Increase Nitric Oxide: Fix Blood Pressure & Inflammation Naturally – The Primal Podcast (Transcript)

One of them is mouthwash. So, Dr. Bryan, my first question. Let’s start from the beginning. What is nitric oxide?

DR. NATHAN BRYAN: Well, it’s a signaling molecule that’s produced naturally in the human body. It’s produced in the lining of the blood vessels. It’s produced, as you mentioned, in neurons in the brain. It’s produced by our immune cells to kill off bacteria and viruses. But it’s this naturally produced molecule. But interestingly, it’s a gas.

And once it’s produced, it binds, it hits its targets, and then it’s gone in less than a second. And this was a new paradigm in cell signaling, you know, 30 years ago. And in fact, it was so revolutionary and so important that a Nobel Prize was awarded in 1998 for the discovery of nitric oxide. Because signaling by a gas really transformed the way we thought about traditional cell signaling pathways, kind of this lock and key type of signaling that we were all familiar with prior to gaseous signaling molecules.

But, you know, you hit the highlights here. It’s naturally produced, it’s involved in most biological functions, from regulating blood flow and blood pressure and reducing inflammation, preventing oxidative stress and immune dysfunction that we see in chronic disease. It activates telomerase enzyme, prevents telomeres from shortening, mobilizes our stem cells, and activates mitochondrial functions. So the energy production of every cell in the body, we start to see this really clear picture of how important nitric oxide is. But probably most importantly, if you lose the ability to produce nitric oxide, there are many things that go wrong and many diseases that manifest.

Why Don’t Doctors Talk About Nitric Oxide More?

RINA AHLUWALIA: So we’re going to talk about every single one of those, all the benefits, because it’s so miraculous, this miracle gas and molecule. And what it does in the body. Let’s talk about why doctors and the medical industry don’t talk about nitric oxide more. What’s the reason?

DR. NATHAN BRYAN: You know, I’m still, you know, I was in academia for 10, 15 years and I taught future physicians in medical school. And I still give probably 30, 40 lectures a year all around the world to physicians, healthcare practitioners. And I think we’re making a dent and making some progress and building the awareness around nitric oxide.

But here’s the truth. The truth is, historically we know that it takes on average about 17 years for new scientific discoveries to become incorporated into standard of care, into clinical practice. You know, so the discovery of nitric oxide was probably, you know, date back 30, 35 years ago. A Nobel Prize was awarded 26 years ago. So we’re certainly past that average of 17 years where there should be an adoption.

But I think the reason it’s been slow is because there’s no safe and effective drug therapy that physicians can use and prescribe for their patients in their clinical practice. You know, there’s hundreds of products in the nutrition, dietary supplement field. But most companies have been unsuccessful at developing safe and effective nitric oxide drug therapies.

You know, we’re aiming to change that through my drug company, Bryan Therapeutics. We’re moving this nitric oxide technology through the FDA, through drug trials. And it’s our intention and our goal to have these, at least one drug approved on the market by next year. And then I think once physicians have, you know, a drug that’s FDA approved that they can utilize in their patient practice, then I think it’s going to be global acceptance and adoption of nitric oxide based therapies.

Dr. Bryan’s Journey to Becoming a Nitric Oxide Expert

RINA AHLUWALIA: Absolutely. Let’s talk about you, Dr. Bryan, because you are an expert in nitric oxide, which is, I would say it’s a little bit peculiar because it’s very specific in terms of a molecule that somebody could be an expert in. It’s fascinating. How did you become an expert in this field?

DR. NATHAN BRYAN: Well, it’s a good question as any career. It’s a journey, right? And we encounter certain things at certain times of our lives that allows us to pivot and then sometimes refocus. But I’ve always had an interest in science and medicine. I had a bachelor’s degree in biochemistry from the University of Texas at Austin. And from there I went in LSU School of Medicine where I got a PhD in molecular and cellular physiology.

And it was during my time at LSU School of Medicine where I was introduced to the new science of nitric oxide. It was the late 90s, a Nobel Prize had just been awarded. So we knew, the scientific and medical community knew that it was a very important molecule. But there was still a lot of unanswered questions. What are the production? How does the human body produce nitric oxide? Why do people lose the ability to produce it and then manifest these diseases?

But perhaps most importantly was, there were no known ways. How do we capture the therapeutic activity of this gas, this fleeting gas that’s produced naturally in the human body? How do we replete and restore nitric oxide production? So that to me was a lot of very important unanswered questions that, and we thought, we didn’t think, we knew that if we could answer those questions, then we could really change the world and change the landscape of medicine.

So that’s really when I delved, you know, kind of headfirst into the science. And I spent the next 20, 25 years trying to understand these unanswered questions. And today we understand how the human body makes nitric oxide. We have a clear understanding of what goes wrong in people that can’t make it. And now once we understood that, then we can start to develop product technology that could restore the body’s ability to produce nitric oxide, but also provide an exogenous source of nitric oxide, a therapeutic dose of nitric oxide, even in patients who couldn’t produce it naturally.

And so that’s, that’s been my 25 year journey in the nitric oxide field. And you know, I’ve kind of pigeonholed myself into this microcosm of nitric oxide research. But I think the implications of this very focused and dedicated research in our efforts is, you know, really has the potential to change the world.

The Four Hallmarks of Chronic Disease

RINA AHLUWALIA: It’s, it’s so incredible what nitric oxide can actually do for every part of the body. Let’s talk about how nitric oxide is related to chronic disease because people think about things that they get diagnosed with. So let’s just say that it’s Alzheimer’s, dementia, heart attacks, strokes, insulin resistance, it could be immune problems. All these different things we’re going to talk about one by one. Let’s start high level in terms of understanding chronic disease and the hallmarks of inflammation. What are the four hallmarks of chronic disease and how does it all trace back to nitric oxide?

DR. NATHAN BRYAN: Now look, that’s a fundamental question that we’ve been after, really medicine has been after for the past hundred years. And unfortunately Western medicine is kind of siloed into these so called specialists, right? But if you look at the hallmarks of every single chronic disease. It doesn’t matter if it’s autoimmune disease, Alzheimer’s, cardiovascular disease disposal, diabetes, there’s four fundamental problems.

Number one, there’s reduced blood flow to that organ. In dementia and Alzheimer’s is reduced blood flow to the brain. And ischemic heart disease, reduced blood flow to the heart and sexual dysfunction, there’s decreased blood flow to that organ. And the consequences of that is you get inflammation, oxidative stress and immune dysfunction. So the low blood flow, inflammation, oxidative stress and immune dysfunction are hallmarks of every single chronic disease.

Now, where does nitric oxide play a role in that? Well, when your body loses the ability to produce nitric oxide, it constricts the blood vessels and restricts blood flow to that particular organ. And then you get an upregulation of adhesion molecules, which is what we call vascular inflammation. That’s when you start to get the immune dysfunction. The immune cells start to extravasate outside the lumen of the blood vessel and elicit this oxidative stress. And then there you have it, you have reduced blood flow, you have inflammation, oxidative stress and immune dysfunction. And that explains every single chronic disease. And all of those result from the primary loss of the production of nitric oxide.

Why We Lose Nitric Oxide as We Age

RINA AHLUWALIA: So a good question would be, why do we lose nitric oxide as we age?

DR. NATHAN BRYAN: Well, if you look at kind of. So there’s two primary pathways where we produce nitric oxide. The first pathway to be discovered was through an enzyme called nitric oxide synthase. This enzyme is found in the neurons in the brain, it’s found in the lining of the blood vessels. But if you look at population based studies, the older we get, the less nitric oxide we make through that enzyme. We call that endothelial dysfunction.

On average, the average American is losing about 10 to 12% of their nitric oxide production per decade. And this starts in the late teens, early 20s. So then by the time we’re 40 or 50 years old, we only have about 50% of the nitric oxide we had when we were younger. And today we understand that we can shift this to the left. We can accelerate that loss or we can prevent the loss.

But the rate limiting step in that loss of nitric oxide production is due to oxidative stress. We oxidize a molecule called tetrahydrobiopterin and then we uncouple the NOS enzyme and we lose the ability to produce nitric oxide upon activation or stimulation that enzyme. And it’s Again, it’s kind of this perpetual feed forward cycle because if we can maintain normal nitric oxide production, we prevent the oxidative stress that leads to a loss of nitric oxide production.

So what leads to that? Well, it’s really the Western lifestyle. It’s a Western diet or the standard American diet, the SAD diet we call it. It’s lack of physical activity, it’s exposure to toxins, cigarette smoke, if you smoke, environmental toxicants. And you know, we live in a toxic world. We’re under a lot of stress, oxidative stress, and eventually that leads to a downregulation of nitric oxide production.

And it’s a high sugar diet, which, you know, is a major, major problem because sugar sticks to the enzyme, not just the nitric oxide synthase enzyme, but other enzymes and makes them inactive. And then there are things, you know, when once we understood there’s a compensatory pathway to restore the production of nitric oxide through the oral microbiome and through diet, then we start to see, okay, what’s disrupting that pathway.

And you alluded to it when we opened up. It’s, it’s mouthwash, it’s anything antiseptic that kills the bacteria in and on our body, it’s fluoride. You know, fluoride’s an antiseptic, fluorides in our toothpaste, it’s in most municipal drinking water. And then it’s things like drug therapy like proton pump inhibitors, statin medications, cholesterol lowering medication, shuts down nitric oxide production.

And so when you look at everything that leads to nitric oxide production, it’s really the average American. To me, it’s no wonder why Americans are the sickest people on the planet. Because everything we do in a western lifestyle, whether it’s western medicine, western diet, drug therapy, all disrupts nitric oxide production, at least to chronic disease.

How the Body Creates Nitric Oxide

RINA AHLUWALIA: Okay, so that was a very condensed approach to what causes the loss of nitric oxide. Let’s go a bit deeper. We’re going to go through one by one. So we know that as we age, nitric oxide production decreases. So that is going to lead to chronic inflammation and disease. Let’s talk about how the body creates nitric oxide. Now you alluded to it before, because if we understand this, we can understand how we can optimize our body so that we can produce more nitric oxide naturally at a zero cost way. So there’s two pathways. You alluded to the first one, it’s called the nitric oxide synthase pathway. Let’s try to explain that one for the audience.

The Nitric Oxide Synthase Enzyme Pathway

DR. NATHAN BRYAN: Sure. So this is a really complex enzyme in biochemistry to produce nitric oxide. So this enzyme converts L-arginine, which is a semi-essential amino acid. We get it from the breakdown of protein in our diet, but it’s also produced through the urea cycle, the partial urea cycle.

So it’s semi-essential, meaning that our body makes it, but we also get it from our diet. And we need to get it from our diet because there’s typically not enough flux or production through the urea cycle to do everything that arginine does. And it’s estimated that only about 3% of the arginine available in the body goes to make nitric oxide. There are other signaling pathways and pathways where nitric oxide is or L-arginine is utilized.

But this enzyme, nitric oxide synthase enzyme takes what we call the guanidino nitrogen of L-arginine and through a multi-step 5 electron oxidation produces nitric oxide gas. And then we get L-citrulline as a byproduct. So L-citrulline isn’t a precursor to nitric oxide, it’s a byproduct of nitric oxide. So that pathway is very well elucidated.

Many eight different cofactors and substrates required to make that enzyme produce nitric oxide gas. It’s kinetically and energetically unfavorable. And so it’s really a tough pathway. But if you’re young and healthy and you do all the things we talk about in this enzyme produces nitric oxide, second to second regulation of blood flow and perfusion and tissue oxygenation. So it’s fundamental and critical for that pathway to be intact.

But again, as I talked about, if you have oxidative stress, you oxidize tetrahydrobiopterin, this enzyme falls apart and it’s no longer able to produce nitric oxide. Even if you give more arginine or activate or stimulate it, it’s not going to produce any nitric oxide.

RINA AHLUWALIA: So it’s important to note that the L-arginine, so it’s a non-essential amino acid. Most people are going to think maybe I can just take the L-arginine and I’m just going to get better. But why is that a bad idea if you’re metabolically damaged? Why is that not a good idea?

Why L-Arginine Supplementation Can Be Harmful

DR. NATHAN BRYAN: Well, because there’s clinical data that tell us that it’s not a good idea. And the reason for that is, and I think these clinical trials that were designed almost 20 years ago trying to restore nitric oxide production in people who have what’s called endothelial dysfunction. These are the first study was in post-infarct patients. So these are patients who had just suffered a heart attack and they had compromised heart function. So we call post-infarct stiffness. So meaning that the heart muscle is compromised and it can’t eject enough blood with each heartbeat.

So the design was, “Well, let’s try to stimulate nitric oxide production to dilate the coronary arteries to restore the pump function of the heart.” And to do this they go, “Well, let’s just give arginine, high dose arginine.” And I believe this was 5,000 to 10,000 milligrams or 5 to 10 grams of arginine.

What they found was that the patients who got, and this was a double blind placebo controlled clinical study, the patients who got arginine actually did worse than the people who got the placebo. And in fact the arginine group had higher mortality, meaning that the patients who got arginine had a higher death rate and the post-infarct stiffness actually got worse. So the conclusions of that study were that arginine should not be given to post-infarct patients because it made them worse.

And then a year later, the same study was performed in patients with peripheral artery disease. So again, these are patients with known endothelial dysfunction. The NOS enzyme is obviously uncoupled. And then if you give arginine to these patients, they too got worse. Intermittent claudication got worse, meaning that when they walked and upon exercise that the blood vessels constricted, they had ischemic pain and the quality of life of these patients actually got worse compared to the placebo.

And now, so those are important clinical observations that were published in really some high impact clinical journals. And mechanistically, now looking back, we can explain that because if you give arginine to a patient where the nitric oxide synthase enzyme isn’t functional, then that enzyme actually makes superoxide and causes oxidative stress instead of producing nitric oxide. So we have a clear understanding mechanistically of why you should not give L-arginine to a patient who has endothelial dysfunction. Number one, they’re not deficient in arginine and number two, it makes them worse.

RINA AHLUWALIA: So you mentioned a few things there. You mentioned the endothelial cells. Let’s just explain what the endothelial cells is for people. And also the between endothelial cells and epithelial cells.

Understanding Endothelial vs. Epithelial Cells

DR. NATHAN BRYAN: I think it’s really important to have a distinction between endothelial cells and epithelial cells. So endothelial cells are endo, meaning it’s internal. So that’s inside our body. And these endothelial cells line all blood vessels and lymphatics throughout the entire body. In fact, it’s our largest organ system. These cells make up the endothelium, which is the largest organ system in the human body.

And so the endothelial cells were once thought to be a barrier function to keep certain blood proteins and blood cells inside the cardiovascular system and keep them out of the intima and the sub-endothelial space. But now we know that the endothelium is an active endocrine organ. It secretes nitric oxide. It’s not only maintaining barrier function, but it down regulates, upregulates adhesion molecules and maintains a barrier function of the blood vessels. So that’s endothelial cells.

Epithelial cells are really outside. The epithelial cells are found in the upper airway. It’s the outside world. It’s the lining of the gut. And the purpose of the epithelial cells are to keep the outside world from the inside world, protecting us from an outside environment. So the gastrointestinal system is really an outside world. So from the mouth to the anus, that is an outside world. Right.

And so the regulation of the epithelial cells is what keeps harmful bacteria from entering into our body. So when we have leaky gut or epithelial dysfunction, then things can transport. We lose that barrier function, we get leaky gut. Peptides or antigens are transported across and we develop autoimmunity.

But the nitric oxide synthase enzyme, as you mentioned, is found in both the endothelial cells and the epithelial cells. But if you have endothelial dysfunction and the NOS enzyme is uncoupled in the endothelial cells, it’s also uncoupled in the epithelial cells. And the beauty of the NOS enzyme in the epithelial cells, if it’s coupled and functional, when we deep breathe, it activates those epithelial cells. It produces nitric oxide.

And we can now deliver nitric oxide into the airways, dilate the bronchioles, improve oxygenation of the blood in the lungs, and better and efficiently deliver nitric oxide, deliver oxygen. And that explains why deep breathing can lower blood pressure and improve oxygenation, because it’s activating nitric oxide, improving oxygenation and oxygen delivery to every cell in the body.

The Enterosalivary Pathway

RINA AHLUWALIA: Let’s talk about the second pathway to naturally increase or how to create nitric oxide production in the body. The first one was the nitric oxide synthase pathway. The next one is the enterosalivary pathway. Can you explain what. And that is based on the oral microbiome or your oral bacteria. Can you explain that one?

DR. NATHAN BRYAN: Again, it starts with important clinical observations or scientific observations. And back in the late 80s, early 90s, it was first discovered that when you swallow your saliva, we can get a burst of nitric oxide gas in the lumen of the stomach. But this nitric oxide is completely eliminated by use of antiseptic mouthwash or killing the oral microbiome. So that was the first kind of observation, that there was some type of connection between the oral microbiome and nitric oxide being produced in the lumen of the stomach.

And now fast forward 25, 30 years, we know that there are nitrate reducing bacteria that live on the crypts of the tongue. And these bacteria were described back in the late 70s because they utilize nitrogen, their facultative anaerobes. So if oxygen’s around, they utilize oxygen to respire, but when oxygen becomes limited, they’ll use nitrogen in the form of nitrate. So when we can feed these bacteria and really the mechanism of action of a plant based diet, a Japanese diet, a Mediterranean diet, all these dietary patterns that afford some cardio protection can be explained by, through nitric oxide.

So here’s how it works. When we eat, for instance, some green leafy vegetables, 90 minutes after we consume that meal, the nitrate is absorbed in the duodenum, the proximal gut, and then concentrated in our salivary glands. Now, 90 minutes after we consume a meal where there’s nitrate present, then the salivary glands are secreting the nitrate. The bacteria on the crypts of the tongue are now utilizing this nitrate and performing this 2 electron reduction to nitrite. And now our saliva is enriched in nitrite.

And then when we swallow our saliva, this is just kind of basic solution chemistry, but there’s something called the PKA in which the pH, in which 50% of the nitrite becomes protonated and produces nitric oxide gas. That PKA for nitrite is about 3.4. So as long as we have sufficient stomach acid production, every time we swallow our saliva, even 6, 8, 10 hours after we ate that meal, we’re getting a burst of nitric oxide gas in the lumen of the stomach.

And that nitric oxide that we’re getting from swallowing our own saliva from the meal we ate hours ago, kills things like H. pylori, the acid, the ulcer causing bacteria. If there was some E. coli or Salmonella or some foodborne pathogen on that meal, it kills it. It’s been shown to inhibit ulcerations from chronic NSAID use. It enhances gastric mucosal blood flow. So now we can actually absorb those nutrients that we get from our diet.

So this is a really a fundamental physiological process whereby it explains nutrient uptake, it explains nutrient absorption, and prevents foodborne illnesses. So when we disrupt that pathway, bad things happen. So if we don’t get enough nitrate from our diet, we don’t get nitric oxide being produced. If we kill the bacteria on our, in our mouth, we disrupt this pathway. If we use antacids, we disrupt this pathway. And there are known clinical consequences to all those.

RINA AHLUWALIA: Now, okay, so that was the pathway to increase the nitric oxide, the enterosalivary pathway. Basically it’s through your mouth. So when you eat something, some food, you want to chew it, and then it’s the creating the production of nitric oxide. So mouthwash, it’s not good. How does mouthwash destroy your oral bacteria?

The Hidden Dangers of Antiseptic Mouthwash

DR. NATHAN BRYAN: Well, all you have to do is listen to the commercials. You know, “it kills 99.99% of the bacteria in your mouth.” And maybe a couple hundred years ago, people thought that was a good idea. But since the microbiome project has been completely mapped, we know that the bacteria that live in and on our body outnumber our human cells 10 to 1.

And these bacteria that live in and on our body are there to protect the human host. It’s a true symbiotic relationship. So we’re harboring these bacteria that are designed to do important metabolic processes that the human host has not evolved to do yet. So we rely on these bacteria for normal function.

And so today we know that no one would tell you to take an antibiotic, an oral antibiotic, every day for the rest of your life because of the known clinical consequences of that. So we just have to look up a little bit higher in the mouth. And so the same principles apply. You cannot destroy the oral microbiome without clinical consequences.

So using daily mouthwash, antiseptic mouthwash that originally was designed to kill oral pathogens that lead to periodontal disease, gingivitis, and cavities. Today we know that this ecology is much more complicated. It’s not just bad bacteria that are present. There’s a whole ecology of the microbiome, and we have to support the microbiome, not destroy it.

And so what mouthwash does, these antiseptic mouthwashes, things like Scope, Listerine, chlorhexidine, any alcohol-based mouthwash, it indiscriminately kills all the bacteria and creates a sterile environment. And when you do that, it disrupts nitric oxide production. We and others have published that if you use mouthwash, your blood pressure goes up, you lose the protective benefits of exercise.

And so there are clinical consequences to this that should be avoided. So again, antiseptic mouthwash destroys the microbiome, decreases nitric oxide production, causes high blood pressure, which is the number one risk factor for the number one killer of men and women worldwide.

And it’s not just antiseptic mouthwash, it’s fluoride. You know, fluoride is an antiseptic. It’s in toothpaste, it’s in water. And again, why do they put fluoride in toothpaste? To kill the bacteria. Why do they put fluoride in the water? To kill the bacteria in the water supply, but it’s also killing the bacteria in your mouth, in your gut. So you have to get rid of fluoride and your exposure to fluoride.

RINA AHLUWALIA: So when I heard that information about mouthwash, my husband was using the Listerine mouthwash and I said, “You have to stop using it.” So what he did instead was to use these Listerine strips, which he said, “Look, that’s not mouthwash. It’s just to improve my breath.”

DR. NATHAN BRYAN: No, it’s actually the same thing, but these strips you put on your tongue. And so it may be even more damaging than the oral Listerine rinse. Because the oral Listerine rinse and the bacteria that we’re interested in that we studied on the dorsal part of the tongue. So if you’re putting these strips on the tongue, it’s penetrating specifically into the lingual bacteria, which are the ones that are responsible for the production of nitric oxide.

RINA AHLUWALIA: I just wanted to clarify that because I think even people might think, “Okay, mouthwash, I use other alternatives.” But it’s anything that you’re putting into your mouth that’s going to disrupt the natural bacteria, good bacteria, the ecology of the bacteria that we need in the mouth.

So you mentioned don’t use mouthwash, don’t use fluoride. Let’s talk about antacids, because you mentioned to have good oral bacteria, you need good stomach acid. Well, many people don’t have good stomach acid. They take antacids. What’s the problem with antacids?

The Devastating Effects of Antacids on Nitric Oxide Production

DR. NATHAN BRYAN: Well, geez, where do I start? There’s so many things wrong with antacids. Number one, your body can’t digest the foods you eat without stomach acid. I think that’s the basis for most foodborne allergies and I think it’s the basis for most, if not all, autoimmune diseases.

Because let’s just take protein for example, you can’t break down protein into amino acids without stomach acid. And the human body is never designed to take up animal proteins or plant proteins and incorporate them into the human body. The way the digestive system works is we take those proteins, plant-based, animal-based proteins, and we break them down into the constituent amino acids. And then the human body uses those amino acids to make our own human proteins. So without stomach acid, you can’t do that. And that’s what leads to foodborne allergies.

But how does it relate to nitric oxide? So as I’ve explained, we have to be able to have stomach acid to get nitric oxide being produced from swallowing our own saliva. But in order to absorb magnesium, we need stomach acid. Magnesium is a central cofactor for the production of nitric oxide through the nitric oxide synthase inside. We need iron for this enzymatic reaction. You can’t absorb iron from your diet without stomach acid. You also need some B vitamins and flavin-dependent cofactors to make nitric oxide. And without stomach acid, you can’t absorb these from the diet.

So what antacids do is they completely shut down the body’s ability to make nitric oxide from both pathways. And then if we look specifically at what’s called proton pump inhibitors, these drugs actually inhibit an enzyme called DDAH, which leads to an increase in a metabolite called asymmetric dimethylarginine, which inhibits nitric oxide production in the lining of the blood vessel.

So antacids completely shut down both pathways to produce nitric oxide. And again, you look at clinical observations, what’s published in the literature. People who have been on PPIs and antacids for three to five years have a 40% higher incidence of heart attack, stroke and Alzheimer’s. And mechanistically we understand that.

So the pathway is completely elucidated, the clinical consequences are very well reported. And so there’s no benefit whatsoever to antacids. In fact, I’ve argued now for 10 years that these drugs are dangerous, they’re deadly and they should be taken off the market. These pharmaceutical companies should be responsible, inform their patients.

But of course, some of them do. You know, it’s not only causing heart attack, stroke, Alzheimer’s, but if you read the label on these proton pump inhibitors, there’s osteoporosis, increased risk of bone fractures, increased risk of kidney disease, end-stage renal disease, the list goes on and on. And now you add increased risk of heart attack, stroke and Alzheimer’s.

The risk of these drugs far outweigh any benefit that they’re providing to the patients. And more concerning is you don’t even need a prescription for these drugs anymore. Anybody at any time can go to the drugstore or health food store and buy these drugs over the counter. And they’re deadly. They’re causing death and destruction and dementia and Alzheimer’s. And people need to know about this, because if people understood and really knew what these drugs were doing to them, no one in their right mind would take them. No one.

RINA AHLUWALIA: Well, it’s like statins.

The Statin Myth and Cholesterol’s Role in Nitric Oxide

DR. NATHAN BRYAN: Yeah, and statins, too. You know, number one, cholesterol doesn’t cause heart disease. So why would you target lowering cholesterol to mitigate heart disease? Heart disease is still on the rise. These statin drugs have been on the market now for 30 years. And if cholesterol caused heart disease, as the American Heart Association predicted in the late 80s, when you lower cholesterol, it would completely eradicate heart disease and cardiovascular disease.

And in fact, by the turn of the century, heart disease has gone up and continues to go up despite getting cholesterol levels below 200. So, again, those clinical observations tell us that cholesterol doesn’t cause heart disease. Statins have not affected the rate of cardiovascular disease whatsoever. In fact, we see it going up.

So what are the consequences of lowering cholesterol? Well, you develop type 2 diabetes, you develop all this myalgia. They’re mitochondrial toxicants causing cancers. But in terms of nitric oxide production, we need cholesterol in the cell membrane. Because it’s this intracellular signaling. We have to maintain some fluidity in the cell membrane. Without cholesterol, we lose that fluidity, these protein complexes fall apart. And nitric oxide is part of that intracellular signaling. And if you get cholesterol below 200, you disrupt that lipid raft and it leads to complete inhibition of nitric oxide production, so then leading to increased risk of heart attack and stroke and cardiovascular disease, which is what we see in the general population.

RINA AHLUWALIA: Many doctors talk about this fact that all these medications, especially statins, actually increase the likes of dementia. There’s actually more risk versus the benefit. But I think it’s to do with the industry marketing. So if you have industry and companies marketing this, obviously people are going to be thinking about that.

I want to circle back to nitric oxide, and I guess I have a bit of a bold question for you. Do you think that if we can boost our nitric oxide in the body, that that is a way to fix all brain disease?

Nitric Oxide: The Key to Brain Health and Blood Flow

DR. NATHAN BRYAN: I not only believe that, I think I know it from the scientific literature because if you look at neurological disease and if you look at the work of Daniel Amen, who has the largest database of SPECT scans in the world, probably no matter what neurological disease he looks at and maps through SPECT scans, which really give us a view of how well perfused or what part of the brain has adequate blood supply, or more importantly, what regions of the brain have complete focal ischemia or lack of blood flow.

And so it doesn’t matter if it’s Parkinson’s disease, dementia, Alzheimer’s, bipolar disease, ADHD, post-concussion syndrome, chronic traumatic encephalopathy, all of that is characterized and shown in SPECT scans that there’s a disruption in the regulation of blood flow to certain regions of the brain. And you cannot correct that until you restore blood flow to that part of the brain.

Now, I think it’s part of the picture. There are other things that contribute to neurological diseases. There’s heavy metal toxicity, which leads to Parkinsonian-type syndrome. There are other toxins that may be present. But if you can restore blood flow to the brain and start delivering oxygen nutrients and restore mitochondrial function and potentiate insulin signaling and glucose uptake, the primary energy substrate of the brain, then you can start to restore normal neurological function.

But I think it’s twofold. We’ve got to restore blood flow to the brain and we’ve got to remove the toxins that may be contributing to the neurotoxicity.

RINA AHLUWALIA: Absolutely. Let’s talk about the six ways to naturally increase your nitric oxide at zero cost as much as we can. What do you think is the number one thing that we can do?

Natural Ways to Restore Nitric Oxide Production

DR. NATHAN BRYAN: Well, I tell people the human body is extremely resilient. We just got to get out of the way. So I tell people the first thing you do to restore your nitric oxide production is to eliminate the things that are causing a disruption. And we’ve discussed those.

So if you’re using mouthwash, you have to stop. The data are very clear that we have to support the microbiome. We cannot destroy it. Number two, you have to get rid of fluoride. Fluoride is a neurotoxin. It completely destroys your thyroid function. It competes with iodine binding to the thyroid hormone. It’s a halogen on the periodic table. We can’t forget the basic chemistry of that.

And then as I mentioned, it’s a neurotoxin. In fact, it’s the active ingredient in rat poison. I mean, the fact that we’re giving fluoride in the municipal water supply and in the toothpaste. And all you have to do is, if you go look at your toothpaste now and if it has fluoride in it, read the back label and it says “if you swallow this, contact poison control.” What? Because fluoride is a poison.

So you have to get rid of fluoride. And if you live in a city where there’s fluoride in the municipal water supply, then you have to undergo the cost of getting a home filtration system that removes the fluoride and the chlorine and the chloramines and everything they’re putting in municipal water.

So those are the three biggies. Eliminate mouthwash, eliminate fluoride. And then the antacids. And if you’re using antacids, you have to stop using antacids. And then most people are deficient. They’ve been on antacids, are deficient in things like magnesium and zinc and B vitamins and iron. And these are things we need to stimulate nitric oxide production, actually produce stomach acid by the parietal cells.

So those are the three things that are cost savings, right? Get rid of mouthwash, buy fluoride free toothpaste and stop using antacids. And now your body’s actually primed to produce nitric oxide on its own.

And then we can actually activate it and stimulate that by moderate physical exercise, 20, 30 minutes of exercise a day. Now there’s data showing that just two to three minutes of high energy, high intensity interval training may be sufficient for promoting nitric oxide production.

A balanced diet in moderation, get rid of sugar. If you’re taking vitamins and getting nutrients through gummies or chews. Gummies and chews are poison. They contain seed oils, they contain sugar that no one needs. So gummies and chews should be eliminated from the dietary supplement market. There are people selling gummies and chews and beets and grapeseed extract and it would be comical if it wasn’t dangerous.

But the companies are spending big money on marketing to try to convince you to get nutrients through gummies and chews. Throw in some more green leafy vegetables, eat natural food, not processed food. A balanced diet in moderation. And then 20 to 30 minutes of sunlight exposure a day. And then people during the winter, just infrared light, infrared sauna, all of these are clinically proven ways to produce nitric oxide.

And as you mentioned when you opened up, these are cost savings. I’m not asking you to buy anything. You don’t need to take a supplement, don’t need to take drug therapy. Just give the body what it needs, get out of the way, and the body does its job.

Nasal Breathing for Nitric Oxide Production

RINA AHLUWALIA: Okay, let me be a little bit more specific. I have some other ways to increase your nitric oxide, but I wanted to ask your opinion on this. Breathe through your nose instead of through your mouth. Is that a way to naturally increase your nitric oxide?

DR. NATHAN BRYAN: Absolutely, provided that the enzyme, the NOS enzyme, is coupled and functional in the epithelial cells. So if it’s uncoupled and you have endothelial dysfunction, then that same dysfunction occurs in the epithelial cells. So we can activate and stimulate through deep breathing. But if that enzyme is uncoupled, you’re not going to get any nitric oxide being produced. So let’s focus on recoupling the NOS enzyme.

Now, when we do deep breathing, and we can demonstrate this through nitric oxide analyzers that detect nitric oxide gas coming out of the upper airways and the sinuses. But, yeah, you can deep breathe.

The other thing, the problem with mouth breathing is you completely change the oral microbiome, the ecology of the microbiome. So we’re designed to sleep and breathe with our mouth closed. And that creates a completely different environment, the oral microbiome, than if we’re constantly using our mouth open breathing at night with our mouth open. The ecology of the microbiome completely changes. It shuts down nitric oxide production, it lowers the pH and causes acidity in the oral microbiome, which leads to periodontal disease, gingivitis, cavities.

So this mouth taping is a viable exercise that you should do to force your body to breathe through the nose, through the nasal sinuses at night. But if you have obstructive sleep apnea, then you’ve got some anatomical issue, then you got to clear the obstruction.

Oral Microbiome and Tongue Scraping

RINA AHLUWALIA: Okay, we’re going to talk about sleep apnea a bit later. When I ask you about the immune system, I’m interested to know how the nitric oxide actually helped with COVID and even long COVID. But I want to get through these natural ways to increase nitric oxide. So you mentioned improve your oral microbiome or your oral bacteria. So that means avoid mouthwash, avoid fluoride, buy the fluoride free toothpaste. What do you think about tongue scraping?

DR. NATHAN BRYAN: Look, tongue scraping, that was part of the paper. Interesting. We published in 2019, tongue scraping is this, I think it goes back to Ayurvedic medicine. This has been used for thousands of years in certain cultures.

And what we found in our paper, and I think there’s other published literature out there, but tongue scraping actually improves the diversity of the microbiome. And we equate it to like if you’re going to plant seeds in your garden, you till the soil, right? You have to till. And the tongue scraping is kind of tilling the soil of the tongue and allowing for a more diverse, breaking up biofilms, allowing for enrichment of that ecology of the microbiome.

So tongue scraping alone is good. What we published in our 2019 paper was if you do tongue scraping and you use antiseptic mouthwash, that’s like the worst combination because that’s when we see the highest increase in blood pressure. And I think what’s happening is your tongue scraping, you’re opening up the pores of the tongue. Now when you use mouthwash, that mouthwash penetrates deeper into the dorsal part of the tongue and you get more effective killing of the nitrate reducing bacteria.

The Truth About Sodium Nitrite and Cured Meats

RINA AHLUWALIA: Okay, let’s talk about food because you mentioned it earlier. So your nitrates get converted to nitrites, which can get converted to nitric oxide. Now people want to think about nitrites. They’re going to think, you know where I’m going with this sodium nitrate. Now a lot of my audience, they following low carb, ketogenic carnivore lifestyle. So big thing is cured meats, processed meats, bacon, hot dogs. We’re told that sodium nitrate is bad for you. What do you have to say about that?

DR. NATHAN BRYAN: Well, similar to this whole concept that cholesterol causes heart disease, nitrite and nitrate being toxic. Again, one of the biggest myths ever perpetuated in the scientific and medical literature.

And again, we have to start, let’s go back historically because there’s always good reason for maybe assuming this or exploring this hypothesis. And this goes back to nutritional epidemiology probably 40, 50 years ago. These are observations showing that people who eat certain food patterns have a certain increased risk of whatever it is cardiovascular disease, cancer.

Well, in the 1950s it was first published that nitrite cured fish. They detected what’s called nitrosodimethylamine or NDMA. And that’s a known carcinogen. And so then people thought, okay, well if nitrite can form nitrosamines and nitrosamines cause cancer, then maybe eating nitrite cured meats lead to an increased risk of certain cancers.

So that provided kind of a biologically plausible mechanism for these nutritional epidemiologists to explore that. And in the literature you’ll find reports of people who eat predominantly processed cured meats, hot dogs, bacon, lunch meats to which nitrite is added, have a slight increased risk of certain gastroesophageal cancers, gastric derived cancers. So those are observations, those are associations, it’s not causation.

And so the biologically plausible mechanism they put in play was, okay, let’s go back. Nitrite forms nitrosamines, nitrosamines cause cancer. That’s the biologically plausible mechanism whereby we can explain these associations.

But then in the late 1970s, it was first reported that nitrite and nitrate are actually produced in the gut of humans. That really was the early observations that eventually led to the discovery of nitric oxide. If nitrite and nitrate cause cancer, then this would be embryonically lethal because breast milk contains nitrite and nitrate.

So today we understand, and again, if that hypothesis were true, then vegetarians would have a 10 time higher rate of cancer than meat eaters. Because 85% of the nitrate and nitrite we get from our diet comes from vegetables. Only 5% of the total human exposure to nitrite and nitrate come from cured meats. The other 5% or other 10% comes from swallowing our own saliva.

And we actually even convinced the nutritional epidemiologist years ago that they got it wrong, because nitrite and nitrate are actually anti cancer. We published on this in 2009 that nitrite in the diet, if we give nitrite, we can prevent certain cancers. The national toxicology program in 2000 reported that nitrite and nitrate at certain doses prevented cancer progression in male and female rats, mice and rabbits.

Mechanistically, we know because it’s affecting mitochondrial function. Cancer only occurs when there’s mitochondrial dysfunction uncoupling the Warburg effect. And nitric oxide and nitrite actually recouple the electron transport chain, maintain normal mitochondrial function, and prevent the Warburg effect. We laid that to rest probably 15 years ago. But nitrite and nitrate do not cause cancer. They have anti cancer properties. And so people should not be avoiding hot dogs, bacon, cured meats because of the nitrite.

Sodium Nitrite: The Cure for Chronic Disease

RINA AHLUWALIA: You said that sodium nitrite is a cure for all disease. Is that because it’s linked to the nitric oxide? It’s the precursor towards creating nitric oxide.

DR. NATHAN BRYAN: Yeah, I published this review paper several years ago. “Sodium Nitrite, the Cure for Chronic Disease.” Kind of a play on words, because it cures. And the reason they use it in the meat industry is because it cures, it cures the meat. So it prevents foodborne illnesses. It prevents the lipid oxidation that you see in the rancidity of non refrigerated foods or ready to eat foods.

And so we want to prevent lipid oxidation inside the human body. And that’s what nitrite and nitric oxide does. But again, it goes back to restoring the function of the mitochondria. It binds to the iron of hemoglobin. So similar to this curing of meat. Nitric oxide and nitrite bind to the heme iron of myoglobin. That’s what causes this pink color, this cured meat, nitrosyl hemochrome pigment.

And that’s how humans deliver oxygen to every cell in the body. Nitric oxide binds to the iron of hemoglobin and that’s how oxygen is delivered to every cell in the body. It’s basically the same principles.

Dark Green Leafy Vegetables and Regional Variations

RINA AHLUWALIA: So eat more hot dogs, eat more bacon, eat more delicious cured and processed meat. Let’s focus now on again with diet, because that’s the natural zero cost way to increase nitric oxide. So you mentioned eat a lot of dark green leafy vegetables. What are the main ones that we should be eating?

DR. NATHAN BRYAN: Well, I say that kind of broadly speaking. But the darker the green leafy vegetables, typically the higher the nitrate. And this is based on nitrogen in the soil, application of nitrogen based fertilizers so that these plants can assimilate the nitrogen, the form of nitrate.

But so again, broadly speaking, it’s like the kale, the arugula, the spinach, the dark green leafy vegetables. But you also have to mitigate this with the oxalates found in these vegetables. Too much oxalates and it can lead to kidney stones and things like that. Some people have higher sensitivities than others.

But I think what we’re finding is, and again in this 2015 paper we published, the nitrate content, there’s regional differences in the nitrate in food grown in New York and Chicago and Raleigh versus in Dallas and in Los Angeles. So it’s very difficult if not impossible to predict how much nitrate you’re getting from the foods you’re eating. But generally speaking, the darker the green leafy vegetable, the higher the nitrogen in the form of nitrate.

Nitric Oxide for Carnivore Dieters

RINA AHLUWALIA: Absolutely. So it’s important context there that it’s good to eat dark green leafy vegetables if you can tolerate it. Because I think when we talk about diet, we have carnivores, omnivores, and then you have vegans or vegetarians. And usually people choose a protocol that’s good for them. Fair enough. I tend to be carnivore. That’s just personally what works for me. So I was just thinking, damn, how am I going to get my nitric oxide? I’m not eating dark green leafy vegetables. If somebody is following a zero plant protocol most of the time. Is there other ways that we can get nitric oxide?

Carnivore Diet and Nitric Oxide Production

DR. NATHAN BRYAN: Yeah, look, I mean we have to stimulate the endogenous production. So a strict carnivore diet, you’re basically not supporting the nitrate, nitrite, the center of salivary circuit from the diet. Nitrate from the diet.

But what we’re finding is that number one, you’re getting a high rich protein diet with the good fats. And this will stimulate the antioxidant response elements and upregulate your antioxidant defense systems. So we’re doing, we’re maybe promoting the endothelial production of nitric oxide, which then oxidized into nitrite and nitrate.

So we’re upregulating nitrate, endogenous nitrate production, which again is put in our salivary glands, secreted through the oral microbiome and then producing nitric oxide through that. But I think what we have to do, if you’re eating a strict carnivore diet, you almost have to pair this with moderate physical exercise and making sure that we’re getting that activation and stimulation of the endothelium to activate this pathway.

The Nitric Oxide Release Workout

RINA AHLUWALIA: Well, that was my next way to naturally increase nitric oxide. There is something called the nitric oxide release workout. Have you heard of that one?

DR. NATHAN BRYAN: Yes, I think this was popularized by Joe Mercola, who’s, it’s comical, but yeah, people tried different ways to bring nitric oxide into the vernacular.

RINA AHLUWALIA: So it doesn’t work.

DR. NATHAN BRYAN: Well, look, I think it works if you’re young and healthy and you’ve got an active endothelium. But this again, this nitric oxide dump, I think as he calls it, is dependent upon the function of the NOS enzyme. If you don’t have a functional NOS enzyme, you can exercise until the cows come home, but you’re not getting any nitric oxide being produced through activation or stimulation of that pathway.

RINA AHLUWALIA: Okay, so I won’t go in explaining what the exercises are because we need to actually work on increasing the functionality of the NOS enzymes.

DR. NATHAN BRYAN: Well, I think it’s not unique to certain exercise. It’s anything that increases heart rate and causes an increase in sheer stress in the lining of the blood vessels. Because it’s that sheer stress that we see in the lumen of the blood vessel upon exercise that starts to activate nitric oxide synthase. Production of nitric oxide.

Humming and Frequency-Based Activation

RINA AHLUWALIA: Okay, keen to hear your thoughts on the next one. Humming.

DR. NATHAN BRYAN: Humming? Yeah, again, that is, there’s certain frequencies that activate the NOS enzyme. But again, that enzyme must be coupled and functional in order for this frequency to then turn on that production of nitric oxide. But yeah, if you’re coupled and functional and you start to hum, we can actually detect nitric oxide coming out of the sinuses, coming out of the mouth.

Red Light Therapy and Sunlight Exposure

RINA AHLUWALIA: Okay, so. And the last one was the red light therapy, which you alluded to earlier. How does red light therapy help?

DR. NATHAN BRYAN: Again, it’s a frequency and it’s a vibration and it’s that frequency of light. The really, it’s full spectrum infrared. But what’s that do? It’s not stimulating nitric oxide production per se, it’s releasing nitric oxide that’s bound the metals.

So when we produce nitric oxide inside the body, it either binds to thios on proteins or glutathione or it binds to metals. So when we are exposed to light therapy, then that red light will penetrate, you know, several millimeters centimeters into the tissue and then release nitric oxide bound to metals.

That nitric oxide is vasoactive, cause vasodilation, activate mitochondrial biogenesis and stimulate mitochondrial ATP production. But again, if you’re nitric oxide deficient, you have less photo labile stores of nitric oxide that can be activated or released with light therapy.

RINA AHLUWALIA: Okay. And then is a natural way or a zero cost way to do red light therapy is sunlight exposure, especially in the morning.

DR. NATHAN BRYAN: Absolutely, yes. Spend 20, 30 minutes out in the sunlight. 20, 30 minutes a day, best morning sunlight or noon. But yeah, then you get full spectrum. You know, you get some UV which also will release nitric oxide bound to thioles. But you’re getting full spectrum exposure that including the infrared and full spectrum infrared.

Cardiovascular Protection and Heart Disease Prevention

RINA AHLUWALIA: Okay. So that was roughly six things that we can do to naturally increase the nitric oxide. I wanted to circle back to the other benefits of nitric oxide because you said that nitric oxide will actually prevent brain disease. Let’s focus on cardiovascular risk because that’s the commonest cause of death in the developed world and in the US how does it, will it prevent heart attacks and strokes?

DR. NATHAN BRYAN: Absolutely. And mechanistically, we understand that. So if you go back to the earliest stages of atherogenesis, where you start to get plaque deposition, and then eventually you get growth in the subentoma space and then smooth muscle hyperplasia that will eventually start to occlude the lumen of the blood vessel, you get stenosis. And so now you have less blood flow going through the coronary arteries.

But it’s not the stenosis that causes heart attack in most cases, because 50% of people who die from sudden cardiac arrest or sudden cardiac death have less than 50% stenosis of the coronary arteries. But what’s happening is that plaque that’s present there is what we call soft plaque or vulnerable plaque. And that plaque actually ruptures, and then you get the thrombus downstream that completely occludes the lumen of the coronary arteries and causes sudden cardiac death or myocardial infarction.

So the earliest stages in that are when monocytes and neutrophils start sticking the lining of the blood vessel, they migrate through, they start to develop foam cells, plaque, you get an upregulation of myeloperoxidase, certain lipoprotein particles that are diagnostic now for the degree of plaque vulnerability.

But nitric oxide actually prevents that whole process from occurring. But even in people with soft plaque, nitric oxide can stabilize that existing plaque, prevent additional smooth muscle hyperplasia, and then prevent platelets from sticking in monocytes and neutrophils from sticking to the lining of the blood vessels. So nitric oxide is extremely cardio protective in preventing the onset and progression of cardiovascular disease, but even stabilizing the plaque and mitigating risk in patients that already have overt cardiovascular disease.

Immune System Benefits and COVID-19

RINA AHLUWALIA: So you see, if we increase it naturally, the nitric oxide, it can help so many different functions of the body. Let’s move on to the next benefit of nitric oxide pertaining to the immune system. How did nitric oxide help with the COVID virus back when that was happening, and also with long Covid, because I think some people are experiencing that still now, for sure.

DR. NATHAN BRYAN: So part of our immune system, and again, this goes back to data from the 1970s, that our body kills off bacterium by the production of nitric oxide. And there’s an enzyme called inducible nitric oxide synthase. It’s a very similar isoform that’s found in our neurons and in our Endothelial cells. The regulation of that enzyme is a little bit different.

But the purpose is when we’re exposed to a bacterium or a virus, then our immune cells, we mobilize an immune response. Our immune cells go to the site of infection, and then after the cytokine storm, this enzyme produces a lot of nitric oxide over a short period of time. And in terms of bacterial infections, the nitric oxide binds to iron sulfur centers of the bacteria and shuts down the respiration and kills the bacteria.

In viruses, the mechanism is a little bit different. It prevents viral replication. So even if a virus has entered inside a mammalian cell and hijacked the DNA, if our immune cells can get there and produce nitric oxide, it prevents that virus from replicating. So we may be exposed to the virus and it may have already penetrated into mammalian cells. But if our body produces nitric oxide, it stops the propagation that viral disease and people don’t get sick.

So again, what we observed back in early 2020 was that the people that were getting sick and dying from COVID were the people who couldn’t make nitric oxide. These were the African Americans, the elderly, the people who had a prior heart attack, diabetics, people who smoked, chronic obstructive pulmonary disease, emphysema. These were the high risk patients that once they were exposed to the COVID virus, they did very poorly.

And the progression of disease was very predictable. Two to three days upon exposure, they developed symptoms. Within five days, they were hypoxic, they were admitted to the hospital. 100% oxygen wouldn’t raise their oxygen saturation, they were put on mechanical vents and they expired within eight or 10 days. And that was very predictable.

But what we found was that if your body, if you were healthy and your body could produce nitric oxide, you could be exposed to the virus. But most people didn’t get sick, they certainly didn’t require hospitalization and they recovered from COVID. And that led us to develop a nitric oxide based drug specifically for Covid as an early intervention. And we basically allowed people to recover from COVID not be hospitalized, and certainly not die from COVID.

So now what we realize is that the spike protein from COVID binds to the ACE2 receptor. And in patients who don’t make enough nitric oxide, they get an over expression of the ACE2 receptor. So now there’s more target for the spike protein to bind to bring that virus into the cell and rapidly propagate throughout the body and make people sick. But in people who make nitric oxide, we downregulate the ACE2 receptor, we prevent the virus from replicating and propagating, and people don’t get sick.

And I was the example. I was in. We had 26 clinical sites around the US during the heat of COVID and I was in Covid centers every week. I was on an airplane every week during the heart of COVID. I didn’t wear a mask, I didn’t get the shot. And I never got Covid. I never got sick from COVID. Yet I was exposed every day. And I haven’t been sick from a viral infection in over 20 years. It’s not that I live in a sterile world, it’s just that I have an active immune system. Produce nitric oxide and I’m exposed, but my body deals with it and we don’t get sick.

Long COVID and Vascular Inflammation

RINA AHLUWALIA: Wow. And how does it help? With long Covid. What is long Covid, by the way?

DR. NATHAN BRYAN: Well, long Covid is vascular inflammation. Again, it’s upregulation of the ACE2 receptors. The spike protein binds. Monocytes, neutrophils, start to stick, platelets aggregate. Our body breaks this platelets down. We get an elevation in D dimers, and you see that in long Covid.

So this explains that the vascular inflammation that persists long after the active COVID infection. And so if we can give nitric oxide, we can downregulate these two receptors and other adhesion molecules. And monocytes, neutrophils, don’t stick, platelets don’t become aggregated and activated, and we maintain normal perfusion, mitigate the inflammation, and long Covid goes away.

Sexual Function and Erectile Dysfunction

RINA AHLUWALIA: So the platelet aggregation that you’re talking about, that’s the other benefit of nitric oxide. So what that means is if you have platelets, little bits of blood in the vessel, and then they stick together, that’s what can form a clot, that’s what can cause a heart attack and stroke. Just so that people can understand what platelet aggregation is, let’s talk about the benefits of nitric oxide for vascular function. Now, this relates to erectile dysfunction. Can we discuss that?

DR. NATHAN BRYAN: Absolutely. So, look, the sex organs in both men and women require adequate blood supply. So similar to where if I want to recall memory, then I have to increase blood flow to the prefrontal cortex for memory recall. If I’m stimulated before sexual activity, then I’ve got to dilate the blood vessels of my sex organs in order to get engorgement to maintain an erection sufficient for intercourse.

And that increase in blood flow is dependent upon the body’s ability to produce nitric oxide. So if your body, if you have endothelial dysfunction and you can’t increase blood nitric oxide production, then you don’t get vasodilation, you don’t get engorgement. And that’s the definition of erectile dysfunction.

And it’s the same thing in women. You know, you have to have clitoral engorgement, label engorgement, to see that increase in pressure for women to have an orgasm. And again, all that is dependent upon the body’s, the cell’s ability to produce nitric oxide, to dilate the blood vessels to get engorgement. Whether it’s in the penis or the clitoris, it’s all dependent upon the ability to produce nitric oxide.

RINA AHLUWALIA: I think that’s something that people will be like, oh my God, I want to talk about sexual dysfunction. But it is a erectile dysfunction is a very common problem and it’s a precursor towards. It means that you have insulin resistance, basically.

DR. NATHAN BRYAN: Well, it’s the, you know, the sexual dysfunction isn’t just a lifestyle disorder. It’s really the canary in the coal mine. Because if you can’t regulate blood flow to the sex organs when you want to have sex, then you can’t regulate blood flow to the heart when you want to exercise. You can’t regulate blood flow to the brain when you want to think or deliver a speech or in. I mean, we see that in the public American politics today, all day, every day.

RINA AHLUWALIA: Are you talking about Joe Biden?

DR. NATHAN BRYAN: It’s dysregulation of blood flow. Yeah. Joe Biden is the poster child for nitric oxide deficiency.

RINA AHLUWALIA: Do you really think so?

DR. NATHAN BRYAN: Absolutely.

RINA AHLUWALIA: Circling back to sexual function, Viagra. So Viagra is used as a drug to help with erectile dysfunction, but it always, always wasn’t the case. Why is that not the answer to erectile dysfunction?

The Reality of Erectile Dysfunction Medications

DR. NATHAN BRYAN: Well, look, it’s a very successful drug on the market in terms of generating revenue for these drug companies. Multibillion dollar annualized drug. But again, go back to the clinical data. What does it tell us? That only 50% of the men that are prescribed these drugs for erectile dysfunction improve their erectile function. So 50% people don’t respond to that.

And so the reason that there’s 50% of the people that respond is because the activity of the drugs like Viagra, the PD5 inhibitors, are dependent upon that patient’s ability to produce nitric oxide. If that patient is completely devoid of any nitric oxide, then the way these drugs work is that nitric oxide turns this switch on, and we call this switch cyclic GMP. Nitric oxide is produced, increases cyclic GMP, and then drugs like Viagra prevent the breakdown of cyclic GMP.

Without nitric oxide, there’s no increase in cyclic GMP. Without an increase in cyclic GMP, Viagra can’t work. The non responders to PD5 inhibition therapy are the patients who are completely devoid of any nitric oxide production. That tells us, number one, erectile dysfunction is a symptom of nitric oxide deficiency. It’s not a symptom of overactive phosphodiesterase.

If that were the case, then the PD5 inhibitors would work in 100% of the population. But we know they don’t. So if we can restore nitric oxide production now, you can take non responders and make them responders, or best case scenario, you get these patients off these PD5 inhibitors and stimulate, activate nitric oxide production, you have normal erectile function.

RINA AHLUWALIA: So do you think that if we naturally increase our nitric oxide production somehow, naturally, even though people might have impaired NOS enzymes, do you think that could wean people off all medications?

Restoring Nitric Oxide Can Reduce Need for Medications

DR. NATHAN BRYAN: Yes. And we’ve witnessed this over the past 10 or 15 years, that if you can restore nitric oxide production, the need for pharmacotherapy is greatly diminished. And let me qualify that statement, because there’s no panacea. There’s not a… Nitric oxide is not an end all, be all, cure all. There’s different reasons that people develop chronic disease, whether it’s hypertension or dementia.

But I think foundationally to all of that is a lack of nitric oxide, which leads to a lack of blood flow, increased inflammation, oxidative stress, and immune dysfunction. So foundationally speaking, if we can restore nitric oxide production, let’s just take hypertension, for example. It’s a huge… Two out of three Americans have unsafe elevation in blood pressure, and yet 50% of the people that are given anti hypertensive medications don’t respond with better blood pressure. It’s called resistant hypertension.

And they’re resistant to therapy because the therapy isn’t affecting their underlying problem of nitric oxide deficiency. So if we can restore nitric oxide production, we get normal vasodilation. Now we’re pumping the same volume of blood through more dilated blood vessels, and the pressure normalizes. So certainly we can get people off antihypertensive medication.

But I think the root cause of any chronic disease is only from two things. The body’s missing something that it needs or it’s exposed to something that it doesn’t need. So if we address those two things and restore nitric oxide production, then there’s never any need for a human to take a drug therapy, a synthetic compound that we’re not born with.

The N101 Nitric Oxide Lozenges

RINA AHLUWALIA: So in the case that people naturally produce nitric oxide, that’s fine. But you also produce some fabulous products, lozenges, which is called N101 Lozenges, Nitric Oxide Lozenges. What is the place for that? Why would somebody use that?

DR. NATHAN BRYAN: Well, we designed it intentionally to, number one, if your body can make nitric oxide, then we have to provide a source of nitric oxide to that particular patient. And so it’s similar to hormone replacement therapy, because we published in 2007, nitric oxide is actually a hormone, so we got to replace that hormone if you’re deficient.

But unlike testosterone or other hormone replacement therapy, we didn’t want to compromise endogenous production of nitric oxide, so we had to think a little bit outside the box. So we wanted to… Number one, if your body can’t make nitric oxide, then we got to do it for you. But number two, once we understood mechanistically what goes wrong in people that can’t make it, oral dysbiosis and an uncoupled NOS, then we understood the enzymatic and the biochemistry that we could recouple the NOS enzyme in the lining of the blood vessel.

So that’s what the lozenge does. And because we designed this as an orally disintegrating tablet that sits in the mouth for five to six minutes, we’re selectively killing the bad bacteria and we’re restoring the ecology and supporting the good, healthy microbiome. So not only is that lozenge providing an exogenous source of nitric oxide, but we’re improving the body’s ability to make nitric oxide on its own.

RINA AHLUWALIA: Absolutely. So the difference between the endogenous and exogenous, so you don’t want to disrupt the inside of the body. Endogenous. And that’s why these companies that try to formulate drugs to increase nitric oxide, I’m sure that must have different effects on other parts of the body, as we see with different drugs. They affect everything. Is that the right train of thought?

Precise Dosing for Safety and Efficacy

DR. NATHAN BRYAN: Yeah, look, I mean, we… With the lozenge design, I want to deliver a certain amount of nitric oxide over a certain period of time because too little nitric oxide is bad, too much nitric oxide can be bad and lead to an unsafe drop in blood pressure and methemoglobinemia.

So the design of the lozenge was delivered in the fact that I want to deliver a certain amount of nitric oxide that’s systemically absorbed, that’s vasoactive, that’s transported along the vascular tree and basically can restore and recapitulate normal nitric oxide production in sickle. So that was the design. I didn’t want to have any off effects and we wanted to recapitulate nature, give nitric oxide at doses that one would normally see through normal endogenous production.

RINA AHLUWALIA: Wonderful. Well, Dr. Bryan, thank you so much. I feel like that was like a scientific academic class.

DR. NATHAN BRYAN: A master’s class. Right.

The Problem with Other Nitric Oxide Products

RINA AHLUWALIA: That was amazing. So again, with the lozenge and with any other products, what do you think about other products by other companies that promote nitric oxide?

DR. NATHAN BRYAN: It’s actually the source of my daily frustrations because, you know, what we’re doing is completely different. And we’re going through the rigor of drug studies through the FDA to demonstrate safety and efficacy. So that has a clear regulatory path. The problem that we deal with in the nutrition dietary supplement and in the cosmetic and skin care is that everybody can say the same thing.

So other companies selling nitric oxide supplements and over the counter products can say the exact same thing that I can. We’re guided by what’s called the DSHEA act, the Dietary Supplement Health and Education Act. You can make drug claims, you can say it supports the normal structure and function of the body. So then you’ve got these companies out there basically saying that their product does the exact same thing as mine does. When we’ve proven and shown clinically that there’s no way these products can work.

So I think 99% of the products on the market that are marketed as a nitric oxide product do absolutely nothing in terms of nitric oxide. Now let me qualify that. I’m not saying they’re bad products. They contain good ingredients, you know, some B vitamins, other important good nutrients that may be providing some benefit. But it’s not a nitric oxide product.

Throwing 52 ingredients in a bag and calling it nitric oxide is a joke. And then you’ve got these companies trying to sell you nitric oxide in the form of a gummy or a chew, which, I mean, it’s outright fraud and it’s deceptive marketing and these companies out there doing it. You know, I’m not making many friends in the marketplace, but these companies have to be held accountable because they’re taking consumers’ money, they’re defrauding them, they’re deceiving them. When they know that these products can’t work, they don’t work.

And it’s really, it has the potential to destroy the entire industry of nitric oxide. And to me, that’s dangerous. And, you know, I hold these companies accountable because I hear it all the time. People go, “Well, Nathan, you talk about nitric oxide, but I’ve tried nitric oxide products and it didn’t help me.” And I go, “Well, of course, what were you taking?” And they tell me something they saw on TV in the form of a gummy and sugar. Well, of course that product doesn’t work. It can’t work.

So don’t blame nitric oxide. Blame the product and the company that’s trying to sell you a nitric oxide product that’s not working. So nitric oxide didn’t fail you, that company failed you. And that’s my biggest beat from somebody who spent 20 years in academia and academic medicine and developed products that actually work, is that we have to maintain the integrity of the field, hold these companies accountable.

Where to Find Dr. Bryan’s Work

RINA AHLUWALIA: Well, Dr. Bryan, thank you so much for maintaining the accountability of the integrity of nitric oxide. If people want to find more of you or more of your research and work, where can they find you?

DR. NATHAN BRYAN: You know, I send people to PubMed, you know, look at the published literature, the scientific literature, look at what’s in the literature. I’ve got my own YouTube channel. Dr. Nathan S. Bryan Nitric Oxide. Well, you know, I do lectures and interviews and podcasts. I’ve got an educational website, DrNathanSBryan.com. We do a monthly blog, some videos on there, really some timely, I think applicable. What I think are common sense ways to restore nitric oxide production. I’m on social media, LinkedIn, Instagram.

RINA AHLUWALIA: You have a book.

DR. NATHAN BRYAN: I’ve got a book called “Functional Nitric Oxide Nutrition.” I’ve got a new book coming out and probably we’ll do a soft launch in the early winter. It’s called “The Secret of Nitric Oxide: Bringing Nitric Oxide to Life.” It’s twofold, it’s part autobiographical. We talk about the discoveries we made early on that transformed the field.

But it’s also educational and trying to inform and educate the reader on the importance of nitric oxide and then really talk about what we just talked about over the past hour. What can you do to maintain and restore normal nitric oxide production to lead to a better life free of disease, increased longevity and increased health span? So be on the lookout for that. Probably in early December we’ll do a soft launch and be on the lookout for that. But I’m really excited and proud of that book project.

RINA AHLUWALIA: Wonderful. Well, all the resources will be in the full show notes of this episode. You can find Dr. Bryan’s book resources PubMed. I try not to say PubMed because people don’t want to read clinical research. Your book is wonderful because it really gives a nice simple view of exactly what nitric oxide is, the benefits, and how we can naturally increase it. So all those information will be available in the full show notes of this episode. But Dr. Bryan, thank you so much for your time and I’m sure we’re going to see you very soon.

DR. NATHAN BRYAN: Thank you Rina. It’s a great joy.

RINA AHLUWALIA: Thank you for joining me on this episode with Dr. Nathan Bryan. You can find the full show notes including journal articles, books and resources at the 5MB labs. There is a link in the description of this video. If you’re learning from and enjoying these episodes, please hit the subscribe button. That is an excellent zero cost way to support this free health podcast.

If you have a question for me or a recommendation of a guest speaker to please leave that in the YouTube comments as I check every single one. You can also find me on other social media accounts. I’m @5minutebody on Instagram and on X formerly known as Twitter. As I share different information to what you’ll see here on YouTube, I share different health tips and advice that I hear from the best experts.

And if you enjoyed this episode, you’ll also enjoy another episode I did with Dr. Georgia Ede. Dr. Ede is a Harvard trained psychiatrist who has spent 25 years researching how we can treat brain diseases like dementia, but also mood disorders like ADHD, anxiety and depression with nutrition. In this episode, Dr. Ede will share how we can restore our brain, especially if our brain is damaged from mood disorders or brain disease, and also ways that we can optimize brain function.

Dr. Ede shares the three main neurotransmitters that are responsible for optimal brain function and nutritional therapies to help improve it. Dr. Ede also discusses the role of saturated fat and cholesterol, their impact on the brain, the role of common medications, for example statins and interestingly, spices and their effect and how they can potentially damage the brain. Finally, thank you for your interest in root cause healing and I’ll see you next week.

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