The Miracle Molecule: Everything You Need to Know About Nitric Oxide | Dr. Nathan Bryan

is it better to have say like a bolus of nitrates at three times you know during the day at three different meals or is it better to have them spread out more through the day basically how often is the ideal of taking in nitrates to have the best effect well the data the clinical data if we look at uh regulation of blood blood pressure and the impact on exercise performance or athletic performance we know that we need at least 300 to 500 milligrams as a bolus as a single serving right so take it in at

once you're not going to get the effect if you're taking 100 milligrams in a meal for breakfast 100 milligrams for lunch 100 Mill you need it as a bolus all at once but the beauty of this pathway is once you consume that it takes 90 minutes for this to become activated now for the next 6 8 10 hours we're slowly titrating that system and slowly generating nitric oxide over time so the best bang for your buck is going to be all you need is just one kind of bolus whether it's ideally at lunch or or

dinner or whenever throughout the day you know depending upon what you're going to be doing if you're about to run a race or do a you know a marathon or triathlete then you probably want to do that before at least 90 minutes before um so yeah I think and and what we're finding is there's really no added benefit to doing more right the body kind of self-regulates you give it what it needs it's going to take the nitric oxide generate it upon demand but giving more nitrate is not going to always generate more nitric oxide

to see better performance better regulation of blood flow or blood pressure important we got into that because you took it the other way I was talking more about like having little doses throughout the day to keep topped up but you're saying you got to make sure you're hitting that Bullis with enough in one serving to actually have the impact so if you were to do what I was talking about you wouldn't have the same impact on the body you got to have enough in one survey have the impact because it goes back to this 5%

reduction efficacy right 25% uptake in the gut 20% reduction by the oral bacteria so let's just say if you if if you're taking in 100 milligrams of nitrate you're going to generate 5 milligrams of nitrite and that's not going to be enough to really see any vasoactive activity dilate blood vessels normalize blood pressure induce mitochondrial biogenesis improve performance so we need to titrate it up enough to at least 300 M where we're getting enough of that to activate these endogenous Pathways okay while we're talking about the 300 migs it gets me thinking about somebody that

gets really ambitious and they try and aim for like 500 milligrams in a Bolis and we know a lot of we've talked about a lot of the benefits of no throughout the conversation one being that the vessels get dilated so what I'm getting at here can we have too much can we over dilate vessels can we overwhelm the body by having too much at once nitrate probably not I mean because when we looked at the night the Japanese diet you know sometimes they're getting 1,500 2,000 milligrams through certain dietary choices and certain foods they eat

and I think that's why this is an efficient such an inefficient mechanism right because if we converted all of that into nitride and nitric oxide then probably after a you know heavy meal of a vegetarian or plant-based meal everybody would get an unsafe drop in blood pressure they' pass out and and go to sleep because they don't have enough profusion pressure right they get Syncopy so the body is very resilient in the fact that it regulates what it needs but it's like a u-shape curve right just like everything in in physiology we know too little

is bad too much is bad so we have to find that sweet spot in terms of nitric oxide so how do you know if there's too much nitric oxide well there's only two signs of toxicity number one you get an unsafe drop in blood pressure and number two you get what's called Med hemoglobin emia where you start to oxidize the iron of hemoglobin in the red blood cell and you oxidize it to form met hemoglobin and then you reduce the oxygen carrying capacity of the red blood cell so you become cyanotic you'll get blue around

the lips um and it's it's a very serious condition but typically you'll develop really low blood pressure before you will ever develop any met hemoglobin emia and when it comes to the other way around when people find out that they're deficient in know how do they typically find their way to your information is it because their blood pressure is running aide and they can't control it I know erectile dysfunction I've heard you talk about that being a canary in the coal mine how do people know symptom wise if they're deficient in N yeah you know

it's a it's a very good question and something we've been trying to answer now for for 25 years and so the first question people always ask was how do I know if I need nitric oxide how do I know if I'm deficient it's a about 15 years ago I developed a salb test strip that we could test your saliva and what really what we were testing were your the the ability of your bacteria in your body to reduce nitrate to nitrate so when we sample saliva we're looking at number one are you ingesting enough nitrate

do you have the right bacteria to convert the nitrate to nitrate because on the saliva test strip we're measuring salivary nitrite and I think that's I tell people that's a good tool to have in your toolbox there's no false negatives if you're low you're low but there are some false posit postives and that's why I've gotten away from the test STP because there's people with active Dental infections oral infections show that they're kind of optimal on the nitric oxide test STP but systemically they're completely depleted right the best example is a 50-year-old hypertensive overweight diabetic

patient with Ed spits on the test strip and it's bright pink well obviously this guy isn't repl in nitric oxide it's a false positive on this test so what what we rely on in the question you brought up we have to rely on symptoms so if you're nitric oxide deficient what happens the first thing that typically happens is you develop erectile dysfunction right because when you lose the regulation of blood flow when you can no longer dilate the blood vessels of the sex organs whether it's the penis or the clitoris and that's dependent upon nitric

oxide so those that vascular bed can't generate nitric oxide to dilate those organs to get engorgement then your nitric oxide diffusion develop a erectile dysfunction that you that's as you said the canary and the Coline that tells you that something's wrong that's usually first second your blood pressure starts to creep up right when you lose the production of a main vasodilatory molecule nitric oxide blood vessels start to constrict they get rigid they get stiff and now with each beat of the heart they causes damage this pulse wave travels really quickly through the vascular tree causes

a lot of damage in theal dysfunction upregulation of adhesion molecules platelet aggregation monoy nutrifil start sticking to the lining of the blood vessel and you start to get plaque then thirdly typically you develop exercise intolerance so if you walk up a flight of steps you become short of breath and you just can't catch your breath or you can't even go out and walk 20 minutes without feeling tired that's a nitric oxide deficiency problem if you're insulin resistant type two diabetic that's a nitric oxide deficiency problem because nitric oxide is required for insulin siging and glucose

uptate and then typically fifth you start develop you lose your memory you develop mild cognitive disorders if not corrected vascular dementia if not corrected Alzheimer's because all of those are a loss of regulation of blood flow to the brain when you don't get blood flow to the brain you can't get the good stuff in you can't take the trash out beta amalo plaque builds up T Tangles the Hallmarks of Alzheimer's so you mentioned the test strips there being an objective way of testing this I know there's also a test I've heard you talk about called

the endopath talk more about what that is and then if you feel that's something that is only warranted if we're suffering from other symptoms like you mentioned or who should get one of those done I think everyone should you know this is a functional test it's a it's a non-invasive functional medical device but it's really the only device that tells us how well our blood vessels are making nitric oxide right and so the basis of this we call this flow mediated dilation a reactive hyperemia so the basis of this test is you put a blood

pressure cuff over your braul artery up on the your near your bicep and then you inflate this cuff to Super systolic level so now there's no blood flow into the forarm so you're completely shutting off the blood supply to the forarm and you do this for 5 minutes and it's a little bit I wouldn't say uncomfortable but you start you know it's like kind of like sleeping on your arm right your arm falls asleep you're going to get tingling um but what happens is when you release the cuff now these blood vessels and tissues have

been deprived of oxygen for 5 minutes and they want to increase blood flow and they do this through the production of nitric oxide so you can look at the degree of vasod dilation what's called reactive hyperemia and that tells you and through a pretty complex algorithm it can tell you your endothelial function or how well the endothelial cells of your blood vessels produce nitric oxide if you get a lot of as dilation that tells us that your blood vessels are making sufficient nitric oxide if you don't get any dilation in response to relieving the the

releasing the blood pressure cuff then that tells us that your blood vessels aren't making any nitric oxide and even though you may not have Ed or high blood pressure any the symptoms we talked about that's really the first sign and symptom that you're on a very slippery slope to developing chronic disease Ed hypertension everything we talked about so now you need to take corrective steps figure out why aren't my blood vessels able to make nitric oxide is it because of my diet is it because of what I'm doing is it because of some drug therapy

I'm taking is it and then you start got to start asking questions and then start doing the things that we've shown clinically to enhance endothelial nitric oxide production all right just so I'm clear the test strip I see how that's going to be testing the second pathway although not perfect you talked about how there can be issues there doing the the the endopat it sounds like it in the beginning when you're talking about it it's testing the endothelium but then you mention taking in nitrates I believe so what I'm getting at is what can we

decipher from each test is it an overlap of the two different Pathways or is it one is testing one and one is testing the other the test strip is kind of measuring what we call total body nitric oxide availability so whether you're getting nitric oxide produced in the lining of your blood vs from the endothelium that nitric oxide is primarily oxidized to nitride nitrate right and so the the human body doesn't discriminate nitrate coming from the diet or nitrate being produced from the oxidation of nitric oxide it just sees nitrate circulating in the blood and

then through the silin receptor it's taken up in our salivary glands and then secrete it in our saliva then we reduce it to nitric oxide so if you're low on the test let's just let's use an example if you test your saliva and it doesn't turn pink and it's completely white that tells us that you're low in nitric oxide but it doesn't tell us why you're low is it because you have endial dysfunction and your endial cells can't make nitric oxide is it because you're not getting enough nitrate from your diet is it because you're

getting enough nitrate from your diet but you're using mouthwash you don't have the right oral bacteria so but now you can start to interrogate each of these and then figure out exactly what's going wrong and why the test strip isn't lighting up but the very important distinction is the test strip is a biochemical test it's measuring a single molecule in one biological compartment the endopath is measuring the functional production of nitric oxide in the lining of the blood vessel so a functional measurement will always be more Reliant and and meaningful than a biochemical test because

there's too many factors that are affecting the biochemistry and the saliva and the n in the the nitrite in the saliva and when it comes to both of those tests how far back are they looking are they just kind of looking at the last 24 hours and how much nitrate we've taken in plus our endothelial function how do we get a picture over a longer period of time is it just doing the tests again and again yeah you know any any test we do whether it's a blood draw whether it's a functional test it's basically

one point in time right it's what's in your blood at the time they did the blood draw same thing with the test it's how your blood vessels are reacting at the time we do the test is it when you're fasted did you just eat a really unhealthy diet because and we've done these studies so if you do it fast and you get you show good enthal function you go and eat McDonald's fries you know anti or an inflammatory diet and you redo that test you're going to have a blunted response to your enial function and

then some of our clinical trials we've done with our product technology you can get a baseline in aial function take the Lin or take our nitric oxide four 5 6 12 hours later we retest now we can improve it so all these tests are basically capturing a single Moment In Time based on what you did before that so I think to get a true sense of how your body's reacting or performing is you do this over time and track it and if it gets better then I tell people don't get away from what's working keep

doing if it gets worse then you got to stop and think what am I doing it's making my endothelial function worse right as you explained that it gets me thinking about the person that goes on a weak vacation and forgets their mouthwash at home and then all of a sudden they try and do a test to see where they're at and you know you mentioned I think it was only four days that the bacteria can start to repopulate and and and start converting so I could see how things could change quite rapidly yeah like I

mean I've been studying the human body for more than 25 years and I'm still just in awe of how resilient it is you know even though we insult the body some people insult their body every day all day for years decades and yet they're still living right the body's so resilient I mean they may not may not be healthy but the body's still performing in some capacity or they'd be dead so and I think it's just remarkable that the body's able to put up with all this abuse that we give it um but yet it

doesn't have to be that way we understand the biochemistry specifically as it relates to nitric oxide that we know what interrupts it we know how to improve it and so for me there's really no excuse and there's no excuse for cardiovascular disease being the number one killer of men and women worldwide even today billions of dollars in research you know we know what causes cardiovascular disease we know how to diagnosis and we know how to fix it what's the problem it's education and awareness right we have to go out and change the way people are

treating cardiovascular disease we have to bring nitric oxide to the four and make it the number one consideration for Physicians seeing patients with poorly managed chronic disease uncontrolled high blood pressure uncontrolled diabetes why is that well think about nitric oxide nitric oxide controls insulin signaling glucose uptake regulation of blood flow to every organ tissue and cell in the body and it decreases inflammation oxidative stress and immune dysfunction every single chronic disease whether it's diabetes heart disease Alzheimer's same three things decreased blood flow inflammation oxidative stress and immune dysfunction nitric oxide corrects every single one if

you're enjoying this episode let me know by clicking like And subscribe below thank you so much and now back to the show so we know you've talked about the fact that n in the body dilates the blood vessels it's made in the blood vessels dilates the blood vessels what other specific functions does it have n numerous functions and again uh many of these I I've not discovered uh when we showed that nitric oxide uh was actually produced by Maman cells that's when so many people jumped in to try to determine what other things nitric oxide

does nitric oxide is important for example in the gastrointestinal tract uh you have a a a uh a physiological response called peristalsis which moves the food once you eat it through the GI tract and the mouth all the way uh you know to the rectum and so nitric oxide functions to relax smooth muscle that's how it that's how it is a vasod dilator it relaxes the arterial muscle and the artery widens nitric oxide widens the Airways like the trachea and bronchioles they widen so more air can flow through in the gut nitric oxide relaxes the

muscle so that the food can Propel through you have a rhythmic a rhythmic contraction which is not mediated by no then you have a relaxation which is mediated by no and that continues throughout the GI tract and propels uh the the the food through there another important effect of no is in relaxing your bladder you know relaxing the bladder is very important because in order to contain the urine before it's um delivered to the kidneys and out uh the bladder has to expand and expand in order to contain the urine otherwise you would have to

you know relieve yourself every 10 minutes and so if you make enough nitric oxide that bladder will expand and you'll be able to retain your urine for a longer period of time many older people especially women suffer from what we call urinary incontinence and so the bladder is very stiff does not expand to to to fill up with urine and so those people have to void their urine you know every half hour every hour and sometimes they cannot control it and that's due to a deficiency of nitric oxide coming from the nerves that go to

the kidney I have one last effect of no uh which I think is very important and I'm most proud of and that is that nitric oxide is the most important chemical substance in the body that actually causes uh erectile function or penile erection and if I may explain that for a minute every nerve in the body releases a chemical a signaling molecule so if a nerve goes to a muscle the nerve releases a chemical at the muscle the muscle then responds to the chemical well in the nerves going to the uh penis in the male

for the longest time no one understood what the neurotransmitter or chemical was so therefore nobody knew what caused penile erection and if you don't have that knowledge then of course you don't know how to treat erectile dysfunction which occurs in hundreds of millions of men throughout the world well we made the discovery in 1990 92 actually in humans that the chemical the neurotransmitter in those nerves is nitric oxide our friend nitric oxide and when n oxide is released into the erectile tissue again it relaxes the smooth muscle so the arteries dilate the erectile tissue dilates

the whole area becomes engorged with blood that that's what penile erection is all about so we made that Discovery and thank God that some of the pharmaceutical companies were looking over our shoulder like fizer Pharmaceuticals and they looked at our research and uh they took what we found we discovered physiology we didn't discover any drugs right we discovered noo was a neurotransmitter well fizer discovered a drug that works by boosting nitric oxide in the erectile tissue and they marketed that in 1998 as selenop or uh Viagra and it and they admit all the time that

you know it's because of my initial research that that Ena them to develop Viagra so they uh developed a nickname for me uh often referring to me as the father of Viagra which uh didn't bother me at all I love that acronym but when my mom was alive she used to get very upset every time she heard that she would always say son why don't you tell them to stop saying that already so when it comes to you guys you know in the lab figuring out the physiology behind what became Viagra how long of a

lag period was there between you know you guys figuring this out putting out the papers getting that scientific knowledge out to the world and then the drug companies jumping on this and creating a drug excellent question this was a record breaking a record breaking speed we we published our work in the New England Journal of Medicine which is you know pretty good medical journal and uh we published it in the early part of '92 while they were doing all this work develop all this and the the uh they came up with a selenop before it

was named Viagra which turned out to be very safe very very very safe in animal models and in humans so the FDA put a fast track on it and it was in 1998 which means six years later six years and that and that's a short time six years after we made our basic science Discovery uh Viagra was um marketed and I have an interesting story behind that because uh it was the the U Vier was marketed in March March of 1998 okay and then just a few months later in October of the same year in

1998 the Nobel Prize in medicine for Nitro oxide was announced and so I kept thinking oh my is this a coincidence or what so I decided I went I checked and I looked up the committee members for the Nobel committee uh for medicine and I discovered that the majority of the committee members were men over the age of 60 that is hilarious so we know that when we're growing produce in different areas of the country we're going to have different amounts of nitrogen we know organic versus conventional is going to have a different amount I

took you on a tangent there so continuing your thought process when it comes to nitrates in the produce so I guess the point I was trying to make is that this and we we've we've Quantified this so we took a standard American diet just what most Americans would eat and we grind it up and we quantify the nitrate content and Americans are only getting about 150 milligrams of nitrate per day through normal dietary patterns and we need at least a 300 milligrams to see any trickle of nitric oxide production because the inefficiencies of conversion so

number one we're not getting enough nitrate uh and then number two those that eat a plant-based diet they're not even guaranteed to get enough nitrate because depending on where they live what vegetables they're eating organic versus conventional you may not even getting enough nitrate to reap the benefits of a plant-based diet so if we took kind of the best case scenario and so we publish on this we took a Japanese diet we took a Mediterranean diet the dietary approaches to stop hypertension and we just took food choices from those dietary patterns and we Quantified the

nitrate that one eating those diets would would consume over a period of a day and we see anywhere in those diets from you know 400 milligrams up to, 1500 milligrams in a Japanese diet of nitrate so now what you're getting is you're getting sufficient nitric oxide being produced from those diets provided you have the right bacteria and you can make stomach acid so that that kind of follows step one the problem is we're not getting enough nitrate from our diet because of the the variability in in vegetables and Regional growing techniques and organic versus conventional

number two and we stumbled upon this probably 20 years ago if you use mouthwash you kill the nitrate reducing bacteria and you now you don't get the benefits of eating a good diet and think about this I mean people people mostly have good intentions right they try to learn as much as they can they try to listen and and assimilate all the information they're getting bombarded with on TV the media advertising and you see the commercials wake up every morning use lisine use scope it kills 99.99% of the bacteria in your mouth well that's not

a good thing you know we and others have published that if you use B wash your blood pressure goes up and you lose the cardioprotective benefit of exercise and you lose the benefits of eating a healthy diet so the worst thing you can do is use mouthwash and I try to put this in perspective because most people this is kind of like the aha moment for a lot of people like oh what I'm doing damage by using mouthwash yes the we've known for many many decades that you don't take an antibiotic every day for the

rest of your life right if you've got an infection you take a regimen of antibiotics 7 10 14 days and then you stop you kill the bad guys but you don't continue to take antibiotics because of the collateral damage it's mostly non selective killing right so we're killing the bad guys but we're also killing the good guys and there are a number of problems that occur from that we kill the gut bacteria get gut disbiosis you get systemic disease well the same thing happens in your mouth when you kill the oral microbiome in your mouth

every day sometimes twice a day there's consequences to that and the number one consequence is it shuts down nitric oxide production causes an increase in blood pressure you lose the benefits of exercise and you can no longer get nitric oxide from this secondary pathway so I tell people all the time look if you're using mouthwash you have to stop I mean the risk benefit kind of quotient there is all risk no benefit so you have to stop and then the other important thing that a lot of people don't even consider either as fluoride you know

most toothpaste have fluoride and fluoride is put in toothpaste because it kills bacteria it's an antiseptic so you have to get rid of fluoride in your toothpaste the other major problem is most Municipal Water Systems are fluorinated they put fluoride in the water and the drinking water why to kill the bacteria so now when you're drinking them water you're killing the good bacteria you're killing the bad bacteria you're shutting down your thyroid function and fluorides and neurotoxin so we have to rid our body of fluoride I want to highlight the importance of this second step

here the fact that we have these bacteria on our tongue and if we're killing them through things like fluoride or mouthwash we're limiting this whole second pathway and we already know that the first pathway is going to decline naturally as we age so I can only imagine the number of people that are getting older their first pathway is degraded down and they're using something like mouthwash or even drinking unfiltered water and getting fluoride and killing that bacteria and then you clarify if I'm wrong but as far as as I know from preparing and reading your

book and and digging into your work there is only these two Pathways so if you're impacting them both in a negative way the first one just by you know we talked about living a healthy lifestyle helps accentuate that but aging is going to dampen it naturally it's so easy to mess this up is what I'm getting at that's right yeah see like I said everything we do from an American lifestyle is designed to shut down n oxide production now what happens your blood pressure goes up that's the number one risk factor for the number one

killer of men and women worldwide which is cardiovascular disease nitric oxide is important for insulin siging so you develop insulin resistance type two diabetes you start to develop mild cognitive disorders and vascular dementia eventually Alzheimer's you don't have the energy to exercise because your mitochondria aren't producing enough energy so everything we know about the onset and progression of age related chronic disease can be traced back to insufficient nitric oxide production then so people have to ask yourself well what am I doing to disrupt my nitric oxide production well you're not getting enough vegetables you're not

getting enough nitrate two out of three Americans use mouthwash every morning and not coincidentally two out of three Americans have an unsafe elevation in blood pressure and think about this if you have high blood pressure you go to your doctor and he puts you on a blood pressure medicine right and 50% of the people that are on blood pressure medicine don't respond with better blood pressure we call this resist hypertension it's resistant to standard pharmacotherapy so why is that well these drugs aren't targeted towards the oral microbiome there's ACE inhibitors that that you know mechanistically

they're affecting the angot tensin converting enzyme shutting down an2 production there's calcium channel antagonist there's beta blockers diuretics so the reason that these patients are resistant to stand therapy is because it's the wrong target they don't have a renin Anga tensin problem they don't have a calcium disregulation they don't have a fluid imbalance so ACE inhibitors arbs calcium channel antagonist and diuretics aren't going to affect their blood pressure hypertension is a symptom of oral disbiosis so now we're finding if you're using mouthwash and you stop and allow this microbiome to repopulate and do its job

blood pressure will normalize and now you can get off medications and Americans especially older Americans are overmedicated they're put on one medication 2 3 4 I know people who are on 10 12 15 different medications and the human body cannot and will not heal or perform when there's that many synthetic enzyme Inhibitors at one time I mean that's not how the human body is designed to work okay so for the person tuning in here they're one of the two-thirds of Americans that have been using mouthwash to this point they're going to stop today but now

they're worried that they've killed the good microbiome in their mouth what do they do how can they accentuate bringing that back I'm assuming there's a way and then how long does it take you know we published on this I think in we published a a similar paper in 2019 and we designed this experiment to answer that question so we took normal healthy individuals that had normal blood pressure and for 7 days we just use mouthwash twice a day and at the end of seven days we measured their blood pressure we did tongue scrapings to figure

out well before and after see what happened to the oral microbiome and then we stopped the mouthwash for 4 days then after 4 days let's see what happens to their blood pressure and let's see what happens to the microbiome so the results of that study were after 7 Days of using mouthwash in otherwise normal tens of patients we saw an increase in blood pressure in fact in one person we saw a 21 mm increase in blood pressure 21-year-old triathlete Dental student his blood pressure went up 21 mm of mercury in one week just by killing

the bacteria in his mouth no change in diet no change in exercise activity the only thing we did was kill his bacteria and we made him clinically hypertensive and then fortunately once we stopped four days later the microbiome had completely repopulated and his blood pressure completely normalized so this population is really resilient in the fact that if you stop killing it daily it repopulates we just got to give these bugs kind of what they need so number one get rid of fluoride get mid of mouthwash and then start eating more green leafy vegetables because these

are what we call nitrate reducers they're faculative anerobic bacteria meaning that if Oxygen's around they can respire on oxygen if oxygen is not around then they respire on nitrate so the more nitrate Rich vegetables you you consume were feeding these bacteria a normal respiratory substrate that they can rely on and respire on and they'll repopulate and the beauty about that is we also published in that study that the greater the diversity the oral microbiome the healthier the microbiome and the better management of blood pressure so we need diversity there's biofilms there's different communities on the

dorsal part of the tongue on the gingival tissue so this the ecology in the mouth is is quite remarkable but it's very resilient so even if you've been using mouthwash for months or years once you stop at least the data from study published study shows that within 4 days these bacteria will completely repopulate now you just got to feed them feed them the good stuff all right so we know from before we touched on this quickly the fact that the bacteria on the tongue feed on nitrates and they can feed on them as food is

being chewed and and before it's swallowed and then also there's a secondary system thankfully that digests and then brings the nitrates back up through the saliva and then we get a second chance at feeding those bacteria no that's kind of this the second what we call A Time release so now each time you secrete you salivate you're secreting nitrate in the saliva and this is a very inefficient system so we can quantify this so the the nitrate that's let's let's call we eat 150 grams of spinach salad 90 minutes after we consume that the nitrate

that's in that spinach only about 25% of that's going to be taken up in the gut right so about a third about a fourth of the load that you're getting from the diet is taken up in the gut and then concentrated in our salivary glands the rest is distributed throughout the circulation filtered through the kidneys you excrete some some is reabsorbed and then only about 20% you only get about 20% reduction efficacy of the bacteria in the mouth so each time you salivate so 25% absorption uh 20% reduction that's 5% of the total nitrate load

we're reducing into or metabolizing into nit Tri nitric oxide so and we we've Quantified that we can we can verify it stochiometrically I mean this is a very beautiful system so I think it's an inherent inefficiency because it allows the body to produce nitric oxide over a long period of time in a Time relase manner provided that we have normal salivary secretion we have normal nitrate reducing bacteria on the CPS of the tongue and that our prial cells in our stomach can produce stomach acid okay so we know when it comes to the bacteria in

the mouth you've mentioned fluoride mouthwash those are both going to kill it what about things like gum people are chewing um tongue scraping I'm just trying to think of different inputs into the mouth and how they might benefit or cause damage there to the to the microbiome yeah there's there's a lot of unanswered questions still so for the most part there's a lot of you know the answer is we don't know but here's what we do know tongue scraping in that same study we found that people who did Daily Tongue scrapings had the greatest diversity

of the oral microbiome and had the best blood pressure but if you tongue scraped and use mouthwash those were the patients who had the greatest increase in blood pressure upon mouthwash so that our interpretation of that data was if you do tongue scraping and don't use mouthwash that seems to be very beneficial and I I equ it to like tilling the soil right when you scrape the tongue you're basically kind of tilling the soil and and and and kind of allowing these these organisms and bacteria to repopulate and diversify and that seems at least in

our study to have better blood pressure management um things like chewing gum I think it depends on if it's sugar uh a lot of sugar in the gum then you know sugar causes an overgrowth of you know acid producing uh bacteria in the mouth and Carries and cavities and and bad things there's other things like essential oils uh that we don't have any answers to things like oil pulling I get questions all the time and these are things that we just don't know we haven't researched it but unless it's antiseptic and kills non-selective bacteria the

good the bad then I think it's probably going to be fine if it's if it's antiseptic it's not going to be good if the oral hygienic practice isn't killing any bacteria like tongue scraping isn't kill anything it's just kind of allowing disturbance of the of the uh terrain um so yeah I think you know again there's a lot of answers that we don't have but what we do have it's very clear that you can't use antiseptic mouthwash you can't add fluoride to your to your body in any capacity whatsoever and then just eat a balanced

diet in moderation with some more green leafy vegetables and sometimes it's really that simple we got a lot to cover you are a true expert when it comes to nitric oxide and let's just start off putting everybody on the same page and talk about what this is and why is it so important well it's it's a long story but I'll make it short at least to start with nitric oxide is a chemical it's actually a gaseous chemical that's present in the Earth's atmosphere and that's been known for many many many years but the key thing

here is that my laboratory discovered a number of years ago that our bodies actually produce this gaseous molecule nitric oxide also abbreviated n and we produce this molecule in Our arteries and other parts of the body really for the purpose of regulating our cardiovascular function normalizing the blood pressure blood flow preventing uh blood clots when you don't want them to occur and that's just part of the thing that nitric oxide does in the body so when it comes to n o how much does it vary between person to person how much we have in our

system that's a great question and um it's extremely variable uh it really depends on after all the research that's been done not just by my lab but mainly by other Laboratories uh lifestyle one's lifestyle will determine how much nitric oxide your body makes and I really mean that for example those people who who follow a a healthy balanced diet together with physical activity will produce a lot more nitric oxide than those individuals who eat an unhealthy diet and lead a sedentary lifestyle some of the greatest research I've ever seen done is on those two topics

that um uh the amount of nitric oxide we make really is dependent on our lifestyle but under normal physiological circumstances you know without taking drugs without taking this or doing that and is there a big genetic component as well there could be not as much information is known about that but it appears that there's some genetic uh differences among individuals where certain individuals may make less nitric oxide than others but that is usually localized to specific parts of the body uh not the entire body in general but a lot more work needs to be done

with that before we can you know understand that what we do know is that uh in the great great majority of people as I said before regardless of genetic makeup uh living a healthy lifestyle is really the way to go to maintain one's nitric oxide levels and also the activity of nitric oxide in your body that took about 25 years to really establish well since you are the true expert and you've won a Nobel Prize in this area we're going to go deep on each of those two specific areas he mentioned you talked about you

know the diet being an influence and exercise let's get into the nitty-gritty on these starting with diet so you mentioned a healthier diet can help promote more no in the body when you say healthy diet what what are we talking about there well you know here what we're talking about honestly is there's no magic diet there's no one diet that's better than another diet I I don't believe in specific diets I believe in a I believe in a well-balanced uh nutritional diet eating uh the the different food groups and eating the healthy foods Within These

food groups and just to make it very simple protein is very important carbohydrate is important and fat is important okay so if we go to protein it is important to eat protein but what it should be healthy protein unsaturated fats uh lean if you like beef which I love you know lean beef is good fish is even better right fish is loaded with protein and it's completely unsaturated and it's loaded with antioxidants like omega-3 fatty acids which everybody's heard of so so eating healthy protein is good and there are many other foods that contain healthy

Pro uh protein including nuts beans and so on and uh we can if we look at carbohydrates we should really if we're if we're talking about fruits and vegetables the the vegetables should be green leafy vegetables anything that's colorful like that will contain lots of antioxidants and the way the antioxidants work is that they can actually increase the activity of your Nitro nitric oxide that's been known for a long time because nitric oxide is very very unstable it only lasts for literally seconds in your body and it gets destroyed by oxidation or oxidative stress so

in the presence of antioxidants one can boost the levels so to speak of nitric oxide and this comes from the the different antioxidants and vitamin C pre present in these different vegetables same thing goes with fruit we have many different kinds of fruits the most colorful fruits are the best for n o because the red the red the green the blue the purple color any color you see in a fruit is attributed to the antioxidant chemicals in the fruit because those antioxidants have that color and so it's good to eat fruits that are rich in

these colors pomegranate for example uh blueberries uh blackberries strawberries they all have color they're all loaded with antioxidants and they've all been shown to boost your nitric oxide uh production and so as you can see you know I'm talking about a healthy balanced diet I'm not talking about well you know you should eat only protein and very few carbs you should eat only carbs and very little protein I do not believe in any of those I think that a balanced healthy diet is the way to go in other words it's a gimmick free diet and

most people don't follow gimmick-free diets you know if you tell somebody you got to eat this and not that they do it and and I think that's the problem that's my own opinion though well I think you make it really manageable and and that does make a lot of sense but within that realm Are there specific Foods I know you mentioned the green vegetables high in antioxidants eating the colorful uh fruits and vegetables but are there certain specific specific maybe a handful of three to five different fruits and vegetables or any food for that matter

that people can consume that have extraordinary benefits when it comes to sure okay so one I would have to say that uh fish and any fish products so that's a big category any fish products will will boost no production if we go to uh vegetables well you know I think that at least some of us older people remember popey and eating spinach and he used to gain strength from eating spinach well we didn't know the mechanism back then but it's incredible it's true spinach contains antioxidants but spinach also contains something called nitrite and nitrate that's

become more popular recently it's it's those are ingredients in fertilizers and you find them in root vegetables and leafy vegetables close to the ground so spinach is a great one because when you consume nitrite and nitrate your body actually converts that to nitric oxide and that's been in the news quite a bit lately eating beets a lot of people don't like beets I love beets thank God beets also are rich in nitri and nitrate and when you eat beets you're actually delivering nitric oxide into your body and then we can throw in some brussel sprouts

for example uh uh and arugula I'm Italian so I'm I'm glad I like arugula so those are some examples if we go to fruit um the best fruit we've done experiments on this and published this but the best fruit for boosting nitric oxide is pomegranate pomegranate juice or any or just the pomegranate fruit and I don't get any money or compensation for saying that okay uh another one of course blueberries blackberries you know in in the berry f family and the pomegranates those would boost nitric oxide more than say would a an apple or a

banana I'm not putting those down they're they're good for fiber and that's also important you know for balanced health and when it comes to boosting I know in the system how quickly does that happen if we're talking about some of these specific foods like aruga and different berries is it like within minutes of consuming that or is it more just eating that on an ongoing basis and then having an overall boost in general in N spectacular question and actually both answers are correct and and and both measurements have been made for example uh I would

say that as soon as you can digest the ingredients and and get and and get the components into the blood that's when you would see an increase in no So within an hour let's say something like that you could definitely see an increase in no if you have let's pick a rugala that's my favorite if you eat that once a week you'll get a boost in about an hour it'll last an hour and come back down but if you eat it every day every day then every day you will get that Spike and if you

eat the other fruits and vegetables I mentioned every time you eat them you're going to get that Spike well Common Sense tells you I mean you don't have to be a rocket scientist to figure out that the more of that that you eat then the higher H the levels and the and and the more you'll maintain those levels of nitric oxide and that's um I think that's important and if you take the opposite point of view and you can make these measurements we did so in my laboratory years and years ago but if you if

you take a I will not mention the brand but if you take a delicious greasy fatty hamburger and you eat that and you're monitoring the nitric oxide levels you'll see a decrease within 20 minutes 40 minutes and that decrease is going to be there for oh 2 to 4 hours now doing that in itself is no problem that's not going to cause a heart attack of course not but for those people who eat hamburgers or that kind of meat every single day you're going to have a prolonged decrease in no and after a decade or

so that's not good because you need a as much nitric oxide as you can make to protect your cardiovascular system against disease you know that Nobel Prize was awarded not just for the discovery of no in the body but also because so many other people expanded on it to show the incredible importance of nitric oxide in maintaining cardiovascular health let's get a little bit more granular in the details here we now know there's different foods that uh can boost and dampen n o let's talk about what happens the physiology in the body so you eat

say we'll talk about one of the foods that Bueno you eat say arugula so once that gets into the digestive system and we start to break that down how specifically is eno produced okay let me tell you and it's not just from arugula but from uh other Foods as well they each do it a slightly different way if we go to uh if we go to Protein healthy protein soy protein protein from nuts for example okay or protein from fish that's maybe the best example what happens is that protein is composed of about 20 different

amino acids amino acids are the building blocks of protein protein is a large molecule has lots of amino acids linked and connected together each of the 20 amino acids has a different function there's one amino acid called ARG Arginine that is required for nitric oxide production the only way no can be made in the body from protein is through Arginine so what happens is that once you digest the protein in your gut and all the amino acids are absorbed into the blood then the Arginine Finds Its way into the blood vessel lining it's called the

endothelium or endothelial cells the Arginine get into the endothelial cells and that's where you have enzymes that produce nitric oxide from the Arginine part of the Arginine molecule is actually clipped off and converted to nitric oxide so just think you have hundreds of thousands of miles of arteries and veins in your body you have 60 million endothelial cells I think and when you get absor when the amino acids when Arginine gets absorbed it's going to go into all of the endothelial cells throughout the body and stimulate nitri oxide production everywhere not just in one particular

area so if we go to antioxidants they don't they're not converted to no the antioxidants sort of take away oxidative stress thereby allowing whatever nitric oxide happens to be present to increase in amount because it's no longer being destroyed by the oxidative stress so so by that mechanism similarly if you eat enough of these carbohydrates and fruits and vegetables you will protect the nitric oxide that is made from the Arginine which comes from the protein so you can see where they work together so if you just ate protein and you had no carbs and no

vegetables and no fruit yes you would make no o but that no would be destroyed so rapidly that I'm not sure what kind of a benefit uh it would have in the rest of of the body that's why it's so important to eat the fruits and vegetables along with the protein because one serves to make the nitric oxide and the other one serves to preserve it so that it can produce the desired effect what is nitric oxide and why does it matter for our health well thanks Jesse it's it's great to be with you and

that's a look that's a very important question and really one we've been trying to answer for the past 30 years but today we know that nitri oxide is a signaling molecule it's produced in the body naturally the older we get the less we make and that's what's responsible for age related disease but it really at its basis it's uh it tells our blood vessels to relax and dilate so it improves oxygen delivery improves blood flow inhibits inflammation oxidative stress and immune dysfunction the key Hallmarks of every sing chronic disease so now we understand how the

human body makes nitric oxide What goes wrong in people that can't make it and now we know how to fix it all right well let's start talking about what happens when the body isn't making it correctly I know there's two different pathway so let's take each one and get into the Nuance there so about I guess probably been 30 35 years ago was first recognized that there's an enzyme in the lining of the blood vessel called nitric oxide synthes and that enzyme converts L Arginine which is an amino acid into nitric oxide so that was

the first Pathway to be discovered now I just want to make a point that the first Pathway to be discovered doesn't necessarily mean it's the most important or prominent it was just the first to be discovered so this enzyme converts Arginine to nitric oxide and you get citrene as a byproduct and it's the second to Second production of nitric oxide that regulates the second to Second blood flow and oxygen delivery to every organ tissue and cell in the body and it's the dysfunction of that that enzyme and we call that endothelial dysfunction so the older

we get the less nitric oxide we make we call that endothelial dysfunction we have decreased blood flow decreased oxygen delivery to every cell in the body then we have inflammation oxidative stress and immune dysfunction so that's the first pathway it's very well elucidated we know the enzymology the biochemistry of that pathway we know what goes wrong in people that can't make it and we know how to fix it now the other P all right before we jump into number two I want to I want to pause here and take some time and get into the

subtle there so arginine is the amino acid you mentioned that is the first step of this pathway we know that as we get older this doesn't work as well talk about where the Arginine comes from if it's an amino acid I assume the diet and then let's get into where things go arai and why as we age does this not work as well no it's a fundamental question if you want to understand chronic disease and keep from getting chronic disease so L arginine is a substrate that this enzyme uses to make nitric oxide and it's

a semi-essential amino acid semiessential meaning that you get part of it from your diet so the breakdown of proteins proteins are made up of individual amino acids arginine is a common constituent of most proteins and then it's also made through the Ura cycle so the human body makes Arginine on its own so even if you're not getting enough from your diet you make enough through the Ura cycle to theoretically saturate the enzyme to make nitric oxide so this whole concept of supplementation of L Arginine has never made sense to me biochemically because there's never a

condition where patients or sick people are deficient in arginine so it doesn't make sense to give the body more in fact we now know that if you give the body more it can actually do more harm than good um so the body makes enough L Arginine to where you don't have to supplement if you supplement there's at least two clinical trials showing that actually patients got worse poinar patients meaning people who have just had a heart attack in 2006 they published a study that the people who were getting high dose Arginine actually had a greater

mortality it was killing more people than the placebo and then a similar study and I think 2011 in patients with peripheral artery disease give them high dose C Arginine they got worse so we knew we we've known for many many decades now that arginine is not the solution for nitric oxide deficiency in fact it can be count uh productive and cause more harm so what happens and the reason people become nitric oxide deficient is the enzyme that converts Arginine to nitric oxide becomes uncoupled so there's a there's a flow of electrons through this enzyme you

many different co-actors and substrates and when this enzyme becomes uncoupled then it can't transport this flow of electrons to the five electron oxidation of Arginine and production of nitric oxide so we now we know what causes enzyme uncoupling it's the oxidation of tetrahydropterin we we provide a certain Redux potential or an electric potential to prevent the oxidation of bh4 you recouple the enzyme and now we can improve endogenous nitric oxide production without the need for supplemental Arginine or citrine or anything like that so that's the basic biochemistry of that pathway okay there's a lot in

there I want to unpack so we know that the substrate Arginine isn't the rate limiting part of this whole thing we know that actually if we take in too much can cause problems I'm curious in those studies where they did find there was problems where people were taking that what was the physiology there well when you when you have an uncoupled nitric oxide synthes enzyme and you give highd do Arginine this enzyme actually produces super oxide which is an oxygen radical and causes more damage causes increased inflammation oxidative stress and immune dysfunction so the patients

got worse the other problem we worry about is if you give high dose arginine you know the body has enormous redundancy in it and it only it regulates what it needs in certain Pathways so if you give high dose Arginine you get an increase in expression of an enzyme called arginase and then you divert the Arginine which would normally go through the nitric oxide pathway away from the nitric oxide pathway and through ornithine and Ura disposal so you can actually divert and and basically have unintended consequences of what you're trying to achieve by giving high

dose Arginine so I tell people arginine is is not your problem or it can be your problem if you're using Arginine based supplements uh save your money uh save your health you don't need them in fact if you don't know what you're doing it can cause more harm okay so let's focus in now on the enzyme so we have this enzyme in the endothelium it becomes uncoupled and this is where the issue is is this just something that happens natural it sounds like it is but is this just something that happens naturally as we age

or there's certain things that we can do to slow that down or are the things we're doing that are speeding that up that we can control all of the above so if you look at populationbased kind of studies what we see is we lose about 10 to 12% of the function of that enzyme per decade so really by the time you're 40 or 50 years old you only have about 50% of that function of that enzyme that you had when you were 20 now we know that that's not NE that doesn't have to be the

case right so I'll be 50 in a couple of months but I have a biological age of a 38y old and know we have 18 20 year old kids who have the biological age and the vascular age of a 50 60y old they have severe endothelial dysfunction so we can now modulate the activity of this enzyme so the rate limiting step is is oxidation or oxidative stress so because we live in a toxic World we're exposed to EMF we're exposed to herbicides pesticides we're exposed to a western diet poor diet processed foods a lot of

sugar all of those conditions lead to NS uncoupling and Nitric ox oide deficiency but if we take into account and eat an anti-inflammatory diet if we get regular moderate physical exercise we're exposed to sunlight know 20 or 30 minutes a day all these things facilitate and we take antioxidants to prevent oxidative stress then we can preserve the function of this enzyme and prevent this age related decline in nitric oxide production and to me that's the Holy Grail in cardiovascular medicine and really Health and Longevity okay so there's these different LIF stuff factors you named a

bunch of them where we can prolong at least the degradation of the uncoupling of that enzyme and food was part of that and this is where it gets a little bit more complex there's a second pathway that involves certain foods where we can boost n so let's bring the second pathway in now and then we're going to tie all this together yeah that's really the remarkable thing about human physiology and I'm always intrigued by how the human body works so we've known know for centuries right diet and exercise is essential for health and well-being and

Longevity but come to find out about 20 25 years ago we discovered a pathway whereby the mechanism of certain diets like a Japanese diet a plant-based diet Mediterranean diet dietary approaches to stop hypertension all of these diets that through epidemiological evidence have been shown to reduce blood pressure reduce cancer rates improve longevity and and lifespan the mechanism of those diets revolves around a molecule called inorganic nitrate and this is a molecule found primarily in green leafy vegetables things like beets arugula spinach kale the darker the green leafy vegetable typically the higher the nitrate content well

when we consume these vegetables about 90 minutes after we consume them the nitrate is taken up in the gut it's concentrated in our salivary glands and now for the next 6 8 10 hours each time we salivate we're secreting nitrate and if we have the right oral bacteria in our mouth the N the bacteria reduce nitrate to nitride and nitric oxide so this is the first metabolic activation step of the diet so we're 100% dependent upon the bacteria that live in and on our body to activate nitrate so that the body can utilize it to

make nitric oxide and now our saliva becomes enriched in nitrite so when we swallow our own saliva we get a burst of nitric oxide gas in the stomach and that nitric oxide from swallow on saliva kills things like H pylori the ulcer causing bacteria eoli salmonella Clum so if you got a A bacteria on the foods or the lettuce or the spinach or vegetables you're eating then it kills it through normal U nitric oxide production in the Lumen of the stomach so you may have caught three important points there number one we need enough nitrate

from our diet number two we have to have the right bacteria and number three we have to have sufficient stomach acid production and then this is where Americans get it completely wrong right and we've Quantified this we know the standard American diet doesn't contain enough nitrate to fuel this pathway two out of three Americans wake up every morning use mouthwash killing the oral microbiome shutting down nitric oxide production and there are 200 million prescriptions written for an acids every year and that's not even counting the overthe counter purchases you can get pryc pricd Nexium all

these over-the-counter products and people have been on these an acids for you know 5 10 15 sometimes 20 years and this completely shuts down nitric oxide production so it's just the the American lifestyle it seems like every every part of the American lifestyle leads to a decrease in nitric oxide production so for me it's no wonder why we have the sickest population on the planet everything we do is disrupting nitric oxide production if you can't make nitric oxide you're going to develop chronic disease cardiovascular disease Alzheimer's diabetes chronic fatigue uh it's what Americans are faced

with today most Americans all right a lot in there TPAC I'm going to try and summarize a little bit here for us so we take in nitrates through the diet dark leafy greens best source the the bacteria in the mouth are going to convert nitrates to nitrites and this happens as the food is passing over our tongue also as we take in the nitrates there's a a pathway in our body that recycles them all the way back through the saliva onto the tongue again so there's the two different ways that that happens then we need

the stomach acid when we swallow that saliva to turn the nitrite into nitric oxide do I have that right you got it well let's start with there's these three pieces that we need to be cognizant of and need to make sure we're optimizing you mentioned them there and I want to get into each of the three and make sure that we know how to do that starting with the dietary piece we know again leafy grain this is where we're going to get our nitrates let's talk about the absolute top sources in that category and then

what we're looking for because for example I know spinach is is a good source or beets which beets is a little bit different not obviously part of the leafy greens but there are different factors as we're growing these and such that can influence how much nitrate are in the produce so let's really pick this apart we know we we we attempted to answer I think the question you're trying to pose is if we wanted to use diet as a firstline defense for preventing nitric oxide deficiency how much spinach celery broccoli kale arugula would you need

to eat to reach that threshold of nitrate so the body can convert it nitri oxide and so to answer that question in collaboration with Texas ANM University we went to five cities across the us and we just took vegetables off the shelf we brought it back to the lab and we analyzed it for the nitrate content and we went went to Raleigh New York Chicago Dallas and Los Angeles kind of five corners of the us what we found was you know it's really pretty shocking to us we we figured there would be some variability but

you know there's as much as a 50 to 80 fold difference in the nitrate content of vegetables bought and grown in New York compared to those bought and grown in Los Angeles or Dallas so then when we uncovered this a little bit more we realized well there's different farming practices uh on different parts of the US there's different soil conditions certainly different climate conditions and then we realize there's certain number of lightning storms in these different areas and so nitrogen is fixed in the form of nitrate primarily through lightning storms so to break the triple

bond of nitrogen you need high energy and really that only occurs through lightning F so we're finding that in areas kind of in the the Rust Belt of the South where there's a lot of thunderstorms the soil seems to have more nitrate in it and then other regions for for whatever reason they may not and then the other shocking thing so the point of that is we really couldn't make any recommendations on how many servings of a given vegetable you would need to eat because it depends on where it was grown what the what vegetable

it was because there's Regional difference then there's High variability from you know celery broccoli kale spinach across vegetable categories and then we did something a little bit on top of that we took organically grown vegetables so ve these are vegetables that have an organic label and then we compared those to conventionally grown vegetables and on average the the organic vegetables had about 10 times less nitrate across the board and now when you you got to think about that for a minute because most people think organic is good I should eat organic but from our studies

if you're eating only organic you become nitrate deficient and I think perhaps more importantly you need nitrogen in the form of nitrate to assimilate other minerals and nutrients so if a vegetable is deficient in nitrogen or nitrate it's not going to assimilate other nutrients so now these vegetables are deficient in things like magnesium chromium selenium all the trace minerals and vitamins and nutrients that we used to get so I tell people you it's really difficult to eat enough organic vegetables to get enough nitrate in your diet to stimulate this nitric oxide production pathway and organic

means that one no herbicides no pesticides but there's a restriction on nitrogen based fertilizers added to the soil inorganically grown vegetables so for instance what I do when I grow my vegetables we we raise our own beef we grow our own vegetables but I so I sample the soil and send it off and for analysis to figure out what's missing in the soil why do I need the supplement and then I add standardized nitrogen to the soil so I know that my soul is enriched in nitrogen so the vegetables that I'm eating and I'm growing

here in my own ranch wouldn't be classified as organic because I'm adding fertilizers but I'm not adding herbicides or pesticides so I think there's a fine balance here and I think people are so caught up in this whole concept of organic and they really don't know what in the hell organic means they've been taught by the media that it's you know it's good it's healthy well I think it's free of herbicides and pesticides but we now know that the vegetables grown in the US since 1940s have about a 78% less vitamins and minerals and nutrients

uh since the 1940s so the pressures of feeding a growing planet population is at the expense of nutrient density let me just pause you right there because there's a lot I want to get into within what you've just shared so we know that in general organic has less nitrate so and you explain the whole nitrogen being added to the soil and the reason for that you mentioned the fact that you're growing your own food so you can add that back in and not add the poisons what do you recommend to people then if they're not

able to grow their own food they don't have you know the time the land whatever it is and they're they're buying from a grocery store and up till this point they've been buying organic can we just make up and there's another piece to this I want to make sure and tees out and this is something I haven't heard you talk about before I think the part about the nitrate not being in the soil is easy enough to understand but you mentioned the fact that it affects the different nutrients beyond the nitrate so I know I

threw a lot at you I want to understand that second part where it's affecting more than just the nitrate and then also on top of that for somebody who isn't going to grow their own food what's the best they can do you there's the whole field of agronomy on how do you maximize product yield and nutrient density and so go back a hundred years ago you know Farmers used to do crop rotation so they would grow crops that would deplete certain minerals and nutrients from the field and they would go back and plant let say

soybean or clover some vegetable that would replete those nutrients back in the soil so crop rotation allowed for fertile grounds now you see these fields that are just all they do is is grow coin all they do is grow soybean or or cotton so there is no crop rotation so we have to assimilate nutrients in the plants that we grow and you do that through nitrogen and and nitrogen assimilation in the form of nitrate so if the soil is deficient in nitrate it's most like going to be deficient in other trace minerals and nutrients but

more importantly is and you can see this fertilized versus unfertilized uh vegetables the fertilized are really dark green they have higher yield the unfertilized is a light green less nutrient less yield so in the organic world you know you can add manures you can add organic compost but again there's so much variability in there there's no standardization of the nitrogen so you don't even know what you're getting in from in fact the manure the compost may not have any nitrogen in it so what I tell people is Buy Local you know go to your local

farmers market talk to your local farmers support the local Growers and then ask them questions say here here's what I'm interested in and you know people who live in really urban areas and inner cities you know it's very difficult so then really the only solution for them is they've got to do what I call a micronutrient analysis you can go get your blood tested and figure out exactly what what are you deficient in and then you can start to develop kind of some personalized supplementation you know we know just broadly from the inhan study from

the US government that 75% of Americans don't get enough magnesium 95% of Americans are deficient in iodine 65 75% are defici in chromium um selenium these trace minerals and this is what causing a lot of chronic disease you know lonus Pauling said you know famously 50 60 years ago that most chronic diseases are caused by nutrient deficiencies if we don't have these trace minerals and nutrients then the body can't do what it's designed to do and you become dysfunctional and you get sick so it's it's a very it's a very interesting question but it's the

solution isn't very simple right so you have to be resourceful but I think the simple thing is by local from your local farmers market and then ask these Farmers questions how are you growing your Foods how are these vegetables do you add herbicides pesticides uh I certainly don't want that in my food supply but also I also want nutrients directly from the source okay so the part I'm still a little fuzzy on the fact that the other nutrients are low in the organic as well is that just because when they add the fertilizer they're adding

other things to the soil and upping those nutrients so I get the fact that the nitrogen isn't being added and that's where the nitrate is lower but is there something to the other nutrients and why they're lower in the organic as well well I'll give you an example so when I fertilize my my land I get nitrogen I get poach uh get potassium and sulur so there's there's a four kind of four main elements that we're adding to the soil so nitrogen in the form of nitrate um and you get potash and so I use

a mix because the soil samples tell me this is what I need for this type of land that I'm I live on and grow in so I know for instance it's 28% nitrogen 14% uh 147 and 3 and half% sulfur so I'm putting all these nutrients in the soil so that now the plant has a way and the nutrients it needs kind of like the human body the plant now has what it needs to assimilate transport all the other nutrients in the soil provided those nutrients are in the soil but if you don't test your

soil and they're deficient in certain things then the plants can't assimilate it because it's not available and I think that's why soil sampling is so important so you know exactly what's in your soil or what's not in your soil and then you can put put in there so that you have a nutrient-dense food that you're growing in that soil so it's it's a matter of availability and just not knowing but it's also important because even if you have those nutrients in the soil without nitrogen in the form of nitrate you don't assemble or transport those

nutrients and assimilate them into the vegetable or the plant that latter part is what I was trying to clarify so that's great let's talk about nose breathing because this is another way that's free people something they can do right away to help boost their n o so a lot of people these days are starting to learn about the benefits of breathing through the nose I've talked about this with a number of guests on the show before but let's talk about from an N perspective you know we could even tie it into an athletic Endeavor or

just life in general yes start breathing through the nose how does that impact Eno oh tremendously because uh uh uh two close friends of mine uh John laurberg and Eddie Whitesburg at the Stockholm in Stockholm at the Carolin Institute found a number of years ago that the nasal mucosa the mucosal cells inside the nasal cavity produce a lot of nitric oxide it was the first discovery it's easy to measure and uh and they wondered you know why does the nose make so much n o the mouth does not make any nitric oxide and so they

did the work one thing led to another and then the Reon reasonable a reasonable answer to that is that when you inhale through your nose that nitric oxide made by your nasal cells gets into your lungs and and goes down into the lungs the nitric oxide on a regular physiological basis will widen the Airways to get more air into your lungs when the no o gets deep into the lungs it dilates the pulmonary Aries so that more blood flow gets into the lungs so if you dilate the airway you have more air more oxygen if

you dilate the blood vessel you get more blood in there obviously you get more oxygen into the blood and that's a great way to oxygenate the blood I mean mother nature is very smart it's incredible but to get that to work you have to breathe through your nose and uh if you breathe through your mouth it's not harmful it's just that you don't get that nitric oxide in there and this breathing through your nose uh when I first read that I decided that when I'm biking outside the main exercise I do is is is cycling

whether it's indoors or Outdoors I'm too old to play ball anymore and do those other things but I always what I always try to do is inhale through my nose every time inhale through my nose and then I try to Exhale through my mouth I don't want want to the nitric oxide that's accumulated in my nose I don't feel like blowing it out into the air by exhaling through my nose so I exhale through my mouth why not I feel that it works I have talked to many many friends who feel that it's important to

breathe in through your nose and in various other shows that I've done and talked to other people and had interviews many many athletes have found the same thing that breathing taking deep breaths through the nose is very refreshing gives you more energy and so on and so forth and it makes else sense and and another reason to breathe through your nose is not just for endurance uh Jesse but it's to keep your lungs from getting infections due to the flu and viruses because you know about covid-19 you know that Corona virus destroys the endothelium in

your lungs that's how it kills people it destroys the endothelial cells in the pulmonary arteries so they don't make no o if you don't make n what happens your Airways shut down your blood vessels shut down and most importantly nitric oxide has been shown by hundreds of people to be antiviral no o kills viruses and prevents them from replicating especially the Corona virus so that that is why inhaled nitric oxide as a drug has been it just has just been tried recently and it's effective in treating covid but the important thing is by breathing in

through your nose you're delivering that no constantly into your nose and you could help protect yourself I think against covid I mean you should of course get vaccines and all that but the more n you breathe in the more you're helping to fight uh and destroy the Corona virus I had to throw that in because very important no that is so in a practical sense then if you're in an environment you know you're exposed to bacteria viruses try and breathe through your nose and get the benefit you just talked about right exactly exactly so we

talked about breathing through the nose we talked about exercise we talked about supplements drug Viagra and Foods all these different ways that we can boost and any other lifestyle things that we can do to help with no like sleep or making sure we're hydrated enough it can be anything anything else that we haven't talked about that can be something we can Implement that's natural those are great answers you know if I still had an active laboratory I'd invite you and come work in my lab uh those are great questions and that's what I always talk

about you know hydration rest and electrolytes you know it's all common sense stuff it's it's all what's good for the athlete you know it's really interesting how what's good for the athlete is good for everybody in terms of longevity and I always say the answer the reason for that is nitric oxide you know why not but getting getting a lot of rest spending a significant amount of your sleeping time in in rem rapid ey movement sleep is important because when you rest uh you you you're not you you're you're you're calming down your body you're

producing much less oxidative stress you you you quiet down the enzymes that make free radicals and other things that destroy nitric oxide so getting rest is is very good hydration probably is the single most important thing because you know we live on a planet and we all of our animals and plants thrive on water water H2O water the chemistry of water is a beautiful subject which I'm not going to talk about but it it's just we get everything from water you have to have ample amounts of water for your cells to function properly water is

required for no production is required for everything so hydration sleep and electrolytes water alone is not as good as water with the proper balance of of sodium and pottassium and chloride you know electrolytes because the electrolyte balance is what really controls how cells communicate with one another and simple electrolytes you know there's a hundred of them in the supermarket they're all good they're all good you know you could drink any one of them and and uh you know if you sweat a lot and to pre to replenish your electrolytes you mentioned earlier consuming a greasy

hamburger and how that deete I know anything specifically you're seeing that we're doing here in the 21st century on a regular basis that's just crushing our n production well we could get into some real political discussions here uh I think that yes I think that the food that is advertised that is given to our children to eat you know and I don't want to get into that makes me cry actually brings tears to my eyes because you know most of the parents most people Jesse don't understand good food from bad food you know they figure

if they go to a store an outlet a fast food store and they buy something in a taste good it's probably not going to hurt them you know I I don't know how to I don't know how to teach those people but anyway I I think that in general what we have our children eat is is not good it's great when parents when they can cook at home make food at home and the children eat that I think that would be good that's one thing the other thing of course in in my view is the

environment which is getting better I'm talking about the poisonous gases in the environment due to Industry I'm not talking about carbon dioxide emissions that's a a different problem in itself but I think that the quality of the air has improved fairly dramatically in the US also Europe probably not in Asia but um that's also important to you know to to keep in in mind we're having a lot of electric cars my God I get on my bike and I'm afraid to ride cuz I don't hear cars anymore they're all buzzing by because of the electric

sound which is great for the environment and keeps your lungs clean of course uh so I see great improvements um there but I think we need to focus on two things one we need to have everybody somehow eat a healthier and balanced diet and number two we have to really get the American people to to engage in more physical activity I walk outside and I it's incredible how many obese people I see and in the last 10 or 15 years they're not just obese Jesse they're Mo morbidly obese why why don't they understand this I

I'm trying so hard to to make my points but it's rough you know it's rough all right let's get practical for somebody that's tuned into this point they're headed to the grocery store they're going to start loading their cart with with a lot of the leafy greens some beets try and get their nitrate level up but then they get to the meat area and they go and grab their bacon and they see nitrate nitrate free and then they're really confused they're supposed to be getting these through their produce but yet their bacon and their meats

are advertising that they're free of these so let's talk about what's going on there well first I tell people turn off your TV and stop watching advertising cuz we're being misinformed I know in today's time that's probably not a surprise but you know I think one of the greatest myths that's ever been perpetuated there's two in the medical Sciences the first one is cholesterol causes heart disease the greatest myth that's ever been perpetuated in the medical Sciences cholesterol doesn't cause heart disease the other one which is near and dear to my heart is that n

tried and cured and processed Meats causes cancer I mean it's completely myth that's been perpetuated now for 50 or 60 years so why is that well years ago they found in the 1950s it was first reported that nitrite cured fish when consumed was causing an increased risk of certain cancers liver cancers gestro certain stomach cancer so this is what we call an association right this is nutritional epidemiology where you take populations who are eating certain amounts of these Foods looking at outcomes years later an association but not causation now to establish causation you've got to

have a biologically plausible mechanism to tie that observation to the increased risk of cancer so in the 60s and 70s they they came up with this thought that nitrite can form nitrosamines nitrosamines can intercalate DNA cause mutations and cause cancer so now the story was complete nitrite cures meat causes nitroamine formation nitramines cause cancer well now their story falls apart because in 2000 the U the national toxicology program of the US government did a dose escalation study to try to answer that question does nitride cause cancer what they found was through dose escalation studies and

mice rats and rabbits found there was no evidence of cancer-causing activity by nitrite in any animal and any cancers in fact at some doses it was anti-cancer so now you start to think well we know that vegetables a plant-based diet vegetarian diet lower incidence of cancers right if nitrate and nitrite cause cancer vegetarians the Japanese Mediterraneans would have about a 100 times higher cancer rate than meat eaters but we know it's just the opposite so nitride and nitrate does not cause cancer and I've I've consulted for companies like craft Oscar Meer these meat companies and

I tell them look you you have to get away from advertising no nitrite no nitrate added cured meat because nitrites absolutely essential for food safety if your sausage and bacon and hot dogs didn't have nitrite it would be an epidemic of foodborn uh illnesses and deaths from ecoli bolism salmonella nitrite is the only thing that preserves the antimicrobial activity of ready to eat Foods uh and so now in the 197 the code of Federal Regulation Chang it says if you're adding nitrate to any cured and processed meat product you have to add a certain amount

of ascorbic acid arrate and today they use arrate right so that prevents any nitrosative chemistry and we actually measured this we published this in 2009 and we took regular nitrate cured bacon and then we took no nitrite added bacon and we brought it to the lab we Quantified the NIT in it and we found that the no nitrite added bacon had five times higher nitrite in it than the conventionally nitri cured bacon so it's really consumer deception because what these meat companies are doing is they're adding vegetable powder which is a source of nitrate then

they add a starter culture of bacteria called staff carnosus and these bacteria convert the nitrate to nitrite on the surface of the meat and then the nitrite cures the meat so they're not adding sodium nitrate directly to the meat they're adding celery salt or or different powders then putting bacteria on it to to form nitrite to cure the meat and what does that mean well it's a variable yield so the the food quality the shelf life of these organically cured products are less um the quality of these products are much less and there's very little

residual nitrite even in conventionally gr eventually cured nitrite added Meats so I tell people don't spend an extra $2 to3 a pound to buy no nitrite no nitrate added meat go and buy it you shouldn't be afraid of it in fact I tell the meat companies used to say supplemented or fortified with nitrate or nitrate because you need that we know it's an essential indispensable nutrient needed for human physiology all right so there's a lot there the fact that when you're buying nitrate free you've in your lab tested and the actual nitrate free had higher

levels because of this celery powder or celery juice and the conversion with the bacteria okay but underneath all of this is the fact that you're saying it doesn't matter it actually be potentially in our advantage to fortify with these well you got to ask yourself yeah that's exactly right so the use of nitrate salts dates back thousands of years excuse me long before refrigeration and these early settlers had to preserve meat so if they went and killed a buffalo or a deer or some animal there was no Refrigeration so how do they preserve that carcass

that's going to get them through the winter how do they do that well thousands of years ago it was discovered that if they use sea salt and to preserve that then it created this cured meat color and so what it was it was was called salt peter pottassium nitrate that was naturally found in sea salt that when the bacteria on that would convert the nitrate to nitrite so this goes this chemistry goes back thousands of years and so and I guess the early 19th century and and later turn of the century it was realized that

the mechanism for this was nitrite being reduced in a low oxygen environment to nitric oxide nitric oxide binds to the iron of myoglobin in the muscle and that forms the nice pink nitril hemochrome pigment and that's the pink color you and all cured meat but it's not just the antimicrobial activity nitrite also inhibits lipid oxidation you know lipid oxidation in humans causes a lot of oxidative stress and disrupts membranes and causes oxidation of fats and membranes nitrite prevents lipid oxidation so that's an essential anti-inflammatory molecule in human physiology so the chemistry of meat curing by

nitrite basically is the exact same in what we would hope to get and kind of curing the own human body of chronic disease so nitrite is absolutely a cure it's a cure for uh for Meats to prevent foodborn pathogen to prevent lipid oxidation and the rancidity and warmed over flavors but it's also a cure in human physiology for curing conditions of nitric oxide deficiency which is heart attack stroke vascular diena and diabetes so that's what we focused on for the past 20 years is how do we provide a treatment a therapeutic a safe and effective

nitric oxide technology that can overcome a lot of these poorly managed diseases so when it comes to the nitrate in conventional meats are they getting that from sea salt and from plants or what are they doing to to get that and add it to the product well in conventionally cured meat products like your normal hot dogs bacon sausage ready to eat uh meat they're adding sodium nitrate so it's just a salt it's a white salt they add it there's restrictions and there's regulations on what type of product how much you have to add to get

an efficient cure and antimicrobial activity for the organ organically cured or no nitrite added cure they're adding it's primarily the industry standard is Cel salt so Cel is a high source of nitrate you sprinkle that as a brine then you add the starter culture the bacteria the bacteria reduce the nitrate to nitrite and that's where you're getting the Cure but in even in you know uncured meat like if you take a steak for example that's uncured unprocessed just call it a ribeye and we grind that up there's still nitride and nitrate in that muscle and

why is that well that cow was once eating grass green grass right that green grass has nitrate in it and cows are ruminants with several stomachs so now they've got a diverse microbiome that's reducing that nitrate into nitride and nitrix o side and it's actually assimilated into the muscle so now when we eat the fresh meat from that cow whether it's hamburger meat or a steak we're getting a source of nitride and nitrate because of what that cow ate grass cows are vegetarians I just happen to eat vegetarians the cow I'm a meat eater right

which brings me to my next question because there's so much popularity these days in the carnivore diet and only eating meat how much of a significant Source would beef be of nitrates and nitrites it's it's not a significant source so I I I think you know I'm not a big fan of either of these extreme diets like a hardcore carnivore or hardcore plant-based I think we get our nutrients from a a balance of food in moderation from a diverse food population I think that's how we evolved and I think that's what's going to give us

the most nutrients we get so when we quantify this and we've actually done this because we wanted to see if if doing a straight carnivore diet for a period of months or years is this going to cause problems in terms of vascular compliance in nitric oxide production and the data tell us that you're really not getting enough nitrate from eating a strict carnivore diet because there's so little in the muscle itself uh that we need the vegetables we need the plants to fuel this pathway and so I think that's why it's important that we eat

a balanced diet in moderation throw in some green leafy vegetables um you know get we need B vitamins and iron and a lot of the micronutrients found in in animal proteins and animal meats that we're not getting from plants and we need the nutrients in plants that we're not getting from from animal proteins and meats so I think I think we need a balance and if you're not if you're not doing that then I think it's you know you should do a micronutrient analysis to figure out what is what's your body missing and then supplement

that nutrient and that's personalized nutrition which this naturally takes us to plant toxins so people on a carnivore diet typically talk about plant toxins wanting to avoid things like ftic acid and lectins and oxalates and we can take the oxalate piece there and expand upon that say somebody's using spinach to get their dark leafy greens to get their nitrates they're going to be getting a a big headit of oxalates at the same time so what would you say to that person well you know some people are sensitive to it and some people aren't obviously if

you're sensitive to oxalates you're prone for kidney stones Gull Stones things like that so everybody's different um and so we have to that's why I think it's impossible to kind of ascribe a one siiz spitsa for everybody you know I think there's some truth in you know blood types and in requiring certain nutrients certain dietary patterns from based on your blood type I think it's dependent upon the gut microbiome some people are sensitive and can't digest things because they have gut dysbiosis so we have to fix the gut and then now they become less sensitive

to to different foods or food allergies but the again the body is really resilient in the fact that if you give the body what it needs the body's going to perform for you but if you're sensitive to certain things then obviously that's a sense and a sign your body your body telling you hey this really doesn't agree with me so let's let's avoid that as you talk about the blood type there gets me thinking about genetics as a whole and this to me would apply more to the first pathway the endothelium how much variance do

you see between different people and how good they are at making NL we know the whole feel when I took genetics as a um sophomore at University of Texas when I was an undergrad that genetics course is completely ant inqu equated to what how we know genetics today so the genetics I learned is completely different than the genetics today and you can no longer blame your disease or your condition on genetics because now this whole field of epigenetics of how we regulate and turn genes on and turn genes off is what controls the day uh

and we know certain foods can be epigenetic drivers and turn certain pathways on expression of downregulate certain proteins up regulate other proteins and it's the nutrients from the diet that control the epigenetic regulation of protein expression so let's take for example and there's all types of different genetic Snips or what's called single nucleotide polymorphisms and so those are just um errors in the genetic code of the sequencing to transcribe and translate that protein so the most obvious or if you've got a snip in your Enos or any of the NOS enzymes then probably that enzyme

even if it's expressed and and made into functional protein it's not going to have optimal activity right because there's a there's a problem in the there's an error in the sequence of that the DNA sequence the amino acid sequence the other problem is MTHFR what we call the methyl tetrahydrofolate reduct that snip is you depending on which reports you read 45 to 55% of the US population so if you have an MTHFR snip then you're by definition nitric oxide deficient because that enzyme is what converts biopterin to tetrahydropterin that's the rate limiting step in nitric

oxide production through the enzyme so mtfr you have an uncoupled NOS you can't make nitric oxide so now you're dependent upon the nitrate pathway because you have severe endial dysfunction all right so where that comes into play is genetic wise like you just talked about and then also aging the good thing about this is we know there are two Pathways and not that you should be neglectful of pathway 2 till you get older but when you do get older if you do have a genetic you know predisposition luckily we can make up for it or

at least largely so with the second pathway yeah you know the there's enormous redundancy in the human body and it didn't make any sense to me that if nitric oxide is so important and critical in everything we read in the science and observe in clinical medicine then why would the body develop a single Pathway to make nitric oxide and then this pathway becomes dysfunctional over time and so I think the way the human body is designed is one can compensate for the other there's a balance of these but if you develop ineal dysfunction then you

become relying upon the dietary pathway if you have good enthal function then you can get away with eating a poor diet and I think I look at kids you know I have young kids 15 and and 12 now and they you know even when I was young I didn't eat a very health healthy diet but yet I was in great shape I was Physically Active I wasn't overweight and I was an athlete so why is that well it's because my endothelial function was good and I could get away from not getting nitric oxide from my

vegetables but now the older I get I realize that now I've got to compensate some I need to throw in some more green leafy vegetables and fill this pathway because you know if I do some bad things and I go out and you know eat an inflammatory meal or I've been traveling a lot and exposed to a lot of toxins then my endothelial function goes down and I've got a compensate over here but I think if we can maintain good inthalo production from our diet then we're truly optimized humans and I think that's what defines

you know human optimization and whether that's you know Improvement in longevity longer lifespan better quality of life better performance in the boardroom the bedroom or on the athletic field I mean for me it's about human optimization let's get into the performance enhancing benefit of n we can this can come from you know a drug it could come from eating the right Foods exercise uh supplements it doesn't matter really let's talk about how that's going to enhance performance you mentioned weightlifters and endurance athletes so a couple of different ends of the spectrum there we know that

n o helps dilate the vessels obviously it's going to increase blood flow throughout the body but I'll have you take it from there and run talk about specifically how taking NL increasing I know will say is going to enhance performance okay sure sure well this comes from several different sources one uh understanding the physiology and pharmacology of nitric oxide but also the laboratory animal experiments that have been done and published and also there's nothing like speaking to humans who actually do this so if you take we don't have to get into what kind of supplement

it is you know but whatever it is that boost Nitro oxide how does that improve Sports Performance and endurance and you've touched on that but but before I do that I have to tell you what the physiology is so when a person begins to exercise of course there's an increase in your heart rate your force of contraction the cardiac output the amount of blood that's pumped out of the heart into your arteries increases of course that increased blood flow very importantly stimulates the inside lining of your arteries to make more nitric oxide that's been known

for a long time I didn't make that Discovery other people did so if you're exercising let's take running for example you're running okay you got this increase in blood flow through the arteries of your legs and also your arms you get more nitric oxide production a lot more from the endothelial cells that no immediately dilates the arteries more and more and more to allow more blood to flow through the skeletal muscle why is that important because blood contains oxygen blood contains all the nutrients but even just as importantly and what I've heard back from the

testimonials of thousands of athletes is that if you take these supplements that increase no what these athletes um notice is that once they're done running a few hours later the next morning they no longer feel the tremendous pains in their uh in their muscles in their calves in their uh uh glutes and so on because the nitric oxide when it increases blood flow not only brings in more nutrients but remember it brings out the waste products that are made by the muscle like lactic acid and other acids that are that are cause pain to build

up it may cause knotting of your muscle tightness of the muscle and so on so uh every Runner of course should massage afterwards but also continue to take the supplements and and from what I've heard and it makes a lot of sense uh you have much less of this kind of pain when you're doing this and I think that's why so many people who engage in uh sports or just running swimming whatever like to take take these um these supplements I mean I've been taking them for for a long long time I still bicycle I'm

80 years old but I still bicycle outside I bicycle inside I have a nice bike hooked up to a computer and I could climb the hills and so on but in my water bottle I I have lots of these supplements and what I found is they do everything for me except one thing uh I could tell you that nitric oxide does not help to grow hair it's the one thing it does not do let's let's make sure I have this correct then so when we're boosting n we're going to have a benefit Jour performance so

we're going to have increased blood flow to the skeletal muscles the active muscles during that performance and then we can also have a benefit later on with a quicker recovery yes yes absolutely yeah no question about that so is this pretty well-known knowledge among athletes among the elite athletes these days like people in the Olympics is are they considering it know and is this part of their protocol to make sure that's boosted you know during training during the actual events themselves you know it's hard to get a lot of information I certainly can't get them

from the people who participate in the U Olympics I can get a little bit of information from individuals who uh are pro cyclists or or almost Pro cyclists and they certainly take some of these supplements the key thing in professional sports is that whatever they put in their mouth is strongly regulated and controlled by whoever runs the team okay when we first developed these products a couple of friends and I we went to UCLA we went to USC UC San Diego and all we wanted was for the team to try to take the supplements before

a football game or basketball game and see if it makes a difference and you know we could never get them uh to do that they wanted to see the hard evidence first and they want they don't want to harm their players you know they don't understand the science right they they're not scientists they they don't get it uh and it was always difficult to do it so only the individual people or groups of people uh who tried it found it to work I could get all my friends in the gym to do it and and

the ones who who do free weights like I said they can't live without it anymore because because taking these supplements gave them a lot more energy in in in performing the weightlifting of various types but but most importantly they didn't suffer from the pain in their leg muscles or arm muscles when they stopped so I I I have tried to figure out ways where I could you you know why can't I get just just get on TV and have a program and talk about this and you don't have to pay me for anything I you

know I have plenty of money I don't need any more money I don't want to make any more money on on supplements I just want the world to realize how important nitric oxide is not just in athletic performance but also in increasing your longevity protecting you against cardiovascular disease you know it's hard to do it that's why I appreciate being on shows like this where where I can say something somebody will listen pass it on to something somebody else and then maybe a few more people will benefit that's what I was going to say this

can be the show exactly and I'm happy to continually do it I want to highlight something you said there there's two different ways of boosting well of producing we'll say n o we talked about you know taking certain supplements or boosting that exogenously during performance but then you you also mentioned too that inherently when we you know take part in say you know a running activity or cycling that's going to increase blood flow stimulate the endothelial and endogenously produce n so there's the two different parts working there together they're two different parts and when you

take the supplement though Jesse when you take the supplement you're fueling the system remember I said that nitric oxide is produced from Arginine and citrine in the endothelial cells well so so the body is going to automatically make it right but eventually you could deplete those amino acids so if you if you eat a healthy diet and if you eat the right things uh uh and take Arginine supplements before you exercise then you're providing more fuel to be sure that the endothelial cells have enough Ardine to make all that no that you need yes you

body does make it from Arginine but you could give the cells more Arginine and they'll take up a lot of arginine up to a certain point then they won't take any more up but it's good to keep that saturated why not all right we're going to move into step three so for somebody that's lucky enough to get by step one and two taking in nitrates they have the bacteria in their mouth they haven't killed that so now they have nitrite which they're going to swallow and go into the stomach we need an acidic environment to

take the nitrite and form nitric oxide you mention the an acids and how that's a problem and and I'd like you to get further into that to start and then we'll talk about other things to do with the gut So biochemically speaking nitr so nitrate to nitrite is a two electron reduction and then nitrite to nitric oxide is just one electron so as a biochemist we count electrons so we have to we have to balance equations when we when we do this chemistry so the pka of nitrite meaning the the the pH in which nitrite

becomes proteinated to generate nitric oxide is 3.4 and that means that a pH 3.4 50% of the nitrite that we swallow is going to generate nitric oxide gas the lower the ph the greater the efficiency of protonation and conversion to nitric oxide so when we do that again the nitrite becomes nitric oxide we can detect it in the lumid of the stomach it kills bacterium kills H pylori the ultra causing bacteria enhances gastric mucosal blood flow so now you've enhanced the blood flow to the stomach so you can absorb nutrients like magnesium iron iodine chromium

B vitamins so it it's facilitating this fundamental physiological response to to nutrient absorption if you can't make stomach acid because you have ayria for whatever reason or you're using an an acid now you shut down stomach acid production you eliminate the nitric oxide benefits of swallowing your own saliva so now you can get overgrowth of bacteria H pyora you can develop gastric ulcers you become nutrient deficient without sufficient stomach acid you can't absorb iron you become anemic you can't absorb B vitamins you can't absorb zinc chromium selenium a lot of these trace minerals and nutrients

but more importantly again you shut down nitric oxide production from the disproportionation of nitrite to no but in 2013 4 there was a paper published that these an acids specifically what's called proton pump inhibitors things like osol pentool they actually inhibit nitric oxide being produced from the enzyme nitric oxide synthes so these drugs PPI specifically are shutting down both nitric oxide production Pathways and people who take these drugs are completely devoid of nitric oxide now the consequences of that are are apparent now in 2015 it was reported that people who have been on ppis for

3 to 5 years had a 40% higher incidence of heart attack and stroke not risk of heart attack and stroke actual heart attack and strokes and then just last week a report came out showing that people who have been on ppis for four years had a 35% increase in Dementia in Alzheimer's so I mean to me this is like the most Awakening you know kind of Eureka moment in in terms of pharmacology these are very dangerous drugs in fact they were never approved by the FDA to be used chronically the FDA approval on this years

ago was for acute use for gastroids Sagal reflux disease or acid reflux use them 3 to 5 days and then get rid of them never use them again unless you have another acute flare it but yet people are using these every day for 10 15 20 years and the consequences heart attack stroke Alzheimer's everything is on the rise so you have to get rid of stomach acid or you have to get rid of an acids and so that's just the nitric oxide consideration the other problem with an acids is it prevents the breakdowns of proteins

into amino acids it's part of our normal digestion process the human stomach is designed to make stomach acid hydrochloric acid to break down proteins into amino acids without stomach acid you don't get breakdown of protein so what happens you have undigested food partic undigested proteins or what we call peptides that are emptied into the gut they transport across the gut you get leaky gut syndrome now your body sees these foreign peptides as an Invader now you're developing antibodies against these peptides and that's the basis for foodborn allergies you know when I was a kid we

didn't have peanut allergies milk allergies all these allergies that kids in school today have and I think it can be traced back to the use of an acids as a kid because you can't break down milk proteins into amino acids you can't break down any protein to amino acids you develop a foodborn allergy and it's the basis for autoimmunity these are very dangerous drugs and should never be prescribed it should be taken off the market over the counter the evidence is very clear now that this data is becoming public what you just talked about there

a couple different studies do you find in the medical world doctors are hearing this and changing the way they prescribe you know it's very difficult to treat to teach an old dog new tricks especially Physicians right because a lot of them think they already know everything so how can you teach me something new uh but some are receptive you know some are very keen on keeping up with the published literature and understanding the advancement of Science and the translation into clinical medicine but here's what's I mean to me it's so obvious looking from the outside

looking in because if you look back kind of from 50,000 foot View and just look at the observations these class of drugs are causing heart attack strokes and Alzheimer okay so that's that's an interesting observation and it's Association right but it's not causation but now we work backwards and figure out mechanistically exactly what's causing the increased risk of heart attack stroke and vasular dimension and Alzheimer's it's because it's shutting down nitric oxide production so now we have a biologically plausible mechanism for the interesting observations on a global population perspective and so now we know mechanistically

that there is causation you shut down stomach acid production you shut down nitric oxide production this causes increase in heart attack and stroke causes decrease in blood flow to the brain you get mild cogni disorders vast demential Alzheimer's you develop metabolic disease so now what do you do number one you have to stop but number two you have to restore the production of nitric oxide and that's kind of how we're trying to integrate this because some people it's very difficult to get off an acids because they've been so dependent upon them for many years so

then how do we address those patients and basically mitigate the risk of them having a heart attack or stroke or developing Alzheimer's when you look at all the people taking these drugs what is that the root of that for somebody that wants to get off of them and get to the root of that issue how do they begin well the problem with Physicians today is they don't have time to to seek the root cause of why the patient's presenting with certain clinical presentation right and so it's just easy if you if you got a patient

that comes to your office and says hey Doc I've got acid reflux well you know for 40 years he written a prescription for an acid so it's easy they're in and out of the office in 5 minutes you get reimbursed for your time and it's a it's an economic model but it's certainly not a a viable physiological model so what I tell people is you have to understand how the human body works so the human body is designed to make stomach acid and so what then you got to ask yourself can Ally how do the

pyal cells convert the how does it create hydrochloric acid in the Lumin of the stomach well that that reaction is very well elucidated you need zinc you need sodium bicarb um you need B vitamins and you need iodine but yet if you can't make stomach acid because you've been on acids for a number of years you're deficient in B vitamins you're deficient in zinc and your deficient iodine so now when you get off these an acids your body doesn't have what it needs for the pryal cells to make hydrochloric acid so you're G to make

you're going to remain acid deficient so I tell people you got to supplement with iodine 12 and half milligrams a day 15 milligrams of zinc salt B vitamins and now you given your body what it needs it has the raw material to make hydrochloric acid in the prial cells now you can make stomach acid you can digest proteins into amino acids you can generate nitric oxide and your acid reflux goes away acid reflux is a is a symptom of insufficient stomach acid production so giving a substance that inhibits further inhibits stomach acid production is counterintuitive

and I think the consequences of that over the past 40 years have been revealed it's not the way to eliminate acid reflux and it's causing more harm and providing zero benefit so this takes time right so what I tell people acutely and number one I think it's a very important point you can't just stop these drugs called Turkey right because you're going to get a rebound of acid production so what what I tell people is you have to wean off so whatever you're taking if you've been taken on a daily basis cut the dose in

half take half a dose for three or four days then take that half a dose every other day for three or four days and then you can stop those drugs but you have to slowly wean off titrate the dose down and then during that process before every meal just take a tablespoon of apple cider vinegar apple cider vinegar vinegar is acetic acid so it's going to acidify the Lumen of the stomach so if your body body can't make stomach acid we're going to deliver acid directly into the alumin of the stomach now you acidify that

Medium you absorb nutrients you break down proteins into amino acids and you don't get acid reflux very simple how do you feel about supplements like HCL and taking digestive enzymes now look I think they're very important and there's a place for those because um you know we need these enzymes and we need to give the body what it needs to break down proteins fats and carbohydrates right and then the bacteria in our gut you know use small chain U amino acids and and berate and and fatty acids uh so we got to feed the microbiome

but we give our body what it needs in terms of amino acids from proteins um carbohydrates and then break down fat so if if our body's deficient in these digestive enzymes in fact I take digestive enzymes typically after every meal especially when I travel because it's not always we don't always eat healthy when we're traveling so we got to give our body all the heal it can get and then yeah HCL Bane hydrochloride I'm a big fan of those because we need to acidify the Lumen of the stomach it's the basis of all digestion and

nutrient assimilation and nutrient absorption okay so taking our story here even further we have the nitrite getting to the stomach assuming there's proper acid there it's going to turn into the nitric oxide what happens to it there because I know the molecule of nitric oxide it doesn't last very long so what I'm picturing it either in the endothelium coming back to our first example how it can be made or it's now in the stomach how do we have a systemic effect that's a very good question I let's go back to the start of this because

when the very first question is what is nitric oxide and maybe I I didn't State this but it's a gas and once it's produced it's gone in less than a second so now you can imagine what's how does this gas this fleeting gas that want to produce this gone in less than a second does it control and regulate so many fundamental physiological processes and it does this to several ways number one it's a gas that fely freely diffuses across cell membranes right so it can diffuse several millimeters in a tissue so it can immediately be

absorbed into the bloodstream it binds to the red blood cell hemoglobin and our red blood cells and so it's transported bound to hemoglobin and in our red blood cells it's oxidized back to nitrite the nitrite is vasoactive in the circul but it also binds to glutathione and glutathione is our Master antioxidant hormone and so that's a tripeptide three amino acids one of them being cysteine which is a sulfur containing amino acid so no binds to the sulfur of glutathione and then it transports and it extends the biological Half-Life from 1 millisecond out to tens of

minutes and hours so now we have a hierarchy of these nitric oxide vasoactive nitric oxide metabolites that are distributed throughout the whole body but again this is dependent upon sufficient nitric oxide production sufficient available fils kind of redox active files and the ability of hemoglobin in the red blood cell to latch onto that nitric oxide and then transport it and that's what oxygenates individual cells and tissues of the body in O bound to hemoglobin okay to make sure I understand this correctly then very quickly this gas is going to disappear but if it has secondary

effects then it can stick around in the body for longer yeah these are called second messengers right so nitric oxide is kind of the primary signaling molecule and then it activates and forms these other kind of chemical adexs right so the first pathway with Ino binds to an enzyme called gual cyas produces cyclic GMP cyclic GMP is a second messenger that's dependent upon nitric oxide production s nitrosoglutathione is a second messenger that's dependent upon nitric oxide production Ino bound to hemoglobin in the red blood cell is a second passenger and transport mechanism for bioactive nitric

oxide gas so it preserves the Vaso activity it prevents it from being gone in less than a second got it and how does glutathione fit in again nitric oxide can bind to the the s for the cysteine residue of glutathione and then this tripeptide actually delivers nitric oxide systemically and so it's certain kind of what we call Redux potential at certain so Redux potential is an electrical potential at which an electron can be abstracted from a biomolecule and it's that redo reduction oxidation potential that allows for nitric oxide to come off at the right time

in the right place from glutathione and then it can dilate the blood vessels it can activate soluble gomate cyclace and all these other second messages and I believe you said for hours once some of these reactions have occurred it can stick around in the body what is the timeline again how far into the future can NL have an effect well there's there's different what we call biological half-lies of different nitric oxide metabolites one when nitride reacts when nitric oxide reacts with oxygen it forms nitrite so just like the nitrite formed in our saliva when no

is formed and Oxygen's around it reforms nitrite then if you just Infuse nitrite intravenously you get a half life of this molecule of about 110 minutes 2 hours and a half life means that after 2 hours 50% of that nitrite is gone and then after another 2 hours another 50% is gone or 75% is gone so usually five or six Half Lives tell us that that what you initially gave is like 99% gone so 5 to six half lives would be 10 to 12 hours for nitrite for osal glutathione it's it's probably a little bit

longer maybe two to three hour half lifee and then no o bound to hemoglobin it's the absolute essential kind of mechanism for tissue oxygenation uh and it's what controls nitric oxide delivery from the arterials all the way to the Venus side so when when the red blood cell goes from the arteries to the vein through the capillaries it's what we call this p50 where oxygen comes off you pick up carbon dioxide but this process doesn't occur without nitric oxide so for that Ino bound to hemoglobin the respiratory cycle you know probably you one minute or

so each time the blood circulates uh you know basically getting six lers per minute pumped through the heart which is full full blood body volume so Ino bound to hemoglobin is probably about a minute half life let's talk about the story of finding out you won the Nobel Prize you talk about this in your book you were about to board a flight you got a call from a friend and you know at that time you weren't expecting this it was it was you know a thought I'm sure had crossed your mind a number of times

that you know it could happen but you weren't expecting it so tell the story of getting that phone call and finding out you had won this this achievement after you know dedicating your life to uncovering and and studying this molecule n know for for at least 10 years preceding the announcement of the prize many of my colleagues research colleagues would always come up to me and say Lou you know you you're going to win the Nobel Prize some day don't worry you know just keep up this work and I would always say I'm not worried

and please don't keep telling me that you're creating a lot of pressure I'm not interested in the prize right now I just want to keep my job you know I just want to do a good job and keep my job and so that went on for years okay so in 98 in October I got invited uh by my friends in Italy uh to go to Naples uh to give a lecture okay now I had no idea the Nobel Prize was going to be announced that time I mean I I didn't follow these things I learned

later that the Nobel prizes are announced in the first or second week in October every year but I didn't know it then it was midterm break at UCLA teaching the medical students so I went to um Naples and Naples by the way is where uh my father was born he died many years prior to the Nobel but uh it's ironic that that that he was born in Naes so on the way to Naples I went to nce France first because I was uh a consultant for a drug company in the south of France and who

would turn down that opportunity you know so I went there and um fine I'm walking around getting ready to take my car to the airport and the day felt great I felt I don't know something in the air just just felt great and of course the beaches of n are always very nice so I get on the plane I get to the airport and I'm online I'm on the Queue ready to get on plane and an airport attendant makes an announcement and says that is there a do ignarro here is there a doctor inaro here

you have an important phone call so I say it's me I'm here she gives me the phone and she says uh uh here you have a phone call but make it quick because we have to board the flight so one of my friends from UCLA had called me and the phone was breaking up a lot that was the early days of the cell phone remember 19 98 and the last words I heard him say was you know have you heard the news and I said what news he said uh you won the Nobel Prize and

right after that no sound the lady Yanks the phone away from me I get on the plane it's a 45 minute flight from n to Naples I didn't know what was going on the flight felt like it was four days not 45 minutes and finally we get to Naples and I get up with my luggage I'm getting off the plane and I look down and I see literally hundreds of people in the tarmac right below the steps where you walk off the plane and and everybody was had a a camera and they were you could

see the flashes going off and I thought immediately that the president of Italy must be on this plane because why else would be so many people be taking photographs I looked around I didn't see anyone I got to the bottom him and uh my friend his nickname is pipo uh he's the one who invited me give to give a lecture at the University uh in Naples he showed me the press release from The kolinska Institute where the Nobel prizes are announced but it was written in Swedish however I see this big word on top and

it starts off n o b l and then a bunch of letters and I didn't understand and then my eyes drifted downward and I saw my name and then I realized that I was awarded the Nobel Prize so after a few people picked me up off the ground they walked me into the uh into the terminal I met the uh the mayor of the city the governor of the region and they wished me away in a limo and needless to say my hotel was upgraded so that was good he talked about being picked step off

the ground by people that were you know there taking pictures and taking in the whole scene talk about the feeling of finding out you have that confirmation again you've put your whole life into this and you get the greatest achievement in your field what does that feel like talk about because this is something 99.999% of us will never experienced talk about what that must have felt like in that moment well it felt incredible I mean it felt like a current of electricity you know going through your body you because you know what you get is

you get a tremendous Adrenaline Rush okay adrenaline or epinephrine is released from certain glands and when that gets into your body it it's almost like an electric current so you all of a sudden you're wide awake I mean I've never taken cocaine but I would from what my friends say you know it was like a a big snort of cocaine and in fact I was wide awake for 3 days I couldn't go to sleep but the the joy of hearing that was fantastic and then and then literally within a minute or so you you you're

you're thinking you know why did you get the Nobel Prize and then of course I realized of course all the work I did and thank God that somebody recognized the importance of this work and now I don't have to go and listen to all of my friends tell me don't worry you're going to get The Nobel Prize one day because it already happen but it's it's an incredible amount of gratitude you know there's no instant gratification when you do basic research basic research is very slow the results are slow to come in it takes years

and years sometimes before you can appreciate or somebody else can appreciate what you've accomplished so it's very very slow gratification but once that announcement of the Nobel Prize is made it's instant gratification ation and it comes all at one time and I just can't can't believe I can't begin to tell you how gratifying it is because I really although I knew my work was pretty good I did not know for sure that I would be awarded this you know there are many many investigators do who do spectacular work who never get The Nobel Prize there's

only 250 people who have received the Nobel Prize in medicine since the first one in 1901 there's not many of us out there so you know I I was not sure so that's what made it all you know really fantastic once I once I got it and then what what was great about the Nobel Prize also is that literally within weeks uh I felt great I lost weight my my stomach pains went away no more ulcers I mean it was like a cure all well I was going to ask about that because there's two different

aspects to this how did life change on a personal level and professional and you're touching on the personal there a bit which I want to get a bit more into you talked about how you didn't have to worry about your friends giving you those jobs about when are you going to win the Nobel Prize CU you know you had done it but this was you know you still were a middle age guy at that time and you you done all this hard work and and you have this this award how did that change things for

you personally having that pressure off of you because you've already had that accomplishment it must have taken an immense amount of pressure off of you tremendous amount of pressure and it really changed my life uh my my life dramatically and perhaps in different ways than it has changed other Nobel laurates at the time I was awarded the prize I have a had a very active research laboratory at UCLA Med Medical School lots of uh NIH research grants I had more money than I knew what to do with I had plenty of people in the laboratory

um that was great and of course for a couple of years at least I continued to do that and I also thought well gee you know because of the Nobel Prize I could probably raise a lot more funds and maybe uh build or have built a cardiovascular research institute and on and on and so I started to consider these things but at the same time because of my getting the prize so many other opportunities came up uh I was invited to serve on a number of different um board of directors I was uh uh asked

to travel to so many different countries throughout Europe and Asia to serve on committees um and get paid for it you know by the way uh to work with pharmaceutical companies to give them ideas to develop drugs and then you know I would get compensated for that uh I had never traveled much before all of a sudden I found that twice a month I was traveling mainly to Italy which I like because that's where I first heard about the prize and several pharmaceutical companies got a hold of me there but I was traveling to to

to Italy I was traveling to Paris quite a bit uh to to Tokyo so many different cities in Europe and I was beginning to like that I was beginning to really enjoy that and doing other things I quickly realized I was not humanly capable of doing both that is I could not run my research program and build an Institute and continue to travel so I had long discussions with uh my wife Sharon who's an anesthesiologist and I said 'you know Sharon I think I'm going to try to build a research institute and she said are

you sure you want to do that that's going to take away all of your free time traveling here you know you won't be able to consult for uh uh pharmaceutical companies Cosmetics companies you won't be able to go to Paris and stay at the Ritz anymore I mean do you want to give all that up uh and and just stay here and do more research resarch and then she said well what more research you going to do that was the key then I started thinking what am I going to do there were lots of things

to do but I have to tell you that the important discoveries yet to make um you know I just didn't know how I was going to approach that so it would have been fun but I decided making a long story short I decided to tame down my work in the laboratory and over about a five or six year period I gradually let my research grants run out I helped my people get opportunities in other Laboratories and then I built up my extracurricular activities and uh began to work with other companies helping them you know develop

nutritional products or helping to improve a a healthy lifestyle working with pharmaceutical companies I almost took on the uh I strongly considered the position of uh directing being director at the uh FDA and also the NIH I was considering all these different activities because you see they were different they were different than what I had done all my life and you know I was happy to receive the recognition uh for making my discoveries and actually more important than than than receiving the recognition I was able to make these discoveries I mean my work led to

the understanding that healthy diet and physical activity promote longevity my work led to Viagra my work led to other cardiovascular drugs being developed so you know I was pleased and I guess I just wanted to go play around now and just travel and do things that were unrelated to my work that's the decision I made and I don't regret it I don't regret it retirement is a great thing let me tell you I'm happy to hear that it all worked out and we talked about how you know the discovery in the lab led to Viagra

on the other end of the spectrum you know once they have this physiology and they figur it out you know how to amp up n o have they been able to do something similar in the supplement realm so we have the drug but have we able to come up with something in the natural realm that that acts similar because I'll just add this to it coming back to we talked about in the food there's two components when we want to raise n we want to make sure we have the antioxidants and the amino acids so

I can see how mixing those together in some kind of concoction could be helpful yes well look you know you're right and that's true and you know before I continue I you know I have to declare I mean there may be a conflict of interest here but you know part of my my work uh in the past 15 years was to work with a u a nutrition company Herbal Life nutrition and help them design uh products that are well known to boost nitric oxide now having said that there are 25 other companies in the United

States that have the same products so I'm not talking about one particular company I'm talking about all of them and the progress that has been made is that and I I I mentioned it a little bit earlier if you consume a certain critical amount of arginine as an amino acid and also another amino acid which I could talk about called citrine if you consume those two together with a simple antioxidant like vitamin C which cost a penny a pound you know if you combine those and you take those every day there's no question that you

boost your nitric oxide production that's been determined in so many different ways sideways backwards and and so on and so yes you can do that the biggest problem in the field though however is these are nutritional supplements okay they are not prescription drugs I mean they're safe they're components of foods you could take a hundred times the dose recommended dose and you won't feel it because they're Foods they're not going to hurt you but the problem is that in order to make certain claims in the United States on products they have to go through clinical

trial okay so the products that I'm just talking about that have Arginine citrine and so on many people have given those mixtures to their friends and other people who have high blood pressure and those products lower the blood pressure they also improve blood flow anybody who's an athlete especially a runner or a weightlifter who takes those products knows how those products increase endurance in fact most of the people who buy these products are sports enthusiasts not people who are afraid to get a heart attack it's really fascinating I mean it really they really work but

you can't make those claims on any of the products because they have to go through clinical trial and when you have a small company that has a product that company does not have $50 million to have a clinical trial if they did I'm I'm sure that the data would would turn out you know to be positive there've been some small clinical trials published in Europe to show you know what I am saying so there's been a great attempt to uh um to to advertise and to show you know the consumer that these kinds of products

um do work and so now many of these products are sold without putting any of that information on the label but but the people the athletes and and and the other people who take the products understand how they work so it's not important so much anymore to put to put those labels on the products if you know what I mean as we're talking about supplements it gets me thinking back to something we mentioned earlier erectile dysfunction which when we hear that we all automatically think about Viagra and the blue pill what I'd like to do

is compare the physiology of somebody taking that versus one of your supplements do they act in a similar way in the body and is the Viagra just more powerful or decipher between the two now look everybody's familiar with with the blue pill and these drugs were approved in 1998 so they've been on the market for 25 years and these drugs are called phosphodiesterase Inhibitors so there's there's a misconception in Medicine by some really smart Physicians just understand the the mechanism of action but there there's a misconception that these drugs are nitric oxide donors these drugs

are not nitric oxide donors in fact they're dependent upon nitric oxide production so when I I mentioned earlier when we started this when Nitric oxide's produced it creates a second messenger called cyclic GMP and that cyclic GMP is what leads to the calcium dependent smooth muscle relaxation in blood vessel dilation and it's drugs like Viagra the phosphides Inhibitors that prevent the breakdown on of cyclic GMP so I tell people nitric oxide turns the switch on and then the Viagra keeps it on because it prevents the breakdown from cyclic GMP and that's the reason you're warned

against 4-Hour erections and unsafe drop in blood pressure that's why you're have all these side effects because now you've lost regulation you've turned the switch on but there's no off right you continuing to have the CYCC GMP around because you're preventing the breakdown but here's what we've also learned in 25 years 50% of the men that are prescribed Viagra or Calis or Levitra the three main uh branded drugs don't respond with better erections so why is that if you're given a phosphides inhibitor why don't they dilate the blood vessels and improve erectile dysfunction it's because

in these non-responders they're not able to make any nitric oxide to activate the second messenger CYCC GMP so now there's no substrate for these drugs to work on so what does that mean erectile function is a symptom of insufficient nitric oxide production and now if you fix their nitric oxide with our technology or something else now the non-responders to Viagra become responders and the responders you can actually titrate down the dose because they need less of the drug to optimize the effect because we're improving the underlying problem in these patients with Ed is we're improving

their nitric oxide production and now allowing the signal Cascade to do its job produce cycl GMP activate the enzymes dilate the blood vessels improve blood flow improve erectile function and then py GMP is broken down you gain regulation again and you don't have a 4our erection but you can perform and then recover and that's how the body is designed to work and I want to tie this back to what we said earlier the Ed is a canary and a coal mine and I'm sure for a lot of people that's what brings people into this world

and wanting Solutions but if you're having a problem in that realm it means you have a huge no issue Beyond Ed and use this as a warning sign to get to the bottom of this and prevent hopefully quote unquote more serious issues such as a heart attack or stroke look if you have endothal dysfunction in the vascular bed of the sex organ right that same that the conditions that allowed for endothelial dysfunction in the corpor cavernosum of the penis for example those conditions are going to cause endothelial dysfunction in the coronary arteries the endothelium in

the heart so if you have endothelial dysfunction in the sex organs you have endothal dysfunction in the coronary arteries you have endothal dysfunction in the cerebral arteries you have aneal dysfunction in the pulmonary arteries the liver the kidneys every organ in the body so it's just kind of socially inconvenient that you're not able to regulate blood flow to the sex organs upon demand but think about this if you can't regulate blood flow to the heart upon demand and dilate the blood vessels when you start to exercise you're going to get aium or angum because you

can't dilate the blood vessels and you're going to get chest pain occlusion of the blood vessels and heart attack or if it happens in the cerebral arteries you're going to get a stroke so this is really the canary and the co mine and it should be a warning signal for people that have erectile dysfunction that hey this isn't just a sexual problem this isn't just a testosterone problem or an estrogen problem and women this is a vascular problem insufficient nitric oxide production and it's systemic it manifest in the sex organs first but you have systemic

disease and it's called nitric oxide deficiency you mentioned there the fact that it affects the sexual organs first how long does that take when somebody has Ed is this they've been having issues with nol for years or do they catch it really quickly with that symptom we know the sex organs are pretty dynamic in the fact that you have to respond with an increase in inv Vaso dilation to a larger degree I mean probably I mean the cor arteries are probably the most responsive because the only way to increase oxygen delivery to the heart increase

the metabolic demands on the heart when exercising is through vasil dilation in the heart there's already 100% maximum oxygen extraction through normal blood flow so to increase oxygen utilization and oxygen delivery you got to dilate the blood vessels in the sex organs you know they're number of things that control Vaso activity you know you have hormone regulation um if you have low testosterone obviously you're going to have some degree of erectile dysfunction but you can have optimal testosterone decreased nitric oxide production and you're never going to get an optimal erection so what we're finding is

that there's a it's a spectrum right it's not just like a switch where one day you have good erectile function the next day you have full-blown Ed it's a spectrum so you start to develop slide erectile dysfunction slide indal dysfunction if not corrected and you're not changing your habits and improving your endothelial function then it's just going to continue to get worse one day you wake up and you're not going to be able to get an erection and that's full-blown Ed so I think with any disease process we can if we catch it early on

we can certainly reverse it and I think it's we demonstrated this in in erectile dysfunction or patients with mild Cog disorders if we catch it early in the process restoring eth thelial function produce nitric oxide then we can completely reverse that vascular dysfunction and that's the goal is that we start to make people aware of signs and symptoms of nitric oxide deficiency stop doing the things that are disrupting it get off mouthwash get rid of fluoride stop using an acids and start doing the things that promote it start exercising 20 30 minutes a day get

moderate physical uh or sunlight 20 30 minutes a day and throw in some more green leafy vegetables that's pretty simple and that actually saves people money and then if all else fails or you want to kind of of a bioh hacket then we have product technology that does it for you we've gone deep into the dietary piece and obviously that's foundational for all this but before we part ways you've touched on exercise and sunlight a couple times and you gave a little bit of a description of what we'd want to do in those Realms but

let's get more nuanced and talk about what the ideal dose would be frequency and what's happening with the physiology with those two specifically well sunlight first there's certain wavelengths of light there's both on the on the UV side of the spectrum and the ultra or the infrared so these different wavelengths of light provide a certain frequency that will liberate nitric oxide bound to what we call photo laball stores whether it's Metals in the tissue or even cistin THS so when we generate nitric oxide as I mentioned nitric oxide gas is gone but it creates these

second messengers and then when we're exposed to sunlight for instance infrared light that frequency will actually knock nitric oxide off of metals so if nitric oxide is captured by a metal it can liberate it become vasoactive that's why you know sunlight lowers blood pressure you know it it does a lot of things and then the UV side will actually cleave in O bound assisting tiles so we have to have enough of these kind of photo laball stores of nitric oxide to be acted upon by the sunlight or infrared or certain wavelengths of light so I

tell people if you're using infrared light or an infrared sauna dose up with nitric oxide prior prior to going out in the sunlight or getting an infrared SAA because we can actually improve the efficiency of light therapy and then in exercise you know we need oxygen to make nitric oxide and we need nitric oxide to deliver oxygen when we exercise we reach an anerobic threshold where we run out of oxygen so the body is no longer able to produce nitric oxide but if we titrate up with nitric oxide first we create a buffer a reservoir

that when we run out of oxygen now we have a kind of a reservoir of nitric oxide that pushes the oxygen gradient extends the anerobic threshold and improves performance so there're both even if you don't titrate up then exercise has been shown to stimulate and activate nitric oxide production because what happens that tissu is running out of oxygen and going hey I need I need to adapt to this exercise because I don't want to run out of oxygen again and the body responds by creating more blood vessels called angiogenesis generating more nitric oxide nitric oxide

improves mitochondrial biogenesis so now the cell has more mitochondria generating more ATP more efficiently with less oxygen so that's the Adaptive effects of exercise and the Adaptive effect of nitric oxide production so loading I think what we do is and I mentioned this earlier if you if you're like us Jesse we're relatively young and healthy and don't have any disease or symptoms then the dosing and the metabolic demands on us are much different than somebody that's you know 60 with high blood pressure Ed and diabetes so for us usually one one dose a day [Music]

sleep uh and those those are three big big ones I mean most people don't get enough sleep U Ed 50% of the men over the age of 40 self-report some type of erectile dysfunction and then blood pressure two out of three Americans have an unsafe elevation in blood pressure and many people are looking for natural remedies for blood pressure so those are the big three for the lozin the the noob beads which is our fermented bead powder we preon convert it we take the oxalates out so it's a it's a beet powder but it's white

uh no beat pulp no bead crystals no oxalates and no bead taste um we use that as an energy source or pre-workout we seen an enormous Improvement in exercise efficiency um the perceived exertion of an exercise regimen is much less and then just more energy I mean you can take it in the afternoon and we really position this to be a replacement for things like Red Bull Monster energy 5our energy these stimulant ridden really dangerous energy drinks that people are are drinking so so why not take a natural source of energy that repletes the body

of nitric oxide improves circulation and improves energy naturally I mean that's the beauty of of these products and if somebody tuning in right now wants to give one of them a try we have a discount I think it's a discount code we'll put in the show notes so people can access that so thank you for that and I just want to thank you for coming on the show this was super informative we went into a lot of detail and I learned a lot I'm sure the audience did as well and I just appreciate the work

you're doing naan thank you well Jesse thank you I mean it's look nothing we do would ever mean anything if we can't get it out to the masses and I think that's what you do is so important because now we can speak directly to the masses and and cover really the tough biochemistry and Physiology but hopefully put it in a in a way that's easily digestible but most importantly that is practical and you can from the moment you get up from watching this you can start making changes and just stop doing the things that disrupt

nitric oxide production and start doing the things that promote it and your body will thank you for it yeah there's a lot of powerful inputs that's what I love about this conversation that people can Implement right away and and see changes and Nathan one last thing we'll end on here the fact that you've been in this world for so long you've done so much research and you have this lineup of products you've written books what's next for you you mentioned you're still relatively young and healthy you got a lot of years ahead of you and

you've done all this work where you going next well I hope I have many years ahead of me you know we never know right but you know I think what excites me every day is getting up is we have a a drug Discovery program I've got a drug company called Brian Therapeutics we're developing nitric oxide drugs We've Got Drugs in in clinical trials for SCH schmico by nitric oxide at the right dose at the right time in the right patient and that's the that's the objective and mission of our drug company is to bring safe

and effective nitric oxide drugs to the market for every major health indication there is out there so that's exciting I've got a new book coming out probably in the late fall early winter called The Secret of nitric oxide uh picked up by Major publisher so we should have that out hopefully um in the winter at the latest but it it it's really to try to build awareness and educational nitric oxide it's partly autobiographical talking about the discoveries we made from 20 25 years ago and how we've seen this into the translation of safe and effective

nitric oxide product technology but more importantly it's to hopefully teach and get people to understand the importance of nitric oxide and what they can do to take control of their own health and be proactive and not reactive well Dr Lou during our conversation here it's very apparent your passion for teaching and sharing you've taught in the past in universities you're you're writing this you've written this book that you're sharing you know your story and all this great information you're coming on podcasts like this you know you could just be retired and just kick your legs

up and enjoy you know the fruits of all the hard work you've done right but again you have I can tell it's just this innate passion for teaching and sharing I'm curious where that comes from well you know I I I'm I'm not sure as I said before my parents were uneducated and so they they didn't really teach me anything um I think it's because I couldn't learn from my parents that I paid particular attention to learning from my teachers right my teachers in Early Education and professors and what I found was that uh most

of them were not good teachers and I struggled in my learning from them and I would always say to myself in the classroom why can't this guy or this lady teach so that we could understand them and I then I decided when I get into teaching myself when I become a professor I'm going to do it the right way and I taught myself I really taught myself how how to teach and because of that you know yes I've won many uh teaching awards given by the students themselves not the faculty because I love to impart

information I mean what good is knowing and having all this information if you can't share it with everybody else it's like a waste and so I have this passion and and motivation not just to do basic research but to teach and to impart information to others which may be a reason why so many people tell me just to shut up and keep eating you know that that could be a problem well it comes back to what you talked about before the problem with the food and and people exercising these days there's so many people who

aren't exposed to the right information and the people that are there's so much conflicting information in the health and wellness space so I can see how people would you know start to get excited maybe inspired and and go down the rabbit hole but then quickly get discouraged because there's so many conflicting uh philosophies we'll say in the health and wellness space there is you know we we need to have news media stations that do more what what you're doing you know I mean I listen to the news and and I've been listening to the news

for 50 years I find that in years past the news media uh were better I find now that news is is is sensationalized you know and and and especially the news on science these newscasters don't know the science and they say certain things which are going to come back to haunt them and they say certain things they get the people all riled up so now we have so many people who don't believe in vaccines who don't believe in this don't believe in that it's a problem and I I I sit here my wife always tells

me Lou calm down you cannot solve the problem yourself you know we need a lot of people to solve the problem but I have this passion you're right you're trying well you haven't been in the lab now for how long has it been oh uh 2014 seven years 2014 okay so it's been a while and I'm sure you know the Baton has now been passed when it comes to n and there's I'm sure a lot of different researchers out there taking what you you've done and continuing to build on it yes what's happened with that

research s since you've been out of the game and then what do you see happening in the near future well what's happening is that uh more drug companies now are focusing their attention uh on developing drugs that can actually boost nitric oxide not through supplements but by other mechanisms stimulating enzymes and you know really gets into a lot of biochemistry uh and there's no drug on the market yet but it looks like there may be two or three drugs on the market reasonably soon that will be useful healthy drugs to treat high blood pressure and

let's say coronary artery disease but what's interesting Jesse is that nitric oxide is a gas that that that let that led other investigators to look at other gases that might also be important and another gas was found to be important and it's called hydrogen sulfide or H2S hydrogen sulfide is the smell of rotten eggs okay it's the chemical that accounts for the smell of rotten eggs but a number of investigators have found that H2S or hydrogen sulfide is very important in controlling uh neuronal function it may be important in regulating cell s that that could

have an effect on dementia Parkinson's disease uh those kinds of diseases H and in fact there are a couple of good friends of mine out there uh who have been receiving getting awarded various prizes for their work on hydrogen sulfide and who knows you know if their if their work is a break through they uh they may have to invite me to Stockholm to visit with them when there go we we'll see what happens but yes this work is leading to um to to other areas and it's also leading to uh work showing that nitric

oxide deficiencies in certain diseases uh may may account for those diseases and we just need to develop some way to increase the nitric oxide the biggest problem in making progress with nitric oxide is the fact that it is a gaseous substance just Like Oxygen but unlike oxygen it has a half life of one or two seconds not thousands of years and so how do you work with that you cannot you know other than giving inhaled nitric oxide which goes only in the lungs you can't give nitric oxide and so it's been there's been a great

dilemma in the chemistry of putting this all together but I have no doubt that that'll be done sometime soon well must be so fun to sit back and watch you've gotten the ball rolling and now you can follow you know all the different paths that have spread out from from that core that you've created you're right I I love it I love to read all the new stuff that comes out and it it does make me feel good you're absolutely right earlier we talked about Arginine and the fact that there's definitely no advantage to supplementing

and putting more of that substrate into the mix there could even be detriment I want to zoom back from that and talk about supplements as a whole and I know you have a lineup of products as well let's talk about your products versus some of the more classical supplements people are tuned into like possibly going to the health food store and not Arginine we've already got into that but other ones and what's useful and what's not yeah you know it's one of my biggest frustrations you know I'm trained as a biochemist and physiologist so my

whole motivation in getting this field was to develop understand human disease to the extent that we could fix it right so we we've we've accomplished that we know nitric oxide enzymology biochemistry inside out now we know how to fix it so the my underlying objective and motivation was to develop safe and effective drugs for nitric oxide get this technology through the FDA so we can have safe and effective drugs for for Physicians to write prescriptions for their patients but we know that that takes about 10 years and $800 million to bring that to Market so

years ago I developed a dietary supplement product technology ology so that we could take what's missing from the diet primarily in the form of nitrate or the ability to convert it to nitride and nitric oxide and then give that back to nitric oxide deficient patients right but the the frustration and the problem in the nutrition and dietary supplement industry is that everybody says the same thing right you got the Arginine folks pushing their nitric oxide product saying it's a nitric oxide product is going to promote nitric oxide help in blood pressure performance blah blah blah

well there's a there was an act called the desay act the dietary supplements health and Education Act uh from years ago maybe 20 years ago that allowed companies to now market and support the normal structure and function of the human body that was how dietary supplements were born but you can make drug claims you can just say they support the normal structure and function of the body but yet 99% of the products out there that are marketed as nitric oxide products do not work we've tested them they don't stimulate they don't activate they don't produce

nitric oxide so these are called neutraceuticals so my challenge was how do we differentiate what I do what my products do which actually generate nitri oxide gas that we can quantify we can verify and we can detect how do I differentiate that from all these other yahoos on the market that are selling nitric oxide products that don't do anything but deceiving and defrauding the consumer so I created a new term called nitr sual so it's on the kind of a play on neutraceutical but what we do are nral and we actually generate nitric oxide gas

and so I've copyrighted and trademarked this term uh we own it and we make products that are nral that are completely different than any other products on the market uh and so any product that we bring to Market we can detect nitric oxide coming off of it we see the physiological effects of nitric oxide we can look at valid endpoints in terms of patients who take it we can see normalization of blood pressure improving exercise performance improve cognition blood flow throughout the body Improvement endothelial function uh everything that nitric oxide is known to do we

can actually quantify and detect that in the products that we develop and then the other the other major problem is you know beets beets became a a kind of a hero vegetable in 2012 in the Olympic Games in London when it was realized that most of these Olympic athletes were drinking liters of beetroot juice because there was evidence that it would produce nitric oxide and then enhance their performance now the market is flooded with beat powders beat gummies beat shws and I mean it's it would be humorous if it wasn't dangerous for the entire industry

because these products can't work you cannot get nitric oxide in a gummy or a chew and so there's nothing super about some of these beat products that are marketed on TV uh in fact it's you know it's outright fraud and it's deceiving the consumer and the customer uh so what we do is we tried to and and my motivation for this is is is authentic because it could kill the entire nitric oxide industry and I hear this all the time and I go well I've I've taken nitric oxide and it didn't seem to do anything

for me and I go what do you mean I go well I took this beet powder that I saw advertised on TV or this beat gummy and it didn't do anything but it's nitric oxide and I go no what you didn't take Nitric Oxide you took a product that was fra marketed as a nitric oxide product so when people come to me and say hey I've tried nitric oxide didn't work it's not that important I go what no no you this could kill an entire industry Nitric oxide's so important for what we're doing in the

history of medicine in the future of medicine that this cannot be allowed to happen so we have to call these companies out we have to demonstrate products that actually generate nitric oxide now when they take our products actually see the effects we can we can support normal blood pressure we can improve performance and now when they take nitr cutical or products that actually generate nitric oxide now they see the effect now they got the aha moment go this is lifechanging so that's the point and we have to call these companies out we have to call

a spade a spade and you know some of these products contain certain nutrients that may be good nutrients but they're not nitric oxide products so stop calling them nitric oxide products so would it be fair to say the big difference between what products you're making versus some of these others that are on the Shelf at the supplement store that say a beet powder at the health food store would be more of a nitrate supplement where you'd need to still create nitric oxide in the body and yours is bypassing the endothelium and those other steps and

creating nitric oxide final product in the body that I can use yeah that would be the best case what you talked about the night the Beet powders being a source of nitrate we've taken I've tested hundreds of these beet powders and 99% of them don't contain any detectable amounts of nitrate or nitrite so they're not even providing the precursors at a level that your body even could convert it so these are dead beat products in fact we use them as placebos in our clinical trials the only thing they do is turn your pee and your

poop Pink and cause a lot of anxiety they do nothing in terms of nitric oxide so what we do is completely different and the whole the whole motivation for this was if your body can't make nitric oxide because you have ineal dis function or because you're not getting enough nitrate or because you're using mouthwash or because you're using an acids then we have to do it for you your body can't make it it's clear I can give you all the substrates precursors but if your body can't convert it to nitric oxide which is your problem

then you're not going to get a benefit from that and I don't want to create a product that creates benefit for one in three people I want to develop a product that's going to provide benefit to every single person that takes it whether they're getting enough nitrate from their diet whether they're using mouthwash or not whether whe they're exposed to fluoride or not or whether they're on an acids or not so my product technology when you take it it generates nitric oxide for you we're not dependent upon the conversion of nitrate we're not dependent upon

the oral bacteria we're not dependent upon stomach acid production we control and dictate the metabolic fate of the product technology that we put in your body but more importantly we fix the enzyme that makes nitric oxide in the lining of the blood vessel we create a certain electrical potential in that product technology that recouples the no enzyme prevents tetrahydropterin oxidation now we improve inth thelial function and know the other thing by giving these bacteria on the CPS of the tongue a source of nitrogen in our Loz we're seeing that we we can increase the diversity

of the oral microbiome we can increase the number of nitrate reducing bacteria so now we're improving the body's ability to make nitric oxide from both Pathways we're giving the body a source of nitric oxide but we're actually improving the body's ability to make it on its own so over time theoretically you would need less and less of my product over time because we were actually fixing the reason your body couldn't make it so that's probably a poor economic model from a business standpoint but it's a beautiful physiological model and now more interested in maintaining the

Integrity of the science than I am in making a profit from selling products because we have to understand why people can't make nitric oxide and fix it that's how the human body is designed to work you went right where I was going to go next the fact that taking a supplement like like that it gets me thinking about is it something I need to take for life and you you addressed it sort of a little bit there the fact that it's going to fix the physiology at least to some extent have a long-term benefit but

have you guys done specific research where people have taken this for a period of time stopped and then say like a year later retested to see if the changes are lasting yeah you know it's it's hard to change people's habits right and humans are conditioned to they want to fix they want to simp fix they want a pill they can swallow to overcome their bad habits right nobody wants to change their diet and start exercising right so people are looking for for a silver bullet and I'm going tell you nitric oxide is not a silver

bullet my products are not a silver bullet that doesn't exist so what we're finding and I'm probably the best example I've been doing this for 20 years been taking my nitric oxide for for about that long and I take it every day not because I think I need it every day it's because the world we live in is so tough toic right the air we breathe I'm on an airplane every week for the past 5 six seven years every week I'm on an airplane going somewhere going into a hotel with a lot of emfs airports

you know exposed to environmental pollutants intoxicants and a lot of times I don't get to eat a very good diet so I take it prophylactically to protect my body from The Assault that I'm getting on a daily or weekly basis so with that said if we lived in Utopia in a perfect world where we didn't have herbicides pesticides environmental toxins the air we breathe was pure then no you would never need to supplement anything and if the food we ate was repl in all the vitamins minerals and nutrients we needed then you would never need

to supplement and it would be true Utopia but unfortunately that's not the world we live in so I think what we're finding is a daily nitric oxide boost is I think fundamental to preventing this age related loss and I think the conversations needs to be to for people being proactive instead of reactive today medicine is a reactive practice humans are reactive right we don't take action until we have a heart attack or stroke or or something we're driven by fear we have to change that we have to be proactive do the things that we need

to do to prevent our body from getting sick and developing these so-called fears of and having heart attacks and strokes because we know how to we know how to completely prevent that so maybe that was a long-winded answer to your question but I think if if you get moderate physical exercise which stimulates nitric oxide you eat a good clean anti-inflammatory diet you get exposure to 20 30 minutes of sunlight a day and you restrict your exposure to things like fluoride chlorine things we're exposed to then typically not your body is going to perform and do

what it's designed to do but very few people live in that environment I live out on 800 acres out in the middle of nowhere we eat our on beef we grow our own vegetables the air we breathe is clean we don't have fluoride in our water we got a full filt I'll see you over there visal fat causes inflammation throughout your body leading to disease it starts when you're young is the first expression of disease in the human body and it continues throughout a lifetime