No.1 Nitric Oxide Expert: Why You’re Always Tired and It’s Not Your Fault

0:00 i'm absolutely convinced this will eradicate and cure Alzheimer's really the data don't lie and I'm a data guy and that the future of medicine and healthcare around the globe is going to be dependent upon this dr nathan Bryan is the biochemist whose cuttingedge research suggests how one crucial molecule can impact our health brain function and longevity that molecule is nitric oxide nitric oxide is a ziggling molecule in the human body which regulates things like blood flow and oxygen delivery and the loss of nitric oxide production is the earliest event in the onset progression of age- related chronic disease so things like erectile dysfunction diabetes Alzheimer's high blood pressure which is the number one driver of cardiovascular disease which is the number one killer of men and women worldwide and 50% of the patients that are treated with prescription medication don't respond with better blood pressure because they aren't targeted toward nitric oxide but most people have never heard

0:47 of this they don't know that if you can't walk up a flight of steps or exercise moderately for 15 20 minutes then you're nitric oxide deficient they don't know that most toothpaste and mouthwash is killing the oral microbiome that's partly responsible for production of nitric oxide but no one is interested in curing human disease because medicine is a business and the epiphany for me came because my dad had a car accident and he developed these non-healing wounds and I saw the failure of the standard of care to treat dad's wounds and so I just thought that there had to be a better way and simply by giving nitric oxide I've healed this wound within 6 months that's crazy so how do I improve my nitric oxide levels it's what you shouldn't be doing and we'll cover those step by step number one you have to avoid this has always blown my mind a little bit 53% of you that listen to the show regularly haven't yet subscribed to the show so could I ask you for

1:36 a favor before we start if you like the show and you like what we do here and you want to support us the free simple way that you can do just that is by hitting the subscribe button and my commitment to you is if you do that then I'll do everything in my power me and my team to make sure that this show is better for you every single week we'll listen to your feedback we'll find the guests that you want me to speak to and we'll continue to do what we do thank you so much dr nathan Brian you have committed much of your life to writing about and educating people on a subject that I know absolutely nothing about but from doing the research for today I'm pretty shocked that I don't know more about this subject so for those people who have just clicked to listen to this conversation can you tell them the mission you're on and why it's so important yeah

2:23 well thanks so much for having this conversation with me i think that illustrates the problem right someone as informed as you don't know anything or never heard of nitric oxide so it's important for us to just make a distinction between um like nitric gas that people you know inhale and that used if you played like uh some of those racing car games you press a button and the car goes really fast if you That's nitrous nitrous nitrous these are two separate things no very Yeah very good point so this is not nitrous oxide nitrous oxide is I mean a medicine is a dental anesthetic right it's a gas it's called laughing gas that's N2O that's the chemical formula what we're talking about is nitric oxide or NO one nitrogen one oxygen but yeah they sound very similar but they're completely different this molecule is is foundational for human health and longevity

3:12 so nitric oxide is a gas it's a naturally produced molecule it's a signaling molecule in the human body and so it's it regulates things like blood flow and oxygen delivery and it mobilizes our own stem cells to help us recover and repair and replace dysfunctional cells that uh improves energy production inside the cell and it regulates blood flow you know when we begin to exercise if we want to recall memory that's dependent upon adequate blood flow to the organs if we're you know it's intimately involved in sexual activity and dilation of the sex organs for sexual function so what we're finding is that the older we get the less nitric oxide we naturally produced and now today that's recognized as the earliest event in the onset and progression of age- related chronic disease so my mission is to inform and educate the global population

4:00 on how important number one what nitric oxide is how it's produced in the human body what goes wrong in people that can't make it and then perhaps most importantly how do we prevent that age related decline in nitric oxide production so everybody can be empowered to take control of their own health and prevent age related disease and that's what the science tells us but as you illustrated most people have never heard of this i mean this graph which I'll put on the screen for anyone watching kind of illustrates what you're talking about and quite notably this decline seems to start when you're 30 years old which is how old I am right now so well you know that's if you look at population based studies at different age groups we see about a 10 to 12% decline in what we call endothelial function per decade so that means so nitric oxide is a gas it's produced in the

4:49 endothelium so the endothelium is the single layer of cells that line every blood vessel throughout the body so the function of these endothelial cells is to regulate vascular tone and to regulate you know solute exchange and extravisation or transport of molecules across that endothelial layer and so when your endothelial cells can no longer make nitric oxide gas they no longer dilate so the blood vessels become constricted you start to get inflammation you get stiff arteries plaque deposition and that's what starts cardiovascular disease or atlascerosis which So someone that's struggling with their nitric oxide levels at the moment what kind of symptoms would they experience well we know there's a hierarchy right so the first sign and symptom of nitric oxide deficiency

5:38 is usually erectile dysfunction and when you think about this when we're stimulated or we're about to have intimacy with our partner we have to dilate the blood vessels so in erections in both men and women are dependent upon dilation of the blood vessels to get engorgment to get increase in blood flow and that's what an erection is but if those blood vessels can't make nitric oxide the blood vessels don't dilate so there's no increase in blood flow there's no engorgment and that's by definition what we call in erectile dysfunction and it's the same in men and women right whether it's the penis or the clitoris or the labia you have to have an increase in blood flow and without nitric oxide there's no increase in blood flow so that's number one and we call that the canary in the coal mine because for years people thought it was a lifestyle disorder right well erectile

6:25 dysfunction yeah but now it's recognized that it's a symptom of loss of nitric oxide and really an accelerated form of cardiovascular disease so we have to focus on the vascular component of erectile dysfunction what other diseases are linked to nitric oxide deficiency so if if you don't correct the ED then what you start to see is an increase in blood pressure and when you think about this mechanistically so we have you know a finite volume of blood that's pumping throughout our body every day every second and if you can make nitric oxide the blood vessels are more dilated so now we're pumping that volume through you know more dilated blood vessels but if we lose the ability to produce nitric oxide now you don't get the dilation now you have smaller blood vessels you're pumping that same volume of blood through smaller pipes and simple physics

7:14 tells us that blood pressure goes up okay so you're going to have cardiovascular challenges well you're going to have high blood pressure or hypertension and at least in the US and I think these these statistics probably are worldwide but two out of three Americans have an unsafe elevation in blood pressure and 50% of the people that are given prescription medications to treat their blood pressure do not respond with better blood pressure it's because most of the drugs out there whether they're ACE inhibitors what's called angotensin receptor blockers calcium channel antagonists the main classes of drugs that treat high blood pressure aren't targeted toward restoration of nitric oxide so that's why we call that resistant hypertension they're resistant to traditional therapies and the reason they're resistant is because it's a nitric oxide

8:00 problem and those drugs aren't designed to affect nitric oxide production or improve it was there a an aha moment in your career where you became particularly interested in this subject because you could have committed your life to studying any facet of health or or science but for some reason you chose nitric oxide as the thing that you chose to focus on what was that eureka moment you know for me it was I was a student at LSU School of Medicine um this was the late 90s maybe early 2000s but a Nobel Prize had just been awarded for the discovery of nitric oxide there were three US scientists that were awarded the Nobel Prize in physiology and medicine in 1998 and I was very fortunate at the time i was a young student probably a first year student and Lou Ignaro who

8:45 had just won the Nobel Prize for the discovery of nitric oxide came and spoke and gave a lecture before the student body and I had a chance to have a conversation with him afterwards and I was fortunate to be invited to have dinner with him that night and he made a very poignant statement to me he goes "If we if the scientific community can figure out how to restore the production of nitric oxide it'll change the world and it'll change the landscape of medicine." because even then what is that 25 26 years ago that it was recognized that a loss of nitric oxide production is leading to the onset and development of many poorly managed age- related chronic diseases so I go that's a very profound statement from a guy who just won the Nobel Prize but that was the first kind of eureka moment for me that stimulated the interest but then my dad and I talk about it

9:32 in the book is a dad is 76 years old in 1984 he had a car accident it left him paralyzed from the midback down so the majority of my life even as a kid I was treating dad's wounds decubitous ulcers pressure ulcers on his feet on his butt and he developed these non-healing wounds he was diabetic he was parapolgic poor blood flow hypertension and he developed a non-healing wound and no wound care doc that I took him to could heal this wound so I started making a topical nitric oxide and I've healed this wound within a per four years of non-healing i healed it within 6 months simply by giving nitric oxide and getting blood flow to that wound killing the infection in the wound and this was in a 60something year old paraplegic diabetic sedentary old man what you went through as a young

10:21 man to me appears to be such an important sort of throughine with all the work that you do and chose to do there is this overarching question which is even like why did you go into medicine why did you want to help people where did that come from in you and I feel like there's clues in that to some degree based on what I I read about your family your early upbringing the divorce of your parents and then ultimately your dad getting in a car car accident and being paralyzed is that an accurate suspicion you know I certainly it directed kind of my my life because I witnessed the failure of the standard of care to treat dad with what I thought should be pretty simple i mean we have again the most advanced technology medical technology best medical schools in the world

11:08 and yet we can't treat a wound we can't address the hypertension we can't address the diabetes medically and so I just thought that there had to be a better way it's still with you now isn't it yeah but I you know I see um you know dad when think I'm having a bad day i just think look I'm not in a wheelchair i got my health so no matter how bad I think I got it it could always be worse so I just wake up every day with a grateful heart and you know some days are good some days are bad but I always realize it could always be better but it could be a hell of a lot worse so I don't complain and who are you what are all the reference points what's the experience you've had

11:57 in your career that have filled up your sort of buckets of knowledge that you bring forth today like what what have you studied where have you been i was in molecular and cellular physiology got a PhD in molecular and cellular physiology and that was I was recruited by Fred Murad one of the other guys who shared the Nobel Prize to join the faculty at the University of Texas Health Science Center in Houston which is the world's largest medical center but it's part of the University of Texas system so I was recruited as a professor of molecular medicine published probably well over a hundred peer-reviewed scientific publications i've edited several medical textbooks on the subject i taught in medical school and then I resigned from academia I guess several years ago uh during COVID to focus on the next phase of my career is taking this 25 years of science and

12:46 research and discovery and now bringing that to the four for safe and effective product technology drug therapies to eradicate a lot of these poorly managed chronic diseases that you know we're faced with today so let me get this straight i'll repeat back to you what I think I understand about nitric oxide and you tell me if it's accurate so this nitric oxide is a chemical that is in all the blood cells of my body and it allows my blood cells to basically expand open up so blood can flow through there so if I it dilates it dilates the smooth muscle so it's not affecting the cells per se but it's dilating the smooth muscle that surrounds the blood vessels that leads to relaxation and dilation fine so my blood cells would then expand your blood vessels

13:31 and more blood would go through there but if I'm deficient that mechanism doesn't work and my blood cells wouldn't expand ultimately expand through the relaxation of the muscles that's right and therefore I would have higher blood pressure which can lead to a series of downstream diseases and consequences and so when we look at the graph that I showed a second ago where we're seeing for anyone that can't see this graph because you're listening on audio we're seeing nitric oxide levels in young people up to the age of roughly around 20 are optimal and then from about 30 to 70 there's this tremendous sort of 80 90% drop when I look at that graph though my question becomes is that not just aging is that not just normal is that not just inevitable well yeah

14:18 there are a lot of things that occur with aging right we lose growth hormone with age we lose u you know many hormones uh nitric oxide is a is a hormone that we we first discovered nitric oxide as a hormone back in 2007 but to understand aging you have to understand what leads to aging so aging from my perspective is the inability to repair and replace dysfunctional cells right every day we wear ourselves out and we just got to and if we can repair and replace dysfunctional cells then we combat or at least prolong the aging process so what the science tells us in nitric oxide is this that loss of nitric oxide production is the earliest event in the onset progression of age- related chronic disease so as that graph implies it is part of the aging process but it

15:06 doesn't have to be right because today we know we can shift that curve to the left or to the right so we can accelerate it and you see this today with 18 20 year old kids that are have high blood pressure they have diabetes they have erectile dysfunction they have learning and and cognitive uh impairment and those are all symptoms of nitric oxide deficiency and to the contrary we if we see 50 60 70 year old patients that would fit on a 30 or 40 year old scale on that graph so this this doesn't have to be the case we know how to prevent this age- related decline in nitric oxide production you know I'm I'm the best example i'm 51 years old but I've got the vascular age of a 36 year old because I employ these principles to prevent this age- related decline in nitric

15:51 oxide production and when you say you've got the vascular age of a 36-y old how how does one measure that you look at the sort of vascular health of your You can So there's there's several objective measures of of biological age obviously we can affect our chronological age right but we can certainly affect our biological age so what you can do there's databases now of what we call croted inima media thickness so they take an ultrasound and look at your corroted arteries and they can look at what's called smooth muscle hyperlasia or the thickness of the inima and compare it to a database of age matched kind of really it's you're comparing against your colleagues so that's one way another way is looking at what's called flow mediated dilitation or endothelial function and again through database of hundreds of thousands or millions of

16:38 patients you can figure out where you fall on that spectrum on endothelial function and then there's um you know other mark markers looking at histone modification of the DNA methylation profiles there's a company or technology called glyen age that looks at certain markers uh that can then define a biological age for each individual so by age 40 we have lost about 50% of our ability to produce nitric oxide in our blood vessels and we lose 10 to 12% of nitric oxide production per decade this is all according to your book and by age 70 to 80 nitric oxide levels in blood vessels can be 75% lower than in young adults a Japanese study found a 75% reduction in nitric

17:25 oxide production in people aged 70 to 80 compared to 20 year olds interesting so in terms of chronic disease that is downstream from me losing nitric oxide level can you give me a bit of a menu of chronic disease that is associated with this nitric oxide deficiency yep we've touched on them so erectile dysfunction um 50% of the men over the age of 40 self-report erectile dysfunction that's in the US so think about that 50% self-report i think the numbers are higher because most 40 year olds that I know are never going to admit that they have erectile dysfunction so I think the numbers are even worse so that's one high blood pressure again 50% of the patients that

18:13 are treated with prescription medication don't respond with better blood pressure that's a huge problem because high blood pressure is the number one driver of cardiovascular disease which is the number one killer of men and women worldwide number three metabolic disease and diabetes we published in 2011 that nitric oxide production is necessary for insulin signaling if the cell can't make nitric oxide you develop insulin resistance so diabetes a global pandemic nine out of 10 Americans are metabolically unfit the other thing is exercise intolerance if you if you try to start an exercise regimen and you can't walk up a flight of steps or exercise moderately for 15 20 30 minutes then you're nitric oxide deficient and then the other one is uh obviously Alzheimer's because Alzheimer's is a vascular disease it's reduced blood flow to the uh to the brain we call

19:01 focal eskemia there's insulin resistance you know Alzheimer's has been called diabetes type three so you can't get it glucose into the cell that's the primary energy source or substrate of the brain oxidative stress and immune dysfunction and then you get um misfolded proteins and that shows up as the tangles and the amaloid plaque that we see in Alzheimer's patients so if we can restore and nitric oxide corrects every single thing we know about Alzheimer's it improves blood flow to the brain it improves glucose uptake so it overcomes the metabolic aspect of Alzheimer's it reduces inflammation in fact a number of my patents are on a method of reducing inflammation it inhibits the oxidative stress we see in in Alzheimer's and neurological disease and it prevents the immune dysfunction and when you do that when you restore blood flow and you get nutrients and oxygen in and

19:49 you take out the metabolic waste products there's no misfolding of protein so you don't get the amaloid plaque you don't get the tangles so this simple molecule nitric oxide gas I'm absolutely convinced will eradicate and cure Alzheimer's really because it it addresses every physiological root cause of Alzheimer's if you can get it administered therapeutically to patients early enough or no I think that's a very key because the success or failure of any clinical trial any drug in any clinical trial is dependent upon the design of the clinical trial and what patients at what stage of disease that you enroll these patients so what are the inclusion criteria and what are the exclusion criteria and there's a stage in every disease whether it's heart disease kidney

20:37 disease Alzheimer's where you've reached a point of no return there's really no medical therapy that's going to reverse that disease because it's progressed to a state that's irreversible so I think what we try to do is take take patients early in the process what we call vascular dementia mild cognitive impairment early Alzheimer's because what I want to be able to demonstrate is two things number one can we stop the progression of disease once it's started can we stop the progression and then number two is we want to enroll patients far enough along to where we can show regression so can you move can you move the needle back and so That's a very kind of a specific and finite patient population when you design a clinical study number one at the at the

21:24 absolute worst we want to stop progression at the absolute best we want to show that we can regress disease and that's the goal of therapy is that you understand the mechanism of disease to the extent that you can treat it you can prevent it you can reverse it and you can cure it is there something you believe that the traditional world of medicine and maybe the traditional media don't believe yeah I believe in the truth and I come from a very objective scientific background so everything that we do is based on objective uh data i say this because I was listening to your interview before and there were several moments in the interview where you'd reference that you'd say things like they don't they don't want you to know this or they don't they won't tell you this no absolutely

22:11 because you know the we talk about epiphies and eureka moments in science but for me one of the kind of complete change in paradigm in the way that I think was changed in when I was in academia and teaching in medical school and doing research in in an academic institution and you start to think what we in the scientific community we un we've cured every disease every disease known to man we've cured it in rats and mice so then the question is why isn't this translated into patient care why can't we do this in humans number one in in animal experiments we control their environment we control their food we control their life cycle we control everything about them you can't do that in everybody has a different diet everybody has different drug therapy that they're

22:58 on or hygienic practices but then what I realized was because when I was in academia we wanted to create this consortium a center of excellence for diseases because my thought process was you know western medicine is siloed right if you have a heart problem you go to a cardiologist you've got a GI problem you go to gastronurologist if you got a neurological problem you go to a neurologist or psychiatrist but none of these disciplines talk to one another so if you go to that neurologist is going to treat that condition much different than the cardiologist would much different than the GI doc would but what if we're looking at the exact same root cause and so my philosophy well let's create a center of excellence and let's bring everybody in the room let's bring the GI docs the

23:46 the neurologists the cardiologists the geneticists the pulmonary docs the kidney docs the renal docs and let's let's understand this kind of wheel and cog because everything occurs at the mitochondria subcellular level and energy production and then basically everything can can manifest from that but what I quickly realized when you when you go to for instance MD Anderson and trying to treat cancer no one is interested in curing cancer no one is interested in curing human disease because the epiphany for me came because medicine is a business it's a for-profit business in fact it's the largest business and economic model in the world trillion dollar annualized market and

24:32 most of these drug companies who influence and pay and support scientific journals JAMAMA New England Journal of Medicine the major publications the major journals and they're influencing regulation and policy and FDA and so when you figure out that there's undue influence by these for-profit companies because the number one rule of business as you know as an entrepreneur and a business guy is acquire a customer and keep that customer as long as you can call it lifetime value of that customer and that's what medicine is they get you they you acquire you as a customer they put you on a drug that drug has side effects they have to put you on another drug to mitigate the side effects of that drug now you got side effects from that polyarm pharmacy they have to put you on another drug to mitigate those side effects and now you look up and people who are 50 to 60 years old and

25:24 older are on 10 12 18 different medications that's the best financial model in the world so it's a great financial model but it's at the expense of our health and the health of everybody living on in the world and in the US you know we have the sickest population in the world now for the first time in the history of western medicine have discussions between physician and patient how do we wean you off this drug that conversation has never had before because it's always if this doesn't work come back and I'll prescribe you more drugs let's do the opposite you come back and let's understand the root of cause of disease let's say okay well if we are addressing this you don't need this medication and if you don't need this medication you don't need this medication and now for the first time you start weaning patients off of drugs and what happens you're now impeding

26:11 upon the market share of these multi-billion dollar drug companies who make their living buying influence regulating policy influencing policy and the FDA is a stepping stone to a board seat of big pharma every former FDA official in the US for the past 20 or 30 years goes on to become multi-million dollar salaried employee from big pharma it has to stop despite spending nearly 20% of the United States GDP on healthcare the US ranks last overall on health outcomes among high income countries including having the highest infant mortality rates and lowest life expectancy it's like unbelievable no I mean that's that's depressing i mean but those are the facts and

27:01 the you have to understand those those are indisputable data right and so when people hear that they go they this but when you look at kind of the system and I don't blame doctors because doctors are get into this field you know I was on the admissions committee to UT medical school for a number of years so we interviewed a lot of these young kids figure out what their motivation was will they have a successful career in medicine and almost everyone I mean there's always the exception but everyone gets into medicine because they want to make make a difference they're driven by curiosity and most of them want to leave a lasting legacy and help people that's what drives uh entry into healthcare but when you look at the system in which they're trained in it prevents them it basically handcuffs them because when you figure out the pay the economic model of

27:50 medicine once you make a diagnosis now you've got a diagnosible disease to which you have a finite number of responses right if you make this diagnosis that's called an ICD10 code which is reimburseable and that's how you get paid so once you make a diagnosis you only have a finite list of things you can do you can't ask that question and go well what's really causing this and spend you know 90 minutes with that patient because most physicians have to see 60 70 80 patients a day to pay the bills to cover their overhead so it's a factory you come in you look at you've got a a transcriber you make a diagnosis okay I can I'm going to prescribe this medication come back in two weeks or six months and we'll see where you are and then it's just it's a term it's a meal

28:36 but as you me the data don't lie right sickest population highest infant mortality in the most industrialized nation in the world and according to the data Americans are spending about 13 years of their life living with disease and that is significantly higher than many other highincome western countries so although life expectancy you know might be 70 80 years old you're going to spend almost 15 years of that time living with disease so your health span is um really probably the more important thing to be focusing on not your lifespan and so when we talk about nitric oxide I've heard you describe it as the molecule of longevity for sure why why' you say that why do you say that well again longevity is this emerging field that's driven by how do we live longer how

29:23 do we increase our health span and longevity right because I think we can all agree that nobody wants to live to be 100 years old if we spend the last 25 of that years incapacitated in a diaper unable to get out of bed right that's not living so when I look at longevity I look at kind of what are the hallmarks of longevity what defines longevity right how do we live longer healthier life free of disease and really there's three objective measures there is a stem cells you know this whole field of regenerative medicine is based on mobilizing our own stem cells or deploying u stem cells throughout the body to repair and replace dysfunctional cells so these stem cells are cells that can basically act as like band-aids repairs for any part of our body well we call them pur potent stem cells so mean that and some of these are bone marrow derived some of these are

30:11 what we call stromal vascular fraction that you get from the atapost tissue or the fat pur potent would mean pur potent means they can that stem cell can go and become a neuron that stem cell can go to the heart and become a functional meioy it can go and become a macrofase or an immune cell white blood cell so pur potent means it can become many things whatever it needs to be in some cases the amount of stem cells present in our bone marrow get smaller with age the number of cells decrease with age but fortunately or unfortunately the older we get the more fat we deposit and so we have a number of stem cells in our fat so we increase the number of stem cells in our fat so the problem with aging and longevity is when we lose the ability to mobilize our own stem cells

30:58 we can't we can't repair and replace dysfunctional cells so we have these what we call zombie cells or scinsesscent cells they're there but they can't do their job they're dysfunctional and that's what leads to age number two it's telomeirs and telomeirs are the ends of the chromosomes of our DNA and so the they're the very end so it's like the um the the tips of the sho strings right that prevent the sho string from fraying and those are like the telomeir so as long as you have a functional telomeir and it prevents it from getting shorter then shorter telomeir shorter lifespan longer telomeres longer lifespan so when telomeirs get shorter it decreases our lifespan and longevity and then the third one is mitochondrial function every age- related chronic

31:44 disease you have a lower number of mitochondria per cell and the mitochondria that are present aren't functional so you get a what's called an uncoupling of the electron transport chain inside the inner mitochondrial membrane and you can no longer effectively produce cellular energy or ATP so nitric oxide is the foundational longevity longevity molecule because nitric oxide is the signal in the body that tells our stem cells to mobilize and differentiate without nitric oxide you have less number of circulating stem cells nitric oxide activates the enzyme toase which prevents telomeir shortening without nitric oxide you don't get activation of tomeorase telomeir shorten and then nitric oxide is the signal in the cell that tells the cell I need more mitochondria

32:32 and I need these mitochondria to be more efficient generate more cellular energy with less oxygen so when you when you restore nitric oxide you address all three aspects of longevity and there's no other molecule on the body that does that you know Brian Johnson don't you yes what do you think of Brian Johnson you know I would never replicate or try to um do what he does i don't think it's the proper approach you know and I I don't I don't mean to criticize people because this whole field of biohacking you know you get people who have no science background no medical background no biochemical background and yet they're out there influencing millions of people that follow them and many times they're giving really bad advice not intentionally it's because of ignorance they

33:21 just don't know they don't know the science they don't know the medicine behind it so before you go and follow any influencer or biohacker number one look at their credentials and if they don't have any science background if they're you know formal technologist or you know come from anything besides science and medicine you really need to do a little bit of deep dive and make sure that what they're giving you is scientifically valid or recommending he seems to be a fan of um the role of nitric oxide as it relates to longevity though he seems to have said positive things about um nitric oxide and its impact on improving your cardiovascular health yeah i think as we advance the science and we we do more to communicate the complex science into you know layman's terms where the the non-scientists non-medical professionals can understand it

34:07 and appreciate it i think more people are going to pick up to that but there's also some well-known biohackers with influences of you know millions of people that still say that nitric oxide is a toxin that inhibits mitochondrial respiration and it should be avoided is there such thing as having too much nitric oxide though because if people hear this conversation today and they rush out and they I don't know overdo their nitric oxide by doing a bunch of uh therapies yeah is that a risk absolutely you know we know water is essential right but we can drink too much water and kill ourselves you see it on the news you know a couple times a year called hypotonic lis so yeah dose dictates poison and so what we have to do is make sure maintain the integrity of the field to make

34:52 sure that if there are nitric oxide products out there that number one you don't overdo it and and lead to you know health issues or kill a consumer kill a patient that could kill the entire field but we also understand that there's only two signs of toxicity for nitric oxide so it's really pretty straightforward number one if you take too much nitric oxide you're going to get an unsafe drop in blood pressure because think about this if you if you take nitric oxide or you're enhancing nitric oxide production through whatever means it's going to lead to systemic vasoddilation now you've got that same volume of blood pumping through much larger pipes and you're going to have a drop in blood pressure and if you lose profusion pressure you're not going to be able to peruse the brain because you got to pump against gravity and you're going to get lightheaded and

35:38 you'll pass out and if that's prolonged it leads to es schemic end organ damage and organ failure and it can be deadly so that's number one and then number two is a condition called met hemoglobinia and that's a big word meaning that your it oxidizes the iron of hemoglobin and reduces your oxygen carrying capacity so you'll become cyanotic you'll get blue around the lips your extremities will turn will turn um you know white from lack of profusion or lack of oxygen but you never see that I mean you really never see clinical met hemoglobinia fortunately your your blood pressure will drop to an unsafe level long before you get any accumulation of met hemoglobinia so on this point of longevity then one of the points you mentioned there was telmir length and I've heard about telmir length because I've heard about studies they've done in rats and

36:24 I think other rodents around telmir length so it was discovered that indiv individuals with shorter telomeres had a death rate nearly twice of those with longer telomeres and you're telling me that there has been research done that shows how nitric oxide can increase telmir length absolutely so we we understand at the DNA level at the nuclear level that nitric oxide is is what's called a collocicalizes with estrogen recep receptor to allow for the turning the the cell to turn on transcription and translation of the tomeorase enzyme so it's not only affecting the genetic transcription of that protein but it's also regulating the function of the enzyme

37:10 so without nitric oxide you have less telomeir tomeorase enzyme and that tomeorase enzyme isn't functional okay so nitric oxide has an impact on the tomease tomeorase enzyme that's right tomeres enzyme so what happens with each cellular division those telomeirs can get shorter right but as long as that tomeorase enzyme is active it prevents the shortening of the very ends of the chromosome okay and just for people that don't understand the um with every replication as we age we're continually replicating ourselves to restore and repair them but in that replication process harm is occurred sometimes yeah and different cell types have different replication rates right so the the epithelium of the gut is highly regenerative right it's it's a replicatable uh you replacing these

37:57 cells all the time because it's the outside environment that you're having to continue to replace those cells neurons to the exact opposite aren't regenerative by nature so we don't typically make I mean we can it was once thought that you can't regenerate neurons but today we know we can but yeah so it affects different organ systems differently but the data are clear shorter telomeres shorter lifespan the other thing that um I wanted to talk to you about before we really get into the heart of how do I improve my nitric oxide levels keep them at a healthy range while I age is nitric oxide's relationship with the oral microbiome i had a conversation on this podcast not too long ago about the oral microbiome again another subject I hadn't thought much about but is there a relationship there no doubt i mean this is this is probably 20 year old science

38:43 um where we find that you know probably 20 years ago the microbiome project was complete and what that means is that the bacteria that live in and on our body were completely mapped out and these communities were identified in the gut started in the gut the gastrointestinal tract and then you know you can you can culture the the this the skin flora there's bacteria that live on our skin there are bacteria that live in our colon there are bacteria in women that that that reside in the in the vagina and so all of these different ecologies of bacteria that live in and on the body are there to do things to help the human host right we call this symbiosis we're providing benefit to the bacteria and the bacteria providing benefit to the human host and so if you use antibiotics

39:33 or antiseptics to kill the bacteria that live in and on our body you get human disease i mean that's clear and the the best example is that there's no physician in the world that would recommend you or I take an antibiotic every day for the rest of our lives right do you agree with that and why is that because the antibiotics are killing the good bacteria they kill the infectious pathogen bacteria but they also destroy the entire microbiome and when you disrupt the microbiome you get systemic disease you get vascular disease you get Alzheimer's you get uh leaky gut syndrome you get autoimmune disease you get high blood pressure you get yeast infections uh you get overgrowth of candida you get parasites so the bacteria are really the police of the human

40:22 kind of surveillance right so the n we have 10 times more bacteria cells that make up the human than we have human cells so we're 10 times more bacteria than we are human and so if you destroy that microbiome then it leads to systemic disease we live in a culture where we're constantly trying to kill bacteria right like especially post pandemic we're using all kinds of hand washes and antiseptics and obviously the the big I guess chemicals that we all typically use are things like mouthwashes with uh which are again trying to just clean out all the bacteria from our mouths what how would you caution someone on using these things and even the like the antibacterial Yeah it's bad news really we give it to our children because we want our kids to

41:08 be clean and not to have kids need to be dirty you find and again you look at epidemological data peop kids who grow up in the in a rural area they're out in the environment they're rolling in dirt they're they're got dirt on them and they have um you know they're inoculated with a lot of bacterium those kids are the healthiest people and and you look later in life they have lower incidence of cardiovascular disease diabetes they have better immune dysfunction less autoimmune disease so there's this whole hy hygienic principle or hygienic hypothesis of disease and I don't think it's a hypothesis anymore i think it's proven out so for me I go back and I go "What why are we doing this why are we using fluoride rinses in dental offices why is there fluoride in our toothpaste why is there fluoride in the municipal water of 72% of municipalities in

41:57 the US when fluoride is a known antiseptic it's a chemical toxicant it's a a thyroid toxic it kills your thyroid and it's a neurological toxin." And so when you go back and look at the history of dentistry over a hundred years ago it was first identified that oral bacteria can be found in the plaque that killed someone from an acute heart attack right people who died from sudden cardiac death they'll take the thrombus or the embleis that oluded that coronary artery and they basically biops it and they find oral bacteria in that plaque that caused the heart attack or stroke so that told us there's an oral systemic link there's bacterial transllocation of the pathogens that's why bleeding gums are a problem because you've got bacteria in the mouth if you

42:46 got bleeding gums there's open blood vessels for those bacteria to get into our blood supply now they become systemic cause inflammation plaque rupture and heart attack and stroke so 100 years ago with reason with good reason they go well let's treat with an aneseptic we have to kill all the bacteria in the mouth so if you have bleeding gums there's no translloca transllocation of that in the systemic circulation and we can prevent heart attack or stroke that was a hundred years ago and we've learned a lot in those hundred years number one it wasn't recognized that we have a microbiome on our body in our body so now when I ask dentists all the time why do you use floor and they go well it's been used for hundred years and I go I don't care what the question is that's the worst answer you could provide just because we're doing it because that's the way

43:33 we've always done it right so now we have to understand how do we selectively kill the pathogens while maintaining a healthy microbiome and so this this field started probably in the I mean some of the first papers were published probably in the 90s showing that there were if you use mouthwash it destroyed the microbiome and we saw an increase in blood pressure these papers were published in the late 2000s we we published on this probably in like 2008 2009 we created what's called an association so people who had the healthiest and most diverse bacteria in their mouth had the best blood pressure people who had the least diverse oral microbiome and we we could not culture any of these nitric oxide producing bacteria appeared to have the highest

44:20 blood pressure so that's what we call association it's not causation but it's a nice association so in 2019 we published a paper showing okay let's now let's see if we do if we take normal intensive patients young healthy people with good nitric oxide good blood pressure and we just give them mouthwash twice a day for seven days to kill the entire oral microbiome and then we do tongue scrapings to see if we're killing the bacteria and we do blood pressure measurements and so we do that twice a day for seven days seven days we bring them back in we measure their blood pressure and then we stop for four days we say okay don't talk don't take mouthwash for four days then come back let's rememeasure your blood pressure and let's do tongue scrapings and figure

45:05 out what's happening to this these bacterial communities and what we found was that if you eradicate the bacteria within 7 days your blood pressure goes up so if you use mouthwash within seven days your blood pressure goes up i think it occurs earlier but what we we looked at seven days we only looked at day one at baseline seven days and then four days after stopping the mouthwash but in one 21-year-old kid his blood pressure went up 26 millimeters of mercury which is put that in context for me that's clinically hypertensive so for every 1 millimeter increase in blood pressure that increases your risk of cardiovascular disease by 1% so within 7 days we increased this kid's risk of cardiovascular disease by 26% simply by giving him mouthwash and explain to me

45:53 in layman's terms the mechanism there what's going on well we're still trying to understand mechanism again we're at the observational level that's really indisputable because these bacteria there's what we call nitrate reducing bacteria and humans do not have this enzyme so nitrate is what's found in green leafy vegetables right these these plants assimilate nitrogen in the soil in the form of nitrate we consume these vegetables the nitrate is taken up in the gut it's concentrated in our salivary glands and the bacteria perform this metabolism of nitrate into nitrite and nitric oxide and humans do not have the the functional enzyme to do this so we're 100% dependent upon the bacteria so then now because nitrate is inert in humans we we rely

46:41 on the bacteria to metabolize this molecule into a usable form where we can make nitric oxide so when you're killing the bacterium now the nitrate is just being recirculated but you're you're you're urinating because it's it's it's filtered across the kidneys you poop it out and you sweat it out so it's completely unchanged unless you have the right bacteria and what we're finding is that that oral production of nitride and nitric oxide being produced in the acid environment of the stomach is somehow regulating resistance arteries in dilation to normalize systemic blood pressure so if I don't have a healthy oral microbiome then you have an elevation in blood pressure and much of the things you you're talking to me about today in terms of dietary um changes won't have

47:32 any effect anyway because I need the bacteria to convert it into nitric oxide as it relates there are many benefits of of many nutrients in foods particular plants that confer some health benefits but when we focus specifically on the benefits of nitric oxide from your diet if you don't have the right oral bacteria you get zero nitric oxide benefits from your diet now you're going to get you know obviously hopefully vitamin A vitamin C vitamin D from foods fiber other phytonutrients but in terms of the blood pressure lowering effects of a for instance a plant-based diet if you don't have the right bacteria you get zero benefits of that have you seen a link between oral health and cancer yes absolutely what have you seen people that

48:19 have dental infections root canals cavitations from previous extraction sites have typically cancer it sets the stage for cancer cell growth and proliferation so and and I've you know I made a controversial statement on a on a previous podcast where I say number one I'm not an oncologist but people who have terminal metastatic disease who aren't ready to die who are sent home to die on hospice somehow find me and go can you help me with this cancer and so the first thing I always send them to is a dentist to see do you have any active oral infections that may have led to the development of the primary tumor in the first place but obviously it's it's metastatic meaning that it's now everywhere it's it's it's migrated outside that primary tumor but almost

49:05 always without fail they have an active oral infection and it may be a symptomatic infection to where they know it and they have a toothache or it may be an asymptomatic infection where they don't even know they got a dental infection what percentage of cancer patients that you see that you then refer to a dentist have an oral infection people with primary tumors solid tumors so we categorize these in bloodborne cancers something like lymphoma leukemia multiple myoma which is a bloodborne cancer and those that have a solid tumor a primary tumor that starts in the breast the colon the prostate the lungs or the liver without fail 100% of them have dental infections but cause and effect is not possible to establish here right because cause and effect no I don't think we're there yet i think probably as the science advances and people start to look at

49:52 this because you may imagine if you have cancer and you've been to the best cancer doctors in the world and you've done surgery you've done chemo you've done radiation you've gone through the standard of care and the cancer comes back it's terminal it's metastatic and you tell when I tell people well you need to go see a dentist i mean many people laugh and they go "Have you what what in the hell did you just say i've got cancer i don't have a dental problem." And I go "Well perhaps you do." Because again if you go back and always look at back what's what's held true throughout ages and if you look at ayurveetic medicine if you look at traditional Chinese medicine if you look at acupuncture you know if you go back and you look if you don't know what to look for you're never going to find it if you know what to look for it's out there

50:41 it's in the published literature but every tooth in the body is connected to an organ system right and so these are these are the meridians the acupuncture meridians you know the analogy is they're circuit breakers so if you if you trip a breaker in your home there's no electricity going through that circuit so your oven doesn't work your refrigerator doesn't work or your lights go out well the body is electric right and how do we diagnose death no electrical activity right either through an EKG or an EEG so the body is electric and we're we're batteries and so if we get if that red light comes on on our phone it says we have a low battery everybody panics and goes and plugs it in and charges right and the human body is the exact same we lose voltage over time and if you've got a trip breaker from an infected tooth there's no voltage there's no circuitry going to

51:32 that meridian that feeds individual organs so the the best example is if you've got a root canal and a 100% of root canal teeth are infected and when you think and people go well that's not true well think about what a root canal is you had a toothache at some point because of an infection so you go to the dentist and they pull the nerve root out of that tooth so you don't feel the pain anymore because there's no nerve root there and they pull the blood supply out of that tooth now you have no blood supply to that tooth and a tooth is a crystallin structure it's a living organ with no blood supply and no nerve root that's a dead tissue so if you were to go in and we'd disconnect your gallbladder for example and just cut the blood supply to it the nerve supply to it within seven or 10 days you'd be dead from sepsis nobody leaves dead tissue in the body and so then what

52:23 happens is when you leave the dentist what do they do they put you on an oral antibiotic but they must have forgotten they took out the blood supply to that infected site so an oral antibiotic isn't going to reach the sight of infection i mean to me when you think when you sit back and think about this and go who the hell does this and why do they do it well it's because what we've always done so then what happens is these anorobic bacteria they don't need oxygen they're sitting there in an anorobic low oxygen environment and they're just eating away at your jawline they're just like us do they they they metabolize they take stuff in they poop waste out those waste products uh accumulate it shuts down voltage and they eat away at your jawline so then you've got osteom necrosis osteomiitis and you don't even know it and an x-ray will not show it and most dentists

53:09 unfortunately still use x-rays instead of a higher resolution CT it's really interesting i was doing some research in preparation for this conversation around this subject of oral microbiome and cancer and the link there and one particular study that was done um published in the New York Post but done by a team of researchers found that this was done at New York University as well so it was published by the New York Post and done at New York University they analyzed saliva samples of over 160,000 participants over 15 years are you familiar with this study and they identified over a dozen bacteria species linked to a high risk of head and neck cancers with certain bacteria increasing the risk by 50% of getting a cancer which is pretty shocking um literally I feel like texting my assistant and asking us to book a oral hygieneist and to change my mouthwash no

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55:30 natural foot movement and rebuild my strength but I think it was planttoicitis that I had where suddenly my feet started hurting all the time and after that I decided to start strengthening my own foot by using the Vivo barefoots and research from Liverpool University has backed this up they've shown that wearing Vivo barefoot shoes for 6 months can increase foot strength by up to 60% visit vivarefoot.com/doac and use code DOAC20 for 20% off that's a vivobarefoot.com/dac use code DOAC20 a strong body starts with strong feet if I've just listened to everything you've just said there and I want to improve my oral microbiome what should I be doing well I think the most important thing we've learned is what you shouldn't be doing right so it's not what should we do it's what we shouldn't be doing number one we have to get

56:18 rid of fluoride you know just this past weekend I was speaking at a dental conference in Salt Lake City and there were there people there from the National Toxicology Program which in the US is the organization tasked with if there's any kind of risk of exposure of environmental toxicant they're charged with doing the toxicology studies to see if there's an increased risk what is the risk and is there a safe level that is without risk and what they report is that fluoride there's no benefit of fluoride and it's all risk it lowers IQ in kids by as much as seven points and it shuts down your thyroid function and it's a neurotoxin and as I mentioned before most toothpaste has fluoride in it and if you read the back of your toothpaste it will tell you at least in the US

57:07 I don't know about in other countries but it says if you swallow this call poison control because it's a poison they're putting poison in toothpaste and then if you also pay attention it says only put a P-siz amount of toothpaste on your toothbrush a P size but everybody that I know fills the entire bristle of the toothpaste with toothbrush with toothpaste so that's about 10 or 15 sometimes 20 P-size amounts of toothpaste and a P-siz amount of toothpaste contains about half a milligram of fluoride now if you're using 10 20 times more than that P size now you're exposed to 5 milligrams 10 milligrams of fluoride and you don't even have to swallow it this is a very small molecule a molecular weight of 19 so it's absorbed directly across the bugal mucosa the oral cavity

57:57 and it becomes systemic i'm not going to use it anymore no you shouldn't what should I use instead you have to use a non florinated toothpaste and what about things like tongue scrapers now tongue scrapers the data again that's time- tested that's an ancient practice and even in our study we found that people who do tongue scraping have a more diverse oral microbiome and they seem to have better oral health why is this my girlfriend's been banging on to me she's always bloody right my girlfriend's been banging on to me about tongue scraping for the last two years and I've kind of just ignored her i've just kind of Yeah babe sure and but when she's not in the bath bathroom I'm not using her tongue scraper because it just looks strange i for me based on what I knew about the oral microbiome and the microbiome generally I'm like should I be scraping off all my

58:43 bacteria well if you're going to plant a garden do you plant a garden on untilled soil listen I know nothing about gardening you're asking the wrong guy so maybe yes I grow my own food okay so you have to till the soil right you got to break up the soil so the seeds actually can be irrated and you just break up that um that bofilm yeah you take the back of the dorsal tongue i mean almost to the point of the gag reflex and you just pull that ideally copper tongue scraper forward and you're going to see this goop coming in there but it's it's like kind of like tilling the soil and it's it's increasing the diversity of the the dorsal part of the tongue the microbiome so my girlfriend was right in that regard yes but what we found was in that one kid we saw the greatest

59:29 increase in blood pressure if you tongue scrape and use antiseptic mouthwash that's the absolute

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