Nitric Oxide: The Body's Wonder Molecule for Cardiovascular and Brain Health

In this fascinating episode, I am very excited to welcome Dr. Nathan Bryant, a leading nitric oxide researcher. 

During our conversation Dr Bryant reveals the critical role of nitric oxide in maintaining optimal health. He explains how this remarkable gas is essential for cardiovascular function, brain health, and preventing chronic diseases. We also discuss the importance of oral microbiome, diet, exercise, and lifestyle in supporting natural nitric oxide production.  

If you would like practical strategies to improve your nitric oxide levels, understand the limitations of current supplements, and discover how this molecule can potentially reduce risks of hypertension, cardiovascular disease, and neurodegeneration then this is a must-listen for you. 

Links mentioned in this episode:

The Nitric Oxide Solution by Dr Nathan Bryant 

Thanks for listening to our podcast and please feel free to get in touch:

• Tweet us at @fmedassociates
• Follow us on Instagram or Facebook @petewilliams_fma
• Email us on info@fm.associates
• For more information about our services please visit our website www.functional-medicine.associates

We would love to hear from you!

Transcript

SUMMARY KEYWORDS

Nitric oxide, cardiovascular health, endothelial dysfunction, blood pressure, oral bacteria, dietary patterns, exercise, neurodegeneration, Alzheimer's, insulin resistance, mitochondrial function, stomach acid, mouthwash, supplementation.

SPEAKERS

Peter Williams, Nathan Bryant

Peter Williams  00:02

Welcome everyone to our new functional medicine bite sized episode. This is one that probably started over 15 years ago. I was at a functional medicine conference. I'm pretty sure it was Austin, Texas, and this guy was talking to me about nitric oxide. He actually gave me his book. He actually signed the book. And this was Nathan Bryant. And Nathan Bryant, at the time, was Associate Professor of Molecular Medicine at the University of Texas, and he was chatting to me about nitric oxide. I had a very, very basic understanding of it, and really didn't really look too much into the book, until about sort of 10 years, 10 years later, when suddenly nitric oxide is becoming almost the one of our body's wonder molecules. So, Nathan, listen, I know you're just sort of, you've moved from no one's really interested in listening to you, and now everyone wants to listen to you. So can you give us a little bit of a background of you, sort of, what you're doing now, what you did before, and where your major sort of aspect of research is, sure,

Nathan Bryant  01:16

yeah, well, thanks, Pete. It's great to be with him. Great to see you again after all these years. Yeah. Thank you, right That was 15 years ago. You know, I was, I was still in academia, but, you know, I started in this field of nitric oxide research in the late 90s, early 2000s when a Nobel Prize was awarded 1998 I was a student at LSU School of Medicine. I was working on a PhD in Molecular and cytophysiology and looking for, you know, a field of study, and this whole concept of new science around nitric oxide was exciting. Had a chance to meet the guys who won the Nobel Prize for its discovery. And, you know, they inspired me to understand the how the human body makes this molecule, what leads to a loss of its natural production, how that leads to chronic disease. And then, perhaps most importantly is, you know, once we answer those questions, then we can start developing product technology and drug therapy to restore the natural production of nitric oxide. So now fast forward, what, 25 years. So when we first met, I was still in academia. You said I was a professor of Molecular Medicine, and I'm giving talks. You know, I'd filed a number of patents. Patents were starting to be issued, and I was looking for people to, you know, take my technology and run with it develop drug therapy. And when I found that really no one was interested in nitric oxide, well then I thought, well, if it's to be it's up to me. So I started my own company. And, you know, for the past 15 years, that's what I've done. I've taken my discoveries, my innovations, and developed product technology. And of course, you know, you can't be good at one thing if you're doing many things. So I had to step away from academia. I retired from academic research, and then became a serial entrepreneur. And you know, today I think it's without doubt, we're the leaders in nitric oxide research, product technology. And you know, we've got drugs now and clinical development and Phase Three for things like heart disease, Alzheimer's and topical drug for diabetic ulcers.

Peter Williams  03:08

So can we give it the sort of what it is, and then the basic physiology? And obviously, for particularly for me, you know, it's an exciting podcast for me, because obviously I'm doing more and more stuff of understanding nitric oxide. I think we're doing some good stuff and work with understanding the concepts of nitric oxide, but it is a real special molecule, if you like. So can you just expand on all of those aspects and give because why it's so important, particularly for cardiovascular health, and of course, that vascular health means also for sort of the neurodegeneration and brain health as well.

Nathan Bryant  03:43

Absolutely. You know that Nobel Prize specifically was awarded for the discovery of nitric oxide as a signaling molecule in the cardiovascular system. So it's a signaling molecule. It's naturally produced. Interestingly, it's a gas that's produced by the lining of the blood vessels. There's an enzyme that that's found in the in the endothelial cells, these single layer cells that line all blood vessels throughout the body. And when this enzyme is functional, when activated, when stimulated, can release nitric oxide gas. And it's it's first properties, or first mechanism of accident was as a vasodilator. So this gas diffuses into the underlying smooth muscle, activates the second messenger system and leads to vaso smooth muscle relaxation, which results in vasodilation, so it opens up blood vessels. And then further down the road, it was discovered that nitric oxide is required for binding of oxygen to hemoglobin, and actually the delivery of oxygen from hemoglobin. But then you know, it's recognized as inhabiting anti platelet function, so inhibits platelet aggregation. It's it's protective from clotting and heart attacks strokes, and it mobilizes our own stem cells. It activates an enzyme called telomerase, which prevents telomere shortening and it enhances mitochondrial ATP production. So everything we know about optimal cardiovascular health, Metabolic wellness is absolutely dependent upon the body's ability to produce sufficient amounts of nitric oxide.

Peter Williams  05:08

So can we sort of, I mean, the description, it's probably a wrong description I try to give people is that it sort of helps to keep the vascular wall in good health. In a sense, it also it vasodilates, which is super important because flow, arterial flow and pressures are really quite important for for injuring the wall. But also it does it work? I mean, maybe I'm getting this wrong, but it works a little bit like washing up liquid. It it stops things from from sticking. Would that be a good description

Nathan Bryant  05:46

No, it is. So that's, you know, we can get as complicated or simple as you like, but because it's a gas, you know, it diffuses in three dimensions. We talk about how it dilates the blood vessels. That's nitric oxide, diffusing into the the smooth muscle and the intima but intravascularly, if the endothelial cells is making sufficient nitric oxide, it down regulates what we call adhesion molecules. So when you become nitric oxide deficient, your blood vessels are like Velcro, right? All the monocytes, the neutrophils, the white cells, the platelets, start to stick, and it you get turbulent flow, and you get, you know, you lose barrier function, and you get extravasation of lipids and monocytes, and so it's the early stages of vascular inflammation.

Peter Williams  06:24

Because, go ahead, well, it will it almost for me again, because obviously the you're always trying to explain these concepts to patients, and it really is the key player of keeping the neighborhood in good shape, I think, is, is, would that be a good description of

Nathan Bryant  06:41

it? No, absolutely. I mean, it has so many physiological, important foundational functions, but yeah, I think that's a great analogy, because it's all about the environment in which that cell is operating. And you got to have good neighbors. The neighborhood has to be in good condition, and nitric oxide is what keeps that neighborhood functional. So it turns it from Velcro, almost like Teflon. Maintains barrier function.

Peter Williams  07:04

So it becomes, again, if we look at the sort of definition of atherosclerotic, cardiovascular disease, it's the abnormal retention, if you like, of the the APOE B containing molecules, so the sort of apogenic lipids. But that doesn't happen as much if you've got a really good looking sort of neighborhood which nitric oxide's role is so in many ways, although it's not the causal mechanism, it's one of the key mechanisms that reduces your cardiovascular risk. Is that, is that correct?

Nathan Bryant  07:38

Well, I would go so far as saying that it is causal, so it's no longer just an association, because what the both the basic science and the clinical data tell us is that and we can measure this. We call this endothelial dysfunction. So we can, we can do functional measurements of how well your endothelium produces nitric oxide. And endothelial dysfunction precedes the structural changes you see an atherosclerotic vascular disease by many years? So loss of nitric oxide is the first event in the onset progression of cardiovascular disease and endothelial dysfunction, hypertension, diabetes, all conditions and symptoms of nitric oxide deficiency are what accelerate that whole atherosclerotic disease process. So loss of nitric oxide is causal for cardiovascular disease.

Peter Williams  08:24

So again, what you're saying there is that when people have increased blood pressure, or starting to have increased blood pressure, is that a direct link for you that nitric nitric oxide production is insufficient.

Nathan Bryant  08:38

I think in the majority of cases, obviously there's, there's problems with random angiotensin. That could be, you know, an adrenal tumor, for example, you're over secreting mineral corticoids, and it's a volume expansion. You could have a dysregulation of calcium, and that's then, that's where the classes of drugs, like ACE inhibitors, ARBs and calcium channel blockers can can somewhat normalize blood pressure. But what we're finding, and what I would like to say, is nitric oxide fixes the physics problem of hypertension, because when you think about when our body produces sufficient nitric oxide, we can dilate the blood vessels. We can dampen the pulse response with each heartbeat, yeah. And then we have a finite amount of blood, right? It's pumping through all these blood vessels throughout the body. So if we can't make nitric oxide, these blood vessels become chronically constricted. Now you've got the same volume of blood going through smaller blood vessels. And if you go back to simple physics, pressure equals volume times resistant smaller blood vessels. Resistance goes up, the volume stays the same. So pressure has to go up. Now, if we can restore the production of nitric oxide, we dilate the blood vessels, same volume of blood, still we haven't lost any blood now that that volume of blood is just going through bigger pipes, and the laws of physics tell us that blood pressure has to come down and normalize. So that's the case with how nitric oxide affects hypertension. And how a loss of nitric oxide production can cause hypertension.

Peter Williams  10:04

And so we know that, as you say, it's directly implicated in cardiovascular disease risk. But also, of course, it given that the vascular system is probably most prominent in the brain, then are we starting to look at nitric oxide with regards to vascular diseases, vascular dementia, early stage neurodegeneration and Alzheimer's. I'm assuming we're starting to find this massive links between those two as well. Again, from from the simplicity of you know how much of a proportion of the vascular system is in those areas?

Nathan Bryant  10:41

No, of course. I mean, you can look at imaging, whether it's spec scans or look at functional MRI and look at profusion of certain regions of the brain. And Daniel Amen has done a great job of this by collecting this, I think, probably the world's largest database of spec scans. And spec scans are really looking at how well the brain is perfused and so in any neurological disease, whether it's mild cognitive impairment, dementia, Alzheimer's, Parkinson's, bipolar, addictive disorders, there's always a loss of regulation of blood flow. And so let's talk about in MCI dementia and Alzheimer's, which will be interesting because we're developing drug therapy against Alzheimer's. But what are the hallmarks of dementia? It's called vascular dementia, because obviously there's a vascular component. There's a photo ischemia in the prefrontal cortex, yeah, and then there's insulin resistance. You know, Alzheimer's has been called diabetes type three. And then if you can't get oxygen, you can't get nutrients into the in the cell, can't make energy, then proteins fail. They become misfolding, and we call that amyloid plaque and tautangles, and so developing drug therapy against the consequence of disease cannot, will not and does not work. That's why all drugs have failed against Alzheimer's, because you're going after the wrong target. What we look at are one of the earliest aspects of neurodegenerative disease. Well, it's low blood flow, it's insulin resistance, it's mitochondrial dysfunction. What does nitric oxide do? Well, it dilates the blood vessel. Now we're going to profuse the brain. We published in 2011 that nitric oxide is part of insulin signaling, and what signals the cell to bring glucose into the cell so it overcomes insulin resistance. It improves mitochondrial biogenesis. Improves ATP production at the level of the mitochondria. And when you profuse the brain and get glucose into the brain. Proteins don't misfold. You don't lose cognition, and you address the root cause of not just Alzheimer's, but all neurodegenerative disease.

Peter Williams  12:29

So if we were what would be so let me maybe change that another way. What is the natural ways that we start to increase nitric oxide production?

Nathan Bryant  12:42

Well, I tell people, there's only two things you have to do. You got to stop doing the things that that inhibits this natural production and start doing the things that activate and stimulate its natural production. So and we can go pretty deep into these but number one, what causes a loss of nitric oxide production when we look at so in order to answer that, we first had to understand, how does the human body make it you body make it and we've talked a little bit about the function of the enzyme lining the blood vessel, but we've also discovered that oral bacteria, and particularly the nitrate reducing bacteria on the crypts of the tongue, the dorsal part of the tongue, are responsible for a nitrogen cycle in the human body that produces nitric oxide, and this is dependent upon the foods we eat. It's dependent upon the adequate and sufficient microbiome, and it's dependent upon stomach acid production. So let's start. We'll start from the bottom and work our way up. We have to have stomach acid to make nitric oxide through this path,

Peter Williams  13:37

and the thing about that is that the significant proportion of the population, as they age, start to reduce their capacity to just basically make stomach acid. And then, of course, we've got a combo. We've got lots and lots of medicines that actually interrupt with that. So do you want to, do you want to sort of expand on that? Yeah.

Nathan Bryant  14:00

So the you there is an age related a loss of natural stomach acid production, I would argue, because it's nutrient deficient, right? I mean, there's some protective mechanism. If you have hemochromatosis or iron load, your body shuts down stomach acid production to prevent iron overload. So there's a protective mechanism, but that's only in a very small portion of the population. But if you, if you inhibit stomach acid production, and these are the clinical data I'm talking about, are on, specifically on the proton pump inhibitors, the PPIs, this is omeprazole, pantoproz, crevasid, those types of even over the counter drugs, but the clinical data showed us that people have been on these drugs for three to five years, have a 30 to 40% higher incidence of heart attack, stroke and Alzheimer's. So those are indisputable clinical observation. It's not increased risk, it's increased events. Then when we look backwards and figure out, why is that? It's because these drugs are completely shutting down nitric oxide production. They lead to an accumulation of what's called asymmetric dimethylarginine which inhibits the nitric oxide synthase production of nitric oxide, and it's inhibiting stomach acid production, or nitric oxide being produced through this interior  salivary circuit. So number one, if you if you can't make stomach acid, not only is it disrupting nitric oxide production, but you can't absorb B vitamins, selenium, chromium, magnesium, calcium, iron. I mean, we need stomach acid to absorb nutrients. Furthermore, we need stomach acid to break down proteins into their constituent amino acids. So for me as a biochemist and physiologist, adequate health begins with adequate stomach acid production. Because if your body can't make stomach acid, you can't control total body pH, your your pancreas don't secrete bicarb during the gastric the acid dump from the stomach, and it leads to complete metabolic acidosis and dysfunction.

Peter Williams  15:51

And what would be your what would be your? Your tips clinically for that, if you you did have that you had patients where you suspected that that was the case, or

Nathan Bryant  16:00

if they're not, if they're non medicated, the easiest fix is to take some apple cider vinegar before every meal. Okay, so that, well, that's just acidic acid, acetic acid, so it'll acidify the lumen of the stomach. So if your body can't make stomach acid, put some acid in there. Okay, then, if you're taking antacids, you have to wean off of these drugs. You can't just stop these cold turkey, because try it and you'll see how horrible it's. You have to wean off of these to slowly, you know, inhibit, to stop this inhibition of stomach acid. So that's that's the most important, you know, for me is to make sure you have sufficient stomach acid production. Wean off these drugs and then slowly start acidifying the little of the stomach.

Peter Williams  16:41

And where are you from a point of view of, I mean, I've got a pretty good understanding of oral aspects, so I'm assuming you would be, you would be looking at, certainly, mouthwashes that contain certain chemicals that are well known for, um, destroying those bacterial groups that deal with the nitrate nitrites from food. Is it? Was it nitrates?

Nathan Bryant  17:08

It's nitrates from food. Okay, can you explain? So this is, this is the second step in the hierarchy, right? So we start at the bottom, because if that's not fixed, you know, we gotta, we gotta address that. But yeah, then the second part of this process is the right oral bacteria. And then again, here's the problem. Almost every toothpaste has fluoride in it. Two out of three Americans use mouthwash. I think that's probably globally. In most westernized countries, probably in the UK too, most people are using an Antiseptic Mouthwash because we're instructed by our dentist. We see the commercials. Everybody wants fresh breath, but what we and others have published that if you use mouthwash, your blood pressure goes up, yeah, and your blood pressure goes up, and you lose the protective benefits of exercise, because you're killing the essential bacteria that are responsible for partly producing nitric oxide. So and then in the US, I don't know about the UK, but we put fluoride in our drinking water, in the municipal drinking water, and why do they do that? Well, it's to kill the bacteria in the pipes. Well, when you drink that water, it kills the bacteria in your pipes, bacteria your entire GI tract and so and it's a neurotoxin, and it shuts down your thyroid function. I mean, fluoride is an extremely electrophilic molecule and causes a lot of oxidative stress, steals electrons from other molecules and makes us rest from the inside out. So you have to get rid of fluoride if you're using mouthwash. You have to stop, because we need these oral bacteria, you know, I think. And you would agree, you would probably know physician or clinician would tell any patient, take an antibiotic every day for the rest of your life, because it's going to destroy the entire gut microbiome and it causes systemic disease. And that's the same principles we shouldn't, you know, sterilize our entire oral microbiome every day, sometimes twice, three times a day, and expect there not to be consequences. There is,

Peter Williams  19:01

yeah, it's quite an interesting area. Nathan, I think, as you say, this sort of integrated dentistry, biological dentistry side, which is, is really looking at this from a point. And I suppose, you know, I suppose a lot of just general clinicians know that we want to utilize medications only when absolutely necessary. So I think most, most dent Well, that's the wrong thing to say. I wouldn't say most dentist, but the dentist I know is if we aren't going to need to use some antiseptic, anti microbial antibacterial agents, we're only really using them for a very good reason, maybe after minor surgery or major surgery, and for a couple of minimum time as all medication should be used Absolutely. It's not that we're dismissing that medication doesn't have a role, but no one thinks about the next step. So we see this all the time. We. Antibiotic treatment with regards to the disturbance in the gut microbiome, and it's the same thing. It's maybe we should at least run something along alongside the the antibiotic to try and try and offset that situation. Can we talk about foods so on the assumption that and again, if we, if we go back and again, this does resonate with so many of the people that we see, and so many sometimes, of some of the really simple interventions, like, maybe we'll just start you with some some betaine hydrochloride. So it's sort of a supplemental, sort of a stomach acid supplement, and they would have a digestive enzyme, and that, a lot of the time, is really helpful for those sort of IBS, like symptoms. But we do that because, as I say, there's a recognition, and sometimes when we certainly some of the gut microbiome tests that come back, particularly because there's, it's a couple of new companies that are looking at the full microbiome now, and we're seeing a lot of the oral bacteria, in the in the in the gastrointestinal microbiome in levels that shouldn't be there. In fact, one of my recent tests showed exactly that. So for me, that says maybe there's two I haven't got enough stomach acid secretions to have those sort of levels. So we are starting to try and put this together in a little bit more detail. Can we move that so on the assumption that first fingers you're saying is, which sounds really crazy, but make sure you got enough stomach acid and would be first maybe be careful about what you put in your mouth, and from a point of view of your oral hygiene, because those bacteria, and they mainly exist only on the back of the tongue is that right, right the back of the tongue,

Nathan Bryant  21:52

yeah, the dorsal parts of the tongue, deep in the crypt, so near the gag reflex. And so we've identified these through tongue scrapings. So we do tongue scrapings to culture these bacteria. We're going to be put them on a P them on a petri dish and we culture and we identify, but, yeah, it's all the way back on typically. And these are facultative anaerobes, so they're pretty far in the Crips of the tongue. So you gotta, you know, apply a little bit of pressure with the tongue scraper.

Peter Williams  22:13

Hey, that was a bit gaggy. Doing that with people gagging and going that far back.

Nathan Bryant  22:18

Yeah, well, it's near the gag reflex. I mean, the Greg we culture these. I mean, we haven't gagged anybody throw up, and we do these experiments in humans. But, yeah, you go back as far as you can without gagging, and pull the tongue scraper forward, and then we collect the bacteria and culture.

Peter Williams  22:33

Just a question on that, then, would you recommend tongue scraping in general for trying to, trying to change the sort of oral microbiome?

Nathan Bryant  22:42

Yeah, we published on this in 2019 and what we found people that did daily tongue scraping once or twice had the greatest diversity in the oral microbiome. Their blood pressure was the best of anybody in the cohort.

Peter Williams  22:55

No, that's really, really interesting. Because, of course, as you know, some of those red group pathogens, like porphymonas gingival is hugely associated with neurodegeneration, particularly. So what you're also saying here is that not only if you're thinking about that, you're you're getting the nitric oxide benefits, but you're also potentially getting the the neurodegenerative sort of risk reduction, if you like.

Nathan Bryant  23:23

That's right and well, and what we also report in that same paper is the people who did tongue scraping but also use mouthwash with the people had the greatest increase in blood pressure after mouth washings, right? If you think about it, you're kind of tilling the soil right and opening up those pores. Then you put mouthwash in it, you get better penetration, get more effective killing, and the blood pressure goes away. So tongue scraping itself is good and beneficial, but there's no condition where mouth washes is beneficial, yeah. I mean, I say that broadly speaking. I mean, we leave it to the best medical judgment of the dentist, if they've got some severe pathogens that are causing systemic inflammation, we have to deal with the pathogen. Yeah. I think, as you said, we have to have judicious use for a specific period of time, and not something that you do every day, twice a day, for 20 or 30 years, which is what a lot of people are doing with mouthwash.

Peter Williams  24:11

Yeah. Okay, that's, that's pretty mind blowing, to be fair. Can we move it on to foods then, and because, obviously, there's the two key things for me, and well, there's actually quite a few. There's food, there's probably exercise. And I would love you to confirm, because I always hear it. I've probably read a few bits on it, but I can't say for sure, but I would like to know your thoughts on breathing through your nose as well.

Nathan Bryant  24:41

Yeah, look, nasal breathing is extremely beneficial, but again, you have to understand the biochemistry of how this is working. So the same enzyme, what we call nitric oxide synthase, that's found in our endothelial cells the lining of the blood vessels is also found our epithelial cells in the upper airway. So just like we can stimulate and activate endothelial. Nitric oxide production with things like bradykinin, acetylcholine and physical exercise, we can activate this enzyme in the upper sinuses, upper airway through nasal breathing. So when we do nasal breathing, it activates these mechanoreceptors, if the enzyme is coupled and functional and makes nitric oxide. Now we're delivering nitric oxide in the pulmonary circulation, dilating coronary arteries, dilating the lower airways, and it's leading to, you know, better matching of ventilation to perfusion. It's leading to better oxygenation. That's why deep breathing can lower blood pressure. And it's not always just an autonomic nervous system response. It's a nitric oxide basal dilatory response. But again, if the if you have endothelial dysfunction and the enzyme isn't functional in the endothelial cells, then that same dysfunction is occurring in the epithelial cells, and we've been able to measure this through exhaled nitric oxide. So we can take young, healthy individuals do nasal breathing and detect nitric oxide coming up. You take a 40/50, year old person with known risk factors, hypertension, erectile dysfunction, diabetes. They do nasal breathing. There's no nitric oxide being produced. It's because their enzyme isn't functional.

Peter Williams  26:06

So can I guess a question from that? So the enzyme is eNOS (endothelial NOS)? Enos, that's right, yeah, we see a reasonable amount of individuals when we're doing snips Who, who do have endothelial snips, is that? And what that is suggesting is that the the enzyme isn't potentially working as well as we would like, because it's been slightly configured differently genetically. And that doesn't mean to say it might not work, but it might not work as well. How much more at risk are they? And would you just on a on a clinical basis, would you spend much more time on those patients really cluing down to understanding, maybe the sort of nitric oxide cycle?

Nathan Bryant  27:00

Yeah, so look, as you know, there's, there's redundancy in the human body, right? There's more than one ways to get to where we're going. So if you have an Enos snip, then you you absolutely have to focus on eating the right diet, having the right oral microbiome, making sure your type of stomach acid production, because these are two independent kind of redundant, compensatory pathways that if one is dysfunctional, the other can compensate and produce the vasoactive nitric oxide. And I think that's why kids can get away with eating a really poor diet, right? Because they have good endothelial function. They're active, and they make enough nitric oxide in the lining of the blood vessel, where, the older we get, some many people rely more on diet because they have endothelial dysfunction. And you know, their entero salivary nitrate pathway is what's kind of leading the day. But so yeah, you have to focus on that. But again, whether it's a, you know, homozygous, heterozygous snip, and depending upon where those snips are occurring, can affect the function of nitric oxide production through that enzyme. So that's a very important genetic test to make, to see if you're predisposed to it. And so the Enos one is obvious, the one that's not so obvious of the MTHFR for the methyl hydrofolate reductase, because this enzyme, as the name implies, is involved in methylation. But if you understand the biochemistry and the shuttling of metabolites in in a cell, in feeding these biochemical pathways, MTHFR is what reduces bioptropin to tetrahydrobioptron. And tetrahydrobioptron is the rate limiting step in nitric oxide production. It's a co factor that allows for the transfer of electrons from the guanidine Nitrogen all the way down to make nitric oxide. And so if you have a disproportionate amount of the redox ratio of BH four to BH two, then you get an awesome coupling. And so MTHFR pay patients have an MTHFR snip have endothelial dysfunction because they've got a disproportion. They have more oxidative tetrahydrobioprin or BH two than they have BH four.

Peter Williams  28:56

So I suppose what you're saying is, and there's two classic snips. Isn't a 677, T and it was at 1298, so if you identify them, which we do, I never knew the I never knew the ARS link. So that's fantastic. So in a sense, what you're saying actually that a higher than normal homocysteine level may be indicative of of an issue with regards to nitric oxide production. With that, with that, with that pass.

Nathan Bryant  29:29

Well, what we measure specifically is the redox ratio between reduced bioptron, which is tetrahydrogen and then oxidized by BH four to BH two. And in our 2000 we were the 2009 paper we published on this, if that was really the rate limiting step, and if we could preserve BH four reduction and prevent BH four oxidation, we could maintain normal nos function and actually improve endothelial and epithelial nitric oxide production. So that's what we focus on. But you know, there's there's redox couplers, right? See if you have an ablation of homocysteine or. You know, ascorbic acid to DHA ratios, or reduced glutathione to oxidized glutathione. All those are kind of redox coupled. There's an electrical potential that each of those operate within to prevent the extraction of electron, which is what oxidation is just it's a loss of an electron. So you have to understand this redox coupling and the electrical potential that's required to remove an electron or oxidize that particular biomolecule. And that's what most people, unless you know you're a card carrying biochemist, don't understand. And then companies who are selling you nitric oxide products certainly don't understand that. So they really can't provide a nitric oxide product that restores natural nitric oxide production.

Peter Williams  30:41

And there's definitely a start in there's definitely an expansion of nitric oxide products that are out there. Does that mean that you're, you're dubious about the capacity to do the job that they need to do?

Nathan Bryant  30:55

Yeah, and rightfully so. You know, I coined a new term, because we don't do nutraceuticals because nutraceuticals don't work whether they're nitric oxide or, you know, vitamin A, vitamin C, vitamin D. This comes from the from third party studies looking the US, 73% of the products taken off the shelf at a pharmacy or a supplement store don't contain what's on the label. Yeah, and this is a problem, but specifically as it relates to nitric ox, nitric oxide products, you know, because the companies that are manufacturing these products don't understand why that person that's taking this product can't make nitric oxide. It's never deficiency in arginine. It's never deficiency in citrulline. So giving arginine your citrulline is not going to fix the problem. And then now that you see this, you know, all these beet products out there, and you know, it's probably one of the biggest myths ever perpetuated that beets are nitric oxide. Beets are not nitric oxide. Number 1 95% of the beets that are on the products that are on the market, and I've tested every one of them, contain no nitrate, contain no nitrite. They're dead beets. We use them as placebos in our clinical trials. So all they do is turn your pee and your poop pink. So they're not nitric oxide products. And so I coined a new term called nitroceuticals. And note the word nitricceutical because we make nitric oxide. And so I trademarked this term. And so what we do, we're not nutraceuticals. I mean, we're developing drug therapy, which is what we originally set out to do. But, you know, because we know how to naturally produce nitric oxide through diet, through lifestyle, through supplementation, I created a new line called nitraceuticals. So Brian, nitraceuticals makes products that produce nitric oxide, and so all these other products on the market are just from companies trying to, you know, as you mentioned, there's, there's a growing awareness of nitric oxide, and when there's a growing market, companies enter because they want to profit on that. Yeah, but number one, look at the companies. And the founders of the companies, they're not scientists. They've never published a paper in the clinical literature. They they hire these physicians or talking heads, again, have no understanding of nitric oxide, and telling you that their products produce nitric oxide, or that beets produce nitric oxide, and it's a problem for me, because it could kill the entire field. Because people say, well, Nathan, I see these beets advertised on TV all the time. I've taken them, you know, because they've convinced me that there's a nitric oxide, it's going to lower my blood pressure. They go but it hasn't helped me. I don't have more energy. I still have diabetes. My blood pressure has actually gotten worse, and my dentist says my oral hygiene has gotten worse because of the sugar and the seed oils I'm taking in these beet products, they go so nitric oxide doesn't work for me, and that's the dangerous interpretation, because nitric oxide always works. That company failed you. That product failed you because they're either intentionally deceiving and fraud and defrauding the customer, or they just don't understand the science to the extent that they can address the root cause. And that's why, you know, I, you know, I got of academia because I wanted to see the next stage of this technology. And actually, you know, I felt like I had an obligation and responsibility to give people products that actually work, so that they can see an effect and understand the importance and and feel the effects of nitric oxide.

Peter Williams  34:06

And what would those effects be? So if you were taking nitric oxide, is there something immediately that you would, you would feel, because I know the the erectile dysfunction market certainly sell products that certainly make you feel like you've got a bit of a beacon for sure.

Nathan Bryant  34:32

Well, let me feel as a subjective word, let me tell you what we've measured, clinically, objectively, to share with you what the effects we we see in an objective manner, and then some people feel this, and some people don't. But within about 12 seconds of placing our laws into your mouth, we see the carotid artery failing. We can measure this through an ultrasound, so we get a baseline picture, but the laws in your mouth releases nitric oxide. We turn the video on, and we can actually watch it. Real Time, the carotid arteries open up. So you want to increase blood flow to the brain, let's dilate the conduit arteries, the main transport of the brain, which are the carotids. Within 15 minutes, we start to see if you got an elevation in blood pressure, your blood pressure comes down. Within 20 minutes, we see a 20% improvement in the function of the nitric oxide synthase enzyme. So 20% improvement in what's called flow mediated dilatation. So we're improving the body's ability to make nitric oxide on its own by 20% within 20 minutes, within 10 within another 20 minutes, we see a further reduction in blood pressure. If your blood pressure is high, if you have normal blood pressure, there's no change in blood pressure. Within about 90 minutes, we start to see an increase in circulating stem cells. So we're activating stem cell mobilization. You have more stem cells in circulation, so you're going to heal better. You're going to repair within, you know, a couple of minutes, I'll go back. We see an improvement in exercise performance within four hours, we see about a 25 to 30% improvement in Athena function within 30 days, blood pressure and pre hypertensive patients come normal within six months. We can reverse heart disease. We can resolve kidney disease. So this, these are the progression of effects we see through randomized, placebo, controlled clinical trials. And some people feel this. Some people not like for me, I'm healthy. I'm 51 years old. When I take my product, I don't feel anything. I mean, if I would go to a workout, I can feel that my workout is better, but I don't feel my blood vessels dilating. I don't feel the stem cells increasing in circulation. But if we take a patient with COPD, a patient with erectile dysfunction, a patient with severe, unmanaged hypertension, and we bring their blood flow, their blood pressure, down and normalize it. Or a person with brain fog, and we start to profuse their brain they go, Holy shit, my vision is getting better. My brain fog is gone. I feel like I have more energy. Those are kind of the subjective things that we hear reported. But I'm not interested in subjective as more as I am an objective things that we can typically prove through objective inputs.

Peter Williams  37:06

Let me ask you a question. Can you move on? Because obviously my original academic background is as an exercise scientist. So one of the key things that I always bark onto regardless who's here is that we need to use exercise for, I mean, one of the key things is because it opens up everything, and then it delivers lots of things, and that's one of the particularly the, well, I mean, cardiovascular, neurodegeneration, you name it. It's sort of, it's, it's at least the thing that we can look into scientific literature and say, we know it works, you just gotta do a bit more consistently than you're doing at the moment. So I'm assuming huge fan of the capacity to move and what it does you would be you that's one of your recommendations, even in some of your office books.

Nathan Bryant  37:58

Well, look, exercise is medicine. It's indisputable. And people don't get old and stop exercising. They get old because they stop exercising. Yeah, I totally we have to move. It's diet. Diet and exercise are the key. You know, people are looking for a silver bullet. You know, we need more signs, no. We need more science. We need more discipline. Yeah, you have to have a good diet, and we have to move. We have to exercise. And if you don't do that, there is nothing's going to save you. There is no magic bullet, there is no silver pill.

Peter Williams  38:26

Isn't it interesting? Because I've done quite a few podcasts on longevity, and I'm also sort of, I'm a little bit older than you, and I've been in the game a long time, and I think I'm increasingly becoming irritated by actually understanding how the business of healthcare works, because I don't see anything really in the longevity research as far as magic pills that are actually really a sort of worthwhile now, don't get me wrong, you can use certain things for certain things, but it feels like there's a billion pound industry that is very quickly developed on hardly any robust science, I would believe. Except, of course, exercise has been as robust as we can get for how many decades you want to go into and and, I suppose that I wonder why it still seems to be the poor cousin.

Nathan Bryant  39:28

Again, there's no money in curing. There's no money and people taking thing once and being done. I mean medicine in these for profit companies. It's the same principles. Acquire as many customers as you can, keep those customers buying your products for as long as you can, and that's what leads to a very profitable, successful company. So these companies are out there trying to convince you you have to take this every day. And, you know, I do the opposite. Sometimes marketing team gets something. I go, Look, if you do all the right things, you don't need my product. And for them, if you start taking my product and we're restoring the function of the enzyme or. Growing the oral microbiome, then you probably need less and less of my product over time. But in the world we live in, unfortunately, we live in a toxic world. Our foods depleted basic animals and nutrients, and we're exposed to toxins. So, you know, for me, it's, I take it every day, but because I know I live, we live in a toxic world, and we just, it's a good daily you know, I drink water every day too. It's just one of my non negotiables. But no in terms of exercise, exercise affects everything we know about longevity. And the muscles in our body are what was called piezoelectric, right? So they're energy producing. They're like battery packs. And so if we don't move those muscles, we lose voltage in that particular meridian. It goes back to acupuncture and traditional Chinese medicine. We're wired through the fashion. There's meridians that go through our teeth, and every organ is on a specific meridian. If you're not providing enough voltage and current through that, then you develop end organ disease. But exercise stimulates activates. Nitric oxide production provides electrical power to certain organs. And if we don't move, we're not charging our batteries. And how do we diagnose death, no electrical activity, EKG, eg, we run out of energy. You know, if everybody in the world our red light comes on, showing our batteries low, everybody panics and goes and plugs it in. Well, you know what we our body tells us, our our our batteries low. We get EV we get high blood pressure. We start develop brain fog. That's your red light coming off, saying, Hey, your battery's low. You need to recharge. How do you recharge? We go exercise barefoot, out on the earth, get electrons, move your body, activate these muscle battery packs, stimulate circulation, improve nitric oxide production. Nitric oxide is a free radical. It donates an electron. What's an electron? It's a negatively charged molecule that we that's how we measure current.

Peter Williams  41:42

So I think we're both in full agreement that all the action is getting yourself fit and healthy and fit and strong. So again, you know the problem is, everyone wants the golden the Golden Pill.

Nathan Bryant  41:57

Well, I would, I would argue that nitric oxide is foundational. Everybody needs it. Everybody should understand what it does. But it's not a magic bullet, no.

Peter Williams  42:08

But I think what we've learned this, why we're on the podcast I was so keen to get you on, is that it's, it's everyone's excited about it at the moment. And I suppose that's good and bad, as you were saying, because there may be a rush to develop something that actually doesn't deliver what you want. And would you would suggest that nitric oxide, if it's the real deal supplementally, is okay for everyone to take.

Nathan Bryant  42:36

So for supplement, it's meant to supplement what's missing. And so in order to do this, I had to go through a rigorous kind of arithmetic problem, how much nitric oxide does a healthy person make in 24 hours through the enzyme? And we quantify this through radio labeled isotopes of Arginine decipher. And then how much nitric oxide does a person make through normal dietary patterns, having the right oral bacteria, having sufficient stomach acid production. And so we quantify this, and then we look at different populations based on diet, mouthwash, use fluoride, toothpaste, use antacid use. And then we figure, okay, the general population is here. We need to be here. So I dial in what's missing. It's supplemental in nature. But for supplements, you have to only give what one could achieve through normal dietary patterns and through lifestyle. So that's the upper limit on what we can do in supplement. So for drug therapy, we're we have to demonstrate not only safety, but ethical. Yeah. So the amount that we use in supplement is much different than the amount we're going to have to deliver to a patient with Alzheimer's or dementia or patient with ischemic heart disease, because they're not only they're grossly depleted for many, many years. That's why they have end stage disease. So as we develop our drug therapy, we'll increase the dose, the potency. But for everybody, a supplemental, a daily supplemental dose, to me, is absolutely essential, just because of the problems and the limitations with diet and lifestyle.

Peter Williams  44:01

And of course, the most of denture you are, the more your blood pressure is elevated, the more you probably you know, the more erectile dysfunction you have. I probably, probably say, probably the the worst cardio metabolic profile that you're probably looking at. Well, this is probably a good thing for because I'm look, we use a lot of supplementation, but that's usually based on individual patients and individual test results. So we're not and it's very rare that we're ever going to guess, yeah, but what So, and that's what we want to be able to do, is make sure that if we're going to give you something, we've definitely got the best chance that we're going to get. Going to get what we think we're going to get out of it. And I totally agree on the supplemental world that I think it's it, it's, it's, I think it's just as bad as probably farmer, from a point of view of there's, you know, and I think you have to pay. Quite a bit to get decent supplementation because of the standard quality assurance that it's gone through to try and say you're going to get what it is on on the tin. But Nathan, the other really interesting thing that we've learned over over two decades now is comes back to what you said about it's a question of whether your body has the capacity to absorb and assimilate. And this brings us back to HCL production, digestive enzyme production, because we've seen people through no fault of their own and no fault of ours, we've used a good strategy supplementally, we've used very high quality supplements, and it's not really worked. And I mean, it doesn't happen that often, but it happens, and the reality of that is because they probably just didn't, they didn't have the capacity to absorb in the simulator. I think a lot of times we go back to the fundamental basics and go, let's just give you the digestive M sign, some hate and some stomach acid, you know, and let's see what happens from there and then hopefully. But again, you know, comes back to the fascination of how important what's happening in the mouth is with regards to your body, which becomes incredibly important, second most important microbiome. And again, it's the sort of our first contact with the outside world, if you like. That's right look at it, and

Nathan Bryant  46:22

that's why mouth breathing is so bad, because it completely changes the oral microbiome.

Peter Williams  46:27

So So talk me through that. Because, again, these are these sound like fluff concepts when you're talking to other people, but you know, we know that we've got you on because because of your background. So when this is coming from you, it all starts to have that much more credibility. When we're saying to people, you know, this is one of the key things about understanding why you should try and breathe through your nose, and actually why when you're asleep, if you're mouth breathing, that that has consequences for us, cardio metabolically based from a vascular perspective. So can you just expand on that?

Nathan Bryant  47:06

Yeah, so, you know, I take important clinical observations, right? I'm not. I'm different than most active additions and biochemist, I don't try to take my favorite molecule or protein and put a square peg in a round hole. What I like to do is take important clinical observations, we know that mouth breathing is extremely harmful, and sleep apnea, at least increase, you know, increase your risk of heart attack and stroke, and they all cause mortality by 10 times. What's the mechanism? Well, I'm not saying nitric oxide is the only mechanism, but part of that mechanism is because if your mouth breathing, you know, the mouth is not an instrument for breathing, the bacteria in there are are made for a certain ecology. And so when we mouth breathe, we're fully oxygenating the oral cavity. We're dropping the pH completely changes the diversity, decreases the diversity. Now you get an acid environment, acid saliva. Not only that, you're bypassing this normal nitric oxide production through nasal breathing. And so we become hypoxic at night. We're not fully oxygenating. We're not mobilizing stem cells. We don't repair and replace tissues. We never really get into deep sleep. And when you when you can't sleep, bad things happen. Yeah? So if you do, you know mouth taping, which I always recommend go see an airway specialist first, to make sure you don't set the anatomical obstruction. Yeah, it's very important to nasal breathe, and biochemically and mechanistically, we can explain all the clinical observations from nasal breathing and lowering your blood pressure to relaxation to mouth breathing and getting just the opposite.

Peter Williams  48:32

Yeah, and I will just back that up, because the dentist we work with, they are fundamentally the first thing is airway management is the course of call that they say to us, there's got to be a way management before we do anything else. And you know, I think what they also do, certainly some earth like and John Roberts, who I work with quite a bit, you know, when you start changing the architecture by putting a sort of full new set of teeth on, is that you may not be doing the right thing at all for that, you're setting yourself up potential problems in years to come in. And he said to me, Listen, if you can hold onto your natural teeth as long as you can, then that's what you should be doing. That's what we recommend. And this, for me, has been a massively expanding world with regards to just how important your alignment is, and that capacity to breathe appropriately is super, super important, mate, I know you're, you're, you're low on time here. So can you summarize to everyone who's going to listen what are the most important things that we need to think about? And also, maybe we should have conversation about how, how we because I know you're trying to get your product into the UK, we're interested in that.

Nathan Bryant  49:47

Yeah, no, look, this goes back to our conversations. Stop eating sugar and high carbohydrates. Get rid of fluoride in your toothpaste if you're using mouthwash, stop and try to wean off antacids, and then, you know, exercise. Every day in a good, clean diet in moderation, I do an 18 hour fast every day. Once a week, I do a 24 hour fast every quarter, I do a 48 or 72 hour fast. That works for me. I think those, those basic principles right there, have made the biggest I'm probably in better shape today at 51 than I was at 35 and yet I've got the basket rates of a 32 year old even as a 51 year old. So I know and I quantify and collect data on what I do. And those have been the pube. Those are those have moved the needle more than anything I do. And I think everybody that record that I recommend that to, and they adopt those principles, they move the needle. And then it's really that simple. But you know, I wake up every morning, usually around five or 530 because I'm every morning, I dedicate at least 90 minutes to me. I sit an infrared song every day for 30 minutes. At 170 during that 30 minutes, I'm praying, doing meditation, then I get up. I exercise for for 30 minutes. I'm doing cardio. I do squats, push ups, working against my own body. I stretch. I do a cold plunge. I watch the sun come up. I sit naked in the grass on my ranch in Texas, watching the sun completely resets my circadian rhythm. But you know, if I if I waited till I had time to do that, I wouldn't have time to do it. To make time to do it. That means I have to get up earlier than anybody else and get that in. So at seven o'clock, you know that 90 minutes of good physical exercise and good mental training, spiritual training, emotional getting me ready to take on the day, and it puts me ahead of the competition.

Peter Williams  51:28

So I think we'll put all of your details on the show notes. And it's just been I've said I know you're busy, because I could have actually just sat here for hours

Nathan Bryant  51:43

chatting about, I feel like we're just getting started. Well, look,

Peter Williams  51:47

we are. And again, this, here's the thing, isn't it is that, you know, as a clinician that's got to speak to patients, it's very difficult to translate all the biochemistry and then get into here's what you've got to do, and here's what this means. But I think, you know, we can conclude on this is that it is, this is a very, very important gas, if you'd like, that is probably one of the key players with regards to vascular health, and that vascular health is associated with the world's biggest killers, because cardiovascular disease is still by far the world's biggest killers, and unfortunately, we're moving into the pandemic of neurodegeneration and Alzheimer's as well. And that really is, again, what you're saying is it's a question sometimes, is that the motorways and the arteries and the roads that supply oxygens and nutrients and blood flow are compromised, and this is one of the key players that helps offset that. Absolutely Nathan, look absolutely pleasure. Thank you so much. I think this will be absolutely cracker of an episode, and I'm pretty sure we're going to get some kick back on this from from quite a lot of people who are super interested in in I mean, certainly what you said about beats as well, and it's not just about that. I mean, again, I think that's absolutely fascinating, because I can definitely say I said to people, yeah, go and buy those beat products.

Nathan Bryant  53:15

Well, it's just

Peter Williams  53:17

pushing what I say to them these days that maybe, you know, they may work, but they may not do.

Nathan Bryant  53:24

I'll follow up with an email, and, you know, put our information in there. But you know, we'll advertise the book, because everything we talked about is in the book. It's the latest, up to date information, yeah, so

Peter Williams  53:35

we'll get all those details, and we'll get Shelley to organize that. They'll go on the show notes and and we can take it from there make real pleasure. Thank you so