Dr. Nathan S. Bryan Unravels Nitric Oxide's Role in Health #127

Q. So, what is this magic molecule that silently orchestrates everyone's health?
A. Nitric Oxide

Dr. Nathan S. Bryan is one of the world leaders in nitric oxide research. In this mind-blowing interview, he helps us understand the crucial role the molecule plays in our physical health.

Many misconceptions about nitric oxide clutter the internet regarding what it is and how it works. Dr. Bryan untangles that mess for us. Then, he lays some truth on us about the surprising impact of various lifestyle choices on nitric oxide production. From erectile dysfunction to heart disease, mouthwash to antacid, fluoride to sunshine, Dr. Bryan connects the dots, educating us about the essential role nitric oxide plays in keeping us healthy.

Is Methylene Blue safe? Dr. Bryan is in a better position to give an educated answer than almost anyone in the world today.
Can diabetic ulcers be healed? Dr. Bryan says "yes" and explains how.

If you care about health, the information in this episode could be a life-changer. Make it a priority.

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Learn More from Dr. Bryan:
YouTube: https://www.youtube.com/@DrNathanSBryanNitricOxide
Website: https://drnathansbryan.com/
Supplements & Skincare site: https://n1o1.com/

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One small step in the right direction is all it takes to get started. 

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Theme Song : Rage Against
Written & Performed by Logan Gritton & Colin Gailey
(c) 2016 Mercury Retro Recordings

Transcript

Jack Heald: 0:37

Hey folks, welcome to the Stay Off my Operating Table podcast for Dr Philip Ovedi on Jack Heald. And we have today somebody who's this is so ironic, phil. I'll give you the details about why I think this is ironic and funny after you introduce our guest. So let's go.

Dr. Philip Ovadia: 1:00

All right, very good. Good for today's conversation. A little bit of a warning this one might get a little geeky. I reached out to Dr Nathan Bryan a while back because he really is one of the world's experts in a topic that I wanted to know more about. So full disclosure. Part of the reason for this episode is so that I can get educated on the subject that Dr Bryan is a world expert in, which is nitric oxide. But before we get into that, let me give Nathan a chance to introduce himself to our audience and give us a little bit of his background.

Nathan S. Bryan: 1:40

Sure Well, thanks Philip and thanks Jack. Great pleasure to be with you. You know, jack, as we were discussing before, I'm a small town country boy, born and raised in Texas, went to a small high school, right to the University of Texas, then graduated with a degree in biochemistry. From there I went to LSU School of Medicine where I did a PhD in molecular and cellular physiology. Then from there I trained up in Boston at Boston Medical Center, really just continuing on this path of nitric oxide, how the human body produces nitric oxide, what goes wrong and people who can't make it. And then how do we fix it. So 25 years in the basic sciences, hundreds of peer reviewed publications, several dozen issued patents, more than 300 lectures around the world, and so that's what I do. I study nitric oxide and everything it is and does.

Jack Heald: 2:32

Well that sounds. I'll confess I'm actually really interested to get into this. But as I was doing my research I saw that one of the things that you are affiliated with is a company that makes a skincare product, and what's funny to me is I am currently. We had a guest on a while back who makes skincare products where the primary ingredient is lard, and I had a guest on another show I produce who also makes skincare products, and about two weeks ago I decided I'm just going to do a contrast and compare on these two products. So I've been putting one product on the left side of my face, the other on the right side of my face every day just to see what happens. My wife this morning said I think your skin really does look better, and again, it was a bar to get over. So if neither of these do the job, maybe nitric oxide is the key.

Dr. Philip Ovadia: 3:43

Well, let's start with some basics, you know. Talk about what nitric oxide is, and maybe even before you talk about what it is, I'd love to hear what got you so interested in it that you've dedicated your career to that molecule.

Nathan S. Bryan: 3:59

Well, it's somewhat ironic. When I finished inorganic chemistry at the University of Texas and I passed the course I think we did there in A or B I made a promise to myself that I'd never get into nitrogen-based chemistry ever again. So that was in the early 90s. And then here I am, 30 years later.

Jack Heald: 4:18

I'm guessing science people understand that, but I'm not a science person. Why?

Nathan S. Bryan: 4:23

Well, nitrogen it's like five valence electrons, it has a lot of reactivity and it's very complex eight different oxidation states. So that's the kind of the part that probably the late people won't understand. But certainly any chemist or biochemist understands the complexity of nitrogen-based science. But after I finished my degree and I was going into LSU, a Nobel Prize had just been awarded for the discovery of nitric oxide and we were very fortunate to have Lou Ignaro, who had just won the Nobel Prize, come to LSU School of Medicine and give a lecture before the student body and I was fortunate to actually go out and have dinner with him that night after his lecture and we discussed kind of the state of the art and the state of the science and he said there's still so much we don't know about nitric oxide.

Nathan S. Bryan: 5:07

We don't know really how the human body produces it. And to get back to your original question, nitric oxide is a gas right and it's naturally produced in the body and once it's produced it's gone in less than a second. So the challenge was how do we recapitulate, how do we really create a nitric oxide-based therapy that could restore this fleeting molecule in the human body? And those were the limitations. And at the time, in the late 90s, early 2000s, there really weren't even any analytical methods to detect nanomolar or fymphomolar concentrations of nitric oxide.

Jack Heald: 5:40

That's 10 to the minus what's fymphomolar?

Nathan S. Bryan: 5:43

Well, these are kind of units of concentration, so it's 10 to the minus 9. Like everybody knows, nanotechnology it's really small right 10 to the minus 9. So nanomolar is 10 to the minus 9 molar concentrations of nitric oxide, which means it's extremely potent. You get a little bit produced and it elicits a biological effect. So really what I did during my entire PhD thesis dissertation was develop analytical methods where we could detect nitric oxide at levels that were produced inside the human body. And once we did that, I think I finished my PhD in about two years.

Nathan S. Bryan: 6:18

I published three first author papers within the year and a half and then we were off to the races, because we had technology now that we could really start to understand nitric oxide in many different disease processes. So we could induce different diseases, from diabetes to acute myocardial infarction, to inflammatory bowel disease, and then see what's going wrong with nitric oxide, where does it go, what does it become and how do we fix this. And in the first several years we were publishing 10 to 15 peer-reviewed papers a year, which is unheard of in academia. So we learned a lot over a short period of time and now today fast forward 25 years we know exactly how the human body produces nitric oxide. We can explain the mechanism of nitric oxide deficiency and today we have technology that we can completely recapitulate and dodge at this nitric oxide production and nitric oxide signal.

Jack Heald: 7:17

Bill. I have a million questions, but you're going to have better ones than I have.

Dr. Philip Ovadia: 7:22

Well, yeah, we'll continue to explore some of the basics. I guess I'm going to frame it as the main reason that people may know about nitric oxide although they probably don't actually know about nitric oxide through this is that many of the medications for erectile dysfunction, like Viagra, work by increasing the body's either production of nitric oxide or making nitric oxide hang around longer in the body. So we're going to be preventing the breakdown of it, and so I guess that makes it obvious that nitric oxide does something to the blood vessels.

Dr. Philip Ovadia: 8:06

But let's talk about what role nitric oxide plays in the body, and you mentioned some diseases like heart disease, which of course is of particular interest to me and my audience, and so talk a little bit about what role nitric oxide may play in that.

Nathan S. Bryan: 8:25

Let's take a step back, because the drugs like Viagra, the Pd5 inhibitors, don't do anything to nitric oxide production or preventing its breakdown. What they do is they potentially nitric oxide signal. So just to get a little bit deep in the science, because I think it's an important in terms of understanding mechanism, is when nitric oxide is produced, that gas that's produced activates an enzyme called guanulocyclase and that produces a second messenger, cyclic GMP. Then Viagra prevents the breakdown of that. So drugs like Viagra work because they potentiate the effects of nitric oxide. They lead to vasodilation, engorgement and that's the mechanism for erections, in both men and women, by the way. But as you know and the data tell us, 25 years of these drugs being approved on the market only 50% of the men respond to phosphodestery inhibition therapy and the reason they're non-responders to therapy is because they don't make enough nitric oxide to activate that second messenger system. So those are the limitations of those drugs. So Viagra, cialisim and Vitre do nothing with nitric oxide production. But if enough nitric oxide is produced they can amplify the effects and overcome symptoms of erectile dysfunction or urinary symptoms of BPH, which they're approved for.

Nathan S. Bryan: 9:45

But the primary role of nitric oxide is to vasodilate, meaning increase the dilation for the internal luminal diameter of blood vessels. So in patients with heart disease, obviously as a cardiologist you appreciate this. But there's a constriction of the coronary arteries, whether it's through obstruction from plaque and fat deposition or it's aphelsferosis. But when you get stenosis or an obstruction of the coronaries then when you begin to exercise you can't get enough oxygen to the working muscle of the heart and so you develop pain. You call that pain angina or ischemic pain. So what nitric oxide normally does when we begin to exercise it dilates the coronary arteries. You can increase the perfusion and increase the metabolic demands on the heart and you can perform normally and you don't get ischemia, you don't get angina. And so those are the basis of drugs for ischemic heart disease, like nitroglycerin or isis were by dinitrate Because they're metabolized into nitric oxide.

Nathan S. Bryan: 10:43

So that was the first role of nitric oxide was just expanding blood vessels, improving oxygen delivery and oxygenation of tissue. But we now know it's involved in the oxygenation of tissue. It's required by hemoglobin to deliver oxygen. It's how our immune system kills off viruses and bacteria and it's critically important in the brain and neurotransmission. It's how neurons and nerves in the brain communicate with one another. So when you develop an inability to produce nitric oxide. Hopefully you can now get an appreciation for the laundry list of symptoms that occur. You develop sexual dysfunction, your blood pressure goes up, you develop basket dementia, cognitive disorders, you develop exercise intolerance, type 2 diabetes and basically many, if not most, of the major diseases that are plagued by Americans today and really that are poorly managed by this current standard of care.

Jack Heald: 11:37

What you just described. It sounds exactly like what guest after guest after guest on this show has described as metabolic dysfunction or metabolism. Exactly right, Is it the same thing? Are we just going maybe a layer deeper with the nitric oxide?

Nathan S. Bryan: 12:04

Well, what I do as a biochemist and physiologist is try to understand the mechanism of disease to the extent that you can fix it through what we call restorative physiology or, worst case scenario, pharmacology. So when we talk about metabolic disease, what does that mean? Well, metabolism is basically defined by the breakdown of the foods we eat in the cellular energy, which is ATP, and there's a long biochemical process that takes the breakdown of foods into ATP, the end product of cellular currency, of cellular energy. So when we look at metabolic disease, what does that mean? Well, you know, exercise intolerance, your blood pressure goes up, you get hyperlipidemia and insulin resistance.

Nathan S. Bryan: 12:46

And nitric oxide controls and regulates all that. You know, I think in 2009, we were the first group to publish that nitric oxide is part of the insulin signaling cascade. So when insulin secreted by the pancreas, it binds to insulin receptors on most cells in the body mainly muscle cells, liver cells and fat cells and it tells those cells to clear glucose from the circulation. And that process is controlled by a protein called a glute 4. But glute 4 signal to go to the membrane and bind glucose is dependent upon the cells ability to produce nitric oxide. So if the cell can't make nitric oxide, glute 4 never gets the signal. What happens? You get insulin resistance. You get hyperglycemia Because the pancreas hey, I need more insulin. You get hyperinsulinemia and that creates the inflammation that's the tall mark of every chronic disease. So a lot of times it's not the hyperglycemia or the elevated in blood sugar it's causing the problems. That causes enough problems on its own, but it's the hyperinsulinemia that mediates all the inflammatory damage, the oxidative stress and the immune dysfunction that you see in cardiovascular disease.

Dr. Philip Ovadia: 13:54

Wow, yeah, now you know why I was so excited to talk to Brian. And we talk a lot about root cause and finding root causes of diseases. Here there are root causes of the root causes, I guess is how I'll say it. We talk about insulin resistance. That's kind of the clinical presentation that we can measure and manage. But the cellular mechanisms underlying insulin resistance are quite interesting and give us even more opportunity. So I guess people might be sitting out there thinking well then, obviously it's real easy to fix my metabolic disease. I just pop some nitric oxide, right, and everything's going to be better. It doesn't quite work that way, but maybe tell us a little bit about why it's not as easy as just you know. Let's just give everyone nitric oxide. Well, you?

Nathan S. Bryan: 14:53

know. Unfortunately that's how Americans are programmed right. Nobody wants to change their diet lifestyle. They want to pop a pill and take a silver bullet and unfortunately in physiology and medicine that doesn't exist.

Nathan S. Bryan: 15:05

You know, we know nitric oxide is foundational, but it's not going to fix every aspect of somebody's disease process and overcome their bad habits, their bad diet, their lack of exercise. So what we have to do is understand what is that patient doing, disrupting their own body's ability to make nitric oxide, and then how can we instruct them to do things that are clinically proven to restore, activate or stimulate nitric oxide? And that's kind of where we started about 20 years ago, and we could only answer those questions once we understood how the human body makes nitric oxide right. So now that we can answer those questions, we can instruct patients on what they're doing. So just kind of the cliff notes is over 20 years we've realized that the microbiome in the mouth, the oral microbiome, contains bacteria that are responsible for production of nitric oxide that regulates systemic blood pressure. So when we do things to eradicate and disrupt the oral microbiome, we shut down nitric oxide production and leads to an increase in blood pressure.

Nathan S. Bryan: 16:05

The oral microbiome the oral microbiome.

Jack Heald: 16:08

Starts in the mouth.

Nathan S. Bryan: 16:09

Starts in the mouth. Exactly. So we and others published, probably 10 years ago, that if you use mouthwash, you kill the oral microbiome, disrupt nitric oxide production and patients' blood pressure goes up. Not only does your blood pressure go up, but they lose the protective benefits of exercise. So two out of three Americans wake up every morning and use mouthwash and, as you know, two out of three Americans have an unsafe elevation in blood pressure. And this is not coincidental. This is causal. We published a paper in 2019 showing that if you use mouthwash, we could pick up the bacteria that disappeared when blood pressure went up and four days after you stopped the mouthwash, we could pick up the bacteria that reappeared. At the time the blood pressure normalized. So now, disruption of the oral microbiome is causal for hypertension and this explains resistant hypertension.

Nathan S. Bryan: 17:01

And, as you know, as a prescribing cardiologist, you get patients with high blood pressure. What do you do? You get an ACE inhibitor, an ARB, a calcium channel antagonist, or a diuretic or whatever indication. And yet 50% of the patients that are put on these class of drugs don't respond with better blood pressure. And why is that? Well, because it's not a random angiotensin problem. It's not a disruption of calcium metabolism or flux. So ARBs, ace inhibitors and calcium channel antagonists aren't going to fix their blood pressure. What we're finding is hypertension is many times a symptom of oral dysbiosis. So if you get the patients off mouthwash, you allow them to restore the diversity of their oral microbiome, their bodies able to produce nitric oxide, and all of a sudden, their blood pressure normalizes. Wow, it's a completely new paradigm in the management of systemic blood pressure and this is revolutionary. This will change the practice of medicine is you know, hypertension is the number one modifiable risk factor for the number one killer of men and women worldwide, which is cardiovascular.

Jack Heald: 18:05

So if you just stop screwing up your oral microbiome, it will naturally rebalance.

Nathan S. Bryan: 18:15

Well, it depends upon look, I wish it were that simple that it depends upon what we feed these bacteria. Right, the bacteria in and on our body outnumber on human cells 10 to 1. And they code for 3 million gene products. The human genome only codes for 23,000 gene products. So we have to give these bacteria what they need to do their job. So if you're eating high sugar, high carbohydrate, you know a bunch of junk food, then you're feeding the bad, opportunistic, pathogenic bacteria what they need and you're depriving the good commensal bacteria of what they need. So what we're finding is that you need more green leafy vegetables, things that are enriched in inorganic nitrate, because these are nitrate ridincers. And then you know you got to get rid of fluoride in your toothpaste. Fluoride is an antiseptic, it's a neurotoxin that kills your thyroid function. And then the other thing. So that's that's, that's just affecting the oral microbiome. So if we just get people to stop using mouthwash, get rid of fluoride, which is probably one of the most toxic molecules on the periodic table, then the oral microbiome can flourish and now the body's able to produce nitric oxide. So that's the first step, and the other problem are antacids, specifically the proton pump inhibitors.

Nathan S. Bryan: 19:27

Yeah, you know. There's data now showing that people who have been on PPI is these are pyrlocemic protonics, so meprosolp and coprosolp People have been on these drugs for three to five years have a 40% higher incidence of heart attack, stroke and Alzheimer's. This is an increased risk. These are increased actual events and this is, to me, is unacceptable. You know the vioxin celebrates 20 years ago. We're causing heart attack strokes and there's a black box warning on these drugs. The same should be for proton pumping. If you can shut down stomach acid production, you completely shut down endogenous nitric oxide production, putting patients at risk for heart attack, stroke and baspidimension Alzheimer's. You got to get patients off antacids, wow.

Dr. Philip Ovadia: 20:11

Yeah, you know, and it's kind of. You know, I'm sitting here thinking about how I guess you know I'll just put it as I stumbled across a lot of this stuff. You know, getting off patient, getting patients off medications, you know, is a major focus of my practice and you know, and you just sort of back into this information without even realizing, like all these molecular mechanisms behind it oftentimes. So it's fascinating to hear about those molecular mechanisms. Besides, you know, maybe, medications and you know mouthwash, you know microbiome. What are some of the other common things that people are doing that's interfering with their ability to make nitric oxide?

Nathan S. Bryan: 21:05

Yeah, I answer that question. Let me just kind of follow up on a comment you made, because I think it's a profound statement you made of getting patients off of medications. As you said, that's never occurred before in the history of Western medicine, because it's always if you, if this medicine don't work and come back, I'll put you on another medicine that doesn't work. Well, and, as you know, most Americans are over-metachated. Polypharmacy doesn't work, and so now this, the molecular mechanism, as you say, is there to where you can start to have a conversation of winning patients off drugs. And that is only that, and only that is what's going to make patients better, because we're regenerative beings by nature. The human body heals itself. Doctors don't heal patients, medicines don't heal patients. Body heals the patient itself. So what else can we do? So you've got to number one get off mouthwash, get rid of fluoride, get off antacids and then throw in some more green leafy vegetables.

Nathan S. Bryan: 21:58

I like a balanced diet and moderation. I'm not a big fan of extreme diet straight vegans, straight carnivore. I think we've evolved to get our nutrients from a diverse mix of foods. And then moderate physical exercise. You know, 20, 30 minutes of aerobic exercise a day just a breast walk is sufficient for stimulating nitric oxide production. 20, 30 minutes of early morning sunlight or infrared light, you know, full spectrum infrared can activate mitochondria, can activate nitric oxide production.

Nathan S. Bryan: 22:30

You can see the benefits of that. So these are all cost saving modalities, right? You're not buying mouthwash anymore and you pay the same, maybe a little bit more, maybe a dollar more for fluoride-free toothpaste. Buy fresh vegetables, farmers market and then just exercise, get out, walk in the sun morning for 20 or 30 minutes. And I mean, in an ideal world that's all we would need, we wouldn't need supplementation, we wouldn't need drug therapy. But, as you know, the problem is not a lack of information, it's the translation of that information, patient compliance and then, when all else fails, obviously we've developed product technology that actually makes nitric oxide and restores your body's ability to make nitric oxide on its own.

Dr. Philip Ovadia: 23:13

Yeah, the one and the only thing I would push back a little bit about there is you said it's not a lack of information. I think it is actually a lack of information, you know, and it's lack of information on the doctor's part oftentimes.

Nathan S. Bryan: 23:32

Well, maybe I misspoke. It's not a lack of science, I should say it's the translation of that science into practical information, not just for the physicians and the health care practitioners but for the patients as well. And I think that's why this interaction is so important because, you know, I taught in medical schools. I taught future physicians, you know, for most of my adult career. And it's not the doctors to blame, it's the system right. And it's very difficult to change the system in which and the curriculum in which we train physicians, because you learn biochemistry and physiology your first year. Second year you learn pharmacology and you forget all the biochemistry and physiology that you learned because, as you know, once you make a diagnosis, you have a finite kind of arsenal of what you can do for that patient in order to get paid, based on reimbursements and billing codes. So it's the financial model of medicine that rules the day. It's not looking at kind of mechanism of disease and what's best for that patient. The financial model always over rules best practice.

Jack Heald: 24:35

Yeah well, we're in violent agreement with you there. Hey, phil, I want to ask this question Fluoride aren't there an awful lot of municipalities that fluoridate their water?

Nathan S. Bryan: 24:48

Yeah, and we wonder why Americans are sick. We got an epidemic of hypothyroidism. You know you need. So fluoride is a neurotoxin. If you remember on the periodic table, it's a halogen. It's found in the same column as iodide and bromide, and all that. So for thyroid function, in order for T4 inactive hormone to become T3 active hormone, you need iodine to convert T4 to T3. And number one Americans aren't getting enough iodine in their diet. Number two we're exposed to fluoride. So any iodine we have in the body fluoride out from T4 binding to thyroid hormone. You need iodine to make stomach acid. There's iodine receptors on ever major cell in the body. So without iodine, we develop metabolic disease, we develop hypothyroidism. So, yeah, I encourage people to get a home filtration system that removes all the garbage out of municipal water supply. Why do they put it in there? Because it's an antiseptic. It kills the bacteria in the water. So what does that mean? It kills all the bacteria in your body too, which isn't a good thing.

Dr. Philip Ovadia: 25:49

Wow, yeah, that I would certainly agree was one of the kind of big mistakes that we made in public health and, like you said, it was done with the thought of we got to get the bacteria out of the water supply to try and kill some of the pathogens in the mouth that were recognized and they said, oh well, we'll just put fluoride in the water and that will reduce dental carries. Cavities was the original intent by killing off some of the bacteria that lead to that, but the unintended consequences were not recognized.

Nathan S. Bryan: 26:32

I guess we could say it's literally throwing the baby out in the bathwater. We do that. That's the advancement of science, right? We did things 100 years ago that we don't do today, because we know more than we did 100 years ago. So why continue those practices? Today? And in dental medicine I talk to a lot of dentists and I go why do you guys still do fluoride, winston? They go, well, it's because we've always done it Well. That's the stupidest response I've ever heard. We used to exsanguinate patients with leeches. We don't do that anymore because we know better. There's better ways. We know that fluoride's a toxin. We know that killing the microbiome is a really bad idea. There's a reason a patient doesn't take an antibiotic every day for the rest of their life because the known disruption of the microbiome and systemic disease that arises from that. So why would we continually expose ourselves to an antiseptic and neurotoxin in a thyroid killer when we know better today than we did 100 years ago when this practice started? What makes those sense?

Jack Heald: 27:34

Wow, okay. So at the microbiology level, as we warned you, I'm the token idiot here, I'm just trying to make sure I've got my head wrapped around this the presence of nitric oxide is what facilitates the process of converting food into cellular energy.

Nathan S. Bryan: 28:03

It's an essential part of that. Obviously, there are many steps in that process.

Jack Heald: 28:07

And with an insufficiency of nitric oxide that is almost by definition, metabolic ill health dysfunction.

Nathan S. Bryan: 28:18

Yeah, well, let's look, we start with-.

Jack Heald: 28:20

I realize I'm simplifying but I'm-.

Nathan S. Bryan: 28:22

No, but this is very important to put it in proper perspective, because in the basic sciences typically people try to work out a mechanism and then try to make it fit in the clinical medicine. That's why most basic science discoveries never make it in the clinical practice. So what I do is completely different. I don't follow the scientific method, hypothesis-driven bullshit, pardon my French. What I do, and what I've done for 25 years, is take important clinical observations and then work backwards and try to figure out mechanisms. So what we know today is that in patients who can't make nitric oxide, their nitric oxide production becomes disrupted. They could be for a number of reasons Fluoride, mouthwash and acids, genetic predispositions Is that you develop high blood pressure, you develop erectile dysfunction, insulin resistance, hyperlipidemia, primarily hyper elevated triglycerides, they become inflamed, you see an elevation and C-reactive protein and they develop exercise intolerance and they have chronic inflammation. And that explains almost every age-related chronic disease known to me. And now again, nitric oxide is not going to fix all those. I mean it can, but the physician has to dig a little bit deeper and figure out what else is going on. And here's what we learn If you give nitric oxide or restore the bodies to build or produce nitric oxide, you can overcome ED. Blood pressure will normalize Several of my patents on the method of reducing inflammation. We lower triglycerides 20% in 30 days and exercise, intolerance improves and everything works better. You improve oxygenation of tissue, oxygen and nutrient delivery to every organ, tissue and cell in the body and everything works better. Now the bodies.

Nathan S. Bryan: 30:07

So what we say is is nitric oxide is foundational. It's not an end-all, be-all, cure-all. But the body will not and cannot heal without first restoring the production of nitric oxide. Then you can start. Okay, do we have thyroid issues? Let's fix that.

Nathan S. Bryan: 30:20

Do we have hormone issues and other endocrine systems? Do we have some latent infection that the body is exposed to that becomes active? Do we have dental infections we need to deal with? Do we have foodborne allergies that maybe result from insufficient stomach acid production? Then you got to go back and fix all those other systems, but nothing else is going to work. Or if you try to fix those other systems without first restoring the production of nitric oxide, you're never going to get anywhere. And that's the problem with clinical medicine today is that nobody's focusing on nitric oxide production, asking their patients what are they doing that may be disrupting, and then starting them on the path to restore their normal nitric oxide production. Number one is most physicians don't have the time to query their patients because you got to keep the bills paid and lights on and they may have five to seven minutes per patient. Can't get a full medical history in that short amount of time.

Jack Heald: 31:13

So you would advocate for everybody who walks into a physician's office to be diagnosed that we find out. Are you using mouthwash? Stop. Are you using antacids stop. Are you getting enough daylight and exercise? And if not, start more daylight or more moderate exercise. Those four things, and in the absence of those four things, you're kind of spinning your wheels, no matter what else.

Nathan S. Bryan: 31:48

That's right, and this is based on the preponderance of evidence in the published literature. So this isn't just me, this is what the literature we've contributed a lot of the early seminal discoveries in this field, that there have been a lot of people, other groups that have reproduced our data, you know, expound upon it. But yeah, the evidence is clear and, as you guys know, the most heart attacks happen in the winter. You know, before 10 o'clock in winter months. So that's where we are now. So especially people need to take care of you know what are they doing. And people in the northern hemisphere typically have higher blood pressure than people living near the equator. So sunlight has an enormous effect on total body health, not just vitamin D but in nitric oxide production.

Dr. Philip Ovadia: 32:34

And is there a way that for physicians or for you know people that are interested for themselves to assess you know whether or not they're nitric oxide deficient?

Nathan S. Bryan: 32:46

Yeah, unfortunately you know there's not. You know, like if you can draw peripheral blood and say, okay, what is your cholesterol, triglycerides, vitamin D, magnesium, things like that, because nitric oxide is a gas that's going in less than a second. There's really no blood labs you can pull to measure nitric oxide. We can look at correlates like elevation and triglycerides or C-reactive protein or oxidized lipoprotein, particle size and number of things like that, but there's really no measure for nitric oxide. There's some functional devices that we can look at that measure reactive hyperenium, that give us an indication of endothemial function, but there's really no blood labs. You know, about 12 years ago I developed the first and only non-invasive point of care salivators because we were understanding when nitric oxide is produced, it's recycled and it shows up in the saliva as inorganic nitrite. So I developed some chemistry old chemistry called the grease reaction, where we could detect nitrite in saliva and that would give us a proxy for kind of total body nitric oxide production. And it was. I tell people it's a good tool to have in your toolbox but you have to understand the caveats of that test. So it's a good engagement tool to test your patients and let them know, because most people are going to be low or depleted of what we call it and there are no false negatives. So if you're negative, you're negative, but it doesn't tell us why you're nitric oxide deficient. Is it because your diet sucks? Because you don't get exercise? You're using mouthwash and acid for right.

Nathan S. Bryan: 34:18

But there are some false positives that we were concerned about, and the false positives come from dental infections. So what we're finding is that if you get an active oral infection, the increase in salivary nitrite is a consequence of a local immune response in the gingival tissue or in the oral mucosa. Leads to false positives, and we first stumbled upon this. You know 50 year old, obese, diabetic, hypertensive patient with ED. He gave them a saliva test and they light it up like a Christmas tree. Obviously that patient isn't replete in nitric oxide. They have all the symptoms of nitric oxide deficiency, but they light up that test strip and then, upon further interrogation, you know he had a horrible dental hygiene and had a number of oral infections, some of them asymptomatic. So then we have to get his oral infections cleaned up. And now he tested low.

Jack Heald: 35:12

So how do you do that? How do you deal with oral infections, given the things we're supposed to avoid?

Nathan S. Bryan: 35:22

Well.

Jack Heald: 35:22

I may. I maybe should ask the dental people. But hey, you're here.

Nathan S. Bryan: 35:27

Yeah, I know the dental community. We do a lot of work with the dental community because these are important questions and I'm trying to. It says my battery is running low. Let me see if I can get some juicy.

Jack Heald: 35:39

So Brian disappears, it's because it's because my battery, yeah.

Nathan S. Bryan: 35:44

So we have to now understand, because there are certain dental infections that contribute to cardiovascular disease. Right, it's called the oral systemic link, and the dental community years ago just started putting everybody on fluoride rinses and antiseptic mouthwash to try to kill the pathogens. And then we came along and revealed that, hey, you're not only killing the bad guys, you're killing the good cuts. So now how do we eradicate the pathogens? By maintaining the integrity of the oral microbiome. Good commensals, and so that's what we're trying to do now is kill the bad guys, maintain the good guys. And then we had selective therapy for oral infections.

Dr. Philip Ovadia: 36:22

Hmm.

Jack Heald: 36:24

So, sounds like the moral of the story is don't get an oral infection.

Dr. Philip Ovadia: 36:27

Yeah, well, yeah, and of course we know that you know the same things that predispose you to oral infections, you know. Again circle back to metabolic disease and many of the things we've been talking about. Now there is a camp out there in the metabolic world who talks about the benefits of methylene blue. You know we're going to get a little get into the weeds here, but you know, at a high level. Basically, methylene blue opposes the actions of nitric oxide and you know people in this camp will talk about that too much nitric oxide can be a problem in the body as well, so I'd love to hear your thoughts on that.

Nathan S. Bryan: 37:16

Well, here are my thoughts based on the published science. So it's not my opinion, it's based on the science. Methylene blue completely inhibits nitric oxide production and nitric oxide based signaling. So its main effect is and we've used it in the research lab for 30 years to oxidize the heme iron of guanoled cyclase, to prevent nitric oxide signaling. So those that use methylene blue basically eliminate the therapeutic benefits of PD5 inhibitors because it oxidizes the iron of soluble guanoled cyclase. So you get no cyclic GMP produced and you can't get an erection. And if you inhibit nitric oxide production, your blood pressure goes up, you get metabolic disease. So obviously there are dose dependent effects of methylene blue, but I would never do anything that inhibits nitric oxide production or nitric oxide based signaling. And that's what methylene blue does. And you got.

Nathan S. Bryan: 38:10

You know, here's I'm part of this biohacking community. But here's the problem with biohacking there's some guy who's a journalist, who has no scientific credibility, no credentials. He wrote a book on methylene blue and everybody follows it. But this guy, I mean, he's not a scientist, he's not a physician, he has no scientific background, but he's created a lot of noise out there and I just tell people you know, understand the source of the information. This is some journalist telling you. I mean, you know you wouldn't go to a journalist if you were having a heart attack. I don't think you shouldn't. How would you go to a journalist for medical information? You shouldn't. And that's the problem with this. So you know, I tell people I don't argue with results, but just be careful and understand what you're doing, based on the underlying science and the biochemistry here. So I tell people stay away from methylene blue. I've never used this.

Dr. Philip Ovadia: 39:02

Yeah, and you know, from my perspective I think it's context dependent. Uh-oh, we lost Dr Brian but hopefully it'll come on back in a minute. But you know, to expand on what he was just saying, you know methylene blue. It's interesting because in the hospital in my world, as a heart surgeon, we actually use both methylene blue and nitric oxide medications like Viagra. You know we use there's a generic form of it, an IV form, and for different situations they have benefits. So methylene blue is useful when people have low blood pressure that is basically resistant to the standard treatments, and medications like Viagra are useful in patients who have high blood pressure, particularly a specific type of high blood pressure in the lungs called pulmonary hypertension.

Dr. Philip Ovadia: 40:04

So I was just saying, nathan, that basically you know the situations where we use methylene blue in the hospital for people with very low blood pressure, because it does exactly what you said it opposes nitric oxide or blocks the production of nitric oxide and therefore raises blood pressure. And there are other situations where we're trying to raise nitric oxide, like pulmonary hypertension, where we're using medications, like you know, sadafinal, which is the generic form of Viagra. So all of this stuff is context dependent and like everything in our body. You know, it's the balance really that probably matters. In the end. There is no either or usually.

Nathan S. Bryan: 40:51

Yeah, that's right. Yeah. So as we predicted, for some reason my computer wouldn't take a charge. So here I am on my phone now, so glad to reconnect.

Dr. Philip Ovadia: 41:01

I need some nitric oxide to get some more ATP in the computer right.

Nathan S. Bryan: 41:05

Yeah, yeah, we'll try that Now. But look, I tell people, look, there's clinical indications for methylene blue. But for people to take this on a daily basis as a prophylactic, I mean it's a really bad idea based on the science. So just I tell people just take caution. You know, I think a lot of the biohacking community has a lot of good tips, but beware of getting medical information from non-scientists, non-physicians, who've never spent a single second a minute in the lab but don't know the basics about biochemistry.

Jack Heald: 41:39

Well, but we could say the same thing about an awful lot of the medical professionals who are spouting their opinions is they don't apparently don't know the basics of biochemistry. There's been a lot of that going around. I mean, as a layman who's had to wade through the, I think the technical term is bullshit. Right, we speak the same language. There's a lot of that going around. I have what is quite possibly a stupid question, but it's been nagging at me since we started this conversation. Nitric oxide is this gas that's produced in your body. That is what do you call it foundational? Yep, it is foundational to metabolic health. If I remember correctly, my wife's father was a dentist and I think he used something called nitrous oxide.

Nathan S. Bryan: 42:31

Yeah, that's right.

Jack Heald: 42:32

That feels really good when you're on it.

Nathan S. Bryan: 42:34

Yeah, no, that's a dental anesthetic. They sound similar. Nitric oxide is NO, nitrous oxide is N2O. It's the completely different molecules. They sound similar. Yeah, what we're talking about is not the dental anesthetic. It's not laughing gas that puts you to sleep. What we do wakes you up, energizes, animates the human.

Jack Heald: 42:55

Okay, I just I wanted to get an answer to that question. I got to tell you that the description of the problem seems to me as a layman, I think I get it insufficient. Nitrous oxide is foundational to most of the lifestyle diseases that we deal with.

Jack Heald: 43:21

Nitric, sorry, nitric oxide, thank you, I have to catch you. Yeah, thank you. Well, that's why we have experts on the show, and restoring the body's ability to produce nitric oxide is actually pretty straightforward and simple. It involves not doing a couple of things and adding a couple of things to your lifestyle, and we specified those Quit using, quit killing the good germs and get some sunshine and exercise.

Nathan S. Bryan: 44:00

That's the president of gas production.

Dr. Philip Ovadia: 44:05

Let's talk about some of the challenges there, though, because of course, you said we're kind of trained to think, all right, well, let's just replace nitric oxide. And many people are probably sitting there thinking, well, if I just replace my nitric oxide, I'm going to improve a lot of my conditions. And the member I think largely the people in our audience will already be doing a lot of the stuff we talked about. We talk a lot about the dietary strategies and getting sunlight and exercise. The mouthwash might be a new one to some people, but let's say, you're doing all that, you're still struggling with some of these metabolic issues. You're thinking that nitric oxide may be an issue for you. What are some of the challenges around nitric oxide supplementation? Because I think this is important for people to understand as well.

Nathan S. Bryan: 45:01

Yeah, this is my greatest source of frustration on a daily basis, because I spent 25 years in the lab understanding this and you got hundreds of companies out there selling consumers nitric oxide products. That number one have no idea on the biochemistry or underlying physiology of nitric oxide. Number two, worse yet, understand it but still are putting products out there that are defrauding and deceiving the customer. So the science of nitric oxide is extremely complex. It requires a five electron oxidation of hydrogen to make nitric oxide or a three electron reduction. We're going to get an inorganic nitrate to produce nitric oxide. And if you don't understand that, if you can't count electrons and understand the flow of electrons through biochemical reactions, then you really have no business trying to sell a market of nitric oxide product. That's my frustration. So there's been nitric oxide products on the market since the late 90s. Many contain arginine, citrulline, a lot of antioxidants, a lot of good ingredients, but you can't put ingredients in a bag and call it nitric oxide. That just doesn't happen and then. So what we do is completely different. So we have product technology that's unlike anything on the planet that any product that I develop actually produces nitric oxide gas. I'm the first and only person in the world that's ever developed a solid dose form of bioactive gas. And so we do this in the form of a lozenge. It has a resident time of about five to six minutes in the mouth and has that lozenge as soon as it hits your saliva it starts generating nitric oxide gas. We can detect it, we can quantify it, we can verify it with a nitric oxide analyzer. We can see with an ultrasound. We can see dilation of your products within about 12 to 15 seconds. So it's vasoactive. And then we fix the reason your body can't make nitric oxide. So I designed this lozenge to have a five to six minute resident time in the mouth and what we're finding is that the nitric oxide released by that lozenge kills the pathogenic bacteria, kills the guys that you don't want. And because we're providing a source of nitrogen to the microbiome, we're waking up these nitrate reducers and we're improving the diversity of the oral microbiome. Now we've improved your body's ability to make it. The other thing we've done is we've recoupled the enzyme that makes nitric oxide in the lining of the blood vessels. So we provide a specific electrical potential, a redox potential, that prevents oxidation of a molecule called tetrahydroboctrin, recouples the NOS enzyme. So now we're improving endothelial function in every single patient by 15 to 20% within four hours. So no other product on the market does what we do.

Nathan S. Bryan: 47:43

But yet in the supplement space, everybody can say the exact same thing that I say, and yet that's the frustration. That's the problem. How do we differentiate our technology from all the other crap that's out there? Are there companies selling gummies and chews that completely shut down nitric oxide production? Number one you can't deliver nitric oxide in a sugar matrix. Sugars are toxin. It's a poison. Glycates enzymes disrupts the oral microbiome. So stay away from chews or gummies.

Nathan S. Bryan: 48:10

And then most beetroot powders on the market don't do anything but turn your pee in your poop pink and red and cause a lot of anxiety. They do nothing to nitric oxide production. But yet there are hundreds of beet products on the market. So that's where consumers there's confusion and consumer hell. I'm confused and I've been doing this for 25 years. But these companies out there they have nobody who's ever published a single paper in the nitric oxide field. They're just trying to capitalize on this growing awareness around nitric oxide and trying to make money. My objective is not to make money. My objective is to understand the science to the extent that we can make safe and effective nitric oxide products so that patients get better. That's the objective.

Dr. Philip Ovadia: 48:52

And one of the key things that you said there, because people will be thinking early in the conversation how you were talking about the short lifespan of nitric oxide molecules within our body. So even if you are directly supplementing nitric oxide, it's all going to be gone in seconds or minutes. So one of the things that you've been able to do is then not only give nitric oxide directly, essentially, but help the body to then be able to better produce nitric oxide on sort of an ongoing basis.

Nathan S. Bryan: 49:35

Yeah, and the other thing, that's not apparent in the technology what we do. But we haven't suddenly changed the physical chemistry of nitric oxide. We haven't changed nitric oxide's biological half-life from two milliseconds and extended that. But what we have done is we understand when nitric oxide produce, where does it go, what does it become, and so we help the body do that.

Nathan S. Bryan: 49:57

So you'll notice, in our skin care products, in any of our products, we put some electron donors in there, primarily in the form of sulfur donors. So when nitric oxide bounced to cysteine, residues from proteins or amino acids like glutathione, now you've extended the biological half-life, the vasoactive half-life of nitric oxide from two milliseconds out to tens of minutes and hours. So we promote this endocrine or hormone function of nitric oxide by giving the body these substrates that nitric oxide can bind to that now it can be circulated and transported throughout the body and it's vasoactive for hours. So that nitric oxide that we're releasing in the oral cavity over that five minutes from the lozenge has a physiological half-life of six to eight hours. That's the magic and that's what we do, that nobody else does.

Jack Heald: 50:51

Can I ask about the skin care? Given the experiment that I'm running right now, I want to understand more about what's happening with the skin care product.

Nathan S. Bryan: 51:09

I never intended to be in skin care and beauty. In fact, it was never my intent to be in the dietary supplement business. I'm trained as a drug discovery biochemist and my objective and mission was to develop safe and effective drug therapy so we could change the world and change the trajectory of chronic disease. But once we figured out how to make nitric oxide, the first question was what else can we do? What other applications are there? And this occurred to me back in 2014 with my dad.

Nathan S. Bryan: 51:38

My dad's a paraplegic from a car accident in 1984. Dad will turn 76 years old next year, so he spent more than half his life in a wheelchair. As you guys know, paraplegic diabetic patients are prone to decubitus ulcers, so dad developed a number of decubitus ulcers. I've been treating these wounds since I was 10, 12 years old, and so dad developed a non-healing decubitus ulcer, a right-issue ulcer on his right butt cheek. He developed osteomyelitis, he was put in the hospital, he was septic and almost died from it, and so once he recovered from the infection, I started taking him to some wound care docs and they said you'll never heal this wound because number one, his age, he's paraplegic and he's diabetic, and these are non-healing wounds. These wounds just won't heal. Well, I refused to accept that, and so I started making a nitric oxide releasing gauze that I would change every day, twice a day a wet to dry wound care change. And when I put this nitric oxide releasing gauze in there, not only did we kill the infection, we got tissue granulation, we re-grew tissue and then we finished it off with a surgical flak. And we did that in eight months. So a four-year-old non-healing wound we completely healed with topical nitric oxide in eight months on a 70-year-old paraplegic diabetic patient, when all odds were against us. So then all the wound care docs were like holy shit, what did you do? How do we get access to this? And that's the reason I brought this topical nitric oxide to market and we're developing it as a drug currently, as we speak, specifically for non-healing diabetic ulcers.

Nathan S. Bryan: 53:23

But in the meantime, we know that the skin is an organ just like the sex organs, just like the heart of the brain, and if that organ doesn't get enough blood supply, what happens? Well, it fails, just like the sex organs would fail or the heart would fail. And failing skin, you lose hydration, you lose collagen deposition, fine lines and wrinkles appear, age spots and your skin sags. So we thought, if we could apply nitric oxide topically and restore blood flow to that organ, we improve hydration, improve collagen deposition, decrease the inflammation, mobilize stem cells so we can actually turn, slough off the old cells, build new cells that work properly and improve the tone, texture and clarity of the skin. And today, five published clinical trials later, we do just that. The topical nitric oxide improves the tone, texture, clarity of the skin. We do biopsies, we improve collagen deposition, hydration, age spots disappear, acne scar remediation, wound care and we really haven't seen a wound that we haven't been able to heal on top of the nitric oxide.

Jack Heald: 54:26

And the mechanism is giving the body at that location the ability to help it, helping it to regain the ability to generate, or at least make use of nitric oxide.

Nathan S. Bryan: 54:46

nitric oxide yeah, we provide nitric oxide for that particular tissue. And let me tell you why this is important and why we thought about this. There's a famous quote I always quoted in my talks that research is to see what everyone else has seen, but think what no one else has thought. And in 2007, my group was the first to publish that nitric oxide was a hormone, and that was the proceedings National Academy of Science paper. So, just like any other hormone, like, let's take testosterone, which is the best practice known, right? So if men become low in testosterone, their testicles no longer produce testosterone, for whatever reason, right? So what do we do? We give intramuscular injections of testosterone, right? We don't have to inject it in the testes, right, true, right. So we just give a source of testosterone. Or you can do it in sublingual trochies, or you can do it in pellets with slow release. So when we discovered that nitric oxide is a hormone, then what do we got to do? Let's just give the body nitric oxide in any biological compartment. We can do it intramuscularly, we can do it intraorally, we can do it topically and then, once nitric oxide is produced, the endocrine of functions of nitric oxide then take hold and we restore systemically nitric oxide based signaling, similar to giving intramuscular injections of testosterone. You restore normal systemic testosterone signaling in production, so you tax-a-down-regulate testosterone production, but what we do is completely restore the body's ability to make nitric oxide. So nitric oxide is a hormone and we were the first and only people to discover that back in 2007. So we put this in the same camp as hormone replacement therapy.

Nathan S. Bryan: 56:28

You don't give precursors to testosterone for testosterone replacement therapy, because the reason they're testosterone deficient is because their body's lost the ability to produce it. The reason people are nitric oxide deficient is because their body's lost the ability to produce it. So it makes no sense to give precursors, substrates and hoping your body can convert it. You've got to give the actual hormone. That's what we do. We give nitric oxide gas. Nobody out there does it. I have a number of patents to protect this. That's what we do. That nobody else does. We've done it in skincare. We've done it in nutrition dietary supplements. We have removed the FDA for drug therapy.

Jack Heald: 57:05

I want to make sure I'm clear on. As I was doing a little bit of research on you and on the nitric oxide, a couple of questions occurred to me. When we lose the ability to produce nitric oxide, that is almost by definition, metabolic dysfunction. What I'm not clear on and you alluded to this in the stuff that I was reading is what causes us to lose it. You mentioned aging, and the question that occurred to me when I read this is is aging in fact just another way of saying we've lost the ability to produce nitric oxide? I'm clearly not a chemist. There were other reasons as well that we lose the ability. Maybe you addressed it, but it just didn't stick. No, I don't. I've lost the ability to memorize because I've lost my nitric oxide.

Nathan S. Bryan: 58:02

Now you make a very good point and I don't think we did address that. I think that's a very important fundamental question that we have to address. If we look at the age-related loss of nitric oxide production, we see on average about 10% to 12% decline per decade, starting in the late early 20s. By the time we're 40 or 50, we have 50%. 75-year-olds have 10% to 15% of the nitric oxide they had when we were younger. Now that we understand what leads to that, we can prevent it. I turned 50 a couple of weeks ago but I got a vascular age of a 34-year-old.

Nathan S. Bryan: 58:38

Now we know that it doesn't have to lead to this age-related decline in nitric oxide production. That is the Western lifestyle, is the standard American diet, it's sedentary lifestyle, it's highly processed junk food, high carbohydrates, lack of physical exercise that lead to a loss of nitric oxide production. How do we overcome that? If we can understand how we can overcome that, which we understand today, we can actually prevent age-related disease. We can't prevent chronological aging, but we can certainly delay biological aging and we call that longevity.

Nathan S. Bryan: 59:18

What we've learned is that the objective measures of aging are telomere length, telomeres at the ends of the chromosome, shorter telomeres, shorter lifespan, the ability to mobilize our own stem cells in the function of the mitochondria, the organelles in the cell that make energy. Well, about 10 years ago I put forth this theory that nitric oxide is the unified theory of aging, because nitric oxide controls and regulates telomere length, mobilization of stem cells in mitochondrial function. If you restore nitric oxide, you have longer telomeres, more mitochondria generating more energy more efficiently, and we actually mobilize our own stem cells so we can repair and replace dysfunctional cells. That's what you need to combat aging. It's really that simple.

Jack Heald: 1:00:02

I'm going to continue to reveal my ignorance. Can we actually lengthen the telomeres?

Nathan S. Bryan: 1:00:10

Well, there's two objectives. Here's what we know, here's what the science tells us. We can certainly prevent shortening.

Nathan S. Bryan: 1:00:16

That controls and regulates the expression, the nuclear expression and the activity of an enzyme called telomerase. As long as the cell has a functional telomerase enzyme, then telomeres don't get shorter with each cellular replication. As long as the cell can make nitric oxide can activate telomerase enzyme, you don't get shortening. What we don't know is have short telomeres, can we elongate them? I don't think that question's been answered. Here's what we do. We certainly prevent the shortening of telomeres. There's some things to be answered in that field. In terms of mitochondrial function, we certainly know that nitric oxide can induce mitochondrial biogenesis. You can increase the number of mitochondria per cell and you increase the efficiency of energy production by those mitochondria. We also know and understand and see this clinically that we can enhance stem cell mobilization to where we can repair and replace and completely resolve dysfunctional tissues. We published a paper in 2011 where we completely solved heart disease in a 15-year-old kid in five months by giving our nitric oxide lozzage.

Jack Heald: 1:01:28

Say that again. Your signal broke up. I understood it. I want to make sure that that is clear.

Nathan S. Bryan: 1:01:36

Yes, there's a rare genetic disorder called arginic succinic acid urein. We were investigating these patients at Texas Children's Hospital. We were following a 15-year-old pediatric patient with uncontrolled hypertension. Blood pressure was 200 over 110. He had severe heart disease, a heart twice the size of a normal 15-year-old. Left ventricular hypertrophy. He had kidney disease. He had pulmonary disease. He had systemic disease that couldn't be explained by his underlying genetic disorder. We completely resolved every single aspect about his clinical presentation with our nitric oxide lozzage. We normalized his blood pressure. We resolved his kidney disease within five days. We completely resolved his heart disease within five months. Within five months his heart was normal structure and function of a normal 15-year-old. We restored his neurocognitive ability. We improved his ability to think, recall, memory In fact he started beating his dad at chess A genetic and inborn air metabolism. We completely rescued his clinical phenotype with nitric oxide. We didn't change his underlying genetic disorder but we completely fixed his phenotype that resulted from his genetic deficiencies.

Jack Heald: 1:02:55

Bill, we got to connect Grace Price with Dr Brian if it hadn't already happened.

Jack Heald: 1:03:01

This is so cool. Our prior episode we interviewed an 18-year-old. She's clearly an extraordinary 18-year-old, but nevertheless 18. We need to have her brain and your brain rub cells together. That would just be extraordinary, bill. I could keep going, for I am absolutely fascinated, but I guess we're at the point where we say, okay, dr Brian, what people are going to hear this and go? I need to know more. I suspect there's multiple places that they can go to learn more, based on whatever it is they heard that got them excited. True.

Nathan S. Bryan: 1:03:49

Well, I like to think In various directions.

Nathan S. Bryan: 1:03:51

Yeah, I'm not here to sell you anything. I'm here to provide you quality education, awareness and information. The first place I send people is my educational website. It's drnathonesbrioncom. I've got my own YouTube channel. We'll post interviews like this, lectures, webinars. If you go to YouTube and just search Dr Nathan S Brian Nitrocoxide I've got my own channel. People interested in reading the medical literature you can find me on PubMed or Medline. I'm searchable by any search engine. Then, for those interested in product technology, again, I think our first approach is always diet, lifestyle. Stop doing the things that disrupt nitrocoxide production. Start doing the things that promote it. For those interested in our product technology, it's n101.com. That's the letter N, the number one, the letter O, number onecom, as in one oxygencom.

Jack Heald: 1:04:45

That's pretty simple.

Nathan S. Bryan: 1:04:48

All right. Okay, well, I've got blowing me up there on the slopes here in Telluride and I came off the mountain to visit with you guys. But I'm about to hit the slopes again.

Jack Heald: 1:04:59

That sounds fantastic Get back at it.

Dr. Philip Ovadia: 1:05:01

No, this was amazing. Thank you, exactly what I hoped for that we'd get into the science behind nitrocoxide and how that translates to clinical benefit. Thank you for all the work you're doing on that and look forward to hearing more and interacting more, for sure.

Nathan S. Bryan: 1:05:22

Thank you, Phil. Look, the basic science means nothing unless we have clinicians like you who really take this information and impart it on your patients and your patient practice. Again, this only works through the application and the translation of the science. It's people like you that will change the world and help us all change the world. Thanks very much.

Jack Heald: 1:05:43

Thanks so much, dr Nathan S Bryan. We'll make sure that all those contact vectors are listed in the show notes, phil, a fantastic one. Thanks, man. I'm looking forward to learning more myself.

Nathan S. Bryan: 1:06:00

Thank you, Phyllis.

Jack Heald: 1:06:02

All right For Dr Ovedia. Dr Bryan, this has been the Stay Off my Operating Table podcast. We'll talk to you next time.

Dr. Philip Ovadia: 1:06:10

Thank you.