm excited for all of it, because, you know, there's not a lot of molecules out there that can have so many beneficial effects across so many different potential use cases. And that's because every cell in our body needs NAD, right?

• 55:40Speaker 01

  Yeah, that's true.

• 55:41Dr. Darshan Shah?

  So can we zoom out and talk about the longevity field a little bit more, if you don't mind? So, you know, there's many other molecules that people are talking about. I know you're a curious individual, and you probably read a lot of these. What's your take on some of the other molecules that people are talking about right now? Rapamycin, metformin. Would you give me some of your thoughts on this?

• 56:04Speaker 01

  So I'd be more likely to take leucine than rapamycin. Okay? So you know why I said that. So, I mean, rapamycin is an inhibitor of the mTOR pathway. If you're a mouse, it's great.

• 56:21Dr. Darshan Shah?

  Right.

• 56:21Speaker 01

  Okay? But mice don't die of falls.

• 56:24Dr. Darshan Shah?

  Right.

• 56:24Speaker 01

  Right? People die of falls.

• 56:26Dr. Darshan Shah?

  Right.

• 56:27Speaker 01

  And healthy aging requires maintenance of skeletal muscle mass. I'm 63 years old. Okay, I have a You look great for 63. Thank you. I have a 44 year old, you know, wife and I have two stepsons. The wife is a marathon runner. So I and two dogs. So I chase a lot of people and and dogs around. So I want to maintain my skeletal muscle mass. I don't want an inhibitor of mTOR in my diet. And so to me, rapamycin is something for a transplant patient. And I wouldn't think it would be indicated for healthy aging. Would I like to see a clinical trial of it? Fine. Would I advise anybody related to me to volunteer for it?

• 57:12Speaker 01

  No, I think it's gonna fail in human. I've looked at the package insert or whatever it's called with it has the long list of of, you know, adverse events and, you know, it's, it's, it's real stuff. I mean, it infection, cancer and other things that could be associated with it. So I don't, even though it's great for mice. I don't think that mice are the world's greatest model for for human aging. You know, metformin is something that has 15 different mechanisms of action. You know, two or three of which inhibit mitochondrial functions, right? Um, it's beneficial in type 2 diabetes.

• 57:57Speaker 01

  Yes, people with type 2 diabetes, you know, have longer lifespans if they're on metformin versus other types of medicines, although those other medicines didn't include GLP-1 classically. They were the older, older stuff. So do I like the trial design of the thing that was planned for metformin? Sure. I mean, I think it's interesting trial design. But ultimately, no, I don't think that that's going to turn into a longevity drug. Right. So I don't think that there is a longevity drug. I don't claim that NR is a longevity drug. Although as something that, you know, is demonstrably useful as an anti-inflammatory, it's, like you said, it's one of the first things that you would give a person to sort

• 58:42Speaker 01

  of boost resiliency, right? Right. If a person doesn't die of a virus, then it might have scored, you know, as a component of their lifespan. But it's not a trial that you can set out to test it. So I think that, you know, the most valuable thing that we have is exercise and lifestyle. Absolutely. And, you know, trying to be, you know, engaged mentally and with other people and have a purpose in life. I don't think that we can do better than that. Yeah. In terms of like technology that has extended lifespan, I don't think I'm going out on a limb to say vaccination has been probably the biggest high-tech thing that we've had.

• 59:27Speaker 01

  I mean, it was, it's actually 1796, if you want to go back to the original reason why it's called vaccination, which is from a cow, right? Yeah. And Fleming, was it? Fleming, yeah. But, you know, vaccination has contributed to extending, you know, human life. And how does it work? You know, you're getting exposed to antigens, so you're educating your immune system so that if you walk into, you know, Disneyland and people haven't taken their measles vaccine, you're probably not going to get measles if you've been vaccinated. But if we start, you know, if we start, you know, casting aspersions on, you know, vaccination science and people start refusing measles vaccines and polio vaccines, we're going to

• 1:00:09Speaker 01

  have these scourge, you know, you know, pandemics that, that Like we're back in the 1920s again. So, so, you know, I think that that's the, but I don't, I don't actually see, I know that everybody wants an edge and everybody wants, you know, a concierge clinic like this beautiful one, but you know that you want to major in the majors, not major in the minors, right? Absolutely. In the 167 hours of the week where you're not seeing the patient, you want them to be sleeping and working out and enjoying their life and all those things, right?

• 1:00:47Dr. Darshan Shah?

  No, and that's what we always start with. You know, it's so important to optimize long nutrition, lifestyle, stress management,

• 1:00:55Speaker 01

  Yeah.

• 1:00:55Dr. Darshan Shah?

  sleep, exercise.

• 1:00:57Speaker 01

  Yeah.

• 1:00:58Dr. Darshan Shah?

  There's really no reason to come in for an IV drip of NR on a weekly basis if you're out there eating ultra-processed foods and sleeping four hours a night.

• 1:01:07Speaker 01

  Right, right.

• 1:01:08Dr. Darshan Shah?

  It doesn't make any sense.

• 1:01:09Speaker 01

  Yeah.

• 1:01:10Dr. Darshan Shah?

  So, yeah, these are all things that are additive to a basis

• 1:01:13Speaker 01

  Yeah.

• 1:01:13Dr. Darshan Shah?

  of good foundational behaviors.

• 1:01:15Speaker 01

  Yeah.

• 1:01:16Dr. Darshan Shah?

  Absolutely.

• 1:01:16Speaker 01

  Yeah.

• 1:01:17Dr. Darshan Shah?

  I'm curious about you, and you're a scientist, very well-regarded scientist, and you have an amazing laboratory at University of Southern California.

• 1:01:27Speaker 01

  No, no, City of Hope.

• 1:01:28Dr. Darshan Shah?

  Oh, City of Hope.

• 1:01:29Speaker 01

  Yeah, yeah.

• 1:01:29Dr. Darshan Shah?

  Okay, that's why you're at City of Hope. Can we talk about your laboratory and what you're studying now?

• 1:01:33Speaker 01

  Yeah, yeah. So, um, August of 2020, I was recruited away from University of Iowa. I was a biochemistry department chair, and City of Hope created a new department for me. It's called the Department of Diabetes and Cancer Metabolism. So about two-thirds of the research at City of Hope is cancer. About a third is diabetes and metabolic diseases. And so we created this new kind of interface department.

• 1:01:58Dr. Darshan Shah?

  Uh huh.

• 1:01:59Speaker 01

  And what I really decided to work on in kind of my new initiative is fatty liver disease.

• 1:02:05Dr. Darshan Shah?

  Hmm.

• 1:02:05Speaker 01

  So the technical name, as you know, is MASLD.

• 1:02:08Dr. Darshan Shah?

  Right.

• 1:02:08Speaker 01

  Right? It stands for metabolic dysfunction associated steatotic liver disease, which is fatty liver.

• 1:02:15Dr. Darshan Shah?

  Fatty liver.

• 1:02:15Speaker 01

  And we found it syndromically in a rare disease.

• 1:02:20Dr. Darshan Shah?

  Uh huh.

• 1:02:21Speaker 01

  So there's over a billion people on the planet that have MASLD. Most are people with obesity, but there are people that are skinny that have fatty liver disease. And syndromically, so in a rare disease context, there are people that are really skinny that almost always have fatty liver disease. And so we started working On that disease. It's called citron deficiency. And we have a paper that's in review right now where we we think that we break open um this disease and we figured out what's happening in in the people with this rare disease that is driving their liver to be always making fat. And never burning fat.

• 1:03:05Speaker 01

  So even overnight, you know, overnight, your body is burning glucose.

• 1:03:11Dr. Darshan Shah?

  Right.

• 1:03:11Speaker 01

  Burning glycogen, burning fat, right? But in their hepatocytes, they have these persistent lipid droplets. So they're constantly driving the synthesis of the fat and they're blocking fatty acid oxidation. And they have an interesting set of food preferences as well because they don't like sweets. And we figured out, yeah, it is interesting and we figured out, um, you know, we we think why they don't like sweets. It's it's due to something called FGF twenty one. And that is circulating uh at a high level in the mouse model. We've shown that when you induce the mouse model of this disease, citron deficiency,

• 1:03:54Speaker 01

  the mice have high levels of FGF twenty one. And so in this rare disease, the liver is dysregulated and it's making a high level of FGF twenty one, which is active in the brain. And it's also making the liver store fat. So now we have all sorts of ideas that are going to be for the specific disease of citron deficiency. And then a larger population that has lean mazalde.

• 1:04:19Dr. Darshan Shah?

  Right.

• 1:04:20Speaker 01

  And potentially common mazalde. And then we also have an idea of how can we get people to make more FGF twenty one.

• 1:04:29Dr. Darshan Shah?

  Right.

• 1:04:30Speaker 01

  With a small molecule. So those are all the things that are going on in our lab now.

• 1:04:34Dr. Darshan Shah?

  Those are all huge problems, right? And so you you kind of by studying this rare disease, you hit upon molecules that could be helpful for massive problems.

• 1:04:43Speaker 01

  Yeah, people may not realize this, but you know, like ten percent of breast cancer is hereditary. Right? So ninety percent of breast cancer is not, it is genetic, but it's. Spontaneous mutations, right? Whereas there are certain families where people, you know, are born with a BRCA1 mutation, right? But what a lot of people don't remember is that the BRCA1 mutation was found in men. It was in rare families where there was male breast cancer.

• 1:05:17Dr. Darshan Shah?

  Ah, that's where they found it, right?

• 1:05:18Speaker 01

  So when you look for these rare presentations of a disease, it's going to have a disproportional, you know, impact into understanding the mechanisms.

• 1:05:29Dr. Darshan Shah?

  Right.

• 1:05:30Speaker 01

  So that's why we thought a syndrome where people are very skinny but have fatty liver, that's going to have a really big insight into a big disproportional insight into the mechanisms of disease. And that's, that's what we're really excited about.

• 1:05:46Dr. Darshan Shah?

  That is exciting. It's a great model for research as well to...

• 1:05:49Speaker 01

  Yeah.

• 1:05:50Dr. Darshan Shah?

  Don't go looking for the needle in the haystack. Find something much smaller than a haystack, right?

• 1:05:54Speaker 01

  Yeah.

• 1:05:55Dr. Darshan Shah?

  Well, congratulations on that.

• 1:05:56Speaker 01

  All right.

• 1:05:57Dr. Darshan Shah?

  And when's that paper coming out?

• 1:05:58Speaker 01

  It's in review, so hopefully reviewers will be excited by it. And, but it can, people can read it on the bio archives on my Twitter page. We have a link to it.

• 1:06:08Dr. Darshan Shah?

  Okay, great. And so with that, where can we find you? Where can we learn more?

• 1:06:12Speaker 01

  Yeah, yeah.

• 1:06:13Dr. Darshan Shah?

  I mean, obviously, we have to keep up with you. You're coming up with some incredible science, so how do we keep up with you?

• 1:06:16Speaker 01

  So there's a lab website. It's brennerlab.net.

• 1:06:21Dr. Darshan Shah?

  Okay.

• 1:06:22Speaker 01

  And people can ask me questions on Twitter. I'm Charles M. Brenner. You have to use my middle initial M to find me. And then, you know, I make the rounds on podcasts and I'm going to be at University of Michigan Michigan next week. I was in New York City a couple of weeks ago and doing seminars. But yeah, yeah, great.

• 1:06:42Dr. Darshan Shah?

  She's from University of Michigan.

• 1:06:44Speaker 01

  Fantastic.

• 1:06:45Dr. Darshan Shah?

  Yeah, that's fantastic. Well, can't wait to have you on again. I feel like in a year from now, you're going to have even more incredible data to share with us and more incredible research. So thank you so much and for doing everything that you do. And thanks for joining the podcast.

• 1:06:57Speaker 01

  Pleasure. Yeah, thank you.

• 1:06:59Dr. Darshan Shah?

  Thank you, Dr. Brenner.

• 1:07:00Speaker 01

  Yep, bye.

• 1:07:04Dr. Darshan Shah?

  What a great conversation that was with Dr. Charles Brenner. I always enjoy talking to him. He's such an incredibly smart individual and he really can break down the science for me. So let's talk about my five top takeaways from this episode. Number one, our NAD system in our cells is constantly under attack. It's not just aging that causes a depletion of NAD. It's daily stressors like overeating, alcohol, UV light exposure, inflammation, viral infections, and even just needing DNA repair. Your body is working overtime to keep up with cellular demands and NAD is getting depleted every single time that you're exposed to these stressors, especially when your immune system fights off an infection or viral infection like COVID.

• 1:07:48Dr. Darshan Shah?

  This activates enzymes that burn through your NAD supply. Supplementation has been shown in many studies to accelerate the recovery from NAD depletion and improve and support your immune system. And that's why it can be a very critical supplementation to take for us on a day-to-day basis. Number two, without NAD, your body won't be able to make energy or repair itself. NAD is a molecule that moves the high-energy electrons to where they're needed to fuel ATP production. They power your mitochondria, they actually help repair your DNA, and they keep your immune system running. These are all incredibly important functions of NAD, and without NAD, you would die.

• 1:08:31Dr. Darshan Shah?

  Boosting NAD may help protect against fatigue and other symptoms, not just by energy production, but also by helping with metabolic disease, inflammation, neurodegeneration, fighting infections, wound healing, and more. So it's important to have boosted NAD stores, especially in this environment that we live in, where we just can't make enough energy right now using the precursors we have in most cases to keep up with the energy requirements. Number three, not all NAD boosters work the same way. So there are many NAD precursors. They include molecules that you've heard of like NMN and niacin and NAD and NR.

• 1:09:12Dr. Darshan Shah?

  Can't really enter the cell directly. What they have to do is they have to convert themselves to NR. And then the NR is absorbed and then turned into NAD. So taking oral or IV NAD actually just kind of hangs out in the bloodstream. Number four, the method of delivery of the IV or oral NAD makes a big difference. So when you give IV NAD, the IV NAD actually hangs out a long time in your bloodstream because it is not absorbed well by your cell. This slower absorption leads to more time in your bloodstream, which is what leads to some of the uncomfortable feeling that people feel when they're getting an IV NAD treatment. And this also can lead to a triggering of your inflammatory response.

• 1:09:55Dr. Darshan Shah?

  And a lot of the symptoms that people feel when they get IV NAD may be due to that triggering of inflammation. The same is true with oral NAD or NMN supplementation. It just does not get absorbed to the cell as effectively as NR does. That's why I love IV NR, an oral NR, which is made by the company Chromadex and a supplement called Niagen, IV Niagen or oral Niagen. This is the best absorbed, least symptoms as you're giving it, and the most efficacious. And finally, number five, the future of NAD research is just getting started. Emerging studies suggest that NR may have the potential for protecting cognitive function, improving fatty liver, supporting heart health, and even accelerating wound healing.

• 1:10:38Dr. Darshan Shah?

  But real science is going to tell us what works the best with, when these studies are done, I'll be sure to report them to you. Thank you so much for joining this episode of Extend. I hope you learned a lot about NAD and NR, and why it's useful and how you should take it. If you know someone that has questions about it or you think this molecule might help them, please forward them this episode. And please give us a rating. It really helps us out. Thank you.

• 1:11:06Dr. Darshan Shah?

  Thank you so much for listening to the podcast today. Please remember to subscribe if you liked this episode and give us a good review and share a link with your friends. It really helps to support all of our efforts. I also want to remind you that the information shared on this podcast is for educational purposes only and is not intended to replace professional medical advice, diagnosis, or treatment. Please consult with your healthcare provider or physician before making any decisions or taking any action based on what you hear today, especially if you have any underlying health conditions or on any medications. Your doctor knows your personal health situation the best, and it's always important to seek their guidance.