Health Longevity Secrets
A podcast to transform your health and longevity with evidence-based lifestyle modifications and other tools to prevent and even reverse the most disruptive diseases. We feature topics including longevity, fasting, ketosis, biohacking, Alzheimer’s disease, heart disease, stroke, cancer, consciousness, and much more so that you can find out the latest proven methods to optimize your life. It’s a mix of interviews, special co-hosts, and solo shows that you’re not going to want to miss. Hit subscribe and get ready to change your life. HLS is hosted by Robert Lufkin MD, a physician/medical school professor and New York Times Bestselling author focusing on the applied science of health and longevity through lifestyle and other tools in order to cultivate consciousness, and live life to the fullest .
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Health Longevity Secrets
Does Mouthwash Cause Hypertension? with Dr Nathan Bryan
Ever wondered how a single molecule can regulate blood flow, support neurotransmission, and boost immune defense? Dr. Bryan unravels these mysteries and cuts through the confusion with nitrous oxide, sharing invaluable insights from his collaborations with Nobel Prize winners. Join us as we explore why nitric oxide is pivotal to our health and longevity, and why it deserves more attention in medical circles.
We also probe into the darker side of proton pump inhibitors (PPIs) and their detrimental effects on nitric oxide production. Through Dr. Bryan's expert lens, we examine the serious health risks tied to long-term PPI use, such as heart disease and cognitive decline, and highlight the hidden dangers of fructose metabolism in suppressing nitric oxide synthase. Our discussion underscores the importance of understanding these complex interactions and the need for increased awareness among both medical professionals and patients.
Not stopping there, we venture into the fascinating interplay between erectile dysfunction drugs and nitric oxide. Dr. Bryan explains how maintaining optimal nitric oxide levels can enhance the effectiveness of medications like Viagra and Cialis, with potential benefits for overall vascular health and longevity. We wrap up with practical advice for boosting nitric oxide naturally, including simple lifestyle changes and mindfulness around oral health products. Don't miss out on this opportunity to enrich your understanding and take proactive steps toward better health!
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Welcome back everyone. Our guest today will be speaking on the fascinating role of nitric oxide in our. Let's start over again. Welcome back everyone. Our guest today will be speaking on the very important role in our health and longevity of nitric oxide. You're going to learn how this molecule affects both our nervous system, our immune system and, most importantly, our cardiovascular system, if you stay to the end. Our presenter for this discussion is Dr Nathan Bryant, who is an international expert in nitric biochemistry and molecular medicine. He's more than 20 years in academic research have led to many seminal discoveries and resulted in dozens of patents. Products from his innovations are some of the most successful nitric oxide products on the market, and we'll talk about those today, so let's go ahead and jump in. Hey, nathan, welcome to the program.
Speaker 2:Hey, thanks for having me. It's great to be with you.
Speaker 1:Yeah, I think the last time you were together you and I were together was a few weeks ago. We were sitting in Costa Rica filming a beautiful TV series that is going to be on. Last I heard PBS and the Discovery Channel, so we'll keep everybody posted. But that was a lot of fun down there and we got to dive into some great discussions on nitric oxide, and hopefully that's what we can do today. I want to start with the basics first. This is arguably you know pound for pound the most important biological molecule there is. I mean, it's a small molecule, so that gives it an advantage, but it's certainly. It's really getting more and more press, it's more and more important and more and more people need to know about it. So what is nitric oxide exactly?
Speaker 2:about it. So what is nitric oxide exactly? Well, you know, as you said, it's a small molecule. It's just one nitrogen, one oxygen. But the interesting thing about nitric oxide is it's a gas. Once it's produced in the body, it's produced as a gas and then it's gone in less than a second. But during that time it's around. It signals a number of important biological pathways, from regulation of blood flow and circulation, tissue oxygenation. It's involved in neurotransmission in the brain. It's how our immune cells kills off invading pathogens. It's involved in mitochondria energy production, stem cell mobilization, extending telomeres. So really everything we know about longevity and health and wellness revolves around the adequate production of nitric oxide and just before we get into it, just to clarify.
Speaker 1:A lot of people have heard the word nitrous oxide, which is another gas which is different from nitric oxide, which we're talking about today. How are those different and what are they?
Speaker 2:Well, really, the only similarities are both are a gas and they sound similar, but their physiological and medicinal properties are completely different, in fact, probably two ends of the spectrum. So nitrous oxide, as you're aware, is a physician, is a dental, it's an anesthetic, general anesthetic, primarily used in dental offices. It's called laughing gas, but you know, that puts you to sleep. Nitric oxide is what animates human. In fact it was described 2000 years ago by Galen as the pneuma, the spirit that animated the humans, and today we know that nitric oxide is that molecule that was described over 2000 years ago. So, even though they sound differently, they're completely different molecules and I think it's a lot of people you know, I hear all the time oh, I love nitrous oxide and I go. Well, you may love nitrous oxide, but what we do is nitric oxide.
Speaker 1:Yeah, and so nitric oxide, which is what we're going to be talking about today. As you said, it's a gas. Now what does that mean? It's not bubbles in our bloodstream, though it dissolves, right, or how does that work?
Speaker 2:Well, at normal atmospheric temperature and pressure, we have solid liquids and gases, and so different molecules are in those different states at different temperatures and pressures. So under normal physiological temperature and pressure, nitric oxide, when it's produced, it's a gas, so it diffuses in all three dimensions, it binds to its primary receptors and then activates all these cell signaling pathways. So that's what's made it a unique molecule. That's what's made it a unique molecule. In fact, it was such a unique mechanism of signaling that in 1998, a Nobel Prize was awarded for the three scientists that discovered it, because it was completely new mechanism in terms of cellular communication.
Speaker 1:Yeah, I was at UCLA at the time on the faculty there and Professor Lou Ignaro from UCLA got the Nobel Prize. It was a huge deal and I understand that you've worked with him and worked together on a number of projects. So that's and the other the other award winners too, I think, on that.
Speaker 2:Yeah, so yeah, look it's.
Speaker 1:Lou's a great guy.
Speaker 2:I've been a good friend, you know. He inspired me early on, shortly after he won the Nobel prize, to really enter the nitric oxide field and was really encouraging early on as a student. And then, as you mentioned, I was recruited by Fred Mirad, one of the other scientists that won the Nobel prize, and he was my department chair for a number of years. We collaborated on a number of different projects and really tried to move the forward of drug discovery around nitric oxide. So that was we were tasked with, you know, trying to understand how we can stabilize nitric oxide molecule to put it in a solid dose form. Or I started to develop rational therapies around nitric oxide.
Speaker 1:Yeah, it's so fascinating and, as you say, it really. I mean, when the Nobel Prizes were awarded, it got a lot of publicity. But the thing is for physicians who haven't been in medical school in the last 20 years, let's say, or if they haven't been keeping up with the literature, which is, you know, increasingly difficult in modern medicine where everyone's in a narrow silo. You know, it's possible that you know, that our physicians, many physicians, are not even aware of nitric oxide, or at least are only peripherally aware of it. But, as you say, it's such an important molecule. I mean, the three big areas we think about are the cardiovascular health, the endothelial glycocalyx, and then it also works on the immune system, you know, and making the immune system better. And as if that weren't enough, it also works on neuronal health in our brain and nervous system. So three, there aren't any more important areas in those three areas for that nitric oxide could benefit.
Speaker 1:So so, where? Where is nitric oxide made? Or where where in our body? How does it? How does that work?
Speaker 2:Well, you know, today we understand that there's two primary pathways to produce nitric oxide. Well, you know, today we understand that there's two primary pathways to produce nitric oxide. The first pathway to be discovered was in our endothelial cells. Those are the cells that line all the blood vessels and lymphatics throughout the entire body. In fact, the endothelium is our largest organ. It's a number of cells that line all blood vessels and lymphatic that form an organ system, and so it's produced by an enzyme found in the endothelium, and that's the second to second regulation of blood flow and circulation and tissue oxygenation. And that's what we understand when we talk about endothelial dysfunction. The dysfunction of the endothelial cells arise from the loss of production of nitric oxide. So now it affects every organ system, right? So if you can't, if the endothelial cells lose the ability to make nitric oxide, so now it affects every organ system, right? So if you can't, if the endothelial cells lose the ability to make nitric oxide, then whatever vascular bed those endothelial cells are found in, whether it's the sex organs, the brain or the heart, you have dysfunction in the blood vessels, so they're no longer condyling, and that's the basis for all, if not most, if not all, age-related chronic disease.
Speaker 2:But fortunately there's enormous redundancy in the human body, especially for a molecule that's so critical and fundamental to life as nitric oxide. So we now understand that it's made in the mouth, in the oral cavity, from bacteria that live in the crypts of the tongue, and these bacteria metabolize a molecule called nitrate, inorganic nitrate, thatic nitrate that's found in certain foods, green leafy vegetables, for example. Then these bacteria metabolize it into nitrite and nitric oxide. Then when we swallow it we get a burst of nitric oxide is distributed throughout the body and that can overcome and actually we help restore endothelial dysfunction. So one can compensate for the other. But when you lose the ability to make nitric oxide, if you have endothelial dysfunction, if you have a poor diet or you have oral dysbiosis or using a mouthwash ran acids, then that really sets the stage for complete nitric oxide deficiency and then you see the onset progression of symptoms in clinical disease.
Speaker 1:So we can interfere with our nitric oxide production, either at the endothelial level in the blood vessels, or there's this second pathway in the oral cavity, made by bacteria that live there, but then we swallow the nitric oxide or it's absorbed into our body there. That's fascinating, and you mentioned one thing I just wanted to underscore about mouthwash that many people still aren't aware of, in particular the effects of mouthwash on nitric oxide production in the mouth. Could you talk about that a little bit?
Speaker 2:Yeah, you know, it's a really a fascinating observation and we published on this probably 10 years ago. But I mean, everybody, especially physicians, know the collateral effects of just oral antibiotics. You know if you have an infection, you put on a regimen of antibiotics, but you know you don't take that for the rest of your life because of the collateral damage, the gut dysbiosis, all the systemic effects you see from that. The same thing is happening with oral antiseptics and yet 200 million Americans wake up every morning and use an antiseptic mouthwash every day, sometimes two, three times a day and it's destroying the oral microbiome, it's shutting down nitric oxide production, it causes an increase in blood pressure and, in fact, you lose the protective benefits of exercise if you use mouthwash so similar to antibiotics. Now you cannot use antiseptic mouthwash to destroy the oral microbiome every day without consequences. And you know, you know the numbers. You know two out of three Americans have an unsafe elevation in blood pressure and two out of three Americans use mouthwash every day. And that's not coincidental.
Speaker 2:We published on this in 2019 that if we took normal intensive patients and we just gave them mouthwash twice a day for seven days, we saw an increase in their blood pressure, in some cases 20 millimeters of mercury. So we made normal intensive patients clinically hypertensive simply by using mouthwash and so we have to get rid of that. There's too much collateral damage and everything's risk-benefit and the risk of mouthwash far outweigh any benefits. And the same thing happens with fluoride. Fluoride's in toothpaste, it's in a lot of mouth rinses, it's in municipal water. Fluoride's an antiseptic. It kills the bacteria and it's a neurotoxin and it shuts down your thyroid function. So if we just stop eliminating mouthwash use and get rid of fluoride in our toothpaste and then filtered out of our municipal water system, now the oral microbiome can repopulate, improve its diversity, restore nitric oxide production and people get better.
Speaker 1:Wow. Well, I guess we can give up on Listerine as a potential sponsor for this program.
Speaker 2:I tell people, look, believe the ads when you see them. This will kill 99.99% of the bacteria in your mouth. It does, and that's not a good thing, but yet they advertise it, and so this is the advancement of medicine. You know, a hundred years ago we were using leeches to exsanguinate people. We don't do that anymore, right, because we know better. You know, years ago it was thought this oral systemic link where people with periodontal disease, gingivitis, have higher incidence of heart attack and stroke and cardiovascular disease. So what do they do? Well, let's just kill all the bacteria. Well now, since the microbiome project, you know, we know that the bacteria that live in and on our body outnumber on cells 10 to 1. And these bacteria are there to do jobs that we as humans can't do. It's a true symbiotic relationship, and you kill these bacteria to your own demise. I mean, we have to maintain a healthy microbiome and there are certain essential metabolic activities that these bacteria are performing, and the one we're focused on is the nitric oxide producing bugs in the bacteria.
Speaker 1:And so it's not only mouthwash. But you're also saying if we should look at our toothpaste, if it has fluoride in it, we should discontinue that for the same reason. That's right.
Speaker 2:You know, if you read the back of a fluorinated toothpaste, it says if you swallow, this, call poison control. I mean fluoride is rat poison from years ago and it shuts down your thyroid function. It's a neurotoxin and it's an antiseptic. So we have to remove fluoride. Fluoride is one of the most toxic molecules on the periodic table and I don't know why anybody ever thought it was a good idea to expose humans to fluoride.
Speaker 1:One of our other speakers I was talking to recently is an Ayurvedic medicine expert, and she was recommending something that I haven't done yet, although I ordered one from Amazon. It's a tongue scraper. How does that weigh into nitric oxide? Is there any effect? Is tongue scraping detrimental? Is it helpful, or is it a completely different topic?
Speaker 2:No, look. We published on this in 2019 because we found that some of the patients that we enrolled in the study were tongue scraping. And so here's what we found People that did tongue scraping had the most diverse oral microbiome and they seemed to have the best regulation of blood pressure. So tongue scraping, I think, is good, and I equate this to the analogy is it's like tilling the soil before you plant a garden. Right, You're tilling up the surface, the crypts of the tongue, You're improving the diversity. But here's what we also found If you tongue scraped and used mouthwash, those were the people who had the highest increase in blood pressure upon mouthwash use.
Speaker 2:And I think what it's doing when you're tongue scraping, you're opening up the crypts of the tongue and allowing the antiseptic mouthwash to get into the crypts and you get more effective killing. So to answer your question, tongue scraping alone is good, at least from our data, from the outcome, from our study. But if you're tongue scraping, you should not under any well.
Speaker 1:Number one you shouldn't use mouthwash under any conditions, but especially if you're using a tongue scraper, you have to avoid mouthwash conditions, but especially if you're using a tongue scraper, you have to avoid mouthwash, and I think we were talking beforehand about antacids too.
Speaker 2:What's the dynamic there with nitric oxide? Well, antacids, and specifically we're talking about what's called proton pump inhibitors these are things like Prilosec, prevacid, omeprazole, pentoprazole. So these drugs inhibit nitric oxide from both pathways. So it shuts down your oral kind of the nitrate nitrite nitric oxide pathway, because we need stomach acid in order for nitric oxide to be produced in the stomach from swallowing our own saliva after we eat a plant-based diet or a salad or a meal with inorganic nitrate. The other problem with proton pump inhibitors is they inhibit an enzyme and we'll just call it DDAH, but this enzyme typically breaks down a metabolite called asymmetric dimethyl L-arginine, or ADMA, and ADMA acts like a inhibitor to nitric oxide production in the endothelial cells. So when you use proton pump inhibitors, it leads to an increase in a molecule that inhibits nitric oxide production and then shuts down nitric oxide production from our diet and that basically completely devoids your body of any nitric oxide. Now what does that mean?
Speaker 2:Well, in 2015, it was published that patients who had been on PPIs for three to five years had a 40% higher incidence of heart attack and stroke not higher risk, actual events. And then a study published last year showed that people who have been on these drugs for at least three years had a 40% higher incidence of Alzheimer's in vascular dementia. So those are the consequences of shutting down nitric oxide production heart attack, stroke, alzheimer's. And you can probably remember back in the early 2000s when you know Vioxx and Celebrex, the COX-2 inhibitors, were taken off the market or black box warning because they were causing heart attacks and strokes. Ppis are actually more dangerous than the COX-2 inhibitors. So I advocate that these drugs should not only be taken off the market but if they're not, there has to be a black box warning around these drugs because they're increasing heart attack, strokes and Alzheimer's and mechanistically, we know exactly the cause of that and it's because it's completely shutting.
Speaker 1:Wow, wow. I think a lot of people aren't aware of this and the importance of nitric oxide, but also how they can damage the nitric oxide production with these, basically, things we find in the home that people think of as being safe and they, you know, feed to themselves and their children and all these kinds of things.
Speaker 2:Well, you know if you look back at when these drugs were approved, they were never approved by the FDA for chronic use. They're only approved as drugs for the acute remediation of gastroesophageal reflux disease. They were never approved to be used daily, indefinitely, in perpetuity. But yet now they're available over the counter. People can go to the pharmacy or the grocery store and buy these drugs over the counter and take them every day, and I know people have been taking them for 10, 15, 20 years and they just take them every day because, well, it becomes habit, they feel like they need it because of acid reflux and heartburn. But there's consequences to that and I tell people all the time you have to find a way to wean off these antacids or else you know the data tell us you're going to suffer a heart attack, stroke or get Alzheimer's.
Speaker 1:Yeah, so that's largely the oral production, but then, as you said, some of those absorbed into the gut and goes into the intravascular ones and the intravascular endothelial production of nitric oxide. I just reread Richard Johnson's great book why Nature Wants Us to Be Fat. He's going to be speaking also here and he talks about his interest is in fructose and how fructose is metabolized in the liver and production of urate, which we used to think of as sort of a benign molecule that maybe caused some gout or something, but otherwise you don't have to worry about it. But he talks about how fructose being broken down into to urate and urate can actually block nitric oxide synthetase and endothelial nitric oxide synthetase particularly. Have you noticed that or do you have experience with urate levels? Is this something we should be looking at also for all these conditions that nitric oxide deficiencies can contribute to? Do you think?
Speaker 2:Yeah, no, absolutely. Look, as you know, metabolism is internally connected to all systems in the body and you know, urate, increased uric acid levels, certainly shut down nitric oxide production. Dr David Perlmutter has focused on this for the past five or six years in his book Drop Acid, and so you can see the vascular complications and the vascular issues with people who have elevated uric acid and are prone to gout, and all of it can be explained by a shutting down of nitric oxide production.
Speaker 1:Yeah, Do you have a number for uric acid levels? I know I think Dave in his book talks, you know, like close to five or not much higher than five, I don't know.
Speaker 2:Yeah anything above normal is going to certainly be, you know, putting you at increased risk. But you know, as I mentioned earlier, the body has a way of responding to different insults or stimuli. So there's always, you know, a response to any insult we give the body. But I think what we have to focus on is all of these metabolites and pathways that seem to interfere with nitric oxide production. Then we have to work backwards and figure out OK, how do we remediate this, normalize the levels and get everything working optimally? You know, because I always preach, that nitric oxide is foundational. But you know, that's not the only thing we have to focus on. I think what the data tell us is your body cannot and will not heal without nitric oxide. But you know, if you've got issues with some you know some predisposition because of a single nucleotide polymorphism or some some other issue, or you've got hormone issues, then we still have to focus on that. But foundationally we have to restore the production of nitric oxide. So now, anything you do thereafter will work better.
Speaker 1:Are there well speaking of SNPs, or single nucleotide polymorphisms in our, in our DNA that you know, many of us now get tested? Are there any particular SNPs related specifically to nitric oxide production that people should be aware of? And if they have these, then they should even more stay away from all the things and maybe even take supplementation of nitric oxide.
Speaker 2:Yeah, well, obviously the NOS isoforms, nos1, 2, and 3, if there's SNPs in those gene products then obviously they're going to be some sort of dysfunction. So NOS1 is your neuronal NOS, nos2 is your inducible NOS and NOS3 is the ENOS. And so those are obvious. What's not obvious to people is the methyl tetrahydrofolate reductase, the MTHFR. So people associate that enzyme or that protein with methylation issues and defects in methylation. But it also is involved. That enzyme is involved in reduction of bioctrin back to tetrahydroboctrin, the reduced form In BH4, tetrahydroboctrin is the rate-limiting step in nitric oxide production. So in patients who have a SNP and MTHFR they have an endothelial dysfunction because they have more oxidized BH2 than they have BH4. And it's that redox ratio that leads to NOSM coupling and endothelial dysfunction.
Speaker 1:Excuse me Now, nitric oxide. It's so, so important. Why aren't more people aware of this, do you think? Why isn't every physician talking about this when they see the patients with hypertension, which almost half of adult Americans have and they call it essential hypertension because they don't really know what it is they tell you to eat less salt, but that's probably not the biggest factor.
Speaker 2:No, that's right. I think we can attribute it to several things. So number one is historically it always takes on average about 17 years for new discoveries to become in the clinical practice. You know, nitric oxide wasn't discovered until the mid 80s and early 90s Really a true understanding of its production and significance and the Nobel Prize was awarded 1990. So now we're last year we were 25 years from the awarding of the Nobel Prize, so that can't really explain the lack of awareness now in clinical practice.
Speaker 2:I think in terms of patient care and the physician-patient relationship, there's not a focus on it because there's no official diagnosis right and there's no prescription you can write for nitric oxide deficiency.
Speaker 2:So it's not part of the billing and the coding and the, the, the payment process of the financials of medicine. Because, as you know, as a physician once you make a diagnosis you have kind of some finite responses to address that diagnosis. Number one not only to get paid but to operate within the standard of care, and I think that's that's been my focus is we have to develop these technology into safe and effective prescription drugs. Because now what we're finding is that hypertension is a symptom of nitric oxide deficiency, erectile dysfunction is a symptom of nitric oxide deficiency Ischemic heart disease can be treated with nitric oxide products. So as we start developing and getting our drugs through clinical trials and getting these drugs approved and on the market, I think it will become the main conversation between a physician and a patient, because now we get to the root cause of most, if not all, chronic disease and we're no longer prescribing Band-Aids to mask the symptoms. We can have a drug that actually gets to the root cause of their underlying disease.
Speaker 1:Okay, I'm sold. Now I've thrown out my mouthwash. I ordered a tongue scraper from Amazon. I'm going to go in and look at my two-faced face immediately. Go in and look at my two-faced things immediately. I know I can check my urate levels with a blood test. Now how do I check my nitric oxide levels or how do I know where I am? Is there a blood test or what can I do with that?
Speaker 2:You know, in the research lab for 30 years we've measured this in the basic scientists and also in some clinical research. But clinically, and you know, there's not a blood test. So, unlike cholesterol or vitamin D or magnesium, you can't. Or urate, where we can draw blood and get a number, there is no number or no labs for nitric oxide. I mean, we've discovered, you know, elevated triglycerides. We can reduce triglycerides with nitric oxide. Elevated C-reactive protein is typically a sign of nitric oxide deficiency. But there's no direct correlate. The only way we can determine it clinically is through you know, these medical devices, what's called flow-mediated dilatation. Historically it was called plecmosography, right Venous occlusion plecmosography. So that gives you a functional assessment of endothelial function or nitric oxide production. These are FDA cleared medical devices. But you know most family practices or family or you know general practitioners don't have these devices, so it's not commonly used. But you know, about 15 years ago we were asked the same question and so I developed a salivary test strip back in 2009, 2010,. Because we understood that the nitrate was concentrated in our salivary glands. When we salivate, it's activated by these oral bacteria. We produce nitride in the saliva. We swallow our saliva, we get nitric oxide. So I developed a non-invasive kind of a point of care diagnostic where you can test your saliva. So we've used that for probably 10 or 15 years and I think it's. You know, I tell people it's a good tool to have in your toolbox, but it shouldn't be the only thing you're using, because there's no such thing as false negative toolbox, but it shouldn't be the only thing you're using, because there's no such thing as false negative. If you show low on that test strip, then it tells us that your body is not making sufficient nitric oxide, but it doesn't tell us why. Is it because you have endothelial dysfunction? Is it because your diet isn't optimal? Is it because you're using mouthwash? Is it because you're using antacids? But you can start interrogating that system and getting to the bottom of it.
Speaker 2:The problem we ran into was false positives, you know, and the false positives come from active oral infections and these can be either symptomatic or asymptomatic oral infections. So people would, you know. The example was, you know, a 50-year-old, obese, hypertensive, diabetic patient with erectile dysfunction. We test his saliva and he lights it up bright pink and it says optimal. Well, obviously, clinically, that patient isn't optimal. He's probably just the opposite. And then what we found was he had active dental infections. So the local immune response from the active oral infection was generating nitric oxide from our immune cells, enriching the saliva and testing positive on the test strip. So those are the false positives, and so I've gotten away from the test strips and really just rely on clinical symptoms as a measure of nitric oxide availability, because that's I think that's the best picture we can put together and then allow the physician to use their best medical judgment on how best to treat that patient.
Speaker 1:Yeah, and given that so many people you know as high as 88% from that famous study everybody quotes have metabolic dysfunction, which is, you know, related with all the diseases that you're talking about, that have a link with nitric oxide there's. We should all be suspicious for it, at least when you were mentioning the oral cavity maybe I misunderstood you. Is the nitric oxide actually produced in the mouth by the bacteria, or is it the nitrates that are produced in the mouth and then swallowed and then absorbed and produced in the gut to make the nitric oxide?
Speaker 2:Well, a little bit of both. So certain communities of bacteria have what's called a functional nitrate reductase enzyme. So they perform the two electron reduction of nitrate to nitrite and now the pKa of nitrite is 3.4. And what that means is in a pH of 3.4, 50% of that molecule becomes protonated and disproportionates to nitric oxide gas. So we can actually detect nitric oxide gas in the exhaled breath in certain people.
Speaker 2:But the majority of the nitric oxide that's biologically active comes from swallowing our own saliva in the acid environment of the stomach, which a normal stomach, healthy stomach has a pH of less than two.
Speaker 2:Then you get this burst of nitric oxide in the lumen of the stomach, which a normal stomach, healthy stomach has a pH of less than two. Then you get this burst of nitric oxide in the lumen of the stomach and that has important physiological functions. So number one it'll kill H pylori, the ulcer-causing bacteria. If you have some E coli or salmonella in the food you're eating, it'll kill those bacteria and you don't get sick from them. It'll prevent ulcerations from chronic NSAID use and enhances gastric mucosal blood flow, improves the mucus production and really preserves the integrity of the gastric mucosa. So that is kind of how the system works. But there's some bacteria that and we've characterized these in the oral microbiome that have nitrite reductase genes. So the nitrate is a two electron reduction to nitrite and then the one electron reduction from nitrite to nitric oxide can occur by the bacteria or just simple solution, chemistry in the acid, disproportionation in the lumen of the stump.
Speaker 1:So if there are challenges with the oral test strips and all, it's not a perfect test. You mentioned the other tests measuring endothelial function relaxation, but it's not in a lot of doctor's offices Maybe concierge doctors have it or something. What is the cost of that device or the per test use? Just ballpark figures and I assume it's non-invasive, right it's? A blood pressure cuff or something.
Speaker 2:There's different devices and the cost associated with these are different. So the one that used and I think probably has the greatest number of validated clinical trials on it, was a device called the Endo pad. It was from a company called itamar out of the out of the middle east, but this used what's called venous occlusion plecosography. But it would actually you put a blood pressure cuff on your brachial artery and you basically restrict blood flow into the brachial artery for five minutes. So it's it's a little bit uncomfortable. You get the tingling because you're basically restricting blood flow into the arm for five minutes. So it's a little bit uncomfortable. You get the tingling because you're basically restricting blood flow into the arm for five minutes. It's kind of like falling asleep on your arm and you get the tingling and the numbness. But then when you release that cuff, either through an ultrasound probe or a fingertip probe, you can look at the degree of vasodilation what we call reactive hyperemia, and that'll give you a score of endothelial function called reactive hyperemia, and that'll give you a score of endothelial function and that now. So those were quite costly in terms of the consumables and the cost to the patient. Now there's what's called non-ischemic plebisography where you can look at, you know, the secondary and tertiary arterioles and look at the structure and function of these, and so it's really a pulse wave or augmentation index that'll give you a picture of how clean your vessels are, how compliant the blood vessels are and how stiff they are. So those non-occlusive lithosography devices, there's no consumable cost.
Speaker 2:The devices themselves, you know, I bought one personally and I think I paid $30,000 or $40,000 for it. But there's no consumables. I think they're reimbursable by some insurance. They have an ICD-10 coding now. So it's a verified diagnostic that you can. You know, if a patient has insurance in your clinical office, then you can reimburse your insurance for it. But I mean to understand how important and prognostic these are to get an early indication of vascular structure and function prior to patients developing ED or hypertension. I don't care how much it would cost. It would be worth it to get an insight into where you are in terms of nitric oxide production worth it to get an insight into where you are in terms of nitric oxide production.
Speaker 1:Yeah, absolutely. Well, speaking of that, ED and all several of our audience have emailed in prior to this interview and they wanted to understand the drugs, the ED drugs, that are somehow tied to nitric oxide. We hear nitric oxide in conjunction with Tadatafil or Cialis or Viagra also. Can you talk about that a little bit? Are these the same things? If I do nitric oxide supplementation, I don't need these others, or vice versa? How do they interact?
Speaker 2:Well, mechanistically, we know how these drugs are working. You know these PD-5 inhibitors. Collectively these class of drugs are called phosphodiesterase inhibitor type 5. So it's a specific isoform of phosphodiesterase that these drugs are inhibiting. And this goes back to the work of Fred Murad, my former mentor, who won the Nobel Prize, and he was the one who discovered that drugs like nitroglycerin work for the treatment of acute angina because they activate an enzyme called guanylyl cyclase. This enzyme produces cyclic GMP, leads to smooth muscle relaxation and you get dilation of the coronary arteries. So cyclic GMP is the second messenger that's produced from nitric oxide and these drugs inhibit the breakdown of cyclic GMP. And these drugs inhibit the breakdown of cyclic GMP. So that's why they work.
Speaker 2:For you know, these drugs were first development for heart disease and pulmonary hypertension because they dilated blood vessels and that's really the focus and the mechanism of these drugs. So obviously for ED, in both men and women, we have to get dilation of the blood vessels in order to improve blood flow and engorgement. So when you can't make nitric oxide, you can't dilate the blood vessels and you develop erectile dysfunction. So now the PD-5 inhibitors even if you have a little bit of nitric oxide, they potentiate the nitric oxide that's produced. But these drugs do not affect nitric oxide production. And now, 25 years later, do not affect nitric oxide production. And now, 25 years later you know, these drugs were approved in 1998, 50% of the men that are prescribed Viagra, cialis or Levitra, these different forms of PD-5 inhibitors, don't respond. So, multi-billion dollars, 50% of the patients don't respond with better erections or better urinary symptoms of BPH.
Speaker 2:They're primary indications. So why is that? Well, the reason they don't respond is because they can't make enough nitric oxide to activate that second messenger system. So what does that mean? Well, if we can restore their nitric oxide production, you can activate guanllate cyclase, you can increase cyclic GMP. And now these drugs have a substrate to work on to improve blood vessel dilation, engorgement and improve sexual function in both men and women. So these drugs are dependent upon the body's ability to make nitric oxide. If you have severe endothelial dysfunction, you can't make nitric oxide, then these drugs cannot and will not work. Severe endothelial dysfunction, you can't make nitric oxide, then these drugs cannot and will not work, Then here's the chance for intervention.
Speaker 2:If we focus on restoring nitric oxide production now, the non-responders to these drugs become responders and you can actually lower the dose of these drugs, making them safer and mitigating the side effects.
Speaker 1:So, if I understand you right, they're really not. They're not replacement for each other, but they're synergistic. And the PDE5 inhibitors, the Cialis, viagra and all really should be used in conjunction with the nitric oxide supplementation program. So you're doing both to get the maximum effect and the minimum dose required for those other ones. One interesting point about these PDE5 inhibitors they're being used now not only for erectile dysfunction and other vascular conditions, but they nitric oxide supplements as longevity drugs.
Speaker 2:Well, I think the data are very clear. It's the foundation for everything we know about longevity. So, going back to, I like to start with important clinical observations and then work backwards and figure out mechanism. And I think that's how backwards and figure out mechanism and I think that's how science and medicine has advanced. So what are the PD5 inhibition data tell us?
Speaker 2:A study during COVID found that people who were on once daily Cialis had lower symptoms and susceptibility to COVID virus. That can be explained. Number two a study out last year showed that people who had been on once daily Cialis or drugs like Vagrim had about a 30 to 40% less incidence of Alzheimer's in vascular dementia. So when these drugs work, yeah, they can dilate the blood vessels of the sex organs, but it's not isolated there. They're dilating your coronary arteries, they're dilating your pulmonary arteries, they're dilating your cerebral arteries and they're improving blood flow to every organ, tissue and cell in the body. And that's a good thing. And I think several years ago there was data out there that you know, many athletes were using these PD-5 inhibitors to enhance their performance during competition, during the Olympics or during swimming On the field, not necessarily off the field.
Speaker 1:right, that's right, that's right. So here's what we know about nitric oxide and longevity.
Speaker 2:Number one it dilates blood vessels. Number two it activates an enzyme called telomerase. And you know this? This telomerase is an enzyme that prevents the ends of the telomeres in our chromosomes from shortening. And shorter telomeres, shorter lifespan, Longer telomeres, longer lifespan. So nitric oxide is what controls and regulates the length of our telomeres.
Speaker 2:Number two mitochondria the energy production organelles of the cell. Mitochondrial dysfunction is associated with every age-related disease. Nitric oxide controls the number of mitochondria per cell and controls the efficiency of ATP production by those mitochondria. So if you make nitric oxide, you have more mitochondria per cell and you're generating more energy more efficiently with less oxygen. And then, number three, nitric oxide is the signal that tells our own stem cells to mobilize and differentiate. So as we get older, we don't lose the number of stem cells, as we once thought. We just lose the ability to mobilize our own stem cells. And because we lose the ability to produce nitric oxide, so we're constantly wearing ourselves out. We just got to repair and replace these cells in order to live longer and better, and you can't do that without nitric oxide. So nitric oxide is really the unified agent for everything we know about longevity improves telomere links, improves mitochondrial function and mobilizes our own stem cells so we can repair and replace dysfunctional cells.
Speaker 1:Now, how can we increase our nitric oxide? What are the dietary ways? And then you have a company that also makes specific supplements for that. Could you speak about those? Sure?
Speaker 2:You know I I'm a physiologist and biochemist by training, so I try to get to and give people the tools they need to allow the body to do what it's designed to do. So I tell people you have to do two things stop doing the things that disrupt it and start doing the things that promote it. So we've discussed these. So stop using mouthwash, get rid of fluoride, get off the antacids. Now your body is actually primed to make nitric oxide and we can help it along. Moderate physical exercise, 20-30 minutes of light aerobic exercise per day. Throw in some more green leafy vegetables that are enriched in nitrate. Typically the darker the vegetable, the more nitrate. And then 20 to 30 minutes of sunlight a day. There's certain wavelengths of light that'll stimulate nitric oxide released into the tissue, dilate blood vessels, improve mitochondrial function and then when all else fails.
Speaker 2:We have product technology that actually produces nitric oxide gas. We've made a solid dose form of nitric oxide gas. I'm the only person in the world who's ever made a solid dose form of a bioactive gas. So that technology is designed for. If your body can't make nitric oxide whether you have a genetic sniff, whether you're on an acids, mouthwash, antibiotics then our products do it for you. They release nitric oxide and then, more importantly perhaps, they restore the ability of you. They release nitric oxide and then, more importantly perhaps, they restore the ability of the body to produce nitric oxide. We're restoring the oral microbiome because this lozenge sits in the mouth, on top of the tongue. You move it around, it kills the bad bacteria, it restores the good bacteria and then we recouple the NOS enzyme in the lining of the blood vessel. So we improve endothelial function by about 15% within four hours.
Speaker 1:Well, what is the dosage of this lozenge? Then you get it, you put it in your tongue, under your tongue, let it dissolve in your mouth. How do I know if I'm getting enough? Or what do you recommend for someone like me?
Speaker 2:Well, it's a very good question and, as you know, dose dictates poison. So what we try to do is understand how much nitric oxide a healthy human would make in 24 hours and then give that back. It's called restorative physiology, it's not pharmacology. We're not giving synthetic compounds and inhibiting biochemical reacts. We're basically giving back the body what it needs. So I designed that lozenge to have a five to six minute resident time, so you put it in your mouth, you don't have to park it under your tongue or on top, you just move it around, kind of like a sweet tart. But as it's dissolving, we can detect anywhere from 15 to 30 parts per million NO gas coming out of the oral cavity and then we can do blood draws. So we have the full pharmacokinetic pharmacodynamics of this molecule. But so I designed that one lozenge to provide enough nitric oxide that a healthy person would make over 24 hours.
Speaker 2:So if you're like us, Dr Lufkin, and you're free of illness and symptoms and sickness, once daily is typically enough. Free of illness and symptoms and sickness once daily is typically enough, kind of as a maintenance dose. Because we live in a toxic world, you know we're nutrient depleted and so we need this daily nitric oxide support. Now, if you've got a patient that's metabolically challenged, obviously the demands on that patient are much different from somebody like us who are proactive and perhaps taking it prophylactically. So we've, you know, one lozenge twice a day is typically good.
Speaker 2:You know, we had a 15-year-old patient we published in 2012 with a severe resistant hypertension due to a urea cycle disorder and we had to dose him one lozenge every four hours. So everybody's different and we just have to number one. If physicians are using this, use their best medical judgment for their patients, but for consumers using this, you know, without the guidance of a physician, we say don't exceed more than two a day, right, One in the morning, one in the evening, 12 hours apart. I've been doing this now for probably 15 or 20 years and I turned 50 a couple of months ago and I've got the biological age of a 36-year-old no blood pressure issues, no symptoms, and so I think it's worked prophylactically for me, because a lot of my 50-year-old colleagues are in much worse shape than I am.
Speaker 1:Yeah, absolutely. Well, I want to be respectful of the time here here. You mentioned that you could give us maybe a couple quick tips just to end for our audience on nitric oxide health or suggestions for them.
Speaker 2:Sure, yeah. So, as we mentioned, I think you just have to give the body what it needs. The body heals itself. We understand how the body makes nitric oxide. We understand what goes wrong in people that can't make it. We understand the clinical consequences and now we know how to fix that. So if you're using mouthwash, you have to stop. It's better to have bad breath than to have a heart attack.
Speaker 2:Get off your antacids, get rid of fluoride in your toothpaste and your mouthwash, get a home filtration system. Remove it from your water supply and then exercise, eat right, get some sunlight and then, when all else fails, we have products that do it for you. It's really that simple. The science of nitric oxide is extremely complex, but the solutions are pretty common sense and practical, and so it's pretty simple.
Speaker 1:Yeah, this has been great. Actually, I've done the whole interview today on a nitric. I just took a nitric oxide supplement before the interview. I feel great.
Speaker 2:Thank you. That's a great product, not because I developed it and invented it, but it provides nitric oxide and people feel the effects of it and so, yeah, those products are found at n101.com. That's one N, the letter N, the number one, the letter O, number onecom.
Speaker 1:The letter N, the number one. The letter O, number onecom. Yeah, and that's it. I wanted to tell you your social media and any other websites. If you could just let people know how they can contact you or follow you at least.
Speaker 2:Yeah, I send people. You know I'm here to provide education. I'm not here to sell products. I'm really trying to create awareness. So I've got an educational website where there's some videos on there. I do a monthly blog. It's drnathansbryancom. I have my own YouTube channel where we'll post interviews and podcasts and lectures like this. If you just search YouTube, dr Nathan S Bryan or Nitric Oxide, my YouTube channel would come up. I'm on Instagram at drnathansbryan, twitter at drnitric. I'm searchable on most search engines, so if you're looking for me, you can find me.
Speaker 1:Well, thanks. Thanks so much, Nathan, for spending this time with us today, and thanks so much also for the great work you're doing in this space.
Speaker 2:Well, thank you, Dr Lufkin. It's a great pleasure and honor to be with you and to call you a friend.
Speaker 1:Keep up the good work. Wow, we just learned all about nitric oxide and I'm definitely going to take a look at my toothpaste. Make sure there's no fluoride. I'm going to get rid of the mouthwash and that tongue scraper will be here before long. But I really want to thank Dr Nathan Bryan for joining us today and sharing his amazing knowledge with us all. Remember that Dr Bryan has a bonus that he's going to be giving us an actual copy of his recent book on nitric oxide, so it'll be to our VIP Pass members. If you still haven't claimed your VIP Pass to access the recordings, transcripts and MP3s and our must-have bonus package, you can get it now by clicking on the button on this page to upgrade before it's too late. And remember, when the event is over, the recordings and all the bonuses sadly go away. Make sure you claim your VIP pass before it's too late.