Unlocking The Power Of Nitric Oxide: Conversations With Dr. Nathan Bryan

Lisa: Well, hey team, and welcome back to Pushing the Limits. Now this week I do a deep dive with a scientist, Dr Nathan Bryan, on nitric oxide. What is nitric oxide? It's a gas that the body produces, and we produce a heck of a lot of it when we're young and less of it when we're old, generally. It's a crucial compound that the body needs for so many benefits. So Dr Bryan is an international leader in molecular medicine and specifically in nitric oxide, so he's going to share with you all about this and what you can do to improve the production of it in your body, how you can test for it, how you can influence it by what diet you have, also what supplements you can take to improve this.

Lisa: Now this is very, very important for cardiovascular health, also immune health, sporting performance, a whole lot of things. Now, as an athlete, I used to take beetroot juice thinking I was upping my nitric oxide, and Dr Nathan Bryan explains why I may have or may not have been able to do that with beetroot juice alone. He talks about the pathways that are involved, two of the pathways that the body uses to make nitric oxide, what happens when you don't have enough of it, things like blood pressure, and how it relaxes the blood vessels. So a super deep dive into this very, very important topic.

Lisa: And most importantly, I think he has come up with ways to get more nitric oxide into the body through supplementation, because when you're older and you have a nitric oxide enzyme that is not coupled and not functioning properly, this may be the only way that you can actually overcome that. And for people who are struggling with things like cardiovascular disease and blood pressure problems and oxygenation, because it's part of oxygen delivery to the body, then this is a super important episode for you to listen to. I have Dr Bryan's lozenges that he has developed now in the shop, so if you are interested in getting that after listening to this important episode, then please head over to lisatamati.com, hit the shop button and put in the search bar "nitric oxide" and it will come up for you. Right, over to the show now with Dr Nathan Bryan.

Lisa: Well, hi everyone, and welcome back to Pushing the Limits. Today I have a superstar in the world of science and health and longevity to guest. I have Dr Nathan Bryan with me. Welcome to the show, sir. It's really wonderful to have you.

Dr Nathan Bryan: Thank you, Lisa. It's great to be with you tonight.

Lisa: Oh, it's been a long time coming, this podcast. I'm sorry we've had a few hiccups along the way, but we're going to be diving into the world of nitric oxide, which is what you've spent your life really studying. So, Dr Nathan, can you just give us a bit of a brief overview of how the heck did you get to be the world's leading expert on nitric oxide?

Dr Nathan Bryan: Well, it's just like any career, it's a journey, right? So I started out, I got a bachelor's degree in biochemistry from the University of Texas in Austin, and I quickly realised that to really get where I needed to be I needed to further my education, because with a bachelor's degree in biochemistry the job market really wasn't great. So from there, I'd always had an interest in science and medicine, so I enrolled at LSU School of Medicine and I first completed a PhD in molecular and cellular physiology. And that was at the time that a Nobel Prize had just been awarded for the discovery of nitric oxide.

Dr Nathan Bryan: So during my PhD work, I was kind of tasked with trying to find ways that we could analyse or detect very small amounts of nitric oxide that are produced physiologically — nanomolar, femtomolar levels of nitric oxide gas. So I developed these analytical techniques and then we really had some tools that not a lot of research labs in the world had. And from there, I think I finished my PhD in a year and a half or two years, and then I went and I was a postdoctoral fellow at Boston Medical Center where I continued the work on nitric oxide. And we were very productive during those years. This was the early 2000s; we were publishing 10 or 12, sometimes 15 papers a year.

Lisa: Wow.

Dr Nathan Bryan: And then I was recruited by Ferid Murad, one of the gentlemen who shared the Nobel Prize, because he was familiar with the work we were doing. And that was when I got my first independent faculty position at University of Texas Medical School in Houston. And from there we just kind of started making discoveries, filing patents, and it turns out we made a lot of seminal discoveries in the field. And I'm the first and only person to ever make a solid dose form of nitric oxide gas. So now we know how the human body makes nitric oxide, we understand what goes wrong in these people that can't make it, and now we have technologies that can restore and recapitulate nitric oxide-based signalling. So that's kind of the 25-year story condensed into two minutes.

Lisa: Into two seconds. And you mentioned Dr Murad, and the Nobel Prize is not given for nothing, and nitric oxide — I think this was in 1998 or something. So you've sort of grown up in this space with nitric oxide. And for the listeners who don't know what the hell nitric oxide is, shall we start there — what it is and what its role in the body is and why it's just absolutely crucial that we're talking about this today?

Dr Nathan Bryan: Well, it's really a signalling molecule, meaning that it's how cells in the body communicate with one another. But interestingly, when it's produced in the body it's a gas, and it's gone in less than a second.

Lisa: Wow.

Dr Nathan Bryan: But during the time it's produced, it activates a number of signalling cascades and controls a number of different important physiological functions. So it's recognised primarily as a signal in the blood vessels, the lining of the blood vessels. So when it's produced, it opens up the blood vessels, so it leads to vasodilation. So when you can open up blood vessels upon demand, you get an increase in oxygen and nutrient delivery, you improve blood flow and circulation, it reduces inflammation in the lining of the blood vessels, which is what causes cardiovascular disease. It's produced in our neurons — it's a neurotransmitter in the central nervous system — and it's how our immune cells kill off invading pathogens. So when we're exposed to a virus or a bacterium, then our immune cells quickly mobilise, go to the site of infection or attachment, and then generate nitric oxide, and it kills bacteria and it prevents viruses from replicating.

Dr Nathan Bryan: So now that we understand the full roles of nitric oxide, one can begin to appreciate that if your body can't make nitric oxide, there are a lot of bad things that happen. Number one, high blood pressure. You develop sexual dysfunction, you become very susceptible to viral infections and bacterial infections, and you start to lose memory and develop mild cognitive disorders, vascular dementia, and if not corrected it will develop into Alzheimer's. So that's kind of, in a nutshell, what nitric oxide is. It's a critical signalling molecule that regulates very basic biological functions, from the uptake of oxygen and oxygen delivery to every organ, tissue and cell in the body, regulating blood flow and circulation, modulating inflammation, and it's critical for our immune function.

Lisa: And so we've got sort of two pathways in the body, which we'll probably get into in a second, where the nitric oxide is produced, so to speak. And if it's only there for a split second, people are like, "Well, is that important?" But when you said signalling molecule, that's always a really interesting concept, a signalling molecule, because that sort of gives instructions to the body to do something. That's really, really important.

Lisa: And as we get older, and as we live in this toxic soup that we're living in, called planet Earth at the moment, where we're surrounded with so many things that are going wrong, from EMFs to pesticides to fluoride in our water to, you name it, medications — yeah, there's a number of pathways that I sort of want to mention to people there. But this is why this starts to go south, this starts to become dysfunctional in so many of us, and it's happening earlier and earlier. It used to be something that maybe in the 50s and 60s you started to be dealing with, but it's happening earlier that we get dysfunction in our nitric oxide. Can you elaborate a little bit on some of those points?

Dr Nathan Bryan: Yeah. I think it's a great segue into how the body produces nitric oxide. There's an enzyme called nitric oxide synthase — it's the enzyme in the body that produces nitric oxide gas. That enzyme is found primarily in the lining of the blood vessels; in fact, it's found in almost every cell type, not just in blood vessels — neurons, epithelial cells. So the function of that enzyme is dependent upon a number of different cofactors and substrates. And so the normal dietary patterns and exposure to things like EMF, glyphosate, pesticides, all render this enzyme dysfunctional. Or if you're under a lot of oxidative stress and you're eating an inflammatory diet and you're not getting enough exercise, exposure to all these toxins, then it leads to this enzyme becoming dysfunctional. We call that uncoupling, and we refer to that as endothelial dysfunction. So the endothelium's inability to produce nitric oxide, we call that endothelial dysfunction.

Dr Nathan Bryan: So if you look at kind of population studies from even 10, 15, 20 years ago, we found that we lost on average about 10 to 12% of our endothelial function per decade, and that's starting in our late teens, early 20s. So historically, by the time you're 40 or 50 years old, you only have about 50% of the function of that enzyme you did when you were younger. But now we're finding 20, 24-year-old young men who have erectile dysfunction and who have a vascular age of a 50- or 60-year-old.

Lisa: Wow.

Dr Nathan Bryan: So now we're starting to see vascular dysfunction and nitric oxide insufficiency very early on. And when you lose the ability to produce nitric oxide, that sets you on a very slippery slope for the onset and progression of cardiovascular disease, which remains the number one killer of men and women worldwide. So we have to figure — now we know how to recouple that enzyme, we know what contributes to the loss of the function, and so to make a long story short, we can recouple that enzyme and prevent this age-related decline in nitric oxide production.

Dr Nathan Bryan: But the beauty of that is that there's second-to-second regulation of nitric oxide. And my argument was, if this is such a critical molecule, then the human body would not develop to have a primary or a singular pathway to make this. And so there's a backup system, and that backup system comes from the diet. In fact, it explains the mechanism of a plant-based diet, a Japanese diet, a Mediterranean-based diet. So a certain compound called nitrate, inorganic nitrate, is found primarily in green leafy vegetables, and when we consume these certain food patterns, then the body can convert that into nitric oxide and really compensate for the loss of nitric oxide being produced in the lining of the blood vessel. So one can compensate for the other. But when you lose the ability to produce nitric oxide from the diet and in the lining of the blood vessels, then you become nitric oxide deficient and you start developing symptoms, disease, and eventually die.

Lisa: And this is why your mum told you to eat your leafy greens — and why I tell my mum now every day to eat your leafy greens. But the problem is also then that our soils are not what they were, and that you can't always know that you're getting the nitrates. And even, I heard on one of your lectures you're talking about...

Lisa: Like organics — great, right? We'll get rid of the pesticides, and all that's great, but we're also not allowed, with organic rules, to use nitrate, and actually that's detrimental. So some of the organic veggies have got even less nitrates in them. And then my mind goes to nitrates — isn't that the stuff that's in bacon, and isn't that bad? Can you comment on that?

Dr Nathan Bryan: Yeah. So if you just look — we've tracked this, and there's data from the 1940s, and we look obviously in the US, but it's probably consistent around the world — the nutrient density of the vegetables from the 1940s compared to 2010, there's a 78% decrease in nutrients in the vegetables. So the pressures of feeding a growing population are at the expense of nutrient density. So it's not just nitrate, it's many trace minerals like selenium and chromium and many important nutrients that most people are missing.

Dr Nathan Bryan: So when we start to look and try to quantify the amount of nitrate that's in specific vegetables, and really in specific regions around the world, we find that there's a huge variability. So the difference in soil conditions, the amount of sunlight, the amount of lightning storms in a particular area, all determine the amount of nitrogen that's fixed in the soil, so that when the vegetables are grown they assimilate nitrate that we then consume. So there's a huge geographical difference — as much as a 50 to 60 fold difference from, say, the southern US in Texas versus the northeast in New York, for example.

Dr Nathan Bryan: And then, as you mentioned, organically grown vegetables typically have five to 10 times less nitrate than conventionally grown. The reason for that — at least in the US, and different governments have different regulatory restrictions — but in the US, to be called organic, number one, you can't add herbicides or pesticides, which is a good thing. But number two, there's restriction on the amount of nitrogen-based fertilisers you add to the soil. So you can add manure, you can add compost, but to get an organic label there are restrictions on a standardised nitrogen-based fertiliser of the soil. So as a consequence these soils are deficient in nitrogen, they're deficient in nitrate, so there's less nitrate to assimilate in an organically grown vegetable.

Dr Nathan Bryan: But this is kind of the aha moment for a lot of people, because they go, nitrate — and as you said, is that the stuff in bacon and hot dogs that we're told to avoid? And it's the exact same molecule, but the media hasn't been forthright with us and honest in all the communications, and there's enormous pressure by big food, and consumers are a little bit confused. It's really deception.

Dr Nathan Bryan: So this whole thing about nitrate and nitrite and cured and processed meats causing cancer and should be avoided started in the 1950s, when it was first recognised that in some fish cured with nitrite, they formed nitrosamines — some pre-formed low molecular weight nitrosamines — and then nitrosamines are carcinogenic, mutagenic compounds. So that's how they kind of put the story together: that nitrite forms nitrosamines, nitrosamines cause cancer, oh, and there's nitrite in cured and processed meats, then they cause cancer.

Dr Nathan Bryan: Well, over the past 30 years that story's completely fallen apart, because in the 1980s it was first discovered that the human body actually produces nitrite and nitrate. In fact, it was those fundamental discoveries that led to the discovery of nitric oxide. So the body would never intentionally produce a carcinogen, right? When we're naturally producing these — these are typically environmental toxicants that once we're exposed to, then they're metabolised in. So that really right there should have put that story to bed.

Dr Nathan Bryan: And then about 20 years ago we started revealing that about 85% of the nitrate that we get from our diet comes from green leafy vegetables, and only 5% of the nitrate we get from our diet comes from cured and processed meats, and the other 10% comes from swallowing our own saliva. So if this whole story were true, that nitrate and nitrite cause cancer, then people who eat a plant-based diet, or vegetarians, or the Japanese, would have 10 times higher rates of cancer than those people who eat processed meat. And we know it's just the opposite: that people who eat a plant-based diet have lower incidence of cancer.

Dr Nathan Bryan: And now we know that nitric oxide controls cell cycle. It actually has anti-cancer, anti-tumour activities. It gets oxygen to a hypoxic tumour, and cancer doesn't like oxygen.

Lisa: Nope.

Dr Nathan Bryan: So now we know that nitric oxide has some very potent anti-cancer effects, and you can do this through repletion of nitrate and nitrite from the diet.

Lisa: That's really interesting. So I've released a book called *What Your Oncologist Isn't Telling You*, which is all about the metabolic approach to cancer, because I had a mum had CNS lymphoma on top of her aneurysms and strokes and GI bleeds, and we were given weeks to live. And so I went full research mode and did the whole sort of dozens of interviews with world-leading experts in this area. And this was a question in my mind, and why two years ago I didn't put nitric oxide into Mum's protocol, because I wasn't sure of the implications at that point. So that's really an important point for me to understand — that that is actually something that's going to be beneficial.

Lisa: And it sort of reminds me, because I have a hyperbaric oxygen therapy clinic, and hyperbaric is very powerful also because it's delivering oxygen to the tissues. And when I read some of your work, that there's actually three gases involved in the respiratory process — I don't want to butcher the science, because I don't have it inside out, but there's not just oxygen, and we breathe out the carbon dioxide and stuff, but there's the nitric oxide helps it get into the tissues. Can you explain that so I don't butcher it?

Dr Nathan Bryan: Sure. Well, let me just go back to the hyperbaric. Hyperbaric is very effective in cancer because it oxygenates the tissue, but hyperbaric works mechanistically because it increases nitric oxide production, which then mobilises stem cells, which then goes and repairs and replaces dysfunctional tissue. So nitric oxide is extremely protective in most, if not all, chronic disease, including cancer.

Dr Nathan Bryan: But when you talk about the three-gas system of the cardiopulmonary cycle — when we breathe in oxygen, oxygen binds to the iron of haemoglobin in our red blood cells, and then it goes from the arteries to the veins through capillaries, and during that transit from the arteries to the veins it senses a switch in oxygen tension. And then the haemoglobin undergoes a change in structure and releases oxygen, picks up CO2, then we exhale out carbon dioxide.

Dr Nathan Bryan: And in 2015, Jonathan Stamler really solved the puzzle on this, showing that that process only works if you have nitric oxide down the haemoglobin in the red cell. So it's nitric oxide that actually controls the release of oxygen, picking up CO2. So the whole Bohr effect, which means you can control oxygen uptake and oxygen delivery based on changes in pH, oxygen tension, carbon dioxide and 2,3-DPG — these metabolites that control the Bohr effect — is really controlled and regulated by nitric oxide gas. Because if your body's not making nitric oxide and there's no nitric oxide signalling in the haemoglobin of the red blood cell, then oxygen does not come off.

Lisa: Wow.

Dr Nathan Bryan: So then people become systemically hypoxic, right? We saw this in COVID. We all survived COVID for the past three years, and the problem was that the patients were losing blood oxygen saturation. So what happens? If your blood oxygen saturation goes below 90, they take you to the hospital, they put you on 100% oxygen — still wouldn't improve oxygenation. They put you on a mechanical vent — still didn't improve it. And then people died. Well, all we had to do was produce nitric oxide, or give nitric oxide, and even breathing room air we saw in our COVID trial that patients would go from blood oxygen saturation of 78 to 96 within eight minutes.

Lisa: Well, taking nitric oxide, I bet that didn't get adopted in all the hospitals of the world, as it should have been.

Dr Nathan Bryan: We had a phase three clinical trial during COVID, and there was a lot of resistance to what we were doing, because it was really a safe and effective early treatment. And at that time, the so-called experts and the people in charge weren't interested in early therapy. They were interested in vaccine mandates. Which, fast forward three years, we know that not only are they not safe, they're ineffective in preventing the transmission, sickness and death from COVID.

Lisa: And yeah, we're seeing a lot of vaccine-damaged people walking in my doors anyway, and a lot of it is hypoxia. There's carditis, myocarditis, all that sort of stuff. But if you trace that back — so my mind goes to, well, the nitric oxide lozenges that we'll get into a little bit later would be beneficial in, say, long COVID or post-vaccine damage or anything like that.

Dr Nathan Bryan: Yeah. The problem is the spike protein, right? It's not really the COVID infection, it's the inflammation caused by the spike protein. So whether it's active COVID infection, or now these vaccinated people whose own cells are now generating the protein for the rest of their lives — they've got to deal with this toxic poison for the rest of their life, because now it's integrated in their own DNA, they're constantly making it. So now the question is, how do we mitigate the effects of the inflammatory damage caused by the spike protein? And nitric oxide is front line to that, because we've seen that nitric oxide downregulates the ACE receptor, which is the primary target for the spike protein attachment, and it prevents the microvascular inflammation, platelet aggregation and the vascular inflammation that occurs as a result of either COVID infection or the vaccine-produced spike protein.

Lisa: Yeah, and we don't know when this is ever going to turn off in the body, and that's the scary part of it. It absolutely terrifies me. But we won't go down that rabbit hole, because we could be here for two days.

Dr Nathan Bryan: It should be criminal.

Lisa: Yeah, exactly, my opinion as well. I wanted to talk a little bit on mouthwash and fluoride and the microbiome in the mouth, and how important that is, because this is where the stuff is, like the nitric oxide — well, I'll let you explain that. Can you explain why we're doing something like — we think it's hygienic to do mouthwash every morning, like millions of us do — why the heck is that destroying our nitric oxide production?

Dr Nathan Bryan: Well, you have to — let's go back and talk about how things are adopted kind of in the global community in medical practice. And most of the time there's good intent. Let's get rid of the past three years, where we know there wasn't good intent to begin with. But historically in medicine there's good intent, and the reason people do things. So we know about an oral-systemic link, meaning that people who have poor oral hygiene have higher incidence of heart attack and stroke and cardiovascular disease. So the approach was, if these bacteria in the mouth are causing cardiovascular disease, let's just kill them. So they use antiseptic mouthwash.

Dr Nathan Bryan: Well, now fast forward 20 or 30 years and the human microbiome has been completely mapped, and we now realise that the bacteria that live in and on our body outnumber our own human cells ten to one, and most of these bacteria — I would say 99% of the bacteria that live in and on our body — are there as what we call symbionts. It's a symbiotic relationship. They're providing central metabolic processes for the human that we can't do, and then the human's providing them a host, kind of a safe host for them to replicate and do their job.

Dr Nathan Bryan: So part of the second pathway we talked about — when you get nitrate from the vegetables and then this can be converted into nitric oxide in the body — it's dependent upon the oral bacteria, because humans do not have a nitrate reductase enzyme. So again, it's the role of the bacteria.

Dr Nathan Bryan: It's the bacteria that live in and on our body, primarily the oral cavity, that perform this first metabolic activation of inorganic nitrate from our vegetables. And then the saliva is concentrated in nitrite, and when we swallow our own saliva we get a burst of nitric oxide gas in the stomach.

Dr Nathan Bryan: So probably 15, 20 years ago, some of the first studies came out showing that if you use mouthwash — people who use mouthwash saw an increase in blood pressure. And then we came on and tried to figure out, okay, what bacteria are responsible for maintaining normal blood pressure, because this is a new paradigm in the management of hypertension. So we found that if you eradicate the oral microbiome through antiseptic mouthwash, then it disrupts the conversion of nitrate to nitrite and nitric oxide, your blood pressure goes up, you lose the protective benefits of exercise, and bad things happen.

Dr Nathan Bryan: So in the US, two out of three Americans, or about 200 million Americans, wake up every morning and use mouthwash — sometimes they do this two or three times a day — and two out of three Americans have an unsafe elevation in blood pressure. Then in 2019 we showed for the first time that this is causal. So when you eradicate the bacteria — we took normotensive, really young, healthy medical students, dental students, and we just gave them mouthwash twice a day for seven days, monitored their blood pressure, did tongue scrapings — and we found that after seven days, in several people their blood pressure would go up 20 to 30 millimetres of mercury just by eradicating the bacteria. We didn't change their diet, we didn't change their exercise, we didn't change nothing. We just killed the bacteria in their mouth and we caused clinical hypertension in these patients.

Lisa: Amazing.

Dr Nathan Bryan: So we have to account for the oral microbiome. And there's a reason that your physician, if you have a bacterial infection that you take an antibiotic for, maybe 10 days at most, right?

Lisa: Exactly.

Dr Nathan Bryan: We know antibiotics are bad for us. You do not take an antibiotic every day for the rest of your life because of the collateral damage and the systemic effects and really the systemic disease chronic antibiotics cause. So the same concept applies in the oral cavity. You should not and you cannot use an antiseptic every day for the rest of your life. You can, but there's going to be some really deadly clinical consequences to that. It's going to be erectile dysfunction, high blood pressure, increased risk of heart attack and stroke, and bad things happen. So I tell people, if you're using mouthwash, you have to stop.

Dr Nathan Bryan: The other problem is fluoride. Fluoride's in water, it's in toothpaste.

Lisa: Yep.

Dr Nathan Bryan: It's not only an antiseptic that kills bacteria, but it kills your thyroid function, and it's a neurotoxin. It's one of the most toxic elements on the periodic table, and yet they put it in water and put it in our toothpaste.

Lisa: I know. They've just done it to us last month, and so we've had to redo a house with filters. And you're still getting it when you go out for a coffee at your local cafe. Mass medication, to me, is just — it's no wonder why we have the sickest population, right? We're doing all this money being spent on these incredible doctors with incredible things, and we're still getting sicker and sicker as a population. And it's just dumb stuff like this. And again, it goes back to the 1950s and one particular study that was done wrong and interpreted wrong.

Dr Nathan Bryan: Yeah. But the beauty of this is that it's not a lack of knowledge, right? We have the information, we have mechanistically, we understand what causes human disease. And so now we just have to apply this. We have to rework the medical care system and the way we train future physicians, and let them understand the mechanism of disease so that we can fix it. And really, pharmaceuticals aren't going to fix anything, because we have to understand the mechanism of disease. Your body's missing something that it needs, or it's exposed to something that it doesn't need. So if we repete missing nutrients and get rid of the toxins and the fluoride in our water and the antiseptics that we're using on an everyday basis, then the body heals itself. That's how the human body is designed. Give it what it needs, it heals itself. You've just got to get out of the way.

Lisa: And when we're talking about cardiovascular disease and dementia and diabetes, these are all the big killers. This is increasing our risk massively for this. Another one of my pet issues is proton pump inhibitors.

Dr Nathan Bryan: Oh yeah.

Lisa: I've got so many clients on proton pump inhibitors and it's a disaster. You do an organic acids test, or you do some testing with them, and you just see the minerals not being taken up, they've got dysbiosis, they've got cardiovascular problems, their protein synthesis is poor. And it disrupts your nitric oxide. What's the connection there? And I'm talking about your Metamucil, your antacids, your Tums, all of these things that people take for acid reflux or heartburn. Where are we going wrong here?

Dr Nathan Bryan: Well, look, I've never understood this. I'm a biochemist and physiologist by training, and you cannot suppress stomach acid production and expect the human body to perform. There's a reason our parietal cells in our stomach make hydrochloric acid. You need it to break down proteins into amino acids. You need acid to absorb things like iron and B vitamins and selenium and chromium and iodine. So without stomach acid, you don't get absorption of nutrients, you don't get protein broken down into amino acids, you start absorbing peptide fragments, and it's the basis for autoimmune disease and all food-borne allergies — it's lack of stomach acid. So that right there creates a problem on its own. That creates most of the world's health problems.

Dr Nathan Bryan: But as it relates to nitric oxide, these proton pump inhibitors actually inhibit an enzyme that leads to a breakdown of asymmetric dimethylarginine. So then you get a build-up of this metabolite and that shuts down nitric oxide production. And the other problem is, when we talk about swallowing our own saliva, even if you have the right bacteria and you swallow your saliva, that nitrite in the saliva is designed to produce nitric oxide gas in the acid environment of the stomach. But if there's no acid being produced because you're on these antacids, then you basically completely inhibit nitric oxide production from both pathways.

Dr Nathan Bryan: And now there's data that people who have been on these drugs for three to five years have 40% higher incidence of heart attack and stroke. And just two weeks ago there was a new study out showing that people who have been on these drugs for four years have a 35 to 40% higher incidence of dementia and Alzheimer's. So these drugs are deadly, they're killing people. And I tell people there should be a black box warning on these drugs, just like there was on Celebrex and the COX-2 inhibitors back in the early 2000s. There's clear evidence that people who take these have heart attacks and strokes. The mechanism is very well defined, and we have to get these drugs off the market and start weaning patients off of these antacids. They're not only dangerous, but they prevent the human body from doing its job.

Lisa: Yeah, absolutely. I'm dealing with a couple of clients at the moment in that situation, and you're dealing with their doctors saying they have to be on it to protect them from ulcers or something.

Dr Nathan Bryan: Well, during COVID they were putting every patient that was admitted in the hospital for COVID — they would give them an antacid. Why? This exacerbated the condition, and I think that's why so many people died unnecessarily, because every protocol they were practising was counterintuitive and it led to increased susceptibility, increased risk, and increased death from COVID.

Lisa: Yeah, it just absolutely boggles the mind sometimes. I've just been dealing with the hospital last week, and wonderful people, wonderful nurses, wonderful doctors — except for a few arrogant consultants.

Dr Nathan Bryan: Oh yeah.

Lisa: I won't go into that story today because we might be here for another year. But you're dealing with paradigm shifts at the moment, and things are changing, and there's a lot more openness in the younger generation that's coming through. There's functional medicine, there's integrated medicine, and we're living in an exciting change. But sometimes it feels very glacial, and year by year, as certain ones are no longer practising, we will get change slowly, but it is a massively long process.

Dr Nathan Bryan: Well, there are very powerful forces going up against us, right?

Lisa: Yeah, huge.

Dr Nathan Bryan: I mean, what we're doing is changing the landscape of medicine and really affecting the financial model of medicine, and it's a trillion dollar industry. Big Pharma doesn't really want to cure any disease. They want to continue to treat disease, because that's the bread and butter, the economic model. But we understand the mechanism of disease today. It's not a lack of information. We don't need any more studies. Billions of dollars are spent on cancer research, cardiovascular disease. We have the information. It's the application of the science in clinical practice.

Lisa: Exactly, which takes 20 to 30 years to get down to the person in the community who needs the thing now. And that's why I do what I do, and share and educate and try and get wonderful people like yourself who have spent 25 years down one big rabbit hole to explain something in detail, so that people can understand that.

Lisa: Now, if we go back to when the Nobel Prize came out, then there was a whole lot of companies that came on the market that had nitric oxide boosting supplements. And I've tried a lot of them over the years, and we didn't see the results necessarily, because as an athlete we were all on big tubs of powder and things like that. Where have they gone wrong there, and why are not all nitric oxide supplements created equal?

Dr Nathan Bryan: Well, it's called advancement of science and knowledge, right? What we know today is much different than what we knew in 1998 when the Nobel Prize was awarded. So that really put nitric oxide on the map. I mean, the Nobel Prize is awarded for discoveries that change the landscape of mankind and humanity, so it's a fundamental discovery for the Nobel Prize to be awarded.

Dr Nathan Bryan: At that time we knew that there was an enzyme called nitric oxide synthase that converted L-arginine, which is an amino acid, into nitric oxide. So then a number of companies flooded the market with nitric oxide products that contained L-arginine. But now, understanding the enzymology and the biochemistry in patients who are nitric oxide deficient, the enzyme that converts arginine to nitric oxide is broken. It's dysfunctional and it does not convert arginine. So giving more arginine does not lead to any nitric oxide. In fact, now many studies show that giving arginine to a patient with an uncoupled NOS can actually cause more harm.

Lisa: Wow.

Dr Nathan Bryan: In two studies, post-infarct patients — so patients who suffered a heart attack — were given high dose arginine to try to improve nitric oxide, to try to improve outcome, and it killed more people than the placebo. They repeated that study in patients with peripheral arterial disease, which have endothelial dysfunction, and they got worse. So giving arginine to a patient that's nitric oxide deficient is like putting gas in a car with a blown up engine, right? They're not out of fuel. You're never

Dr Nathan Bryan: out of arginine, you just lost the ability to convert it. So that was kind of the first products that hit the market. And then in 2012, in the London Olympic Games, it was revealed that most of these athletes were drinking litres of beetroot juice, because there was some really good clinical study showing that beetroot contains nitrate which could be converted to nitric oxide and improve your performance.

Lisa: Yeah, I did it.

Dr Nathan Bryan: So then a number of companies brought to market beetroot juice. I've tested probably every product on the market, and most of these don't contain any nitrate, no nitrite, no nitric oxide activity whatsoever. So these are just — we call them dead beets. They're dead beet products. They don't do anything except turn your pee and your poop red and pink and cause a lot of anxiety.

Dr Nathan Bryan: So those are the two main products out there, and the companies that do this are just trying to capitalise on the market and the awareness around nitric oxide, but they have no idea about the underlying science and what it takes to make nitric oxide in the human body. Those were my frustrations, and that's what led me to develop nitric oxide products, because we know how the human body makes it, we know what goes wrong in people that can't make it, and we can fix this and provide a source of nitric oxide.

Dr Nathan Bryan: Our whole process was: if your body can't make it, then we've got to do it for you. But we also understand why your body can't make it, and we can fix that. So that's what we do that no one else does. And now there's companies out there who certainly know better, but they continue to defraud and deceive their customers by selling beets or gummies and all this other crap that they know better, but yet they're still trying to do it to capitalise on the growth of the nitric oxide market. So I tell people, just buyer beware. Don't believe the people who spend the most money on advertising. Look for real science and people who understand the enzymology and biochemistry of nitric oxide.

Lisa: Yeah, and that's the key thing, because it's the nitric oxide synthase, the uncoupling of the enzyme — that's the problem, isn't it? So you've got two sub-products. For those watching on YouTube, that's one of them, that's the lozenge that I'm on and Mum's on. And that is something you take like every 12 hours and it dissolves in your mouth. So explain this one versus the second product that you have.

Dr Nathan Bryan: Sure. Well, I have to remind people that nitric oxide is a gas, right? And so when it's produced, it's gone in less than a second. So there's only finite ways you can deliver nitric oxide. You can't deliver nitric oxide in a gummy, you cannot deliver nitric oxide in a capsule. So there has to be a way that you can generate this gas.

Dr Nathan Bryan: So again, I figured out that we could create this matrix, that we put these components together, then when you put it in your mouth, it slowly dissolves. I intentionally designed that to have a residence time of about five to six minutes. But as that matrix and that lozenge is falling apart, these active components are coming together and we're generating nitric oxide gas. So again, it's the only solid dose form of nitric oxide gas.

Lisa: Yes, yes.

Dr Nathan Bryan: So we're delivering a specific amount of nitric oxide that we can quantify, we can verify, and we can detect with a gas-phase nitric oxide analyser, and we deliver that over a certain period of time. So the whole concept was, we want to give the body what it normally would produce. If your body can't make it, then we've got to do it for you. We never want to give the body more than it was used to seeing.

Dr Nathan Bryan: But we also have components in there that recouple the NOS enzyme. So without getting too into biochemistry, there's a certain what's called an electrical potential, or redox potential, that's required to prevent the removal of an electron from biomolecules, and we know the rate-limiting step in that. So we maintain that redox potential so that we maintain the enzyme, the nitric oxide synthase, coupling. So now, when you take that lozenge, four hours later we see about a 15% improvement in the body's ability to make nitric oxide on its own. So we accomplished exactly what we hoped to accomplish. If anybody can't make nitric oxide, we do it for you. And it's vasoactive, meaning that when you put that lozenge in your mouth, if we use an ultrasound, we can see a dilation of the carotid within 12, 15 seconds.

Lisa: That's crazy, because I did a carotid scan yesterday on Mum. She'd had a lozenge an hour before.

Dr Nathan Bryan: It's probably going to show it's great.

Lisa: Yeah, there will be — probably if I'd done it before we had them, maybe not so much. But this is how quickly it impacts, and someone who's in their 70s, 80s. This is the other thing: you've got test strips as well, so we can actually test them. I haven't got those in yet, but hoping to get those, because I'm thinking with my clients, if we can test them, if you can see, hey, your NOS enzyme isn't working, you're not producing nitric oxide, we need to do something here. And they have limitations, but yeah, the test strips are a little bit...

Dr Nathan Bryan: I've gotten away from the test strips. I developed those back in, I think, 2010, and really the purpose was because people would ask, how do I know if I need nitric oxide? And you can't go and do blood labs like you can for cholesterol or vitamin D. So I developed this salivary test strip, and really, even then, we knew what we're measuring in the saliva is salivary nitrite, and really the ability of the oral cavity to reduce nitrate to nitrite.

Dr Nathan Bryan: So the issue with those test strips is there's no false negatives — so if you're low, you're low, right? We just don't know why you're low. Is it because you don't have the right bacteria? Is it because you're not getting enough nitrate from your diet? Is it because you have endothelial dysfunction? We don't know. The problem with the test strips is there are false positives, and we see this in patients with active dental infections. So you may have all the clinical symptoms — high blood pressure, erectile dysfunction, diabetes, exercise intolerance — but yet you use the test strip and it turns bright pink. Well, obviously that patient isn't making sufficient nitric oxide because of the clinical symptoms. What we're picking up is an active immune response in the oral mucosa due to an active oral infection.

Lisa: Yeah.

Dr Nathan Bryan: So I tell people the strips are good, because if you're low, you're low. But don't be fooled by false positives. So we really have to rely on symptoms. If you have erectile dysfunction, if you have an unsafe elevation of blood pressure, diabetes, exercise intolerance, you start to lose your memory — then those are all symptoms of nitric oxide deficiency.

Lisa: Yeah, exactly. But I think it's still powerful just to know, like, if you are low, with that limitation that, okay, you might get some false positives, and if you are positive but you've got all those signs, still take the...

Dr Nathan Bryan: Yeah, still — the majority of people are going to show low, right? And that's the beauty, because people think they're doing all the right things, and that's the conversation I have all the time. You've got these well-trained athletes who are eating a plant-based diet, exercising every day, they're in great shape, but they're using mouthwash, and yet their blood pressure is starting to elevate. They're completely white on the test strip and they go, what's going on? I'm doing all the right things. Yeah, you're doing all the right things, but if you use mouthwash or antacids, you completely abolish all the benefits of the good things you're trying to do.

Lisa: Okay, like all the athletes — because I've got a background as an ultra-endurance athlete, and so a lot of athletes listening to this will be like, you mean I've been training my ass off for the last 20 years for no apparent reason and I'm not getting anywhere? That might be why. Okay, get rid of that, and the fluoride if you can.

Lisa: And you've also got — if we can just jump over, because I know you've got to go shortly, and this is — I'd love to have you back on if you've got time sometime in the future, so we can go a little bit deeper into some things. But you have also developed a line of skincare. When I first saw this, I was like, what the heck? Skincare — great, I'm always looking for something to make my skin look nice, but I never sort of connected the dots. Can you tell us a little bit of your background about your story about your dad, why you got into the skin side of things and the cosmetics?

Dr Nathan Bryan: Yeah. I never intended or never thought I would be in skincare and beauty, but this goes back probably eight or nine years ago. My dad, who's a paraplegic from a car accident in 1984 — he just turned 75, so he's been in a wheelchair for more than half his life — and so we've dealt with decubitus pressure ulcers most of my childhood and adult life. So he developed a non-healing ulcer maybe in 2013, 2014, and every wound care doc I took him to said we couldn't heal this wound because he's older, he's diabetic, he's paraplegic.

Dr Nathan Bryan: And he got a massive infection in the wound, and so he was probably going to die from sepsis. And I just treated the wound with nitric oxide and developed the nitric oxide-releasing gauze. I put it into the wound and I covered it up, and the next day he was completely fine. His fever was normal, the wound looked good, it was completely granulated. And to make a long story short, we did this for a period of a year and completely healed this wound. We killed the infection, and I could see blood flow getting into the wound, we got tissue granulation, and eventually we did stem cells, we did a surgical flap and completely healed the wound. And now we're six years later and he hasn't developed any other wounds, and he's never gone through that period of time without developing some skin breakdown.

Lisa: Yeah.

Dr Nathan Bryan: So then the wound care docs, when I told them what I was doing, they go, how do we have access to this in clinical care? So obviously, to go through FDA clinical trials and get a topical drug on the market for wound care takes many years and hundreds of millions of dollars. So I developed a line of skincare products that's a dual chamber, that you mix these two together and you rub it on your face or rub it on different body parts, and it generates nitric oxide gas and it improves blood flow.

Dr Nathan Bryan: And when you think about this, the skin is an organ just like the heart, just like the brain, just like the sex organs. And if that organ isn't getting enough blood supply, then it fails. So what does a failing skin look like? Well, you lose collagen, you lose hydration, fine lines and wrinkles show up, you get acne, rosacea, psoriasis, autoimmune problems. So the nitric oxide, again, the same fundamental principles apply: if your body can't make nitric oxide, then we do it for you, and we actually improve the structure and function of the blood vessels in the skin. So you can actually see this product working before your eyes. When you apply it, you can see your skin will turn pink, so we're recruiting capillaries. I do demos on the back of my hand and you can see the veins pop.

Lisa: Wow.

Dr Nathan Bryan: As you add it on there, it diffuses into the skin, we improve blood flow. I think we've got five published clinical trials on that. We improve collagen deposition, you improve hydration, lines and wrinkles go away, polycystic acne, scar remediation, rosacea. There's really no dermatological condition where the nitric oxide that we're providing in that topical doesn't provide benefit. It's remarkable.

Lisa: I haven't got that one.

Dr Nathan Bryan: Well, it's a new category in skincare, because as you know, most skincare products are designed to hide or mask the fine lines and wrinkles or the blemishes. We get to the root of the problem. Why does your body have fine lines and wrinkles? Why does skin sag and develop age spots? It's because there's not enough blood supply to there. So if you can't get the good stuff in and take out the trash, you can't mobilise stem cells to regenerate and repair and replace those dermal cells, then you look old. So we provide nitric oxide, and nitric oxide does all that.

Lisa: Oh, get me some of that stuff, because I'm 55 tomorrow.

Dr Nathan Bryan: You're going to love it.

Lisa: I've got to stop, I've got to slow it down, getting that turkey neck thing going on.

Dr Nathan Bryan: Yeah, we can help.

Lisa: Yes, it's really exciting. I've been in the world of peptides and love GHK-Cu and all of that sort of stuff, but this is a completely different, a bit of a different shift in there.

Dr Nathan Bryan: Yeah, and now we've got what's called here in the US an investigational drug application in front of the Food and Drug Administration in the US, so we're developing this now into topical drugs for wound care.

Lisa: Wow.

Dr Nathan Bryan: Because we've seen — there's not a single wound that we haven't treated with our topical nitric oxide that we didn't heal. We've got four or five year old non-healing wounds that we were healing in a period of weeks or months.

Lisa: Wow.

Dr Nathan Bryan: Burns, diabetic ulcers, diabetic foot ulcers. It's a game changer in terms of wound healing.

Lisa: If we can't wait for the — like you've got an ageing mum whose skin is thin and just rips like nothing and ends up with ulcers — just use the normal skin serum? Or people with ulcers that I see regularly in the hyperbaric clinic. Because waiting for drugs and FDAs and things, you know, we'll be on a skeleton on a bench by the time they come through sometimes, sorry.

Dr Nathan Bryan: Well, we're hopeful, because this is so transformative and unlike anything wound healing has ever seen, that we'll fast-track this through FDA. So I anticipate, once we start the trials — we're healing these wounds so quickly and unlike anything any current standard of care does for these wounds — that I anticipate within the next two years we'll have a topical drug on the market that will completely change the landscape of wound care.

Lisa: Wow, this is just absolutely amazing, because I have been dealing with those sorts of problems with Mum when she was in a wheelchair for a couple of years before we got her back out of it. And just every older person is dealing with skin breakdown, becoming thinner, and all of those sorts of issues, and diabetic ulcers.

Dr Nathan Bryan: That's right, and it's just a blood flow problem. It's caused by poor blood flow, and then you apply pressure on certain pressure points, you further compress the tissue, further restrict blood flow, and it leads to skin breakdown. So when you apply nitric oxide, we overcome all that. And if you can just move the pressure, move the patients around. I think about this in nursing homes and long-term care facilities. This is a major problem.

Lisa: It's huge. We had to keep shifting Mum every couple of hours so that she didn't develop [problems], and she still developed some stuff. And this, with the hyperbaric oxygen, would be a beautiful combo, is what I'm thinking. Add some intravenous vitamin C in there and you're going to be really looking super young and super good.

Dr Nathan Bryan: The answers are out there, right? Especially in these complex patients, nitric oxide is foundational, but it's not a silver bullet, it's not the be-all and end-all. You still have to address these other concerns. But for us, we found it to be absolutely foundational. The body cannot and will not heal without nitric oxide. And so now we have to get this into the hands of as many people as we can, to not only provide a source of nitric oxide that their body is not making, but really improve their body's ability to make it. And when you do that, the patient gets better.

Lisa: You have a second product, so you've got the nitric oxide lozenges that sit on the tongue, and then you've got another product that just ups the nitrate levels in the body, is that right?

Dr Nathan Bryan: Well, that's the beet powder. People understand beets — the media and these companies have done a good job about educating consumers on the health benefits of beets. And so we did the same thing. We created a beet [product]. Number one, not all beets are created equal, as I told you — 99% of the beet products out there don't do anything. Number two, beets are the third least liked vegetable in the world.

Lisa: Yeah, including me. I don't like the taste of beet.

Dr Nathan Bryan: So what we did was something different that's never been done before. Number one, we control the growing process from the beets, from the seed to the time of harvest, the soil conditions, and then we take the beet powder and we ferment it. So we basically pre-convert our beet, so we're not dependent upon the individual's oral microbiome. In most beet products, maybe one out of three people get a benefit from it, because one out of three people have the right oral bacteria. What we do is we pre-convert it for you, and then we take out the beet pulp, we take out the oxalates, we take out the beet colour and the beet taste. So now we have a white, super concentrated nitric oxide beet powder, and we add electrolytes to it, we add mitochondrial ATP, and we give it a mixed berry flavour. So you've got a really beautiful white powder that doesn't taste or look like beets but provides nitric oxide. In fact, you have to take it as a shot. As soon as you put it in water, you mix it up and take it as a shot — just put it in two to three ounces of water and then throw it back. You can't sip on it, because as soon as it hits solution, it's generating nitric oxide gas.

Lisa: Right, so you just have to get it in really, really quick. Got to get it in, mix it and take it back. Which is best for the athlete — a combination of these products, these two, or just one or the other?

Dr Nathan Bryan: For athletes, the lozenge is meant to be your daily nitric oxide, so as a daily vitamin C or a daily vitamin D. The lozenge really gives you that sustained nitric oxide for a certain period of time and recouples the enzyme. Now, we really position the beet powder as a pre-workout for athletes, or as an energy drink. We have to get young kids off things like Red Bull and Five Hour Energy and Monster, because these are very dangerous stimulant-ridden drinks that kids shouldn't be [taking]. So we provide a natural energy source. What is energy, right? It's an improvement in circulation, it's improvement in mitochondrial function and actually ATP production — that's the energy currency of the cell. So we provide nitric oxide, we provide electrolytes for hydration, and we provide mitochondrial ATP. So it's the best energy drink on the market, and it's never been done before. And that's a very powerful product that we hope will take off and really give people a safe source of energy.

Lisa: Absolutely. And when you put both of these together, is that safe, or can you overdo it? Like, you're going to have two lozenges a day, 12 hours apart, is what I'm doing for Mum. If I was to get the beet stuff going as well, am I overdoing it, overcooking the goose, so to speak?

Dr Nathan Bryan: No. As long as you allow, say, four to six hours in between them. So personally, this is what I do. I take a lozenge in the morning, I'll typically go to the gym and work out in the afternoon or the evenings, so I'll take the beet powder as I'm walking into the gym. Again, it's quick acting, you don't need to take it 90 minutes before or 15 minutes before, you can take it as you're walking into the gym. You're going to get a great workout. And then when I travel a lot, I'll take a lozenge typically before bed. So I take usually two lozenges a day, the beet powder before I work out.

Lisa: Gotcha, that's a perfect combination. And obviously you're using the skin creams, because your skin looks pretty damn good.

Dr Nathan Bryan: Use that every day, yeah.

Lisa: Dr Bryan, you've just been absolutely amazing. I will let you go, because I know you've got about five minutes before you go deliver a lecture.

Dr Nathan Bryan: That's right.

Lisa: In a hotel room?

Dr Nathan Bryan: Yeah, stuck in another hotel room.

Lisa: Travelling, getting this message out, doing the amazing work that you're doing. You've written a number of books as well. Can you just tell us where do people go? I'm going to get your products, we're going to try and work a way to do that, so people check in in my shop and stuff, and reach out to me if you want to get it. But where do they contact you, what books do they read, where can they read some of the science?

Dr Nathan Bryan: Well, the first place I send people is to my educational website. I've got a website called DrNathanBryan.com. I'm not trying to sell you anything, I do a monthly blog, but really I'm trying to provide the up-to-date knowledge and information and science behind nitric oxide so that people can make informed decisions on what to do, how to modify their lifestyle, change some things up, stop using mouthwash, get rid of fluoride, get off antacids. Sometimes that's simple enough. I'm on PubMed — I've published over 100 peer-reviewed papers in the scientific literature. I'm on Instagram at Dr Nathan S Bryan, LinkedIn at Dr Nathan Bryan, Twitter at DrNitric. What else? And then I've got a book called Functional Nitric Oxide Nutrition, that's been published now for about four years. I've got a new book coming out in January called The Secret of Nitric Oxide: Bringing Nitric Oxide to Life. So stay tuned to that one. That's part autobiographical, talking about how we made these discoveries that really transformed nitric oxide, and kind of our personal journey, but also the real science around nitric oxide, and really trying to build the global awareness so people understand nitric oxide and the importance of it, so they can take control of their own health and start to apply these things into their everyday life. Because we know the healthcare system isn't going to take care of us, we have to learn to take care of ourselves.

Lisa: And I've read your first book, and that was absolutely fabulous. I look forward to the second one, and maybe when that comes out you can jump on the show again and walk us through that. You're an absolutely amazing person. I thank you so much for the passion that you bring to this space. You're really helping millions of people around the world with what you're doing and bringing the science to light. I know that it's not easy bringing these things to market — as a supplement producer myself, I know that it's not an easy road, and doing drug discovery and all of that sort of stuff, oh my God, and trials and everything. So thank you so much for all the work you do. You're just absolutely amazing.

Dr Nathan Bryan: Well, thank you, Lisa. Keep up the good work. It's been great to spend an hour with you, and we'll certainly do it again.