Episode 48: Nitric Oxide: The Essential Molecule for Life & Longevity | Dr. Nathan Bryan

Show Notes

Most of us only hear about nitric oxide in the context of nitroglycerin for chest pain or the little blue pill for erectile dysfunction. But nitric oxide is so much more than that. It is a master regulator that dictates blood flow, oxygen delivery, and energy use in every tissue you have, and when any tissue loses adequate blood flow, that is where disease begins.

In this episode, Dr. Ravi Kumar sits down with Dr. Nathan Bryan, who has spent almost thirty years answering one question: how do we maintain adequate nitric oxide production in the body throughout our lives? Dr. Bryan walks through the two completely different ways your body makes nitric oxide and why almost all of us are quietly shutting both of them down without realizing it.

The first pathway is the nitric oxide synthase enzyme inside the lining of your blood vessels. It takes L-arginine and converts it directly into nitric oxide gas on demand. The second pathway is the entero-salivary loop: dietary nitrate from leafy greens is concentrated in your salivary glands, oral bacteria reduce it to nitrite, you swallow it, and stomach acid converts it into nitric oxide. Two fountains. One pathway requires a healthy enzyme. The other requires a healthy oral microbiome and adequate stomach acid.

Now look at what modern life does to both. Two out of three Americans use mouthwash, sterilizing the very oral bacteria that are essential for the second pathway. Seventy-three percent of US municipalities fluoridate the water, and 95 to 97 percent of Americans use fluoride toothpaste, both of which kill those same bacteria. Two hundred million prescriptions are written for antacids every year, eliminating the stomach acid required for the final conversion step. And on top of all that, the food itself has 76 percent less basic nutrients than it did in the 1940s due to over-farming and nutrient-depleted soil. It is, as Dr. Bryan puts it, no wonder Americans are sick.

The conversation traces the hierarchy of nitric oxide deficiency through the body. Erectile dysfunction is the canary in the coal mine, an early warning that systemic endothelial dysfunction has begun. Then blood pressure rises. Then insulin resistance and metabolic disease. Eventually, mild cognitive impairment, dementia, and Alzheimer’s disease, which Dr. Bryan describes as essentially type 3 diabetes, focal ischemia and insulin resistance in the brain. Every step in that progression is the body trying to tell you something, and most people never get the memo.

Dr. Bryan also dismantles the 1956 cured-meat scare and explains why nitrite in bacon is not the carcinogen it has been made out to be, especially since 1972, when the US government required ascorbic acid to be added to cured meats to block nitrosative chemistry. The real mechanism behind cardiovascular benefits of the Mediterranean diet may not be the antioxidants at all, but the dietary nitrate from green leafy vegetables feeding the entero-salivary loop.

The episode closes with a practical playbook. Stop the things that destroy nitric oxide production: ditch the mouthwash, ditch the fluoride toothpaste, wean off antacids you do not truly need, cut the sugar that glycates your enzymes. Add the things that restore it: 18-hour daily intermittent fasts, 20 to 30 minutes of sunlight a day, moderate exercise, nasal breathing, leafy greens. And for those who want to go further, Dr. Bryan walks through the science behind his nitric oxide-releasing lozenges, modeled on the same nitric oxide gas therapy used to save “blue babies” with pulmonary hypertension.

Episode Resources

Dr. Ravi Kumar on LinkedIn
Dr. Nathan Bryan on LinkedIn
N1O1 Product website
Restore Your Nitric Oxide: Shop Dr. Bryan’s nitric oxide-releasing lozenges and oral care line here. Use code KUMAR10 for a discount.

In this episode, you will discover:

Nitric oxide as a master regulator: Why this short-lived gas controls vasodilation, oxygen delivery from hemoglobin, stem cell mobilization, mitochondrial efficiency, and even telomere length, making it foundational to longevity, performance, and disease prevention
The “canary in the coal mine”: Why erectile dysfunction is the first sign of nitric oxide deficiency in both men and women, and how the same endothelial dysfunction that shows up in the sex organs is also showing up in the coronary, cerebral, hepatic, and pulmonary arteries
Type 3 diabetes: Why Alzheimer’s disease is essentially focal ischemia plus insulin resistance in the brain, and how nitric oxide is the missing link between metabolic disease and neurodegeneration
The two fountains of nitric oxide production: The nitric oxide synthase (NOS) enzyme that takes L-arginine and produces NO on demand, and the entero-salivary pathway that recycles dietary nitrate through the oral microbiome and stomach acid
The mouthwash trap: Why chlorhexidine, Listerine, and other antiseptic mouthwashes raise blood pressure within seven days by killing the very oral bacteria you need to convert nitrate into nitric oxide
The fluoride problem: Why the 2024 National Toxicology Program report linked fluoride exposure to lowered IQ in children, why 73 percent of US municipalities still add it to drinking water, and why brushing with fluoride toothpaste is, by its own warning label, a poisoning event
The 1956 cured-meat scare and why bacon is not your problem: Why the original epidemiology was wrong, why the 1972 federal requirement to add ascorbic acid to cured meats blocked nitrosamine formation, and why “uncured” or “no nitrite added” celery-powder bacon is actually less safe and less shelf-stable than traditionally cured meat
The Mediterranean diet and nitrate: Why the cardioprotective benefits of the Mediterranean, Japanese, and DASH diets may be driven primarily by the dietary nitrate in leafy greens, not by the antioxidants
Why eating your greens may not be enough: A 50-city survey showed Texas celery has up to 50 times more nitrate than New York celery, and 76 percent less basic nutrients in US soil since the 1940s makes consistent dietary nitrate intake nearly impossible
The 18-hour intermittent fast: Why Dr. Bryan considers caloric restriction and intermittent fasting the single most transformational, free, and accessible intervention for restoring metabolic flexibility
The nitric oxide lozenge science: How an orally disintegrating tablet can generate 20 to 30 parts per million nitric oxide gas (the same dose used safely in premature babies with pulmonary hypertension), why it works as a hormone bound to glutathione and inorganic nitrite, and how it also restores the oral microbiome and prevents tetrahydrobiopterin (BH4) oxidation that drives age-related NOS uncoupling
Nitric oxide and immune resilience: Why nitric oxide downregulates the ACE2 receptor (the binding site for SARS-CoV-2 spike protein), why poorly vascularized tissues are prone to infection, and how nitric oxide directly suffocates bacteria by binding to their iron-sulfur centers
Restoration is real: Published 2019 data showing the oral microbiome fully repopulates within four days of stopping mouthwash, with blood pressure normalizing and microbial diversity increasing

Key Takeaways

Nitric oxide is foundational, not optional. Without sufficient production, the body cannot heal or perform optimally, regardless of what else you are doing right
The body has two completely independent ways to make nitric oxide. Modern hygiene and pharmacy habits sabotage both: the NOS enzyme through sugar-driven glycation, sedentary lifestyle, and certain drugs; the entero-salivary loop through mouthwash, fluoride toothpaste, and antacids
Erectile dysfunction is rarely “just” erectile dysfunction. It is the first measurable sign of systemic endothelial dysfunction, and the same process is happening in the coronary, cerebral, hepatic, and pulmonary arteries
The 1956-era fear of nitrite in cured meat is outdated. Since 1972, federal regulation has required ascorbic acid in cured meats to block nitrosamine formation, and current testing shows no detectable nitrosamines in properly cured meats. “No nitrite added” celery-powder bacon is less safe and less shelf-stable
The 2024 National Toxicology Program report linking fluoride exposure to lowered IQ in children is part of a growing body of evidence that should change public policy on water fluoridation
The oral microbiome is resilient. Four days off mouthwash is enough to restore microbial diversity and normalize blood pressure in published studies
A 76 percent decline in basic soil nutrients since the 1940s means even a “good diet” of vegetables may not deliver consistent nitrate. Soil testing and supplementation are now part of the conversation
The single most transformational, free intervention for metabolic flexibility is an 18-hour daily intermittent fast. Eat your last meal at six, sleep, coffee in the morning, eat at noon
Nitric oxide is part of the innate immune system. It downregulates ACE2 receptor expression, mobilizes immune cells to the site of infection, and directly kills bacteria by binding to their iron-sulfur centers
The principle that has built modern Western medicine, applied pharmacology, has reached its limits for chronic disease. Returning to applied physiology, removing what the body does not need and replacing what is missing, is the path back to health

Transcript

[00:00:00 –> 00:03:11] Dr. Ravi Kumar: Welcome to the Dr Kumar Discovery podcast. I’m your host, Dr. Ravi Kumar. And on today’s episode, I’m sitting down with Dr. Nathan Bryan, one of the world’s leading experts in nitric oxide biology. Now when most of us hear nitric oxide, our minds go to one of a few places. Maybe the dentist’s office, maybe recreational drugs, maybe nitroglycerin for chest pain, or that little blue pill for erectile dysfunction. But here’s the thing. Nitric oxide is so much more than all of that. It’s a master regulator throughout your entire body. It controls blood flow, nutrient delivery, and energy use in every tissue you have. And when any tissue in your body loses adequate blood flow, then that’s when disease begins. So maintaining healthy nitric oxide production isn’t just about your heart or your sex life. It’s foundational to optimal health, period. Now my guest today, Dr. Bryan, has spent almost thirty years of his career trying to answer one question. How can we maintain adequate nitric oxide production in our body throughout our lives? And what he’s discovered and what he lays out in his book, The Secret of Nitric Oxide, Bringing the Science to Life, has genuinely changed how we should be thinking about longevity, disease prevention, and everyday performance. I read his book cover to cover, and it inspired me to reach out to him for this conversation. So by the end of this episode, you’re gonna understand what nitric oxide actually does in your body, why almost all of us are deficient and don’t know it, and two completely different ways your body makes it. We’ll also talk about why your mouthwash, your toothpaste, and your antacids might be quietly sabotaging your health. And then we’ll talk about what you can actually do to restore your nitric oxide balance. And one more thing before we dive in is a quick disclaimer. I’m a doctor, but I’m not your doctor. This show is for informational purposes only. Everything you learned from my conversation with Dr. Bryan is meant to empower you. So take this knowledge, ask better questions, and work with your own doctor to build a more informed, healthier life. And, also, just to be clear, this show is separate from my role as assistant professor at UNC. Alright. Let’s get into it. My name is Dr. Ravi Kumar. I’m a neurosurgeon in search of the causes of human illness and the solutions that help us heal and thrive. I want you to join me on a journey of discovery as I turn over every stone in search of the roots of disease and the mysteries of our resilience. The human body is a mysterious and miraculous machine with an amazing ability to self heal. Let us question everything and discover our true potentials. Welcome to the Dr Kumar Discovery. Dr. Bryan, thanks so much for joining us. Can you start off by telling us what nitric oxide is, and why it’s so important to human health?

[00:03:11 –> 00:04:12] Dr. Nathan Bryan: Well, thanks Ravi for having me. It’s great to be with you, and, um, yeah, nitric oxide is a signaling molecule. It’s a it’s naturally produced. Interestingly, it’s a gas, and it’s one of the few gaseous signaling molecules. And the discovery of nitric oxide was a kind of a new paradigm in cell signaling. But nitric oxide regulates important biological function. It’s it was first discovered to be a vasodilator, meaning that when it’s produced, it relaxes the smooth muscle around blood vessels, it leads to dilation so we get better circulation, better oxygen delivery. It regulates oxygen delivery from hemoglobin. It mobilizes our own stem cells so we can repair and replace dysfunctional cells. It activates the mitochondria so they become more efficient at generating cellular energy. And it also prevents our telomeres from getting shorter. And this is an emerging science when we’re finding that shorter telomeres, shorter lifespan, longer telomeres, longer lifespan. So everything we know about human optimization, longevity, disease prevention is all reliant on the body’s ability to produce nitric oxide.

[00:04:12 –> 00:04:44] Dr. Ravi Kumar: Yeah. That’s fascinating because I think a lot of us have heard of nitric oxide, and we usually think about it in the realm of cardiovascular disease and sexual function. Those are kind of the two main things where we’ve heard about it maybe from our doctors, because people take nitroglycerin for angina, and they take, uh, phosphodiesterase inhibitors, like Cialis for erectile dysfunction. But you’re saying that it’s basically involved in all these other physiological processes that lead to overall general health and longevity, which is something that most of us have never heard. Yeah.

[00:04:44 –> 00:06:27] Dr. Nathan Bryan: You know, this is when you talk about nitroglycerin, you know, there’s that’s actually what led to the discovery of nitric oxide. It was Fred Murad in 1977 discovered that drugs like nitroglycerin, which are called organic nitrates, they work in dilating the coronary arteries and relieving acute angina because they release this they metabolize into nitric oxide gas. So it was a very important discovery and and realization of the mechanism of action of of these drugs that have been used for, what, more than a 100 years prior to discovery of nitric oxide. And then the other thing, the the PDE5 inhibitors, those don’t affect nitric oxide production. They potentiate nitric oxide signaling. And that’s why these drugs only work in about 50 percent of the men in which they’re prescribed. But, yeah, that all of these drugs, you know, drugs provide kind of a mechanism of action to help us elucidate different pathways. But there’s limitations to both of those. I mean, you develop tolerance to organic nitrates and PDE5 inhibitors only work in 50 percent of the men. As you start to understand the science of nitric oxide, how it’s produced, when it’s produced in the human body, it’s gone in less than a second. So what I tried to do, I guess, probably almost thirty years ago is figure out when nitric oxide is produced and it’s gone in less than a second, where does it go, what does it become, and how does it signal? And over the past twenty five years, we’ve discovered many other and many other groups have discovered these things, these physiological effects of nitric oxide outside the cardiovascular system. Because it was discovered as a saving molecule in the cardiovascular system. But we know it affects protein structure and function. It’s affecting the genetic expression. It’s it leads to epigenetic regulation of of certain genes. It can turn genes on, turn genes off. It can activate enzymes. It can deactivate enzymes. So it’s it’s much more than a vasodilator. We call it a foundational molecule, because your body cannot and will not heal or perform optimally without sufficient nitric oxide production.

[00:06:27 –> 00:06:50] Dr. Ravi Kumar: Talk to me about two different types of people. Like, one person who’s making adequate nitric oxide, they’re at the peak of their human health, essentially, in that realm. And then someone who is on the decline, they’re make not making adequate nitric oxide, or they have some disease process that’s inhibiting it. What do they look like? How do they look different clinically?

[00:06:50 –> 00:07:38] Dr. Nathan Bryan: Well, if you’re replete in nitric oxide, uh, you have an optimal blood pressure, uh, you have a lot of stem cells in circulation. So if you’re working out, you have a cut or a wound, you heal rapidly. Uh, you have adequate metabolic flexibility, meaning that you don’t get these spikes in blood sugar. Your insulin is active. Your cells are sensitive to insulin. You can perform. You can go longer, stronger, faster than the competition. Libido’s good. Sexual function is is optimal. Men wake up with with morning erections. Women’s have optimal sexual performance, multiorgasmic, good lubrication. And you think your executive function, your cognitive function is is better than than the rest. So that that’s what we’re all looking for. How do we live the longest and live the best Right. Quality of life without disease, without symptoms? So that’s what we’re all shooting for.

[00:07:38 –> 00:07:50] Dr. Ravi Kumar: Okay. Yeah. Of course. And so are all those effects that you just talked about, that optimal healthy state with adequate nitric oxide, is that all from vasodilation, or is it from these other signaling mechanisms that it has?

[00:07:50 –> 00:10:37] Dr. Nathan Bryan: Look, everything is about blood flow. The nitric oxide is more than regulating blood flow. Because when we look at the effects of insulin, insulin binds to insulin receptors on cells and it transduces an intracellular cascade that eventually tells that cell to bring glucose into the cell and cleared from circulation. Well, it’s nitric oxide that signals GLUT4 to go to the membrane and bring that glucose in. So it’s part of the insulin signaling pathway, and that is completely independent of the vasodilatory effects of nitric oxide. So there’s different ways and different mechanisms of how nitric oxide’s working, and it’s much more than just dilating the blood vessels. But when we talk about those effects and how do you optimize your performance in all aspects of your life, we know that clinically because we may be able to corroborate this. Because if you can’t make nitric oxide so let’s let’s then illustrate that person who’s nitric oxide deficient. And what we’re finding is there’s a hierarchy of symptoms that manifest. Your body’s always talking to you. And if you don’t listen, then you you progress down this road of eventually heart attack, stroke, and Alzheimer’s. But the first sign and symptom of nitric oxide insufficiency is erectile dysfunction, and that occurs in both men and women. Because if you just think about the vasodilatory effects of nitric oxide, if you can’t dilate the blood vessels of the sex organs when we’re activated, we’re about to be intimate, then you can’t get engorgement and you do not get an erection. And that’s all because the blood vessels, the endothelial cells, the nerve endings in the sex organs aren’t producing nitric oxide because the enzyme isn’t working. It’s called endothelial dysfunction. So endothelial dysfunction leads to erectile dysfunction. But if you have endothelial dysfunction in the vascular bed of the sex organs, it’s a systemic disease. It’s not unique to that vascular bed. It’s same thing occurs in the coronary arteries, the cerebral arteries, the hepatic arteries, and the pulmonary arteries. Mhmm. So that’s number one. We call it the canary in the coal mine. And then number two, your blood pressure starts to go up. Because if you lose the main vasodilation molecule or vasodilatory molecule, then you’ve got the same volume of blood going through smaller pipes, resistance goes up, and pressure goes up. That’s number two. And two out of three Americans have an unsafe elevation in blood pressure. Number three, we’ve mentioned you start to develop insulin resistance and metabolic disease because the cells can’t make nitric oxide. When you secrete insulin from the pancreas, then you developHyperglycemia and eventually diabetes. You develop exercise intolerance because if you can’t dilate the blood vessels of the coronary arteries or the skeletal muscles when you begin to work out, then you tire easily. You can develop chest tightness and angina and exertional angina. And then number four, if you if you don’t listen to your body and you progress along the way, then eventually you develop mild cognitive impairment, faster dementia, and Alzheimer’s. Alzheimer’s is really the end stage of chronic nitric oxide deficiency because it’s it’s focal ischemia in the brain, hypoperfusion, and it’s insulin resistance in the brain, diabetes type 3. And all of those are the end result of insufficient nitric oxide production.

[00:10:37 –> 00:11:56] Dr. Ravi Kumar: Yeah. That’s fascinating. I mean, just so the audience understands this, and this will be kind of like a summary of what you just mentioned, nitric oxide is this basically signaling molecule that causes vasodilation in blood vessels. So it allows more blood flow into tissues. And it also acts in the signal transduction between insulin and these GLUT4 receptors in cells that basically come up to the cell surface, grab onto glucose, and pull it into the cell. So, you can imagine this nitric oxide is creating more blood flow, and then it’s allowing cells to pull in energy in the form of glucose. And if you don’t have enough of that, you end up with poor blood flow and not enough energy metabolism, which leads to all these disease states, which we see in many different states. It’s always in this setting of inflammation and hypoxia from poor nutrient and oxygen delivery to the cells, and nitric oxide is like a key. It’s a key that churns that and opens things up to allow for this this process that keeps your tissues healthy. So it’s almost like a fundamental molecule, and it’s it’s totally fascinating. Tell me about the two different ways that we actually make nitric oxide in our body because, you know, I read your book, and there’s these two fountains of nitric oxide. Can you explain that to us?

[00:11:56 –> 00:14:51] Dr. Nathan Bryan: Yeah. There’s two ways that the body makes nitric oxide. There’s an enzyme, and it was first discovered in the endothelial cells. It’s also produced in our neurons in the brain, but it’s called nitric oxide synthase. So the enzyme synthesizes nitric oxide. And so this this enzyme takes l arginine, which is a semi essential amino acid, and converts it into nitric oxide. And then a byproduct of that reaction is l citrulline. And that’s just that’s the biochemistry and enzymology of that reaction. And so this is the second to second regulation of blood flow and dilating blood vessels and regulating blood flow on demand. And so we understand the enzymology and the biochemistry of that enzyme, and we know what leads to loss of its function, and we know how to restore the function. And then the other way is through our diet and really through the action of oral bacteria, because we can we can recirculate the nitrate that we get when nitric oxide’s produced in the lining of the blood vessels. It’s oxidized to inorganic nitrate. That nitrate is reabsorbed in the kidneys, and we get nitrate from the diet, primarily green leafy vegetables. So this this pool of nitrate is always concentrated in our salivary glands, and then when we secrete the saliva, we’re secreting nitrate. And then if we have good oral microbiome, these bacteria respire on the nitrate, they’re facultative anaerobes. And so they reduce that nitrate into nitrites. It’s a two electron reduction that humans don’t have the capacity to do. We’re a 100% relying on the oral bacteria. And now our saliva is enriched in nitrites, so we swallow our saliva. As long as we have sufficient stomach acid production, that nitrite turns into nitric oxide. And this is how we take components from the diet and make nitric oxide. And that nitric oxide that’s produced from swallowing our own saliva and eating a good diet and having good bacteria. It enhances gastric mucosal blood flow. It inhibits ulcerations from chronic NSAIDs. It prevents ulcerations from H. pylori. It kills things like H. pylori, E. coli, all opportunistic, you know, food borne pathogens. As long as you have good stomach acid and nitric oxide produced, you don’t get sick from food borne pathogens. Now that we understand those mechanisms, you can start to implicate diet and lifestyle and invoke a mechanism of action, and explain why diet and lifestyle is cardioprotective. It prevents disease. It reverses disease. It cures disease because now we can invoke a specific mechanism of action. But you have to understand what’s required to do this. Number one, you have to have a functional enzyme in the lining of the blood vessels. Number two, you gotta eat a good diet. You gotta have good oral bacteria, and you’ve gotta make stomach acid. And we know that most people don’t eat a good diet. Two out of three Americans use mouthwash, killing all the bacteria in their mouth, sterilizing their mouth every day, twice a day sometimes. We know 73 percent of the municipalities in The US have fluoride in their drinking water, killing the bacteria in our body, on our body. And there’s 200,000,000 prescriptions written for antacids every year, and two out of three Americans report using an over the counter antacid. So to me it’s no wonder why Americans are sick because everything we’re doing is leading to a a chronic loss of nitric oxide production, and we can explain everything that’s happening in these chronic diseases.

[00:14:51 –> 00:16:37] Dr. Ravi Kumar: I mean, that’s really neat because we knew for many years that when people would nitroglycerin, their stomach ulcer pain would get better. And they found that out because they were having stomach ulcers, but they thought it was angina. So they’re like, okay, give them, you know, nitroglycerin, and then they’re like, oh, yeah, it gets better. Well, it was the nitrate or the nitric oxide, uh, from that being converted to nitric oxide in the stomach that was making that stomach pain better, and restoring mucosa. Yeah, and killing the H. Pylori, yeah. So this entero salivary circulation is totally fascinating to me because your body is, I mean, the body always amazes me because it creates these amazing mechanisms for recycling and enhancing and concentrating nutrients where they need to be. And so just for the audience, you know, when you’re eating leafy greens, like Dr. Bryan was talking about, that’s the largest source of nitrates in the human diet. Those can get converted in your mouth by these bacteria if you’re not nuking your mouth with mouthwash, essentially, and killing your your oral microbiome. There’s bacteria that will convert that nitrate to nitrite. Nitrite goes down your stomach and gets exposed to your stomach acid, turns to nitric oxide. It also gets absorbed into your systemic circulation where it can be converted peripherally. But, your body then concentrates that nitrate that’s still in your bloodstream in your salivary glands, so that bacteria can help you out and make nitrite, which turns to nitric oxide. So it’s this, it’s this like amazingly engineered system. And I I think it’s so cool. And let me ask you this, these Mediterranean diet, DASH diet, all these diets that bring down blood pressure and have been shown to do so in clinical trials, is that because of the nitrates and the leafy greens and the vegetables that are eaten on these diets?

[00:16:37 –> 00:17:27] Dr. Nathan Bryan: I think it can partly be explained by that. You know, they they always try to, you know, blame the antioxidant, not blame the antioxidant, but account for the antioxidants in a Mediterranean diet to lower blood pressure. But if you try to recapitulate that that diet by giving the same antioxidants, you don’t get the same effect. And I think where we came in and we published on this, I believe, in 2009, 2010, that it may be the nitrate content that’s recycling in the nitric oxide, dilating the blood vessels, reducing inflammation, and could account for the cardioprotective benefits and blood pressure lowering effects of things like a Mediterranean diet, Japanese diet, and even the dietary approaches to stopHypertension. But I think, you know, these dietary components work in unison. You know, you take things out and you isolate them, you lose a lot of the biological activity. But I think it’s the nutrients, nutrient replete foods in that matrix that provide the best benefit.

[00:17:27 –> 00:18:12] Dr. Ravi Kumar: Hey, guys. I need a quick favor. If you’re getting value from this show, would you please take thirty seconds to rate and review us on Apple Podcasts? I know it seems like nothing, but it genuinely changes how many people the algorithm puts the show in front of. And if an episode hits home for you, send it to someone who you think needs to hear it. I’m doing this to cut through the noise and bring you clear, honest information on health topics that actually matter to all of us. So please help me get the show to more people who need it. Cheers. So tell us about how bad chlorhexidine mouthwashes and these other mouthwashes with, you know, botanical antimicrobials are for for the mouth and what it does to your whole body because I think there’s a pretty strong link with hypertension, isn’t there?

[00:18:12 –> 00:20:52] Dr. Nathan Bryan: There is. You know, we first stumbled on this probably, I guess, maybe ten or fifteen years ago. But there were some studies coming out showing that if you took normal intensive patients and you gave them chlorhexidine, which is a stringent antiseptic, it’s a prescription medication used for chronic halitosis and severe world infections. And this is a surgical scrub too, so it tells you how effective it can be at killing bacteria, all bacteria, not just bad bacteria. What they found was that the there was an increase in blood pressure after seven days. That increase in blood pressure correlated with a decrease in nitric oxide production. And so we were doing these same studies, and so we that was an interesting observation. And then I was working in collaboration with the dental school, the school of dentistry at UT Medical School in Houston. Okay. Let’s do tongue scraping and see if we can identify the bacteria that are responsible for this effect. And if you eradicate them, you decrease nitric oxide production and blood pressure goes up. So we were using Chlorhexidine to basically reproduce those same studies, and we and others have been able to reproduce that. So the story goes if you use mouthwash, it’s killing all the bacteria. And even Listerine, you know, you see the commercials and they say it kills 99.99% of the bacteria, and they apparently they’re proud of that. But it’s it’s making people sick. But But no, it’s it’s killing all the bacteria, the good, the bad, the ugly. And what’s happening is you’re destroying the microbiome, you’re decreasing this 50% of the total bodies that’ll be produced nitric oxide. When you decrease nitric oxide production, your blood pressure goes up. You develop runaway inflammation, oxidative stress, and immune dysfunction, and it’s really starts you on this very slippery slope to age related chronic disease. And, you know, when I look back and why do we do this? Can you go back to over a hundred years ago when it was first recognized that people with poor oral hygiene have a higher risk of heart attack or stroke. Not higher risk, higher incidence. And that you could actually culture oral pathogenic bacteria in a thrombus that cause sudden cardiac death in patients upon autopsy. So a hundred years ago, we didn’t know that there was a microbiome. We thought that all bacteria were infectious pathogens. So the therapeutic solution was let’s kill all the bacteria in the mouth. Well, now fast forward a hundred years, we know that humans are 10 times more bacterial than we are humans. We have 10 times more bacterial cells in and on the body than we have human cells. And now we also know that if you destroy the microbiome, you destroy the human host and cause chronic disease. But yet we haven’t implemented that in in that change, certainly in dental medicine. I think now they’re becoming a greater appreciation in in general medicine on the importance of the microbiome. But to get back to your question, anything that’s antiseptic is extremely damaging to the human host, because we have to support the microbiome. We can’t continue to destroy it every day, sometimes multiple times a day.

[00:20:52 –> 00:22:12] Dr. Ravi Kumar: I think that’s something most people have never heard that, hey, this mouthwash might be bad for you, might be killing the bacteria that are making the basic components that keep your blood pressure controlled. This whole concept of the oral health affecting your whole body health, that’s completely misunderstood and underappreciated in medicine, honestly. Something we’re still learning about, obviously, but yeah, keep take care of your teeth because that’s very important. Okay. So, this is my next question, and I think this is going to blow everybody’s minds. It blew my mind. And, you know, I’m fairly well educated, but I didn’t discover it until I read your book and then I researched it on my own. But we keep talking about this nitrite, sorry, nitrate to nitrite conversion, and then nitrite turns to nitric oxide through reduction. But the keyword there is nitrite. And we’ve been told for my whole life that sodium nitrate in cured meat is carcinogenic. But now we’re finding out, through your work and many others, that nitrite is actually fundamental to human health. So which is it? Is bacon giving us cancer? And I want you to bring this full circle and link it to nitrosamines, and why that might be the the real culprit here.

[00:22:12 –> 00:25:46] Dr. Nathan Bryan: Well, again, you have to go back in history and figure out, okay, how did this start? What was the basis for this kind of hypothesis? And it goes, there’s there’s usually a valid reason, like the oral systemic link and and giving an antiseptic. When 1956, there was a important papers published showing that in nitride cured fish, you could detect low molecular weight nitrosamines. And low molecular weight nitrosamines are known carcinogens. The biggest one is dimethyl nitrosamine, causes liver cancer. It’s a very strong, uh, carcinogenic agent. So then when when nutritional epidemiologists came in the in the seventies and eighties, they started linking certain dietary patterns with certain increased risk of certain diseases and cancers. That’s what nutritional epidemiology does. And what they found was that people who consumed a greater proportion of cured meats appeared to have a slight increased risk of certain gastric cancers, stomach cancers, esophageal cancers. So in nutritional epidemiology, you have to check a number of boxes to make it kind of a biologically plausible mechanism. So you start with an observation, and then you come up with a biologically plausible mechanism. And their mechanism was the nitride in cured and processed meats can nitrosate low molecular weight amines form nitrosamines that accounts for the increased risk of certain gastric cancers from people who eat them. But in these studies, they also put in processed meats. But processed meats aren’t cured meats. Processed meats just means that it’s it’s altered from its original form. So ground beef, for example, or ground turkey, that’s processed meat. It’s not cured. There’s no nitride added to it. So over a period of years, this mechanism of action in this biologically plausible mechanism of action starts to fall apart. Because in the nineteen seventies and eighties, it was realized that 85% of the nitrate and nitrite we get from the diet comes from eating green leafy vegetables. So if their hypothesis was true, then vegetarians would have 10 times higher rates of cancer than meat eaters. And we know that’s not the case. It it’s the exact opposite. So that that falls apart. But then the other thing is we found that there’s really no naturally occurring low molecular weight amines, tertiary amines, or or actually secondary amines. Those are the only ones we we worry about. And then in 1972, the US government got involved and changed the code of federal regulations whereby they said any nitride added any nitride cured meat, you have to add ascorbic acid because that inhibits any nitrosative chemistry. Now the meat companies don’t use ascorbate. They use erythrobate. We’ve done this. We’ve tested it. We’ve looked at residual nitride. We’ve looked at nitrosamines. And there’s no detectable nitrosamines in nitride cured meats, especially since 1972 because you inhibit that nitrosative chemistry. So this whole kind of hypothesis falls apart. In fact, I published on we I edited a book with Joe Loscalzo, who’s chair of medicine at Harvard Medical School and chief of cardiology at the Brigham. I think our first edition was in it’s called Nitride and Nitrate in Human Health and Disease because so many people had the same question you asked. Because we were turning this whole story for fifty years on its end and go, what do you mean nitrite and and bacon doesn’t cause cancer and we shouldn’t avoid it? And it’s because they didn’t understand the chemistry and the epidemiology and all these endogenous systems whereby we we make nitrite and nitrate endogenously. The kidneys reabsorb it. It’s concentrated in our salivary glands. The human body would never intentionally reabsorb a toxic substance and invoke a mechanism for it. So it completely changed them. In fact, Walter Willett, one of the premier nutritional epidemiologists at Harvard, wrote a chapter in the book on nutritional epidemiology and said, look, the the mechanism was wrong. We call that innovation, right, and moving forward. We know things today that we didn’t know fifty years ago, and it changes the strategy and certainly changes the recommendations, or should change the recommendations, should change public policy, and should change patient care based on new information.

[00:25:46 –> 00:26:55] Dr. Ravi Kumar: Yeah. Absolutely, because if you think about it, we’ve been scared of sodium nitrate, which is fundamental to our biology, and the US government started adding, you know, ascorbic acid and then this analog of vitamin C, which prevents this basically conversion to nitrosamines. So you’ve got this cured meat that’s not gonna become bacterial contaminated, that actually might play, have this substance that plays a fundamental role in your biology. Instead, we’re replacing it with nitrate free or uncured bacon, which now has like celery powders and things like that, which has an basically an unknown or an improperly controlled level of sodium nitrite, except now it’s from a vegetable, and might not have the antioxidants that the traditionally cured bacons have in them to prevent the nitrosamine formation. So it becomes this cycle of basically misinformation and misunderstanding that leads to this dogma that determines how we eat meats, which is totally misguided. It fascinated me when you mentioned that in the book, and I looked it up, and I was like, oh my gosh, This is gonna blow everybody’s everybody’s mind.

[00:26:55 –> 00:28:01] Dr. Nathan Bryan: Yeah. It’s it’s consumer deception, I mean, by these meat companies. And I’ve, you know, met with Kraft, Oscar Mayer, and said, look, you should be, you know, advertising this. This is a nutrition that it’s it’s an indispensable nutrient. But here’s I want to I think your audience should understand this. The the uncured or no nitride added they what they do is they’re adding celery powder, which is enriched in nitrate, and then they add a culture of of staph carnosis, which is a bacteria culture to reduce the nitrate to nitrite. So you cannot have a cured meat product without some nitrite. They just don’t add the salt, but they’re making it synthetically to these bacteria cultures. But there’s so much variability from culture to culture, you never know what quality of cured meat the end product is, and you always have some residual bacterial cultures on that meat. So it’s less safe, it’s less shelf stable, and you the variability in that product, and you’re paying twice as much in some cases. You know, you’re paying much more for a no nitride or organically cured meat product. So save your money, buy the traditionally-cured. It’s better for you, it’s safer, and it’s a it’s a longer shelf life. And it tastes better.

[00:28:01 –> 00:28:15] Dr. Ravi Kumar: You know, definitely, there’s there’s definitely a flavor to, uh, nitrite curing of meats. Most people don’t realize it’s not just something for curing. Actually, that flavor of ham and bacon that you love, a lot of that comes from the nitrite that’s added.

[00:28:15 –> 00:28:26] Dr. Nathan Bryan: There is no replacement for nitrite in terms of food safety, from preventing Okay. Clostridium and all these other foodborne pathogens that would make people deathly ill. That’s absolutely essential for food safety.

[00:28:26 –> 00:28:46] Dr. Ravi Kumar: Yeah. And, well, very interesting. So now tell us, why does nitric oxide production decline? We already kinda hit on this mouthwash use and not taking care of your oral microbiome, but what about the endogenous synthesis throughout your body? Why is it declining throughout life? Like, why do I make less nitric oxide today than I did when I was 20?

[00:28:46 –> 00:31:44] Dr. Nathan Bryan: Well, that doesn’t necessarily have to be the case. So if you look at the published studies and just screening people from 20 to 30, 30 to 40, not including any type of criteria. You’re just looking at age, using age. And in these studies, we’re really looking at the function of the enzyme. So you can infuse bradykin and or acetylcholine in the coronary arteries, the brachial artery, and look at the result in vasodilation. So this is measuring endothelial function. It’s measuring the production of nitric oxide in the endothelial cells of the blood vessels. And what these data clearly show is that starting in your early twenties, you start to lose about 10 to 12% per decade. So by the time you’re forty to fifty to sixty, you have, on average, 50% that you had when you were in your teens or early twenties. Then by the time you’re 60, 70, 80 years old, you know, you’re 10% of what you had in early. And so the question then was, what leads to a loss of production or the loss of function of that enzyme? And now we’re starting to understand that. But it’s it’s really the Western lifestyle. It’s a poor diet. Anything that leads to an increase in blood sugar is gonna render that enzyme dysfunctional. Because when you think about this, anything blood sugar, what we call glucose, is sticky. It’s like glue. That’s what it’s properly named. It’s it’s if you’ve ever spilled the soda on the countertop and come back the next day, it’s sticky. And that’s the sugar. Sugar is sticky. So when you have an elevation in blood sugar, glucose, for an extended period of time, it sticks to proteins. It sticks to hemoglobin. And we call that hemoglobin A1C. It’s how much sugar is bound to hemoglobin. But it also sticks to enzymes. And enzymes have to undergo conformational change. In in biochemistry, it’s all about flow of electrons, and you have to these enzymes have to change their shape and structure. If it’s glued together with glucose, it can’t undergo these conformational changes, so it can’t do its job. And that’s that’s diabetes. That’s why diabetes have diabetics have macular degeneration and neuropathy and poor healing wounds because they have no circulation, and the enzymes don’t work. They can’t deliver oxygen because hemoglobin is locked in a conformational state. And so that’s number one. Sugar is the enemy there. Number two, it’s a sedentary lifestyle. Modern physical exercise activates and stimulates the nitric oxide synthase enzyme. And if you’re not exercising, if you’re sedentary, then you’re not stimulating this enzyme. It leads to a loss of function. And then there’s other things like the proton pump inhibitors, drug therapy, certain drug therapy shuts down the function of the enzyme. So that’s what we’re finding that if we if we can stop doing the things that are disrupting the function of the enzyme, and we can start doing the things that can stimulate it and activate it, you don’t see this loss of function. Yeah. And I’d I’m 52 years old chronologically, but I’m 29 biologically. And looking at many different kind of factors, it is looking at carotid intimaity thickness, looking inothelial function, looking at, you know, epigenetic methyl methylation patterns and and glycon age and these different, uh, kind of, uh, biological aging mechanisms or test. But we you don’t have to do that. So on average, we see it, but we know how to reverse it. We know how to prevent it.

[00:31:44 –> 00:32:36] Dr. Ravi Kumar: Okay. So, basically, optimizing metabolic health through managing blood glucose levels, which you mentioned hemoglobin A1C, that’s the percentage of your hemoglobin molecules that have this glucose stuck to it. It’s called agglutination. And that is not just happening to hemoglobin. That’s happening to all these proteins all around your body, and that’s a marker of how well you’ve controlled your blood sugar. So you should aim for hemoglobin A1C, less than 5.7, lower is better. So that comes through exercise and a proper nutrient rich diet. And then taking care of your oral microbiome, so not using mouthwash, fluoridated toothpaste, and not taking a PPI or an H2 blocker or any other antacid that keeps you in this perpetually low acid state in your stomach because that’s where you convert nitrite to nit nitrous oxide in the local environment there.

[00:32:36 –> 00:33:45] Dr. Nathan Bryan: Yeah. And that that’s the the most benefit in all that is in is intermittent fasting. You know, when you look at the data on caloric restriction intermittent fasting, it’s pretty phenomenal and undeniable. And you know, Americans are overfed. We graze throughout the day. You know, we were told that breakfast is the most important meal of the day, and you should eat three squares every day. And then what I’m finding is that if you can do an eighteen hour fast every day, it completely resets your your metabolism. And your body adapts to that, and you become more metabolically flexible. And you don’t store energy as fat, and you be I mean, it completely changed. I’ve been doing an eighteen hour fast daily fast for probably four to five years now, and it completely changed my metabolism, you know, the way I feel, the hunger pains. And, you know, once a week, I’ll do a twenty four hour fast. And then once a quarter, I’ll do a, you know, forty eight or seventy two hour fast. But that’s and that’s a little bit more difficult. But an eighteen hour daily fast is very easy to do. It’s not that complicated. You eat your last meal at six, go to bed at nine or ten, you wake up at six, you have a cup of coffee, work out, and then eat at noon the next day. It’s simple. And I think it’s the most most, uh, I think transformational thing people can do. And it’s cost savings.

[00:33:45 –> 00:33:57] Dr. Ravi Kumar: And it’s free, and it’s available to everyone. There’s no drug cost there. I mean, everyone wants the injection or whatnot, but, you know, fasting, intermittent fasting, exercise, it’s free to everybody. And you’re

[00:33:57 –> 00:34:01] Dr. Nathan Bryan: gonna save on drug costs. You’re gonna be able to get off drug therapy.

[00:34:01 –> 00:34:20] Dr. Ravi Kumar: Yeah, exactly. So, let me ask you this. Let’s say you’ve been using mouthwash for a good portion of your life, or intermittently. I I think like half of Americans use mouthwash. Can you restore your two out of three, really, that high. Wow. Can they restore their oral microbiome? Is there a way to do that? Yeah.

[00:34:20 –> 00:35:39] Dr. Nathan Bryan: We published on this in 2019, and the data in in our study, we found that four days of stopping mouthwash, the oral microbiome completely repopulates. And it may happen sooner, we just happen to look at four days. So we we did baseline, and we measured blood pressure, we did tongue scrapings, we got a full metagenomic analysis, the oral bacteria, then we started the mouthwash twice a day for seven days, remeasured, and then we stopped them for four days, and then brought them back, and then remeasured blood pressure, did tongue scrapings to look at how how rapidly or do these bacteria repopulate. And after four days, they stop using mouthwash, I mean, blood pressure normalized, the diversity of the microbiome had actually increased, and it seemed to be normal. So the good news is, if you’ve been using mouthwash or fluoride for years or decades, you can stop. And these bacteria in these communities are so resilient, they’ll repopulate. And then what we’re focusing on now through development of nitric oxide friendly toothpaste and mouth rinse, is how do we create an environment that allow these good bacteria to improve their diversity, create an environment where that ecology is is sufficient for nitric oxide production, and then you never have to worry about it. Because now we’re creating environment where these bugs and and the good thing about the bacterial communities, if you have a good diverse healthy microbiome, they don’t allow for these opportunistic pathogens to come in. They’re the police. It’s only when you destroy the microbiome that allow these opportunistic pathogens to come in, and that’s what makes people sick.

[00:35:39 –> 00:35:46] Dr. Ravi Kumar: Yeah. What about fluoridated toothpaste? Do they kill these bacteria that are reducing nitrite for us?

[00:35:46 –> 00:36:54] Dr. Nathan Bryan: Absolutely. I mean, fluoride is put in toothpaste Yeah. Because it’s antiseptic. It’s It’s put in the drinking water because it kills the bacteria in the water supply. Mhmm. So when we brush with it, or drink it, or bathe in it, or cook in it, we’re killing the bacteria in and on our body. And you may have seen in 2024, the National Toxicology Program published a paper showing that fluoride in drinking water lowers IQ in kids by as much as seven points. And that was just looking at the fluoride that’s in the drinking water. That didn’t even account for the fluoride that we’re being exposed to in toothpaste. And I encourage you, if you use a fluoride based toothpaste, read the back label. Because it’ll tell you only use a pea sized amount of toothpaste on your toothbrush. Because that pea sized amount contains about half a milligram of fluoride. But everybody I know puts their entire bristle full of toothbrush toothpaste. Now you’re getting ten, fifteen, twenty, thirty milligrams of fluoride. And it’ll also tell you do not swallow this. If you swallow the fluoride toothpaste, call poison control. But the molecular weight of fluoride is, what, nineteen, twenty I can’t remember the periodic table. It’s a very small molecule. You don’t have to swallow it. It’s absorbed immediately through the buccal cavity, through your gums. So every time you brush your teeth with fluoride toothpaste, you should call poison control, because you’ve just poisoned yourself. It’s on the label.

[00:36:54 –> 00:37:47] Dr. Ravi Kumar: Yeah. And and the crazy thing about fluoride is, you know, it’s put in the drinking water. It is a uninformed mass medication of people. You know, that that kind of stuff is against the medical ethos. You know, we there’s informed consent is a very sacred principle in medicine. You do not treat anyone or give them any medication forcibly. They have to have their own autonomy. They have to say, yes, I know what you’re giving me, I understand the risks, and yes, I want it. But here we are putting fluoride, which is a medication, there’s no argument there, in the water without consent. Without consent. And and that’s not an argument that fluoride isn’t, you know, doing something to the enamel of the teeth. I’m not making that argument at all. I’m just saying it is uninformed mass medication of people, and that’s just what it is, which is, to me,

[00:37:47 –> 00:38:20] Dr. Nathan Bryan: crazy. I mean, it goes back to the Nuremberg trials. We’re violating that every day. The US government is violating that. Yeah. But I think now we’re on the right track. You know, there’s there’s efforts now to get fluoride out of the drinking water because it provides no benefit. It doesn’t prevent cavities. It doesn’t help re mineralize the teeth. There’s no benefit. What’s the risk? It lowers IQ in kids. It’s an antiseptic causing dysbiosis. It’s a known neurotoxin, and it shuts down your thyroid function. So if there’s no benefit and it causes all these risks, that’s a very easy quotient. You just eliminate exposure to it globally.

[00:38:20 –> 00:39:19] Dr. Ravi Kumar: Yeah. No. I think that’s something that everyone should do their research on and and be informed because when you got knowledge, it empowers you to take care of yourself. So that’s something everyone should look into. Okay. So the next thing I wanna talk about is this concept that you can actually restore adequate nitric oxide levels, either through diet or supplementation. And this is something that you’ve been very active in through academia and commerce, through your own businesses. Yep. I really wanna hear from you on this because you mentioned something in the book that I thought was very fascinating. You said that you travel all over the world, you had young kids, and you’re not getting sick at all. You know, you’re not getting upper respiratory viruses, and you attributed that to maintaining adequate nitric, uh, oxide levels in your body. So can you kinda unpack that for me and tell me how do we supplement? How do we get adequate nitric oxide through diet? And why does that keep us healthy like you had mentioned?

[00:39:19 –> 00:42:19] Dr. Nathan Bryan: Well, it all goes back to adequate blood supply and being able to mobilize an immune response if we get attacked. We live in a, you know, an infectious world. Some people get sick Mhmm. And some people don’t. They’re resistance to illness. So we know from basic pathology books that poorly vascularized tissues are prone to infection. Diabetic wounds, best example. Highly vascularized tissues are resistant to infection. So whether it’s, you know, we have a cut or it gets exposed to respiratory viruses, the human body is designed to deal with it. So nitric oxide is part of our innate immune system. So let’s take upper respiratory virus. We’ll take coronavirus as an example because we all deal with that. So the the virus enters our human cells and has to attach to the human cells, it has to enter the human cells for it to replicate. The virus needs a human cell to replicate. So in people who are nitric oxide deficient, you get an upregulation of the ACE2 receptor. Well, ACE2 receptor is the binding site for the spike protein on the coronavirus that enters our cell. But in people who make nitric oxide, part of its mechanism is it down regulates the ACE2 receptor. So we may be exposed to viruses. I was exposed. In fact, we had a drug study. We were in phase three for an early therapeutic for COVID. And so we had 26 clinical sites all over The US. And every week, I was in an airplane in COVID clinics. I didn’t wear a mask, and I never got COVID dealing with very, very sick COVID patients. But because I don’t have an ACE2 receptor that’s expressed, there’s no entry site for that virus. It’s not just the seasonal flu virus. It’s it’s other respiratory viruses. And if it were to enter, then what happens is our body sees that as an attack. We mobilize an immune response. Our white blood cells go to the site of infection or attachment. And then four hours after we see that, we start generating a ton of nitric oxide. And that nitric oxide prevents the virus from replicating. So even if it gains entry into the cell, if we make nitric oxide and get the immune cells there in timely manner, then it shuts down their resp their replication. So they can’t replicate, they can’t proliferate throughout the body. Same thing with a bacterial infection. We mobilize an immune response, we generate nitric oxide, and that binds to the iron sulfur centers of the bacteria, and the bacteria we basically suffocate them. We shut down their respiration and it kills them. So it’s all all of that. Our our immune response is dependent upon good cardiovascular system, mobilizing an immune response, vascular reactivity, and the ability of the immune cells to produce nitric oxide, but to get to the site of infection. If you have poorly vascularized tissues, pulmonary disease, for example, emphysema, COPD, your lungs aren’t well perfused, so those infections sit in there because they’re isolated from your immune system. So for it’s all about blood flow and being able to mobilize an immune response. And so, you know, that’s we see that in my kids, you know, they they did they don’t get sick, you know, when they close down the schools, when 50 percent of the people call in sick. My kids are young, healthy, running around. I’m on an airplane every week, and they get sick. But I also listen to my body. My body well, if I start to get run down, I take corrective actions. I’ll sit in a sauna, you know, for thirty minutes, heat my body up. I exercise. I do nasal breathing. I take my nitric oxide, uh, supplements to make make sure that my body is replete to its ability to make nitric oxide.

[00:42:19 –> 00:42:26] Dr. Ravi Kumar: Okay. So how do you supplement with nitric oxide? What’s the process for that, and can someone do it just with diet?

[00:42:26 –> 00:45:39] Dr. Nathan Bryan: Look, the objective is that you wanna do everything through diet and lifestyle because the human body is designed to do its job. We just gotta give the body what it needs, remove the body what it doesn’t need, the human body heals itself. We’ll regenerate it by nature. So that’s the best case scenario. So stop doing the things that disrupt it as we mentioned. Get rid of fluoride, stop using mouthwash, or wean off antacids, stop eating anything that cause an increase in blood sugar, and then start exercising, a balanced diet in moderation, twenty, thirty minutes of sunlight a day, and then nasal breathing. That should be sufficient. But the reality is the food we eat is deficient in most nutrients. The air we breathe is is polluted and toxic. So we almost, you know, I feel like we almost have to supplement with certain things, and certainly supplement with nitric oxide. And, you know, I tell people there’s only two people in the world who need to supplement with nitric oxide. It’s people who are sick and wanna get well, and it’s people who are well and don’t wanna get sick. So if if you’re following one of those two categories, I think it’s a good idea to to supplement whether you need it or not. And I’ve been taking this for probably twenty five years. When I first realized I could make nitric oxide gas, I’ve been taking it. And so that was I was a young man then, probably 27. I’m 52 now, but I take it not because I need it. I take it because I don’t wanna need it. And I do the things that maintain adequate, you know, production. Look, I never set out to make a dietary supplement. In academia, we’re designed to understand the mechanism of these to the extent that we can develop drug therapy. And so that that was the path I was on. But once I realized that we could recapitulate nitric oxide production through natural products, do these things that the body’s naturally doing, and I could just capture them, then and we could bring this to market as a consumer product with I think today it takes about ten years and $800,000,000 to get a drug to market. Mhmm. And I launched my first consumer product with, I think, $200,000 and sold hundreds of millions of dollars since a bit more than a billion dollars because we had we we understand the the science. But look, nitric oxide is a gas. And so it’s not a pill you can swallow. It’s not a beet powder you can take. It’s not a gummy or a chew you can chew on and take. It’s a gas. And so what what I’ve been able to do is create a solid dose form of this nitric oxide gas. So it’s an orally disintegrating tablet. You put it in your mouth. And over five to six minutes, this matrix falls apart. And then we’re generating 20 to 30 parts per million nitric oxide gas. And kind of my model for that was nitric oxide therapy has been used, I I think, since the late eighties and early nineties in premature babies born with pulmonary hypertension. And this is remarkable because you can take these premature babies, these blue babies, and hook them up to nitric oxide gas, to a nasal cannula, and with a matter of seconds, turn that blue baby into a nicely perfused pink baby. And so if I knew that if twenty to thirty parts per million nitric oxide gas was safe in the most vulnerable high risk population in the world, a premature baby with pulmonary hypertension, then it would be safe for the general population. So that would that was my mark. And so how do I create a product technology in an outpatient setting that you could take this, generate therapeutic amounts of nitric oxide? It’s not only safe, but moves the needle. So we had to understand when nitric oxide produced, where does it go? What does it become a hesitant signal? And then once I understood that, then I could recapitulate and and produce nitric oxide in a manner in which the body is used to seeing. Right.

[00:45:39 –> 00:45:47] Dr. Ravi Kumar: So is it basically nitrite and ascorbic acid to to create a reduction process a reductive process there, or how’s it working?

[00:45:47 –> 00:47:31] Dr. Nathan Bryan: At the end of the day, that’s it’s it’s solution chemistry. So we had to first understand how much is needed, what is the the chemistry and the flow of electrons that allow for this continuous production of nitric oxide, And then how do we create an environment where we improve the half life of nitric oxide from two milliseconds, which is its intravascular half life, out to tens of minutes or hours. So that when this lozenge is gone, you still see the blood pressure lowering effects hours later. And that you still see the exercise performance benefits hours later, long after that lozenge. And so you have to put components in there that actually allow for that endocrine function of nitric oxide, formation of these relevant nitric oxide metabolites that have vasodilatory activities and that can signal as nitric oxide does. But then the other trick to this most people don’t realize was I didn’t wanna just continue to give nitric oxide. I wanted to restore the body’s ability to make it. And part of the magic in this orally disintegrating tablet is changing the oral cavity. It’s killing the pathogens. It’s providing a substrate for these nitrate reducing bacteria to respire, so we’re improving the oral microbiome. But we also understand what leads to NOS uncoupling. And it’s oxidation of tetrahydrobotron, which is an essential cofactor for nitric oxide production. So if we can prevent b h four oxidation, then we could maintain NOS coupling, maintain NOS production of n o, and prevent this age related decline in nitric oxide production. So part of that involves a lot of physical chemistry and electrical potential needed to prevent BH four oxidation. Because in biochemistry, we’re electric. Right? What’s the electrical potential needed to extract an electron from a biomolecule? And so once you understand that electrical potential, you can prevent stealing an electron from b h four, which we call oxidation, and you can maintain the function of the NOS enzyme. So it’s a very complicated way to provide a very simple solution in that orally disintegrating tablet.

[00:47:31 –> 00:47:41] Dr. Ravi Kumar: Okay. So is it the nitric oxide that’s created in this tablet, is it transported as nitric oxide to the rest of the body, or is it transported in a different form?

[00:47:41 –> 00:48:51] Dr. Nathan Bryan: It’s in a different form, and we published this in 2007. We were the first group to to show that nitric oxide is actually a hormone. In this 2000 paper we published in the proceedings National Academy of Science, we showed that nitric oxide is transported. It binds to the cysteine residue of glutathione, which is the primary water soluble antioxidant, millimolar concentrations glutathione in the red cell in the circulation, and it’s transported as inorganic nitrite. So when we’re producing nitric oxide, again, you have to know where it goes, uh, where it goes, what it becomes, and how it signals. And we were able to map this out, and I think I published this in 2001 in another proceedings National Academy of Science paper, understanding certain conditions we can dictate and control the metabolic fate of nitric oxide and provide for these endocrine mediators and endocrine function of nitric oxide. So, you know, there’s some studies in modeling. There’s a there’s a cell free zone between the the, uh, red blood cell and the endothelial cells along the glycocalyx, where nitric oxide gas may survive for an extended period of time. But it’s really the the carrier functions of glutathione and inorganic nitrite that provide for the vasoactive, and really the cell signaling aspects of nitric oxide that survive long after the molecule is actually gone.

[00:48:51 –> 00:48:59] Dr. Ravi Kumar: Okay. So with this lozenge, you just put it in your mouth once a day, and that’s all you need for the day, or how does it work? How does the dosing work?

[00:48:59 –> 00:50:10] Dr. Nathan Bryan: Well, we looked at pharmacokinetics and pharmacodynamics. Again, when it’s produced, where does it go, what does it become, how long does it stay around? So for twenty four hour coverage, in a healthy person like me, I take it twice a day. Once in the morning, twelve hours apart, once in the evening. And then you get kind of this steady state. So about the time the pharmacokinetics start coming down, you take another dose and then you you get a more steady production. But that’s kind of what we call for prophylaxis. That’s for somebody who’s otherwise healthy. But then in people who have, you know, ED, high blood pressure, diabetes, all these other problems that tell us that it’s it’s a really their needs for nitric oxide are much different than mine. Suddenly, we have to dose accordingly, and we, you know, we kinda leave that up to the best medical judgment of the physician or the practitioner to dose accordingly. But we know that taking one lozenge every four hours is still safe and very effective. We published this in American Journal of Human Genetics in a 16 year old pediatric patient we were treating for a rare genetic disorder with severe resistant hypertension, And we found that that dose is extremely safe and effective at lowering blood pressure even in, you know, this kid who got a blood pressure of two fifteen over one ten, then no prescription medication would bring it down. And our nitric oxide lozenge completely normalizes blood pressure, one over four hours.

[00:50:10 –> 00:50:29] Dr. Ravi Kumar: So every four hours for someone who’s sick or thinks they have low nitric oxide levels until they normalize their healthy equilibrium. And then for someone like you or me who feels like they’re they’re okay twice a day, basically keeps you replete of nitric oxide. What if you wanna just do it with vegetables? Is that possible?

[00:50:29 –> 00:51:55] Dr. Nathan Bryan: It’s almost impossible. You know, because that was the question we tried to ask in 2015, because we wanted to get enough nitrate, three to four hundred milligrams of nitrate, just through eating certain patterns or certain vegetables. The question was how much broccoli or silver or spinach or beets would I need to eat to get that three to four hundred milligrams of nitrate. And what we found was it depends upon where you lived and which vegetables you were eating. And we published this, uh, in 2015. We went to New York, Chicago, Raleigh, Dallas, and Los Angeles. And we just bought vegetables off the shelf, brought them back to my lab, we analyzed them. And there’s as much as a 50 fold difference in the amount of nitrate and celery in Dallas than New York. So it’s impossible to predict if you’re gonna get enough nitrate from the food you’re eating. The other problem is even if you’re getting sufficient nitrate, 73 percent of the people that live in these municipalities with fluoride in the drinking water aren’t able to convert that nitrate to to nitride or nitric oxide. And then, you know, if you’re using mouthwash, two out of three Americans, and if you’re using fluoride toothpaste, which is about 95 percent of Americans, 97 percent of Americans. So even if you are trying to get enough if if you get a nitrate from the diet, you’ve eliminated the body’s ability to convert that into usable forms of nitric oxide because you don’t have the right oral bacteria. And then if you’re using any acid, again, you’ve eliminated that terminal step in nitric oxide production. So to answer your question, it’s nearly impossible to do it from your diet alone.

[00:51:55 –> 00:52:07] Dr. Ravi Kumar: So what about people living out in basically areas that are not touched by civilization as much? Like, you know, they’re not living in a modern society. Are they also in nitric oxide decline?

[00:52:07 –> 00:53:29] Dr. Nathan Bryan: It’s difficult to say. You know, I I live on 800 acres out in the middle of nowhere out in Central Texas, and so I grow my own vegetables. But what I do is I I do soil samples, and I see what’s missing in the soil in certain times of year, and then I replete it back. So my vegetables and I add fertilizer. So my what I eat is wouldn’t be considered organic because because you can’t get an organic label if you’re adding nitrogen to base fertilizers to the soil. But that’s the only way you can standardize it. And different you know, I’m kind of in a sandy lawn. It’s different from black land or or land with clay or things like that. So the nutrient is dependent upon the area. I think that’s why it’s so important that we do soil samples, send it off to your USDA regional office, figure out what’s missing, what’s the acidity, or what’s the pH of the soil. You may have to balance the pH, add the nutrients back, and now the the food that’s grown in that soil is gonna be replete in in nutrients. But if you just look across The US in general, this was published several years ago, that the the food grown in America from the nineteen forties to the twenty tens, in the same farmland, there’s 76% less basic nutrients in the food grown today than it was in the nineteen forties. That’s because we’ve gotten away from crop rotation, we’re we’re over farming the land, stripping the the soil of nutrients, we’re using herbicides and pesticides, killing the good, nitrifying bacteria in the soil, and it’s leading to food that’s basically nutrient depleted.

[00:53:29 –> 00:53:43] Dr. Ravi Kumar: Okay. So your premise is, listen, eat healthy, exercise, do all the things we talked about, but most people, in your opinion, should be supplementing with some type of supplement that creates nitric oxide in the body.

[00:53:43 –> 00:54:53] Dr. Nathan Bryan: I mean, that’s my recommendation. I think I’m living proof of it, and I’ve seen it time and time again. But, you know, the benefit of what I do, I wake up every morning and get emails, texts, and phone calls, and messages that people we’ve changed, and they’ve listened to a conversation like this, and they stopped using fluoride and and or or gotten off their antacids or stopped using mouthwash. It’s life changing. So just simple steps like that. You know, just last week, I had a a buddy who was working out at gym, and he was talking about he heard me on Diary of a CEO, and he was telling, you gotta listen to this guy. And he goes, that’s my good friend. He goes, tell him that I heard his Diary of a CEO podcast. I got rid of my fluoride toothpaste, stopped using mouthwash, and I’d suffered with hypertension for ten years. Because in a week after I stopped using fluoride and stopped using the the mouthwash, my blood pressure’s normal. I’m getting better workouts in the gym. And he’s not supplementing anything. He just stopped doing the things that are inhibiting the natural product. This guy was healthy, tried to live a healthy life, doing all the things that he thought was right, but he had no idea. And just stopping those things sometimes is sufficient. But everybody’s different. You know, it’s it’s very difficult as you know. There’s no one size fits all. You have to personalize everything we do.

[00:54:53 –> 00:54:57] Dr. Ravi Kumar: Yeah. I mean, the body wants to heal, and, uh, you just have to sometimes get out of its way.

[00:54:57 –> 00:55:00] Dr. Nathan Bryan: Get out of the way is right.

[00:55:00 –> 00:56:28] Dr. Ravi Kumar: Okay. So, Dr. Bryan, I before we, you know, wrap up, I wanted to talk about something else, Because after reading your book, one of the things that struck me the most was your personal story. And I think this is just an interesting thing to bring up because it’s kind of a story of triumph in the face of, like, some pretty big adversity, both when you were a kid and as an adult. And I’ll just premise it here, and and you can fill in the details. But you as a kid, you basically took care of yourself. I mean, you had a highly dysfunctional childhood. You know, you’re renting your own apartments, putting your working nights, excelling at school still. Then you went on to college and eventually ended up in academia, which is like, I don’t know how that happened with a kid with your lack of opportunity, but you you somehow built got through it. And then in the middle of your adult life, you had an unspeakable tragedy that we all fear more than anything. So and you still came out to be this guy who’s, you know, one of the world’s leading experts in nitric oxide biology, and someone who doesn’t just find the biological curiosities, but you actually apply it to human health and bring it to the world, I think it’s just completely fascinating how well you did and how good you came out with all this that happened. So can you kinda tell us how how do you find your way forward in such a successful way after all that?

[00:56:28 –> 00:58:39] Dr. Nathan Bryan: Well, I think it’s strong faith. I don’t know. I think that’s that gets me through, and I I realized early on that God had a plan for me, and I think there’s two important dates in a person’s life. It’s the day you’re born and the day you realize why you’re born. Some people have that epiphany early on, and some people unfortunately, some people never never come to that realization of why they were born. But we’re all born, we’re given a purpose. But, you know, then, you know, obviously, it’s trying. And the the world we live in, you people suffer and you go through bad things. You know, I I grew up in a loving family. It was highly dysfunctional, but I never I never felt that I wasn’t loved. And then when these bad things happen, you know, the challenges we overcome, the death of a child, you know, you just you don’t question why. You just figure out, okay, what’s what’s the lesson here? What am I trying to learn from this? And, you know, I just try to keep a positive attitude and realize it’s not what happens to us that matters, it’s how we respond to what happens to us. And bad things don’t happen to us, they happen for us. So we have to realize that, and that’s it’s very difficult to overcome that because it’s some you know, many times in my life, I feel like I’m knocked down, I get up, and I’m punched in the face again, and knocked down, knocked down, you go. Okay. What is it time to give up? And now the answer is no. It’s never it’s never time to give up. You have to now when I look back and I go this it it’s really been a remarkable journey and realize I could have never scripted this. This is not what I kinda imagined my life being on this journey that I’ve gone through. Um, but I realized, you know, looking back that, you know, God guided me in these directions certain times and put people in certain events in my life at certain times to get my attention, made me pivot, and, you you know, I’ve learned from it. And, you know, I look back and I am where I am today because of all the things that have happened to me. You know, would I change some things? I mean, if if I could go back and change things, it may have changed the course of my career and and where I am now and what I’m doing. But I think that’s you know, that I I wanted to put that vulnerability in the book because we all struggle with things, and people have challenges and, you know, bad things happen to them. But it’s it’s not the end of the world. I was hoping it would be inspirational, and no matter how bad you think you got it, it’s you know, can always be worse. And so I I don’t complain, you know, because I I know that no matter how bad my day is, it could always be worse. It could be better, but it’d be a hell of a lot worse too, and I don’t complain.

[00:58:39 –> 00:59:10] Dr. Ravi Kumar: Yeah. Well, that’s pretty remarkable. That’s a great attitude, and, obviously, you’ve used it to great success in your life despite all this adversity. So to wrap it up, Dr. Bryan, what would you leave our audience with? You know, these are my audience wants to live a better, healthier life. They want to slow or stop the processes that like really take away from their wellness as they get older. What would you tell my audience is your number one tip for living an amazing life?

[00:59:10 –> 01:01:03] Dr. Nathan Bryan: Well, nitric oxide’s foundation. Look, I don’t wanna leave the the impression that it’s a panacea, it’s a magic bullet, and end all be all, cure all. It’s not. It’s not gonna solve all your problems. But here’s what I’m very confident saying that if you’re sick, and sick and tired of being sick and tired, then look as nitric oxide and all these things we talked about as a potential contributor to your condition. But not just that, as a potential solution. And so implement these these very simple things. I mean, it takes a lot of discipline and accountability to stop eating a a poor diet, to get up in the morning, to move, to exercise, to go spend twenty, thirty minutes of out in the sunlight a day and and try to, you know, judiciously use medications. If you don’t need medications, then stop using them and give the body what it needs. And at the end of the day, hundred years well, probably several hundred years ago, the principles of medicine was applied physiology. Right? Going back to the days of the invent of of Western medicine. Today, unfortunately, medicine is applied pharmacology. And the human body will never heal or form optimally when we’re taking synthetic compounds inhibit biochemical reactions. And so I think we have to get back to the fundamentals. Remove from the body what the body doesn’t need, and replete the body what’s missing. And then focus on nitric oxide. And again, very simple. Chloric restriction intermittent fasting, low glycemic index foods, no sugar, get rid of fluoride, get rid of mouthwash, don’t take antacids, and then get up twenty thirty minutes of exercise every day, nasal breathing, deep breathing, prayer, meditation. It’s it’s it’s not just physical. It’s emotional, it’s spiritual, it’s physical. And but, you know, I think when people understand what nitric oxide is and what it does and what it can do for them, it’s life changing. And, you know, I’m very fortunate to wake up every morning and hear these life changing stories of people who just acted on this information and this conversation we’re having today.

[01:01:03 –> 01:01:09] Dr. Ravi Kumar: Well, I think that’s fantastic advice. If anyone wants to get a hold of you or see your work, uh, where can they find you?

[01:01:09 –> 01:01:47] Dr. Nathan Bryan: I would encourage people to read the book, The Secret of Nitric Oxide, Bring the Science to Life. You know, this was a two year project to retell the story of nitric oxide, take the complex science and make it into an easy digestible kind of a read. Subscribe to my YouTube channel, Dr. Nathan S. Bryan Nitric Oxide. You know, there’s a lot of misinformation out there, companies selling deeds and trying to convince you it’s nitric oxide. They have no idea about the chemistry or what it takes to make nitric oxide. What else? I’m on social media, Instagram, Dr. Nathan S. Bryan, same on LinkedIn. And then for those interested in our products, it’s N1O1.com. That’s the letter N, number one, letter O, number one dot com.

[01:01:47 –> 01:02:02] Dr. Ravi Kumar: Yeah. And I can endorse the book because I read it and I loved it, and it was very enlightening. I think a lot of what we talked about today is a premise to what that book is about, so I would highly encourage everyone to read it. Thank you so much, Dr. Bryan.

[01:02:02 –> 01:02:04] Dr. Nathan Bryan: Thank you, Ravi. Good being with you.

[01:02:04 –> 01:04:09] Dr. Ravi Kumar: Okay. So I hope you enjoyed my conversation with Dr. Nathan Bryan. I thought it was a fantastic conversation, but I know there was a lot of information. So here’s what I want you to walk away with. Nitric oxide is foundational to your health. It’s not a magic bullet, and it’s not gonna solve every problem. But if you’re feeling sick, or just not 100%, this is a place to start looking. And the beautiful part is, a lot of what moves the needle here costs you nothing. Just ditching the mouthwash, being thoughtful about fluoride exposure, weaning off antacids if you don’t truly need them, eating more leafy greens, moving your body twenty to thirty minutes a day, getting some sunlight, maybe trying an eighteen hour daily intermittent fast like Dr. Bryan does. This stuff is free. It’s available to everyone, and the science behind it is genuinely solid. If you want to go deeper, I can’t recommend Dr. Bryan’s book highly enough. It’s called The Secret of Nitric Oxide, Bringing the Science to Life. He takes this complicated biochemistry and makes it genuinely readable and understandable, even if you don’t have a science background. And if you want to try one of his nitric oxide lozenges for yourself, I’ve got a discount code in the show notes for you, and that’ll give you 10% off. And if you use it, it’ll help the show out. So if you found this episode interesting or intriguing or thought of someone when you were listening to it, do me a favor and share it with that person. Maybe it’s a parent who’s been fighting high blood pressure, or a spouse whose energy isn’t what it used to be, or a friend who’s just feeling off. Information like this genuinely changes lives when it lands in the right place, And I wanted to reach those people, so please help me do that. So until next time, stay curious, stay skeptical, and stay healthy. Cheers.