Scientist Explains The Powerful Role Of Nitric Oxide In Preventing Alzheimer's Disease And How To Protect Our Brains With Nathan Bryan, PhD

This episode explores the crucial role of nitric oxide in combating chronic diseases, particularly its preventive effects against Alzheimer's through maintaining vascular health.

1. Crucial Role of Nitric Oxide: Nitric oxide is vital for vascular health and preventing chronic diseases, including Alzheimer's.
2. Negative Impact of PPIs: Long-term use of proton pump inhibitors can severely disrupt nitric oxide production, leading to increased risks of chronic diseases.
3. Holistic Health Practices: Emphasizes the importance of managing diet, lifestyle, and medication to maintain nitric oxide levels.
4. Interdisciplinary Health Approach: Advocates for a collaborative approach between dentists and physicians to address chronic diseases stemming from oral health.
5. Awareness and Prevention: Highlights the need for increased awareness about the role of nitric oxide and the potential harms of commonly used medications like PPIs.

1: Introduction to Nitric Oxide

Dr. Bryan discusses nitric oxide's fundamental role in health and its mechanisms of action. Nathan Bryan: "Nitric oxide is considered the holy grail in preventing and reversing the underlying causes of chronic diseases."

2: Connection Between Nitric Oxide and Chronic Diseases

Explains how nitric oxide impacts various chronic diseases by improving vascular health. Nathan Bryan: "Loss of nitric oxide function is a precursor to many chronic diseases due to its role in vascular health."

3: The Dangers of Proton Pump Inhibitors

Discusses the widespread use of PPIs and their adverse effects on nitric oxide production and overall health. Nathan Bryan: "PPIs, while commonly prescribed, have long-term consequences that include increased risk of Alzheimer's and heart disease."

4: Practical Advice for Enhancing Nitric Oxide Levels

Offers practical tips for maintaining healthy nitric oxide levels, including dietary recommendations and lifestyle changes. Nathan Bryan: "Maintaining a diet low in processed foods and high in nitrate-rich vegetables can boost nitric oxide levels naturally."

• Incorporate Nitrate-Rich Foods: Include beets, garlic, and leafy greens in your diet to enhance nitric oxide levels.
• Avoid PPIs for Long-Term Use: Consult with healthcare providers on alternatives to long-term PPI use.
• Regular Exercise: Engage in physical activities that promote cardiovascular health and boost nitric oxide production.
• Monitor Oral Health: Avoid antiseptic mouthwashes that can disrupt the oral microbiome and decrease nitric oxide production.
• Educate Yourself on Medications: Be aware of the side effects of common medications like PPIs on your vascular and overall health.

This episode is brought to you by Cozy Earth, Fatty15, and Birch Living.

Cardiovascular disease still ranks as the leading cause of death for both men and women. Surprisingly, half of those affected show no symptoms before an event. Low levels of nitric oxide—a molecule that promotes vasodilation and smooth blood flow—could be primarily responsible. By recognizing the signs of deficiency, we can raise our levels and lower our risk.

Today on The Dhru Purohit Show, Dhru sits down for round two with Dr. Nathan Bryan to discuss why nitric oxide is the holy grail of molecules for long-term health. Dr. Bryan shares the four hallmarks of disease, the consequences of antacid overuse, and the correlation between lower nitric oxide and the risk of Alzheimer’s disease. Dr. Bryan also explains which lifestyle factors can hinder and boost nitric oxide production, how to test your levels, and symptoms that signal a deficiency.

Dr. Nathan Bryan is a renowned biomedical researcher known for his groundbreaking work on nitric oxide (NO) biology. Dr. Bryan's research has significantly advanced our understanding of NO's critical roles in cardiovascular health, immune function, and neurobiology. Beyond academia, he advocates for public health, translating his research into practical solutions for improving human health.

People

Nathan Bryan, Dhru Purohit

Companies

Leave blank if none.

Books

Leave blank if none.

Guest Name(s):

Nathan Bryan

Content Warnings:

None

Speaker A
Doctor Nathan Bryan remind our audience why nitric oxide is truly the holy grail when it comes to chronic disease and why we should care about this topic. Yeah, nitric oxide is considered really the holy grail because it's involved in everything we know about the onset and progression of cardiovascular disease, which remains the number one killer of men and women worldwide. So the functional loss of nitric oxide, the loss of nitric oxide in the lining of the blood vessels precedes the structural changes that we see in cardiovascular disease by many years, sometimes decades. So when you lose the ability to make nitric oxide, that sets the stage for the onset and progression of vascular disease. And as we know today, there's a vascular component to every disease, whether it's Alzheimer's, diabetes, autoimmune disease, liver disease, pulmonary disease.

Nathan Bryan
We have to maintain the normal structure function of the blood vessels, and that's the role of nitric oxide. You've shared before, and it's worth a recap. There's four hallmarks of disease. How do those play into our topic today? Well, if you look at any disease and, you know, medicine is practiced by specialists, right?

Cardiologists only deal with the heart, you know, pulmonologists, the lungs, and, you know, neurologists in the brain. But whether it's a neurological disease, whether it's pulmonary disease or coronary disease or heart disease, there's four common denominators. It's always low blood flow. We call that hypoxia or ischemia to that organ. And then there's inflammation, oxidative stress, and immune dysfunction.

So it doesn't matter what specialist you are or what type of medicine you practice. If you've got a sick patient, those are the hallmarks of their condition. And nitric oxide is what dilates the blood vessels, improves blood flow to the organ, it decreases inflammation, it prevents oxidative stress, and it basically prevents the immune dysfunction we see in chronic disease. So it is really the fundamental basis for the onset and progression of chronic disease. And let's go back to that word that you used in the beginning, the holy grail, right?

Speaker A
Really, like, extrapolate that further and connect the dots between nitric oxide and those four hallmarks just to make sure our audience really understands that. Yeah. So we look at, really, my job in academia. I was in academic medicine for 15 years. And so our job was to understand the mechanism of disease to where you could develop rational therapies.

Nathan Bryan
And so you can develop rational therapies unless you understand the root cause of disease. And so if you can figure that out, then it's certainly considered the holy grail. It's what everyone's looking for, right? For longevity, for lifespan, for health span. So when we talk about, you know, decreased blood flow to that particular organ.

So in patients with advanced coronary disease or cardiovascular disease, what happens is, over time, their coronary arteries, their blood vessels become narrow. And it's either because of chronic constriction and loss of vasodilation, or it's because you start to get plaque deposition. It occludes into the lumen of the blood vessel, and you get stenosis. And then over time, that plaque can become unstable and rupture, and that's a heart attack. If it happens in the coronary arteries or a stroke, if it happens in the cerebral arteries, nitric oxide actually dilates the blood vessels.

If you're chronically constricted, you can dilate the blood vessels and improve oxygen delivery, improve blood flow to that particular vascular bed. And then what happens when you lose the ability to make nitric oxide? You get an upregulation of what's called adhesion molecules in the lining of the blood vessel. And now monocytes, neutrophils, fats, start to stick. They migrate through the endothelium and start to develop that plaque.

So that's what we call vascular inflammation. And then once they transmigrate across the lining of the blood vessel, then you get the immune dysfunction and you get the oxidative stress. So everything that happens, consequently, to loss of nitric oxide is what leads to the onset of disease. So our whole focus is, if really the basis of chronic disease is the loss of nitric oxide, then how do we restore the function of nitric oxide? How do we restore the body's ability to make it?

Or how do we give nitric oxide in a therapeutic way? Because what we're finding is, if we do that, we can dilate the blood vessels, we decrease the adhesion molecules, so then we mitigate the inflammation, oxidative stress, and immune dysfunction. And there's evidence now that if we in patients that have advanced disease, coronary artery disease, atherosclerosis, we can actually reverse disease. We can regress that disease process. And so to me, I mean, if you look at the definition of holy grail, I think there's nothing better that fits that definition than nitric oxide.

Speaker A
Let's connect the dots by talking about a real world disease that a lot of people are very well aware of. And some of the more recent research that I became aware of through you and how that is connected to nitric oxide and the story of nitric oxide. So there is a super common drug. Millions of people are on it, talk about this drug and what we know when it comes to its connection with Alzheimer's disease and where nitric oxide fits in. And I'm assuming you're talking about the proton pump inhibitors.

Yep. So there's over 200 million prescriptions written for these drugs every year. 200 million. Is that in America alone or. That's in America alone.

And remind us, why do people use that or why do they get this prescription? Well, these are called proton pump inhibitors, and they're anacids. They're FDA approved for the treatment of acute gastroesophageal reflux disease, or gERD or acid reflux. And so these drugs were first approved in the late eighties, and the clinical trials, and the reason was it was when people have acid reflux, they get buried esophagus, which leads to erosion and then cancer can eventually lead to gastroesophageal cancers. So the thought process at the time was that it's an overproduction of nitric oxide or overproduction of stomach acid.

Nathan Bryan
So if we could suppress stomach acid production, you could get acute symptomatic relief of the acid reflux. But the FDA approved these drugs for acute use, three to five, maybe at most, a couple of weeks treatment, then you wean off of them. But yet today, I think in the late nineties, the first over the counter proton pump inhibitor was approved, Prilosec, and then later prevacid and the nexium. And so now you've got different brands of over the counter proton pump inhibitors. And people have been on these now for 35, 15, 20, sometimes 25 years.

Speaker A
And they were never intended to be used that way. No, there was never any safety data on those drugs for long term use. And now the safety data is coming from patients who have been taking this unknowingly and subjecting themselves to enormous risk. So these drugs basically shut down stomach acid production by a pyloric seals in the lumen of the stomach. And so for me, trained as a biochemist and physiologist, that's never made sense to me on why you would want to inhibit stomach acid production.

Nathan Bryan
Because we need stomach acid to break down proteins into amino acids. We need stomach acid to absorb things like b vitamins, magnesium, iodine, selenium, chromium, most micronutrients. And we need stomach acid to make nitric oxide. And so shutting down nitric, shutting down stomach acid production obviously will have unintended consequences. And now we're seeing that come to the fore.

And, you know, in 2015, it was first reported that people have been on ppis for three to five years, have anywhere from a 20% to 40% higher incidence of heart attack. Wow. And now the what? The study that just came out a couple of months ago showed that people had been on these drugs for at least four years, had as much as a 30% to 40% increase in Alzheimer's and dementia. That's super, super scary for those that are listening.

Speaker A
I mean, heart attacks are scary, and they're the number one killer of people, men and women, worldwide. But there's something uniquely extremely scary about Alzheimer's disease. And the fact that a common prescription drug that many people are on, which never was approved or have safety data for long term use, is actually increasing your risk of Alzheimer's disease. That's nuts. This episode is brought to you by cozy Earth.

I've recorded over 400 podcasts a date, and experts of all types have continuously reminded my audience that their number one factor for better health and longevity is. Can you guess sleep? Whether you're looking to optimize longevity, lose weight, or protect against chronic disease, prioritizing your sleep is super duper important. And when it comes to creating an optimal sleep environment, high quality bed sheets truly make a world of a difference. I know they did for me.

Enter cozy Earth. Cozy Earth's best selling bamboo bed sheets are insanely, insanely soft and comfortable. I love them because they're moisture wicking, breathable, temperature regulating, so I sleep cool and sound all night long. My wife loves them because they're no pill, super durable, and because I no longer wake her up by ripping off the sheets in a heated frenzy. True story.

Right now, cozy Earth is offering my listeners 30% off site wide at checkout. Just go to cozyearth.com drew. That's dashru. To get 30% off site wide, that's cozy. Cozy earth.com dhru.

Take advantage of this amazing sale right now. This episode is brought to you by fatty 15. I am so excited to share with you guys about an incredible scientific breakthrough to support our long term health and wellness. It's called c 15, and it's the first essential fatty acid to be discovered in 90 years. The concept is actually pretty simple.

Essential nutrients keep our cells healthy. And when our cells are healthy, that keeps us healthy. It ends up that many of us are deficient in c 15, which results in weaker cells that make less energy and quit working earlier than they should. All of that makes us age faster, sleep poorly, feel sluggish. Does any of that sound familiar?

By replenishing our cells with the essential c 15 nutrient, fatty 15 strengthens and repairs our cells, improving mitochondrial function and protecting us against damaging free radicals. So what's the result? Better long term metabolic, liver and heart health. Now, C 15 works in multiple ways. First off, it repairs age related damage to cells.

It protects them from future breakdown. It boosts mitochondrial energy output, and it activates pathways in the body that help regulate sleep, mood, and natural repair mechanisms that support our overall health. This functionality leads to a lot of exciting benefits now. And as we age, it even leads to smoother joint functioning, deeper sleep, and healthier hair, skin and nails. Now that's essential.

Fatty 15 is science backed, award winning, vegan friendly, and a pure c 15 supplement that is free of flavors, fillers, allergens or preservatives. C 15 is the only ingredient. Fatty 15 is seriously on a mission to replenish your c 15 levels and restore your body's long term health. And through today's promo code, you can get an additional 15% off their 90 day subscription starter kit by going to fatty 15 dot Dashru. That's Fatty Fata 15.

One five.com drew and use the code drew at checkout. Well, Alzheimer's, I think today is the most feared disease in the world. And it's not because, I mean, obviously it's a huge burden on the patient, but the burden really falls on the family members. And I think anybody who's dealt with an Alzheimer's, patience, patience, sees the burden it has on the family because sometimes these people live three, four, five, sometimes seven or eight years, and it's just, they're just existing but with no whereabouts. They don't know their family members.

Nathan Bryan
You know, they're basically, you know, have to be, have 24 hours care. So I think if you look today and, you know, I've done some research and kind of reviewing the literature last week, these drugs, even today, it's known to cause proton pump inhibitors, increased risk of hip fractures or bone fractures because you can't absorb calcium, so your bones don't remodel, you develop brittle bones, you don't absorb magnesium, so you develop low magnesium. And magnesium's involved in like 87 something, chemical reactions, biochemical reactions. 800. I saw the latest data, it's 800.

I mean, a couple years ago it. Was 600 and the latest is 800. So we need magnesium. And proton pump inhibitors prevent the absorption of magnesium. And then there's known cases of kidney failure and kidney disease, and then overgrowth of clostridium difficile and infections.

And now the risk of heart attack, strokes, and now Alzheimer's. I mean, how long does the list have to grow on risk, known risk, known heart attack, strokes and dementia and Alzheimer's before the regulators or the manufacturers of these drugs put a black box warning on it and say, look, for me, it's always risk benefit. What's the risk of this drug versus what's the benefit? I mean, and the benefit is, you know, relieving stomach acid secretions, which really provides no benefit. And the risks are way up here.

And it's multi systemic disease. It's kidneys, it's lungs, it's gi, it's heart attack, strokes, it's neurological. So the risk far outweigh any benefits on this. And if consumers are properly informed, our patients are properly informed of this, no one in their right mind would ever take these drugs. Yeah.

Speaker A
At least long term. Long term is right. I've had family members that have had to be put on these drugs, but they've had integrative, functional, or even just open minded doctors that are more on the up and up of the research and have said, listen, we want to put you on and we want to get you off as soon as possible, which means we have to be aware of what else actually helps get to the root of, why are you having this gerd? Why are you having this stomach acid? Maybe we can talk about that in a little bit.

First, let's connect the dots. How is that something like Alzheimer's disease would be more likely to happen if your nitric oxide is lower? Connect those dots for us, Doctor Justin. Yeah. So today we understand exact etiology of Alzheimer's and vascular dementia.

Nathan Bryan
So, again, if you look at kind of the underlying problems of Alzheimer's or what leads to Alzheimer's, through spec scans, scans of the brain, we see that there's reduced blood flow to certain regions of the brain. So in spec scans, it tells us how well profused the brain is in Alzheimer's patients. There's areas of what we call focal ischemia. There's parts of the brain that are getting very little affinity blood flow. So if you can't get oxygen, nutrients, and blood supply to that part of the brain, then those cells can't function.

Right. So what happens is you develop insulin resistance. You can't bring glucose into the cell. There's no blood flow and oxygen getting to that cell. And without glucose as an energy substrate and without blood and oxygen, those cells can't do their job.

So what happens? Proteins become misfolded. And what is that? Well, those are the tautangles and the amyloid plaques that you see in Alzheimer's patients. And then if you're not perfusing that region of the brain, then that part of the brain atrophies.

When you get brain atrophy, the brain gets smaller. So that's everything we know about Alzheimer's. And so what does nitric oxide do? It improves blood flow to the brain. It potentiates insulin signaling and actually allows glut four translocation to bring glucose into the cell.

So now, if you're adequately perfusing all parts of the brain and you're getting glucose into the brain as an energy substrate, then that part of the brain can do its job. Proteins don't misfold. You don't get tautangles, you don't get amyloid plaque. And the body basically regenerates and heals itself. You know, one of the first times that I had recome across your work in interview form was you were on my friend doctor David Perlmutter's podcast, and he is neurologist who's known for a lot of his work on the brain, and he talks a lot about Alzheimer's.

Speaker A
He was one of the first people that I'd heard used the term type three diabetes when it comes to Alzheimer's. So what are some of the lifestyle things that people are doing? Of course, this applies to all aspects of nitric oxide, but in particular to nitric oxide and Alzheimer's. What are some of the lifestyle habits that you look around America, you're traveling all the time, you're in airports, you're in different cities, you live in Texas, you see all people of all walks of life. We're recording in Los Angeles right now, what are the most common things that you see, lifestyle wise, that are detrimental, that are leading people to encourage these cascade of things that you just mentioned that are contributing to their risk and development of Alzheimer's disease?

Nathan Bryan
Well, it's the known risk factors. I think the most common problem people are doing is sugar consumption and over consuming carbon consumption. Can I pause you for 1 second? You said it's the known risk factors, and yet we don't hear from, you know, the Alzheimer's association. We don't hear from these big groups.

Speaker A
So I don't know how known it is, so I apologize. Well, it's known in the scientific community. I don't think it's known in the consumer world. Yeah. So one part you said is sugar consumption.

Talk a little bit more about that. So sugar. Sugar is one of the most addictive molecules that we know, right? And it's in everything. It's in.

Nathan Bryan
I mean, and what, so sugar leads to glycation. So it's. Sugar is very sticky. So it sticks to proteins, sticks to enzymes, and part of what it does is it sticks to the enzyme that makes nitric oxide and basically shuts down this flow of electrons that makes nitric oxide. And it also sticks to hemoglobin.

And we call that hemoglobin, a one c. But hemoglobin is just one kind of marker, protein. But if it's sticking to hemoglobin, sticking to other proteins and enzymes and rendering them dysfunctional, so then what happens if we consume too much sugar? We get over secretion of insulin by the pancreas, but the problem is we become insulin resistant. So chronic exposure to elevated levels of sugar leads to insulin resistance, and now we have hyperinsulinemia, hyperglycemia, and that's what leads to the chronic inflammation we see in diabetics.

And obviously, diabetics have a much higher risk of developing Alzheimer's than non diabetics. I think it's almost double something like that, isn't it? I don't know what the statistics are, but, I mean, it's enormous. And diabetes is completely preventable, treatable and curable, and reversible based on diet. So, to me, there are no excuses anymore.

The pace of scientific innovations and knowledge in medicine is going at a rate today faster than any other time in history. So we know the mechanism of disease, we know what causes diabetes, we know what causes Alzheimer's and what causes cardiovascular disease. So it's not a lack of information, it's the lack of integration of that scientific information in the clinical practice. And I think it's because there's, you know, doctors and physicians want, they don't have enough time to spend time with their patients to get to the root cause. They look at your symptoms, they don't even do a physical exam anymore.

And once they make a diagnosis, they have to write a script that's approved for that particular diagnosis. There's finite responses to that, and then it's off to the next patient in the next four to five minutes. So, but what we have to do, and I think that's the beauty of this conversation, is empower patients, inform consumers, so you can actually make changes yourself without having to go to a physician and getting on additional drugs. You know, we write more prescriptions drugs in the US than any other country in the world, and we have the sickest population in the world. So it's clear to me that drug therapy is not the solution for chronic disease.

So what we have to do is get back to what we call restorative physiology, understand what goes wrong and the mechanism disease, to the extent that we can correct it. And so if we give the body what it needs and remove from the body what it doesn't need, the body. Heals itself, you know, because you mentioned sugar as being one of the top ones, and there might be some other ones that we also talk about when it comes to, again, increased risk of Alzheimer's. That connects back to this idea of nitric oxide playing a major role in it as this holy grail of all chronic disease. Um, you know, you have sugar in your diet, I have sugar in my diet.

Speaker A
Any kind of carbohydrate you're going to eat is going to break down into sugar in the diet. What is the best biomarker to see that you have excess sugar in the diet? Because some people hear this and they think, oh, I got to cut out all sugar that I have in the diet. Right. And, um, they have a little bit of, uh, sugar phobia about things like honey, et cetera.

I mean, at the end of the day, all sugar turns into the same sort of. That's right. It's glucose at the end of the day. At the end of the day, it's all glucose inside of the body. But is there a biomarker that people should be getting tested, asked for on their blood work?

That is an indication. Of course, your doctor will always tell you when you're diabetic. Right. Because you've crossed the threshold. But what they won't always tell you is that you're pre diabetic or that you're pre, pre diabetic.

So what is a marker you like to tell people to pay attention to? Well, obviously, fasting glucose is kind of your acute phase marker. Um, you know, it needs to be. They say normal is less than 100. Your fasting glucose levels, it really needs to be below nine or your best 80.

Nathan Bryan
Um, and then your hemoglobin, a one c, is kind of your long term, kind of your average blood glucose levels over, say, the previous four to six months. The other marker that we're finding is triglycerides. If your triglycerides are elevated, it's really a marker of overconsumption of carbohydrates and starting to develop some type of insulin resistance. But I think going back to your point, look, well trained athletes fuel on carbs, right? Because it's part of their fuel.

There's a hierarchy of fuel in the human body. There's sugar, there's fats, and there's protein. So if you run out of sugar, you start breaking down fats. If you start breaking. If you run out of fats, you start breaking down protein.

So proteins are like the last kind of frontier. You don't want to be breaking down proteins as a fuel. So we can consume sugar as long as we burn it if we're physically active. Like, if I'm going to go run four to 5 miles, I'm going to need a little bit of carbohydrates as a fuel to get me through that five or six mile run. Now, if I'm going to go wake up and get in my car and drive to my office and sit for 8 hours, and I'm not going to burn any energy or consume any fuel, then the last thing I need is sugar, because then if you're by, if you consume it and your body doesn't use it, you store it as fat.

And then I think we all recognize people are accumulating a lot of fat over the last decades or half century. So it's all about consumption versus expenditure. And so for me, if I'm honest with myself, I try to eat a balanced diet in moderation. I eat a lot of protein, I eat a lot of red meat, I eat some vegetables, but I try not to eat many carbs, especially late at night. My last meal, I eat every day at 530, and I don't eat after that.

And then, you know, I eat lunch the next day. So I do a 16 to 18 hours fast every day. But then your body kind of utilizes that and then stores it. And then, obviously, if your body is well trained and you can internalize that, then your fasting glucose the next morning will be, you know, 80, 90, or certainly below that. Would you also add fasting insulin to the list of tests that people should be paying for?

You know, insulin is critically important, too. I think fasting insulin is good. There's certainly, if you're insulin resistant, you know, you may, or you're developing insulin resistance, your blood sugar may be moderately balanced. But if your insulin levels are still up here, and it's really what we're finding is that it's the high insulin that is probably more damaging than the high glucose because that starts an inflammatory cascade. So, yeah, so fasting insulin, fasting blood glucose, levels.

Hemoglobin, a one c, and triglycerides, I think those are the top four. And I've generally heard a lot of doctors say that they like their patients to be five or below, right? Like somewhere between two and five when it comes to fasting insulin. You know, once you start getting above five, six, seven, even though your doctor may not tell you that you're pre diabetic, you may be out of the optimal range of where you want to be. Evan.

Well, that's the that's the problem with with the normal labs, right? So normal, when you establish normal guidelines, you basically do a bell curve, and one standard deviation outside of that is considered. So one standard deviation, n, is considered what's normal. So, for instance, what was normal labs 50 years ago is completely different than what's normal labs today. In fact, if you took labs and you had a physician from 100 years ago and you took labs today from a patient, that would be considered normal and took it to that position 100 years ago, he would say, you're sick.

Something needs to be done. But because the population, as a general, as entirety, has moved to this new normal, normal is not healthy. Normal is not optimal. Normal is like your, like normal to your colleagues. And if you walk around and travel like I do, the last thing I want to be is normal to the people that I'm walking around, because most people, you know, nine out of ten people are metabolically unfit.

You know, what is it? The data now are three out of four Americans are overweight, and half Americans are obese. Two out of three Americans have an unsafe elevation in blood pressure. I mean, is that normal? It's certainly not optimal.

Speaker A
That was my follow up question. As you know, you mentioned sugar being problematic when it comes to this pathway of nitric oxide connection to Alzheimer's, you know, being overweight or obese. Obviously, by body composition metrics, BMI can be a little bit different depending on if somebody is working out an athlete, how much muscle mass they have, but that's also a problem. Is that correct? Yeah.

Nathan Bryan
You can be a skinny fat person, right? Yeah. So you don't have to be obese by BMI to be metabolically unhealthy. You could have. You could.

You could be normal weight, normal high, have a normal bmI, but have, you know, 30% body fat, not a lot of lean muscle, and, you know, still have metabolic challenges. So it's, to me, it's all about not just these kind of physical markers or anthropatric markers of BMI, but it's how metabolically fit are you? And how good is your endothelial function? What are your fasting insulin levels in these markers we just talked about? And can you go out and walk briskly or run or jog for 20 or 30 minutes without getting short of breath and chest tightening and things like that?

If you can't, then there's a problem. Let's go back to nitric oxide, and this is think this is a good opportunity. Even if people heard our first episode together, which, uh, you know, has almost a million views on YouTube, um, remind people just what is nitric oxide and what is its core role in the body? Well, it's a gas. That's what makes it kind of this unique signaling molecule.

It's a gas. It's produced in the lining of the blood vessel. And once it's produced, it opens up the blood vessels. It's also produced in our brain by our neurons. It's involved in long term memory potentiation.

It's involved in nociception or pain sensitization or pain feeling pain. It's how our immune cells fight off viruses and bacteria. So when we have an infection or we're exposed to a virus, our immune cells go to that site of infection, and then they generate a lot of nitric oxide over a short period of time, and it shuts down bacterial respiration. It prevents virus from replicating, so it's involved in every biological function. So we thought 25 years ago that if you become nitric oxide deficient, you develop high blood pressure, you develop erectile dysfunction, and that's still true.

But the other thing we're learning is you become insulin resistant, you become immunocompromised, you're more susceptible to bacterial and viral infections, because if you can't stop the virus from replicating, when you're exposed to one, then it propagates, replicates throughout the body, and you get sick from viral infections. But yet, if your body makes sufficient nitric oxide, we can be exposed to viruses all day, every day. But our body goes there, shuts down its replication, and we never get sick from it. But it's what we call a signaling molecule. It's how cells in the body communicate with one another.

And a Nobel prize was awarded in 1998 for the discovery of nitric oxide because. And these, these are to get a Nobel prize, it has to be discoveries that changed the landscape of mankind, right, or really impacted mankind. Foundational shift in paradigm. Foundational shift in paradigm. So the signal transduction by gas that penetrates through cell membranes and activates signaling mechanisms in other cells was a completely new paradigm in signal transduction because prior to that, similar to hormone signaling, there was this lock and key type stuff.

So you had this receptor and you had this ligand, and if it fit in there, in this type of lock and key type, then it activated that signaling. But nitric oxide is a gas. It's gone in less than a second, and it just diffuses through membrane. What's the specificity, what's the selectivity for turning on these signal transduction pathways? And 25 years ago, we didn't understand that.

Today we certainly do. But it binds to metals. It activates hemoproteins and turns them on. It post translationally modifies proteins and affects their structure and function, and then turns some genes on, turns some genes off, activates some proteins, turn some proteins off. So we understand the mechanism of nitric oxide signaling.

You've heard it called a miracle molecule, and I think that was probably appropriated 30 years ago, but it's not a miracle molecule. Miracle means we can't explain it. We can explain everything about the signaling aspects of nitric oxide and all its biological functions. So it's not a miraculous molecule. We all know that getting a good night's sleep is super important, not just for our overall health, but for being a functional, happy, productive human being.

Speaker A
I can tell you that when my sleep suffers, the next day is rough. That's why I'm so psyched about today's sponsor, birch mattress by helix. I've been sleeping on my birch mattress for three plus years now. And it's the real deal. They're certified eco friendly, organic, and fair trade.

Plus they're made from natural, non toxic materials. And that's super important to me because with birch, I'm avoiding a ton of vocs and off gassing chemicals that most other mattresses emit. And they mess with the quality of your sleep and your health. And here's the thing. Birch knows there's no better way to test out a new mattress than by sleeping on it in your own home.

That's why they're offering a hundred night trial. A hundred night trial to try out your new birch mattress. And because they believe so strongly in the quality of their mattress, each mattress includes, get this, a 25 year warranty. That's a hundred night trial and a 25 year warranty. I freaking love my birch mattress.

And right now, you can get your own for 25% off plus two free eco rest pillows@birchliving.com. drew so get ready for the best, most eco friendly sleep of your life. Visit Birch birch living.com. dashru Drew today to get 25% off plus two eco rest pillows. So what we learned from you last time is that nitric oxide, super important for the body in so many different areas and deeply connected to our development of chronic disease, if it doesn't end up staying at the appropriate levels.

Nathan Bryan
That's right. It's. There will naturally, even in people who are healthy, there'll be some lowering of nitric oxide as we age. So there's some age dependency. That's accurate.

I think we're starting to see that it doesn't have to be the case. So if you look at the general population, we certainly see an age related decline in nitric oxide production. But what we're finding is that we can shift this curve to the left and accelerate it because there's 2030 year old people have the vascular age of a 60 or 70 year old. Or we can shift this curve to the right and prevent, or at least delay the age related decline in nitric oxide production. Yes.

So it's pretty plastic. So we, we can modulate it. But on average, I think it's fair to say that the older we get, the less we typically make. Yeah. So my second part of that, which you perfectly explained there, and I'll share my own words, is that there's some connection to it lowering as we age.

Speaker A
But the biggest issue is our modern lifestyle is accelerating the decreasing or the aging of our ability to produce nitric oxide. And there are so many low hanging fruits that we can all do to prevent that from happening, but most people are just not doing them. Is that fair to say? I think that's exactly right. It's the western lifestyle, it's the american lifestyle that completely leads to complete deficiency.

Let's go down the list again, as a reminder. It's a good refresher. Let's start off with diet. First of all, everybody cares about diet. They're wondering what are the most destructive foods or ways of eating or types of diets that are out there that are destroying our body's ability to produce nitric oxide?

Nathan Bryan
Well, it's sugar, as we mentioned. I mean, sugar destroys the oral microbiome. So we know that there are bacteria in and on the body that help produce nitric oxide. Sugar completely destroys the microbiome. It glycates the enzyme.

It leads to a lot of oxidative stress, which oxidizes an essential cofactor that makes nitric oxide, which basically develop endothelial dysfunction. So the enzyme in the lining of the blood vessel can no longer make nitric oxide. So that's number one. Number two is, you know, farming practices from the 1940s to 2010s, there's data showing that there's a 78% depletion in basic micronutrients in the food that's grown in America from the 1940s to the 2010s. So the.

The pressures of feeding a growing population is at the expense of nutrient density. So years ago, 100 years ago, there was crop rotations, there was fertilizing in the fields. There were no herbicides or pesticides. It was old time farming. Now there's no crop rotation.

There's GMO, there's herbicides. Pesticides destroys the nutrients in the soil. And so the foods that we're eating were basically depleted of most micro and macronutrients. So the foods we're getting are leading us to a nutrient deficient society. And without certain nutrients, then you develop chronic disease, develop low magnesium and, what, 800 different biochemical reactions so the body can't do its job?

And then things like selenium, chromium and iodine. I mean, all of these things based on the Nhantz study, show that most Americans are depleted in these absolutely essential minerals and nutrients. So diet is a huge problem. It's not just what we're getting in terms of sugar and carbohydrates, but it's what we're missing from our diet. Then the other big thing is a sedentary lifestyle.

You know, we're not active. We don't move. We have to exercise. That stimulates and activates nitric oxide production. And then the other big thing which we open up the show about is just daily practices that people do.

And it's drug therapy like proton pump inhibitors, it's use of mouthwash, antibiotics, antiseptics that destroy the microbiome in and on the body. And then, you know, things like fluoride in your toothpaste, which is an antiseptic. So the daily things we're doing that expose our body to are completely shutting down nitric oxide production. So if we remove the things from the body that are shutting down nitric oxide production and now giving the body what it needs to promote and activate it like a balanced diet in moderation. Some green leafy vegetables, moderate physical exercise, 2030 minutes of sunlight.

Now the body is actually primed to make nitric oxide on its own. And it's really that simple. You mentioned one that we didn't cover last time, sunlight. What's the role between getting sunlight exposure and you can tell us at what time of day, if it makes a difference, and creating appropriate and abundant levels of nitric oxide in the body. Well, sunlight does a lot of things.

I mean, it converts vitamin D into active form. It activates our mitochondria. So the mitochondria are kind of like the mammalian chloroplast of plants. It's the energy producing organelles of the cell. But back in the 1950s, there was this concept put forth as photo relaxation, whereby certain wavelengths of light would actually dilate blood vessels, and you could potentiate this by loading those blood vessels with nitric oxide.

So today, and I think we published on this probably in 2002, that we could identify these, what we call photo label stores of nitric oxide. So then when we expose a patient or a subject to sunlight after we've given them nitric oxide, you can potentiate the blood pressure lowering effects of exercise. And so this has been a known phenomenon for 100 years. So people in Scandinavia, for example, in northern regions, have much higher blood pressure on average than people who live near the equator. Oh, wow, I didn't know that.

It's direct correlation with the amount of sunlight in vitamin D. And vitamin D activates and improves nitric oxide production. So in populations that are vitamin D deficient, they're typically nitric oxide deficient, but fixing the vitamin D and normalizing vitamin D won't always improve nitric oxide production. So they're too independent. But I think we can safely say that we need to improve vitamin D in order to optimize nitric oxide.

So what we're finding is that the certain wavelengths of light, and there's the uv spectrum, and then there's the far infrared, so the ultraviolet is a frequency of energy that will cleave nitric oxide that's bound to a thiol on a protein or in some enzyme, and so it'll actually release that nitric oxide and make it vasoactive, and it can dilate blood vessels. And then if you look at the other end of the spectrum in the infrared, it's really almost mainly far, but almost full spectrum infrared, then that frequency of energy will release nitric oxide bound to metals. And so what we're finding is if you've got a patient that's nitric oxide deficient, they have less of these photo label stores. So if they go to the sun or have red light therapy, then they're going to get very little clinical benefit of that. But if we take that same patient and we restore and replete their nitric oxide and then put them in sunlight or expose them to red light therapy, then you can potentiate the effects of that.

So now there's more nitric oxide being released from that wavelength of light. So just to recap there, we talked about diet and excess sugar inside of the diet being one of the number one things. Would you also say just excess calories, like an abundance of calories, primarily calories coming from ultra processed foods being a large contributor? Yeah, I think there's two considerations. Calories are kind of.

And there's different sources of calories. Right. But I think at the end of the day, if we're just looking mathematically or stoichiometrically, you gotta consume the calories that you put into your body or else they're gonna be stored as fat. So like Michael Phelps, for example, in the olympics, he had to consume, what, tens of thousands of calories, 25,000 calories, to basically allow him to perform at that high level. Yeah, but yet the guy has, what, 12% body fat, where if a regular person, non active person had consumed 25,000 calories, which some people do, and they're 3400 pounds.

Right. So it's always calories in, calories out. But I agree that the quality of those calories are much different too. Calories from protein is much different quality than calories from sugars or carbohydrates. And how the body utilizes that.

Speaker A
Absolutely. So sugars, excess calories primarily from ultra processed food, which is the way that most people are eating. I think depending on, you know, the age group that you're looking at, you know, it could be 50% to 70% of the diet is coming from ultra processed foods. And then obviously depending on zip codes, some zip codes are a lot higher. Not having access, not having education, unfortunately, not having exposure, um, not having modeling, you know, in the families that you grow up, if your family isn't cooking at home, you're much more likely to eat ultra processed foods.

Sedentary lifestyle, you mentioned. We know that if you get less than, I think it's like four to 6000 steps a day, that's considered sedentary, right? Yeah, four to 6000 steps. Most people, if you actually wear a pedometer, if you actually have an apple watch and you look at it, a lot of people, if you're not actively going out of your way to go on a walk every day, or at least two, it's very hard to break out of that, you know, eight to 10,000 steps that are there. I see people drive around a parking lot for 20 minutes to prevent walking an extra 20 yards.

Nathan Bryan
Trying to find a parking spot that's close, park at the end of the parking lot and walk. Yeah, exactly. So if you're getting 4000 steps or lower, that's a sedentary lifestyle. You're not going to be pushing your body. You're going to be in this comfort crisis, as Michael Easter talks about, and that's going to have impact on your ability to produce nitric oxide long term.

Speaker A
So diet, you talked about, you talked about the fitness aspect, you talked about the lifestyle habits. We went on the deep, deep, deep rabbit hole about how mouthwash, which I thought, because I hang out with a lot of people who are generally healthy, and I told my family about the dangers of mouthwash a long time ago. I had no idea until our interview together that you share that two thirds of Americans are using mouthwash every day and that mouthwash is destroying the beneficial bacteria in our mouth, which is directly connected to our ability to produce nitric oxide. That's right. That's accurate.

Nathan Bryan
No, that's. I mean, all you have to do is listen to the commercials. These mouthwash say it kills 99.99% of the bacteria in your mouth. And that, by the way, is not a good thing. Yeah, but yet companies are advertising that.

I mean, think about again, I take important clinical observations and then work backwards to figure out mechanism. There's a reason we don't take an antibiotic every day for the rest of our life. Right. If we have an infection, yeah, you need an acute dose of antibiotics, but the damage it's doing to the commensal bacteria in the microbiome is completely devastating. And now we know that disease starts in the gut.

And most chronic diseases can be traced back to dysbiosis. And they got. So the bacteria that live in and on our body outnumber our human cells ten to one. The human genome codes for 23,000 gene products. The bacteria that live in and on our body code for 3 million gene products.

So these bacteria that live in and on our body are there to do things that we as humans can't do. It's a true symbiotic relationship. And so when you start destroying this ecology of the bacteria that live in and on our body, you develop systemic disease. So going in, and, you know, most people focused on the gut microbiome early on. 25 years ago, we started looking at the oral microbiome.

Because disease starts in the mouth, right. And what do we put in our mouth? And then what are these bacteria doing? So years ago, it was recognized that there were certain bacteria, faculty of anaerobes on the dorsal part of the tongue that could produce nitric oxide that we could detect when you swallowed your own saliva. And then you completely eradicated this by inhibiting stomach acid production.

You completely eradicate it by using an antiseptic mouthwash. So, today, fast forward 2030 years, we certainly know which bacteria are present and responsible for nitric oxide production. And it's very clear that things like chlorhexidine, alcohol based mouthwash, anything that's labeled antiseptic fluoride in your toothpaste, it indiscriminately kills all bacteria. It's not selective just for the pathogens. It kills the non pathogenic commensal bacteria, which are there to do things to provide the human host with an essential metabolic product.

And in many cases, it's nitric oxide. I heard another stat that you shared on a friend's podcast. You said, not only are two thirds of Americans using mouthwash, but also, based on your estimates, two thirds of people that are out there have low nitric oxide. Is that accurate, and how are you measuring that? So two out of three Americans have an unsafe elevation in blood pressure.

Speaker A
Okay. That really means anything above 120 over 80. I think that the statistics are probably even higher than that because it's vivid. I mean, now, it's recognized that any millimeter of mercury over 120 over 80 is a 1% increase in developing cardiovascular disease. So if you get a blood pressure of 130 over 8130 over 85, your doctor's probably gonna say, well, that's not bad.

Nathan Bryan
Well, you got an extra 10% increase in developing heart disease or cardiovascular disease. So we have to get that down to 120 over 80. And again, the guidelines have changed. And it's not because we have evidence that it's okay. It's because drug therapy can't get a patient to 120 over 80.

The best reduction in blood pressure by a single anti hypertensive drug is gonna be four 6 mercury. So if you've got a patient that has blood pressure of 150 over 100, they're going to have to be on, you know, half a dozen different anti hypertensive medications to get their blood pressure 20 over 120 over 80. And then what happens? We develop all these side effects. You got to mitigate the effects of those drugs with other drugs.

The next thing you know, you've got a patient that's on a dozen different drugs. And the body, there's no way the body can heal or operate when it's being inhibited by that many chemical reactions or synthetic inhibitors of biochemical reactions. You sort of made the connection earlier, but let's make it now here. Connect nitric oxide and high blood pressure. This is so important because so many people have high blood pressure.

Speaker A
It was one of the top questions that people were asking is that a lot of your recommendations in our first episode together, would those be the same recommendations you'd have for somebody who has high blood pressure? So what is nitric oxide's role in high blood pressure? Well, we all have a finite volume of blood, right, that our heart pumps through these blood vessels every day. It's a known volume, five to six liters, depending upon your body mass. But we also have a finite number of blood vessels.

Nathan Bryan
So if your body can make sufficient nitric oxide, then we can dilate those blood vessels. So now you've got bigger pipes with that same volume of blood pumping through. So it's lower pressure. Now, if you lose the ability to produce nitric oxide, you can't vasodilate. So now you're chronically vasoconstricted.

Now you've got that same volume of blood going through smaller pipes, and that's an increase in pressure. And so what that means is when you have constricted, stiff blood vessels. Now, with each bead of the heart, that pulse wave travels really quickly down the vascular bed, down the vascular tree, and it causes damage. It causes sheer stress on our endothelial cells, damages the endothelium, and then things damages that barrier function. And if our body can make nitric oxide, the blood vessels are dilated, but more importantly, they become soft and compliant, so they dampen that pulse wave with each heartbeat.

And you can do this through augmentation pressures and look at the reflective wave with each heartbeat. But in terms of blood pressure, it's really just the loss of the vasodilation due to nitric oxide. And so we're finding that it's that the oral bacteria are responsible for the vasodilation of systemic blood vessels, or resistance arteries, that are responsible for maintaining normal blood pressure. And that was a completely kind of a change in paradigm, too, because people thought, how did the oral bacteria, how are the oral bacteria affecting the second to second production and regulation of blood flow and blood pressure in the resistance arteries? And what we're finding is it's nitric oxide being produced.

We swallow our saliva, it's transported as nitrozoglutathione, and it's vasoactive, so it can dilate those blood vessels along the entire vascular tree. Wow, the body is truly a fascinating miracle. Well, it's like the hip bones connected to the knee bone, the mouth is connected to the blood vessels. I mean, it makes perfect sense to me. You know, it also explains resistant hypertension, the oral bacteria, because if you go to your doctor and you have high blood pressure, he's going to put you on a prescription medication.

And if all you have to do is look at the American Heart association, any agency that keeps track of statistics, 50% of the people that are given a prescription drug for hypertension don't respond with better blood pressure. In fact, 50% of the people that are given any type of blood pressure don't have their blood pressure managed. And so why is that? Well, there's certain class of antihypertensives. There's what's called ace inhibitors, which inhibit the conversion of an angiotensin converting enzyme.

There's arbs, angiotensin receptor blockers. So there's a working on kind of the kidney aspect of the regulation of blood flow. It's called the renin angiotensin system. And then there's things like calcium channel antagonists, which modulate the amount of calcium being released in lining of the blood vessel, and it can dilate blood vessels. And then there are things like diuretics that basically just excrete a lot of fluid from the body, and you basically decrease the volume and volume overload.

Or there are things like beta blockers that just base, that pace the beat of the heart or the rate of the heartbeat. So then you don't have the heart pumping as often, so there's decreased pressure. But again, even with those four main class of antihypertensives, 50% of the people don't respond with better blood pressure. Now, what we're finding, we published this in 2019, I believe it was five years ago that the hypertension is a symptom of oral dysbiosis. So now, when you ask your patients, are you using mouthwash, do you have fluoride in your toothpaste?

And two out of three people are going to say yes to the mouthwash, and ten out of ten people are going to say yes to fluoride. So then they go, okay, stop using fluoride in your toothpaste, get rid of the mouthwash, come back 30 days, let's look at your blood pressure. And remarkably, the blood pressure normalizes that quick. It could change in some patients that quickly? Yeah.

In our study, we found that it completely reversed. So we would give mouthwash twice a day for seven days, stop for four days, bring them back, and see what the changes were. Not only in their oral microbiome, but in their blood pressure. So seven days of mouthwash, we saw at worst, a 26 millimeter increase in blood pressure. Just seven days of mouthwash use.

We didn't change their diet. We didn't change their. These people weren't medicated, but we could make people clinically hypertensive in one week by giving them mouthwash. Crazy. But then, you know, you said the body's so resilient.

And I was a little bit surprised at this. Four days after we stopped the mouthwash, their oral microbiome had completely repopulated and their blood pressure completely normalized. So it's kind of like smoking. You know, if you've been smoking for years and you stop, you know, you can almost see the benefits within a couple of days. I mean, there's going to be some chronic kind of damage that's going to take years to overcome.

But with mouthwash and the ecology of the microbiome, if you just stop after four days, they completely repopulate, produce nitric oxide, and your blood pressure becomes meta normalized. Do you think that. So step one, obviously get off a mouthwash, right? Step two, if you can, which most people can, it's going to be cheaper than also bottled water. It's going to protect you from a lot of things like pfas in the water.

Speaker A
Get a high quality filter for the home so you're not drinking water that's blasted with fluoride. Well, municipal water is very dangerous. I mean, municipal water is nasty water. In fact, I encourage everybody to get a home filtration system because, you know, it's recycled. There's drug metabolites in there that are small molecules that basically pass through any filtration that's put through municipal water, plus municipal pipes in many conditions.

Nathan Bryan
I mean, the flint, Michigan story from years ago, I mean, the pipes and many of these municipalities are decades, you know, years old. Yeah. That are corroded. And so we're getting exposed to a lot of these. And I have a personal experience with this.

My dad lives in a small town in Lexington, Texas, and the water quality there is horrible. And it was making him sick, and nobody could figure out why he was getting sick. Wow. Until I go, look, there's something in your house that's making you sick. We did mold testing.

We tested everything. And I went there and got a drink of water, and I go, what is this? I mean, it's not the water you're drinking. It's the water you're cooking in. It's the water you're bathing in and.

Speaker A
It'S chronic exposed 24 hours a day. 24 hours a day. And since we did that, we mitigated the water that's 76 years old, a paraplegic, and he's doing great. Wow. What do you think?

Nathan Bryan
But it was a medical mystery we had to go and figure out because every doc and specialist we took him to put him in the hospital, run tests, run labs, hydrate him. And what I've. What finally was the epiphany to me was when he wasn't home, he was well. And most people when they go to the hospital, they get sicker. But dad, when he left the house, he got better.

So then I told me, I go, there's something in his home that's making him sick. Wow. And so we had to dig, dig, dig, and finally it was the water. So get him a filtration system. And basically the water over overwhelmed the filtration system.

So then we had to constantly clean the filters and replace the filters. But it's a huge problem. What was going on? Were you able to find any more information out? Was it the degradation of the pipes?

Speaker A
Was it. We know in certain places fracking has contributed to water quality issues. It could be if he's in a rural area, pesticides. Were you able to narrow it down in terms of what was getting into the water? No, we don't.

Nathan Bryan
I mean, this is opening Pandora's box, right? Start to interrogate this. And, you know, there's enormous liability on the municipality because it's not just my dad. I mean, how many other people. Dad's just a little bit fragile because of all his comorbidities and his age.

But you know, there's people that are otherwise healthy that are getting exposed to this, that are probably going to. It's going to manifest later in life. But you know, what they do is they test it for the standard testing. Right. And so if you don't test for what you.

What's not in the standard testing, then how do you know? And so all of these things that they sent off for their, for the water supply were within the normal range of what's. What's allowed. But yet my question was, what about this, this, this and this? And they go, we don't test for that.

Speaker A
Yeah. If you don't test, there's no liability. That's right. Yeah. Well, I'm glad your dad is doing better, at least from that situation.

And it's a telling story to remind us all that even if you're not in that position, you still don't want to be contributing to all these risk factors that we have when we're exposed to really terrible water situation. We're learning more and more that the water in a lot of places is pretty bad. EWG has a website that I think it's called the clean water map. We'll link to it in the show notes, but you can type in your zip code. I was alarmed to see that here in Los Angeles they found this, uh, you know, some rate like radioactive active isotopes in the water.

In, at some level they found levels of arsenic and uh, you know, a whole bunch of other compounds that are there. And now we're finally understanding that there's hundreds of thousands of different types of pfas, um, pufas, pfas, all these different, you know, forever chemicals. They're in the water. And even the government itself, they did this big press release and study that was done in a bunch of municipalities. They were saying that in their estimates, 60% to 70% of the water nationwide in America has these forever chemicals in them.

When you looked into the study, they're only testing for four forever chemicals and there's hundreds of thousands of them. So in your case of your dad, uh, did you get reverse osmosis? Is there a filter that you recommend to our audience? Yeah, I. Look, we.

Nathan Bryan
I did a lot of investigation. There's, there's several good water companies out there. The one I use is a company called PH Prescriptions out of Florida. They get a really good reverse osmosis. They replete them with.

Replete the water with certain nutrients. They charge the water, even make a hydrogen water system. So there's lots of good systems out there. Those are just ones that I know and trust. I have a home filtration system in my, my house, I've got a chemical free pool.

You know, I have a pool with no chlorine, with no chemicals in it. It's ozonated use uv light and it basically it's a super rich oxygen pool. That's great. So we were on the topic of protecting the oral microbiome ditch fluoride. It's always funny when you go to these high end gyms around Los Angeles and any other city too.

Speaker A
I think Equinox was doing this back in the day. I don't want to throw them under the bus. I like them as a company. But you'd go work out, you'd go to the, you know, the men's restroom there and there's like mouthwash everywhere, right? Cause I guess that's what the audience is asking for.

But hopefully, knock on wood, if you're at equinox, you're listening. Or any other gym that's out there. There's plenty of non traditional mouthwashes that are out there that are going to be better for you, that are going to be, like, xylitol based. Are those okay when it comes to nitric oxide? You know, there's a lot we've learned, but there's still a lot we don't know.

Nathan Bryan
Um, we, in fact, just this past weekend, I gave a keynote address at a dental conference in Knoxville, Tennessee. So the dental community is slowly being receptive to this because this was really disruptive to the standard of care in dental medicine, because every time you go to the dentist, they go into fluoride rinse. They encourage you to use mouthwash. So you kill the periodontal bacteria and the gingival bacteria that causes periodontal disease and gingivitis. But now we're recognizing that the collateral damage of the non pathogenic commensals is probably much worse than the pathogens that, you know, on the gingival tissue that may be contributing to periodontal disease.

So now what we're trying to do is figure out how do we selectively kill the bad bacteria while maintaining the ecology of the good bacteria. And so we, you know, I've been working on this for many, many years of trying to figure out how do we develop, because a lot of people, you know, I still encourage people to brush your teeth. I'm not saying don't brush your teeth. So how do we create a toothpaste that doesn't have harmful chemicals in it, like fluoride, but can actually remineralize the teeth, maintain a healthy microbiome, and give you a fresh breath? So we're working on a toothpaste.

We've just, I think, got our final prototype in, and we're making a mouth rinse, because a lot of people, rightfully so, have halitosis, have bad breath. And it's. It's offensive when you. When you talk to these people. And it's not their fault.

It's. There's just their. It's. It's dysbiosis. And so those people feel like they need to use mouthwash.

And I think there, there may be some reason for that. But again, what's the collateral damage of killing the stinky bacteria that's causing halitosis without destroying the good bacteria? Right. And how much of halitosis is in the mouth versus in the gut? Well, it's all systemic.

Everything that's excreted from the skin or in the mouth or in the breath is all reflection of systemic health. Yeah. So I developed a mouth rinse that appears the early data are coming out that we can selectively kill the pathogens, and we're actually improving the microbiome and the nitric oxide producing bacteria. That's exciting. So the next thing we're going to do is we're going to take our mouthwash and we're going to give it to patients with high blood pressure and see if we can normalize their blood pressure with a mouth rinse.

That's great, because that would be. I think that's a game changer. Well, in the meantime, if you're using fluoride toothpaste, we already said ditch the traditional mouthwash, get rid of the fluoride toothpaste. I know a lot of people and dentists that I, you know, look up to, they'll use, like, hydroxyapatite. Right.

Speaker A
As one solution that it actually remineralizes. I use one called fig Fygg. Not affiliated with them. Just a big fan of the company. It's developed by this guy, Mark Burhenne, who I think, you know, ask the dentist.

He's a really good guy. Biological and functional dentist. And, and we'll look out for yours in the future when it's ready as well, too. The mouthwash. Clean up your home water by getting a reverse osmosis.

Reverse osmosis. Tongue tied. But also that re mineralizes the water because you need minimalism. Yeah. You don't want distilled water, you know?

Right, right. You can add some minerals in, you can add some electrolytes. You can add some stuff. But, yeah, you don't want to be drinking distilled water long term. That's not going to be good for you.

And then in addition to. In addition to that, how much dysbiosis in the mouth is also, I know this may not be necessarily your area of expertise, but people might need to go and work with a biological or a functional dentist and somebody who helps them also take a look at their diet and talks about the relationship between diet and oral microbiome. Yeah, that was the beauty of this dental conference that I was speaking at this weekend. It's called the Integrative Dental Medicine Scholar Society. I recommend anybody check these people out because their whole mission and objective is to get physicians and dentists working together because there's so many chronic, poorly managed diseases that can be traced back to oral dysposis or infections in the mouth.

Nathan Bryan
And in dental medicine, a lot of these infections can be asymptomatic, right? You don't know you have an infection. And the best example is in root canal teeth. If you have a toothache and you go to your dentist, he's going to take out the nerves to that tooth, so you no longer feel the pain from the infection. He's going to take out the blood supply from that tooth and then he's going to put you on an oral antibiotic.

But I think he just forgot that he took out the blood supply to that area that was infected, so the antibiotic can't get to that site of infection. So then what happens? You're going to live for the next 510, 1520 years with an active infection that's asymptomatic, but yet these anaerobic bacteria are just eating your jaw away. They're secreting these metabolites, these toxins that are poisoning your system. Yeah, they circulate throughout your blood, but.

You don't know it. And if you get an x ray, the radiolucency is going to show you the osteonecrosis from that infection. So you have to go get what's called a 3d cone beam. It's a ct scan, and that will show you the radiolucency of an asymptomatic infection. And so you have to get that resolved and you have to get that mitigated.

You go in there and a lot of times extract the tooth, clean up the infection with ozone gas, put some platelet rich fiber in there to regrow that bone tissue. In many cases, do a bone graft. But really, that's a very important issue that's completely unnoticed in dental medicine and is contributing to chronic disease. I know I had my own personal dentist who's based here in LA, in Santa Monica. Doctor Rosita Roshjian.

Speaker A
She's at Serenity Dental center. She came on the podcast two years ago and made this video and it just blew up on YouTube. It has more than a million views. And she's talking about the dangers of doing a root canal, how to avoid getting them, are they always necessary? And when they are necessary, how to go and find a dentist to do them the right way to avoid what you're talking about so that you don't end up having to get a cavitation later on.

We had a former employee, she had pots like symptoms. She was super chemical sensitive. She had been healthy her entire life, but she had a couple teeth that were removed incorrectly. One of them was a root canal. And until she started researching on her own and kind of going to doctor Google and doctor YouTube, she ended up finding a dentist who did a ct scan on her and said, you have these infections.

And I think. I don't know for sure, but that could be playing a part in what you're experiencing. And she had to have these cavitations, and she had to have her, you know, these improper root. Root canals cleaned out. And in her case, it was multidimensional, but it was a huge step in the right direction.

Almost 50% got better just from getting rid of those issues. Well, I've seen patients with ALS type symptoms, neurological symptoms that were poorly managed for ten or 15 years, and we just have a conversation about root canals. And, you know, they roll into the dentist, into a wheelchair and they walk out. Wow. They walk out when they clean up the infection.

Nathan Bryan
I mean, it's the most. Same thing with my dad. You know, my dad was chronically ill. He had a car accident in 1984. He's paraplegic and had a number of chronic conditions.

And same thing. We couldn't get him better. So I took him to a dentist, got all the mercury removed from his mouth, got the root canals, teeth extracted, cleaned up the infections, and remarkably, he's doing great for 76 year old paraplegic. Wow. And then I've never seen a cancer patient that didn't have an oral infection.

Zero. 100% of the cancer patients I've consulted with, it's been dozens, if not hundreds. I've never seen a cancer patient that didn't have an oral infection. Yeah. A link worth exploring there.

Yeah, certainly. I'm not saying it's causation, but it's just the numbers don't lie. But I think it's something I encourage. That's the first question. When people come to me and they say they got cancer, a primary tumor that's even metastatic disease, I go, do you have any root canals?

And some people look at me like I'm crazy. I got cancer. I don't have a toothache. Well, it's not an obvious correlation, but get it checked out. Yeah.

Speaker A
Worth looking into. Well, let's bring it back to nitric oxide. And we were talking about the things that are leading contributors to low nitric oxide. We talked about diet, we talked about activity levels. If people are living a sedentary lifestyle, we'll pull on that thread a little bit more in a second.

We talked about the habits that people have. Mouthwash. We went on this rabbit hole of filtered water, which led to a great conversation about root canals. This is why we love podcasts. Um, but I want to ask you a question.

In in addition to those, is there anything else that we missed that are top contributors for why people have such low nitric oxide levels? Anything we missed in that? Well, I think it's what we started out with, the proton pump inhibitors. And I think if we go back to that and look at kind of mechanisms. So, again, if we take kind of indisputable clinical evidence, showing by real numbers, people had been on ppis for four years, 30% increase in Alzheimer's and dementia.

Nathan Bryan
So then, if you take that data and extrapolate that back and try to understand, mechanistically, what is it that from these drugs that are causing an increased risk in Alzheimer's? And so ppis are doing several things we talked about. You lose magnesium, you lose the absorption of magnesium, other vitamins and minerals in the lumen of the stomach. But when you lose the acidity of the stomach. So part of this enterosalivase circuit, where the bacteria producing nitric oxide, what they're doing is they're reducing a molecule called nitrate, which is no three minus.

And these bacteria perform this two electron reduction to inorganic nitrite. And now our saliva is enriched in this molecule nitrite. And now when we swallow our saliva, the pka of nitrite, and biochemically, that means the ph at which 50% of that nitrite would become protonated and form nitric oxide gas is 3.4. So when we swallow our own saliva, as long as there's stomach acid production, we get a burst of nitric oxide gas in the lumen of the stomach. It's absorbed across the gastric mucosa.

It's transported by binding to cystine, thiols and glutathione and inorganic nitrite. And so when we suppress stomach acid production, we no longer get that nitric oxide benefit, so that shuts down systemic nitric oxide production. And then thirdly, the PPIs are specifically inhibiting an enzyme called ddAH, and it's a hydrolase enzyme. Anyway, what it's doing is it's allowing the buildup of a molecule called asymmetric dimethyl L arginine, or aDMA. And if you look at the medical literature, you'll see that elevations in AdMa, basically, it's an inhibitor of nitric oxide production.

So, in essence, what the PPIs are doing is they're completely shutting down nitric oxide production. In the lining of the blood vessel, in the mouth, in the stomach. And so when. When they're doing this, what happens? You lose regulation of blood flow.

You develop insulin resistance. What does that lead to? Alzheimer's. Wow. Just on that thread, my mom, after dealing with a loss in the family, somebody very close to her and to me, and then additionally, she took this trip to India.

Speaker A
This was a couple years ago, and there was a lot of stress and travel. For the first time, she developed acid reflux like symptoms that were there. And I called around to my network, and ultimately, I got connected to this integrative ent doctor who specialized in that. Unfortunately, he's not practicing at the moment. He's navigating.

He's public about this. So I'm not putting out anything that's there. He's navigating his own health issue that's there. Doctor Benjamin Asher. And he helped my mom temporarily kind of put her through this phase process, because initially, her doctors gave her a PPI.

They told her this was good, even though they're not integrative or functional. They said, listen, we don't want you on this long term. We know we don't want you on this long term. But the challenge was, they didn't know what else to tell her to do. Most doctors that are out there, they're well meaning, and they want to give patients relief.

It's just that they may not be educated on, well, how do we get to the root issue of why it seems to be that these stomach acids are an issue, and if PPIs provide relief, well, if the patient's feeling better, I don't want to immediately take them off of them, even if I know they're not meant for long term use, because then what do I tell the patient to do? Right? So, the doctor, in her case, my mom's case, didn't know what to tell her, but we said, mom, listen, we got to get you working with somebody else. And one of the first things the doctor did is that he removed a lot of the dietary triggers that influence it. Not that these foods are unhealthy, but that for somebody who's dealing with stomach acid issues and would be a candidate for a PPI, uh, there's things like citrus and green tea and even things like chocolate, which are fine normally, but when your stomach acids are kind of thrown off, they can exacerbate the issue.

So he dialed in some diet, removed some things. A lot of functional doctors would. Would do this as well. Then, in addition, he brought in some supplements. He actually recommended this one supplement that's over the counter in the UK called Gavastan.

It's fenugreek and a couple other things. You can't get it in the US, but we ordered it from Amazon and somebody sent it over from the UK. My mom went on that and a few other things like that. He has some articles we'll link to him in the show notes. And just by being pretty strict with their diet, avoiding coffee, avoiding tea for a little while, making sure for a temporary period of time, she had to sleep kind of a little bit elevated, right?

Because what would happen is that her stomach acid would flare up at night. She'd try to sleep, she couldn't sleep. She'd get anxiety because she couldn't sleep well. And then the stomach acid is driven up the next day. In fact, her doctors in the beginning thought that she should be placed on an anti anxiety medication.

And luckily, through the help of my sisters and my brother in law, who's a doctor that she lives very close to, Doctor Neil Patel, they're like, look, it's not anxiety. Anybody who's not sleeping is going to have this type of situation. So knock on wood. The combination of all those things under this doctor Asher ended up, uh, working. But I just wanted to highlight that having dealt with and supported somebody close to me firsthand, I know that it can be tricky, but, uh, hopefully we can put some articles below.

I know Chris Kressner has some great articles and some other resources if you have anything that's great, because I will tell you that a lot of people, they know that the PPIs are not helpful long term, but they're just not sure what else to do. And they need a little bit of guidance. And you can't. Here's the thing. You can't stop these drugs cold turkey.

Yes, you can't stop them cold turkey. Cause you get a horrible rebound effect and hyper secretion of acid. So what I tell people is to wean these off, especially if been on them for a number of years, is whatever dose you're taking, start taking half and take that half dose for ten days. Then after ten days, take that half dose every other day. Do that for ten days, and then you can stop.

Nathan Bryan
So now your body's slowly adjusting to this new norm. But during that time, you get, what I tell people is, before a meal, take a tablespoon of apple cider vinegar, because vinegar is just acetic acid as a ph of two. So when you can, when you, when you take that vinegar, it acidifies the lumen of the stomach. Now, when you eat, you can break down proteins into amino acids. You can actually absorb basic nutrients.

But the other thing we have to do is we have to restore these missing nutrients. So the chemistry of the pyloric cell to make hydrochloric acid, you need iodine, you need zinc, you need sodium bicarb, you need sodium chloride, and you need b vitamins. But yet if you been on ppis, you can't absorb zinc, iodine, B vitamins, any of that. They interfere with absorption. Yeah.

So then you have to start supplementing these basic nutrients. So now what we want to do is we want to get your pyloric cells producing stomach acid at the right level so you can break down proteins into amino acids. Because it's almost a paradox. Because acid reflux is a symptom of insufficient stomach acid production. Right.

Speaker A
You actually need more stomach acids that are appropriately distributed throughout the day to actually break down your meals. Yeah. So it's never made sense to me pharmacologically, way inhibit stomach acid production. Right. Because if you can't make stomach acid, you can't break down proteins.

Nathan Bryan
Your body sees it as a foreign substance and your body's trying to get rid of it and expectorate it. And that's the reflux you're seeing. So if you can make sufficient stomach acid, you acidify the lumen of the stomach, then your body can break it down. You'll have gastric emptying into the duodenum, and that digestive system works perfectly fine. But all of that's dependent upon stomach acid production.

Speaker A
You know, the first time that I'd heard about the apple cider vinegar hack that was there, it was this guy. He got into a lot of trouble. And he probably was saying some things that he definitely shouldn't have said. Then he was sued by the government. Kevin Trudeau, do you know the name?

He wrote this book. It was called Natural Cures. They don't want you to know. He used to be huge on infomercials and everything. One day I went into, like, a natural food store and they had the book there.

And I was just kind of, I was curious. I was, like, flipping through it, and one of the, one of the number one tips was in there was about how to support healthy stomach acids. And I remember reading it, it was, take an apple, take a little teaspoon or a little capful of apple cider vinegar before you have a meal. And I remember telling one of my friends, and they were like, no, that's actually pretty legit, you know, that actually works. I was like, okay, cool.

He didn't get in trouble for that. He got in trouble for all the stuff that was there. But that was the first book that I'd heard about that concept in. Yeah, it's remarkable. I mean, I use it all the time, and people who've been, you know, kind of stuck on acid reflux drugs for many, many years.

That's great. That's fantastic. Now, a question that a lot of people ask is, how would I know if I am not producing enough nitric oxide? What are the things that are available to me in the full gamut? Maybe some things are going to have a cost, and some things are going to be no cost things you could just look at your life.

So walk us through those, starting with the simplest, cheapest, easy way to know, most likely, that you are not producing enough nitric oxide. Well, there's no labs that we can draw, like your cholesterol or vitamin D or magnesium or things like that, because nitric oxide, as I said, is a gas. Once it's produced, it's gone in less than a second. So what we have to rely on are symptoms. So the first, typically, if you're losing the ability to produce nitric oxide, there's a hierarchy of symptoms that will show up.

Nathan Bryan
The first one is usually erectile dysfunction, because if you can't dilate the blood vessels in the sex organs to get engorgement to get an erection, and that's in both men and women, by the way, then that tells us your blood vessels aren't making nitric oxide. So erectile dysfunction, and it's in men and women, it's not just a penile erection, it's a clitoral erection. In order for women to have an orgasm, get an increase in labial pressure and clitoral pressure. And that pressure comes from an increase in blood flow. Yeah.

Speaker A
A lot of people don't know this. We've had many experts on the podcast come and tell. But women get an internal boner. That's right. And their clitoris actually can enlarge by, like, two, 2.5 times in size through.

Nathan Bryan
And that's what starts the orgasm process. So you have to have that intra labial, intraclitoral pressure in order for women to reach orgasm. Right. And as you shared before, it's not everything. With women, there's the psychological component, hormonal component, other stuff.

Speaker A
With men, it's a little bit simpler. It's primarily blood flow, which is why there's a male viagra but attempts to make a female viagra have not really panned out because of just difference in physiology. That's right. So that's, number one, if you have some degree of sexual dysfunction that tells your body you're not making nitric oxide. Number two, if your blood pressure is above 120 over 80, and obviously, the higher, the higher degree of nitric oxide deficiency.

Nathan Bryan
And then, number three, you start to develop metabolic disease. Insulin resistance, elevation in blood glucose, elevation in insulin levels. And then fourth is typically, you start to develop exercise intolerance. So if you try to get on a treadmill or just walk 15 or 20 minutes and it gets short of breath, you tire easily. Then obviously, your body's not making nitrogen to dilate the blood vessels of not only the heart, but the skeletal muscle to increase or to meet the increased metabolic demands.

And then, if not corrected, obviously, then we start to develop dementia and Alzheimer's and end stage disease. So the first thing is just taking a snapshot of your life, looking at symptoms. Because nitric oxide is a gas, you can't even really kind of capture it. So you have to deal with other ways to look at it. But in addition to symptoms, there are other sort of proxy ish ways of looking at nitric oxide.

Speaker A
There's a common one that a lot of people heard of. I'd love you to chime in on it. I've had varying experiences with it. But these are these nitric oxide strips that you can buy for, you know, a few dollars on Amazon. Um, do they work?

How should you use them? Or generally, do you find them not helpful? Well, I was the original developer of those strips. I developed those in 2009 or 2010. And really, the.

Nathan Bryan
The reason for that was because people asked me, and this was when we ran into the nitric oxide field, because. And developing products and people go, how do I need. If I need. How do I know if I need nitric oxide? It's a valid question.

Right. And so, based on the known chemistry of how nitric oxide is produced, what it becomes, where it goes, and through this enterosalivary circuit and the bacteria, I developed this saliva test strip. And so what we're detecting with that is salivary nitrite. And so what we're really measuring with that test strip is the ability of the bacteria, the presence or the absence of the bacteria that reduce nitrate from the diet into nitrite and then nitric oxide in the stomach. So I think it's a good.

You know, I developed those. I abandoned the patents on those in 2013 because it was just, we were usually giving the strips away, and it's old chemistry. It's called the grease reaction. It's a hundred year old chemistry that I just put on the end of a test strip, and my objective was try to get a method of use patent on it. But, you know, at the time, patent prosecution costs were much higher than any potential return we were going to get on the strip.

So anyway, I abandoned the patents, and now there's half a dozen companies making these strips. But here's the problem. I think they can have some utility, but the problem is there's false positives. And so you can have people with active oral infections that put that slide test strip in their mouth. They'll light it up, and if you read out, it'll say optimal or normal.

But yet they have all the clinical signs of nitric oxide deficiency. So the problem is it gives them a false sense of security. They go, well, look, you say nitric, I need nitric oxide, but I've just proved to you here that I don't need nitric oxide. Evan? Yeah, it's usually, it's a color change.

Section, so it's a bright pink. The brighter the pink, the brighter the. Little pink, the more that's there. And so what we're finding is it is those people that have, you know, they have hypertension, they have Ed, they're diabetic, they have metabolic disease, and yet they'll light the test strip up. So what we're finding is that test strip is not reflective of systemic nitric oxide production.

It's reflective of an oral infection. So what we're testing there, what we're picking up there is a local immune response from fighting some infection in the oral cavity. So I don't use the test strips anymore just because of that. Uh, I think, you know, now, as we've advanced the science, I tell people there's only two people that need nitric oxide. And if you fall within one of those two groups, then you don't need to test.

So those two groups are, if you're sick and want to get well, or if you're well and don't want to get sick, you need nitric oxide. So why do you even test? I mean, I've been taking nitric oxide for 20 years, and not because I need it. It's because I don't want to need it. And I turned 50 in November, and yet I can still run almost a seven and a half minute mile, and I don't have any symptom.

My blood pressure is 118 over 68. I exercise every day. Every day, and I don't have any issues whatsoever. But I don't wait until I develop sickness or symptoms or disease to start taking action. I take action and being proactive instead of reactive.

Speaker A
Now, one more tool in toolbox. And I didn't do it necessarily only for nitric oxide. And I'm also always curious and I'm trying things. I texted you and told you that, uh, you know, I was going to go visit my. I visited my cardiologist in St.

Louis, doctor Michael Twyman, who's been on this podcast and is very familiar with your work and considers you a colleague and one of the gamut of tests that they have. Maybe we'll show a little clip here while we're talking about it, is he has a test that, I don't know how long this test has been around, but I think at least a decade or so. Yeah, probably 15 years more. It's called an endopath test. And can you describe what this test is and why some people use it as a proxy to look at the level of nitric oxide you're producing?

Nathan Bryan
Well, that, that test is a functional test, and functional tests always trump biochemical tests because it tells the function of the blood vessel. So the endopad is a device. That's the pad is pulse, arterial tonimetry. So basically, it's looking at reactive hyperemia. So if you did this test, you know that he puts a blood pressure cuff on your upper arm, and then he puts a probe on the end of your finger.

And what this particular device is measuring is a lot of things. It's measuring your heart rate, but it's measuring temperature. It's measuring a lot of different things. So when you occlude the blood flow into the brachial artery, into the arm for five minutes, so that completely shuts down any profusion to the. And you probably got a little bit of tingling.

You're like sleeping on your arm. And then after five minutes, he can release that cuff. And then now that that vascular bed that's downstream of that occlusion has been oxygen deprived for five minutes. So if those blood vessels can make a lot of nitric oxide, then they're going to dilate immediately and get more blood flow and oxygen to that tissue that's been starved of oxygen. But if the blood vessels can't make nitric oxide, they're not going to dilate at all.

And so we call that reactive hyperemia. And reactive hyperemia is a direct measure of the body's ability, the endothelial cells, the blood vessels ability to produce nitric oxide. So if you have good endothelial function, you're going to generate a lot of nitric oxide, you're going to get a lot of vasodilation, you're going to get a lot of reactive hyperemia and good endothelial function. If you have poor endothelial function, no nitric oxide, no vasodilation, and you're not going to perform very well on that. Endoped yeah, but it's a beautiful measure of endothelial function.

Speaker A
Right. Which directly connects into your risk of heart disease in the future. The better your endothelial health, the more likely that youre not going to have a cardiovascular event and end up having blocked arteries at some point in time. Thats right. And nitric oxide plays a huge role in that.

Nathan Bryan
Well, thats how we define endothelial function today is the ability of the endothelial cells to produce nitric oxide. So the functional loss of endothelial function precedes these structural changes we see in cardiovascular disease by decades. So if you, if you have poor endothelial, if you have obstructive coronary disease, then you've been nitric oxide deficient for decades. But if you can maintain normal endothelial function, and I've done the same tests, I have good endothelial function. You have good endothelial function, then that basically prevents us from the onset and progression of cardiovascular disease.

But I think it's, it's good to do follow up tests. I do CIMT, I do the ankle brachial index, do blood pressure measurements in my arms, my, my ankles, and just do a full workup because you have to get a whole clinical picture. But I think the most important thing you can do if you're going to do one test, do the endothelial test, the endopath test. Yeah. I think it's, I don't, I didn't pay for it a la carte.

Speaker A
But I think you can go on their website. We'll link to the, it's reimbursable. It has an insurance code, ICD ten code. It's reimbursable. And if you pay out of pocket, I think it's a couple hundred bucks.

Nathan Bryan
Yeah. It's that expensive? Yeah. At the end of the day, it's not that big a deal for, for really a good insight into the lining of your blood vessels. What was interesting for me is that my strip from the nitric oxide strips, which I also did in his office, they were like medium, but I scored very well on the endopad test.

Speaker A
So I know that one of the things they were telling me, they were like, oh, well, if you didn't, if you drank something in the last, like, hour, or if you had too many liquids before, that could neutralize some of the saliva. So it's not a perfect science, but we still like to do it. But that's why I don't use them anymore. Yeah, because you'll see people out there. Yeah.

Nathan Bryan
If you take a drink of water and you test your saliva, you've just diluted that saliva by, what, 80%, maybe 100%, you know, so you're diluting it out. Yeah. Well, one of the things just that I wanted to mention additionally is through Michael and also through my friend Doctor Gabriel Lyon, I learned about the clearly scan, the clearly hard scan, which looks at actual buildup of hard plaque, which we've had for a long time, but is using this CCTA technology to now also look at soft plaque buildup with their algorithm. And one of the things that was told to me, and we made a whole podcast episode about it where I walked people through my scan and we looked at the results and everything. Again, what Doctor Twyman will link to in the show notes is that he said, you know, your level of soft plaque and hard plaque and your overall endothelial function was the cleanest that I've seen for somebody your age, that is a male, I think he said that he might have seen a female that was cleaner than my heart health, and he did a whole breakdown as to, even though my apob is quite high, when I'm not on ezetimide, which I've started, I've made the decision to start that even though my ldl was high and my apob was high, there is a protective element from having just strong nitric oxide production and having strong endothelial health.

Speaker A
So, uh, you know, and in my case, I'm a hyper reabsorber, I have a bunch of genetics that are related to that, of why I keep cholesterol in the body. So, just another reminder, when we're talking about heart disease and we're talking about Alzheimer's and, you know, these chronic diseases that are out there, even if you might be more classically predisposed to having something, and obviously, cholesterol, LDL ApOB is debated that are out there. And I welcome all the debates from all the sides. I've had a lot of the people on that have argued for different sides. Um, even though that there is a predisposition maybe genetically, or maybe you are a hyper producer or you have familial hypercholesterolemia, nitric oxide, and keeping it high is going to be one of those major protective elements.

Anything you want to add to that? No, I think you're. You're spot on the comment I have about the calcified plaque and people going to coronary calcium test. If you ask ten cardiologists, you probably get ten different opinions. But I think looking at the data, it's not the hard plaque and the stable plaque that causes rupture and causes heart attack, it's the soft plaque.

Nathan Bryan
You know, 50% of sudden cardiac deaths are in people with less than 40% stenosis of the coronary arteries. So it's not the physical obstruction of the stenosis, it's the viability of the plaque. Calcified plaque is hard, stable plaque and really very little risk of rupturing, causing acute mi. It's that soft, pliable or soft vulnerable plaque. And, you know, some people with less than 10% stenosis can have soft plaque that erupts you and have sudden cardiac death.

So I think as we improve the imaging modalities of not just to detect the calcified hard plaque, but really looking at the soft plaque, that's really puts people at risk, I think that's going to be a major advancement. And is there a direct connection between the soft plaque and nitric oxide that you would say? Yeah. So nitric oxide will help stabilize that plaque. Right.

So what happens is you start to get an upregulation of the oxidative stress, the inflammation. You get myeloperoxidase, this oxidative enzyme that eventually leads to degradation of this fibrous cap on the plaque. And then the plaque ruptures, and then you get platelets and all that sticking to it, and you get a clot and you basically occlude them coronary artery. And so nitric oxide basically stabilizes that plaque downregulates. Myeloperoxidase prevents platelets from aggregating, so even if you have a small leak, it'll prevent platelets from sticking to existing platelets and forming a clot.

So nitric oxide is extremely vascular protective and cardio protective in acute mi or people that are subject to or at risk for having a heart attack. No, we didn't touch on it, but I'd be amiss to not at least acknowledge it. Stress is a big component of lowering nitric oxide levels. Is that something that you've seen? Yeah, look, autonomic nervous system is very important in the regulation of all hormone systems.

We have to classify nitric oxide as a hormone today. We published that in 2007 that nitric oxide is an actual hormone. So anything that disrupts the autonomic nervous system, when we get more in the sympathetic, the fight or flight mode rather than the rest and digest, then it. It throws our entire hormone system out of whack. And so we've got to be able to manage stress, normalize our autonomic nervous system, and deal with stress.

Look, we live in a stressful world, but, you know, it's not what happens to you that defines you. It's how you react to what happens to you that defines you. And I think we have to. And I made a conscious decision years ago because I was under enormous stress and my health suffered from it. But I make a conscious decision that if I can't control it, I cannot worry about it.

So I don't worry about anything I can't control. So what does that mean? I don't worry about anything, because really, how much control do we have over anything in our life? And I think once I made that conscious decision and I turned my tv off and I don't watch the news, and I worry about the things that occur in my daily life and what I have control over and how I react to things, it's been a life change for me. Turning off the news was a big component for you.

Absolutely, because I find I'd get there and I would get angry, and I go, why am I angry? How's this affecting me? Well, I can handle it. I can handle this. I just turn it off.

I haven't turned my tv on since 2020. That's great. Well, there's a lot of great tv that's out there that is in the news. So hopefully you're catching some of those great shows on occasions. Maybe.

Speaker A
We talked a lot about what harms the body. As we are gearing up and entering into this sort of latter part of the interview, I want to get into your recommendations of things that we absolutely want to have people doing. You know, we talked about the dangers of the modern, industrialized, ultra processed american diet that's now being shipped all around the world, high in sugar, high in calories, you know, all of the trappings that are there, artificial flavors and junk and pesticides, et cetera. What are some of the. In addition to, you know, you talked about moderation, making sure you get adequate amount of protein, healthy diet of, you know, vegetables, meat, et cetera.

Are there any key foods that support the production of nitric oxide. Kind of broadly speaking, it's the dark green leafy vegetables. But, you know, again, going back to a paper we published in 2015, it depends upon where you live, how the vegetables are grown, what type of vegetable you're eating, because as much as a 50 to 80 fold difference in the celery grown in Dallas and Los Angeles is Chicago and New York or Raleigh, North Carolina. So the whole point is you really can't. We really can't determine if the foods we're eating are giving us enough nutrients.

Nathan Bryan
So that's why I encourage people to do micronutrient analysis. Do your own blood work and see what exactly you're missing. And then custom tailor a dietary program or supplement program that gives your body exactly what it needs, what you're missing, and then replete it back. Do, do you have a favorite one, just to cut you off there? Because I've heard people make this recommendation before, and then the audience is like, well, which one?

Speaker A
I've seen, like, the nutri, nutrival from Genova. Are there ones that you like when it comes to dietary nutrients? Spectra cell. There's a company, Spectra Cell, years ago, that had a pretty comprehensive micronutrient test. I think a lot of it.

Nathan Bryan
Look, the laboratory companies have expanded pretty broadly now. So I think there are a lot of companies out there that do some pretty comprehensive micronutrient exams. Spectra cell was one I used years ago. But here's what I do, because I think if you. You can either test or you can just do things that have nutrient density in them.

So the one thing that I do, and again, this is how I've personalized my own kind of nutrition and lifestyle program. But as I mentioned, I do a 16 to 18 hours fast every day. I wake up every morning sitting on infrared sauna for 30 minutes at 170 degrees. And before I do that, I go and take an algae product. I take chlorella and spirulina.

So these are, like, nutrient dense algae products. So they're not only providing a lot of basic micronutrients, but they contain binders. So now when I sit in the sauna for 30 minutes and I'm mobilizing toxins, these binders are present and onboard, that they bind them and you can excrete them out. But it's also during that 30 minutes that I do my prayers, I put my halo app on, and I do the rosary or whatever, and really just start my day with gratitude. And to me, again, that's the best way to start.

You're getting flight. Because I usually wake up at five or 530 before the sun comes up, but that starts my day. Detoxing, gratitude, prayer. And then I take a product from a company called wild mamas, and it's basically wild mamas. Wild mamas.

It's marketed as a prenatal. Obviously, I'm not expecting to be pregnant. I think if it's good for a pregnant mother, then it's probably good for me. Okay, but this is. It's a multivitamin.

Well, what it is, it's organ meat from wild bison. Okay. Okay. It's wild bison on the range that they take and they harvest, and they put it in capsules. So take six capsules of that, and basically provides all the organ.

Speaker A
Desiccated organs. Desiccated organs. And then they also have a salmon roe product that provides all the benefits of the fish oils, that's free of mercury, free of toxins. And so that's. That's how I start my day.

Nathan Bryan
It doesn't break my fast, but that really gets me going in the day. And I mean, like I say, I do a workup, usually twice a year with a concierge doc, a full workup, you know, three to 4 hours in our office, physical exams, CIMT oral exams. And I seem to be doing well. So a little algae, a little spirulina, little wild bison organ. I like the name of the company.

Speaker A
Wild mamas. And you mentioned what other thing you mentioned the wild mamas, and then the salmon row. The salmon row? Yeah. That's how you start off your day.

And then when you break your fast and you have your first meal, what's your go to? What do you like to have in the morning? I usually eat lunch around eleven, 3011, or 1130. That's personally, when you have your first meal. That's right.

Nathan Bryan
But it's usually. It's always protein. It's usually beef, chicken, or pork with a, you know, some side vegetable or maybe a potato or rice or something like that. But it's not. It's probably 600 calories.

I mean, it's not. But, you know, I have an active ranch, 800 acre ranch, got a couple hundred head of cattle, and so there's always something to do. So for me, I'm physically active, and so sometimes I have to fuel to maintain some work if we're baling hay or working cattle or doing whatever. Absolutely. In addition, you know, you also have developed, and we gave your company a plug previously.

Speaker A
I want to just mention it now as well, too. You've developed a nitric oxide supplement. When do you take that and how much are people taking? So, yeah, we make a nitric oxide releasing lozenge, and so we actually make the gas itself. So, similar to hormone replacement therapy in men or women, and testosterone or estrogen, we actually give that molecule back.

Nathan Bryan
Right. So if you're deficient in testosterone, what do we do? You can give testosterone and an intramuscular injection, a cream or a sub sublingual troche, and the same thing with nitric oxide. You can't, we don't give you precursors and hope your body converts it into testosterone because you can't. Right.

That's the reason you're low in testosterone and the same principles with nitric oxide. We can't give you precursors and hope your body makes it. That's the reason your body's deficient. You've lost the ability to make it. So we make an orally disintegrating tablet that you put in your mouth that dissolves over five to six minutes.

But during that five to six minutes, it's releasing 20 to 30 parts per million nitric oxide gas. We can detect it, we can quantify it, we can verify it, and it restores the oral microbiome, and it fixes the enzyme in the lining of the blood vessel. So if your body can't make nitric oxide, we do it for you, and we fix the reason your body can't make it. So I usually start out that, usually after I get out of the sauna, I'll take the lozenge to now basically enhance my circulation, because when you're. When you're.

When you're in the sauna, you're heated up to 170 degrees, so that that itself creates vasodilation. Then when I get out of the sauna, I take the lozenge to potentiate that to allow for better detoxification. And then I'll usually take, you know, one in the evening or before bed. Got it. And you mentioned, and we talked a little bit about this before, but you mentioned that, you know, your body loses this ability.

Speaker A
It's related to an enzyme in the body, is that correct? That's right. Can you explain that? It's called the nitric oxide synthase enzyme. It's found in the lining of the blood vessels, it's found in our immune cells, and it's found in our neurons in the brain.

Nathan Bryan
So this is a. It's like two twins that come together that allow for this flow of electrons to produce nitric oxide. But when there's oxidative stress, it becomes uncoupled. And now that enzyme will reduce molecular oxygen into superoxide instead of nitric oxide. So now it's producing an oxidative, oxidative stress and oxygen radical instead of this protective nitric oxide molecule.

So what we focused on is try to, how do we recouple that NOS enzyme and prevent the superoxide production, produce nitric oxide at adequate levels, and then allow for the signaling aspects of nitric oxide to occur. And that's the riddle we've solved that no one else has solved. That's great. And would you say that it's a fair assessment to say that, you know, we still want to be doing all these lifestyle habits because we're not yet at the place either with supplements or drugs that one thing can replace, you know, a lifestyle of inactivity or not having an appropriate diet. These supplements, including your own, these are insurance policies on top of foundational.

That's right. Diet, lifestyle, stress management that are going to be things that are going to keep us healthy. Doctor Justin. Yeah, I say all the time, you know, nitric oxide is foundational. It's critically important, but it's not a panacea and it's not an end all, be all, cure all, because you still have to address other issues.

Right. So if you're deficient in magnesium, nitric oxide is not going to replete that, although we have magnesium in our product. But if you're deficient in vitamin D, you know, you obviously need to address the vitamin D. Nitric oxide's not going to normalize your vitamin D level. But what we're finding is that until you restore the body's ability to make nitric oxide, really nothing else is going to occur thereafter, because if your cells can't communicate, no matter what you do, they can't function.

So let's, let's set the foundation, let's normalize nitric oxide, and then that allows you to focus. And what it'll allow you to do is the other things that may not have been the symptoms, that may, you may have been attributed to something else may go away if you just restore nitric oxide. So now we've upped the game a little bit, and now what remaining symptoms, what symptoms may remain? Now, you can attribute to that and address that, but if you try to cherry pick these and just without fixing nitric oxide, then you're chasing your tail. You have to first and foundationally restore nitric oxide, and then everything else will work itself out.

Speaker A
You know, drugs are a part of our culture. I'm not talking about psilocybin and stuff. I'm talking about traditional pharmaceutical drugs, and they play an important role in disease management. We are over medicated as a society, and people are on a bunch of stuff for root issues that could be largely fixed with diet and lifestyle, but they are an important part. I mentioned myself earlier.

After weighing the pros and cons and looking at a bunch of different, you know, conversations with people that I respect, and talking with my cardiologist, I decided to start on ezetimide in particular to help block some of the reabsorption of cholesterol. And I saw the improvements that it made on my APOB. I'm going to still do all the lifestyle stuff that is leading to me having, you know, a super clean, you know, artery system right now. Right now. And, you know, I'm thankful that, you know, we have certain things that are out there, and I still want to do the education that's on the podcast and have experts like yourself.

So why I mentioned all that is that there are people, including, I think you have a group that's looking at this, and there might be some other people looking at this, too, that hopefully one day we'll have some maybe pharmaceutical interventions when it comes to nitric oxide. Can you chat about that a little bit? Yeah. Look, I got into this field in science and medicine 25 years ago to understand human disease to the extent that we could fix it. And we fix it, at least in the US, with this model going through the FDA and getting approved indications for drugs.

Nathan Bryan
So certainly we understand how the human body makes nitric oxide. We understand what goes wrong in people that can't make it. We know the clinical consequences of that, and now we know how to fix it. So, through my company, Brian Therapeutics, we've got active programs in drug discovery where we're moving through the FDA. But I want to make a clear point here, because I was trained in drug discovery and drug development as a biochemist and physiologist.

But I think the way that we've developed drugs over the past several hundred years, there is an application, but there's always consequences, and those are side effects, because most drug companies use pharmacology. So you understand the function of an enzyme, and then you create a synthetic compound that inhibits that biochemical reaction. And these are the Cox two inhibitors. These are non steroidal anti inflammatories. They're proton pump inhibitors.

There's ace inhibitors, hence the word inhibitor. They're inhibiting a biochemical reaction. And when you do that, there's always consequences. So what we do in our company is we utilize a system called restorative physiology. We never employ pharmacology.

We know what nitric oxide, we know how much nitric oxide is being produced in a healthy person, and we give that back. We're not inhibiting a biochemical reaction, we're not creating biologics and faking the immune system and creating monoclonal antibodies. We're giving back an essential signaling molecule and hormone nitric oxide, at the right doses, at the right time, in the right patient. And I think what we're finding, I don't think, I believe, and I know that there will be no side effects to that. So we've got active drug programs for ischemic heart disease.

We've got a drug for Alzheimer's, and I make a topical nitric oxide for diabetic ulcers and non healing wounds. Evan, fantastic. So those are being worked on. That's right. And they'll maybe be in the pipeline one day.

Speaker A
Hopefully not going to work. Development is a very costly and tough situation to do, but that's the hope that you guys are working on. Yeah, I think our ischemic heart disease drug, we're working on that now. My anticipation is we'll have a drug approved on the market in early 2025. The Alzheimer's program is probably a two year project.

Nathan Bryan
So probably 2026, we'll have an Alzheimer's drug approved on the market and a similar timeline for our topical drug for diabetic ulcers a couple of years. Fantastic. Well, while those are options that are on the table, you know, I so appreciate you coming on the podcast again, coming back on the podcast today and reminding us about why nitric oxide is so foundational to our health and how it's key, and why it's key to start early in making sure we address the root issues that are degrading it as we age. And as you've shared with us today, there's a lot that we can do between our diet, our lifestyle, and avoiding the top things that are destroying it. And of course, as an insurance policy, we can also seek out supplements like the ones you've mentioned below.

Speaker A
Um, Doctor Nathan Bryan, this has been fantastic. Remind everybody, where can they follow you and your work and keep in touch? And how would they find out about all the projects that you're up to? Well, I encourage people to follow my YouTube channel, Doctor Nathan S. Brian Nitric Oxide.

Nathan Bryan
I've got an educational website, doctor nathansbrian.com comma, and we do a monthly blog. Get some videos on there for those interested in the product technology. It's n 10, one.com. that's the letter. N the number one, the letter.

Our drug company is briantherapeutics.com. i'm searchable on PubMed if you want to read our published scientific papers. I'm findable on most search engines. But yeah, I think the next stage of this technology is really to get through the FTA, because the source of my daily frustrations are other dietary supplement companies out there selling nitric oxide products that really have no basis. They can't work.

I mean, you can't get nitric oxide in a gummy or a chew, in fact, that destroys nitric oxide. You can't take nitric oxide in a capsule or a pill, but yet they're all saying the same things that we're saying. So the only way to move this forward and to really differentiate what we do is go through the rigor of the FDA, demonstrate safety, demonstrate efficacy in a number of different disease indications, and then, and only then will nitric oxide be front and center and be a daily conversation piece. It'll be like the fish oil of the 1980s. Well, I look forward to that time.

Speaker A
But right now, I really encourage everybody, get your workouts in, improve your cardiovascular health. Stay away from mouthwash. That's something that we've all learned from you. Find a functional or biological dentist that can help clean up your oral health. Askthedentist.com has a great directory on there, a bunch of people that are there.

Clean up your diet. You know, make sure you're fasting insulin, hemoglobin, a one c, triglycerides, fasting glucose are all within range. There's so many things that are available for us to be able to do right now if we want to improve our nitric oxide levels and minimize our risk of chronic disease. And thank you for coming back on the show and reminding us about all that. Thank you, Drew.

Nathan Bryan
Good being with you.

Speaker A
Hi, everyone. Drew here. Two quick things. Number one, thank you so much for listening to this podcast. If you haven't already subscribe, just hit the subscribe button on your favorite podcast app.

And by the way, if you love this episode, it would mean the world to me. And it's the number one thing that you can do to support this podcast is share with a friend. Share with a friend who would benefit from listening. Number two, before I go, I just had to tell you about something that I've been working on that I'm super excited about. It's my weekly newsletter, and it's called try this.

Every Friday. Yes, every Friday, 52 weeks a year, I send out an easy to digest protocol of simple steps that you or anyone you love can follow to optimize your own health. We cover everything from nutrition to mindset to metabolic health, sleep, community, longevity, and so much more. If you want to get on this email list, which is, by the way, free, and get my weekly step by step protocols for whole body health and optimization, click the link in the show notes that's called try this. Or just go to druparowit.com that's dash Rupurohit.com and click on the tab that says try this.