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

Episode Date: May 29, 2024

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.   In this episode, Dhru and Dr. Bryan dive into (audio version / Apple Subscriber version): Nitric oxide as the holy grail molecule (00:00:02 / 00:00:02) Four hallmarks of disease (1:01 / 1:01)  Antacid medications: lack of research and the consequences of extended use (4:41 / 4:41) Lower nitric oxide and the risk of Alzheimer’s (14:00 / 10:45) Lifestyle habits that contribute to Alzheimer’s and biomarkers to check (17:15 /13:01) What is nitric oxide and its core role in our bodies (27:00  / 23:39) Lifestyle factors that hinder nitric oxide production (33:00 / 28:22)  Nitric oxide and high blood pressure (46:00 / 41:04)  Filtering water in your home and oral dysbiosis (51:00 / 46:30) Navigating antacid medication usage and tapering off (1:11:00 / 1:06:50) Testing nitric oxide level production (1:15:00 / 1:10:06) The role of stress on our nitric oxide levels (1:29:00 / 1:24:53) Foods that support production and supplementation (1:32:00 / 1:27:10) Final thoughts: (1:44:00 / 1:39:40)  Also mentioned in this episode: N1O1.com (get 10% off any of Dr. Bryan’s nitric oxide products with the code DHRU)  Bryan Therapeutics EWG Fygg Toothpaste  For more on Dr. Bryan, follow him on Instagram, Twitter, YouTube, and through his website,    Right now, get 30% off your Cozy Earth sheets. Just head over to cozyearth.com/dhru and use code DHRUP. Fatty15 is offering an additional 15% off its 90-day subscription Starter Kit. Go to fatty15.com/dhru and use code DHRU to replenish your C15 levels for long-term health.  To get 25% off your Birch Living mattress plus two free eco-rest pillows, head over to birchliving.com/dhru today. Learn more about your ad choices. Visit megaphone.fm/adchoices

Transcript
Discussion (0)
Starting point is 00:00:00 Dr. 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
Starting point is 00:00:40 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. 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? Cardiologist only deal with the heart, you know, pulmonologists, the lungs, and, you know, neurologist, the lungs, and, you know, neurologist, and the neurologist, or a coroner disease, or heart disease, there's four common denominators. It's always low blood flow. We call that hypoxia or ischemia
Starting point is 00:01:21 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 use in the beginning, the holy grail, right? Really like, replicate that further and connect the dots between nitric oxide and those four hallmarks,
Starting point is 00:02:00 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. 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
Starting point is 00:02:36 with advanced coronary disease or cardiovascular disease, what happens is over time, their coronary arteries that are 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. And so nitric oxide actually dilates the blood vessels.
Starting point is 00:03:04 So 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. 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,
Starting point is 00:03:33 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 a 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,
Starting point is 00:04:01 we decrease the adhesion molecules, so then we mitigate the inflammation, oxidative stress, immune dysfunction. And there's evidence now that if we, in patients that have advanced disease, cornea-ard disease, arthroscopis, 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. Let's connect the dots by talking about a real world disease that a lot of people are very well aware of.
Starting point is 00:04:30 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? 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 an acids. They're used, their FDA approved for the treatment of acute
Starting point is 00:05:12 gastroesophageal reflux disease or girt or acid reflux. And so these drugs were first approved in the late 80s. And the clinical trials, and the reason was it was when people have acid reflux, they get baritosophagus, which leads to erosion and then can eventually lead to gastrophageal cancers. So the thought process at the time was that it's an overproduction of nitrox or overproduction of stomach acids. So if we could suppress stomach acid production, you could get acute symptomatic relief of the acid reflux. But, you know, the FDA approved these drugs for acute use.
Starting point is 00:05:48 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 90s, the first over-the-counter proton pump inhibitor was approved, Prilosec, and then later prevised and the nexium, and so now you've got different brands of over-the-counter proton pump inhibitors.
Starting point is 00:06:10 And people have been on these now for three, five, 15, 20, sometimes 25 years. And they were never intended to be used that way. No, there was never, 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 apolloric seals in the loomine
Starting point is 00:06:37 of the stomach. And so, you know, 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. 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, chroming, most micronutrients, and we need stomach acid to make nitric oxide. And so shutting down stomach acid production obviously will have unintended consequences. And now we're seeing that come to the fore.
Starting point is 00:07:11 And, you know, in 2015, it was first reported that people have been on PPI for three to five years have anywhere from a 20 to 40% higher incidence of heart attack. Wow. And now the study that just came out a couple of months ago showed that people had been on these drugs for at least four years at as much as a 30 to 40% increase in Alzheimer's in dementia. That's super, super scary for those that are listening. I mean, heart attacks are scary and they're the number one killer of people,
Starting point is 00:07:39 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. 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.
Starting point is 00:08:12 And I think anybody who's dealt with an Alzheimer's patients, patients seize 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. You know, they're basically, you know, have to be, have 24-hour 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, increase risk of hip fractures or bone fractures because you can't absorb calcium so your bones don't remodel.
Starting point is 00:08:51 You develop brittle bones. You don't absorb magnesium. So you develop low magnesium. And magnesium is involved in like 87 something chemical reactions, biochemical reactions. There's no... It's 800. I saw the latest data. It's 800.
Starting point is 00:09:05 I mean, I should... A couple years ago was 600 and the latest is 800. Yeah, 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 claustridium, 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,
Starting point is 00:09:35 known heart attack strokes and dimensional Alzheimer's, before the regulators or the manufacturers of these drugs put a black box warning on it say, look, for me, it's always risk benefit, right? 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 risk are way up here. And it's multi-systemic disease, it's kidneys, its 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 no one in their right mind would ever take these drugs.
Starting point is 00:10:15 Yeah, 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 I've said, listen, we want to put you on and we want to get you off as soon as possible,
Starting point is 00:10:33 which means we have to be aware of what else actually helps get to the root of why are you having this gurd? 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 it that something like Alzheimer's disease would be more likely to happen if your nitric oxide is lower? Connect those dots for us. Yeah.
Starting point is 00:10:53 So today we understand exact ideology of Alzheimer's in vaster dimension. 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 readings of the brain. So in spec scans, it tells us how well profuse 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, if any, 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
Starting point is 00:11:38 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 profusing that region of the brain atrophies. And you get brain atrophies, 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, it actually allows glut4 translocation to bring glucose into the cell. So now if you're adequately profusing 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
Starting point is 00:12:20 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 re-come across your work in interview form was you were on my friend Dr. David Perlmutter's podcast. and he is a neurologist who's known for a lot of his work on the brain, and he talks a lot about Alzheimer's. He was one of the first people that had heard use the term type 3 diabetes when it comes to Alzheimer's. So what are some of the lifestyle things that people are doing?
Starting point is 00:12:53 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? Well, it's the known risk factors. I think the most common problem people are doing is sugar-coachers.
Starting point is 00:13:33 consumption, an over-consuming carbon. Can I pause you for one 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. So I don't know how known it is. So I apologize. Well, it's known in the scientific community.
Starting point is 00:13:52 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 is one of the most addictive molecules. that we know, right? And it's in everything. It's in, 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
Starting point is 00:14:22 that makes nitric oxide. And it also sticks to hemoglobin, and we call that hemoglobin A1C. But hemoglobin is just one kind of marker protein, but if it's sticking to hemoglobin, when sticking to other proteins and enzymes and ruining 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, is we become insulin resistant. So chronic exposure to elevated levels of sugar leads to insulin resistance. Now we have hyperinsulinia, hyperglycemia, and that's what leads to the chronic inflammation we see in diabetics.
Starting point is 00:14:57 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 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. You know, 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.
Starting point is 00:15:27 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.
Starting point is 00:15:57 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 beginning. 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 U.S. 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
Starting point is 00:16:28 goes wrong, and the mechanism is these 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. You know, you have sugar in your diet, I have sugar in my diet, 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,
Starting point is 00:17:01 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 they have a little bit of 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.
Starting point is 00:17:37 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. You know, it needs to be, they say normal is less than 100. Your fasting glucose levels. It really needs to be below nine of your best 80. and then your hemoglobin A1C is kind of your long-term, kind of your average blood glucose levels that were, say, the previous four to six months.
Starting point is 00:18:07 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.
Starting point is 00:18:35 If you run out of fats, you start breaking down proteins. 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 five 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 eight hours and I'm not going to burn any energy or consume any fuel, then the last thing I need is sugar.
Starting point is 00:19:05 Because then 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, 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 5.30, and I don't eat after that.
Starting point is 00:19:43 And then, you know, I eat lunch the next day, so I do a 16 to 18 hour 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 80, 90 or certainly below that. Would you also add fasting insulin to the list of tests that people should be paying attention to? 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,
Starting point is 00:20:16 or you're developing insulin resistance, your blood sugar may be moderately balanced, but if your insulin levels is 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 in inflammatory cascade. So yeah, so fasting insulin, fasting blood glucose levels, hemoglobin A1C 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?
Starting point is 00:20:44 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. Well, that's the problem 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,
Starting point is 00:21:11 so one standard deviation in is considered what's normal. So, for instance, what was normal labs 50 years ago is completely different than what's normal labs today. And 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 physician 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 you're like normal to your colleagues.
Starting point is 00:21:48 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, or three out of four Americans are overweight and half Americans are obese? Two out of three Americans have an unsafe elevation and blood pressure. I mean, is that normal? It's certainly not optimal. 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
Starting point is 00:22:30 who's working out, an athlete, how much muscle mass they have. But that's also a problem. Is that correct? Yeah, 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 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 anthropetric markers of BMI, but it's how metabolically fit are you and how good is your endothelial function.
Starting point is 00:23:11 What are your fasting insulin levels in these markers we just talked about? And can you go out and walk briskly or run or jogging? for 20 or 30 minutes without getting shorter 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 I think this is a good opportunity. Even if people heard our first episode together, which, you know, has almost a million views on YouTube. Remind people just what is nitric oxide and what is its core role in the body?
Starting point is 00:23:42 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. 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 no seception or pain sensitization or pain feeling pain. It's how our immune cells fight off viruses and bacteria. It's so when we have an infection or we're exposed to a virus or immune cells, go to that side 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, you know, 25 years ago that if you become nitric oxide deficient, it was a, you develop high blood pressure, you develop erectile dysfunction,
Starting point is 00:24:34 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.
Starting point is 00:25:04 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 are, to get a Nobel Prize, it has to be, discoveries that change the landscape of mankind, right, or really impacted mankind. Foundational shift in our understanding. 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.
Starting point is 00:25:41 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
Starting point is 00:25:56 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-translarsely modifies proteins and affects their structure and function and then turn some genes on,
Starting point is 00:26:12 turn some genes off, activate some proteins, turn some proteins off. So we understand the mechanism of nitric oxide signaling. You know, you've heard it call it a miracle molecule, and I think that was probably appropriate 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.
Starting point is 00:26:35 So it's not a miraculous molecule. 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 it'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 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
Starting point is 00:27:19 and accelerate it because there's 20, 30-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 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 explain there, and I'll share my own words, is that there's some connection to it lowering as we age. 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
Starting point is 00:28:05 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 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.
Starting point is 00:28:21 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? Well, it's sugar, as we mentioned. I mean, sugar destroys the oral microbiome. so we know that their bacteria in and on the body that help produce nitric oxide. Sugar completely destroys the microbiome. It glikates the enzyme. It leads to a lot of oxidative stress,
Starting point is 00:28:47 which oxidizes an essential co-factor 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 pressures of feeding a growing population is at the expense of nutrient density.
Starting point is 00:29:20 So years ago, 100 years ago, there was crop rotations, there was fertilizing in the fields, there were no herbicides or pesticides. It was, you know, farming, 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 macro-nutrients. So the foods we're getting are leading us to a nutrient-deficient society, and without certain nutrients, then you develop chronic disease,
Starting point is 00:29:50 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 inane study show that most of the body, 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.
Starting point is 00:30:24 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 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.
Starting point is 00:30:48 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, physical exercise, 20, 30 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,
Starting point is 00:31:09 sunlight. What's the role between getting sunlight exposure? And you can tell us at what time of a 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 kind of like the mammalian chloroplast of plants, right? It's 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.
Starting point is 00:31:50 So today, and I think we published on this probably in 2002, that we could identify these what we call photolabial stores of nitrogen. 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 a hundred 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. So it's direct correlation with the amount of sunlight and vitamin D and vitamin D activates and improves nitric oxide production. So in populations that are vitamin D deficient, they're typically
Starting point is 00:32:31 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 thial on a protein or in some enzyme. And so it 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,
Starting point is 00:33:09 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 laboac 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,
Starting point is 00:33:39 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. The calories are kind of, and there's different sources of calories, right?
Starting point is 00:34:07 But I think at the end of the day, if we're just looking mathematically or stoichiometrically, you've got to consume the calories that you put into your body or else they're going to 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,
Starting point is 00:34:34 had consumed 25,000 calories, which some people do, and they're 3, 400 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.
Starting point is 00:34:51 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, not having modeling, you know, in the families that you grow up.
Starting point is 00:35:18 If your family isn't cooking at home, you're much more likely to eat ultra-process foods. sedentary lifestyle, you mentioned. We know that if you get less, and I think it's like four to six thousand steps a day, that's considered sedentary, right? Yeah. Four to six thousand 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 who drive around a parking lot for 20 minutes. minutes to prevent walking an extra 20 yards.
Starting point is 00:35:54 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 4,000 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. So diet you talked about, you talked about the fitness aspect.
Starting point is 00:36:18 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 shared 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. I mean, all you have to do is listen to the commercials.
Starting point is 00:36:54 These mouthwash, say it kills 99.99% of the bacteria in your mouth. And that, by the way, it's not a good thing. Yeah. But yet companies are advertising that. I mean, think about, again, I take important clinical observations, right, 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, you know, disease starts in the gut and most chronic diseases can be traced
Starting point is 00:37:29 back to dysbiosis in the gut. So the bacteria that live in and on our body outnumber our human cells 10 to 1. 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,
Starting point is 00:38:06 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 anerobes 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 20 or 30 years, we certainly know which bacteria are present and
Starting point is 00:38:40 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.
Starting point is 00:39:08 He 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. Okay, got it. And that really means anything above 120 over 80. I think that the statistics probably even higher than that. Because it's, 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 80, 130 over 85, your doctor's probably going to say, well, that's not bad. Well, you've got an extra 10% increase in developing heart disease or cardiovascular disease.
Starting point is 00:39:53 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 going to be four, six millimeters of mercury. So if you've got a patient that has blood pressure of 150 over 100, they're going to have to be on half a dozen different antihepotentive medications to get their blood pressure 20 over 120 over 80.
Starting point is 00:40:26 And then what happens? We develop all these side effects. You've 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 there's no way the body can heal or operate when it's being inhibited by that many chemical reactions or synthetic inhibitors about chemical reactions. You sort of made the connection earlier, but let's make it now here. Connect nitric oxide and high blood pressure.
Starting point is 00:40:50 This is so important because so many people have high blood pressure. 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.
Starting point is 00:41:17 But we also have a finite number of blood vessels. 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,
Starting point is 00:41:40 and that's an increase in pressure. And so what that means is when you have constricted, stiff blood vessels, now with each beat 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, you know, damages that barrier function.
Starting point is 00:42:04 And if our body can make nitric oxide, the blood vessels are dilated, but more importantly, they become soft and compliant. ampen that pulse wave with each heartbeat. And you can do this through augmentation pressures and look at kind of the reflective wave with each heartbeat. But in terms of blood pressure, it's really just the loss of the vasodilation
Starting point is 00:42:23 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
Starting point is 00:42:50 arteries? And what we're finding is it's nitric oxide being produced, we swallow our saliva, it's transported at S-nitrozo-glutothion, 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 connect to the knee bone. The mouth is connected to the blood vessels. I mean, it makes perfect sense to me. But, 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.
Starting point is 00:43:27 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. And 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 anti-hypertensives. There's what's called ACE inhibitors, which inhibit the conversion of of an angiotensin converting enzyme. There's ARBs, ancientininin receptor blockers. So there's a working on kind of the kidney aspect of the regulation of blood flow. It's called the Renan angiotensin system. And then there's things like calcium channel antagonists, which which might
Starting point is 00:44:08 modulate the amount of calcium being released in the 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 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 anti-hypertensives, 50% of the people don't respond with better blood pressure. And 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.
Starting point is 00:44:51 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 10 out of 10 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.
Starting point is 00:45:15 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. changed 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.
Starting point is 00:45:45 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 is 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,
Starting point is 00:46:15 they completely repopulate, produce nitric oxide, and your blood pressure becomes better 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. 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.
Starting point is 00:46:42 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. I mean, the Flint, Michigan story from years ago. I mean, the pipes in many of these municipalities
Starting point is 00:47:02 are decades, you know, years old 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 it 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 and it's the water you're cooking in, it's the water you're bathing in.
Starting point is 00:47:36 And 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.
Starting point is 00:47:47 Wow. 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 test, run labs, hydrate him.
Starting point is 00:47:58 And 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.
Starting point is 00:48:21 So we get him a filtration system. And basically the water overwhelmed the filtration system. So then we had to constantly, you know, 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? Was it we know in certain places,
Starting point is 00:48:39 you know, fracking has contributed to, you know, 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. I mean, this is opening Pandora's box, right? So when you start to interrogate this and, you know, there's enormous liability only municipality. Yeah.
Starting point is 00:48:57 Because it's not just my dad. I mean, how many other people, dad is just a little bit fragile because of all of his comorbidities in 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's not in the standard testing, then how do you know? And so all of these things that they sent off for their water supply were within the normal range,
Starting point is 00:49:29 of what's allowed, but yet my question was, what about this, this, this, and this. And they go, we don't test for that. 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. Yeah.
Starting point is 00:49:44 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 a really terrible water situation, we're learning more and more 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've found this, you know, some like radioactive isotopes in the water at some level.
Starting point is 00:50:19 They found levels of arsenic and, 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, PFAs, 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, did you get reverse osmosis? Is there a philipal?
Starting point is 00:50:58 that you recommend to our audience? Yeah, I, look, we, I do 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.
Starting point is 00:51:19 Those are just the ones that I've 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's ozinated, 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.
Starting point is 00:51:40 Ditch fluoride. It's always funny when you go to these high-end gyms around Los Angeles and any other city too. I think Equinox was doing this back of 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 men's restroom there, and there's like mouthwash everywhere, right?
Starting point is 00:51:57 because 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 Zylot's all 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. 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
Starting point is 00:52:29 to the standard of care in dental medicine because every time you go to the dentist, they'd want to fluoride rinse. They encourage you to use mouthwash so you kill the peridonal bacteria and the gingerville 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
Starting point is 00:52:56 how do we selectively kill the bad bacteria while maintaining the ecology of the good bacteria. And so 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 right now.
Starting point is 00:53:14 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 offensive when you talk to these people.
Starting point is 00:53:40 And it's not their fault. It's just their, it's dysbiosis. And so those people feel like they need to use mouthwash. And I think 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.
Starting point is 00:54:05 Everything that's excreted from the skin or in the mouth, through 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. biome 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
Starting point is 00:54:28 going to give it to patients with high blood pressure and see if we can normalize your blood pressure with a mouth rinse. That's great. Because that would be, I think that's a game change. 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 look up to, they'll use like hydroxyapitite, right, as one, you know, solution that it actually remineralizes.
Starting point is 00:54:51 I use one called FIG, FYG, not affiliated with them, just a big fan of the company. It's developed by this guy, Mark Berhenna, who I think you know, asked the dentist. He's a really good guy, biological and functional dentist. 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, tongue-tonged tongue-tied. But also that remineralizes the water because you need that. You don't want distilled water.
Starting point is 00:55:24 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 that, how much dysbiosis in the mouth is also, you know, I know this may not be necessarily your area of expertise. But people might need to go and work with like a biological or a functional dentist.
Starting point is 00:55:48 And somebody who, you know, helps them also take a look at their diet and talking. talks about the relationship between diet and oral microbiome. Yeah. Now that was the beauty of this dental conference that I was speaking at this weekend. It's called the Integrative Dental Medicine Scholars Society. I'd recommend anybody check these people up because their whole mission and objective is to get physicians and dentists working together. Right.
Starting point is 00:56:10 Because there's so many chronic, poorly managed diseases that can be traced back to oral disposis or infections in the mouth. And in dental medicine, a lot of these infections can be asymptomatic. addict, right? You don't know you have an infection. And the best example is in root canal teeth. Right. So if you go to, 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
Starting point is 00:56:49 side of infection. So then what happens, you're going to live for the next 5, 10, 15, 20 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 bloodstream. You don't know it. And if you get an x-ray, the radiolucency is going to show you the osteoacrosis 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 radio lucency of an asymptomatic infection. And so you have to get that resolved and you have to get that mitigated.
Starting point is 00:57:23 You could 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 it's contributing to chronic disease. I know. I had my own personal dentist who's based here in L.A. in Santa Monica, Dr. Rosita Rostian, she's at Serenity Dental Center. She came on the podcast
Starting point is 00:57:56 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 healthier her entire life, but she had a couple teeth that were removed incorrectly.
Starting point is 00:58:31 One of them was a root canal. And until she started researching on her own and kind of going to Dr. Google and Dr. 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 canals cleaned out and in her case it was multi-dimensional 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 a ls type symptoms neurological symptoms that were poorly managed for 10 or 15 years and we just
Starting point is 00:59:11 have a conversation about root canals and you know they roll into the dentist into a wheelchair and they walk out wow they're walk out when they clean up the infection. I mean, it's the most, same thing with my dad. You know, my dad was chronically, he had a car accident in 1984, he's peripelagic, 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, he's doing great for 76-year-old paraplegic. Wow. And then I've never, I've never seen a cancer patient that didn't have an oral infection.
Starting point is 00:59:49 Zero, 100% of the cancer patients I've consulted with, it's been dozens of 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 me, that's the first question when people come to me
Starting point is 01:00:09 and they said they got cancer or 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 and like I got cancer I don't have a toothache it's not an obvious correlation but get it checked out yeah 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
Starting point is 01:00:43 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. But I want to ask you a question. In addition of those, is there anything else that we miss 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 mechanism, so again, if we take kind of indisputable clinical evidence showing by real numbers, people who had been on PPI for four years, 30% increase in Alzheimer's and dementia. So then if you take that data and extrapolate that back and try to understand mechanistically,
Starting point is 01:01:20 what is it 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 loom of the stomach. But when you lose the acidity of the stomach, so part of this entero-salivary circuit or the bacteria producing nitric oxide. What they're doing is they're reducing a molecule called nitrate, which is NO3-minus,
Starting point is 01:01:48 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 PCA of nitrite, and biochemically that means the pH at which 50% of that nitrite would become protonate and form nitric oxide gas is 3.4.
Starting point is 01:02:08 So when we swallow our own saliva, get, as long as their stomach acid production, we get a burst of nitric oxide gas in the lumen of the stomach. It's absorbed across the gastrumucosum. It's transported by binding the cysteine thials and glutathione and organic 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 hydrolyse enzyme, but 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,
Starting point is 01:02:50 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 they're doing this, what happens? You lose regulation of blood flow, you develop insin resistance. What does that lead to? Alzheimer's. Wow. You know, just on that thread, you know, 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. This was a couple years ago. And there was a lot of stress and travel. For the first time, she developed
Starting point is 01:03:38 acid reflux-like symptoms that were there. And I called around to my network, and ultimately I got connected to this integrative E&T 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. Dr. Benjamin Asher. And he helped my mom temporarily kind of put her through this phase process, because
Starting point is 01:04:08 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. You know, 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 PPI is providing, 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?
Starting point is 01:04:50 Yeah. Right? So the doctor, in her case, in 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,
Starting point is 01:05:11 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 exasperate the issue. So he dialed in some diet, remove some things. A lot of functional doctors would do this as well.
Starting point is 01:05:27 Then in addition, he brought in some supplements. He actually recommended this one supplement that's over the counter in the UK called Gavistam. It's fenagreek. and a couple other things. You can't get it in the U.S., but we ordered it from Amazon and somebody sent it over from the UK.
Starting point is 01:05:44 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?
Starting point is 01:05:58 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, Dr. Niel Patel,
Starting point is 01:06:21 they're like, look, it's not anxiety. Is 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 Dr. Asher ended up working, but I just wanted to highlight that having dealt with and supported somebody's close to me firsthand, I know that it can be tricky, but hopefully we can put some articles below. I know Chris Cressor 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 here's the thing, you can't stop these drugs cold turkey. Yes, you can't stop them cold turkey.
Starting point is 01:07:00 Because you get a horrible rebate. effect and hyper secretion of acids. So what I tell people is to wean these off, especially we've been on them for a number of years, is whatever dose you're taking, start taking half, and take that half dose for 10 days. Then after 10 days, take that half dose every other day. Do that for 10 days. And then you can stop. 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, it's a pH of 2. So when you can When you take that vinegar, it acidifies the looment of the stomach.
Starting point is 01:07:35 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 b-carb, you need sodium b-carb. But yet if you've been on PPI's, 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 sales producing stomach acid
Starting point is 01:08:07 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, 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 why you would inhibit stomach acid production. Right. Because if you can't make stomach acid, you can't break down proteins. Your body sees it as a foreign substance and your body is trying to get rid of it and expectorate it.
Starting point is 01:08:39 And that's the reflux you're seeing. So if you can make sufficient stomach acidify the loom of the stomach, then your body can break it down. You'll have gastric emptying into the duoden and the digestive system works perfectly fine. But all of that's dependent upon stomach acid production. 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
Starting point is 01:09:12 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 a 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 that actually works. I was like, okay, cool. He didn't get in trouble for that. He got in trouble for all those 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
Starting point is 01:09:47 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 that you can 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.
Starting point is 01:10:26 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, it's 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. The first one is usually erectile dysfunction. Because if you can't dilate the blood vessels in the sex organs to get engorgement,
Starting point is 01:10:53 to get an erection, and that's in both men and women, by the way, then the first one, And 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 clitorin 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, 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.
Starting point is 01:11:18 That's right. And their clitoris actually can enlarge by like two, two point five times in size through blood flow. That's what starts the orgasm process. So you have to have that intral labial interclitoral pressure in order for women to reach orgasm. Right. And as you've shared before, it's not everything with women. There's the psychological component, hormonal component, other stuff. With men, it's a little bit simpler.
Starting point is 01:11:39 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 nitricoxic. Number two, if your blood pressure is above 120 over 80, and obviously the higher, the higher degree of nitric oxide deficiency. And then number three, you start to develop metabolic disease, insulin resistance,
Starting point is 01:12:07 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 shorter breath, you tire easily, then obviously your body's not making nitric oxide 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 in-stage disease.
Starting point is 01:12:35 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. 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
Starting point is 01:13:00 that you can buy for a few dollars on Amazon. 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 reason for that was because people asked me, and this was when we were entering the nitric oxide field
Starting point is 01:13:20 because in developing products and people go, how do I need if I need nitric oxide? It's a valid question, right? And so based on the known chemistry of how nitric oxide's produced, what it becomes, where it goes, and through this intero-salivary circuit in the bacteria, I developed this saliva test strip.
Starting point is 01:13:39 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
Starting point is 01:14:08 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 strips. So anyway, I abandon 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.
Starting point is 01:14:33 And so you can have people with active oral infections that put that 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 I need nitric oxide, but I've just proved to you hear that I don't need nitric oxide. Yeah, it's usually a, it's a color change spectrum. Yeah, so it's a bright pink, the brighter the pink, the higher the levels.
Starting point is 01:14:59 The brighter the 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 you have to light that 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. I think, you know, now as we've advanced the science, I tell people there's only two people that need nitric oxide.
Starting point is 01:15:35 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, and I exercise every day, every day, and I don't have any issues whatsoever.
Starting point is 01:16:08 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. Now, one more tool and 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, you know, I was going to go visit my, I visited my cardiologist in St. Louis, Dr. 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,
Starting point is 01:16:51 but I think at least a decade or so. Yeah, probably 15 years or 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? Well, that test is a functional test. And functional test always trump biochemical test because it tells the function of the blood vessel.
Starting point is 01:17:12 So the endopad is a device that the pad is pulse arterial tonymetry. 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,
Starting point is 01:17:40 so that completely shuts down any profusion to the, and you probably got a little bit of tingling. Yeah, your arm gets numb, tingling. You're like sleeping on your own. And then after five minutes, he can release that cuff. And then now 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,
Starting point is 01:18:01 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.
Starting point is 01:18:21 So if you have good anethel 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 hyperremaeum and good anethelial function. If you have poor endothelial function, no nitric oxide, no vasodilation, and you're not going to perform very well on that endopat.
Starting point is 01:18:36 Yeah. But it's a beautiful measure of endothelial function. Right, which directly connects into your risk of heart disease in the future. The better your endothelial health, the more likely that you're not going to have a cardiovascular event and end up having, you know, blocked arteries, you know, at some point in time. That's right. And nitric oxide plays a huge role in that.
Starting point is 01:19:00 Well, that's how we define endothelial function today is the ability of the endothelial cells to produce nitric oxide. So the loss, the functional loss of endothelial function precedes these structural changes we see in cardiovascular disease by decades. So 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 test, I have good endothel function, you have good endothel function, then that basically prevents us from
Starting point is 01:19:32 the onset and progression of cardiovascular disease. But I think it's good to do follow-up test. I do CIMT, I do the ankle baracial 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 endothel test. The endopad test. Yeah.
Starting point is 01:19:56 I think it's, I don't, I didn't pay for it all a cart, but I think you can go on their website. We'll link to this. It's reimbursable. It has an insurance code. I CD10 code. It's reimbursable. And if you pay out of pocket, I think it's a couple hundred bucks. Yeah.
Starting point is 01:20:06 It's that expensive. Yeah. At the end of the day, it's not that big deal 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 end of pad test. 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. Well, that's why I don't use them anymore. Yeah, because you'll see people out there.
Starting point is 01:20:38 Yeah, if you take a drink of water and you test your saliva, you've just diluted that saliva by, what, 80%, maybe 100%, so you're diluting it out. Yeah. Well, one of the things that I wanted to mention additionally is through Michael and also through my friend, Dr. 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 CCTV technology. 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, with Dr. Twyman, we'll 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.
Starting point is 01:21:34 I think he said that you 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 a Zetamide, 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. So, you know, and in my case, I'm a hyper-absorber. 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
Starting point is 01:22:16 and these chronic diseases that are out there, even if you might be more classically predisposed to having something, and obviously cholesterol, LDL, APAB 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. even though that there is a predisposition, maybe genetically, or maybe you are a hyperproducer or you have familial hyper-collestrialemia, nitric oxide and keeping it high is going to be one of those major protective elements. Anything you want to ask about?
Starting point is 01:22:50 No, I think you're spot on. The comment I have about the calcified plaque and people go into coronary calcium test, if you ask 10 cardiologists, you'll probably get 10 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.
Starting point is 01:23:10 It's the soft plaque. You know, 50% of sudden cardiac deaths are in people with, you know, 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. Calified plaque is hard, stable plaque
Starting point is 01:23:25 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 erupture 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?
Starting point is 01:23:56 Yeah, so nitric oxide will help stabilize that plaque, right? So what happens is you start to get an of the oxidative stress, the inflammation, you get myeloproxidase, 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 include the coronary artery. And so nitric oxide basically stabilizes that plaque, downregulates myeloproxidose, 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 cardioprotective in acute MI or people that are subject to or at risk for having a heart attack.
Starting point is 01:24:42 No, we didn't touch on it, but I'd be amidst 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. You know, 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,
Starting point is 01:25:11 then 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 that, 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.
Starting point is 01:25:44 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 but I have control over and how I'd react to things, it's been a life change for me. Turning off the news was a big component for you. Absolutely.
Starting point is 01:26:07 Because I found I'd get there and I would get angry and I go, why am I angry? How is this affecting me? But I can handle that. I can handle this. I just turn it off. I haven't turned my TV on since 2020. That's great.
Starting point is 01:26:19 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. We talked a lot about what harms the body. As we are gearing up and entering into the 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 other trappings that are there, artificial flavors and junk and pesticides, etc. 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.
Starting point is 01:27:06 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.
Starting point is 01:27:40 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 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? I've seen like the Nutrival from Genova.
Starting point is 01:28:06 Are there ones that you like when it comes to dietary nutrients? There's a company Spectrocell years ago that had a pretty comprehensive micronutrient test. I think a lot of that, 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 of micronutrient exams. Spectrocell was one I used years ago. But here's what I do because I think if you can either test or you can just do things that have nutrient density in them.
Starting point is 01:28:36 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 hour fast every day. I wake up every morning sitting in infrared sauna for 30 minutes at 170 degrees. and before I do that, I go and take an algae product. I take Corella and Spirulina. So these are like nutrient-dense algae products. So they're not only providing a lot of basic micronutrients,
Starting point is 01:29:04 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 on board 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 hallow app on, and I do the rosary or whatever and really just start my day with gratitude.
Starting point is 01:29:25 And to me, again, that's the best way to start. You're getting flight because I easily wake up at 5 or 5.30 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. Wild Mamas? Wild Mamas. It's marketed as a prenatal. Obviously, I'm not expecting to be pregnant.
Starting point is 01:29:46 But I think if it's good for a month. a pregnant mother, then it's probably good for me. Okay. But this is... So it's a multivitamin? Well, what it is, it's organ meat from wild bison. Okay, okay. It's wild bison on the reins that they take and they harvest and they put it in capsule.
Starting point is 01:30:02 So take six capsules that and basically provides all the organ... Desiccated organs. It's desiccated organs. And then they also have a salmon row product. So it provides all the benefits of the fissules that's free of mercury, free of toxins. And so that's how I start my day. 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's doc, a full
Starting point is 01:30:30 workup, you know, three to four hours in our office, physical exams, CIMT, oral exams, and I seem to be doing well. So a little algae, little spirulina, little wild bison, desicated organ. I like the name of the company, Wild Mamas. Wild Mamas. And you mentioned. what other thing, you mentioned the Wild Mamas, and then the salmon row. The salmon row, yeah.
Starting point is 01:30:54 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, you know, go to? What do you like to have in the morning? I usually eat lunch around 1130, 1130, 1130. That's personally when you have your first meal. That's right. But it's usually, it's always protein.
Starting point is 01:31:11 It's usually beef, chicken, or pork with, 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.
Starting point is 01:31:31 So for me, I'm physically active. And so sometimes I have to fuel to maintain some work for bailing hay or working cattle or doing whatever. Absolutely. In addition, you know, you also have developed and we gave your company a plug previously. just mentioned 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 lozange. And so we actually
Starting point is 01:32:00 make the gas itself. So similar to hormone replacement therapy and men or women in testosterone or estrogen, we actually give that molecule back. Right. So if you're deficient in testosterone, what do we do? You can give testosterone in an intramuscular injection, a cream or a sub-sulingual troche. and the same thing with nitric oxide. 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.
Starting point is 01:32:27 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 orly disintegrating tablet that you put it in your mouth, it dissolves over five to six minutes, but during that five to six minutes,
Starting point is 01:32:42 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 lozance to now basically enhance my circulation. Because when you're in the sauna, you're heated up to 170 degrees. So that itself creates vasodilation. They want to get out of the sauna, I take the lozenges to potentiate that to allow for better detoxification,
Starting point is 01:33:22 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. 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.
Starting point is 01:33:39 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. So 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, it's 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 gauce enzyme and prevent the superoxide
Starting point is 01:34:12 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 diet, lifestyle, stress management that are going to be things that are going to keep us healthy. Yeah, I say all the time.
Starting point is 01:34:51 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 is not going to normalize your vitamin D levels. But what we're finding is that until you restore the body's ability to make nitric oxide,
Starting point is 01:35:19 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 set the foundation, let's normalize nitric oxide, and then that allows you to focus. And what it will allow you to do is the other things that may not have been, the symptoms that may have been attributed to something else may go away if you just restore nitric oxide. So now we've up the game a little bit. And now what remaining symptoms, what symptoms may remain, now you can attribute to that and address that.
Starting point is 01:35:52 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. 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.
Starting point is 01:36:12 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 a Zetamide, 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 a super clean artery system
Starting point is 01:36:45 right now, right now. And I'm thankful that 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
Starting point is 01:37:06 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 U.S., with this model going through the FDA and get an approved indications for drugs. 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. We're moving through the FDA.
Starting point is 01:37:40 But I want to make a clear point here because I'm, you know, 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 Cox2 inhibitors. These are non-steroidal anti-inflammatories. They're proton pump inhibitors. There's ACE inhibitors,
Starting point is 01:38:15 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 it. that back. We're not inhibiting a biochemical reaction. We're not creating biologics and thanking 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
Starting point is 01:38:55 side effects to that. So we've got active drug programs for schemic heart disease, we've got a drug for Alzheimer's, and I make a topical nitric oxide for diabetic ulcers and non-healing wounds. Fantastic. So those are being worked on. That's right. And they'll maybe be in the pipeline one day, hopefully. Yeah, look, I think we're-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 Schemic heart disease drug, we're working on that now. My anticipation is we'll have a drug approved it on the market in early 2025. The Alzheimer's program is probably a two-year project, so probably 20-26 will have an Alzheimer's drug approved it 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
Starting point is 01:39:39 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 that you've mentioned below. Dr. 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
Starting point is 01:40:24 YouTube channel. Dr. Nathan S. Brian Nitrocock said. I've got an educational website, Dr. Nathans.S.brien.com. And we do a monthly blog, get some videos on there. For those interested in the product technology, it's N101.com. That's the letter N, the number one, the letter O, number one.com. Our drug company is brine therapeutics.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 FDA
Starting point is 01:40:58 because the source of my daily frustrations or 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 peel. 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
Starting point is 01:41:23 the rigor of the FDA, demonstrate safety, demonstrate efficacy in a number of different disease indications. And then, then and only then will nitric oxide be front and center and be a daily conversation piece. It'll be like the official of the 1980s. Well, I look forward to that time, 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. You know, find a functional or biological dentist that can help clean up your oral health. AskTheDentist.com has a great directory on there,
Starting point is 01:41:57 a bunch of people that are there. Clean up your diet. You know, make sure you're fasting insulin, hemoglobin A1C, 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. Thank you, Drew. Good being with you. Hi, everyone, Drew here.
Starting point is 01:42:26 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 it 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.
Starting point is 01:42:52 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 Drew Perot.com.
Starting point is 01:43:26 That's D-H-R-U-P-U-H-I-T-com and click on the tab that says, try this.

There aren't comments yet for this episode. Click on any sentence in the transcript to leave a comment.