[00:00:01] Speaker A: Welcome to Real Medicine, real lives. I'm Dr. Yasser Sambal, and together we're showing medical expertise in a human way.
Welcome to Real Medicine, Real Lives. I'm your host, Dr. Yasser Sombal. And today I want to take something that sounds highly scientific and bring it to real life. The phrase is nitric oxide. It may sound like something that belongs only in a research lab, but this molecule plays a powerful role in how blood moves, how vessels relax, how tissues heal, and how the body communicates with itself. And here's why this matters. When that system breaks down, the effects can be shown up in serious conditions. Heart disease, poor circulation, diabetic wounds, and even areas of the brain in health research.
My guest today, Dr. Nathan Bryan, an international leader in molecular medicine and nitric oxide biochemistry. He has spent more than 25 years studying nitric oxide, plus published more than 100 peer reviewed scientific articles, developed several patents, and is the founder and chairman of Bryan Therapeutics, Inc. A clinical stage biotechnology company developing nitric oxide based therapies. Dr. Bryan, welcome to the show.
[00:01:06] Speaker B: Thank you, Dr. Sambo.
[00:01:07] Speaker A: So today we're going to open the episode by making nitric oxide understandable for the viewers. You know, people may have never heard of it. This segment should establish why molecules matter and what is it that it does in the body and why losing nitric oxide function can affect healthy ways and patients may not expect.
So when I say the term nitric oxide and I'm probably just as confused today as I was 20 years ago in medical school about it. So I can only imagine the viewers, but why is when viewers hear that, they hear a chemistry term and not a health story? And how do you explain nitric oxide to patients in a way that they can understand it?
[00:01:44] Speaker B: Well, Dr. Sonwol, thanks for bringing this to the attention to the masses. You know, nitric oxide is a signaling molecule. It's a gas that's produced in the lining of the blood vessels and it causes blood vessels to dilate or relax. So when we make nitric oxide, our blood vessels become soft, compliant, they're responsive. So we can get blood flow to every organ, tissue and cell in the body. It regulates blood pressure, it mobilizes stem cells and it activates our mitochondria. So everything we know about cardiovascular health, longevity, disease prevention is dependent upon the body's ability to produce nitric oxide gas.
[00:02:14] Speaker A: And so, you know, I mean, I remember all of that. And so when people think of nitric oxide and you want to break it down to them in simple terms, for example, you know, so that they understand it. Because most people don't come in and say, you know, well, my nitric oxide isn't working right?
[00:02:30] Speaker B: Not yet.
[00:02:30] Speaker A: Yeah. So, you know, when you want to break it down for them, how do you break it down in a simple fashion for somebody like me, for example, as a physician who, you know, I do more clinical side, more than research based side, but how do I break that down to them in a simpler fashion?
[00:02:45] Speaker B: Well, it's a signaling molecule. You know, cells in the body have to communicate with one another, and nitric oxide is a signaling molecule. In fact, a Nobel prize was awarded in 1998 for its discovery as a signaling molecule in the cardiovascular system. But it regulates blood flow, it regulates oxygen delivery, it regulates how the body utilizes oxygen to make cellular energy.
It improves exercise performance, it dilates blood vessels for sexual performance, for cognitive and executive function.
So it's what we call a foundational longevity, human optimization molecule.
[00:03:14] Speaker A: And so, you know, some of the things you described a little bit of, if you can elaborate a little bit more, what does nitric oxide do inside the body that makes it so essential?
[00:03:22] Speaker B: Well, it regulates blood flow and circulation. It mobilizes our own stem cells. So when we have more stem cells in circulation, we can repair and replace dysfunctional cells. It prevents the ends of our chromosomes from getting shorter, the telomeres. So telomerase activates an enzyme called telomerase. So it basically allows us to live a longer, better, healthier life free of disease. The challenge is, you know, it's not part of the clinical conversation between patient and physician. And we're hoping to change that, but we have to start looking at symptoms that arise as a result of loss of nitric oxide production.
[00:03:53] Speaker A: And so now that you brought up symptoms. So nitric oxide is clearly very important for the body. You know, does a lot of things, whether it's blood flow regulation, etc.
Involved with DNA, et cetera and so forth. So, you know, what, what kind of symptoms do people, for example, can experience that are related to nitric oxide? Not working correctly.
[00:04:14] Speaker B: Well, we've learned a lot over the past 40 years. So we're finding that the first sign and symptom that manifest as a result of loss of nitric oxide is erectile dysfunction. Because if you lose the ability to dilate the blood vessels, the sex organs, you don't get engorgement and you get an erection that occurs in both men and women. Number two, your blood pressure goes up. Because if you lose the main vasodilatory molecule, then your Blood vessels become stiff and rigid, and so your pressure goes up. Two out of three Americans have an unsafe elevation of blood pressure. Number three, you start to develop insulin resistance, metabolic disease and diabetes.
Then you develop exercise intolerance. You can't sustain an exercise regimen because you can't dilate the blood vessels to perfuse the heart or the skeletal muscles. And then fifthly, if all of those occur and you don't correct it, you start to get mild cognitive impairment, dementia, and eventually Alzheimer's, which we're finding is an end stage of nitric oxide deficiency.
[00:05:05] Speaker A: And so, you know, kind of like, you know, you're driving your car, you get the signal, your oil needs to be changed, et cetera.
We can attribute a lot of diseases, you know, if somebody comes to me. So how did I get heart disease? Well, I can say, well, there's a genetic component, a cholesterol component, risk factors such as diabetes, you know, all this kind of stuff. So what are some of the risk factors that lead to somebody having a nitric oxide deficiency that causes these problems?
[00:05:30] Speaker B: Well, first we had to understand, how does the human body make nitric oxide? Once we understood that, then we could start to implicate things that are disrupting the natural production. So it's the standard risk factors. It's a sedentary lifestyle, it's poor diet, it's use of antiseptics like mouthwash, fluoride, toothpaste, because we've discovered there's a bacterial component to nitric oxide production, specifically oral bacteria. So fluoride eradicates good, bad bacteria. Antiseptic, mouthwash. We're finding drug therapy like proton pump inhibitors. Those drugs completely shut down nitric oxide production. And now we're finding in clinical observations, there's about a 40% higher incidence of heart attack, stroke and Alzheimer's in patients who have been on PPIs for the past three to five years.
[00:06:13] Speaker A: Yeah, I actually remember that data. When I was in fellowship, there was a lot of data about patients who take proton pump inhibitors, who people have had PCI or coronary interventions, and how it increased the risk of stent thrombosis, et cetera.
And I remember that data coming out and there was this big hype about not putting people that had a coronary Zealand like omeprazole, but they need to be on Protonix. And somehow there was all this switching everybody and it was a big mess. I remember that.
[00:06:43] Speaker B: Well, the data are very clear now. I mean, just looking at the clinical end points and looking at really data or mining extremely Large data fields and patients. It's very clear.
[00:06:53] Speaker A: And so you kind of can you. You know, I tell people all the time when they ask me about their heart disease, I always say your heart is kind of like your house. It has architecture, plumbing and electricity.
[00:07:05] Speaker B: That's right.
[00:07:05] Speaker A: And they're all kind of intertwined. So when people have heart failure, it's an architecture problem, but that may be due to a plumbing issue, meaning they have blockages, or they can have an electrical problem that caused their heart to be on overdrive, like afib that was unnoticed, for example.
[00:07:18] Speaker B: Right.
[00:07:19] Speaker A: How could you put nitric oxide in that context? So it makes it simple for people to say, I get it. You know, it's like the ship that does whatever, or, you know what I mean? Just something in layman's terms so they understand it.
[00:07:31] Speaker B: Well, nitric oxide affects everything about the house, the plumbing and the electricity. So when we start to exercise, for example, we have to dilate the coronary arteries to increase blood flow and oxygen delivery to the heart to meet the increased metabolic demands of the heart. And so nitric oxide is what dilates the blood vessels. So what we found is that loss of nitric oxide production in the lining of the blood vessel we call the endothelium precedes the structural changes by many years, sometimes decades. So if you have stenosis of the coronary arteries, you've got obstructive coronary disease. That tells us you've been nitric oxide deficient for many, many years. So that's one, it's affecting the vasodilation of the coronary arteries. And then, number two, we have to deliver things like calcium, magnesium, and get oxygen into the individual cardiomyocytes to elicit that electrical potential. So if you have ischemic heart disease, providing the AV node or the SA node, then it's going to cause an electrical issue. So everything we know about contractility, electrical physiology of the heart is dependent upon adequate delivery of oxygen nutrients to every cell in the body. And that's dictated by the production of nitric oxide.
[00:08:37] Speaker A: And so I would assume nitric oxide is. Is it something that develops suddenly? Is it something that gradually develops over time? And how much time, on average, should people, you know, it takes for them to develop a nitric oxide deficiency?
[00:08:51] Speaker B: It's a good question. And the clinical data are very clear. We lose about 10 to 12% of our nitric oxide production per decade. And that's looking at endothelial function, the production of nitric oxide in the lining of the blood vessels. But you can accelerate that or decelerate it depending upon diet, lifestyle, other things. But really what we're finding is by the time we're 40 or 50 years old, we've lost about 50% of the nitric oxide we had when we were younger. And it's not coincidentally, that's the age that most people feel the effects of aging, they don't perform as well as they did in the bedroom, the boardroom, or on the athletic field.
[00:09:23] Speaker A: And is there. So about 50% is where people should start to feel symptomatic.
[00:09:28] Speaker B: Usually that's the case because 50% of the men over the age of 40 self reported erectile dysfunction.
You know, two out of three Americans have an unsafe elevation in blood pressure that gets worse the older we get. So this is a stepwise progression of a gradual loss of nitric oxide production.
[00:09:43] Speaker A: And is there a simple lab test people can get to see what's my nitric oxide level or am I deficient or et cetera? Is that something that's commonly used in practice?
[00:09:54] Speaker B: It's not, unfortunately. And nitric oxide is a gas, and once it's produced, it's gone in less than a second. So we can't capture it in peripheral blood like we can cholesterol or vitamin D or other important metabolites. So we have to rely on symptoms. Then you start to query the patient on what's their diet, what's their lifestyle, are they using fluoride toothpaste, are they using antiseptic mouthwash, are they on proton pump inhibitors? And then start to eliminate the things that are disrupting nitric oxide production, start doing the things that activate and stimulate it. And that's really the first line of defense in preventing the loss of nitric oxide production.
[00:10:25] Speaker A: Great. And just briefly, if you can, tell us, so after 25 years in this field, what convinced you that nitric oxide deserves this kind of level of attention?
[00:10:33] Speaker B: Well, number one, a Nobel Prize in 1998 was really a hallmark discovery, and really only life changing discoveries are awarded a Nobel Prize. But two, the clinical translation of the basic science, which has been really slow over the past 30 years, we're starting to see this implement into critical care. You know, drugs like nitroglycerin, which have been used for more than 100 years for the treatment of acute angina work because they release nitric oxide. And so we're starting to see, and as we develop our drug therapy, we're starting to see, you know, amelioration of ischemic heart disease, not only stopping the progression, but actually Reversing the disease and then looking at the effects of nitric oxide in Alzheimer's and not only stopping the progression, but reversing the disease.
[00:11:11] Speaker A: Gotcha. Well, this has been such an important foundation because it reminds us that real medicine often starts with understanding the body's basic signals. When those signals work, healing is possible. When they fail, disease can begin long before the symptoms feel obvious.
So we're gonna take a quick break and when we come back, we're gonna continue this discussion with Dr. Brian about nitric oxide and how it affects the body.
Stick with us. We'll be right back with more real stories, real breakthroughs and real lives transformed.
And we're back. I'm Dr. Yasser Sombol. Let's dive right back into today's medical conversation.
Welcome back, everybody, to Real Medicine, Real Lives. Stay connected to the show and every NOW Media TV favorite live or on demand, anytime you like, Download the free Now Media TV app on Ruko or iOS and unlock non stop bilingual programming in English and Spanish on the move. Catch the podcast
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welcome back. We're going to be talking continue this discussion with Dr. Nathan Bryan, Founder and Chairman of CEO Bryan Therapeutics.
Founder, Chairman and CEO of Bryan Therapeutics. And we're talking about the nitric oxide, one of the body's most important signaling molecules. In this part of the conversation, I want to connect the science to something every viewer understands, the heart, the blood vessels and circulation.
Because when blood flow is compromised, the entire body feels the consequences.
So this segment should turn nitric oxide into a visual practical concept. I want to compare the cardiovascular system to an internal highway or plumbing system where the nitric oxide helps keep vessels flexible, responsive and able to deliver oxygen and nutrients. Dr. Bryan, welcome back.
[00:12:59] Speaker B: Thank you, Dr. Sumbal.
[00:13:00] Speaker A: So I'd like to start out by explaining the body with simple images. So if the cardiovascular system is the body's highway system, what role does nitric oxide play on that highway?
[00:13:11] Speaker B: Well, it eliminates the traffic jams. So we've got 60,000 miles of blood vessels. We took all the blood vessels in the body and put them end to end. And so if we're going to deliver cargo, oxygen and nutrients to every cell, then we've got to have an open highway. And so similar to if we order stuff on Amazon, we get the order, it can be on the truck. But if there's a traffic jam, you're not going to get delivery of the cargo. And that's the role of nitric oxide in the blood vessels so it can take this traffic jam and go from a one lane highway to four lane highways to get better and efficient, more efficient delivery of oxygen and nutrients to every organ, tissue and cell in the body.
[00:13:46] Speaker A: Yeah. And so maybe you can give the viewers an idea of why is it that this relaxation of blood vessels that you talked about in the previous segment is such a big deal for heart health?
[00:13:58] Speaker B: Well, we have to regulate blood flow. And you know, as a cardiologist, if we're going to increase the demands on the heart, we've got to increase blood supply to the heart. And similar, if we're going to recall memory or lift weights or run, we've got to increase blood flow to the skeletal muscle, or after a meal, we've got to increase blood flow to the digestive system.
But it's all about regulation of blood flow. And so nitric oxide, when it's produced, can dilate the blood vessels. So now we get specific increase in blood flow to certain regions and then we typically shut down or reduce blood flow to other regions. And so if we lose the regulation of blood flow, we can no longer regulate blood flow to the heart, we can no longer regulate blood flow to the brain or even the sex organs for sexual activity. So it's all about regulation of blood flow. And that's the primary role of nitric oxide.
[00:14:43] Speaker A: And so what does poor nitric oxide production mean for circulation over time?
[00:14:50] Speaker B: Well, so nitric oxide is what we call a vasodilator. So when it's produced, it opens up the blood vessels. When we lose the ability to produce that, the blood vessels become stiff and rigid. Then you start to get the plaque deposition, the plaque, the lipid formation, and then over time, you get plaque, that plaque becomes unstable and that plaque ruptures. And, you know, as a cardiologist, that's what we call a heart attack or myocardial infarction or an ischemic stroke.
So nitric oxide is what regulates all that. It's not just the function of the blood vessels, but the structure of the blood vessels makes them soft and compliant. So with each beat of the heart, that pulse wave is dampened by soft, compliant blood vessels.
So as we steadily lose the ability to make nitric oxide, we develop high blood pressure, which is the number one driver of cardiovascular disease, the number one killer. The blood vessels become damaged with each beat of the heart because there's a lot of shear stress occurring. And then you get inflammation, oxidative stress and immune dysfunction. And those are the drivers of chronic disease, including cardiovascular disease.
[00:15:44] Speaker A: So to make a simple analogy, I'm wondering if you would agree with me or not, and maybe you can make this even better. But I would say what you're saying is when you lose nitric oxide, it's like you're hitting a brick wall to a certain extent. Right. So the blood flow is hitting a brick wall because it's finding a poor channel to pass through.
And so every time it gets there, there's more stress on it. And that stress causes the wall to kind of slowly break down over time.
[00:16:08] Speaker B: That's right.
[00:16:08] Speaker A: Does that make sense?
[00:16:09] Speaker B: Yeah, perfect sense. And it also makes the heart pump harder, have to work harder, because you're pushing the same volume of blood against higher pressure. And then you develop an enlarged heart and cardiomyopathies and ischemic heart disease. So everything we know about heart disease and cardiovascular disease can be traced back to a loss of nitric oxide production.
[00:16:28] Speaker A: Yeah. And, you know, that's a great, great thing you said because I tell my patients all the time, you know, people that especially that develop heart failure and they wonder, well, how is my heart function normal, but I can develop heart failure, you know, a thing called diastolic heart failure, what we call normal heart failure, normal function heart failure. And I give them that exact analogy. And it's really of, you know, your heart muscle just gets stiffer over time as we age. And I don't, I don't necessarily introduce the nitric oxide concept, but that's what happens. It's part of the normal aging process. And so as it gets stiffer, that muscle loses its relaxation ability and that, you know, the heart is kind of like a balloon. It should expand to let blood in and it's just squeezed to let blood out. And so when it loses that, it's unfortunately got to just fill as much as it can. And the circulatory system, you know, if people are aware of it, it's a one directional system. It's really a one directional valve. And so when it can't go forward, it has to go somewhere. So it goes backwards and that backwards goes into your lungs and into your belly and into your legs and so forth. And so, I mean, I think this is really, really important for people to understand because that's kind of how it works. And so how does aging affect the body's ability of nitric oxide? I mean, let's just say somebody's ultimately healthy. They don't have high blood pressure, they don't have diabetes, they don't have, you know, they're not unfit they're not obese, but most likely they probably have some lower nitric oxide production. So how does the body itself stop making nitric oxide?
[00:17:55] Speaker B: Well, again, we have to focus on the function of the enzyme. We have to understand how that enzyme works, the lining of the blood vessels, what leads to a loss of its function, function loss of nitric oxide production. And what we're finding is there is this age related decline. But I think more importantly we figured out that there doesn't have to be an age related decline. And I do a lot of testing on myself, so I'm 52 chronologically, but I've got the vascular age of a 29 year old. And we can do this through advanced diagnostic aging. We can look at endothelial function and what's called flow mediated dilatation.
And then there's other people, as you probably see 24, 25 year old kids that have the vascular age of a 50, 60 year old. So we can shift this curve to the left or to the right. But what we're starting to understand is you don't have to lose nitric oxide production as you get older. And I think that's the holy grail in medicine is how do we prevent the loss of this critical molecule and prevent age related disease.
And that's what everything we're finding around nitric oxide is. Let's focus on things that are disrupting the natural production and then let's start doing the things that activate, stimulate, maintain normal enzymatic production.
Then we can maintain optimum nitric oxide levels into our 60s, 70s, even 80s.
[00:19:00] Speaker A: So you mentioned younger people. And you know, sometimes I've taken care of younger people that have had heart attacks in the 30s and 40s.
And they always ask me, you know, how did I get this? You know, I don't smoke, I don't whatever. And I say, well, you know, you probably just have a genetic predisposition to it. Is there is part of nitric oxide, for example, in the younger population? Because as you said, the older population, I can, I think people can comprehend and that comprehension comes from just aging risk factors, they develop over time, etc. But in the younger population, is that more of a genetic problem? Is that a lifestyle problem or is it a combination of both?
[00:19:37] Speaker B: I think it's the genes and the environment. Right? You can't blame your disease on genes unless you're born with an inborn air metabolism. And you know, our lifestyle affects the genes. We know how to turn genes on and turn genes off through what we call epigenetic. Regulation.
But certainly there's a genetic component. If you have what's called a single nucleotide polymorphism in the gene that makes nitric oxide, then that's a problem. The methyltetrahydrofolate reductase, or mthfr, leads to a nitric oxide deficiency. But I think it's a combination of diet and lifestyle and genetics that rapidly progress this disease, where you see heart attacks in younger people. But I think what we're finding, it's mostly diet and lifestyle. The science is complex, but I think the solution is very simple. It goes back to what cardiology has been taught for more than 100 years. It's a good diet in moderation, moderate physical exercise, and avoiding things that we know cause heart disease.
[00:20:27] Speaker A: So, you know, it's going to be. My next question is if you can elaborate just a little bit on the connection between nicotoxide production and diet and lifestyle modification and how that two correlate.
[00:20:40] Speaker B: Yeah, certainly. So we know what causes cardiovascular. It's a poor diet and sedentary lifestyle. So things like a high glycemic index diet, high sugar, high simple carbohydrate. So anything that leads to an increase in blood sugar, you know, sugar's sticky, it sticks to proteins, it sticks to hemoglobin. We measure that as hemoglobin A1C. But it sticks to other proteins and enzymes and basically renders them dysfunctional.
And then, you know, so a high antioxidant diet. So if we eliminate sugar, throw in some more green leafy vegetables, a balanced diet in moderation. You know, we're overfed in America and most industrialized nations. And so all of that points back to a loss of nitric oxide production, not only at the level of the enzyme, but even in the oral bacteria. Because a high sugar, high carbohydrate diet completely changes the oral microbiome, leads to an acidic saliva, causes oral dysbiosis. And we know there's a clear link between oral hygiene and the risk of cardiovascular disease.
[00:21:35] Speaker A: And so if you were to tell the viewers, what's somebody with family history, risk factors, what is the practical takeaway from this science that you would tell them?
[00:21:45] Speaker B: Well, pay attention to nitric oxide. It may be the missing link in the cause of your disease, but it may provide the solution to poorly managed chronic disease. But, you know, the data is very clear. If you're using mouthwash, you must stop. We've got to support the oral microbiome, not destroy it.
More judicious use of antibiotics, get rid of fluoride in your toothpaste and then, you know, eliminate simple carbs and sugars, anything that leads to an increase in blood sugar, eliminate. So if we stop doing the things that disrupt nitric oxide production now, we release the brakes on the body's ability to make it. And then we have to move 20, 30 minutes of exercise every day, 2030 minutes of direct sunlight a day, nasal breathing as opposed to mouth breathing.
And those things have been clinically proven to enhance nitric oxide production and overcome these deficiencies.
[00:22:31] Speaker A: Gotcha. Well, so what I'm hearing is that circulation is not just about whether blood is moving. It is about whether the body has the right signals to move the blood. Well, that shift in understanding can change how we think about prevention, aging and long term health.
So as we come to the next this break, we're going to come back more and talk to Dr. Brian about nitric oxide and about how it affects circulation and link it to brain disease, things such as Alzheimer's. Stay with us. We'll be right back.
Stick with us. We'll be right back with more real stories, real breakthroughs and real lives transformed.
And we're back. I'm Dr. Yasser Sombol. Let's dive right back into today's MEDICAL conversation.
Welcome back, Everybody, to real medicine, real lives. I'm Dr. Yasser Sombol and we're continuing our conversation with the Dr. Nathan Bryant, who works with nitric oxide research and is now being applied to some of those challenging areas in medicine, including heart disease, Alzheimer's disease, diabetic ulcers and non healing wounds. This is where the conversation becomes bigger than one molecule. It becomes a conversation about systems, how the heart, blood vessels, brain and tissues are all connected.
This segment, we want to expand the medical relevance of nitric oxide beyond cardiovascular health.
The key narrative is that many diseases are not isolated to the organ to one organ.
Blood flow, inflammation, cellular signaling, tissue repair and vascular function may all be connected.
Dr. Bryan, welcome back.
[00:24:04] Speaker B: Thanks, Dr. Sumbo.
[00:24:05] Speaker A: This has really been a fascinating conversation. And so, you know, obviously as a cardiologist, blood flow, all that kind of stuff is something that really appeals to me. And so your company has been working on across heart disease, Alzheimer's disease, diabetic ulcers, non healing wounds. So what really connects those areas scientifically?
[00:24:23] Speaker B: Well, it's the blood vessels and it's nitric oxide because every organ, tissue and cell in the body is dependent upon adequate blood flow and circulation, which is dependent upon nitric oxide production. So disease manifests differently in different people. Some People, nitric oxide deficiency manifest early on as heart disease or heart attack and stroke, or it's erectile dysfunction or now we're finding a clear connection between mild cognitive impairment and the progression to vascular dementia and then eventually Alzheimer's disease.
[00:24:50] Speaker A: And so when people think about Alzheimer's, they usually think just about somebody losing their memory.
So how do you connect blood flow in Alzheimer's disease and vascular health?
[00:25:02] Speaker B: Well, when we need to recall memory, we've got to increase blood flow, specifically the prefrontal cortex, to get those neurons to recall information that was stored long ago. And without adequate blood supply, there's no memory recall. And this has been imaged through SPECT scans or functional MRI showing that in patients with brain fog, mild cognitive impairment, dementia and Alzheimer's, there's a progression of a loss of perfusion to the brain called focal ischemia or no blood flow. And then what happens is you start to lose your memory. But not only is Alzheimer's a vascular disease, now it's recognized as a metabolic disease. In fact, in some circles it's been called diabetes type 3. So we get insulin resistance in the brain.
So Alzheimer's is a vascular, metabolic disease characterized by decreased production of nitric oxide. In 2011, we published a paper showing that nitric oxide is required for insulin signaling and to get glucose into the cell. So with adequate nitric oxide, we're going to dilate the blood vessels, we're going to fuse all regions of the brain. We're going to get glucose into the cell so those neurons and cells can do their job. Without nitric oxide, you don't get dilation, you get hypoperfusion and you get insulin resistance. And then when the cells don't get oxygen nutrients they need, you get misfolding of proteins that eventually show up as amyloid plaque and tau tangles. Diagnostic for Alzheimer's.
[00:26:17] Speaker A: And it's interesting about this memory thing. And so have they ever looked at it in normal people? Let's say with the age correlation with people that have Alzheimer's. So a 50 year old that has Alzheimer's versus one that doesn't. And some people say I just have a really hard time remembering things. And do those nitric oxide levels correlate in both of those patients? I mean, is it. Or, you know, for example, if I said I can't really memorize it, I'm really good at analyzing stuff, but I can't memorize things. Right. I mean, us in medicine, we're really good at memorizing, and that's how we get to that point. Whereas engineers are really analytical. And it's why I sucked at physics in college, right, Because I'm not very analytical to a certain extent.
But do you correlate nitric oxide in that situation as well? Does that make a difference?
[00:27:00] Speaker B: No, it does. In fact, you can trace the course of disease and the progression of disease just by looking at cerebral blood flow and through SPECT scans and looking at how well profuse certain regions of the brains are. So it doesn't matter if it's a 50 year old with dementia or a 90 year old with dementia. The clinical picture is the same. There's loss of regulation of blood flow and there's insulin resistance in the brain and you get misfolding of proteins. So it can all be correlated back. And I think that's where Alzheimer's drug companies have missed the mark. They're developing drug therapy against the plaques, against the tau tangles, the amyloids, and that's the consequence of the disease, it's not the cause of disease. So developing drug therapy for the consequence of disease obviously will not and does not have an effect.
[00:27:40] Speaker A: And since you brought that up, I'm interested to hear your thoughts. So you said nitric oxide is a gas. We can't really measure it, we can't really quantify it by a blood test or what not. How do you develop a drug that increases nitric oxide production?
[00:27:56] Speaker B: That's been the challenge really for big pharma for the past 30 or 40 years. So in order to do that, number one, we had to understand how the human body makes it. And it's a gas. So once it's produced, where does it go, what does it become and how does it signal? Those were three fundamental questions I spent 25 years answering. So what we do is, and then understand, how do we fix the nitric oxide problem? How do we restore the function of the enzyme? How do we restore the oral microbiome to allow this continuous production, nitric oxide. So our philosophy is, if your body can't make nitric oxide, then we provide it for you.
So my company, we make a solid dose form of nitric oxide gas, and we do this in the form of what's called an odt, an orally disintegrating tablet. So you put this product in your mouth, it slowly dissolves and it releases therapeutic amounts of nitric oxide gas, in fact, 20 to 30 parts per million, the amounts that it gives to premature babies with pulmonary hypertension.
So my target was if that dose of nitric oxide is safe in the most Vulnerable high risk population in the world, premature babies, then it's safe for the average adult. And so it's vasoactive. We know that when we put the lozenge in your mouth, it dilates blood vessels. We can look at ultrasound of the carotid. We can look, expect scans after a certain treatment time, increased blood flow, increased glucose uptake. And so it's addressing the root cause of nitric oxide deficiency. But more importantly, you don't get what's called tolerance or tachyphylaxis, which is common in a lot of drug therapies. We actually enhance the body's ability to make this naturally over time.
[00:29:21] Speaker A: And so since you said you have a disintegrating tablet that you guys have tested, etc.
Has it been correlated with any other than nitric oxide levels, which increases, obviously. Has there been any clinical correlation with it to, for example, regression of Alzheimer's, improvement of cardiovascular health, et cetera? And has that been tested, you know, in a trial, whether a randomized trial or whatever, clinically, somehow we have.
[00:29:48] Speaker B: We've done a number, probably a dozen of randomized placebo controlled clinical trials. The gold standard in drug therapy. So what we're finding is it dilates the blood vessels so it can normalize blood pressure in hypertensive patients.
We had a pediatric patient at Texas children's hospital from 2011, paper we published so we could reverse his kidney disease. We reversed his heart disease and normalized his resistant hypertension when all drug therapy had failed.
We've done some early pilot studies in Alzheimer's. We can improve blood flow to the brain. We improve cognition when giving them cognitive exams, improve exercise performance.
What else?
A number of clinically meaningful endpoints that we've looked at in these randomized placebo controlled clinical trials. We lower triglycerides. In fact, I have a number of patents on methods of reducing triglycerides. We lower inflammation, 37% reduction in C reactive protein within 30 days, and issued patents on methods of reducing inflammation.
[00:30:41] Speaker A: So what is the reason this is not common therapy? You mentioned earlier, it's hard for big pharma to get this done and whatever. So what's the reason that hasn't become more mainstream and standard of care?
[00:30:56] Speaker B: I think there are a number of reasons. Number one, Western medicine, you don't treat what you don't measure, what you can't measure, right?
The problem is what counts can always be counted. And what counts, what's counted doesn't always count, Right? So it's hard for medicine to treat something when you can't measure a target or measure an end product. Cholesterol and vitamin D is easy. You get a number and you treat to a number nitric oxide. We're not afforded that luxury because it's not something we can measure in the blood.
And so because there's no diagnostics for nitric oxide deficiency or an official diagnosis and there's no official treatment or what's called standard of care if you have this condition. And then this is a potential treatment option, except for ischemic heart disease and nitroglycerin. But there's limitations to those drugs. But I think, I hope, and I think, well, I believe I'm past those levels of conviction that as we develop this more as drug therapy and get drugs approved through the FDA for specific conditions, the information is going so rapidly in the technology that we're going to be able to determine. We've got functional devices, we can measure endothelial function and nitric oxide production and then test, treat, test.
So test the patients, treat them, look at the effectiveness of therapy, and move the needle on clinically relevant biomarkers or end points.
[00:32:10] Speaker A: Are any of these treatments, other than in trials, being used or not yet?
[00:32:15] Speaker B: We've developed consumer products over the past 15 years. So I've had consumer products on the market, nitric oxide, dietary supplements, a skin care line of products, and an oral line of products now designed to enhance the body's production of nitric oxide. But these are consumer products not intended to treat, prevent or cure any disease. But I think it's important that consumers have access to these products based on sound science as we develop them through drug therapy.
[00:32:41] Speaker A: I think it's really interesting you brought up the point of, you know, it's not mainstream for other reasons because you can't measure it by blood testing. But you would think that outcomes or, or just proving that somebody's cognition got better, that has Alzheimer's, based on taking nitric oxide therapy, would be an outcome that doesn't necessarily have to be measured by a blood test. I mean, it's no different than medical devices, right? I mean, we put stents in people, but we don't measure a blood test to say the stent improved your life. We measure it by do they have recurrent heart attacks, do they come back for repeat revascularization, do you know, what's the overall composite mortality, et cetera. And none of those are blood tests per se. So I would think this could fall for something so important and clearly has a lot of benefit. You would think an outcome based on clinical findings rather than laboratory findings would be just as important to try to get this. I mean, I can't imagine the amount of people that would help just being able to do something like that, especially.
Yeah, I mean, it just makes sense to me. But unfortunately, this is the world we
[00:33:50] Speaker B: live in, so we're advancing that to the extent we're doing clinical trials. But, you know, in the real world, it takes about 10 years and $800 million to get a drug approved.
[00:33:58] Speaker A: So, yeah, we need to be more like Europe and Japan.
So this is the part of medicine that feels both complex and hopeful. And when we stop seeing the body as separate parts and start seeing it as connected systems, we can begin to ask better questions. And better questions can lead to better care.
So hang out. We'll be back with Dr. Brian to continue this conversation about nitric oxide.
Stick with us. We'll be right back with more real stories, real breakthroughs and real lives transformed.
And we're back. I'm Dr. Yasser Sombol. Let's dive right back into today's medical conversation.
Welcome back, everybody, to Real Medicine, Real Lives. You want to stay connected to the show and every other NOW Media TV favorite live or on demand anytime you like. Download the free Now Media TV app on Ruko or iOS or unlock nonstop bilingual programming in English and Spanish on the move. Catch the podcast
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welcome back, everybody. I'm Dr. Jetser Sombol. We're back with Dr. Nathan Bryan. And so I want to close the conversation today with an area that affects patients in very personal way, healing. For people living with diabetes, poor circulation, chronic wounds or non healing ulcers, the question is not theoretical. It is daily life. It is pain, risk, mobility independence, and sometimes the fear of losing a limb.
So this final segment should bring the episode of home of emotionally. The focus is wound healing, diabetic ulcers, patient impact, innovation, and what viewers can now do to better understand and protect their health. Dr. Bryan, welcome back.
[00:35:37] Speaker B: Thanks, Dr. Sombol.
[00:35:38] Speaker A: So wounds obviously are a really, really big deal. And as a cardiologist, I actually see, I don't necessarily treat wounds, but I see patients with wounds that may have vascular issues that, you know, we need to improve to help the wound heal. And so when a wound doesn't heal, give the viewers an idea of what is happening inside the body that's leading to that wound not being able to heal.
[00:36:03] Speaker B: It's what we call microvascular dysfunction. So the small blood vessels that are feeding that wound bed, you're not getting enough oxygen. So it's an ischemic wound bed, meaning there's not enough blood supply. Without adequate blood supply, you can't elicit an immune response and get tissue granulation.
So infections set in. Most non healing wounds are infected and there's no blood supply to that wound. And so all of that is a consequence of insufficient nitric oxide production.
[00:36:26] Speaker A: Mm, yeah. And so that could lead. Obviously we talked about this because it ties into poor circulation and so forth. And so that circulation is important to bring the important nutrients to that wound to heal. Correct. And so why are diabetic ulcers and non healing wounds so difficult to treat?
[00:36:44] Speaker B: Well, again, it goes back to all the comorbidities that lead to that non healing wound. It's an elevation in blood sugar, it's high hemoglobin A1C. It's poor circulation. So when it's compromised immune function. So it's been known for hundreds of years that, well, vascularized tissues are resistant to infections. Poorly vascularized tissues are prone to infections. If you can't get our immune cells to that site of infection, then those infections persist. It's isolated from our immune system and you can't heal a wound that's chronically infected.
The standard of care is always how do we treat the infection? And then unfortunately, we treat the wounds the same way we did 50 years ago.
Hyperbaric oxygen wound vac. But now, without any addressing of the root cause, what led to that non healing wound. And it's all about blood flow and circulation.
So when we're starting to develop a topical nitric oxide for wound care, nitric oxide does two things. It kills the infection.
And we've done studies on this. Pseudomonas, mrsa, all the known pathogens and non healing wounds. Nitric oxide kills the infection, but more importantly, it's opening up the capillaries, getting the blood flow to the wound. You get a hyperemic response, we mobilize stem cells and the wound heals itself.
[00:37:54] Speaker A: And is that actually in practical use now or is that something that's still under research?
[00:37:59] Speaker B: No, it's. So we're developing it through the fda, but we've got products on the market for the past seven or eight years. That's a topical nitric oxide. We position it as a beauty or skin care product.
All this came to to my realization back in 2014. My dad's a paraplegic from a car accident in 1984.
So dad was diabetic, paraplegic, developed a non healing osteonecrotic wound and almost died from it. And all the wound care docs I took him to said we'll never heal this wound. He was 64 years old at the time, diabetic, paraplegic, right? A c ul ulcer. And I just refused to accept that. And I knew that I could make nitric oxide so I started doing a wet to dry dressing every day, putting nitric oxide, releasing gauze in there.
Within six months we completely healed a four year old non healing wound. So that was remarkable, not only from my personal story and my dad, but the wound care docs that have been treating dad's wound couldn't believe what was happening. They'd never seen this before in clinical practice. So that was my impetus to we have to develop this as a drug therapy.
[00:38:55] Speaker A: And so do you ever go around? Because I've actually seen patients, for example, you know, the first notion is always, you know, get a Doppler, you know, ultrasound of their legs, see what the blood flows like, whether its arterial flow, whether it's venous flow and you know, see whether or not that's impacting any of the wound healing. And I've done angiograms on patients that have completely normal arterial flow to the leg. There's no blockages, everything looks great, but no matter what, their wound won't heal. And so have you, have you taken that and for example, gone around for wound centers and etc. And tried to get people to buy into this notion of using that to see whether or not, you know, you can get them to use it and the wounds can heal? Because I think that's a big problem in this country and you know, it's led to a lot of, you know, limb salvage, et cetera, amputations. I mean the amount of gangrene, etc. It only gets worse. And so I'm just curious, you know, how you've maybe tried to promote that for people in order to, you know, help with wound healing.
[00:39:54] Speaker B: Well, I think going back to the ultrasound or the Doppler, many times it's not the main conduit arteries there, it's microvascular dysfunction. So the main arteries, it's like in ischemic non obstructive coronary disease or anoka, their main blood vessels are completely open, but the microcircuit, they have microvascular dysfunction. So what we're finding is that we can see that. In fact, you can actually see the wound bed turn pink when you apply the topical nitric oxide because it's recruiting capillaries and Dilating blood vessels. You can actually see the wound bed turn a nice pink color, showing this hyperemic response and getting blood flow to it and it kills the infection. But yeah, we've, you know, I present a lot on my dad's case, personal case, and then we've had other wound care centers, you know, Yale Medical center up in Connecticut reproduce this non healing wound in a diabetic paraplegic ischial ulcer many times we've got other wound care centers all around the US really all around the world treating non healing wounds with this. But you know, it's not standard of care because the product isn't approved by the FDA yet. We're working through the FDA to get this approved as a topical drug.
But more importantly, I think the right to try and to use these consumer products to treat a non healing wound that's otherwise resistant to therapy.
[00:41:03] Speaker A: And so what should families know when they're caring for somebody with a chronic wound?
[00:41:08] Speaker B: Well, focus on the things that are disrupting nitric oxide production and causing the non healing wound. If they're diabetic, they got to manage their diabetes. You know, paraplegics and quadriplegics, they're sedentary by design. So you know, mobility is an issue. But I think we have to start asking the questions. Are they using fluoride toothpaste, are they using mouthwash? A lot of these patients are on chronic antibiotics that destroy the microbiome, disrupting nitric oxide production and then focus on that. And then what we're finding is and apply the nitric oxide product technology, we can improve blood flow, improve circulation, mobilize stem cells and lead to better response to the wound.
[00:41:46] Speaker A: Yeah, I mean, I think wound care is such a big deal in this country. And so, you know, what would nitric oxide innovation mean for patients who are at risk for infection, disability or amputation?
[00:41:58] Speaker B: Well, I think it's, hopefully we can get them before they're at risk for amputation. And you know, medicine unfortunately is a reactive practice. We have to change that to being proactive. So if we can start to recognize signs and symptoms that eventually lead to the gangrenous wounds and limb amputation and take steps early on in that process, then I think we can salvage a lot of limbs. But I think as we develop this drug therapy and get this in the hands of wound care centers, it's a huge issue because 65,000Americans die every year in nursing homes from wounds that get infected and develop sepsis. And to me that's totally unacceptable. But we Just have to be more aware of root cause. It's all about circulation, blood flow, immune function and all that's dependent upon the body's ability to produce nitric oxide. So as we start to educate and inform on this and hopefully develop it into clinical practice, I think it's going to change. It's a game changer in wound care. We've never seen a wound we haven't been able to heal with a topical nitric oxide.
[00:42:54] Speaker A: And so, you know, you've been in this field obviously for a long time, 25 years of experience, multiple publications, you've clearly done great work. And so where do you see this field going in the next five, 10 or 15 years?
[00:43:09] Speaker B: I truly believe. Well, I know nitric oxide is the future of medicine because what we know is every single age related chronic disease can be associated with a loss of nitric oxide production. So when we look at chronic disease kind of from a scientific standpoint, there's four things. There's low blood flow or compromised circulation, there's inflammation, oxidative stress and immune dysfunction.
And nitric oxide corrects all four of those.
So as we start to develop novel diagnostics and biomarkers and recognize patients of nitric oxide deficiency and then start drug therapy that restores and repletes nitric oxide production, it's a game changer. But we have to first make sure, number one, is it safe? Number two, is it efficacious? What dose do we need to treat a wound? What dose do we need to treat Alzheimer's versus heart disease versus diabetes? And that's really the mission of our drug company, is figuring out how do we safely and effectively deliver nitric oxide in a drug, in a dosage form that's best for that particular indication.
[00:44:05] Speaker A: And do you see that, for example, let's just take it for wound care alone. Do you see that something being maybe within the next five years available to people?
[00:44:16] Speaker B: I think in our drug study now for ischemic heart disease, I truly expect that we have nitric oxide based drug therapy approved on the market within the next two years. Our Alzheimer's, I think is going to be a little bit longer because we have to monitor these patients for longer times. This is a progressive disease. So I think within five to six years we'll have an Alzheimer's drug approved on the market. And probably within three to four years we should have a topical nitric oxide drug because it's remarkable the wound healing effects of nitric oxide topically. You don't need long term studies to do this. You see remarkable changes within 30 days.
[00:44:50] Speaker A: Great. So before we close this segment, I'd really like the viewers to be able to know how they can reach out to you, how they can get in touch with you. Maybe they have a wound that hasn't healed. And maybe they could be part of some of your research and see whether or not they can get their problem solved.
[00:45:06] Speaker B: I'm all about education and awareness.
I'd encourage you to subscribe to my YouTube channel. Dr. Nathan S. Bryan, Nitric oxide. I've published a book last year called the Secret of Nitric Bring the Science to Life where it explains what nitric oxide is, why you should be concerned with it, and these practical things we talked about to lead to enhanced nitric oxide production. You can follow me on Instagram @DrNathan S. Bryan same on LinkedIn. And for our consumer products, obviously these are, these are consumer products, not drugs. But it's n101.com. That's the letter n number one, letter o number one dot com.
[00:45:39] Speaker A: Some of those products you offer, those are for wound healing as well.
[00:45:42] Speaker B: These are consumer products. These aren't drugs. So these are dietary supplements, topical products, oral line of products. But these are. We haven't gone through the FDA for these. We're taking that same core technology that's in these consumer products and developing this drug therapy. The concept, the science is exactly the same. But drug therapy, dietary supplements are not drugs.
[00:46:01] Speaker A: Gotcha. Dr. Bryant, thank you so much for helping us understand the part of medicine is often invisible but incredibly important.
Today I learned that nitric oxide is not just a molecule, it's a signal. It is communication. It is circulation. It is repair. And for many patients, understanding that signal may open the door to better prevention, better treatment, and better hope. I'm Dr. Yasser Sambal, and this has been real medicine, real lives, because the best healthcare does not just heal the body, it restores hope.
See you next time.
