The Longevity Magic of Nitric Oxide with Dr. Nathan Bryan

So I realized in order to have a decent career I needed to go and further my education and I took a two to three year kind of not really a sabbatical , but kind of kind of figure out what I wanted to do in life .

And then in 1999 or maybe 2000 , I enrolled at LSU School of Medicine in a PhD program in molecular and cellular physiology and it was there that I got introduced to the science of nitric oxide . It was a new field .

A Nobel Prize had just been awarded for the discovery of nitric oxide in 1998 , and I was very fortunate to meet Lou Ignaro when I was a student there .

We organized a conference and had him come in and give a lecture on kind of the journey to the Nobel Prize and had a chance to have dinner with him that night and he was a naive student asking a lot of naive questions , and it turned out they weren't that naive , they just weren't many answers to the questions that I asked , and so for me it was a very

rich source of you know , a chance to make a difference and to make contributions to science .

I trained with a guy , a pharmacologist , that had been in the nitric oxide field for probably 20 years prior Martin Fielish and then from there , you know , my role and really the work on my PhD was really in analytical chemistry , because we had to develop sensitive and selective instrumentation or methods to produce or to measure nitric oxide at physiological levels ,

which is nanomolar or femtomolar concentrations , and so once we figured that out , then we really had tools that no one else had in the field . So , you know , as a student , I think , I published six first author papers .

I finished my PhD in a year and a half , Then , from there , went and did a cardiology fellowship or postdoctoral fellowship at Boston University School of Medicine , where I spent two years as a postdoc and again publishing 10 , 12 papers a year .

And then I got recruited by Fred Murad , one of the other gentlemen that shared the Nobel Prize , to join his team at the Institute of Molecular Medicine at University of Texas Health Science Center in Houston and from there , you know , I was afforded a lot of the resources and just really intellectual freedom to ask any question that I wanted in the field and we

made a lot of discoveries . I filed a number of patents and I got several dozen issued patents in the field now and it's really been a remarkable journey . But you know , it's really the being able to ask fundamental questions and then being able to design experiments to answer those questions is really one of the great aspects about being a basic scientist .

There are many different theories and all our speakers seem to have a slightly different , nuanced view of it , so maybe you could start off by just telling us the way you look at aging and longevity .

Because we can't . You know , we're exposed to so many toxicants in the environment and just daily activities that we have to replace and repair these old , dysfunctional cells . And so aging to me is just the inability to replace these aging and dysfunctional cells .

And so when we understand what that takes , then you can employ strategies to give the body what it needs to repair and replace dysfunctional cells .

And then it's not just extending the quantity of life or the number of chronological years , but the quality of life , because I think you and we would all agree that nobody wants to live to be 120 years old if we're not functional and we have to have somebody take care of us .

So nitrous oxide is the dental anesthetic that you get typically when you go to the dentist's office . It's called laughing gas and that's not nitric oxide . Nitric oxide is NO , and it's a gas but it's a vasodilator .

So I like to tell people nitrous oxide will put you to sleep and nitric oxide is what allows you to function and have a sense of alertness and wellness .

But when it's produced , it has many functions and its first function to be discovered was as a vasodilator , meaning that once it's produced in the lining of the blood vessel it causes the smooth muscles surrounding the vessels to relax and dilate , and that causes a normalization of blood pressure .

It regulates blood flow to every organ , tissue and cell in the body . It's a neurotransmitter in the central nervous system . It's produced by our neurons and , as I mentioned , it's a molecule made by our immune cells , macrophages , neutrophils .

And , as I mentioned , it's a molecule made by our immune cells , macrophages , neutrophils , monocytes , and it's critically important in killing invading pathogens , from viruses to bacteria .

And really , guys , you know , over the past two and a half years we've really learned a lot about nitric oxide in the immune response , because we realized early on that the people that were getting sick and dying from COVID were the people who couldn't make nitric oxide .

These were older patients with high blood pressure , diabetes , previous heart attack , african-americans , hispanics . So it makes sense because you know , without getting too deep in the weeds , when you're exposed to a virus or a pathogen which we're exposed to every day . We live in a microbial world and some people get sick and some people don't .

So how do you explain the difference between people who get sick and who don't ? And , for instance , I'm probably the best example . So when we're exposed to a pathogen let's take COVID , for example it's a respiratory virus that attaches to the epithelial cells , the ACE receptors .

So when our body recognizes that it mobilizes our immune response , we go to the site of attachment and those immune cells generate a lot of nitric oxide . It shuts down the virus from replicating and propagating throughout the body so you don't get sick . So in people who can't make nitric oxide or mobilize the immune response , there's no defense mechanism .

So the virus attaches , it replicates , propagates throughout the body and people get sick and unfortunately a lot of people died from that . So that's the importance of nitric oxide in a basic immune response and being able to mobilize a host of things .

diseases associated with that . And then one more is immune function and , as you mentioned , covid and everything else that the immune function does . It's amazing . So I guess I don't know if I even need to ask this . But why is nitric oxide so ? So how is it related to longevity ? And then we'll dive in a little bit there .

So if you infuse an agonist that would generally produce nitric oxide in the lining of the blood vessel and then look at the results of vasodilation , so there's about a 10 to 12% loss of what we call endothelial function per decade . You know this starts , you know late teens , early twenties , and a lot of this depend upon diet and lifestyle .

But in general , in population-based studies , if you look at the average , you know by the time we're 40 years old we only have about 50% of the nitric oxide we had when we were younger .

And so now the science is clear , with , I think , over 185,000 scientific publications on nitric oxide , the science is really clear that it's the loss of production of nitric oxide that's the earliest event in the onset progression of every major age-related chronic disease .

And now , if you take that back to the question you asked of longevity , I think there's three main thoughts about longevity and the mechanisms of living longer . So one is telomere shortening . So for your listeners , obviously the telomeres are the ends of the chromosome , that with each cell division they get shorter .

But you can control the shortening of the telomeres . So the science tells us that the shorter the telomeres , the shorter the lifespan . So if we can prevent telomere shortening or extend our telomeres and that's associated with longevity , so that's one .

Number two is loss of stem cell function , and so nitric oxide is the molecule that tells our own stem cells to mobilize and differentiate . Going back to this concept , I presented earlier that if the stem cells don't get the signal to go and repair and replace tissue , then they don't and we age rapidly . Then the third one is mitochondrial function .

Every age-related chronic disease is characterized by mitochondrial dysfunction . The mitochondria are the energy-producing organelles of the cell . Mitochondrial dysfunction so the mitochondria are the energy producing organelles of the cell and it's nitric oxide that controls mitochondrial ATP production .

It's nitric oxide that controls the number of mitochondria and how efficient they generate energy with oxygen .

So I you know I presented this probably 10 years ago that nitric oxide is the unified theory of age , because it controls the enzyme that prevents telomere shortening , it controls stem cell mobilization , differentiation and it controls mitochondrial biogenesis and mitochondrial function .

So if you can't make nitric oxide , your telomeres get shorter , you lose stem cell function and you develop mitochondrial dysfunction . And if you develop all three of those at the same time , then you're going to age rapidly and not have a very good quality of life .

longevity . There's such a great interest in developing clocks to measure aging with the DNA methylation clocks or the chemical clocks , and basically people are making clocks of anything that changes reliably with aging . I wondered , it seems like , does nitric oxide decrease in a reliable manner ?

So that would be a reliable as a as some sort of clock for aging as well ?

And now you can measure this through epigenetic changes in DNA methylation , as kind of a biological clock . You can look at vascular aging and look at vascular function measurements that are indirect measure of nitric oxide production . So when I talk about this age-related decline in nitric oxide production , you know that doesn't have to be the case .

You know , we now know that there are things you can do and strategies you can employ to prevent this age-related decline in nitric oxide production . That's what we've been focused on really for the past 20 or 25 years in my research lab and research program .

So we know , you know again , I'm the best example , I think , because I'm constantly measuring me and kind of what I do and how it affects , you know , our health and longevity and our really functional output . So I was , I just turned 49 on Saturday , but I have a , you know , a biological age of a 32-year-old when we look at vascular measurements .

So just because your chronological age doesn't have to match your biological age , you know , to the contrary , I've seen 20- , 25-year-old kids who have a biological age of a 60-year-old . And to the contrary . You know , if they're 60 , 70 year old , people have a biological age of 40 or 50 year old .

So you know there are things you can do that will move the needle and change this biological clock , depending upon what you're using as your clock and what's your endpoint in biological measure chronological age , but your biological age is close to 30 .

Or you can look at this non-occlusive platmosography that looks at vascular structure and function . So there are algorithms , there's FDA cleared medical devices out there that will give you your biological age based on the structure and function of your blood vessels and the ability of those blood vessels to produce microcoxine . That's what I've used .

I haven't used any of these other DNA methylation clocks , as you guys probably do . You get pitched all the time on testing these and trying to incorporate them into .

Testing these and trying to , you know , incorporate them into , but until they're really validated that's for prognostic or diagnostic utility , then you know I think there's limit there's limitations in what they need .

So it's this feed-forward mechanism that , if you lose the ability to produce nitric oxide , it causes decreased blood flow to certain regions of the brain , develop neurological dysfunction , mild cognitive disorders if not correct , advanced dementia and Alzheimer's .

In stress , cortisol , the stress response , actually shuts down nitric oxide , not only decreases its activity and functional activity , but also its expression . So we have to do a better job of managing stress , because that , just you know , mounts on and perpetuates the symptoms of loss of nitric oxide production .

Obesity and even some pharmacological drugs , you know , we now know , that antacids , specifically proton pump inhibitors , lead to an increase in a molecule called asymmetric dimethylalarginine or ADMA , and that's been shown , you know , to lead to a 30 to 40% higher incidence of heart attack and stroke in people who have been on PPIs for three to five years .

That was work from a good friend , john Cook , out of Houston , methodist , I think , back in 2015 . So if you , if you shut down stomach acid production , you know you shut down nitric oxide production and a lot of bad things start to happen .

You lose acid base regulation , you can't break down proteins into amino acids , so you get , you know , foodborne allergens and antibodies directed against certain peptide fragments . So we know that antacids are extremely bad and in fact , as you know , they were never approved for chronic use . They were approved for acute use , for chronic gastroesophageal reflux disease .

But yet people are taking these every day for many , many years , sometimes decades , and the consequences are very clear . So there are a number of , and really everything we do it appears to disrupt nitric oxide production .

The American lifestyle , the American diet , you know , sedentary lifestyle , not sweating the foods we eat everything contributes to loss of nitric oxide production . So it's really very tough and it's it's hard work staying healthy and preventing this loss of nitric oxide production .

But I think , you know , I'm not sure if there's a clear association between really a good prognostic value of coronary calcium . Obviously a high coronary calcium is not good . But what we really focus on in terms of vascular biology is , you know , the pliability of the plaque or the stability of the plaque .

Because you know you can have as little as a 10% occlusion in the coronary arteries and have an unstable plaque and have an acute myocardial infarction , and then there are people that have , you know , greater than 90% stenosis , that have lived with that for many , many years and never have a cardiac event .

So for me it's not about the degree of of uh , of the stenosis or the occlusion in the blood vessels , it's about the stability of the plaque . And we know that if you can stabilize the plaque then people are more resistant to acute MI . And nitric oxide has been clearly shown to stabilize plaque .

It prevents the inflammation , oxidative stress and immune dysfunction , prevents platelets from sticking to the clot or to the plaque , so it's extremely cardio protective . But to answer your question , there's no randomized placebo-controlled clinical trials on nitric oxide affecting coronary calcium scores that I'm aware of .

Are there specific signs that would make us think nitric oxide , or is it more generalized things ?

So unlike your cholesterol or vitamin D , and you can't draw blood and say , oh , your numbers are bad . So we really have to rely on symptoms and , as you may imagine , when we look at the effects of nitric oxide on human physiology , the symptoms are pretty broad .

So if you have an unsafe elevation in blood pressure , I mean you're not making nitric oxide to help dilate the blood vessels and normalize blood pressure . And two out of three Americans have an unsafe elevation in blood pressure . So that's one . The first sign and symptom is really sexual dysfunction .

That occurs in both men and women , because if you can't regulate blood flow through the production of nitric oxide to dilate the blood vessels of the sex organs , then you cannot get an erection , whether it's in men or women .

So sexual dysfunction is what we call the canary in the coal mine and it's really a sign and symptom of an underlying cardiovascular condition and nitric oxide deficiency , diabetes , you know , insulin signaling requires nitric oxide and if you can't generate nitric oxide in the cells then insulin doesn't get the signal , you don't get glucose uptake .

So insulin resistant diabetes is a sign of nitric oxide deficiency . Mild cognitive disorders if you can't remember where you left your keys . So when we recall memory we have to increase blood flow to the prefrontal cortex and you do that through the production of nitric oxide to perfuse that region to recall memory .

So if you can't make nitric oxide , then develop mild cognitive disorders which develop into vascular dementia and , if not corrected , alzheimer's and then just loss of exercise capacity . If you get winded going up a flight of steps or walking , you know , then that tells us that your body's not making nitric oxide .

If you get , you know , these vaso-occlusive crises or pain in the legs , then peripheral artery disease is a sign of nitric oxide deficiency . So really I think any major clinical symptom that we present with can be associated with nitric oxide .

So I just used some really old chemistry called the grease reaction that we've used for many , many years in the research lab and applied that chemistry to the end of a test strip where you can apply your saliva to that test strip and if it turns bright pink , then that tells us that your body's able to recycle the nitric oxide production pathway through this

enterosalivary circuit . So I think there I tell people they're a good tool to have in your toolbox , but it shouldn't be the only tool you're using , because there's no such thing as a false negative on this test . If you're negative , you're negative . Now then we have to kind of interrogate and figure out why are you nitric oxide deficient ?

But there are some false positives . So in the best example you know , I had a 50 year old , overweight , hypertensive diabetic patient with erectile dysfunction use that test strip and he turned it bright pink . Well , obviously this guy is not replete in nitric oxide .

He obviously has all the clinical symptoms of nitric oxide deficiency but he likes that test strip of bright pink and so with further interrogation we found that he had an active oral infection . So the immune response in the oral cavity generates a lot of nitric oxide that shows up on the test strip .

But systemically this guy is completely devoid of any nitric oxide that shows up on the test strip . But systemically this guy is completely devoid of any nitric oxide production . So those are those kind of caveats so to answer your question . They're useful as a tool but again you have to be aware of some false positives .

I've seen on your website , I think , or on your podcast , talking about certain mouthwashes to avoid . Is that just because of the test strip they'll interfere with , or is that systemically they'll interfere with nitric oxide production , and maybe you could explain what the mechanism is ?

So it's now realized that nitrate , found primarily in green leafy vegetables , can be reduced or metabolized by oral bacteria to nitrite and then to nitric oxide , and humans do not have this enzyme . Humans do not have a functional nitrate reductase enzyme , so we're 100% dependent upon the bacteria , primarily oral bacteria , that live in the crypts of the tongue .

These are faculty of anaerobic bacteria and we've been characterizing these now for more than 20 years . So what the science clearly tells us now is that if you disrupt this oral microbiome , you disrupt nitric oxide production from the diet .

So now what we found and I was on the doctor's show , I think last year , where we revealed that if you use mouthwash , your blood pressure goes up and we in a number of other groups published on this but you also lose the protective benefits of exercise .

So this told us that disrupting the oral microbiome is disrupting systemic nitric oxide production , and the mechanism still isn't clear . How is nitric oxide being produced in the oral cavity , affecting the second-to-second blood pressure regulation in the lining of the blood vessel . So we're still trying to figure that out mechanistically .

Blood system so we're still trying to figure that out mechanistically . We have a pretty good indication that it's probably just inorganic nitride or NO that's bound to glutathione , that's vasoactive that's produced through this pathway .

So the whole point is , if you disrupt the oral microbiome , you shut down nitric oxide production , your blood pressure goes up and you become nitric oxide deficient .

And now that creates a very interesting new kind of clinical readout , because two out of three Americans use mouthwash every day , wake up in the morning , swish mouthwash and I don't think it's coincidental that it's two out of three Americans that have an unsafe elevation in blood pressure .

So we published on this I believe in 2019 , that if you eradicate the bacteria through daily mouthwash use in young , normal , intensive , healthy individuals , you can make them clinically hypertensive in seven days and then , fortunately , if you stop , within four days of stopping mouthwash , you restore the diversity of the oral microbiome and restore nitric oxide production

and you can see a normalization of blood pressure . Wow , of the oral microbiome and restore nitric oxide production and you can see a normalization of blood pressure and it's really any antiseptic mouthwash . So what we've used in these studies is chlorhexidine .

It's a prescription antiseptic that's used primarily for chronic halitosis and some serious periodontal disease of gingivitis . But you know we've also done it with things like scope and Listerine , alcohol-based mouthwash , and they all disrupt the oral microbiome and all disrupt nitric oxide production .

So I tell people , just like you have to get off antacids , you have to stop using mouthwash .

It's killing the good bacteria , it's killing the bad bacteria , disrupting the diversity of the oral microbiome . And I tell people , you know , the same reason you don't take an antibiotic every day for the rest of your life is because of the known consequences of disrupting the gut microbiome and getting systemic disease .

So it makes no sense to take an oral antiseptic to disrupt the oral microbiome every day for the rest of your life .

Fluoride is an antiseptic and that's the reason they add it to municipal water supply to kill any potentially infectious bacteria that may be found in the water supply . So , just like the fluoride in the water , the fluoride in the toothpaste acts as an antiseptic and it kills the oral microbiome .

So I tell people you have to get rid of fluoride in your toothpaste . Fluoride's's a neurotoxin . It kills your thyroid function . It competes with binding of the thyroid hormone with iodine . Most people are deficient iodine .

and our toothpaste too , and then this the symptoms we have to test for it are fairly common , that most of us have anyway . So it sounds like then , the best thing is to do things that will increase our nitric oxide levels , just assuming that they're low based on our age and everything else . So how do you regulate that ? When is enough and enough ?

And maybe first start talking about what things we can do maybe diets , supplements and even pharmacology drugs , medical prescription drugs .

common question . So people ask well , how do I restore nitric oxide production and get my levels up to where they need to be ? And I tell you , you have to do two things . It's very simple Stop doing the things that disrupted and start doing the things that have been clinically proven to promote it .

So we've talked about what to stop doing get rid of mouthwash , get rid of fluoride , get off antacids . And then so what's clinically proven to enhance nitric oxide production ? Well , modern physical exercise . You know , that's why exercise is medicine , because it stimulates nitric oxide production . It's probably one of the simplest things you do .

And Americans aren't as active anymore . The old saying in Cooper Clinic , who's become a good friend of mine , dr Cooper , he says people don't stop exercising because they get old . People get old because they stop exercising . And I think there's a very important lesson to be learned there . We have to move , we have to stimulate nitric oxide production .

You know , sunlight there's certain wavelengths of light , that frequency of energy stimulates nitric oxide production , releases nitric oxide that's bound to metals , releases nitric oxide that's bound to cysteine , thiols on proteins or even glutathione . So there's both kind of wavelengths in the UV range as well as the near and far infrared or full spectrum infrared .

And then the other is , you know , diet . Green leafy vegetables contain this molecule called inorganic nitrate that the body can then convert into nitric oxide .

And you know that's a challenge because we published a paper in 2015 trying to figure out how much servings of vegetables like broccoli or lettuce or kale or spinach would you need to eat in order to get enough nitrate to manage your blood pressure , and there's regional differences in the amount of nitrate that's found in vegetables , so it depends upon soil conditions

, this whole field of agronomy , so it's very difficult to determine if you're getting enough nitrate from the vegetables you're eating .

So you know what we've done and kind of trying to provide solutions to every step in the pathway that becomes disruptive is develop technology that does it for you , and that's the basis for many of my discoveries and technologies that we wanted to .

You know , in our drug discovery program with Dr Murad at the Institute of Molecular Medicine , the whole concept was , if your body can't make nitric oxide , then we have to do it for you , and then we now understand the enzymology and the biochemistry of the enzyme that we can restore the function of that enzyme and actually improve the body's own ability to make

nitric oxide . And you know that's , I guess , my claim to fame is I was the first person to develop a solid dose form of a nitric oxide gas .

So we create this , this lozenge , this orly disintegrating tablet that when you put in your mouth and it's designed to have a resident time of about five to six minutes , but during that five to six minutes we're liberating about 30 to 40 parts per million NO gas and in fact , that's the same amount they use clinically in the pediatric intensive care unit for

premature babies born with pulmonary hypertension , or even adults with pulmonary hypertension or during cardiopulmonary bypass surgery . So that's a clinically relevant dose of nitric oxide that's being produced in the oral cavity . It's vasoactive . We can see dilation of the carotid arteries within about 12 seconds of putting that lozenge in your mouth .

We've had a number of studies showing that it can normalize blood pressure , improve exercise performance . But also , four hours after this and we published on this I exercise performance . But also , you know , four hours after this and we published on this , I believe in 2011 or 2012 , we see about a 15% improvement in endothelial function .

So meaning that we've recoupled the nitric oxide synthase enzyme and now improved the body's endogenous production of nitric oxide . And now we've taken that technology and we're developing FDA approved drugs using that same concept . We've got a COVID drug in phase three clinical trials .

We've got a drug going into phase three clinical trials for ischemic heart disease , alleviating the symptoms of exertional angina , and then for this newer condition called ischemic non-obstructive coronary artery disease , which is a small vessel disease affecting women more so than men . They develop signs and symptoms of ischemic heart disease .

You take them to the cath lab and angiogram reveals that there's no obstruction in the large vessels but the small vessels branching off the big vessels are clamped down and they become ischemic . But it's non-obstructive . So our nitric oxide opens up those small blood vessels and really has enormous clinical benefit for ischemic , non-obstructive coronary disease .

And since it was all natural product chemistry , we really didn't need an IND or an investigative new drug application to do this . So we brought this technology to market many years ago and so it's available as an over-the-counter .

I've since developed a second generation of these lozenges , but really the whole concept of that is you take it once or twice a day and , as you know , as a physician it's very difficult , if not impossible , to describe a one-size-fits-all as kind of a regimen .

So if you're young , healthy and pretty much in good health , then we'd say one lozenge a day is sufficient . If you've got some challenges , then we recommend one lozenge twice a day . That's really been shown to provide .

You know , the pharmacokinetics and kind of the pharmacodynamics of this technology allows for one lozenge twice a day to give you 24-hour coverage and then we ?

They don't enhance nitric oxide production . What they do is they potentiate nitric oxide signal . So I tell people , nitric oxide turns the switch on and these PD-5 inhibitors keep this switch on for many hours and that's the reason people are warned against four-hour erections unsafe drop in blood pressure and all the side effects that come along with it .

Hour erections unsafe drop in blood pressure and all the side effects that come along with it . So nitric oxide binds to an enzyme . Without getting too deep into the science , it creates a second messenger called cyclic GMP and it's cyclic GMP that's responsible for the smooth muscle relaxation . So these PD-5 inhibitors prevent the breakdown of cyclic GMP .

So if your body can make a little bit of nitric oxide activates the second messenger , then you potentiate the vasodilation . That's the reason it works in erectile dysfunction . Don't respond . And the reason they don't respond to these medications is because there's not sufficient nitric oxide being produced in these patients to activate cyclic GMP .

So there's no substrate for these drugs to work on . But here's what we've learned really over the past 10 years and people who have taken these drugs , and I think so . The point is , if we can enhance nitric oxide production , we can decrease the dose of these drugs and make them safer , more effective .

So I really like the once daily five milligram Cialis , and the reason for that is is that studies have shown now that people who were taking five milligram daily Cialis during COVID had a lower incidence of infection and severity of the disease .

Now there's clear evidence that people who have been on these drugs for many , many years , decades , have a lower incidence of infection and severity of the disease . Now there's clear evidence that people who have been on these drugs for many , many years , decades , have a lower incidence of Alzheimer's and vascular dementia .

So there's something to be said about maintaining perfusion and circulation to every vascular bed . Whether it's the vascular bed in the sex organs , whether it's the vascular bed in the coronary arteries or the brain . You have to maintain that circulation to get oxygen nutrients to the individual cells . So those are good , but again , there's limitations to those .

But I think if you use them , you know judiciously and you know titrate down the dose , but really get to the root of the problem . People are , patients are prescribed PD-5 inhibitors because they're nitric oxide deficient . So I think my objective is to train physicians and even patients , say let's get to the root cause .

Your root cause isn't an overactive phosphodesterase enzyme , your root cause is a nitric oxide deficiency . Let's address that , then there's no need for PD-5 inhibition therapy . And I think there's a number of different mechanisms that can be exploited on that . Because in Western medicine there's never this discussion by most physicians of how do we wean you off drugs ?

Right , let's come back , and if this isn't working , I'm going to put you on more drugs . Well , going back to this concept , we all started with that . Many of these drugs interfere with the body , the heel itself . So the more drugs you're on , the less ability you have to repair and replace dysfunctional cells and tissues and your longevity is really compromised .

And you know , one would expect heart disease and everything else to be risky . And it's it's interesting that the the clinical indication for the FDA approval was for blood flow to one particular organ .

You know we can't forget that Pfizer started this drug program for patients was either in , I believe it was pulmonary hypertension trying to dilate the blood vessels of the pulmonary circulation to alleviate pulmonary hypertension , which is still a poorly managed disease , and one of the side effects and common responses from the participants were better erectile function .

So they abandoned the pulmonary hypertension and obviously exploited the market for erectile dysfunction . I think they've done very well .

But if you can't make nitric oxide , then not only do the resident stem cells not get the signal to mobilize , they don't differentiate . And so then you know when people getting a lot of stem cell injections , you know early on there were teratomas and a lot of adverse events from that .

So again , if you , if your body doesn't have what it needs to get the signal to repair and replace , then even giving stem cell , exogenous , stem cell therapy isn't going to fix the problem . And our whole process is we're trying to recapitulate physiology , restorative physiology , and that's the basis for our drug discovery .

We're not developing pharmacology , we're developing restorative physiology .

But I think on a broader level , you know , what I've learned in 20 years of science is that chronic disease , whether it's Alzheimer's , diabetes , autoimmune disease or cardiovascular disease , is caused by two things , and two things only the body's missing something that it needs or it's exposed to something that it doesn't .

There's really no room for drug therapy because you know , going back to you know early days , in the early 1940s . You know most chronic diseases are caused from a nutrient deficiency . We know that most Americans 95% of Americans are deficient in iodine , 75% of Americans are deficient in magnesium , and these are critical cofactors for enzymatic reactions .

Then the other is the body's exposed to something that doesn't need , whether it's mold , mycotoxins , environmental toxins , latent viral infections , something from the environment . So if we replete the missing nutrients and eliminate the toxins in the body , body heals itself . We're regenerative beings .

We just got to get out of the way and stop doing the things that disrupt .

I wonder , aside from the nitric oxide space , which is so exciting , what are the other areas , anything else in longevity that you're most interested in and most excited about ?

But that's like fitting a square peg in a round hole , right , because everybody has their favorite molecule but it may not be clinically relevant . So what I did and that was the beauty of working at the Texas Medical Center was we get to collaborate with a lot of really talented physicians .

So we take really complex clinical observations , bring them back to the lab , model them in the lab , then go back to the clinic . So really what works is bedside to bench , back to bedside . You have to model the disease , understand the etiology of the disease , and now you're not fitting a square peg into a round hole .

So now what I like to do is take physicians who have complex cases and then let's figure out how does nitric oxide play a role in the etiology of that disease and then start employing simple clinical strategies . That gives physicians new tools to use in their armament .

But so I , you know , obviously I pay attention to the literature and other things that are relevant . You know , I wasn't at all interested in immunology until obviously all of us were forced to become interested in immunology in 2019 or 2020 .

But now it's fascinating because now we have a clear understanding of nitric oxide drool and respiratory bowel infection , which otherwise wouldn't have probably been that emphasis for us understanding .

And then , obviously , we live in a world where people are searchable , so you can search me online .

And for those that have published several books , I've got a new book coming out this year called the Secret of Nitric Oxide , and so that will be really , really it's twofold . It's a personal journey , kind of my journey from discovery and basic science to really to create awareness around nitric oxide .

I've published several textbooks , but my latest book , called Functional Nitric Oxide Nutrition , is an easy lay read I'll give this as a free gift to your listeners an e-copy of that but really provides it's a 90-minute read that will give you kind of an in-depth understanding of nitric oxide and really how you can employ some strategies in your own life to restore

your nitric oxide .