Latest / hol+ with Dr. Taz MD | The Future of Medicine is Holistic / Nitric Oxide And Your Health: The Root Problem No One Checks | Dr. Nathan Bryan
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- (4) Podcast Dr Nathan Bryan - YouTube https://www.youtube.com/watch?v=gTR--WepE20 Transcript: (00:00) Didn't they just publish new guidelines around cholesterol to saying to correct it down to like a hundred at your total? I think I saw that recently. If you want to make a chronically sick population, that's a great idea. But no, look, it's it's malpractice at this point because what I look at are risk benefits. (00:17) What are the benefits of taking cholesterol medication versus the risk, right? Number one, cholesterol does not cause heart disease. So, it makes no sense to target as a treatment. all the primary, secondary, tertiary prevention trials, tens of thousands, hundred thousands of patients. (00:34) When you look at the absolute risk, there's no benefit to statin medication in preventing heart attacks. So, if there's no benefit and it's all risk of any treatment, it's a very simple quotient and you don't do it. If you take normal intensive patients that are unmedicated, good diet, good perio, full oral exam, and the only thing we do is give them aneptic mouthwash twice a day for seven days, their blood pressure goes up. So that's that's causation. So we're killing the oral microbiome. (01:00) We're shutting down nitric oxide production and their blood pressure goes up. What is the right use of a statin in the context of cardiovascular disease and in the context of longevity? Scientifically speaking, there's no benefit. Wow. There is no safe judicious use of a cholesterol lower medication. So wait, I'm going to say that again just to make sure everybody heard that. (01:20) You are saying scientifically there's no safe use of a statin. That's right. My next guest, Dr. Nathan Bryan, a pioneering scientist, health innovator, and biotech entrepreneur who has reshaped the conversation around nitric oxide longevity and human performance. Why do we need to care about nitric oxide? Well, it's probably one of the most important molecules produced in the human body. It regulates important things like blood flow, tissue oxygenation, mitochondrial function. (01:46) It mobilizes stem cells so we can repair and replace dysfunctional cells. It mitigates inflammation. Loss of nitric oxide is one of the earliest events in the onset and progression of chronic disease. Fascinating. With over a 100 peer-reviewed publications and dozens of patents, his discoveries ignited a billion dollar market and continued to transform lives. (02:07) Formerly a professor of molecular medicine, Dr. Brian left academia to challenge misinformation in the health industry and delivers science-based solutions directly to the public. He is the author of The Secret of Nitric oxide, bringing the science to life, and is recognized for making cutting edge research accessible and actionable. (02:29) Please join me in welcoming Dr. Nathan Bryan to the show. Before we dive into today's topic, I just want to say thank you to all of you who've been watching and sharing Whole Plus. Every week, we explore how science and spirit come together to help you heal your body, your relationships, and your world. (02:47) If you've been watching for a while, but haven't subscribed yet, please take a second to do that now. It's the easiest way to support the show and make sure you don't miss new conversations that can truly change how you see your health. Let's get started. Dr. Brian, welcome to the show. Well, thanks so much for having me. I'm thrilled to have you on here. (03:06) We're going to talk about something we don't normally talk about. We're going to talk about nitric oxide. And I don't want everybody to flip or change the channel or whatever you guys are doing quite yet. This is really important. And it's important in the context of longevity, cellular age, inflammation. A lot of the things everyone's coming into my exam room and either asking me about or we are finding. (03:28) Why do we need to care about nitric oxide? Well, it's probably one of the most important molecules produced in the human body. It regulates important things like as you mentioned blood flow, tissue oxygenation, mitochondrial function. It mobilizes stem cells so we can repair and replace dysfunctional cells. (03:46) It mitigates inflammation which is the silent killer in most chronic diseases. Um, so now we're learning that the loss of nitric oxide is one of the earliest events in the onset and progression of chronic disease. Fascinating. And how did you stumble upon this? Was this you woke up one day and realized nit nitric oxide exists or or what exactly happened here? No, I think God has a a sense of humor cuz I had a degree in biochemistry from the University of Texas and once I got my bachelor's degree, I swore I would never want to deal in nitrogen-based chemistry again. Mhm. Because it's so reactive. You know what? I did a biochemistry degree, too. And I'm kind of like, why (04:14) did I do that? But any So, but think back. Right. Right. Exactly. Yeah. But after that degree, I I was at LSU School of Medicine. and I was working on a PhD in molecular and cellular physiology and in 98 a Nobel prize had just been awarded for the discovery of nitric oxide. So it was an exciting time in science. (04:32) We knew a lot about this molecule but there was so much we didn't know and I was had a chance to meet Lou Ignaro who had just won the Nobel Prize for discovery of nitric oxide and you know he encouraged me to to continue in this science and advance the science because and he told me the night at dinner when he came and gave a lecture that if we meaning the scientific community can figure out how to safely and effectively deliver nitric oxide in an outpatient setting that would change the world. Wow. That was 1998. That was the late 90s. Yeah. So I was (05:00) working under a pharmacologist Dr. Martin Felish uh who had been in the nitric oxide field for the previous 20 years. And you know it was interesting. It was a challenging science because when nitric oxide's produced it's gone in less than a second. (05:18) So once it's produced where does it go? What does it become? And how does it signal? Those were kind of the unanswered questions in the field. So then I developed some analytical methods we could now detect a fingerprint of inobiology in different disease states. So then we could answer you know when nitric oxide's produced we know where it goes we know how it signals and we know what it becomes. (05:37) So now we can trace these biomarkers at certain stages of nitric oxide deficiency and then correct it along the way. So what was so let's talk about that what was the finger say that again the fingerprint of a fingerprint ofology. Okay what is that? So you know and as you know as a physician when you look at symptoms right we we look at labs we look at biomarkers right and these are kind of static biochemical measures correct yes so like cholesterol is pretty stable in the blood uh most hormones are pretty stable in the blood where we can detect (06:06) them and get a number but nitric oxide once it's produced it's gone in less than a second so we can't draw blood and measure it measure nitric oxide now in the research environment we can measure these oxidative metabolites of nitric oxide We can measure nitric oxide bound to proteins, bound to metals and quantify what this looks like during different kind of redux states and different disease processes and even different stages of disease. (06:32) And then understanding the metabolism of nitric oxide, we can kind of work backwards and go, okay, here's what's happening. When you lose the ability to produce nitric oxide, there's a there's decrease in these metabolites. there's usually an upregulation of superoxide, hydroxal radical, oxidative stress, inflammation, and then immune dysfunction. (06:51) So, we kind of knew what the end biomarkers were, but we didn't know mechanistically what led to these biomarkers that many p or many physicians were used as treatment modalities in treating that number. So then for us it was and really when I started my own independent research career was we were charged with understand the mechanism of disease to the extent that you can develop rational therapies and with nitric oxide that's what I was doing along with Fred Murad who was my department chair the one of the other guys who shared the Nobel prize was how do we safely and (07:21) effectively deliver nitric oxide at the right dose at the right time in the right patient and that's been our goal for the past 25 years. so interesting to me because you know I and many other clinicians spend a lot of time in the exam room especially in the integrative functional sort of world where we're looking at physiology we're mapping out pathways we're looking for exactly what you just mentioned we're looking for inflammation we're looking for oxidative stress we're looking for you know like detox load or toxicity toxicity load but you're (07:50) mentioning that as almost like an end marker whereas we're thinking of it as being like oh my gosh we're being so proactive and preventive because we're measuring for these things thinking that they're like directly going to correlate to disease manifestation or disease burden 10 years from now, 20 years from now, that type of thing. I think what you're saying is that's still too late. It is. (08:13) I mean it certainly is because what we what we know from the both the basic science and the clinical data is that the functional loss of nitric oxide precedes the structural changes we see in cardiovascular disease es schemic heart disease hypertension erectile dysfunction endothelial dysfunction um by many decades. (08:33) So by the time you have an elevation in C reactive protein by the time you have erectile dysfunction hypertension obstructive coronary disease you've been deficient in nitric oxide for many years. Wow. So, but I think it's important that to to still recognize those because they're clinically relevant, right? But then work backwards and really at the earliest point of what leads to those um end products or clinical biomarkers and then address that because sometimes it's not just enough to give antioxidant therapy. It's not just enough because if you're not removing the source of the oxidative stress or (09:03) restoring the most potent anti-inflammatory antioxidant molecule nitric oxide, then you're going to have little clinical outcome. clinical utility. So if we think of all of this like on a spectrum and if the end now is no longer just disease, it's actually some of these sort of quote unquote functional medicine concepts that we just labeled and the middle is the depletion of nitric oxide. (09:26) What is driving that depletion? What are some of the triggers or the things that are causing maybe I mean we all know there's going to be depletion over time, right? But what are some of the things that are driving maybe a more rapid decline in that versus something else? I think it's the American lifestyle. It's it's an America. (09:46) Is it an America problem or you think it's problem? It's a global problem now because most the most advanced country in the world but the sickest people, right? But no, it's it's things like a high cholester or a high carbohydrate diet. Anything that leads to an increase in blood sugar. So they have these advanced glycosillation in products. So glue glucose sticks to proteins, sticks to enzymes and makes them dysfunctional. (10:09) Um and then it's um you know sedentary lifestyle. It's environmental toxicants both from the herbicides and pesticides on the food glyphosate. Um and then you know even there are certain frequencies like the 5G has been shown to disrupt the electron transport and you know electron flow and enzyatic reactions and then you know the what I focused on really the past 20 years is what else is leading to rapid loss and we know it's you know we recognize there's an oral microbiome as well as the gut microbiome that's responsible for the natural production of nitric oxide. So anything that's aneseptic (10:45) antibiotic disrupts nitric oxide production. things like fluoride in your toothpaste, fluoride in the drinking water, uh antiseptic mouthwash, and then the big culprit are ant acids, specifically the proton pump inhibitors. Really, because those drugs completely shut down nitric oxide production, we've been prescribing those for god knows how long. They're overprescribed. (11:08) You know, they were never approved by the FDA for chronic use. They were only approved for the acute use for esophageal reflux for a limited time, for three to five days. And yet people taking these for 15 20 years. Yeah. And the consequences are clear now. I mean people there's at least two studies out. One I believe in 2015 showing that people who have been on PPIs for 3 to 5 years 40% higher incidence of heart attack. Not increased risk. (11:33) These are actual events. And then late last year a new study came out that 40% increase in Alzheimer's in dementia. And so I take these clinical observations of and these clinical outcomes and okay why are we seeing this mechanistically what's happening and we know that the proton pump inhibitors are completely shutting down nitric oxide production. Wow. (11:57) So you're decreasing cerebral blood flow focal eskeemia misfolding proteins in resistance in the brain that's Alzheimer's. If you have existing plaque it makes that plaque unstable vulnerable it ruptures. There's your heart attack and stroke. M what about some of the other conventional pharmaceuticals that are used chronically now I mean I'm curious about so many of them ADHD medications birth control pills statins metformin where what where do those all statins are the other big culprit you know because if you get your cholesterol below 200 a lot of bad things happen you can't make vitamin D do you know not to interrupt you but do (12:26) you know like didn't they just publish new guidelines around cholesterol to saying to correct it down to like 100 at your total I think I saw that recently want to make a chronically sick population, that's a great idea. But no, look, it's it's malpractice at this point because what I look at are risk benefits. (12:44) What are the benefits of taking cholesterol lower medication versus the risk, right? Number one, cholesterol does not cause heart disease. So, it makes no sense to target as a treatment. All the primary, secondary, tertiary prevention trials, tens of thousands, hundred thousands of patients. (13:04) When you look at the absolute risk, there's no benefit to statin medication in preventing heart attacks. So there's no benefit. What's the risk? Well, you disrupt intracellular signaling because you you disrupt the membrane fluidity because there's need to have cholesterol in you. You develop diabetes. They're mitochondrial toxicants. They cause myalgia, muscle cramps, and they're causing cancers. (13:26) So if there's no benefit and it's all risk of any treatment, it's a very simple quotient and you don't do it. What's the right role? Okay. So again, we were sharing before we started this episode like I've got a husband with a strong family history of heart disease. He had his first MI at first and only MI, I'm going to put it out there at 41. And it's been interesting to watch his journey as a functional medicine or holistic doctor because I remember the day of the heart attack. (13:56) They bring up like I think it was close to 40 60 60 milligrams of a statin to give him right away and another slew of medications, beta blockers, this that and he like literally could not function or move, you know, in the post of that. And since then the medication load has lowered, but there's definitely been a cognitive fallout and we've had to switch things multiple times. (14:19) You know, I had a patient just the other day as well who was like, "Oh, I heard like everyone should be on a statin." like it's just it's just helpful for everybody. You know what is the right use of a statin in the context of cardiovascular disease and in the context of longevity? Scientifically speaking there's no benefit. Wow. (14:40) There is no safe judicious use of a cholesterol lowering medication. So wait, I'm going to say that again just to make sure everybody heard that. You are saying scientifically there's no safe use of a statin. That's right. You know, some physicians may argue, well, there's a pleotropic effect. It stabilizes existing um plaque or vulnerable plaques. (14:58) Um but again, it's risk benefit and even in the secondary prevention trials, there's been no proven benefit of cholesterol lowering medication. Then why is it out there that everyone needs to be on a statin? Well, I think it's misinterpretation of data and it's big pharma pushing their agenda because the goal, you know, for big pharma, it's just like any for-profit company. You have two objectives. (15:22) Get as many customers as you can and keep those customers as long as you can. And they're the best in the world at that because it's a multi- trillion dollar annualized industry. And they get a customer, they keep the customer for life, right? Once you start these medications, there's never a discussion, at least in standard alopathic medicine, to get people off of medications. (15:41) It's like you're on it for life. We're going to add more medication. So I think it's it's a misinterpretation. uh you know there was some early promise in the 80s right when these um HMG COA reductase inhibitors were first discovered and manufactured and these are what we call the statins today that it could because at the time it was thought that cholesterol would cause heart disease right because again misinterpretation data of epidemological data and even the American heart association at the time the statins were approved (16:11) said that it will eradicate cardiovascular disease by the turn of the century and where are we today we're 25 years past the turn of the century and we still cardiovascular is still the number one killer of men and women worldwide. Right? In fact, it hasn't gotten better. It's gotten worse. (16:29) If you look at the number of PCIs per year in the US alone in a 4-year period in the early 90s, it was about 1,600 PCI, these peraneous coronary interventions or, you know, stances interventions. Today, there's about four to 5,000 a year. So we went from 1,600 about 400 a year to 10 times that today and everybody's on a statin and yet the numbers are going up. So you cannot no longer ignore the data. (16:59) We have to pay attention to data and then make changes based on new developments, new innovations, new information and knowledge in the scientific literature. So if you are a cardiovascular patient, somebody like my husband or somebody else who has a known family history of heart disease who might have a stent and you have high cholesterol scientifically, is there a threshold at which it's worth starting one of these medications or does it need to be approached in a different way? For example, uh you know, I guess I'm selfishly asking too as a clinician, (17:29) like you know, if a total right now my guideline is if a total cholesterol is over 200, that gets my attention. If it's under 200, it honestly doesn't. The only differentiation I'll make is if somebody has high small particle B, which has a tendency, it's a fractionation of the lipids that you can ask for. It can be run through regular, you know, regular labs, the lab core request. (17:53) But when we fractionate those lipids and we see high small small particle B, that's where I might be like, okay, I need to take this seriously because this has more of a tendency to, you know, to form plaque and can be more of a risk. Am I correct? Am I thinking scientifically or does that actually need some adjustment? No, I'm thinking it's an adjust. Look, our body makes cholesterol, right? Right. We have an enzyme. (18:16) That's what the statin medications, they prevent the indogenous production of cholesterol. But we also get cholesterol from our diet. And so the body balances what it consumes through the diet versus what it needs to produce indogenously to maintain normal optimal levels. So if you look at the Framingham study, right, which is the largest prospective clinical uh cohort probably in the certainly in the US, probably maybe in the world, the people who live the longest have a total cholesterol of 240 to 260. Okay, that gets no press. (18:47) Of course not. And again, unless you have a fatal cholesterolmia, hyper cholesterolimeia, and your total cholesterol is maybe five or 600, maybe maybe you you you try to lower it. But again, cholesterol does not cause heart disease, so why target it? And I like the advanced lipid panels because if you looked at oxidized lipoproteins, if you look at the particle size and number um that has more bearing on diagnostic prognostic utility than total cholesterol or total HDL, total LDL to me those are completely useless. Useless. So what should we be screening for on our cardiovascular patients or if (19:27) we have you know that kind of family history? What what should we be screening for? I don't know how you feel about things like Appo B, LP little A. These are all the questions I get over and over again. No, I think those I think they're certainly more clinically useful than total cholesterol, but you know, certainly myoproxidase, elevated NO is pretty pretty good biioarker for susceptibility of plaque rupture. (19:54) I still like the LP little A C reactive protein, the amount of inflammation in the lining of the blood vessels. Um but me it's it's it's all about vascular reactivity and endothelial function because when we look at the progression of cardiovascular disease the onset and progression what happens is number one you lose the barrier function in the end in theal cells you lose the v vascular reactivity because the endothelal cells produce nitric oxide dilates the blood vessels and then they also downregulate the adhesion molecules. So if if your endthelial cells in your blood vessels are making sufficient nitric oxide you (20:26) have normal blood pressure you have normal vaso reactivity you downregulate the adhesion molecules so you have less monocytes neutrfils uh macrofasages platelets that are sticking you maintain the barrier function and you have healthy blood vessels you don't get smooth muscle hyperplasia you don't get plaque deposition and you're free of cardiovascular disease so I think we need to focus on not just the biochemical biomarkers but look at the functional component the function of the blood vessels and we can do that through flow media (20:57) dalitation look at the schemic um plmosography and look at how well do the blood vessels respond to certain agonist or stimuli because that tells you the function of the blood vessels and not kind of a static biochemical marker and that could be the fundamental issue that we're having is that we're just looking at static markers rather than what's actually happening. (21:20) Is there a way in the exam room to measure endothelial function and endothelial reactivity? There are there's some FDA cleared medical devices that look at what's called flow mediated dilotation. Um, and really that's the gold standard. So you put a blood pressure cuff on the brachial artery and you just pump it up to super systolic levels to where there's no inflow into the form and you you olude that blood vessel for five minutes. (21:44) Okay? And then you release it and then you can look at the reactive hyperemia or the dilation of the brachial artery downstream. And if it dilates then it tells us that blood vessel is making nitric oxide. It's responding to that brief period of hypoxy and eskemia and your blood vessels are making nitric oxide. (22:03) But when you release the cuff and there's no vasoddilation that tells us without a doubt those blood vessels aren't making nitric oxide. But that's not something somebody can do at home is right. a traditional cuff. You can't no you have to either have an ultrasound or there's some companies who use a fingertip probe. Um you can look at uh you know non-eskeemic plethmosography and looking at pulse wave analysis looking at the stiffness of the blood vessels and how fast that pulse wave travels with each heartbeat. (22:28) But there's different devices out there that are functional measurements uh and they're very very useful and clinically relevant. Or you can look at symptoms because what we're finding now is if you're deficient nitric oxide, there's a there's a hierarchy of symptoms. So number one, you start to develop erectile dysfunction. Is that the first symptom? That's usually the first symptom. Wow. Okay. (22:45) Because think about it, if you can't dilate the blood vessels, the sex organs, because your body can't make nitric oxide, you don't get engorgment. You cannot get engorgment. Right? So it's in men, it's very simple. It's a blood flow problem. In women, sometimes it's hormonal, it's psychological, but again, it's a vascular issue. And 50% of the men over the age of 40 self-report ED. (23:05) I think it's much higher because most men aren't going to self-report ED. Right. Well, what about all the women who are coming in with low libido? Should I be thinking about it with them as well? For sure. Okay. I mean, but again, I think nitric oxide is what we call foundational. Okay. So, when we restore nitric oxide, you're still going to have to address other hormone deficiencies, but I think it's foundational to start there. (23:24) So then number two if you don't correct that so if you have endothelial dysfunction in the vascular bed of the sex organs you have that same dysfunction in the coronary arteries the arteries of the brain the liver it's systemic second you develop an increase in blood pressure because nitric oxide kind of fixes the physics problem of hypertension because we all have a finite amount of blood pumping through all our blood vessels and if we make nitric oxide then with each heartbeat we dampen that pulse response we have the same volume of (23:53) blood going through more dilated blood vessels. So pressure is normal. If we can't make nitric oxide, now our blood vessels are chronically constricted. Then we get that same volume of blood going through smaller pipes. And simple laws of physics tell us that pressure has to go up. (24:10) And 50% of Americans have an unsafe elevation in blood pressure. Now, we know that 1 millimeter mercury increase in blood pressure above 120 increases your risk of heart attack and stroke by 1%. Wow. So if you've got a patient with a blood pressure of 140 over 90, they have a 20% greater risk of a heart attack or stroke than if you could get that blood pressure down to 120. (24:34) And how do you like to get that blood pressure down? Would you resort to medication management first or what's your Well, we always start with what's affecting their nitric oxide production. Okay. Do they have fluoride in their drinking water? Do they have fluoride in their toothpaste? Are they using an aniseptic mouthwash every day? Are they on ant acids? How do antiseptic mouthwashes impact nitric oxide production and maybe even fluoride? How does fluoride impact? Well, these are antiseptics, right? So, anything that destroys the bacteria that live in and on our body. Okay. So, about 20 20 25 years ago, we and (25:04) others discovered that the oral microbiome, there's some what we call nitrate reducing bacteria that metabolize nitrate from our diet, converted into nitrite to nitric oxide, and that dilates blood vessels. And so for for years it was thought to be an assoc an association right we published in 2014 that people had the least greatest diversity in the oral microbiome had elevated blood pressure. So it was an association but not causation. (25:29) that in 2019 we published a clinical paper showing if you take normal intensive patients that are unmedicated good diet good perio full oral exam and the only thing we do is give them aneptic mouthwash twice a day for seven days their blood pressure goes up so now that's causation so we're killing the oral microbiome we're shutting down nitric oxide production and their blood pressure goes up and furthermore you lose the protective benefits of exercise. (26:01) So this is extremely important now in modulating indogenous nitric oxide production by targeting the oral microbiome. And now we're doing the reverse. So we're taking patients with resistant hypertension which as you know they're resistant to standard therapies right and now we we simply ask them are you using fluoride toothpaste? Are you using mouthwash? I developed a fluoride free toothpaste that targets the microbiome. (26:20) So, we switch their toothpaste, we get them off antiseptics, and their blood pressure comes down. Amazing. So, I mean, think about how profound that is because huge. Hypertension is the number one driver for the number one killer of men and women worldwide. (26:38) And 50% of the people that are given prescription anti hypertensive medication don't respond with better blood pressure. So for people listening or for clinicians listening, you know, you've got a patient in the exam room or you know personally at home with your home cuffs that your blood pressure is now 130 over 80 or 90 or you know somewhere in that range before we start thinking medications. (26:58) We should almost be doing a checklist of sorts looking at the oral microbiome. It sounds like it's you're saying it's first look I would have not thought of that to look at the oral microbiome first. So looking at the oral microbiome first, repopulating that by reducing fluoride and antiseptics. Yep. That's our starting point. Where would we go from there? Uh ask them if they're on ant acids. Okay. (27:23) You know, there's I think 200 million prescriptions are written for ant acids every year. Yeah. And now you don't even have to have prescription. You can get pyloc previs get these over the counter over the counter proton pump inhibitors. Um and then you've got to work with those patients and wean them off those drugs. You know, these aren't drugs you can stop cold turkey. You'll rebound. Rebound. It's going to be miserable. (27:41) So, you have to figure out a way to wean them off these over time. And now you've released the brakes on the body's ability to naturally produce nitric oxide. And then what we can do? Well, we can change their diet, get rid of simple carbohydrates, anything that leads to an increase in blood sugar. (27:58) Uh throw in some more green leafy vegetables which are enriched in inorganic nitrate. Uh moderate physical exercise. You know, we used to say 20 to 30 minutes of moderate physical exercise a day is sufficient. Now, we know that, you know, four to six minutes of high-intensity interval training, anything that gets your heart rate up, your breath rate up will activate and stimulate nitric oxide production. Four to six minutes. Four to six minutes. We can all do four to six minutes. Time is no longer an excuse. (28:20) We can't say we're too busy. So, and that's high intensity. So, that's where does that heart how much of a heart rate rise would you recommend? You know, for me, I'll tell you what I do personally, and it's worked for me because I get up every morning. (28:37) Um, I usually sit in infrared sauna, but before I do that, does that raise nitric oxide? Well, it helps. It It modulates nitric oxide production. So, it's helping you to detoxify, get rid of things that are inhibiting nitric oxide production. And then the red light is activating our mitochondria, releasing nitric oxide that may be bound to metals. But I do 100 squats, 100 push-ups. Okay? And then I do some stretching. (28:56) 100 push-ups. So, every morning when I get up, whether I want to or not, I'm at five right now. But, okay. Well, I started out doing four sets of 25, both squats and push-ups. All right, now I'm up to two sets of 50. Okay, but that I do 12 minutes. So, that takes me about four minutes to do 100 push-ups, 100 squats, and then I do stretching. (29:16) And then a lot a lot of time if I'm at home, I'll do like 10 40 yard sprints. Okay. But all in I'm 20 minutes. Yeah. And I've got an excellent workout in. I'm sweating, my breath rate's up, my heart rate's up. I mean that high-intensity interval training, your heart rate may get up to, you know, 140, 150 or higher. Is it a good idea to use your heart rate as a measure of how how much intensity you've got? Like for example, rough rule of thumb, should you double your heart rate? Should you go one and a half times your heart rate? Is that a way to know (29:42) that you're in that zone that I'm assuming also helps you increase nitric oxide production? I don't know if that's been studied in the on its effect on nitric oxide production, but obviously you have to have clearance. I mean, you don't want to go in with a poor functioning heart and try to increase your heart rate, right? Not not what I'd recommend. (30:00) But no, I think what's happening is we're we're fully oxygenating. The other big thing is nasal breathing. You know, if you can focus on nasal breathing instead of mouth breathing because just like our endothelial cells, our epithelial cells have a nitric oxide synthes enzyme. And we do nasal breathing, it activates. We're delivering nitric oxide down to the pulmonary vasculature. (30:19) It's dilating the bronchios, dilating the pulmonary arteries, and we're improving oxygenation. Wow. So correcting any airway abnormalities becomes important too for sure. That's the other thing. You know, most Americans are mouth breathers and it's leading to detrimental outcomes. I mean the mouth is not an instrument for breathing. (30:37) It's an instrument for talking. So when you do mouth breathing, you're completely changing the oral microbiome. You're completely shutting down nitric oxide production and you're bypassing this nitric oxide production pathway through the nasal sinuses. And where does sleep and uh weight, hormones, where does that fit into the nitric oxide puzzle? I think it's certainly downstream. (31:02) I mean, nitric oxide is what I say is like that first domino because in biochemistry, biology, and physiology, there's always cell signaling, right? So, I like to think of nitric oxide as the first domino. So, if you knock over that first domino, everything else takes care of it. If you start downstream, like halfway through and start that, then you've missed all the opportunity. Yeah. But again, nitric oxide is a hormone. (31:20) We first focus on restoring that. Wait, hang on. You're saying nitric oxide is a hormone. Yeah, we were the first group to publish on that in 2007. Can you explain that to us? I'm thinking antioxidant or I'm thinking I don't know what I'm thinking, but I wasn't thinking hormone. (31:39) Well, hormone So, hormone is is a a molecule that's produced in one gland or one part of the body and has systemic effects. Like estrogen produced in the ovaries, systemic effects. uh testosterone in the testes and man has systemic effects. Well, nitric oxide is produced in the mouth by the oral bacteria. It's produced in our endothelial cells. It's produced by our immune cells. It's produced in our neurons. (31:57) And so people thought, well, it only has an autorine or paracrine effect. Meaning because it's a gas with such a short halflife, it can only act in the cell in which it was produced or a neighboring cell. Call that autorine or paracrine. In 2007, we published in the precedes national academy of science that nitric oxide that we were overproducing in the heart could protect the liver from eskeemia reprofusion injury. (32:22) And so the nitric oxide produced in one biological compartment had systemic effects and it had hormone-like effects. So we discovered that nitric oxide is a hormone. And so when we do hormone replacement therapy, right? Right. We don't have to inject estrogen in your ovaries. Right. We don't have to give testosterone in our testes. Thank God. (32:41) We can deliver it anywhere in the body, right? You can do it transermally. You can do it intramuscularly. You can do it u you know sublingually with a there receptors everywhere. They're receptors and it's taken up in the blood. These are very small. These nitric oxide is a very small molecule and it goes systemic. (33:00) So I made an orally disintegrating tablet, a solid dose form of nitric oxide gas that when I deliver this nitric oxide in the oral cavity, a certain amount of nitric oxide over a certain period of time, it completely recapitulates nitric oxide production and signaling. So what we do is hormone replacement therapy with nitric oxide. So interesting. I didn't think of it in that context. Okay. (33:18) So, let's talk because I've been obviously like, okay, if that's the problem, if nitric, you know, nitric oxide decrease or lack of production is the problem, how do we replace? Obviously, we have all the other ways of replacing it. You stop doing the things that are needed. Stop doing the bad things and you've gone through some of those, but then is there another step we should be taking? Can you replace it? And then for somebody like me, advising people, you know, how do I measure it? like how do I say yes, this is the step to take now, you know? Well, our goal is to give the body what (33:49) it needs so the body can do its job. Right. Right. The human body is much smarter than any of us. Right. We just got to get out of the way. And the problem with medicine is we get in the way all the time. All the time. Yep. And there's like a 20-year lag between what you're finding more probably you're saying actually like probably like a 30-year lag between what you see in the lab and in science with what we actually practice in the clinic. Well, on average it's about 17 years. Okay. (34:12) From new discoveries becoming standard. No, but that's average, right? So, some may take five, some may take 30. I could be an Alzheimer's man then. You know what I mean? That's a really long exactly. Well, we got to talk about that, too. But first, go how do we replace? How do we measure? How do we replace? What do we do? Well, first we had to understand how does the human body make nitric oxide and what leads to its natural reduction in the natural production. And so, now that we understand that, we can address (34:37) that. So, it's it's as we discussed, get rid of fluoride in your drinking water and toothpaste, stop using antiseptic mouthwash, wean off ant acids, get moderate physical exercise, 20 30 minutes of sunlight a day. I like the first sunlight in the morning. Uh, and then, you know, just move. (34:55) And then now your body is able to produce nitric oxide naturally on its own. But if you have some genetic predispositions, these snips, these single nucleide polymorphisms, if you've got an MTHFR, if you've got a snip in your ENOS or Inos, then you're, you know, genetically uh deficient in the ability to produce nitric oxide. (35:13) So then you may have to take some, you know, like what we make supplements or we're developing drug therapy, the things that again, if your body can't make it, then we we provide it for you. So you can take nitric oxide. Can I measure nitric oxide on a patient or not really? You know, years ago, about 15 years ago, I developed a salivary test strip and at the time it was the only point of care non-invasive diagnostic for nitric oxide. I don't use them anymore. (35:36) I abandoned the patents on them probably in 2012 or 2013. Now, several companies are out there selling these nitric oxide test strips, but they're not nitric oxide test strips. What we're measuring is salivary nitrite. So the really what they're measuring is the presence or absence of oral nitrate reducing bacteria that then reduce the nitrate to nitrite which we're picking up in the saliva. Is that reliable? You know there's false positives. There are no false negatives. (36:02) So if you're deficient in your saliva then you're deficient in nitric oxide. Okay. But it doesn't tell us why. Is it because you have endothelial dysfunction? Is it because you're on an acid? Is it because you're using mouthwash? Uh do you have a disruption in the silent receptor uh in the salivary glands? Uh is there a problem with nitrate excretion in the kidneys? Um people with you know acute kidney injury or renal insufficiency. (36:26) So all of those take into account what we're doing in measuring this interoscelerary recirculation of these nitric oxide metabolites. So you know I don't use them anymore because I think clinically how the patient feels and these other you know better management of blood pressure C reactive protein goes down. (36:45) One of my patents on a method of reducing C reactive protein we see a 37% reduction in C reactive protein within 30 days nitric oxide when using our nitric oxide lost we see about a 40% reduction in triglycerides and if you want to do lipids as a biioark triglycerides are really the the culprit. Yeah. and really should be the target of therapy, not cholesterol. (37:07) Um, but we see about a 40% reduction in triglycerides and people have triglycerides greater than 150. Wow. And then better blood pressure. So if your inflammation goes down, your triglycerides go down, your blood pressure becomes improved, and your sexual function improves and your cognition improves. (37:25) Those are what's meaningful and it may have no bearing on their cholesterol may have no bearing on anything else, but clinically they're better. Are there any current studies or trials going on where someone we do replace nitric oxide and we see better cardiovascular outcomes? I've published there's probably been I don't know maybe a dozen 10 or 12 placeboc controlled randomized clinical trials on the nitric oxide technology that I developed out of the University of Texas Health Science Center Houston. But yeah, what we see is within six months we see about 11% plaque (37:56) regression. Okay. And the croted uh we see a normalization of blood pressure. We see mobilization of stem cells. Uh we see reversal of left ventricular hypertrophy within five months. We see reversal of kidney disease within five days. Uh what else? We see an improvement in exercise performance and well trained athletes. (38:19) Um in COVID, we had a drug in phase three trials for for early treatment of COVID. We saw better tissue oxygenation, blood oxygen saturation, familiaration of symptoms in COVID patients. But most importantly, we established safety, right? And so because what we're doing is what we call restorative physiology and not pharmarmacology. (38:38) It's extremely safe at the levels we're we're administering. So is that an emerging field? Restorative physiology. And other than nitric oxide, what what's in that field right now? Well, I kind of started that field because I understand as a biochemist and a PhD in physiology that how these biochemical systems work. So again, our objective is to understand the enzyology, the protein chemistry that leads to cell signaling and how the body operates. And so we're never deficient in an in a in a synthetic compound that inhibits a (39:09) biochemical reaction, right? And I think that's where pharmarmacology has gone wrong, right? because we look at symptoms that manifest as a result of some biochemical problem and then we treat the symptom. But that would be like blaming the firet trucks on the fire, right? So the fire trucks always show up at the fire but they're not causing the fire. (39:32) And when you look at biomarkers or symptoms of disease, that's what pharmarmacology does. It tracks the symptom and inhibits that reaction, right, that's associated with that disease. But again, association is not causation. That's why medicine doesn't work most of the time. (39:51) So what we try to do is and nothing we do is synthetic, right? And there's been some resistance in that because it's if you can't patent something, you can't monetize it. You can't monetize it and big pharma about monetizing. But you know, I've kind of figured that out because I have dozens of issued patents where we're developing nitric oxide based product technology. (40:08) So what we do is only on nitric oxide, right? So we understand how the human body makes it. We understand what leads to a loss of its production. And now we can fix it. And it's not pharmarmacology, it's restorative physiology which you know hundreds of years ago this whole field of medicine going back to hypocrates y it was applied physiology that's medicine but today unfortunately it's called applied pharmarmacology right and it doesn't work. (40:32) We have to get back to the root cause and most we understand root cause in many things. It's caused by exposure to toxins or nutrient deficiencies. If we remove the exposure to toxins and res missing nutrients, the body so much gets better. Yeah. The body heals itself. We're regenerative by nature and nitric oxide mobilizes stem cells. (40:49) So now we've got an increase in circulating stem cells. We can repair and replace dysfunctional cells. So why are we not all on nitric oxide? Well, I don't know. I mean, that's that's kind of the beauty of these conversations because there's so little awareness around it, right? You know, I still give a lot of uh talks to to uh physicians, clinicians at medical conferences and I'm still surprised by the complete lack of awareness around I think there's a growing awareness and there's more companies trying to enter this field in the dietary supplement space and some (41:19) companies trying to develop nitric oxide based drug therapies as we are. Uh but until there's approved drugs on the market that make the headlines, um you know, I think we're still going up against some very powerful forces that don't want right this technology to see the light of day. (41:37) Because think about this, if we can improve chronic Alzheimer's patients, heart disease patients, diabetes, by giving a molecule in an outpatient setting, nitric oxide, that corrects most of this along with diet and lifestyle changes. And now we can wean patients off of drugs, have the conversation of, well, you're no longer you no longer need a cholesterol lowering medication, right? Um, your GIRD's gone, so you no longer need an acid. (42:01) Um, you don't need your blood pressure medicines. So the ACE inhibitors, the ARBs, the calcium channel blockers are gone. You're basically disrupting medicine. It's it's the most disruptive technology in our lifetime. I think it's incredible and fascinating and so hopeful. I'm actually thinking about this 80-year-old patient I saw recently. I'm curious to see what you think. (42:19) uh congestive heart failure that then developed into cerosis of the liver that's now developing into ascites multiple medications multiple things is nitric oxide a fit for her I think it's a start and again understanding the ideology of what caused that so heart failure right number one so nitric oxide is not just a vasoddilator I'm going to dilate the coronary arteries but at certain doses it's what we call a positive ionotropic compound so it's going to increase the contractility of the heartm M so now ejection fraction is going to improve. You know in in cerosis we have what's (42:51) called portal hypertension. So there's reduced blood flow through the portal circulation. Nitric oxide dilates those portal veins where 70% of the art and even the arterials that supply the liver. Um so and and we published that in 2007 that nitric oxide can protect the liver from an elevation from eskeemia reprofusion injury. (43:10) Lower liver enzymes improve profusion. Um, and when you reduce the pressure, you eliminate the ascites. So, I think it's a great place to start a great place to begin, but you just have to look other places and see what else, you know, as you right have other toxicities that are leading to liver dysfunction. Let's switch for just a second. (43:28) I think the promise for cardio uh vascular health is so exciting. I mean, this is something like you already said, number one killer of men and women. Women always forget that that's a major player for them and it turns the whole conversation around the risk factors upside down on its head. So I think that is so fascinating. (43:46) What about its role? I think I know your answer but I still want to hear you say it. But what about its role in metabolic health? We know that you know I think the stats are 30% of adults over 60 are obese. Obese not even overweight numbers are higher for overweight. What about metabolic health? What about Alzheimer's and dementia which is an epidemic as well? What what's the role in those scenarios? Well, nitric oxide is part of insulin signaling. (44:13) And my group was the first group in 2011. We published the first paper showing that nitric oxide is required for insulin signaling and glucose uptake. And so to understand the insulin signaling when when you have an elevation in blood sugar, it tells the pancreas to secrete insulin. So then insulin goes binds to the insulin receptors primarily on fat tissue, muscle cells and liver cells. (44:36) And then there's an intracellular signaling cascade. It activates PI3 kynise AMP kynise which is the target of metformin. Mh. And then the terminal step in that is glute 4 transllocation. It's a cytoolic protein that goes to the membrane and brings glucose into the cell. (44:54) But that was really there was a gap in understanding of how does glute 4 get the signal from kynise or p3 kynise. And what we found was that they converge on nitric oxide synthes. So metformin can activate phospholate specific tyroscene residue on enos activate it to produce nitric oxide and then nitric oxide binds to glute 4 modifies two cysteine residues and then that structural that change is the function of it goes to the membrane and brings in glucose. So nitric oxide is really the mediator of something. (45:23) In diabetic patients who can't make nitric oxide, the reason they're insulin resistant is because their enzyme that makes nitric oxide doesn't work. So you can give glucage or metformin and it's supposed to activate nitric oxide production and increase glucose uptake, but it typically doesn't work. You're going to increase the dose because the the sensitivity of that reaction is not there. (45:45) So what we did in this paper is we give nitric oxide, we restore the function of the enzyme, we activate glute 4 and we improve insulin signaling and we improve glucose uptake. So our interpretation from that 2011 paper was that insulin resistance and metabolic disease is a symptom of nitric oxide deficiency. (46:04) So what about the GLP1s and that whole world and well the GLP-1s are affecting kind of the the hunger sensations of the brain. Right. Right. So it's decreasing or increasing the satity to where you don't want to eat as much. But again, until you restore the cell signaling aspects of any signaling molecule, not just the GLP1s, but you can actually finish that reaction and make that reaction more sensitive, sensitize it, just like we do, we sensitize insulin's effects. (46:32) We can sensit sensitize the effects of those. But again, let the body do what it's designed to do. fix that disruption in cell signaling and then the cells communicate and do what they're designed to do and do what they need to do. Decreasing your medication burden and I'm assuming you see the same thing with Alzheimer's and dementia. Alzheimer's and dementia. Yeah, we've got some studies showing that we can. (46:52) So, number one, Alzheimer's is a metabolic and vascular disease. Yeah. So, it's called diabetes type three. If you look at this progression from mild cognitive impairment to vascular dementia to Alzheimer's, there's a disruption in blood flow to the brain. We call it focal eskemia and you can measure this through functional MRI or spec scans. (47:12) But in the earliest stages there's disruption of blood flow to the brain. So what does nitric oxide do? Well, it dilates the blood vessels. So now we get full profusion of the brain. What does it do? It enhances glucose uptake and improves insulin signaling in the brain. So nitric oxide overcomes the metabolic and vascular issues of Alzheimer's. (47:30) Wow. And so when you do that, when you deliver oxygen to the brain, when you get glucose into the cell, you can make cellular energy. You don't get misfolding of protein, you don't get loss of cognition, and you don't get Alzheimer's. And the last group because I'm curious, our kids, you know, the ADD, the ADHD, the anxiety, the depression, same conversation. (47:57) Look, if you look at spec scans, and this is work of of Daniel Aman. Yeah. Love him. Yeah. Even in young kids with attention deficit disorders, addictive disorders, you know, even by any neurological condition, it's a blood flow problem. And so if there's not if your blood if parts of your brain aren't getting profused and you can't deliver oxygen, nutrients, then those parts of the brain can't perform and they manifest as attention disorders, they manifest as addictive disorders. (48:22) Um, and then so it's a progression of disease, but it's always a vascular metabolic issue. All of those, all of them. and kids who, you know, if if I look at the diet of kids that my kids go to school with and what they put in their lunch box. Yeah. And I want to go to their parents and go, "And you wonder why your kid is disruptive. (48:39) " Right. Uh so it's what they eat, it's what they're exposed to, and it's a toxic burden and not focusing on adequate metabolism and blood flow. You mentioned something too that I'm also concerned about. I know glyphosate's out there. We we recognize all of that, but the 5G which is becoming prevalent and changing frequency and a lot of some of the assessments that we do in practice and a lot of what I like to look at is frequency and how that is impacting kind of overall health. (49:08) How do we override something like 5G? Like that's an environmental burden, you know, is taking nitric nitric oxide going to help with that or like what what do we do there? It's not going to address the issue. So what what we do there's certain frequencies that disrupt and as a biochemist I look at the transfer of electrons right we count electrons there's always a a redux potential that allows for a flow of electrons through any biochemical reaction and these certain frequencies or voltage these electromagnetic frequencies can disrupt that so it's causing a lot of (49:40) problems so the issue is I wear a lot of quantum energy devices that kind of mitigate the 5G I have them in my house do they work do they work um and which ones Do you like I don't know objectively if I've ever seen any data of it working, but understanding quantum physics and these quantum fields we're exposed to. (50:00) It makes sense, right? At least me to me theoretically. Um, you know, but I'm on a plane every week. I travel probably 200 days out of the year or more. But I I have them in my home. I wear them on planes and I bring them in my hotels just to protect myself. Um, but I I do probably I I certainly get better sleep now that I've employed that, especially in big cities and hotel rooms, especially in Vegas where it's filled with toxins. Yes, toxicity central there for sure. (50:30) Well, you know, a lot of this some of us are getting excited about. We're like, okay, there's an answer. Nitric oxide might be the answer. It reminds me a little bit about my excitement around glutathione. Like, you know, like, is glutathione the answer? you know, and I'd be curious to see what you think of glutathione, but even whether it's nitric oxide or glutathione or any of these things, like taking the right form, adding them in, you know, knowing if you're not wasting your money or if you're using your resources effectively. As a clinician, too, I don't ever want (51:00) to recommend something that I don't think is going to have a clinical result. You know, how how do we help everyone navigate that world and that territory? Well, to answer your first question, glutathione is extremely important. It's all it's an essential co-actor in the production of nitric oxide. (51:18) Is it okay? And it's a transport molecule of nitric oxide. So when in produced, it binds to the cysteine residue of glutathione and forms what we call an es nitros glutathione and that transports nitric oxide activity throughout the entire vascular tree. But we have millimar concentrations of glutathione. I have you know nanomolar pomolar concentrations of nitric oxide. (51:36) So I think glutathione is important. I use a transdermal glutathione. Yep. Uh it rapidly absorbs the phicinetics and dynamics are pretty superior than anything I've seen. Um but look, the supplement industry is the wild wild west. Right. (51:55) Right. And I think there was a study published last year where a third party went out to the local u supplement stores and bought all the supplements off the shelf tested and they found that like 70% of them didn't have what was on the label. Yeah. So that's a problem. Number two is the nitric oxide products that are on the market, you know, typically don't work because there's two there's two class of nitric oxide products. There's the arginine and citrine based products. (52:18) Then there's your beetroot based products that you see advertised on TV. So number one, the arginine and citrine products are typically useless because these are semi-essential amino acids. Number one, arginine is a byprod or citrine is a byproduct of nitric oxide. It's not a precursor. And these are sem essential amino acids. (52:37) We get them from the breakdown of protein, both plant, animal protein. And it's made through the partial ura cycle that's present in every cell in the human body. So we're never deficient in these these amino acids. So it doesn't make sense to supplement. The problem is the enzyme that converts arginine to nitric oxide is uncoupled. (52:55) So giving more arginine is not going to fix the problem. Not going to solve the problem. So that's number one. Save your money. Don't don't take arginine or citruline products. Number two are the beetroot products. You know, you see it advertised on TV. Those gummies are yummy. Well, they're made of seed oil, right? They're made of sugar. Yeah. (53:14) And they cause cavities and they don't provide any benefit, right? Um because beets have to have a certain amount of inorganic nitrates. Number one, beet products, if you're taking them, you must have the right oral microbiome and you must have stomach acid production or else you're just going to secrete the nitrate in your sweat, in your feces, and your urine completely unchanged. (53:32) Um, and two, you have to have a certain amount of that. And so, you can't deliver a bioactive amount of bead in a gummy or a chew or a capsule. So, it's just it's a math problem. And these companies either they don't understand it or they refuse to understand it. Interesting. (53:50) So, beet products typically are not nitro. In fact, we use a lot of these beet products as placeos in our clinical trials. Interesting. Because they're perfect placeos. It's a dead beat. It's a dead beat. I like beat. So save your money. Do not bite. I like that. So not So then what do we do? How do we evaluate a good a good nitric oxide product, a good product in general? What how does that connect to those? Maybe you know we've talked about the atrisisk populations of cardioabolic and you know Alzheimer's and dementia. What about just the person trying to (54:22) biohack or trying to get ahead of this? Well, you know, obviously I'll disclose that I have a a very strong bias. Yeah. For what I do, right? Because I've been 25 years in the research lab understanding this biochemistry. So, I make products. I did I never got in this field to make dietary supplements. Right. (54:41) Right. I'm more interested in developing drug therapy. But because I saw all these companies out there selling nitric oxide products that do not, cannot, and will not work and we have an obligation. Because these companies that are doing this could kill the entire field. And I hear this all the time. (54:59) People come, Nathan, I I've been using this bead product. I saw it on TV advertising. I bought it, but it hasn't helped my blood pressure. Uh hasn't helped my sexual function, and I feel I maybe even gotten worse. He goes, "So nitric oxide doesn't work for me." And I go, "No, that's that's that's a gross misinterpretation. That company failed you. (55:16) That product failed you. Nitroxid will always work." And so what makes our products different is if your body can't make it, we do it for you. And so I coined a new term maybe five or six years ago called nitrauticals, not neutrauticals, but nitruticals. So that anything that we do, our products produce nitric oxide. If your body can't make it, then we do it for you. (55:40) But more importantly, we fix the reason your body's not able to make it. We restore the function of the enzyme in the lining of the blood vessel. And because this lozen stays in your mouth for 5 to six minutes, we're changing the oral microbiome. We're improving the diversity. We're improving nitric oxide output in the oral microbiome. And now your body's able to produce nitric oxide better naturally on its own. (55:58) Fascinating. And can you tell us the name of your products or Yes. So our consumer products are under the N101 brand. N101. the letter N number one letter O number one.com. So one nitrogen one oxygen which is nitric oxide. Fascinating. And then are you working you mentioned you're working on drug therapy as well. (56:16) What is what does that look like? So we have a company called Brian Therapeutics Inc. We're clinical stage biotechnology company but we've got a drug we had a drug in COVID for early treatment for COVID. Uh unfortunately um at that time the administration wasn't interested in early therapies. They were interested in putting a shot in everybody's arm around the world. Mhm. (56:34) Um we've got a drug now we're moving into phase three for es schemic heart disease. Um you know the standard the cornerstone therapy for es schemic heart disease patients is isor by d nitrate or nitroglycerin which are effective vasoddilators but people develop tolerance to them condition called tachiflaxis and actually long-term outcome studies actually get worse. So through our nitric oxide delivery we still dilate the coronary arteries. We can prolong exercise induced anga. (56:58) There's no tolerance development. So, I think I predict, you know, probably in the next year, maybe 18 months, we'll have this drug approved and on the market and then we're working on Alzheimer's. Um, so Dr. David Pearl Motor's running my Alzheimer's drug trial, designing the studies. (57:15) But again, the early data show that we can improve cerebral blood flow. We can improve cognition because we're addressing and correcting the metabolic and vascular phenotypes of Alzheimer's. And then, you know, I I make a topical drug for diabetic ulcers. (57:32) And this was um you know the my dad who's a parapollegic from a car accident in 1984. I've dealt with decubitous ulcers, pressure ulcers most of my life since I was 11 years old treating him. Um but non-healing wounds in diabetics paraplegics. I'm my dad had a four-year-old um osteoncrotic osteomiitis decubitous ulcer rightial ulcer and he almost died. He got septic and almost died. (57:57) And then all the wound care docs I took him to said, "You'll never heal this wound. He's diabetic, 60 years old, he's paraplegic, and there just nothing we can do." And in 2014, I started making a topical nitric oxide. So every day I would do a wet to dry dressing, put a nitric oxide releasing bandage into the wound bed, release nitric oxide, we killed the infection, we got tissue granulation, you could see the wound bed light up because we're increasing blood flow. Uh, and that started this whole process. (58:21) And within six months, we healed that wound. Fascinating. So all of this is in development still in development. So we have the prototypes, the dual chamber and we sell a a skin care product um in skincare and beauty called N101 nitric oxide activating serum for fine lines and wrinkles and aesthetics. (58:40) Can it reverse all your fine lines and wrinkles? It certainly helps. You know our clinical data show that we can improve collagen deposition. Injectables for everybody. Get away from the injectables. Let the body Let the body heal itself. Let the body do it. Yeah. Yeah. We see collagen deposition improve hydration. fine lines and wrinkles go away. You're going to disrupt that industry, too. Yeah, I know. It's been very successful. (58:56) It's, you know, it's a game changer in skincare and beauty. But we're, these are the proof of principles that we bring to the consumer market to derisk and build upon our drug discovery pipeline to get these drugs through the FDA so that we can use them clinically for specific indications like diabetic ulcers and non-healing wounds. (59:19) You know, 65,000 Americans die every year in nursing homes from wounds that get infected and they get septic and die. And to me, it's a tragedy and it doesn't have to be that way. And our population is only aging. So, you think with this technology that you and your team are developing, we can reverse cardiovascular disease, Alzheimer's and dementia, diabetes, and that we can all look better too in the process. (59:43) Look, our goal is to live as long as we can free of disease, right? We're not immortal beings, right? But our goal is to, you know, live the longest, happiest, healthy life as long as we can and have the best quality of life. And so I think again, not just the basic science, but the clinical translation of basic science really cooperates everything you just said that we can mitigate the onset progression of cardiovascular disease. (1:00:07) We can not just stop and slow the progression of dementia, Alzheimer's, but we can regress it and even prevent it. Um, and yeah, improve performance. So my goal is to optimize human performance and that's performance in the bedroom, the sports field, the executive room, cognitive performance, uh, every aspect of performance, but nitric oxide is a foundational molecule for them. I love that and I love to shifting medicine away from applied pharmarmacology to regenerative physiology. I think that's so hopeful and I know so many of us that are in the field and really trying to rethink how (1:00:36) we practice and rethink what's being delivered, you know, from a patient standpoint, you know, we want this. We we want solutions that work and don't increase the body's burden because we know, you know, whether it's overs supplementation or over medication, both strategies are not the right way. (1:00:55) So, thank you so much for sharing all this incredible knowledge with us. I feel totally inspired by it. Now I don't regret going into biochemistry anymore. How's that? Because I can follow, you know. But if is there a place or somewhere where folks who are wanting to learn more or wanting to connect with you, where can they go? You know, I'm more interested in education and awareness. I send people to my YouTube channel. Okay. It's Dr. Nathan Esprian nitric oxide. Subscribe. (1:01:18) We do a lot of content, a lot of education information. So my goal is to take the information and impart knowledge. And you know, there's a lot of misinformation out there. get, you know, the incorrect information out there. Um, I'm on Instagram, Dr. Nathan S. Brian, LinkedIn, Twitter, Dr. Nitri or X. (1:01:38) Now, u, and then for those who want to follow our drug discovery journey, it's brianther therapeutics.com. And our consumer products are n101.com. N101. Lots of great places. We'll put all of those up on the screen and tie them to the show notes as well if you had trouble catching that. But Dr. Brian, thank you for taking time out of your schedule to join us. (1:01:55) And for everybody else, thank you for watching and listening to this episode of Whole Plus. We're going to change medicine however we need to get there, one patient, one conversation at a time. We'll see you next time. Thank you for spending this time with me here on Whole Plus. If this conversation helped you see your health in a new way, take a second to subscribe. (1:02:13) It's the best way to support the show and stay part of the community. And if you're ready to keep going, your next episode is right here on the screen. Go ahead and watch it. It might be exactly what you need