Dhru Purohit Show - How Low Nitric Oxide Drives Heart Disease, Poor Sexual Health, and Chronic Inflammation with Nathan S. Bryan, Ph.D.

Episode Date: July 17, 2023

This episode is brought to you by Birch Mattress by Helix and InsideTracker. Each year, approximately 700,000 lives are lost to cardiovascular disease. Shockingly, half of these individuals experience no prior symptoms before an event. Low levels of nitric oxide—a molecule that promotes vasodilation and smooth blood flow—could be largely responsible, and by recognizing the signs of deficiency, we can take steps to raise our levels and lower our risk. Today on The Dhru Purohit Podcast, Dhru sits down with Dr. Nathan Bryan to talk about why nitric oxide is the single most underrated molecule when it comes to our short- and long-term health. Dr. Bryan is an international leader in molecular medicine and nitric oxide biochemistry. He’s been involved in nitric oxide research for the past 20 years, and his many seminal discoveries have resulted in dozens of US and international patents. Dr. Bryan's discoveries have led to product and technology innovations that have improved patient care worldwide. He is the founder of Nitric Oxide Innovations, LLC, a privately held, clinical-stage biopharmaceutical company that is actively engaged in the discovery and development of nitric oxide-based therapies. In this episode, Dhru and Dr. Bryan dive into (audio/ Apple subscriber) -What happens in the body when we don’t produce enough nitric oxide (1:46 / 1:46) -The link between nitric oxide and heart health (3:46 / 3:56) -How nitric oxide is produced in the body (10:04 / 7:11) -Habits that boost nitric oxide production (12:02 / 9:08) -How mouthwash inhibits nitric oxide production (18:20 / 16:20) -Nasal breathing and nitric oxide production (27:15 / 24:19) -The impact of proton pump inhibitors on creating nitric oxide (32:30 / 29:31) -High blood pressure and its link to nitric oxide (42:25 / 38:29) -How morning sunlight creates nitric oxide (45:22 / 42:05) -Early signs of low nitric oxide levels (58:26 / 55:33) -Foods that reduce nitric oxide levels (1:07:20 / 1:04:27) -How to test your nitric oxide levels (1:12:20 / 1:09:23) -Leafy green vegetables to boost nitric oxide production (1:20:56 / 1:18) -Future products and prescriptions for boosting nitric oxide (1:34:30 / 1:31:30) Also mentioned in this episode: -VENDYS -N1O1.com (get 10% off any of Dr. Bryan’s nitric oxide products with the code DHRU)  -nitricoxideinnovations.com For more on Dr. Nathan Bryan, check out: @drnathansbryan drnathansbryan.com. This episode is brought to you by Birch Mattress by Helix and InsideTracker. Birch Mattress by Helix is made from organic latex, organic cotton, New Zealand wool, and American steel springs. To get 20% off your Birch Living mattress, head over to birchliving.com/dhru today. InsideTracker provides detailed nutrition and lifestyle guidance based on your individual needs. Right now, they’re offering my podcast community 20% off. Just go to insidetracker.com/DHRU to get your discount and try it out for yourself. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

Welcome to the Drew Perot podcast. Each week we explore the inner workings of the brain and the body with one of the brightest minds in wellness, medicine, and mindset. This week's guest is Dr. Nathan Bryan. And on today's episode, we're talking about why nitric oxide is the single most underrated molecule when it comes to our short and long-term health. In fact, if you care about the topics of heart disease, optimal sexual health, Alzheimer's disease, avoiding it rather, high blood pressure, and even long-term, longevity, you're going to want to know and learn more about why you need this super crucial molecule called nitric oxide. Now, a little bit more about Dr. Brian. Dr. Brian is an international leader in molecular medicine and nitric oxide biochemistry. He's been involved in nitric oxide research for the past 20 years and has made many

seminal discoveries in this field. His discoveries have resulted in dozens of issued U.S. and international patents and the product technology resulting from his discoveries and inventions have improved patient care worldwide. Dr. Brian is the founder of multiple companies, including Nitric oxide innovations, a privately held clinical stage biopharmaceutical company that is actively engaged in the discovery and development of nitric oxide-based therapies. Stay tuned for a fascinating episode all about nitric oxide and why we need more of it in our life with Dr. Nathan Bryan.

Dr. Brian, welcome to the podcast. A pleasure to have you here. I'd love to start off with the basics. You know, nitric oxide is such a crucial molecule for everybody who's listening, but a lot of people are undereducated on how crucial it is. What happens in the body when we don't produce enough nitric oxide? What's actually not taking place or what does take place that's actually not good for us? Well, thanks, Drew.

It's great to see you. And thanks for me. invitation to join you. And you make a very important point. So to answer your question, we know that loss of nitric oxide is the earliest event in the onset and progression of most, if not all chronic diseases. So if you become deficient in nitric oxide, what happens? Usually the first sign and symptom is an increase in your blood pressure or sexual dysfunctional what we call a rectal dysfunction. That occurs in both men and women. You know, two out of three Americans have an unsafe elevation and blood pressure. Fifty percent of men over the age of 40, self-report, some degree of

erectile dysfunction. So those are the main two. The other kind of that are not as obvious to the general public, but, you know, it's clearly been elucidated in the, in the basic sciences is you develop insulin resistance and metabolic dysfunction. Your triglycerides go up. You become exercise intolerance. So if you, you know, if you get shortness of breath walking up a flight of stairs or, you know, just going for a casual walk, then that's a symptom of nitroxide deficiency. If you forget where you left your keys and you start developing mild cognitive disorders, then, you know, that's a loss of regulation of blood flow to certain readings of the brain that's secondary to a loss of nitric oxide production. So all of those things, really every single thing we know

about, you know, global health problems can be traced back to insufficient nitric oxide production. It's amazing. Once you start to truly learn, and I saw a podcast of yours recently where you're on a colleague of ours podcast, and as you were breaking down every single way that our body can say, ouch, when it doesn't have enough nitric oxide, even me, who studies the subject and has had many people on this podcast talk about the importance of nitric oxide, I've been sort of amazed and I've been not only amazed, but it's had me want to double down and make sure I take care of the basics to ensure that I'm producing enough nitric oxide. And we're going to cover some of those basics.

You know, one that you didn't mention that I'd just love to talk about a little bit more before we break down the mechanism and what nitric oxide is, is endothelial health. Talk about nitric oxide and endothelial health. Why the key to cardiovascular disease and avoiding cardiovascular disease or minimizing the likelihood of a cardiovascular vent or stroke is so tied into endothelial health and nitric oxide? Well, you know, it's a concept and subject matter that's very near and dear to my heart because I've been studying nitric oxide and endothelial function in basketball for more than 25 years. And the fact that cardiovascular disease remains the number one killer of men and women worldwide is

simply unacceptable because we know what causes cardiovascular disease. We know how to diagnose it and we know how to treat it, prevent it and cure it. And it all surrounds the endothelial production of nitric oxide. So just for your audience, you know, they're obviously well educated, but the endothelium is the cells that lie in all blood vessels throughout the body. You know, your endothelium is your largest organ. And it's the function of those endothelial cells that basically control blood flow to every organ tissue and cell in the body. It's what mitigates and controls inflammation, oxidative stress, and immune dysfunctions, the key contributors to all chronic disease.

So when you develop endothelial dysfunction, and we characterize that by the inability of the endothelial cells to produce nitric oxide gas. And that was the first pathway to be discovered back in the late 70s, early 80s, on how nitric oxide is actually produced. So when we get a signal, like when we get sheer stress, when we begin to exercise, or you have the release of some agonists like acetylcholine, histamine, bradychina, that signals the endothel cells to produce nitric oxide. And as long as that enzyme, which we call nitric oxide synthase, is coupled and functional,

then the endothel cells produce nitric oxide, you dilate the blood vessels, you suppress inflammation, and you have normal vascular function, and we have that good endothelial function. But when you have oxidative stress that leads to gnawis uncoupling, then all these activators and stimulators, that would normally produce nitric oxide, you don't get any nitric oxide produced by the enzyme in the endothelium, and that's what we call endothelial dysfunction. And as you can appreciate that it's endothelial dysfunction that's at the root cause

of every major chronic disease. So you lose the ability to control and regulate blood flow to those organs, those vascular beds. You have an increase in inflammation where platelets, monocytes, and neutrophils start sticking to the lining of the blood vessel. you get transmigration of immune cells, cholesterol fat, that then starts the plaque deposition, plaque instability, plaque rupture, and that's heart attack and stroke. So the mechanism of onset and progression of cardiovascular disease that leads to heart attack and stroke is completely elucidated.

There is no question in the scientific literature about what causes cardiovascular disease and now how we can safely and effectively prevent, treat, and cure the number of one killer of men and women worldwide. Today's episode is brought to you by the birch mattress by Helix. So we all know that getting a good night's sleep is super important, not just for our health in general, but for being a functional and thriving human being. I can tell you that when my sleep suffers, the next day is rough. That's why I'm so psyched about today's sponsor, Birch mattress by Helix.

I've been sleeping on my birch mattress for three years now. True story. And it's the real deal. The Birch mattress is certified, eco-friendly, organic, and fair trade, plus they're made from natural non-toxic materials. That's important for a couple reasons. First, with Birch, I'm avoiding a ton of VOCs and off-gas and chemicals that most other mattresses emit and that mess with the quality of my sleep and probably yours too. Secondly, I can sleep better at night knowing that I'm supporting a company that does right by their employees in the environment.

You just can't find that at a typical mattress store. I absolutely love my Birch mattress, and right now you can get your own for 20% off plus two free eco-rest pillows at birchliving.com backslash Drew. So get ready for the best most eco-friendly sleep of your life. Visit Birch, B-I-R-C-H-L-I-N-G, dot com slash Drew. That's D-H-R-U to get 20% off plus two eco-rest pillows today. What if I told you that you could get access to a person? personalized, action-oriented health plan that's literally always at your fingertips and based

on data from your actual body, your own body, that would seriously level up your health game. Am I right? That's why I'm super excited about the company Inside Tracker. They use data from your blood, DNA, and fitness trackers to give you personalized and science-backed recommendations on things that you can control to optimize your health today. Things like food, supplements, workouts, and lifestyle choices, including ways. to optimize sleep and stress. By the way, Inside Tracker has a super crucial test for cardiovascular health called ApoB.

ApoB measures your body's ability to efficiently transport and remove cholesterol, and is currently the best blood biomarker to assess cardiovascular disease risk. And knowing your ApoB level can help you take action because you can totally change it for the better through healthy diet and lifestyle habits. And starting in July, Inside Tracker has added insulin, which is the key biomarker for sustained energy and an early warning sign of chronic disease. When you get started today, you can receive 20% off using my code. So just head over to insidetracker.com slash drew, D-H-R-U to save today.

That's inside, I-N-S-I-D-E, Tracker.com slash D-H-R-U to save 20% today. Well, we'll come back to cardiovascular disease because I have so many questions about that and some personal experience on sort of looking at my endothelium health with my cardiologist that I'd love to chat with you about. But let's start again at the basics here. We have mostly a late audience that's listening. We've done some episodes on this, but it's always a good refresher. What is nitric oxide and how is it produced inside of the body? Now look, it's a gas. And you know, one of the kind of interesting things about the importance of nitric oxide in human physiology is it's a gas. And once it's produced, it's gone in less than one second. But while it's

produced, it activates a number of what we call second messengers. So it has receptors, it binds to it, and then starts these entire signaling cascades that regulate basically every single cellular and biological function. So it's a gas produced in less than a second, and it's a signaling molecule. So it's how cells in the body communicate with one another. And so we've touched on a lot of the physiological effects of nitric oxide. But really that's what it is. It's a signal and it controls oxygen delivery. It controls circulation and blood flow, controls vascular inflammation. So our ability to heal, the other thing it does is it stimulates our own, or mobilizes our own stem cells to differentiate and go to sites of injury

and repair and replace dysfunctional tissues. So as you know, humans are regenerative beings. The human body heals itself provided we give it what it needs and that the human body gets the signal to go and repair and replace dysfunctional tissues. And that's really the most important anti-aging effects of nitric oxide. Now, because the odor we get, the less nitric oxide we make, the less we're able to heal and repair and recover from injury. But if we have sufficient stem cells around and we have nitric oxide to tell those stem cells, hey, wake up, mobilize, go do your job,

and repair these dysfunctional tissues or cells, then we heal. And I think that's the basis. And what I think is the holy grail in anti-aging medicine. and really any regenerative medicine. What are some of the habits that we have that contribute to the production of nitric oxide? Let's talk about that first because then an area that you're very passionate about is the habits that many of us have that decrease nitric oxide. So what are some of the habits and what are the ways that we naturally encourage healthy production

of nitric oxide in the body? Well, you know, the whole field of nitric oxide is extremely complex. In fact, it's probably one of the most complicated complex. reaction mechanisms in the human body. But lifestyle and habits such as moderate physical exercise, a balanced diet and moderation, lots of green leafy vegetables, 20 to 30 minutes of sunlight exposure today, those are the three main stimulators or activators of nitric oxide production. So it really boils down to diet and lifestyle, maintaining a healthy microbiome.

So these are really simple kind of life. style strategies and common sense techniques that you can use to not only promote nitric oxide production, but to prevent this age-related decline that leads to age-related disease. So I want to tease out some of the ones that you talked about in the beginning. Some of these areas of what happens to the body when we don't have enough nitric oxide. And then we're going to get into action items and other things in a minute. So one of the things that you mentioned is that when we don't produce enough nitric oxide, we are not as metabolically healthy.

So connect those dots for us. What is it about the absence of healthy levels of nitric oxide that can impact things like insulin signaling? Well, when we talk about cellular metabolism, there's kind of a broad aspect about that. So certainly one is, you know, substrate availability and energy production. And obviously that involves insulin signaling, glucose uptake, and maintenance of healthy insulin and glucose levels in the body. The other is terms of mitochondrial function, how well the mitochondria can utilize oxygen to produce cellular energy. So all of those are kind of what I refer to as metabolism and energetics of the cell. So in terms of nitric oxide, and we published this, I believe in 2011, we were the first research lab to show that nitric oxide is absolutely essential for insulin signaling.

So let's talk about insulin resistance in metabolic disease and type 2 diabetes. So the insulin is secreted from the pancreas. The insulin secretes and it binds to insulin receptors on most cell types, but primarily they're fat, skeletal muscle, and in liver cells. That's what controls glucose uptake and maintenance of hypoglycemic index. Nitric, if your cell can't produce nitric oxide, then there's insulin, there's a disruption in insulin signaling, and we call that insulin resistance. Because when insulin starts this signaling cascade, all of those converge on nitric oxide

synthase enzyme, but if that enzyme is uncoupled and dysfunctional, you don't make nitric oxide so there's a disruption in that cellular communication. But the terminal step in insulin signaling and glucose uptake is a protein called glute 4, which signals to go to the membrane buying glucose and bring it inside the sill and clear it from the circulation. So if that cell can't produce nitric oxide, then you don't get glucose uptake. You develop hyperglycemia. That signals the body, hey, I need more insulin. So the pancreas secretes more insulin.

Now you have hyperinsulinemia, hyperglycemia, and that's the inflammatory response that leads to the vascular damage and all the metabolic perturbations in patients with insulin resistance type 2 diabetes. So if you can make nitric oxide or we can give a source of nitric oxide, you can potentiate insulin signaling, you can complete that signal in the cell, and you can lead to increase glucose uptake, downregulate the insulin secretion from the pancreas, and completely overcome the metabolic disturbances of insulin resistance. So nitric oxide is required for insulin signaling and glucose uptake. It's fascinating when you really understand that. You know, we know that

80% of Americans, at least, are not metabolically healthy by the standard definition of what metabolically healthy looks like. And then it becomes a catch-22 because if you are not producing enough nitric oxide, you're more likely to develop diabetes and some of these other aspects of poor metabolic health. But then once you have those, you don't produce enough nitric oxide in the first place. So it becomes a downward cycle. It's almost like if we look at our society today and our modern industrialized, Westernized society, it's like if you wanted to create the perfect recipe to destroy this super

important molecule that's in the body that's responsible for so many different functions, you'd put somebody in the Western diet, the Western world, the Western version of stress, and that'd be the perfect recipe to destroy nitric oxide. You know, if a terrorist group or another country was doing this to us, we'd be up in arms, but right now we're not because in a way we don't realize that we're doing this to ourselves. Would you agree with that? No, absolutely. Look, this is subtle biological warfare.

And I always, you know, sometimes jokingly, but it's really not a joke. It's very serious. And it's a life and death situation. But if I wanted to make you sick and I wanted to make you dependent upon pharmacotherapy for the rest of your life, I would put you on a Western diet. I would tell you to follow the government's food pyramid or recommendations on food. I would give you a proton pump inhibitor or an an acid to completely suppress stomach acid production. I'd give you a cholesterol lowering medication to get your cholesterol below 200 where you couldn't make testosterone.

You could make estrogen or vitamin D. You disrupt the lipid rifts in the cell membrane. You prevent cell signaling. You disrupt nitric oxide production. And I would put fluoride in the municipal water supply. kill the oral microbiome, I would overprescribe antibiotics to kill the gut microbiome, to kill the oral microbiome. That's how I would completely destroy a human's life and make them completely dependent upon pharmacotherapy and extract as much value as I could from those individual

patients. So this is biological warfare, and everything we've learned about nitric oxide biochemistry and physiology over the last 30 years points to the fact that all these things disrupt nitric oxide production. And then when you can't make enough nitric oxide, you get inflammation, oxidative stress, and immune dysfunction, you lose regulation of blood flow, you have heart attack and stroke, and that's the end of the story. So this is biological warfare that fortunately, we understand, and now we can mitigate it completely reverse. It's fascinating. You know, there's one item that you're so passionate about that you left out. You kind of hinted towards it. You say you destroy the oral microbiome. In addition to everything you mentioned, antibiotics and poor diet,

in high stress and the Western life, you'd get everybody, which I think I heard from you, that 200 million Americans use mouthwash. You'd put everybody on mouthwash, which would be another crucial component of destroying nitric oxide. Why is mouthwash so bad for us if we care about our long-term health,

if we care about longevity, and if we especially care about this topic, nitric oxide? Well, you know, we got interested in this about 20 years ago, and there was the huge microbiome project, trying to characterize all the bacteria that live in and on our body. And we've learned so much through that. You know, the bacteria that live in and on our body outnumber on human cells 10 to 1. So these bacteria are not kind of pathogenic, infectious.

These are what we call symbionts. So they provide a critical metabolic function to the human host. And so we destroy these bacteria at our own peril. So whereas most of the microbiome project was kind of focused on the gut microbeauts, gut microbiome, but 20 years ago, we got interested in the oral microbiome because there was some emerging data showing that there were some nitrate-reducing bacteria or nitric oxide producing bacteria that were essential for regulating systemic blood pressure. Now, that was a completely new concept in terms of vascular biology and the regulation

of systemic blood pressure. So we started this whole project of trying to characterize what bacteria were responsible for producing nitric oxide and then regulating blood pressure. And we've fully characterized these bacteria on the dorsal part of the tongue. We know a lot about them. But most importantly, if you eradicate these bacteria by using mouthwash, then it leads to an increase in blood pressure. You lose the protective benefits of exercise and you become nitric oxide deficient. And these are the numbers, I think, I got from some, maybe the world. health organization or some statistics that two out of three Americans wake up every morning and use

mouthwash. So they're killing not only the bad guys, and they actually advertise this, kills 99.9% of the bacteria in your mouth. That is a very bad idea because you're disrupting the good bacteria that are providing essential metabolic functions, and one of the most importance is generating nitric oxide or reducing nitrate to nitrite. And when you eradicate that process, your blood pressure goes up, which is the number one risk factor for the number one killer of men and women worldwide heart attacks, and you lose the protective benefits of exercise. And this is really where people have that aha moment because I think for the most part, humans have good intentions. So we try to do what's the best for us. We try to do things that

keep us healthy and free from sickness and illness. So they tell us, you know, the bacteria, and this has been going on for hundreds of years, it's called the oral systemic link. If you have oral dysbiosis or periodontal disease, gingivitis, it leads to an increase in the risk of cardiovascular disease. So they take a sledgehammer approach and goes, oh, we've got to kill all the bacteria. Well, there's a lot of collateral damage. We can now isolate the pathogens while maintaining the good healthy oral microbiome and really do the host a favor. But there's clear evidence now that if you use mouthwash, it kills the good bacteria as well as the bad,

you decrease nitric oxide production, your blood pressure goes up, We're now finding that your early onset of things like erectile dysfunction, mild cognitive disorders. You lose the protective benefits of exercise. And so I tell people the most important thing you can do if you're doing this is stop using mouthwash. And the other thing people don't realize is fluoride. You know, fluoride's in toothpaste. It's an antiseptic. It's a neurotoxone that kills your thyroid.

And many people are using fluoride-based toothpaste. And so to me, it's no coincidence or no mystery while America. why Americans are the sickest population on the planet? Because you alluded to it, everything we do is disrupting nitric oxide production and putting us on a very slippery slope for cardiovascular disease, metabolic disease, insurresistant, diabetes, Alzheimer's, everything we know about the etiology of every major chronic disease. It's so powerful when you realize that truly, if we care about the future health of this country, obviously the people that are alive, but future generations to come that are not alive,

right now, we have to have a national uprising when it comes to health. And that's where I feel like podcasts, many of my colleagues that are in this space, books, educators like yourself, people that are doing research like yourself, where now the information can get directly to the public, whereas before we had so many gatekeepers involved. And that's how we perpetuated, you know, nine out of ten dentists think that you should brush with fluoride. And, you know, you would feel that there was this term that was often used, you know, fairly recently during the pandemic, the science is settled. So let's move on. We'll cover the next thing. What's the next prescription we have to put people on? And as we know now, the science isn't settled. The science is

an ongoing discussion and we have to be willing to question things if we're actually going to be willing to turn things around. So that's my little monologue on the situation. I can see you nodding your head, so it sounds like you agree as well. You're right. I mean, I taught in medical schools. I taught future physicians when I was at University of Texas medical school. And, you know, I've published over 100 peer-reviewed scientific papers. So here's what I've learned over kind of that early part of my career, 20 years in academic medicine, is that the general public doesn't read scientific papers on PubMed. And there's so much resistance in the curriculum of teaching physicians, future physicians, that the curriculum's already established, and it's very difficult

to change that, because really that's the financial model of medicine. And medicine is a business, and we can't forget that. So I don't refer to patients anymore, or people who go see physicians, patients. You have to consider them customers. Their business just like, and I'm not bad-mouting physicians, because I think most physicians out there are really good-hearted people who have the best interest of their patients in mind. but the system in which they're trained in and they control them and control their medical licensing

and control how they diagnose, treat, and patients is all a financial model. So, and I think that's why these podcasts and really ways to reach the public directly, without having to go through a physician and these so-called gatekeepers, but the information's out there. And then we have informed consumers that are properly educated so they can make informed decisions on what's best for them and their health. and now what we try to do is we empower the patient to go and ask the question the tough questions to the physician.

And now what we're finding, it's kind of a complete loop because then it forces the physicians because no physician wants to be asked a question he doesn't know the answer to. So it forces them to go kind of update and educate themselves on this emerging science and then it opens their eyes. And then now we have more informed people, both consumers and healthcare practitioners, that will hopefully be, you know, motivated to learn this new science. But, you know, there's 190,000 scientific papers published on nitric oxide in the scientific literature.

So for me, and that's kind of why I left academia, we have all the information we need. I don't need to go do more research, basic science, and figure out how does the human body make nitric oxide, what goes wrong in people that can't make it, and how do we fix it? We have that information. So now my objective and really mission, personal and professional mission, is to not only create awareness and education around nitric oxide, but bring safe and effective nitric oxide-based therapies or product technology to every major market segment in the world.

And when we do that, when we accomplish that, it will change the world, it will change health care, and it'll now empower patients to be able to take care of themselves, and it'll be the original mission of medicine is to, you know, inform the patient to where they know how to heal themselves and to avoid going to a physician. That's the objective. Powerful.

You know, I want to go back to the basics of nitric oxide. You know, talk to us a little bit about nasal breathing, and what role that plays in the process of creating nitric oxide in the first place. I'd love for you to cover that a little bit. Yeah, so we talked about endothelial dysfunction. And the nitric oxide synthase enzyme is found in the endothelium. Well, that enzyme is also found in the epithelial cells. So the endothelium is what lines the lining of blood.

vessels, the epithelium is what lines the guts and the nasal sinus is kind of the outside world. And so when we do deep breathing or nasal breathing, there's mechanoreceptors on these epithelial cells that when we activate them, it turns on the enzyme that makes nitric oxide. So when we practice deep breathing nasal breathing, it stimulates and activates nitric oxide production. And then that nitric oxide that's produced in the epithelium will be delivered into the upper and lower airways. It's a broncholidilator.

you'll dilate the bronchules, and you'll get better oxygen uptake and oxygen delivery. But just like if you develop endothelial dysfunction, then those same conditions occurred in the epithelial cells. So you have epithelial dysfunction. Now, if that enzyme is uncoupled in the epithelial cells and you do deep breathing or nasal breathing, that enzyme is unable to produce nitric oxide. So you don't get any nitric oxide produced if you have an uncoupled gnaw. So when we've been able to detect that we can measure exhaled nitric oxide in young people that have a coupled NOS enzyme and do deep breathing exercise, we can do that same measurement in exhaled patients with endothelial dysfunction. They do deep breathing and they don't get any nitric oxide produced. So we have to get

to the root cause of that. And so we have to recouple the NOS enzyme, restore the enzymatic activity of that enzyme. And now when we do deep breathing or nasal breathing, now we can actually generate nitric oxide and get the benefits of that. lowers blood pressure, you know, it activates the parasympathetic nervous system. It's calming, but you have to restore the function of that enzyme. So for most of the people that are listening today, if their breathing pattern, you know, separate from diet and stress, which we'll get to in a second, if they are breathing as human beings were designed to breathe during sort of day-to-day function, and we've had people like James Nestor on the podcast, Dr. Luignaro, who I mentioned to you

earlier. And so our listeners are a little bit familiar with this, but it's good to connect the dots and hear your perspective. So if most people who are listening today are generally throughout the day breathing through their nose and don't have sleep apnea that they know of, many people have sleep apnea and they don't know it, they haven't been diagnosed yet, would you consider that their breathing routine is in a good place to, at least on the breathing side, produce nitric oxide? or do you encourage additional sort of yogic breathing or sort of classes or any other intentional breathing methods to further enhance or optimize nitric oxide production? It's a vicious cycle. We need oxygen to make nitric oxide through that enzyme. If we don't have oxygen or sufficient oxygen, you don't make nitric oxide.

And then without nitric oxide, you can't take up oxygen and deliver oxygen by the red blood cell. So it's really this perpetual cycle. that if you have sleep apnea, whether it's obstructive or some other physiological issue, then we have to restore the breathing that actually delivers oxygen. But here's the issue with nitric oxide production. Oxygen is never the limiting factor in nitric oxide production. L-Rgenine is never limiting, rate limiting in nitric oxide production. So it's the oxidation of tetrahydrobiopterin,

which is an essential co-factor for nitric oxide production. So if we can maintain BH4 reduction, then that maintains the coupling of this NOS enzyme. You get this beautiful 5-Electron oxidation of arginine to make nitric oxide. So if we can maintain the redox balance of BH4 to BH2, then we maintain the coupling and function of that enzyme. And fortunately, through my 20 years of research, we know how to do that, and we've identified product technology that does that. So to answer your question, it's obviously very important to practice these breathing techniques, but if you don't have the functional enzyme that makes nitric oxide, then you're going to have limited kind of benefits of that.

So what we do, what we try to practice is, number one, an anti-inflammatory diet that prevents the oxidation of BH4, moderate physical exercise. I'm not a big fan of reaching that anaerobic threshold that then oxygen becomes limiting for mitochondria, you get into fermentation, you get lactic acid build up, and you have poor recovery. So all of these things that we talked about when we opened up the podcast, moderate physical exercise on anti-inflammatory diet, and you maintain a normal healthy redoxygen, it prevents BH4 oxidation, the NOS enzyme maintains its coupling and maintains nitric oxide production. So it's really that simple, but you can't fix one without the other.

You know, just like we talked about mouthwash, one of the things that you're very passionate about educating people on are this classification of medications called proton pump inhibitors. Help our audience understand, for those that are not familiar, what is that? When is it used? And how does that not only impair nitric oxide production, but also could be linked to or maybe linked to or is linked to? you'll tell us higher incidences of cardiovascular events for individuals who are on it long-term. So yeah, proton pump inhibitors. We'd love for you to talk about that. Yeah, so this is a class of drugs that are broadly classified as an acids.

So they're FDA approved for the acute treatment of gastroesophageal reflux disease. So if you have esophagitis or you get reflux, then you prescribe these medications. the FDA approval was only for acute use. These drugs have never been approved for chronic use. And so what we're finding now is that, I don't know, maybe 10 or 12 years ago, you may recognize that these drugs went from prescription only to over the counter. So you have prolosec, previsit, OTC. So now people can take these every day without the guidance or the oversight of a physician.

And they take them for 10, 12, 15, the rest of their. life. And so here's what we're finding from not just the epidemiological data from chronic use, but at the cellular level of mechanistically what these drugs are doing. So these are called proton pump inhibitors. They suppress hydrochloric acid production from the pridal cells in the lining of the stomach. And so when you suppress stomach acid production, you can't break down proteins into amino acids. And for me, it's the basis of all autoimmune disease. disease because when you can't break down proteins into amino acids, we have these peptide fragments that are absorbed across the lining of the gut.

We develop antibodies against them. And now we develop in a foodborne allergy. And these become antigens that our immune system then recognizes. Then we develop autoimmunity because we don't know what self versus non-self. The other important discovery was that these class of drugs inhibit an enzyme called DDAH. And this enzyme metabolizes or leads to an accumulatory. of a molecule called asymmetric dimethyl l-Arginine, and that's called ADMA.

Now, ADMA is an inhibitor of nitric oxide production. So there's two ways the body makes nitric oxide. Perhaps we forgot to mention that. We talked about the Noss enzyme, but the other is through diet through the reduction of nitrate to nitrite to nitric oxide. If you suppress stomach acid production, you prevent nitric oxide from both pathways. So this is like global nitric oxide inhibition by taking an acid. specifically the proton pump inhibitors.

And so you inhibit the gnaz production of nitric oxide. You prevent the nitric oxide that's produced from green leafy vegetables, vegetarian diet, the metabolism by the oral bacteria that generates nitric oxide in the lining in the stomach. So mechanistically, we know exactly what happens through proton pump inhibitor therapy. Now, if you look epidemiologically where you take populations of people, and this was published by my good friend John Cook at Houston Methodist, I think in 2015.

And he mined a database of, I think, 35 to 40,000 patients who had been taken PPI's for three to five years. And then he compared it to an age-match group that hadn't taken these drugs. And the patients that had been on PPI for three to five years had about a 35 to 40 percent higher incidence of heart attack and stroke. Wow. This isn't risk. These are actual heart attacks and strokes. So now we understand that these drugs. number one, aren't safe.

And inhibiting stomach acid production is, again, one of these things that if I wanted to make you chronically ill, I would give you a PPI for the rest of your life and tell you to take it every day for the rest of your life. Because your body cannot and will not heal without stomach acid. You can develop autoimmune disease. You're going to become nitric oxide deficient. And you're going to develop ever-known chronic disease known to mankind. Yeah.

It's such a powerful lesson for a lot of folks that obviously are suffering, which is a is why they're reaching for these drugs in the first place, but are they using a quick fix that is creating a longer term issue versus it takes a little bit work, it takes a little bit of work, but there's plenty of resources out there on, okay, why do you have all this extra stomach acid and how do we actually help your body regulate? From the literature that's out there, and I know this is not your exact area of expertise, but just so people don't feel like the answer is just to stop medication, what should they be doing if they're on these proton pump inhibitors? It's a lot of the basics that you've talked about before,

but do you want to chat about that for a second? Yeah, the other problem, without stomach acid, you know, we need stomach acid. There's a reason that we as humans make stomach hydrochloric acid in the lining of the stomach. So we need acid to absorb things like iron, B vitamins, selenium, chromium, trace minerals, nutrients, iodine. And so if we can't make stomach acid, then we become nutrient deficient. And going back to the days of Linus Polling, you know, he said every major human disease is basically some nutrient deficiency. So if you can't absorb nutrients, then the body doesn't have the raw material it needs

to regenerate cells that work properly. And so now, so what do we got to do? We got to fix the problem. So we always ask the question. I'm trained as a biochemist and physiologist. So what is the reaction mechanism to make hydrochloric acid in the parietal cells? Well, these cells need sodium bicarb. They need sodium chloride.

They need iodine. They need nitrate. And they need zinc. But yet, if you've been on these drugs, you don't, you don't absorb iodine. You don't absorb zinc. And you lose the buffering capacity throughout the entire body. So to fix this, I tell people, and I'm not against pharmacotherapy. You know, I'm trained as a drug discovery biochemist.

So we're in the process of making safe and effective drugs. But you have to understand the mechanism of these drugs. And so what we try to understand is let's give the body what it needs so the body can actually fix itself. So you can't just stop these drugs cold turkey because you're going to get rebounds, hyperchloric acid or hypersecretion of HCL. And it's going to exacerbate the condition. So I tell people you've got to slowly wean off these drugs. and then once you, you know, if you're taking one, one pill a day, then take that one every other

day, and then after three or four days, take it every two to three days, do that one or two times, and then you can completely wean off these drugs. But now, how do we fix the problem? So this is going to take time. You didn't develop these conditions overnight, so it's not going to, you can't expect them to be corrected overnight. So if you tell people, take a tablespoon of apple cider vinegar before every meal. So apple cider vinegar is just acetic acid with an apple flavoring. And so that'll acidify the lumen of the stomach. Now when you consume your meal, you're able to break down proteins into amino acids. You're actually able to absorb things like iodine, iron, zinc, B vitamins. Now the cell has what it needs to actually make and secrete stomach acid and it regulates

it. And so then it's basically self-fixing. And you don't need drug therapy for this. You just need replete the nutrients and then acidify the lumen of the stomach with apple cider vinegar. But over time, you can actually get off the apple cider vinegar because your prydocils are now have what they need to make sufficient hydrochloric acid to digest your food. Powerful. I love that tip. Along with that, would you add in? Because again, there's probably various degrees of people where they are with their diet that are listening, that moving to an anti-inflammatory diet, moving away from ultra-processed foods and moving away from hyper sort of palatable, hyper-sugary foods is going to be generally the things that you're going to want to do

in addition to that because many of these ultra-processed foods are part of the reason that you're having the problem in the first place. Do you agree with that or do you have any thoughts? Now, look, I'm a big fan of a balanced diet in moderation. I'm not a big fan of extreme diets like straight vegan, straight carnivore. I think we've evolved, you know, to get our nutrients from many different sources. But I think the problem is, you know, everybody's busy. The Western diet is replete with processed foods with a lot of food additives and artificial sweeteners, artificial flavorings, and the human body is never designed to see these artificial chemicals. And so it kind of confuses the cells on what to do with it. And it causes disruptions. So yeah, I think

it's important to avoid processed food, especially high carbohydrate, you know, a lot of sugar. you know, I'm a pretty simple person. I'm a meat-eaten scotch drink in Texan, and I, you know, I eat my beef, we raise our own beef, we grow our own food. So I know exactly what we're putting in the food that we eat, how we grow our food, no herbicides, no pesticides. I do soil samples, so I know that the food that I eat and the vegetables we grow are replete in every major nutrients. You know, most Americans aren't afforded that opportunity to be able to grow their own food. But I think every community has local farmers or farmers market where they can go and get to know their local growers and support the local growers. But, you know, I think it's critically important to avoid soft drinks, especially things with aspartame, sucralose, sugar-free sodas. Because I think the evidence is clear to me that a high-carbohyd, highly processed, high-sugar diet is what leads to metabolic disorders and most, if not all chronic diseases. I want to talk about high blood pressure for a second. With somebody who has high blood pressure,

which there's this deep link and connection to nitric oxide, what can they begin to start to do to unwind that and start to heal or restore the body's natural ability to heal itself? No, it's a great question. It's a huge public policy issue and global health issue because it's the number one risk factor for heart attack and stroke. So if you can normalize your blood pressure, you know, for every, I think, one millimeter drop in blood pressure, you reduce the risk of heart attack and stroke by like 2%. So a 10% reduction in your blood pressure leads to a really significant reduced in risk in heart attack and stroke. So there's high blood pressure has many different ideologies. I would say in kind of reviewing the literature, probably 90% of the hypertensive cases

are due to simple nitric oxide deficiency. Nitric oxide is the main vasodilator that dilates and regulates vascular tone. And if you lose that, then you get this chronic constricted state. So you have the same amount of volume going through a smaller pipe, so you have an increasing pressure. So I tell people, stop doing the things that disrupt nitric oxide production. If you use in mouthwash stop, get rid of fluoride, buy fluoride-free toothpaste, get a home filtration system that removes fluoride from the water supply.

If you're on in acid, you have to stop. get 20 to 30 minutes of sunlight exposure a day, and then start exercising. That went some more green leafy vegetables, and when that doesn't work, or then we have product technology that does it for you. And if that doesn't work, what we're finding is the other 10% of the people that have high blood pressure, it can be due to heavy metal toxicity, so they have an increase in metal for mercury amalgam fillings, cadmium lead exposure to heavy metals. So these will scavenge any nitric oxide that's being produced before it has a lot of,

a chance to to activate the smooth muscle and dilate the blood vessel. And then the other, which is very small percentage, are people with, you know, adrenal tumors that hypersecrete, you know, mineral corticords, corticosteroids, and lead to an increase in blood pressure. And those, those patients are really easy to pick out because they're non-responsive to any class of medications. And then you just got to go to an ultrasound with adrenal glands, see if they got an adrenal tumor, then remove it, and then their blood pressure normalizes. But that's a very, very important. And then it's a very small percent of the population. Most, I would say 90 percent or more, it's a nitric oxide problem. So then all we've got to do is restore their nitric oxide production. You know,

you mentioned morning sunlight, and we've had Dr. Andrew Huberman on the podcast, and he's become such a big proponent of getting so many individuals excited about this very core basic thing and how sunlight, both in the morning and in the evening, helps to set our circadian biology for the day. So what do you? it about sunlight that links into and plays into the mechanism of creating and maintaining healthy nitric oxide? What's actually happening inside of the body? You know, in 1950s, Bob Furchcott, who was one of the really, really nice gentleman who shared the Nobel Prize, has a history of many important discoveries. He was just awarded the Nobel Prize for discoveries around

endothelium-derivorlaxing factor in nitric oxide. But in the 50s, he introduced this concept called photo relaxation, that certain wavelengths of light could actually dilate blood vessels and lead to an increase, or an increase in vasodilation, a relaxation, and a reduction in blood pressure. And so those were the 50s. And, you know, we published on this in 2001, 2002. But there's two wavelengths of life that will liberate nitric oxide. And so we call these photolabal stores, right? So you have to have a certain pool of these nitric oxide stores. for the sunlight to be activated to release these stores. So if you're chronically nitric oxide deficient,

then obviously you have a decrease store of these photolabial nitric oxide metabolites that can be liberated by light. So ultraviolet light will actually cleave nitric oxide bound of cysteine tiles. We use this in the research lab to detect nitrozothials. So the UV light specifically is a frequency and an energy that will cleave a cobaltiles.

cleave a covalent bond of NO bound to a cysteine bile. And then there's ultraviolet light or infrared light that the frequency will actually release nitric oxide bound to metals. And so it's both ends of the spectrum from the visible spectrum and even invisible with UV that releases nitric oxide. But again, if you don't have these photolabos stores titrate it up, then you're really going to get very little nitric oxide being released from exposure to sunlight. So what I tell people to do, when you get up in the morning, you know, do things that are going to increase your nitric oxide production, you know, walking out in first sunlight, then you're going to stimulate nitric oxide production. The light's going to enhance those effects. And then in the evening, you know, if you eat

a moderate diet or a balanced diet in moderation, more green leafy vegetables, you take some of our product technology, then, you know, I'm a big fan of infrared saunas or infrared light because that light can penetrate far enough into tissue to release nitric oxide, lower blood pressure, and lead to decreased inflammation. And in fact, most of these, some of these LED light beds and devices are FDA cleared for neuromuscular pain or ischemic pain. And I think the mechanism of these types of light therapy is if it's eschemic pain and we're releasing nitric oxide, you dilate the blood vessels, improve blood flow, and the ischemic pain goes away. I want to return back to this topic of endothelial health.

Recently, by connecting to a cardiologist who I've been working with, he was the one that told me about this heart scan that's developed. I have no affiliation with the company, but it's called the Clearly scan. I don't know if you're familiar with this test, but it basically is advanced, it's an advanced CT scan that looks at the endothelial of the heart and actually tells you, how much plaque you have in different arteries that are there. And the health of your endothelial, where it's been disrupted, where it's been ruptured, where you have plaque buildup and where you don't. And off of this idea, this cardiologist we've interviewed before, his name is Dr. Michael Twyman, his whole argument that he was presenting to our audience was

that, yes, diet is so key, right, like a healthy diet, you know, not a high carb, high sugar diet, but also not a high, super high fat diet. Like we're designed to eat a lot of different things as human beings. And that a lot of these arguments about keto versus, you know, vegan versus that, they are when it comes to cardiovascular disease, it's sort of a mute point because they're not all factoring in one of the most important thing, which is, are you predicting your endothelium in particular? So just because your APOB might be a little elevated, and I am definitely an individual

that has genetically high and hyper cholesterolemia. It runs my family. I got this test done called the true genetics test that my cardiologist told me about. And I had a bunch of these genetic snips. I don't know if that's the right term that sort of have somebody be more predisposed to be producing more cholesterol, more APOB. And yes, we generally know that lower APOB levels is where we might want to be bringing down to like in our teens and stuff and nobody's talking about this more than Peter Atia,

but this endothelial health is something that we've been missing out on. Because if our endothelium is strong, which is directly connected, as you shared before, about nitric oxide, then these particles are less likely to be damaging us in the first place. Is that your understanding as well, or do you have any thoughts on this subject as it comes to endothelium, diet, APOB, LDL, and the interplay between all these things. Yeah, no, look, I'm a big fan and a good friend of Dr. Twyman, so I'm very familiar with his work. But, yeah, so I agree.

It's not, you know, 50% of people who die of sudden cardiac death have less than 50% occlusion of the coronary artery. So it's not the degree of stinosis, and there are people that have 90% stinosis of the coronary arteries that have lived for decades with very little exertional anginaum. And then there are people who have sudden cardiac death and my carlo infarction that have less than 10% stenosis and plaque, but that plaque becomes unstable, it ruptures, and that's a heart attack. You develop an embolice and a thrombus. So it's not the degree

of plaque deposition, it's the stability of that plaque. And it's the role of the endothelium to maintain the stability of that plaque. And if we have endothelial dysfunction, then we get a lot of these monocytes, neutrophils, macrophages that stick to the lining of the blood vessel, they migrate through, and then it starts to modify that plaque into fatty streaks. A lot of myeloproxidase gets involved in that, and that creates this inflammatory cascade. And then platelets start sticking to it, and then that plaque ruptures, and then you create a thrombus. And if it includes the LAD or any part of the cordon arteries, then that's a heart attack, called it myocardial infarction.

So the ability of the endothelial cells to produce nitric oxide, to mitigate the vascular inflammation, to mitigate the up-regulation of adhesion molecules that activates platelets and monocytes is really what leads to heart attack and stroke and protects people from death from heart attack or stroke if they can maintain normal nitric oxide production. So I'm not a big fan of this cholesterol theory on cardiovascular disease because, again, 50% of the people have heart attack have normal cholesterol. all. LDL particles really have no prognostic value whatsoever in terms of risk. Now, if you look at the amount of oxidation of the LDL molecule and these other lipoprotein particle size and numbers and the degree

of oxidation, then, yeah, I think those are meaningful biomarkers. But the standard lipid panel that most docs and cardiologists use are absolutely useless in terms of prognostic value or diagnosing risk for cardiovascular disease. Yeah. You know, I want to talk about your background a little bit. Tell us about how you got so deeply passionate about this. How does a scotch drinking, Texan, you know, raisin beef or knows his local provider, how does he get passionate about this subject about nitric oxide? Well, you know, I've always been interested in science and medicine. I was, you know, obviously made good grades in high school. And right at a high school, I went into the University of

Texas at Austin, and I got a degree in biochemistry there, and I had a chance to do undergraduate research and really introduced me into this whole world of understanding the molecular basis of human disease. And really, really opened my eyes to this complete intellectual freedom that taught me that I can answer any question, really ask any question I wanted, and then be able to design a meaningful experiment to get an answer to that important biological question. And to me, that was just fascinating because now we could, at least if we were properly trained, in kind of some experimental methods, then we could, I think, make an impact more so on the basic science. So I'd always had kind of a motivation.

I knew I always wanted to do research. But I thought if I had an MD PhD degree, I could go in and, you know, really translate a lot of the discoveries. So then I enrolled at LSU School of Medicine in Shreveport. and I enrolled in the PhD program in molecular and cellular physiology, and this was in, I think, late 90s, early 2000s. And the Nobel Prize had just been awarded for the discovery of nitric oxide in 1998. And I think I was a first year student there, and Lou Ignaro, who you mentioned, who's been a good friend of mine for 20 years, came and gave a lecture on kind of this whole Nobel Prize discovery and the awarding of the Nobel Prize. And it was a fascinating story. And I had a chance to be one of

the students that went out to dinner with him that night and asked a lot of questions. And, you know, he said something to me that I'll never forget and said, well, what, where does, you know, if a Nobel Prize has been awarded for the discovery of nitric oxide, what else is there to answer? And he says, Nathan, he goes, I'm really surprised that a Nobel Prize was awarded because we know it's important, but we don't know how the body makes nitric oxide completely. We don't know all the biological effects of nitric oxide. We don't know what goes wrong in people that can't make it. And we certainly. don't know how to restore or replete nitric oxide production. And so that was my kind of epiphany

to go, wow, there's still a lot of unanswered questions in this field. And so I did my entire PhD thesis on really nitric oxide. How do we quantify and detect this molecule that's produced but gone in less than a second? How do we develop methods, sensitive and selective methods to detect physiologically relevant amounts of nitric oxide? So we figured that out. We solved that riddle. I think I completed my PhD in a year and a half for two years. I published, I think, six first author papers as a student. And so I was hooked. I knew that we had important technology that we could really solve a lot of problems in terms of understanding the mechanism of action of nitric oxide production and the biological effects. So when I finished my PhD, I went to Boston Medical Center

and I was a fellow in the Department of Medicine and cardiology. And again, we continue. We continue, on this trail of trying to understand all the ways the body makes nitric oxide, and then how can we replete this or develop technologies safe and effective for humans? And then, you know, Fred Mirad, one of the guys who also shared the Nobel Prize, was familiar with my work. And, you know, he recruited me to join the faculty of UT Medical School in Houston. In I think 2005, I gave a faculty seminar, and he hired me. I think I started in, I don't know, late 2005 or 2006. And so that was my first independent research position as an assistant professor of molecular medicine. And for the first year, I didn't hire anybody. I went in and I just had all these ideas in my head. And I thought,

well, let's provide proof of principle. And I started filing patents through the University of Texas that I thought would be extremely important in ways that we could produce nitric oxide. Because during this previous probably three to four years, we had a way to make nitric oxide. Now, the question was, how can we take this kind of composition of matter or chemistry that we'd develop and put this in a form that we could administer safely and effectively to humans? And then, you know, three or four years later, the patent started being issued, and today I have, I don't know, several dozen issued patents. And, you know, due to a number of issues with conflicts of interest and kind of just my new direction in my career, I think in 2015, I retired. tired full-time from academia and now just my objective is to continue to develop and innovate safe and effective nitric oxide product technologies that we can get in the hands of everybody

on the globe. Fantastic. Beautiful story. You know, before we talk about, and I'd love for you to share, you know, your work, your products, everything you're working on, it's always fascinating. I love guests to be able to share that and share it with our audience. A few more things that I want to get a chance to go through. So I want to return back to the opening where you said, one of the earliest indications of

improper nitric oxide production in the body, separate from blood pressure and hypertension, is this idea that most people would notice would be their erectile dysfunction. And you said that it's not only something that happens in men, but this idea that nitric oxide plays a role in sort of sexuality and sort of not just for men, but for women. Let's talk about men first. And obviously, people are very aware of, you know, medications like Viagra. So why does something like erectile dysfunction happen and how is that so deeply connected with nitric oxide? And then let's talk about the female side of things. How does that play

in a role there? I think that'll be new for a lot of people to hear. Yeah, well, you know, it's all about blood flow, right? So an erection, either a penile erection or a clitoral erection is dependent upon blood flow. Blood flow is dependent upon the production of nitric oxide, which leads to dilation of the blood vessels so that you get an influx or engorge them in the blood. So in the penis, you know, males are pretty simple organisms, right? It's simply just mainly a blood flow problem. So it's both the endothelial nitric oxide synthase that's found in the lining of the blood vessels and the corpus cavernosum, but also the sex organs are highly innervated with nerve

endings. And we call these non-adrenergic, non-colonergic nerve endings. So when we have some visible or visualized, visual stimulus that activates these nerve endings. And if you have a functional nitric oxide synthesis enzyme, those nerve endings produce nitric oxide. It leads to vasodilation, stimulates the corpus cavernosum to generate nitric oxide.

You get further vasodilation, and you get an erection sufficient for penetration and intercourse. But if that enzyme is uncoupled, then you still get this kind of the visual stimulation, but the nerve endings don't generate nitric oxide. The blood vessels in the penis don't generate nitric oxide and you don't get engorgement. We call that erectile dysfunction and there's a kind of a, you know, a kind of linear response. You have mild ED and, you know, some people just cannot get an erection whatsoever.

So the physiology, the anatomy is a little bit different in the women, but the underlying physiology is exactly the same. So for women to become stimulated and have an orgasm, they have to get an increase in pressure, both clitoral pressure and labial pressure. that increase in pressure comes from an increase in blood flow, which comes from an increase in nitric oxide production. And so again, if you can't make nitric oxide, you don't get vasodilation, you don't get engorgement, you don't get the increase in clitoral pressure and labial pressure, and women become anoregasmus. So we call that the canary in the coal mine, because if you have erectile dysfunction, that is

not unique to that particular vascular bed. If those blood vessels and nerve endings can't generate nitric oxide in sex organs, then the blood vessels of the heart can't generate it, the blood vessels of the brain can't generate it, in the liver, the lung, the kidney, every major organ in the body has that dysfunction. Now, it's just more apparent and obvious because it's socially inconvenient, but it's a canary in the coal mine because that's the first sign and symptom that you have endothelial dysfunction that leads to erectile dysfunction, that if not corrected, it's going to lead to cardiovascular vascular disease, vascular dementia, Alzheimer's, insulin resistant, type 2 diabetes,

and goes back to how we started this episode of everything we know about chronic disease can be traced back to loss of nitric oxide production. So obviously we're thankful for different medications that are out there. And Dr. Gnarro, who's a friend of yours, as you mentioned, has his work was sort of directly responsible for things like Viagra. But is it also worth saying that if you are a male, And you are in your 40s, 50s, and 60s, even though it's been so become so normal because everybody's living this Western lifestyle, which includes the diet, the stress and all the other problematic things, the mouthwash, the proton pump inhibitors. And because erectile dysfunction is so normal, even you hear about it these days, I turned 40 last year, hearing about friends in their 30s that have it, you know, who haven't taken care of their health.

but should it be said for again men that really you know again we're thankful for medication for those who need it but a good sign of health is being able to maintain an erection pretty easily and straightforwardly not just in your you know 30s but in your 40s 50s 60s and even potentially beyond because an erection is your core sign that your endothelial health is functioning well So there's no reason that that should be impaired as we get older. Is that an okay statement to make? Or do you think that no, there's going to be some loss of erection, even if you have healthy nitric oxide production as you get older?

No, I think you have to look, nitric oxide is critically important. In fact, it's the end product for proper blood flow and erection. But it's, and I say, look, it's foundational for everything we do and everything we know about physiology and medicine. But I want to make it very clear. It's not a panacea. It's not an end-all, be-all, cure-all. It is not a silver bullet. There's no such thing as a silver bullet. I think if we have to look kind of at a broader picture, and that's why this whole concept of personalized medicine is still important. So for men, you can have kind of optimal nitric oxide production, but if you're low in testosterone, you're not going to get the optimal erection. So we

have to look at other things. But you can have optimal testosterone, insufficient nitric oxide production and you're not going to be able to get an erection. So I think nitric oxide is foundational, but I think we have to, you know, prevent falling into this whole notion and concept that this is the new normal. You know, most people at the age of 40 have erectile dysfunction. You know, I'll be 50 later this year. And to me, that's unacceptable that people are accepting this in the 30s and 40s, that, oh, this just comes with age. You know, we're getting older. That's why we have ED. No, that's not the case. If you take care of your body and you do every, give you the body, what it needs to, the body heals itself and performs optimally. And nitric oxide is foundational for that. So that's

not normal. It's not normal to have erectile dysfunction even when you're 50, 60 years old. You know, I know people I consult with a lot of physicians and know a lot of physicians who treat young kids in their late teens, early 20s with drugs like Viagram PD5 inhibitors for ED. That is a major problem. And then I know people in their 60, 70, and early 80s who don't take any drug therapy that still have an actual active sex life and have good erectile function. So don't fall into this category of this is the new normal.

And I think that's what limits innovation through science. We have to continue to innovate. And the more we learn, the more we have to be able to translate basic science into new safe and effective clinical medicine that basically gets to the root cause of disease. You know, we're never deficient and a HMG co-aid reductase inhibitor.

So giving cholesterol lowering medications is not going to make you better. We're never deficient of any synthetic drug that's going to give in to you. So our concept in terms of drug design and drug discovery is we call this category of medicine restorative physiology where everything else is pharmacology. So if we have something that's missing in the body and we do this with nitric oxide, we know how much nitric oxide a healthy person makes in 20, hours, we develop technology that recapitulates that amount of nitric oxide over a certain period of time. So we never give the body something that it's not used to see. And same thing, you know,

that fixes a lot of things, but if you're deficient in, you know, magnesium or iodine or chromium or beef items, then we also have to fix that. So again, I want to make it very clear. Nitric oxide is foundational, but it's not going to fix the whole host of other problems that individual patients may deal with. But I will tell you this, and we know this from the basis, science in the clinical data is that your body cannot and will not heal without proper nitric oxide production. So that's where I tell people to start. And once you restore nitric oxide production, replete and recapitulate what nitric oxide

does in the human body, now you can start integrating these other treatment modalities of nutrient repletion, exercise, red light therapy, sunlight, you know, all these other things that we've known for many, many decades and centuries that are health promoting and can actually prevent the onset and progression of disease. You know, just like you isolated mouthwash in particular for being so egregious at sort of killing the bacteria that are so crucial for nitric oxide production, are there any foods? You know, you've already shared that you are an individual who talks about moderation and want to eat healthy.

It's always tricky with moderation because everybody has a different degree of what moderation means. If you go to Times Square or I live in Los Angeles, if I go to Hollywood Boulevard, and I interview everybody and I say, hey, do you live a healthy life? one person will say, yeah, I try to be healthy. I live a healthy life. I eat healthy. But for them, you know, two Coca-Cola's a day is healthy because their friend has five

Coca-Cola's a day, right? So everybody has a different definition. So I like to get a little granular. So just like you highlighted mouthwash as being quite egregious, are there any food or food categories that in particular are quite damaging to the production of nitric oxide? Like are, you know, overconsumption of any particular foods? like fried foods. Is that in particular bad? Is there anything that we should be just uniquely aware of when it comes to diet? Yeah, you know, I think the major problem, and, you know,

it's these advanced glycosylation end products that occur. So when you have sugar, when you drink sugar beverages, fruit juices, simple carbohydrates that are metabolized into glucose, when the body doesn't properly dispose of that because of developing insulin resistance, then that sugar sticks to proteins and enzymes, and it disrupts the function of it. So it's no different than the nitric oxide synthase enzyme. That if you have glycation in products on that enzyme, it disrupts the flow of electrons, you don't get any nitric oxide produced. Plus, it's inflammatory, and it causes a lot of oxidative stress.

So then you're going to oxidize BH4, lead to Nosson coupling. So I think that's probably the major category. And, you know, there's companies out there selling gummies that have sugar in them that are sold to make nitric oxide. I mean, that to me, as a nitric oxide biochemist, there's nothing more aggravating to me than these companies out there selling products that they know. There's two types of people. They're ignorant people that just don't know, but ignorance is curable. Then there's companies out there that deliberately try to deceive their customers in selling them these products that there's no way in hell they could ever generate nitric oxide. In fact, they're causing more damage to them.

And I think it could kill an entire industry of nitric oxide because people take this and I hear it all the time. I go, well, I've tried nitric oxide in the past, and it didn't do anything for me. They go, what do you mean, nitric oxide? Well, I took this in form of a gummy and didn't do anything. And I go, well, that's not a nitric oxide product. These are companies actually out there intentionally trying to deceive you to sell you product. And I want to call those companies out, and that's one of my main objectives, is to create awareness and the proper education around nitric oxide so that consumers can be

informed about what products work, what products don't, what companies are honest and credible, and which ones are not. So I think those sugar products, gummies, chews, beverages, and then the other seed oils, you know, the cell membrane has to have a certain degree of fat and cholesterol in there to maintain this intracellular coupling and signaling. And if we eat a lot of bad fats or lower our cholesterol below 200, then these cell membranes become disrupted. We lose the signaling aspects. The protein complex that makes nitric oxide falls apart. We lose the insulin signaling aspects of it. But I think to answer your question, the most important thing or damaging food is sugars and processed carbohydrates.

Yeah. And because a lot of people have questions about this, and we've got a chance to interview experts like you and other individuals who are really metabolic health and insulin and sugar is kind of like their core study. We always just encourage people, go get your A1C tested, for example, in the case. case of the advanced glycation end products, we have a whole news that are coming out about this. One of the best things that's there is to know if you're heading in the right direction or the wrong direction is your A1C is a really good marker of how much of those you've accumulated. And if you're normal, you're less than 5.7. And if you are 5.7 to 6.4, that's usually pre-diabetes.

And if your A1C comes back at 6.5 and above, you're obviously diabetic, but that's a another indication that you're just accumulating a lot of these ages, which actually age us as well. So, you know, you can get your A1C tested, and that's going to be a proxy for helping us understand the things that are also not just making us more likely to have diabetes, but are also damaging our nitric oxide production. Yeah, no, you're spot on. I mean, hemoglobin is one protein that we measure clinically for hemoglobin A1C, but any protein or any enzyme, if sugar is stuck to hemoglobin, it's going to be stuck to the gnause enzyme,

it's going to be stuck to catalase, SOD, all these other important anti-inflammatory antioxidative enzymes. You know, on the topic of testing, I've heard you talk about this before, and this is a great part of the interview to review it with our audience. Talk about nitric oxide testing. You know, we're not there yet to exactly, because this molecule disappears so quickly, but there are some proxy ways from my understanding that we can test it. Can you chat about that? Yeah, you know, that's been one of my main objectives for the past 13 or 14 years, because in the research lab, we can do this.

You know, we do clinical trials. We can sample plasma or, you know, even cerebral spinal fluid or different biopsy samples, and we can quantify a lot of these nitric oxide metabolites and get what we call a fingerprint of in oveno biology and then give us some direction of what may be going wrong in that individual patient. But clinically, there really is no, and there has not been. any nitric oxide kind of measure or test, blood test. So when I think it was 2009 or 2010, I was the first to develop a kind of a non-invasive

point of care salivary test for nitric oxide. And again, nitric oxide is a gas, but we can measure these oxidative metabolites like nitrite or nitrate. And so I developed a nitrite test strip. So it's some old chemistry called the grease reaction. We put on the end of a test strip. He's applied some saliva to it. And then if it turns dark pink, there's nitrite in your saliva.

And it kind of tells us that your total body nitric oxide availability or this proxy for NO may be a good indicator. But so I told people it's a good tool to have in your toolbox, but it shouldn't be the only tool you're using. And then about, you know, five or six years ago, I got away from this. So there were a number of companies that started manufacturing and selling my test trips. But I got away from it because there were a number of false positives.

And this occurred primarily in a lot of dental offices. So you would have a 50-year-old, hypertensive, diabetic, obese man with ED come into the office. He would spit on the test trip and would light up bright pink. So he goes, oh, my nitric oxide levels are great. Well, no, systemically, they're not. So, well, through further investigation interrogation, we found that this guy had really severe dental infections.

So that local immune response in the gingible tissue or from the local infection was activating, an immune response that led to increased nitric oxide production in the mouth, oxidation to nitrite. So these were the false positives. So I've gotten away from those test strips. You know, they're good to use ever now and then to kind of monitor your progress. If you're low, you're low. There is no false negatives. And then I tell people, okay, well, go out and eat a plate of spinach or broccoli or celery. Then 90 minutes later, you can retest. And then if it goes from no color to bright pink, then that tells us that you have the right bacteria.

you have the right nitrate reducing bacteria in your mouth. So this intero-salivary circuit works. And really, I think that's probably one of the good utilities of those test strips. But you have to understand the nuances of what you're doing and how you're testing and what you're interrogating to get some meaningful data from those test strips. So to bring it all together, I like them to use them kind of to monitor to start a conversation around nitric oxide. But again, it shouldn't be the only measure of nitric oxide because of the positives. So generally speaking for most people who are listening today, if they are going to be going down the pathway of wanting to improve or maintain healthy nitric oxide production, the test strips might be not the thing that is going to be the first action item for most people. It's going to be to audit their basics.

moderate exercise, which according to a lot of the research that's out there, do you agree that that's the 150 minutes that's recommended that's out there of activity in the week? And in particular, as we get older, including in at least, you know, two minimum two sessions of strength training. That's generally what some of the folks in this podcast have talked about. Would you add anything additional into the moderate exercise category? No, I think, look, you don't have to overdo it. I think, you know, 15 to 20 minutes of exercise a day, several days a week is sufficient. You know, everybody's different. You know, the metabolic demands on my body when I exercise are much different than, you know, a 6-4, 300-pound guy that's out of shape.

So it's hard to ascribe kind of a one-size-fits-all, but I think if we look at the composite of data, the modern physical exercise, 15 to 20 minutes of aerobic exercise, I like strength training because resistance training not only builds your bones, prevents sarcopenia, osteoporosis, and osteopenia. But there's a concept called ischemic preconditioning. So when you have brief periods of ischemia, which is no blood flow, which is what happens when you lift weights, so the muscles will actually constrict the blood supply. And then that's called intermittent hypoxia or ischemia. So that tells that particular vascular bed, oh, I don't want to run out of oxygen like that again, so I need to upregulate my nitric oxide production, create new blood vessels.

And so now you get hyper-perfusion to that. you increase vasculary, increased mitochondrial density, increased mitochondrial functions where you can now generate more cellular energy with less oxygen. So those are concepts that are very well validated, not just in the basic sciences, but have been proven out in clinical trials. So yeah, I like that. And personally, I do 20 or 30 minutes of running or biking to warm up. And then I'll do high intensity interval training for probably 10 or 15 minutes, then I go 20 minutes of, you know, moderate, not heavy weights. I'm not looking to be a bodybuilder or build muscle mass. I'm just looking to maintain some tone and prevent, you know, loss of muscle and loss of bone density. And that works,

it seems to work great for me, but, you know, that's me and that's personal. But, you know, I'm, like I said, I'll be 50 this year, but, you know, my endothelial function of a vascular age of a 38-year-old. If we look at other kind of these objective endpoints of biological age, you know, from epigenetic modifications and other things, I'm certainly, you know, decades below my chronological age. You know, I'm still very much at the beginning, but about a year ago when I turned 40, I got very serious about wanting to focus on strength training and working out with the training group that's here in Los Angeles, primarily because, you know, growing up vegetarian and Indian and just being like the skinny Indian kids.

I started to realize that, wow, okay, I'm going from being skinny to being skinny fat, even though I eat very healthy because I'm not actually focused on prioritizing protein as well as strength training. So an interesting thing that happened is about like three to four months into my strain training. I started to have a phenomenon that I've heard that other men sometimes have too is that with my diet dialed in, with my breathing dialed in, with me not having sleep apnea, avoiding mouthwash, but then now adding in strength training on top of everything else, I was having evening sort of nighttime erections as if I'm like, you know, a 14-year-old again. Yeah.

Is that directly related to nitric oxide being more available in my body? Do you have any thoughts about that? No, I think certainly nitric oxide is the end mediator of that vasodilation and the erection. So we're improving endothelial health. We're improving intethelial function. improving the production of nitric oxide. And now it's just not the regulation of blood flow to the pelvic region to the penis and the sex organs, but it's an increase in profusion to the coronary arteries.

You're going to get increased profusion and improve inothelial function in the cerebral arteries. So your memory is going to become better. You're not going to have much brain fog. The perfusion to skeletal muscles is going to be improved. And nitric oxides improve is involved in mitochondria biogenesis. So now every cell in the body has more mitochondria that can produce more. more energy with less oxygen. So now everything you do becomes more efficient.

So we were going through some of the basics as a little bit of recap. Before we talk about, you know, can products, supplements, other topicals be a part of people's approach to getting more nitric oxide production in the body. So we already talked about the strain training component. You already mentioned a lot of the lifestyle habits that are damaging. We talked about certain medications. Don't go off of them cold turkey, you know, work with your provider to sort of wean them down or find a provider that's actually more knowledgeable, like a functional medicine or integrative doctor,

mouthwash is a no-no. Obviously, there's plenty of healthier mouthwashes that are out there that don't disrupt, you know, bacterial function inside of the body. On the diet side, you've talked a little bit about greens. Is there a minimum viable dose based on the literature that's available of what people should be shooting for? Now, we already know that most of America in this Western diet is chronically fiber-deficient, And that has all sorts of impacts on gut motility, constipation, but also diversity in the microbiome.

I think most Americans are getting less than 15 grams of fiber a day, right? A lot of Americans are getting five grams of fiber a day, which is ridiculous to me, that it could be that low. So is there a recommendation of the minimum viable dose of greens that somebody should be shooting for in particular to not just support fiber, but to really target the nitric oxide side of things? You know, we asked that question back in 2014 because we thought if we could just make recommendations on people that had high blood pressure, two out of three Americans, and to just throw in a certain serving size of broccoli, celery, spinach, arugula, kale, whatever, then that would have a major impact on public health. So in order to answer that question, I teamed up with some investigators in food science at Texas A&M University. And we went to New York, we went to Chicago, Raleigh, Dallas, and Los Angeles, where you are. And we just went to a retail grocer and we bought vegetables off the shelf. We brought it back to my lab.

I analyzed it. We did extractions and we just measured the nitrate content of these vegetables. And what we found was shocking that the amount of nitrate in, for example, celery in Dallas versus New York or Chicago was 50 to 80 times different. Wow. So let's just let's put that in perspective. So if you lived in Dallas or Los Angeles, you could go to a retail grocery and buy six stocks of celery, eat that and get enough nitrate to generate nitric oxide to lower your blood pressure. If you lived in New York, you'd have to eat about 80 stocks of celery. So there's farming differences. There's this whole field of agronomy, growing practices, soul condition, lightning fixation, lightning storms in certain geographical regions that control the amount of nitrogen. or nitrate in the soil. So to answer your question, there's no way in hell we can make recommendations on how much serving of broccoli, celery spinach you can eat

because it depends upon where you live. And the other interesting finding from that study was we took conventionally grown vegetables versus organically grown. And organically grown vegetables had on average about 10 times less nitrate than conventionally grown vegetables. So you cannot eat enough organic vegetables to get enough nitrate to fuel this nitric oxide

production pathway. And if you think about that, to get an organic label in the U.S., obviously, you can't add herbicides or pesticides, but there's restrictions on adding nitrogen-based fertilizers to the soil. Without nitrogen, these vegetables can't assimilate other nutrients. They don't convert it to nitrate, so there's no nitrate that accumulates into the vegetables. So when we eat these organic vegetables, we can't get enough nitrate from these to stimulate nitric oxide production. So that creates a conundrum, right? Because I think organic is extremely important because we certainly don't want glyphosate and all these other herbicides or pesticides on the food that we eat, but we have to add nitrogen to the soil in order to give these plants the nutrients they need to

assimilate not only nitrate, but other nutrients. So what I do, and I learned this through research and studies, I take our soil, I live on 800 acres in the middle of Texas, about an hour outside of Austin. So I sample the soil. I see what it's deficient in. I add nitrogen-based fertilizers. I add other missing nutrients. And then I grow those vegetables, but I don't add herbicides or pesticides. So now what I eat is not organic, but it doesn't have any herbicides or pesticides. It's better than organic because it has the nutrients. It's nutrient dense, nutrient replete without any chemicals on. So obviously most people here don't have that acreage or maybe don't have a team that can help them out with farming. Right. Right. So.

word work. So there's still going to be generally benefits to obviously including greens in our diet. Some people get that from maybe a green powder. Some people get that from that. But in particular, if people are dealing with some of these more chronic conditions, right? If you have all the basics dialed in, you could be in a place where you have decent or good nitric oxide production. Is that fair to say? But if the best indication that you're not is if you're dealing with ED as the canary in the coal mine, you're dealing with restriction of blood, blood flow in certain areas of the body, ED being connected to that, if you're somebody that's dealing with blood pressure issues, as you mentioned, that's going to be the best sign that, hey, you have an issue that you need to address. Is that correct? Into thinking about it that way? Yeah, so I think, you know, people ask me, how do I know? How do I know if I'm nitric oxide deficient? And that was really kind of the motivation for developing that test trip because people want to know, and I think it's important for them to know. But, you know, as I mentioned earlier, the limitations on the test strip, you can have false positives.

So really the only way we know, and there's some really good FDA cleared medical devices out there that look at what we call flow mediated dilatation or FMD. And so there's a couple of them out there. I have no affiliations with them, but it really, it's a measure of endothelial function. And the best one of these is called ischemic plethmosography. So you can, you can occlude the blood. flow into the brachial artery, for example, put a blood pressure cuff on and pump it up to super systolic levels, and you occlude blood flow into the forearm for five minutes. And then when you release that cuff, you can measure the degree of reactive hyperemia, either through a temperature

probe on the fingertip or through an ultrasound of the brachial artery in the forearm. And if that blood vessel immediately dilates with the reactive hyperemia, then that tells your body that those endothelial cells in that particular blood vessel are making nitric oxide. If you don't get any hyperemic response or vasodilation when you release that cuff, then you have endothelial dysfunction. And that's really the only functional diagnostic for nitric oxide deficiency and endothelial dysfunction. All these other biochemical biomarkers are kind of proxies, but really I'm always a big fan of functional measurements versus biochemical measurements because you're really looking at the function of the blood vessel in the vaster bid rather than some, you know, oxidative

metabolite or biomarker. It's a direct correlation. How prevalent is this test? And is it something that you'd have to go to a research lab for? Or are they going to be physicians or technicians that are out there that you could, you know, go to and maybe book an appointment and pay for this test out of pocket to get it done? You can. So again, as you pointed out earlier, it's all about finding the right practitioner to look at your and practices personalized functional integrative medicine. Now, these devices are out there. They're used in some clinics. It's not near as pervasive as it needs to be. But, you know, one's called the endopat. It's probably the most popular, the one that has the most validated clinical data on it. There's a device called the Vendis, V-N-D-Y-S.

But there are a number of physicians that will use this as diagnostic for endothelial dysfunction. and then you can actually monitor your progress. The good things are in physicians who still take insurance, you know, there's a reimbursement for these. So it's not just sometimes it's not an out-of-pocket expense. Your insurance may cover it. But again, individual policies are different and individual practitioners are different. Yeah, I haven't done the endopat test.

Dr. Michael Twynam, he recommended me to clearly, which we get a little bit more information on. But one thing that I do know about endopat is from a friend of mine is that they do have a find a physician database on their website so you can find somebody and you can go and request this test and some of them take insurance and some of them you might have to pay out of pocket. But we can link to that in the show notes. No, Drew, I think it's a, and I think that it's a very important and I think probably one of the most important test you can get info on because here's what we know from from both

the basic science and the clinical data. The functional loss of nitric oxide production precedes the structural changes and the onset of cardiovascular disease by many years, sometimes decades. So when you lose the ability to make nitric oxide, you may not have hypertension or ED yet, but if you start to see the reactive hyperemia and the functional activity of the NOS enzyme in the fetal cell start to become compromised, then that's when you need to take corrective action. So there's two types of people out there. There are people who are sick, who have been mismanaged, and are looking for solutions to make them better. They already have disease. They're already sick. They have symptoms. And nitric oxide is

absolutely essential for them because most times it'll make them better. But then there's people like us, Drew, who we're healthy. We don't have any symptoms. We don't have any problems. But it's important for us to collect data, to know our own physiology, that if we start to develop endothel dysfunction before we start developing ED or high blood pressure and any of these other symptoms, then we need to know that. Then we need to stay corrective actions before the onset progression of symptoms. Because as we all know, it's easier to prevent disease than it is to cure it or treat it. So we have to be proactive. I think that's the beauty of what you guys are doing there and getting this information out there. So now patients don't have an excuse. The information is out there.

They just have to find it and employ these very simple strategies and be proactive to their own health and not reactive. Such a powerful reminder. And just so I make sure I understand you clearly, you feel at least right now that's widely available, one of the best ways to cast. that's sort of pre just like we talk about pre diabetes right and even some people talking about pre-alzheimer's or pre-automune you want to catch it in its earliest stage so you can do something about it because once you have Alzheimer's disease as dr dale bredison has talked about or dr. Terry wals who's been on this podcast before and has talked about you know autoimmune diseases that are out there or my friend dr. casey means who's passionate about metabolic health

If you don't catch these things early, it's hard to, as you mentioned, fix it later. So in your opinion, one of the earliest ways to catch low and non-functional nitric oxide levels in the body, which is a direct reflection on our endothelial health, you would recommend the best and most widely available that's not so cost, you know, non-accessible people would be this endopat test. Yeah, I think it's one of many. I think it's the one that's probably most readily available out there. And look, I look for strong basic science in any technology, whether it's a medical device or some product technology, and then validated and randomized controlled clinical trials. And the endopad, that company has done a really good job

of putting this in clinical trials and marking it and showing people what their endothelial function is. And then if they have dysfunction, employ these strategies, and then they can actually monitor their progress and see changes right before their eyes. And, you know, we as humans in today's world are program for instant gratification. But, you know, people who are sick, they typically didn't get sick overnight in most cases. Over the past three years, a lot of people get sick overnight because of the jab.

But most people living with chronic disease, it didn't happen overnight. It's a progression. So don't expect it to change overnight. But if you change your diet and lifestyle and employ these strategies we talked about, then over time you will see that change. not only will you see it empirically on these devices, but you'll feel it. You'll start feeling better.

You'll be able to exercise more. You'll enjoy life more. You get better blood pressure control. You'll get better erections. Everything we've talked about. So this has been fantastic. Dr. Brian, thank you so much. And we still have more that we want to talk about.

But just to recap, we talked about the importance of working out. We talked about the importance of dietary components. Obviously, there's some nuances that are out there. But just so anybody doesn't feel too discouraged, still getting your greens is generally going to be good. It's going to be good fiber for you. It's going to support your diversity of your microbiome. You know, choose the ones that are good for you. If you don't like that, find a good quality, you know, green powder that are out there. There's a lot of them. Endopat test. We have a link to it in the show notes. You can find a physician near you. I just typed it in near me where I live in Los Angeles.

There's three or four physicians right nearby me that do this test. I'm interested and curious. I'll probably get it done. And also we talked about morning sunlight and evening sunlight and how sun's sunlight and infrared light can be a huge part of that process. We talked about the big no-nose. We talked about sugary, sweetened beverages and how they damage the body. I talked about ultra-processed food. Just so everybody's aware, we're not talking about processed almond butter and, you know, processed, you know, generally food that's minimally processed.

We're talking about ultra-processed food, which usually is hyper-padable fast food, hyper-palatable, engineered foods, foods that are designed to, you know, we all. know what they are. They're in the grocery store. They're at the fast food stores that are there. And of course, stress management is also something that you talked about a little bit before as well. And then correcting if you have sleep apnea, that's a big component. Now, in addition of those items that we covered there, there's also this category of potential products and also prescriptions. You know, part of what you're working on is you're working on some, hopefully future prescriptions that could be included in people's routine that could help us.

us be better at sort of creating nitric oxide by fixing some of the missing links that are there in the first place. In addition to that, you're involved in some products as well. And I'd love you to talk about the products first. And then maybe a little bit about what your long-term roadmap is for a prescription one day that has, you know, a lot of our audience, you know, they hear prescription and immediately they think like, well, shouldn't we be a little bit more cautious about prescriptions? But I get really excited when people with your background are developing prescriptions because they're thinking about how to develop it from that sort of functional lens where they're not making a huge sacrifice in another area to try to correct, you know,

another thing that we then need, you know, drugs for later on to fix that situation. So let's talk about the products. What are the potential products that are out there that are recommended that could help us with nitric oxide production? Well, you know, I created product technology years ago, and I was the first and still the only person who ever put a solid dose form of a bioactive gas. So I have an orally disintegrating tablet that you put in your mouth that slowly dissolves over five to six minutes. And as that lozenge is dissolving, this matrix falls apart and we generate about 20 to 30 parts per million nitric oxide gas.

And to put it in context, that's the same amount of nitric oxide they give in the pediatric intensive care unit for premature babies born with pulmonary hypertension or even in the adult cath lab for patients undergoing cardiopulmonary bypass. So it's a vasoactive, bioactive dose of nitric oxide that we deliver in a solid dose form in the form in the lozenge. You know, beet products have been the rage for the past, you know, 10 or 12 years. There are dozens, if not hundreds of beetroot products on the market. I've tested all those 95, 98% of them don't work. They don't do anything. So we created a fermented beet powder that we pre-convert.

So it's not dependent upon the bacteria. It's not everything we do is not dependent upon bacteria. It's not dependent upon stomach acid production. That way we control and dictate the metabolic fate of everything we do with nitric oxide. And so every single person who takes this gets the same exact effect because we're not relying on human physiology. We're relying on providing a bioactive source of nitric oxide. So our whole concept was if your body can't make nitric oxide, then we've got to do it for you. We've got to give you nitric oxide.

Similar concept of hormone replacement. If your body can't make testosterone, then you've got to take it. Can't make estrogen, we got to take it. But we go a step further. We understand the enzymology and biochemistry now to the extent that we can recouple the Knoz enzyme and actually improve the body's own ability to make it. And this is exactly opposite to like testosterone therapy. So if you take testosterone chronically, it completely shuts down your testicular production

of nitricotone. You get testicular atrophy. And now you become dependent for the rest of your life on testosterone. We didn't want to do that. We don't want to depend upon our product technology as your only source of nitric oxide. It's a great economic model, but as a physiologist and biochemist, it's not the best model to make patients better. So now what we do is if you take our product technology over time, we recouple the gnause enzyme, and now your body's own ability to make nitric oxide becomes improved.

So now you're less dependent upon our product technology over time. But because of the world we live in, because of EMFs that we didn't talk about, because of all the toxins in our environment and the food we eat, we're constantly getting attacked on our, compromising our nitric oxide production. So I encourage people to take it, you know, daily or periodically just as a daily kind of a prophylactic dose of nitric oxide. So we have the orly disintegrating tablet. We have the fermented beet powder that we put electrolytes in there for cellular hydration and we put mitochondrial ATP in there to help with energy production. So those are kind of our consumer products.

And what's the brand name that it would be under? And obviously we'll link to it in the show notes so anybody can find it. And I think that your team is even going to provide some discount for individuals if they want to check out the product who haven't tried it before. Yeah. So we're migrating over. So I've had several companies in the past, depending on difference of development and different market segments.

But it becomes way too complicated. So we're trying to simplify life. So all of these products can be found at N101.com. It's a parent company. called pneumonitric oxide. We called it numa nitric oxide because numa translates into the breath of life. And it goes back to Galen, who was a physician around 200 AD, that had this concept that there was this gas, this spirit that animated the human. And this is long before the cardiovascular system was ever elucidated. And so he called this Numa, the breath of life. And so through several hundred

years of research we've discovered and really all the concepts that were developed from thousands of years ago, nitric oxide is the Numa that animates the human. It's the chi that's been described for thousands of years in Chinese medicine. So the company name is called Numa nitric oxide. Our brand name is N101. Those are our consumable kind of supplement nutritional products. And through a lot of experimentation, we found out that topical nitric oxide has enormous benefits for skin care and beauty. So I created a skin care line called Numa Nidot, again is through pneumonitric oxide, but we developed a dual chamber nitric oxide serum that when you mix these two components together, they generate nitric oxide gas. You apply it to the skin. It improves

blood flow, recruits capillaries, causes a hyperemic response. We improve collagen deposition, improve hydration, fine lines and wrinkles go away. It's an amazing, in fact, it's a new category in skin care and beauty. And we've got five published clinical tries on it. Most skincare products out there are trying to mask or hide the defects and the color spots and the fine lines and wrinkles. Again, what we do is completely different. We get to the root cause. We supply blood supply to the cells of the dermis, improve cellular turnover, improve hydration.

And then we've got a glycolycolic wash and a face cream and eye cream that goes with that. So those are our consumer products, N101.com. But again, my job is not to sell you products. My job is to provide you information and education so you can make informed decisions. And just so happens we have safe and effective product technology on the market. But to get to the more important question, my long-term mission was to bring to market safe and effective drugs. And for us, safety is the issue because most drugs on the market, in fact, all drugs currently on the market have side effects. What we do is completely different than any other drug.

program that's ever been done. Most drugs are inhibitors of biochemical reactions or enzyme inhibitors. There's always collateral damage and side effects. What we do in this restorative physiology type concept is we just give the body what's missing in terms of nitric oxide. And because we're not giving more than the body would normally not ever see, we haven't seen any side effects and we don't anticipate any side effects. So we've established safety. And now we're moving into phase three clinical trials for things like the Schemic heart disease. We've just brought Dr. Perlmutter on to lead our Alzheimer's and neurodegenerative drug discovery program. We've got a drug for Alzheimer's going into phase three trials. We're taking

our topical nitric oxide technology and developing it into a topical drug for diabetic and non-healing ulcers. You know, that's a remarkable game changer in wound care. We're seeing three and four-year-old non-healing ulcers. We apply the topical nitric oxide and we heal non-healing wounds in three to four months. Incredible. There's been no innovation in wound care for for 50 years. We still treat wounds today, the same today we did 50 years ago. Negative pressure, wound vax, and control the infection. Nitric oxide kills the infection, causes hyperemia, you get tissue granulation, and the wound heals itself. It's a game changer, and I think I'm absolutely convinced that this is the future of medicine, and it'll be the way we treat patients

for the next 100 years. That's what I'm excited. Yeah, no, that's very exciting to me. For anybody who's listening, you know, I think that we need interventions at all levels, right? We need products. We need drugs because when you look at the amount of people who are suffering and are dealing with all the unhealthy ramifications, which many times, if you look at like the literature and the data on this, it's just because they were born in a zip code or to a family that didn't have any education. They didn't know how to cook. They didn't know anything about eating their greens. they didn't have access to podcasts, they're working three jobs and they're dealing with hypertension. They're dealing with this situation. So we need interventions at all levels. We need safer

drugs that are out there. And for the us that are in the very super privileged situation where we have the benefit of being able to learn from individuals like you and get access to your information on YouTube and audio, amazing, awesome. Let's us be the best examples that we can. Let's work out. Let's eat healthy. Let's do all the things. Let's tell our friends about the importance of nitric oxide. And then when your book comes out, which I'm super excited about, let's give a copy of your book to our physicians because they're undereducated about this topic too. So we need interventions at all levels and we need solutions that meet people where they're at. I don't feel that we're going to solve this epidemic of chronic disease just by teaching everybody how to cook.

I maybe thought that like years ago, but then the more that you learn, the more you realize, especially now that we're exporting the Western diet and lifestyle to the rest of the world, you know, India is one of the fastest growing places, which is where I'm from, of hypertension, of diabetes, you know, the Middle East and what they're suffering. The entire world is getting sick and they're getting sick faster than we're getting sick now. So we need a lot of solutions at different levels. So I'm super excited that you're involved and we need better people like you involved in creating drugs. Well, you know, that's that was my motivation for developing these consumer products because if we wait, you know, drug discovery is a very time consuming capital extensive and expensive enterprise.

So if we had to wait until we had all, our drugs approved through clinical trials. You know, on average, it takes 10 years and about $800 million to get drugs to market. And fortunately, we know how to make nitric oxide. I'm going to do this safely and effectively in consumer-based products that have been clinically shown to restore and recapitulate nitric oxide-based signaling. So those products are out there for the masses. And now to take the science to a new level and to actually go through the rigor of clinical trials and getting FDA approval, you know, now we can hit really a global market. because most consumers are savvy enough and informed where they, you know, I think, I don't know what the statistics are, but I think 85%, the majority of Americans take supplements on a daily basis.

Now, most of these supplements are probably not doing much. Are they replacing missing nutrients, repleting missing nutrients? But a lot of the products out there are, you know, falsely advertised. So as we go through the clinical trials and get prescription drugs approved, now physicians can actually have this product technology in their armament. that even if they don't recommend supplements, as most allopathic physicians don't, they have a prescription they can write, that they can feel confident that it's not only safe, but it's going to be effective for whatever indication they're prescribing it for, because we've done the homework and the rigor of FDA trials showing safety and efficacy

and a number of different indication. So we're just starting with ischemic heart disease, Alzheimer's, diabetic ulcers, but we'll hit other things like heart failure, pulmonary hypertension, metabolic syndrome, diabetes, there's really no indication where nitric oxide at the right dose at the right time and the right patient would not be beneficial. So we'll link to all that in the show notes below, your website and everything. As I always share on my podcast, I have no affiliation. You know, you and I just got a chance to meet, but I'm so passionate about what you're doing

and you're teaching about it. And I love anybody who I look up to is putting out good information to talk about their products or their offerings or anything else they have. So we'll link to that in the show notes. If I was going to start somewhere and I wanted to include something like this, should I start with the beat packet or should I start with the lozenge? What's your recommendation? I think, look, the lozenge is probably going to be the best because it's really, you know, we control and dictate the metabolic fate of that NO that's released in there. So the lozenges is beautiful because it's convenient.

You can take it on the go. It dissolves in five to six minutes. It tastes great. It doesn't have a bad taste to it. But that gives you a source and a meat. source of exogenous nitric oxide. And most people, you know, when I take it, I really don't feel a difference. But if, you know, sicker you are, the people, people actually feel the difference.

The bead powder is really designed kind of as a pre-workout or energy drink. And, you know, we only brought that product to market because, you know, try to compete with things like the, really the unhealthy and unsafe things like Monster Energy drink, Red Bull, five-hour energy. That's a multi-billion dollar industry. Sure. And so we can provide a natural energy source through nitric oxide. through increased circulation, oxygen delivery, hydration, and mitochondrial ATP production,

it's actually good for you. And people feel that product. So, you know, my kind of personal regimen is I take a lozgen in the morning, one in the evening. I typically work out and go to the gym in the afternoons, and before my workout, I'll take the beet powder. But again, everybody's different. You know, you can take, they're both going to work. But I think in terms of a daily nitric oxide support, the lodging is going to be the best way. If you want an afternoon energy or a pre-workout,

then the NOB's bead powder is going to be your product of choice. Great. Thanks for that breakdown. Dr. Brian, as we wind down here, give us some final words about just a reminder of how important nitric oxide is for anybody that's been sleeping on it that feels like they don't know enough people that have been talking about it. They haven't been seeing it on the news.

They're maybe just hearing about it for the first time. You know, give us some final words on just how important this molecule is. if you care about longevity, if you care about healthy aging, if you care about Alzheimer's, and just anything else that you want to leave us, leave our audience with. This whole concept of longevity, people wanting to live longer, but not just longer, but a longer quality of life. And there's some objective measurements of this. And there's three main measures.

There's telomere length, the short of the telomeres, the short of the lifespan. There's mitochondrial function. You know, every major chronic disease associated with mitochondrial dysfunction and lower numbers of mitochondria. And then there's our own stem cell. The older we get, the less stem cells we have, the less active they become. And about 15 years ago, I created this concept of this unified theory of aging because nitric oxide is what controls telomerase activity and telomere length.

Nitric oxide controls and regulates the number and efficiency of mitochondrial function. And nitric oxide is what controls and regulates stem cell mobilization and differentiation. So by every objective measure of longevity and health and wellness, nitric oxide controls and regulates all of those. So I guess the take-home message is your body cannot and will not heal without nitric oxide. But again, it's not a panacea, it's not an end-all-cure-all, but I think it's foundational for everything else. You may be trying these other things and banging your head against the wall and frustrated with the results. But start with nitric oxide, then do the exercise, change the diet, employ these other strategies,

stop the mouthwash, stop the in acids, get rid of fluoride, get some sunlight. And it's really that simple. Again, it's a very complicated, complex science, but the strategies that we can employ to improve nitric oxides are really common-sense principles. Fantastic. Dr. Brian, thank you for joining us on the podcast. Super appreciate you being here. Thank you very much, Drew. I enjoyed it. Hi, everyone, Drew here. Two quick things. Number one, thank you so much for listening to this podcast. If you haven't already, subscribe, just hit the subscribe button on your favorite podcast app. And by the way, if you love this episode, it would mean the world to me. And it's the number.

number one thing that you can do to support this podcast is share with a friend, share with a friend who would benefit from listening. Number two, before I go, I just had to tell you about something that I've been working on that I'm super excited about. It's my weekly newsletter, and it's called Try This. Every Friday, yes, every Friday, 52 weeks a year, I send out an easy-to-digest protocol of simple steps that you or anyone you love can follow to optimize your own health. We cover everything from nutrition to mindset to metabolic health, sleep, community, longevity, and so much more.

If you want to get on this email list, which is, by the way, free and get my weekly step-by-step protocols for whole-body health and optimization, click the link in the show notes that's called Try This or just go to Drew Perot.com. That's D-H-R-U-P-U-R-H-I-T dot com and click on the tab that says, try this.