Why Your Blood Pressure, Hormones & Metabolism Won’t Fix Themselves

Companies do not have scientists. Companies do not. They got these talking heads. They read it. They follow the leader. They go, oh, well, we'll call it a microchart set product. Oh, here's a beet product. I saw it on TV. I'll buy the cheapest beet product I can. I'll put it in a gelatin.

and was settled as nitric oxide. And it would be humorous if it wasn't dangerous. Because for me, it could kill the entire field, right? Because people tell me all the time, well, I've been taking nitric oxide, Nathan, and... It didn't improve my ED. It didn't improve my blood pressure. And so nitric oxide doesn't work for me. And I go, no, no, no. That's a misinterpretation. That product didn't work for you. That company failed you.

Nitric oxide always works when given at the right time, the right dentist, and the right patient. Welcome to Metabolic Matters Podcast. where we embark on conversations with thought leaders, disruptors, change agents, and passionate souls. I'm your host, Dr. Naysha Winters. Diagnosed with terminal cancer at 19 years old,

my journey led me to become an integrative oncology specialist and champion of metabolic healing. Together we'll delve into what truly matters to our guests and how you can metabolize that wisdom to transform your own. metabolic health. Now let's meet today's guests. Welcome to Metabolic... Matters, the show where we uncover how science, systems, and stories shape human health. I'm your host, Dr. Naysha Winters. Today...

We are shining a spotlight on a molecule that is as tiny as it is mighty, nitric oxide. It's been called the miracle molecule, but most people have never even heard of it. let alone understand its impact on energy, immunity, aging, and chronic disease. Joining me today is Dr. Nathan Bryan, one of the world's leading experts in nitric oxide biology.

He's a trailblazer in molecular medicine and innovator bringing life-changing therapies from the lab to the clinic. Whether you're a biohacker, a patient, or simply curious about how to live longer better. this conversation's gonna open your eyes and maybe even your blood vessels. Wow, this is a long time coming, this conversation. In fact, I met you, I was just thinking.

I met you for the first time at a gathering in Boulder almost two years ago this month. And of course, yeah, isn't that crazy? And so, you know, I'd of course known of nitric oxide, I've known of you and your work, but I'd never gotten to be with you personally. And I feel like I have heard about you and this molecule every week since that moment we were together. And so it's really, really timely to finally get you on.

to have this conversation. So welcome, welcome, welcome Dr. Nathan Bryan. And please give a little bit of background of who the heck you are and what brought you into this space. Well, I'm just a small town country boy from Texas. I got involved in this whole field of nitric oxide, I guess going on almost 30 years now. I got a bachelor's degree in biochemistry from University of Texas and then quickly realized I need to further my education, the job market for...

bachelor's degree in biochemistry wasn't still. I went, I was a student at LSU School of Medicine. I was working on a PhD in molecular and cellular physiology and a guy who won the Nobel Prize came and gave a talk before the student body on his discovery of nitric oxide and what led to a Nobel Prize. That really started me on this path of nitric oxide. We know it was an extremely important molecule, but...

You know, we'd learned a lot. We knew it was a signaling molecule in the cardiovascular system, but we didn't really understand all the pathways of production, what led to a loss of the natural production. And certainly 30 years ago, there weren't any safe and effective product technology.

You know, I got my PhD and then I think less than two years, I published two or three first author papers. We discovered a lot of things and then went to Boston Medical Center and did a fellowship in Boston University School of Medicine in the cardiovascular department. At my first independent research career, I was recruited by Fred Murad, one of the other guys who won the Nobel Prize. He was our department chair for a couple of years, and that's where we started our drug discovery program.

Holy cow. So I love this. You were literally just a student who heard an amazing speaker, that little, little pilot light in front of you, and it became your entire vocation. So what was that moment?

not necessarily in your career, because that seems pretty obvious, but what was the moment in your lab that you realized this was really integral to human health, that this was really a game-changing? signaling molecule, what was that aha for you? What was maybe your first discovery that just hooked you literally for life? Well, once we had developed ways that we could detect nitric oxide gas.

Because nitric oxide, if it's to go back, it's a gas. And once it's produced, it's gone in less than a second. So to develop rational therapies, you've got to figure out how to recapitulate the natural nitric oxide production and signal. So I developed analytical methods where we could detect nitric oxide gas coming off of, you know, biopsies, tissues, even plasma in the blood and red blood cells. And we could change oxygenation status and detect nitric oxide coming off.

So really, I had several aha moments in these so-called eureka moments in science. Number one was when I started screening natural product libraries and I found natural products where I could... put together conditions, understanding the biochemistry, and I could generate nitric oxide. I could liberate nitric oxide. I create nitric oxide delivery mechanisms and systems where I could turn on nitric oxide and predict.

nitric oxide release, nitric oxide pharmacokinetics dynamics. And so that was my first thought to go, this is extremely important because now I can titrate in any level of nitric oxide I want based on individual patients. So that was extremely eye-opening. And I'll never forget, we documented it in our lab report. I only had one lab technician at the time. And so we were excited. It was like, you know, when you're in an academic setting...

When you're trained to go into academia, they go, look, if you make any discoveries, do not tell anybody. You submit an eviction disclosure and you submit it to the Office of Technology Management. We'll do due diligence on it. We'll file patents. But if you ever disclose it.

It got patentable. So just get gratitude in knowing that you are the only person on the face of the world, face of the earth that knows what you know at that moment. Wow. So that's what we did. I just started filing adventure disclosures. And so, you know. Eventually, those patents were issued and, you know, we developed product technology and started a number of companies. And so now we're moving now into drug therapy based on those same discoveries. Why do you think this...

molecule is still so overlooked in mainstream medicine despite it being so essential to life. Well, unfortunately, and you know this, allopathic physicians only think it's important to treat what you can measure. and it's a lamp, right? So unfortunately, you can't go and draw blood and go, oh, well, your nitric oxide is low. I'm going to give you this drug to, or this symptom is a consequence of some.

reaction in the body. So I'm going to give you a synthetic compound that inhibits that reaction. But for nactic oxide, it's always a deficiency, right? It's never about an overproduction. It's always a deficiency. So that's number one. Number two, we know it takes, on average, about 17 years for new discoveries to become standard of care and really, you know, full awareness. But, you know, nitric oxide network, what, 26 years after the Nobel Prize is awarded, so we're past that.

The other thing is there's no nitric oxide-based drug therapies that normal allopathic physicians can prescribe, and that's their modus operandi, right? Make a diagnosis, prescribe a drug. And again, if you can't measure it, it's not important to them.

So I think there's a lot of things that contribute to that. Part of the importance of this conversation is to try to change that narrative and understand that it's really not any different than what many physicians, especially the integrative and functional doctors.

is figure out the deficiencies, figure out the toxins, remove exposure to toxins, replete missing deficiencies. We call this restorative physiology. It's not pharmacology because pharmacology doesn't work. We're never deficient in a drug compound.

So give examples to folks. I mean, right before we started this recording, I was telling you I had an interaction today with a standard of care cardiologist who completely poo-pooed this concept despite... this patient that we are consulting on together has every symptom of a nitric oxide deficiency. So Doc, can you walk us through what that might, how it might manifest clinically in somebody?

how somebody might feel with a nitric oxide deficiency, maybe what symptomology or patterns in their physiology might be pointing at, hey, we got a problem here with our nitric oxide. Well, it's documented now over 30 years of clinical observation, and there's a hierarchy. And again, it's not for everybody, but typically, if we look at the average demographic population, the first sign and symptom of nitric oxide deficiency is erectile dysfunction.

sexual dysfunction. Because if you think about the hemodynamics of erections in both men and women, we have to increase blood flow. We get engorgement. That's what an erection is. So to get an increase in blood flow, we got to dilate the blood vessels of the sex organs.

And that's what nitric oxide does. If your endothelial cells and your blood vessels can't produce nitric oxide, we don't get vasodilation and we don't get incoherent. And that's both the penile clitoral erection. So that's number one. And we call that the canary in the coal mine because it's the first.

sign and symptom. But it's a bigger reflection of a systemic disease because if you've got endothelial dysfunction in the vascular bed that feeds the sex organs, the same endothelial dysfunction occurs in the coronaries, the cerebral vessels, it's systemic.

So that's number one. That's your body telling you, hey, I can't make nitric oxide on demand. Number two, your blood pressure starts to go up. And if you think about this from the physics of hemodynamics, it makes perfect sense because we all have a finite amount of blood volume in our...

circulating at any given time. If we make nitric oxide, we're dilating the blood vessels or improving the compliance of the blood vessels with each heartbeat. If you can't make nitric oxide, now your blood vessels are chronically constricted. And you've got that same volume of blood going through smaller pipes.

And simple laws of physics tell us that pressure goes up. Two out of three Americans have an unsafe elevation of blood pressure. Number three, you develop metabolic disease. You know, my group was the first to publish in 2011 that nitric oxide is part of insulin signaling. So when insulin binds to the insulin receptors, it starts this intracellular signaling that activates AMP kinase, activates PI3-AKT kinase, but both of those converge on nitric oxide synthase enzyme.

And then if the cell can't make nitric oxide, then we discovered that it's the nitric oxide that activates GLUT4, that tells GLUT4 transporter to go to the membrane and bring glucose into the cell and utilize it as an energy source. But without nitric oxide, we call that insulin resistance.

So insulin resistance is a symptom of nitric oxide deficiency. Number four, you start to develop exercise intolerance. If you can't dilate the coronary arteries, get blood flow to working skeletal muscles, you can't exercise. And then fifthly, Brain fog, mild cognitive impairment, dementia, Alzheimer's. So each stage is our body telling us there's a progressive loss of nitric oxide and you need to pay attention and take steps to restore the natural production.

I believe you just described the vast majority of people living on the planet today. And look, that's the reason that no one's getting better without addressing rude cause. Because cholesterol-lowering medication doesn't address it. In fact, it makes it worse. You know, things like the cardiologist should know things like nitroblastin, isosorbide. They use those for ischemic heart disease, angina, which are nitric oxide-producing.

drugs that have to be metabolized. The problem is people develop tolerance to them. And then now they give inhaled nitric oxide to, you know, cardiopulmonary bypass patients, premature babies with pulmonary hypertension for the past 30 years. So it's used clinically, but in an inpatient setting. Right. Right. Wow. It's amazing. So this conversation was like exactly today. A gentleman, 72 years old, who started on a lipid-lowering agent 20 years ago.

And now he's on three. And I just saw his lipid profile. His overall cholesterol level is 75. Okay. Exactly. And his A1C is 5.9. And so he's in my world, that's already diabetic. Standard of care calls that almost diabetic, but that's like being almost pregnant. He's on two medications for his erectile dysfunction. He's now on three blood pressure medications and it's still in the high 130s over 90s zone. So what you're speaking to is they just kept keep layer caking on the same medications.

and making little, if any, impact. But now he's dealing with a cancerous process. And so he is just someone who is like the classic client I have a consultant on. who's just been on this very slow highway to further and further metabolic mayhem, to further and further nitric oxide degradation. to further and further mismanagement of this collection of symptoms and ailments. So how do you, like I tried to have the conversation last night with his GP. Thought that would be my starting point.

did not fall well because he's been stented now. He's got a stent in his leg. He's showing a 60% occlusion of atherosclerotic occlusion in his vasculature. And of course, they're all terrified to even consider. lowering or pulling any of these drugs and actually taking. They were actually concerned it was going to make him hypoglycemic with a therapeutic diet we were putting him on. They were questioning our use of things like magnesium.

You know, they were questioning our use of things like even homocysteine, you know, methyl donors in helping this man methylate because his homocysteine is in the high teens. And so this is like, how do you... suggest a clinician like myself meets the general practitioner or cardiologist with a conversation that is actually rational.

and not inflammatory and not antagonistic because I kind of just want to slap them. You have to present them with science. I mean, mechanistically, I can tell you exactly what's wrong with this patient. Yeah, because it goes from cell signaling and everything is about how the cell responds to an external environment. And here's the deal. If your cholesterol gets below 200, you can make vitamin D, you can make estrogen, you can make testosterone.

And the fluidity of the cell membrane becomes compromised because there's cholesterol. The cell membrane is a phospholipid bilayer. And in that bilayer, there's cholesterol. There's certain lipids that have to respond. and allow this extracellular receptor, and there's what's called seven transmembrane receptors, that then transduce that extracellular signal inside the cell. Without cholesterol, you lose that membrane solidity. Furthermore,

That lipid bilayer acts as an insulator because the inside of the cell with respect to the outside of the cell is negative, about minus 25 millivolts. If you eliminate the cholesterol, you lose that capacitance effects of the cell. The cell loses its cell potential. And then what is that? Plus 30 millivolts is where cancer starts to pop. So it explained, and again, the endothelial cell has to have lipid rafts, has to have cholesterol.

to get that signal to maintain barrier function, to activate nitric oxide production. With a cholesterol of 70, has endothelial dysfunction. He's got an upregulation of adhesion molecules, monocytes, neutrophils, platelet stick, lipid starts to deposit.

Statins are mitochondrial toxicants, so no wonder he's developing cancers. But I think more importantly, he's losing the electrical potential across the cell, and that's the Warburg effect. So every clinical presentation about this patient can be explained by one medication. Yeah. And it's in a long and lingering. Yeah. Exactly. Exactly. And it's funny, you know, they are also giving him testosterone.

because he can't make his own, because there's no lipids to do that. So this is the crazy train, and yet I am getting called the quack by questioning the narrative, right? Like, I'm sure you're accustomed to that, but... You just explained that literally in 30 seconds. And it was a rational, science-based, you know, evidence, both informed and evidence-based discussion. And that's what I try to present to his team. And there is such cognitive dissonance around this.

They're so afraid of shifting this pattern, afraid of what their peers will say versus what is right for the patient. And so I just think this is such a powerful conversation.

You just went through, because this patient was the perfect example of what a classic nitric oxide symptomology deficiency looks like. So what lifestyle, I mean, you kind of alluded to this, but perhaps what types of lifestyle behaviors will add to nitric oxide improvement or degradation. But you've got to release the brakes on his body trying to respond and heal itself, right? So there's a reason our body makes cholesterol.

Because we need it. And when people are prescribing cholesterol-oriented medication, it implies that they're smarter than our creator. They know better than the creator of our body. And that's blasphemy. So what we got to do, you got to start.

and taking away medications. And that's a very difficult conversation to have with allopathic physicians because, number one, if they practice outside the standard of care, they're subject to lawsuits and losing their medical license. So it's cover your ass medicine.

And it's risk management. But you've got to do what's best for the patient. It's obvious that what they've been doing is not working. I mean, the other analogy I'd use, if my car keeps breaking down, I keep taking with the mechanic, he doesn't fix it.

Nobody in their right mind would keep going back. You'd fire that mechanic. If you're somebody who's sick and sick and tired of being sick and your doctor's not making you better, fire that doctor. He is not doing his job. But you have to start getting people. It's elimination.

It's like elimination diet. If something's offending, if you get GI distress or eczema or autoimmunity, eliminate things. Start eliminating drugs. I mean, statins, there's no reason in the world anybody should take a cholesterol-lowering medication. There's no benefit. And what's the risk? Well, low vitamin D, immunocompromised, low testosterone, cancer, diabetes. I mean, there's some lawsuits that give. So if it provides no benefit and it's all risk, that's an easy quotient.

You throw it in the trash and you fire that doctor who tells you to take it. You'll find somebody who knows. MitoVita isn't another supplement line. It's cellular medicine in a bottle. Created with Dr. Ahmed El-Saka and myself, each formula is clean, practitioner designed, and terrain approved to support pathways like blood sugar balance, sleep, and mitochondrial function. Explore the line at mitovita.com. Let's get back to your mitochondria.

And luckily, people like David Diamond and others have done the research and really shown us the absolute data results of what these... medications in real life are actually doing, which is very, very little. But what we know that they're doing on the harm side of things is actually quite

quantifiable as you just described. And so it's interesting because that's exactly what created the risk was me starting to say, hey, you're on three different drugs for the same condition and it's still not helping. Let's get you off at least two of the three.

And that's when everyone started pushing back. Like it was fine when they thought, you know, pat me on the head of this woman is going to help a little bit with nutrition. But when I started messing up with their turf is when it got really sticky. Right. I'm not coming at it from a dogma or belief system because.

Maybe there is a time and place, but for this gentleman, you literally just spoke to exactly the why of his, why he's in the position he's in currently. All you got to do is just cite the clinical trials. What's in the published literature? There's no benefit in primary prevention.

There's no benefit in secondary or tertiary prevention. So why put people on cholesterol? Then cause heart disease, why treat it? It makes no sense. Absolutely. Well, and it's one thing I also heard you say, which I really appreciate. You also take...

issue with various high-risk communities. And so specifically, you've talked about nitric oxide's role in underserved populations, particularly in the African-American communities where cardiovascular risk... diabetes, prostate cancer, all the things are just off the chart. So do you see nitric oxide therapy as a potential equalizer in just health equity? No, for sure.

collaterally involved in what was called the AHF trial back in the early 2000s, and that was a fixed-dose combination of ISDM and hydralisy. And so if you look at the original clinical trial in a general cohort population, the drug failed to show efficacy. And this was a heart failure medication. But when they did kind of a deep dive and they found that there was a cohort in that study that responded extremely well. And when they unblinded, it was the African-Americans.

So then they designed a study. It's called the AHIF, African-Americans in Heart Failure Trial. And when they gave that fixed dose combinations and back up a little bit, African-Americans typically fail to respond to standard therapy in heart failure. But this fixed-up combination of isotropic dinitrate and hydralazine, the African-American population responded. Decreased morbidity, decreased mortality, and the steering committee stopped the trial halfway through.

because it was unethical not to give the placebo patients the active drug. And that drug was approved. So there's a known clinical benefit of enhanced nitric oxide, and more importantly... genetically and kind of epidemiologically and even lifestyle contributions show that African Americans are deficient in nitric oxide. First, overexpression of G6PD.

of expression of NADPH oxidase, their diet, their lifestyle, it all leads to a loss of nitric oxide production. And for me, that explains the health disparities in, you know, diabetes, certain types of cancers you mentioned, hypertension, heart failure. I mean, so if we can address that and start to bring awareness around things that are doing, focusing on supporting the microbiome, you know, exercise, elimination of things like mouthwash, right in your toothpaste.

and then allow the body to normally naturally produce nitric oxide, we can overcome health disparities. This is so, so big. I mean, my wheels are turning so much of just thinking of the implications of this. And that's where... When I met you, of course I learned. I mean, actually, one of the things I'd like you to hit on is one of the things I learned in my training way back in the day, maybe 20 or so years ago, was the difference or the concept between

endothelial nitric oxide and inflammatory nitric oxide. Is there still relevance to that discussion? And is that something you could speak to? Because I almost feel like it's almost like a modulatory that of course... it's not like you can have too much, but you can have, well, I'll let you go there because you're the expert here. So I want to learn what we now say around that clarification between theoretically two forms of nitric oxide.

Well, there's what we call the constitutive isoform, which means they're always expressed, they're always active, and that's the nitric oxide synthase that's found in the endothelial cells. Okay. And then our neurons in our brain express their own neuronal nitric oxide synthase. And it's part of long-term memory potentiation. It's part of retrograde memory and all this neurotransmission. But there's also an isoform that's called inducible or INA.

And this is necessary, right? So if we have a cut, if we have an injury, if we have an infection, then that INOS, four hours after we see exposure to a pathogen, or we have a wound, for example. That enzyme is nuclear, it's expressed legally, and then it's active, but it takes about four hours. So then it goes to the site of infection.

and it generates a lot of nitric oxide. It's not regulated by calcium. The answers are calcium-dependent. This is a calcium-independent source of nitric oxide. But it's designed to generate a lot of nitric oxide over a very short period of time. So nitric oxide binds to the iron sulfur centers of bacteria. It prevents virus from replicating. So that local acute overexposure of nitric oxide shuts down virus replication, bacterial respiration. But it also enhances blood flow to that.

And that's why wounds or infections get, you know, warm and red. And it's the, you know, the pain, that local inflammatory response, which is necessary. And then it shuts off. The cells no longer make it.

The monocytes, neutrophils, macrophages shut down the nuclear expression and it goes away. The problem is when people are chronically infected, right? And poor vascularity, poor circulation leads to... susceptibility to infection. Because we can't mobilize an immune response, right? It's like the fire trucks trying to get to a fire on the 405 in LA. There's a traffic jam. You can't get the fire trucks to the fire. And so...

you have uncontrolled inflammation. And then in 2004, we published a very important paper on inflammatory bowel disease showing that that chronic overexposure of INOS completely shuts down constitutive nitric oxide production. Wow. And this is the paradox. Chronically inflamed patients, if you look in the blood and the biopsies and tissues, you'll see in the literature, overexpression of nitric oxide is causal to that disease.

But they always develop vascular phenotypes to these autoimmunities, these chronically inflamed. That's because it's like, and people say, well, nitric oxide is toxic and pathogenic and contributes to the biology of that disease. Now, B, well, that was like blaming the fires on the fire trucks. Because the fire trucks always show up, at least we hope to, nitric oxide always shows up to a site of infection, to a site of inflammation. And so it's there because it has to be there. It's not there.

It's the police trying to, you know, clean up the environment and clean up the neighborhood. And shutting that down, which we've done in many clinical trials in septic patients, inhibiting nitric oxide production, both constitutive and INOS. Patients get worse. Septic patients died at a higher rate. And so that local immune response to overproduced nitric oxide is protective in nature. It's not contributing to the disease. And inhibiting it makes things much worse.

So we were misunderstanding what we were seeing at that time. Now look, it's a misinterpretation of data. And unless you're a basic scientist, they can read the medical literature and the data, the data, right? The problem that's in the interpretation, and most people only read the abstract. They see the introduction, the methods, and then the conclusion or the interpretation.

So I would guess, at least in the nitric oxide literature, I would say greater than 50% of the published papers, it's a misinterpretation of their own data. And I've reviewed hundreds, probably thousands. publications that journals send to me to review. And it's like, hey, the data are great, but they've completely misinterpreted what they even observed.

Wow, this just gives me such a flashback of two other places I can think of where we're misinterpreting the data, which one is in the cholesterol conversation, which started us off here. Again, a similar idea, like we're blaming the laying down of cholesterol or even calcifications are a response to inflammation, not the cause of the process. I think that's really fascinating. And then the same.

discussion comes up a lot in the B12 space. So serum B12 looking elevated in cancer patients, we're saying, oh, B12 causes cancer. We're like, wait a second. So I love that you're showing yet another interesting paradox in... you know, medicine and chemistry and physiology that says, perhaps it's more like you said, that it's the fireman, not the fire that we're looking at. You know, that same misinterpretation occurs in Alzheimer's, right?

People are developing, companies are developing drugs against the tau tangles and the amyloid plaque. That's the consequence of the disease. It's not causing the disease. So why in the hell would anybody target drug therapy, especially monoclonal antibodies, against the consequence of the disease?

And that's why these drugs have failed. They will fail because they cannot work because they're not addressing the root cause. Again, they show up because of the disease. They don't cause the disease. So targeting them for drug therapy will not work. That's why they've all failed. Wow, and that is actually the way we do oncology. We look for a particular target, and then we look for a specific single agent to treat that target.

And then we wonder why our outcomes aren't that extraordinary, because to your point, it may be that it is a reflection of an expression of why the disease, but not the cause of the disease. It's a side effect of the disease process. You have the physiologic.

state or the metabolic fingerprint, as you alluded to. So stinking fascinating. So you have developed some testing. and some product around this. Can you talk about where, because I know it's also something, you know, that is constantly evolving. I mean, in the two years that I've known you, you've come up with newer formulations and newer testing. So, you know, I'm imagining this is constantly pivoting and fascinating, you know, place to be learning from and to be.

sharing from. So can you talk to us a little bit about what it is that you have developed and maybe a comparison contrast to what's on the market today? Because there's a lot of crap out there too. The main source of my daily frustration. Look, because, and I'll get to that, but look, what we've discovered from my 25 years in research and a number of similar discoveries and understanding the enzymology and the biochemistry of nitric oxide production, how the human body makes it.

and then what leads to a natural loss of its production. But unless you understand those two very important concepts, there's no company out there, there's nobody who should even consider even thinking about developing a nitric oxide product. So, we don't have testing. You know, years ago, I developed a salivary test strip, but quickly realized that it really wasn't a good reflection of systemic nitric oxide production. Because what we're measuring is salivary nitrite, which is...

You know, it can be the cellulary nitrate can be increased in an acute immune infection or immune response to an oral infection. And we know a lot of people have oral infections, whether they're symptomatic or asymptomatic. So I don't use the test strip anymore.

I tell people, there's no need to test. Because for me, there's only two people in the world who need nitric oxide. There's the people who are sick and want to get well. There's the people who are well and don't want to get sick. So why do you need to test? Now it's just a matter of how much nitric oxide do I need as a healthy 51-year-old to maintain optimal levels, to be preactive and be proactive and prophylactic versus...

your 72-year-old metabolic patient with early-stage cancer. That is much different. Metabolic needs are much different. And that's why we rely on the best medical judgment of clinicians like you to figure that out. But what we do is we make a solid dose form of nitric oxide gas. So if your body can't make it, we give you nitric oxide. And it's hormone replacement therapy, right? It's a replacement, not a restoration because you can't really do it.

That's right. And so we give nitric oxide. And to dial in the right amount, you have to know, okay, how much nitric oxide does a healthy person make over a certain period of time? And to do that, we have to do radiolabeled isotope studies of how much.

Radio-labeled L-arginine is converted to L-citrulline, and you get nitric oxide as a byproduct. And then based on normal dietary patterns, how much nitrate is consumed, how much is reduced to nitride, and how much is generated in nitric oxide in the acid environment.

assuming you have the right bacterium and assuming you can make stomach acid. And then we have a number. And then we look across different populations and demographics and go, okay, it looks like they're probably generating in a, again, there's a lot of one size fits all.

but here's how much we need to give back, right? And the example is vitamin D. If you've got a vitamin D of 30, what do we do? We treat you to Haiti or Optum. That's simple because it's a number. Niko Gox said there's not a number.

And so what we don't do is we don't give you arginine or citrulline because your body makes enough of those to bind to nitric oxide synthase enzyme to make nitric oxide. So there's no need to supplement arginine or citrulline. In fact, if you do, you can actually make the patient worse. Post-infarct patients, it killed more people than placebo. Peripheral disease, elarginine, makes people worse.

And then the other products you see on the market are the beet products. And it's, you know, one of the biggest, beets are not nitric oxide. Any company selling beets are selling you dead beets. Because to understand how the beets work, you have to have a certain amount of nitrate. Number two, most Beats products don't have any detectable nitrate or nitrate in them. Number two, even if they did, you have to have the right oral bacterium. But two out of three Americans use mouthwash.

Nine out of 10 Americans are using, I think 99 out of 100 Americans are using toothpaste with fluoride in it, filling the entire microbiome in our mouth, on our skin, in our gut. And then the other big culprit is acid blockers or proton pumping hitters. They completely shut down nitric oxide production. And that gentleman we just talked about, he's on two of those, by the way.

Well, yeah, there's his mechanism of vascular disease and atherosclerotic disease. Yeah, it just, it's so maddening. And I'm like screaming into a tunnel, you know, when no one's listening. So you're giving me such great resources and tools to speak to.

But what you just spoke about, I mean, first of all, I review people's terrains day in, day out. I train clinicians all over the world to look at people's terrains. And specifically what I mean is we're looking at these metrics. We're measuring, you know, salary rate. levels for IgA, various things there. We're measuring microbiomes, both in the mouth and in the digestive tract and in the genital urinary tract. We're measuring... Just their basic labs can show us their nutrient status.

And then to what you described about the pharmaceuticals, I mean, alone, just so many people on an acid blocker, you know, it's just insane to me. This is now negligence. And this is a conversation you need to have.

with the cardiologist as a prescribing physician because now there's studies showing that people who have been on proton clump inhibitors, the omeprazole, the pentoprazole, the prescriptions, or the over-the-counter, prolasec, previncenexium. If patients have been on these drugs for at least three years,

they have a 40% higher incident of heart attack, stroke, and Alzheimer's. We're not talking about increased risk. We're talking about actual events. These drugs are more dangerous than the selective COX-2 inhibitors from 25 years ago.

The Viarch Celebrex were taken off the market because they were causing heart attack and stroke. Now there's a black box morium. The PPIs are even more dangerous. They're more deadly. This is negligent. It's medical malpractice to keep a patient on a proton cup inhibitor. for longer than their FDA-approved use, but just three to five days. Cool. This is the part, this is why I love having colleagues like you to help fill in the gaps of my blind spots as far as...

Because I focus so much in the oncology space. These pieces are, and interestingly enough, we use those drugs a lot in the oncology space. Every single patient getting chemotherapy is put on that class of drugs to help them with their therapy. admitted to any hospital in the U.S., regardless if it's trauma, it's insulin illness, or heart attack, stroke, you're given Omeprazole.

You don't even have a choice. They give you, it's part of your daily medication, and they wonder why people don't get better in the hospital. If I had the time and the bandwidth, I would go to law school, and I would go after physicians and pharmaceutical companies who continue to sell proton-clip inhibitors.

because it's negligible practice. Love your heart so much. Love your wisdom, love your heart, and love your willingness to speak the truth on this because it is a David Goliath story on, you know, on this one here. Wow. Wow. That story.

Well, I really appreciate that you brought up this beet thing because we are seeing a ton of products on the market, a ton that claim that the beet and then all the people out there telling you to just juice your beets and take your betaine on all the different things to raise nitric oxide. I love that you're myth-busting this right in the nubs there. Are there any dietary practices that at least support a healthier endogenous nitric oxide process that you...

you know, could share with our listeners. Yeah, it's mainly elimination of sugar and high carb. Anything that leads to an increase in blood sugar. And look, I'll explain this because it makes perfect sense. So glucose is glue, right? It's sticky. And anybody who's ever spilled the soda or iced sweet tea on a tabletop and come back the next day, it's sticky. When it's sticky inside our body, it sticks to hemoglobin. We measure this as hemoglobin A1c.

So it's a long-term measure of how elevated your blood sugar is. And so hemoglobin, it's a protein, but to deliver oxygen, it's got to have to go a conformational change, right? When it goes from the arteries to the veins to the capillaries, it has to go from an R to T transition. at exactly the P50, 50% of the oxygenation, hemoglobin, changes conformation, offloads oxygen, picks up carbon dioxide. But if there's glucose stuck to it, it glues this protein stuck in a single conformation.

So you can't deliver oxygen. You can't pick up CO2. Diabetics, what are they? They're hypoxic. They're ischemic. They have metabolic acidosis. It also sticks to enzymes like nitric oxide synthase. And enzymes have to transfer electrons. They have to change their conformational state. If there's too much glucose, it can make nitric oxide. So it's elimination of sugar, methane that leads to an increase in blood sugar.

Seed oils, again, are really bad. Again, they change the membrane fluidity and affect intracellular signaling. And then, you know, green leafy vegetables, you know, on average, typically have a high concentration of nitrate. But, you know, again, this depends upon which vegetable it is, where it's grown.

The vegetables grown in Dallas and Chicago were much different than New York or Raleigh or Los Angeles. So there's regional differences. But I think what works, I think when we look at the functional vascular or endothelial function. It's a high protein, good quality fat, low carb diet, moderate physical exercise. For me, an 18-hour daily fast.

15-hour fast works. I mean, the data on intermittent fasting and court restriction are pretty indisputable. And then exercise. We have to exercise. We have to move. We have to detox. So that works for me. I'm 51, but I've got the vast rates of a 32-year-old that every day I start with an infrared sauna. If I'm traveling, I stay in a hotel with it. During that 30 minutes, I'm praying.

Resting gratitude on developing a middle game plan for my day. And then, you know, I exercise, you know, at least 45 minutes every morning. I do a cold plunge. Then I don't eat my first meal till noon, but I eat my last meal at six.

I feel better today at 51 than I did when I was in my early 30s. You are such an inspiration. It's so funny. So I'm here in an Airbnb. Let me just show you besides the cat who's hanging out. There's my portable inflatable cold one. And my portable part of red sauna, so my morning, starts very much like yours. And then on that back, you see that little red lamp? That's the red light in my room that I forgot to turn off this morning, so you're going to see that.

So those are my little hacks when I'm traveling as extensively as I am. And I know you are on the road as much, if not more than I am. We have to bring those things in because each time... Can we even talk about that for a moment? Each time you get into an airplane, what that's doing to your nitric oxide levels. What can you say about that?

one night in a really poor air quality hotel or terrible light exposure conference event, the damage that's doing to your mitochondria and likely to your nitric oxide signaling molecules. Yeah, well, I've become a hotel snob because I spend more than 200 nights a year in hotels. But, you know, I carry an ozone generator with me. I carry a diffuser with essential oils to give me a certain frequency. I wear the blue blocker glasses at night.

And so I take care. And then when I'm getting on a plane, as soon as I walk on the plane before they pressurize the cabin, I take my nitric oxide lozenge. And then I'm constantly kind of contracting my ankles and moving my knees and walking when I can. You know, then you wear EMF protection. You know, I've got some, you know, the Leela quantum technology and just try to protect ourselves the best we can. But it's very difficult. We live in a toxic world. It's hard work staying healthy.

It is. It is. If you can't stay in your own little bubble, like your beautiful ranch out there in Texas, you know, like you just told me, I think you're taking off again to New York here and then another, you know, you're just all over the map.

you've got to do the best you can. I mean, this is the place. Remember, it's probably been within your career. I know it's been within mine. When I first got out of medical school, I can remember back in the 90s saying to people, moderation. We don't get to say that anymore. We've lost that luxury of moderation because we're being bombarded with far more than humanity has ever faced before. So I think that's very, very interesting. You know, one other thing you mentioned.

And this product shows up everywhere. So you mentioned the arginine concern. So very, very big because most of the nitric oxide and most of the erectile dysfunction, at least in the natural... you know, integrative medicine, functional medicine, naturopathic medicine world contain arginine. And I, like you, I had noticed, like, I mean, I had some really amazing, I mean, I had a lot of patients who had some really good responses to that.

But I also saw a lot of really bad responses to that. And it really pushed me away from wanting to use those products that contain the arginine. And then years later, people like Dr. Nell Syed out of Imperial College in London. started actually doing research about arginine and its impact in the cancer process. So then I got double scared off from arginine products and wanting to bring that on board, despite knowing that nitric oxide is important.

Can you say a little more about why we want to stay away from arginine nitric oxide inducers? Yeah, well, number one, we're never deficient in arginine. So arginine is a semi-essential amino acid. So, meaning we get it from the breakdown of protein, both plant and animal protein, depending upon your diet. And every cell in the body has the partial urea cycle present.

The partial urea cycle is what's called argillose succinate synthase, argillose succinate lice, and it shuttles arginate, the nitric oxide synthase. Citrulline is a byproduct. So we make more than what we actually need. And to understand the enzymology and the biochemistry.

In biochemistry, there's what's called the Michaelis constant. It's the binding constant, the concentration of a molecule that can theoretically saturate 50% of the binding sites. For arginine, that concentration is 5 micromolar. But intracellularly, even in plasma, it's 100 to 200 micromolar. What that means is we have 20 to 40 times excess arginine in what's needed to theoretically saturate 50% of the binding sites. So we're never deficient in arginine.

So it makes no sense to supplement arginate. The other problem is when the NOS enzyme is uncoupled and you feed arginate, it forces that pathway. And now we've got a disruption in the flow of electrons. and we reduce molecular oxygen to superoxide. So now we're generating superoxide radical and exacerbating oxidative stress and causing more harm. And I think that's the conclusions of the post-infarct patients.

the PAD patients, but the common denominator in those is endothelial dysfunction. The enzyme isn't functional. So the same thing with ED patients. Their enzyme isn't making nitric oxide because it can't convert arginine to nitric oxide.

You can push to the cow's cup home. It means like putting gas in a car with a blown-up engine. It's not going to get you where you need to go. We have to focus on restoring the function of the enzyme, which is what my products do. And now you're able to utilize endogenous arginine. And the other thing, you push it too much, you direct our gene away from nitric oxide production through ornithine and exposure because you can get into nitrogen imbalance. That's the body's response.

to hyperammonemia or to prevent hyperammonemia. Companies who don't, companies do not understand. Companies do not have scientists. Companies do not, they got these talking heads. They read it, they follow.

the leader and they go, oh, well, Marzine, we'll call it a nitric oxide product. Oh, here's a beet product. I saw it on TV. I'll buy the cheapest beet product I can. I'll put it in a gelatin and we'll sell it as nitric oxide. And it would be humorous if it wasn't dangerous. Because for me, it could be.

kill the entire field, right? Because people tell me all the time, well, I've been taking nitric oxide, Nathan, and it didn't improve my ED. It didn't improve my blood pressure. And so nitric oxide doesn't work for me. And I go, no, no, no. That's a misinterpretation.

that product didn't work for you. That company failed you. Nitric oxide always works when given at the right time, the right dose in the right patient. And that's what we do that no other company does. So beets are not nitric oxide. I mean, these companies spending millions and millions of dollars on TV advertising is killing an entire industry. And that's why I think it's so important.

that we move forward with these drug trials and get real nitric oxide product technology, drug therapy on the market, not only so allopathic physicians can write prescriptions for them, but so consumers can have faith that the products that they're taking deliver nitric oxide. And then they get a benefit from it. Hi, everybody. I am Dr. Nisha Winters. And if you've been listening to me for a while,

You know my North Star is this. Stop chasing symptoms and start rebuilding health from the ground up. That's why we created Metabolic Regen. an education platform rooted in the Terrain 10, the framework that I've learned to apply to myself and to tens of thousands of patients over two decades of clinical practice and cancer care.

This isn't about cramming more protocols into your brain. It's about learning to think differently, to see patterns, to read the body's terrain, and to meet patients, or even yourself, where you are. Whether you're a clinician just starting your integrated journey or a seasoned practitioner ready to bring metabolic and mitochondrial medicine to your toolkit, Metabolic Regen is here to support you.

Inside, you will find immersive courses, real case studies, mentorship, and a global network of like-minded colleagues, all of us pulling together to change the story of medicine. If you're ready to be part of that shift, join us at metabolicregen.com. Let's rebuild medicine from the mitochondria out.

Wow. Wow. So well said. And I really appreciate you rounding that out because you're right. Things are not created equal. And this is really huge. Holy cow. So you have definitely, like you said, you've seen a lot of products come and go. I've tested everyone. Every night I got to work, I tested. Wow. So walk me through, what are you most excited about and what is on the horizon in research? What is the future?

of this molecule? And, you know, like, what's the role that you're playing in that future? Well, I'm absolutely convinced that nitric oxide-based therapies will be the future of medicine because it's... You know, it's not a panacea. Let me make that clear. It's not a silver bullet or a magic pill. But what it is, it's foundational. Because when we look at nitric oxide and what it does, it dilates blood vessels. It improves oxygenation.

It recouples the electron transport chain of mitochondria. It mobilizes stem cells so we can repair and replace dysfunctional tissues. It activates an enzyme called telomerase and prevents our telomeres from getting short. So everything we know about human optimization... biohacking. Health, wealth, longevity is dependent upon nitric oxide. So I'm excited because we're at the fore of getting drugs approved through the FDA. We've got a drug for ischemic heart disease.

We're about to begin a phase three clinical trial probably first quarter of next year. We've got a drug we're developing for Alzheimer's because nitric oxide affects the vascular metabolic aspects of Alzheimer's as we discussed. And then we make a topical drug for diabetic ulcers.

There's 65,000 Americans that die every year in nursing homes from non-healing wounds that get infected. Wow. Not a single wound that we've treated, the nitric oxide, that we haven't been able to heal. Including my own dad, who's a paraplegic from a...

The car accident in 1984, I've dealt with decubitus pressure ulcers for 40 years. And he had a four-year-old down healing wound that every wound care doc I took him to said, you'll never heal this wound in a 60-year-old paraplegic diabetic patient. And I started making a nitric oxide releasing gauze. It was my first kind of personal demonstration and observation. And nine months later, we healed a four-year-old non-healing wound. We healed up an osteonecrotic septic patient and healed the wound.

That was kind of the impetus for the topical nitric oxide because then the wound care doctor was like, what did you do and how can we have access to this? Exactly. Wow. It is a skin care for fine lines and wrinkles, but we're developing a technology for wound care.

you know, we're leading the front and, you know, we're a target. You know, I've been sued, I've been attacked, I've been followed and just to great dangerous territory. But, you know, I've got the truth on my side. I've got science on my side and we're continuing to move forward. You know, it's going to be very disruptive what we're doing. But I think the climate's right. This administration is open to this. And, you know, we're going to change the world. And no one can stop us.

And it's so beautiful to watch, like get to know you and get to see you out there in so many stages. It's just been incredible to see your integrity and that of your company out there. finish off with what I call my rapid fire questions doc, because this helps people get to know you a little bit better. You've already alluded to some of these things, but I kind of like it coming at people so they can come back and listen to this again and again. Are you up for that? Let's do it. Okay.

Here we go. Number one, first word that comes to your mind when you hear nitric oxide. Heal. I love it. Okay. You kind of already talked about this, but I think it's worth mentioning. Coffee or beet juice? Which boosts nitric oxide more? Coffee. I mean, probably a zero, but I put a big coffee over beans. Yeah, there you go. If nitric oxide had a superpower, what would it be? Healing the body.

I mean, all aspects of healing, everything we know about healing is dependent upon nitric acid. I love it. And I do want to just reiterate here, that case that we've talked about throughout our conversation today is, is the face of the typical... American patient and likely global patient today. And so the fact that 93% of Americans are considered metabolically unhealthy, you've heard from this conversation that almost every place where metabolic health...

or diseased land, nitric oxide has a role in reversing that. I just think that's really, really powerful. So that superhero piece makes sense to me. All right, what's the most surprising place in the body that nitric oxide shows up? Surprising place in the body. You know, it's not surprising to me, but I think the general population would be in people who are doing nasal breathing. You know, because the epithelial cells contain nitric oxide synthase, and when it's active...

We do nasal breathing. We produce nitric oxide gas. We deliver to the pulmonary circulation. We dilate the bronchioles. We match ventilation to perfusion. We improve tissue oxygenation. And we can lower blood pressure. So mouth breathing. completely bypasses that as my mouth breathing is so bad. Oh, that's huge. That's huge. That's huge. All right. And that makes me just, again, a million other questions come up, but that enough is a really good comment to make.

All right, biggest myth about nitric oxide you wish would disappear today? That beads are nitric oxide. There you go. And then you alluded to this, that it's not quite possible, but do you personally measure, I mean, are you guys working on an actual measurement, a metric that could measure nitric oxide levels? And if so, what's that looking like on the horizon?

Yeah, I mean, I have a nitric oxide analyzer. So it measures nitric oxide in the gas space. So I can test products, whether they produce nitric oxide or they enhance endogenous nitric oxide production. There's medical devices that measure what's called flow-mediated dilatation.

venous occlusion platensography, so we can look at them, vascular reactivity of the ability for blood vessels to produce nitric oxide. And there's a number of those FDA-cleared devices on the market, but unfortunately, too few clinicians. use it, but they're very valuable tools. So interesting. Well, first of all, I want to just let people know again, this man has worked with Nobel laureates himself since the beginning of his career. I fully anticipate you having your own.

one of these days in celebration of all the work you've done over your 30-year illustrious career. So I'm looking forward to that day, my friend. But are there any parting words or anything I missed asking you that you really want to make sure we share with the folks?

Now, I just encourage people to get educated, get informed. You know, my goal and my objective is to take information and impart knowledge. And there's a lot of information out there, but it takes a lot of discretion to take information. and impart knowledge. And I'll just do a shameless plug on my latest book, The Secret of Nitric Oxide. But, you know, in this, I tell the story of nitric oxide, what it is, what it does, what led to the Nobel Prize, and then...

intermixed and there's my own personal journey of discovery, kind of the hardships we've had to overcome. But, you know, it's meant to be educational, but, you know, knowledge is important, but only if you put it to use. Exactly. I'm so excited about that book. I've been knowing it's, you know, it's, I've been anticipating it. So looking forward to reading that. You know, a guy that if I have your address, I'll get that guy to send you. We got some connections. We'll make that happen. I love it.

And Doc, where can people find you? Where can they find this product? And how can they best stay in touch? Well, first, I'm all about education and awareness. So I send people to my YouTube channel, Dr. Nathan S. Bryan, Nitro.com. I'm on social media, Instagram, Dr. Nathan S. Bryan, LinkedIn, Twitter, I'm Dr. Nitric. And for people who are interested in product technology, it's n101.com. That's the letter N, number one, letter O, number one.

Amazing. Amazing. So many ways. And keep your eyes out for this man and his research. There is a lot happening right now, and I'm very excited about the many levers. This little molecule and your knowledge behind it can... bring into the space of healing. We need all the help we can get. We're just getting started. We've come a long way, but we're just getting started. So saddle up. I'm in, I'm in, I'm in, I'm in.

Thanks again for your precious, generous time today. And I look forward to more conversations in the future. Thank you so much, Dr. Winters. I appreciate you. What an amazing conversation with Dr. Nathan Bryan. So grateful for him being here to help us decode the science and the story of nitric oxide. His work reminds us that health isn't just about avoiding disease.

It's about unlocking the body's own ability to heal, repair, and thrive. For our listeners today, this conversation sparked some curiosity. Please dive deeper into Dr. Brian's research and products at his n1of1.com and no2u.com. Links are also below in the show notes. And if you loved this episode of Metabolic Matters, which I'm sure you did, please make sure to subscribe, share it with a friend, and leave us a review. Every conversation we bring here is about empowering you with knowledge,

especially because your metabolism doesn't just matter. It's the key to your vitality. So until next time, folks, let's stay curious, stay well, and keep creating health from the inside out. Thank you for tuning in to Metabolic Matters. We hope today's conversation offered insight and inspiration that you can carry into your own journey. Be sure to check out the show notes for links.

and more on today's topic. If you enjoyed this episode, please follow the show, leave a five-star review, and share it with someone who needs it. You can also connect with us on Instagram. and beyond at Metabolic Matters. Special thanks to Julie Newmark and Whiskey Flower for providing our music. Your sound brings this space to life. Until next time. Stay curious, stay empowered, and keep metabolizing what matters.