I am delighted to connect with Dr. Nathan Bryan, an international leader in Molecular Medicine, biochemistry, and nitric oxide today. He was the first ever to describe nitrites and nitrates as indispensable nutrients for cardiovascular health. Having been involved in nitric oxide research for the past 18 years, he has made many seminal discoveries in that area.
After hearing Dr. Bryan speak on the podcast of a colleague, I decided to bring him into the Everyday Wellness Community. In today’s discussion, we explore the role of nitric oxide as a signaling molecule crucial for communication within the body and examine how modern lifestyles affect nitric oxide production, looking at how to differentiate between the two nitric oxide pathways and understanding why our lifestyle choices significantly impact that. We discuss the importance of the oral microbiome and symbiosis, the harmful effects of fluoride, proton pump inhibitors, and mouthwash on our health, and cover the symptoms of low nitric oxide production, the impact of modern farming practices on the nutrient quality of our foods, and the differences between organic and conventional crops. Dr. Bryan highlights the importance of gender differences in nitric oxide production, particularly during perimenopause and menopause. We also explore various factors to avoid, the benefits of tongue scraping, the role of hydrochloric acid, and the importance of genetic testing for supporting nitric oxide production, and Dr. Bryan shares his view on how lifestyle choices and nitric oxide supplementation are as crucial as HRT in the aging process.
I am confident you will love this conversation with Dr. Nathan Bryan as much as I enjoyed recording it.
IN THIS EPISODE YOU WILL LEARN:
What nitric oxide is and why it is essential
Dr. Bryan explains the process of nitric oxide synthesis in the body.
The importance of oral bacteria in nitric oxide production and blood pressure regulation.
Why nitrate is essential nitrate in the oral microbiome, and how it impacts the digestive system
How fluoride can harm the oral microbiome and lead to nitric oxide deficiency.
Why should the use of proton pump inhibitors be avoided?
Why nitric oxide, derived from green leafy vegetables, is essential for cardiovascular health
How nitric oxide production decreases with age, particularly in women after menopause
The benefits of tongue scraping and why you should not do it with antiseptic mouthwash
Lifestyle factors that impact nitric oxide production
The benefits of nitric oxide supplements
Bio: Dr. Nathan Bryan
Dr. Bryan is a successful CEO, scientist and international leader in molecular medicine and nitric oxide biochemistry. His patented discoveries and inventions that have improved patient care worldwide and are responsible for more than one billion dollars in global product sales.
By way of background, Dr. Bryan was recruited in 2006 by Ferid Murad, M.D., Ph.D., 1998 Nobel Laureate in Medicine or Physiology to join faculty at the University of Texas Health Science Center, at Houston after a two-year post-doctoral Kirschstein fellowship at Boston University School of Medicine in the Whitaker Cardiovascular Institute.
Since then, he has been dedicated to nitric oxide research and has made many seminal discoveries in the fi eld resulting in dozens of issued US and International patents.
“If you destroy the oral microbiome, it shuts down nitric oxide production, your blood pressure goes up, and you lose the protective benefits of exercise, develop erectile dysfunction and other symptoms of nitric oxide deficiency.”
-Dr. Nathan Bryan
Connect with Cynthia Thurlow
Follow on Twitter
Check out Cynthia’s website
Submit your questions to support@cynthiathurlow.com
Connect with Dr. Nathan Bryan
On his website
On the N101 website
You will find 100’s of peer-reviewed articles by Dr. Nathan S. Bryan on PubMed. Also, look out for his new book, coming out this fall, called The Secret of Nitric Oxide: Bringing Nitric Oxide to Life.
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I had the honor with connecting with Dr. Nathan Bryan. He's an international leader in molecular medicine, biochemistry and nitric oxide. He was the first to describe nitrite and nitrate as indispensable nutrients required for optimal cardiovascular health. He has been involved in nitric oxide research for the past 18 years and has made many seminal discoveries in the field. I actually listened to him on a colleague's podcast and decided that I must bring him to the Everyday Wellness Community.
[00:01:01] Today, we dove deep into the role of nitric oxide as a signaling molecule responsible for communication, the impact of our modern-day lifestyles on nitric oxide, production, differentiating between the two different nitric oxide pathways and why our lifestyle choices have a large net impact on this particular signaling molecule. The importance of the oral microbiome the role of symbiosis, why fluoride, proton-pump inhibitors and mouthwash are detrimental if not profoundly impactful to our health, symptoms of low nitric oxide production in the body, how our modern-day farming conditions have impacted, not only the micronutrient and nutrient quality of our foods, but the differentiators between organic versus conventional crops.
[00:01:56] The importance of gender differences, including changes in perimenopause and menopause specific to nitric oxide production, things to avoid the impact of tongue scraping, the role of hydrochloric acid, why genetic testing is critically important for supporting nitric oxide production in our bodies, the impact of lifestyle and lastly, nitric oxide supplementation. Dr. Bryan believes it is as important as HRT is in the evolution of the aging process. I know you will enjoy this conversation as much as I did recording it.
[00:02:35] Well, Dr. Bryan, so good to have you on the podcast. I stumbled upon your work and I knew that I wanted to bring your message and your research to my Everyday Wellness Community. Welcome.
Dr. Nathan Bryan: [00:02:45] Thank you so much. Great to be with you.
Cynthia Thurlow: [00:02:47] Absolutely. Let's start the conversation around the importance of nitric oxide and what exactly it is. Because some of my community members and listeners that are clinicians, they probably will dust some cobwebs out of their brains, remembering that they learned about nitric oxide, but perhaps, for the extended community that may not be familiarized with it, what is it and why is it so important?
Dr. Nathan Bryan: [00:03:12] Well, it's a signaling molecule. It's naturally produced in the body. It's how cells in the body communicate with one another. But it's most recognized for its signaling in the cardiovascular system. So, it acts as a vasodilator. So, when it's produced in the lining of the blood vessel, it diffuses into the smooth muscle, where it basically relaxes the smooth muscle, and that leads to blood vessel dilation. So, when you dilate blood vessels, obviously, you improve oxygenation, you improve nutrient delivery. It's a neurotransmitter in the central nervous system, so it's a critical molecule in neurotransmission.
[00:03:45] But it's also how our immune system kill off invading pathogens from viruses to bacteria. So, that was the landscape of nitric oxide 20 or 30 years ago. But today, we know that it's much broader than that. It's the molecule that tells our own stem cells to mobilize and differentiate. It improves mitochondrial function and mitochondrial biogenesis, and really the mechanism of actions of things like intermittent fasting, caloric restriction. And then it prevents our telomeres from getting shorter, so it extends longevity. So, this whole field of longevity is really dependent upon the body's ability to make nitric oxide.
Cynthia Thurlow: [00:04:17] And it's my understanding that as we age, we have less and less nitric oxide available as a signaling molecule. I think the estimation was 10% to 12% per decade reduction. So, by the time you're 40 or 50, you have less circulating nitric oxide that's available. What is it about our modern-day lifestyles that impacts how much or how little nitric oxide is available to utilize in the body?
Dr. Nathan Bryan: [00:04:43] [laughs] No, [Cynthis laughs] you're exactly right. So, when we look at population-based studies, like the general population, you do see this stepwise decrease in nitric oxide production with age. But now we know that doesn't have to be the case. In fact, we can prevent this age-related loss of nitric oxide, or we can accelerate it, but it's really based on what we do. And it's the Western lifestyle. It's a sedentary lifestyle, it's processed foods, it's use of mouthwash, antibiotics, antiseptics. So, really, everything we do in the western world leads to a loss of nitric oxide production. But fortunately, we've learned so much over the past 20 years. We know what leads to this loss of nitric oxide, we know how to overcome it. And now, we can actually prevent this age-related loss of nitric oxide.
[00:05:27] I think I'm always the best example because I'm always the N=1 guinea pig anytime we start something. So, I turned 50 in November. But yet, if you look at my average nitric oxide production or endothelial function, I'm where a normal 32 or 36-year-old would be. And then we see 20 and 24-year-old kids, still call them kids, that have the vascular age of a nitric oxide production of a 60 or 70-year-old. So, this is a moving scale. But I think what people need to understand is, look, you need to understand what your capacity to produce nitric oxide is. And if it's compromised, then you need to take steps to make sure your body produces sufficient amounts of this molecule.
Cynthia Thurlow: [00:06:05] And are there specific signs that-- If someone's listening to this podcast and they're curious, if their nitric oxide production is not optimal, are there signs to them, to the outside world, obviously, other than utilizing mouthwash? Because I know that we'll get into that. Are there signs that they could be looking for that might identify that they in a position where they have less circulating nitric oxide available to use?
Dr. Nathan Bryan: [00:06:31] Yeah, absolutely. So, we've got a clear clinical picture of this over the past 20 years. You have to rely on symptoms, because you can't go to your doctor with a blood panel and get numbers for your vitamin D or cholesterol or triglycerides, because nitric oxide is a gas. Once it's produced, it's gone in less than a second. So, we have to rely on symptoms. The first symptoms that typically occur or manifest early on are sexual dysfunction, because if you can't dilate the blood vessels of the sex organs, you don't get engorgement and you cannot get an erection. This isn't just a male disease. This happens in female too. So, whether it's a penile or clitoral erection, all that's dependent upon the blood vessel's ability to produce nitric oxide which leads to vasodilation, which leads to engorgement. So, that's usually the first thing. We call that the canary in the coal mine.
[00:07:17] And then the second one that'll typically start to show up as you see an increase in blood pressure. So, now we know that any increase in blood pressure above 120/80 is a loss of nitric oxide production. And then you start to develop metabolic disease, because nitric oxide is involved in insulin signaling. If you have type 2 diabetes or insulin-resistance or any type of metabolic disease, which 9 out of 10 Americans are metabolically unfit, so that's a large percentage of the population. And then you start to develop exercise intolerance. If you can't walk up a flight of steps without getting short of breath, and your body's not making nitric oxide.
[00:07:52] And then the long term, if you have all this and it's not corrected, then you start to get vascular dementia, mild cognitive decline and then eventually, you'll get Alzheimer's. So, those are the hierarchy of symptoms that manifest or present when you've lost the ability to produce nitric oxide.
Cynthia Thurlow: [00:08:07] And it makes so much sense. I recall as a new nurse practitioner, I finished my nurse practitioner program in 2000, and I remember a very astute vascular surgeon was explaining to me that when you see erectile dysfunction, think of diabetes. He was so far ahead of his time and helping people understand, although that can sometimes be an uncomfortable conversation to have with your clinician, it's an important one to identify what could potentially be like a brewing. You mentioned the canary in the coal mine, but for many individuals, they get uncomfortable having those conversations. But it is a surefire sign that something is awry. Knowing that 92% to 93% of Americans are not metabolically healthy, this is a really epidemic proportion of individuals that are impacted by this.
[00:08:53] So, let's get back to talking a little bit more about some of the pathways involved with nitric oxide production. I know that there is one pathway that is converting nitric oxide synthase. We're going to get a little sciency, but we're going to make it relevant to everyone. One thing that I want to preface what I'm about to say is there's a lot of well-meaning supplement companies. I say this because a lot of times, people send me free things and want me to talk about it on social media. But knowing what I know now, a lot of things I've been sent are actually not efficacious or even effective. And so, let's talk about the production.
[00:09:29] There are several different pathways of nitric oxide production, but let's start with probably the one that is probably less commonly known, as opposed to the one that you were alluding to before talking about nitric oxide and saliva in the gut. Let's talk about the other pathway, that nitric oxide synthase, which converts to L-arginine into nitric oxide, and how that process actually works.
Dr. Nathan Bryan: [00:09:51] Yeah. So, that was really the pathway where nitric oxide was discovered. This goes back to the mid 1980s and early 1990s, because it was first realized that in cell culture, in our immune system, that you could accumulate nitrate, but you had this will require arginine in the culture medium. Without arginine, the immune cells couldn't make this molecule that was leading to shutting down bacterial respiration and preventing virus from replicating. So, fast forward, I think, 10 years, and there was a group that discovered this nitric oxide synthase enzyme. It's that enzyme that's found in the lining of the blood vessels that basically does this five-electron oxidation of L-arginine which is in a semi essential amino acid. And through this very complicated complex multi-step reaction produces nitric oxide.
[00:10:37] And then you get L-citrulline as a byproduct. So, citrulline is a byproduct of nitric oxide production. It's not a precursor, but this is recycled through the urea cycle and you can reform arginine from citrulline, but it's very complex biochemistry. The very important consideration is that the body is never deficient in L-arginine. We get it from the breakdown of proteins, whether it's animal proteins or plant proteins. Amino acids make up proteins. And in most proteins, there's usually L-arginine. But even if we don't get enough from our diet, we make it through the urea cycle. The partial urea cycle is present in every cell in the body. It provides essential metabolic substrates, and basically disposes of nitrogen through urea and through the kidneys and then expel it through the urine.
[00:11:27] So, it never made sense to me as a biochemist of why you would give L-arginine, because there's never a condition where L-arginine is limiting in the ability to make nitric oxide. But most people in supplement companies, if you're low in magnesium, what do you do? Well, you just give magnesium till we can get your levels up. Same thing with vitamin D. If you have low vitamin D, well, let's give you vitamin D until we get your levels above 80 or around 80. But with arginine, even the sickest of sickest patients, they have 20 to 40 times more than what's required to produce nitric oxide. So, the point here is it makes no sense to supplement L-arginine, because the problem in nitric oxide deficiency is the cell has lost the ability to convert arginine to nitric oxide, and that's due to the uncoupling of the NOS enzyme. So, we have to focus on the enzymology and the biochemistry, recouple that enzyme. Now, that cell actually uses arginine that's produced endogenously, not extracellular arginine to make nitric oxide. So, that's a very important consideration.
[00:12:27] All these supplement companies who are selling arginine based nitric oxide products, it's a complete waste of time and money. And now we know that if you do this in certain patient populations, you actually make them worse. Post infarct patients or patients who just had a heart attack, they were given arginine and, the increased death and mortality. In fact, they didn't even complete that clinical trial, because the steering committee thought it unethical to continue that trial because arginine was killing more patients than the placebo group. And then the same thing happened with patients with peripheral artery disease. If you give them arginine, their condition gets worse. Intermittent claudication gets worse and the disease gets worse. So, arginine is not the solution.
[00:13:08] I've been doing this for 25 years. There's never a condition where arginine is beneficial in the production of nitric oxide. [crosstalk] Extra supplemental arginine, I should say. Now the body has regulatory mechanisms intracellularly that control arginine metabolism, arginine flux and recycling from L-citrulline that, but it makes no sense to give arginine or citrulline supplement.
Cynthia Thurlow: [00:13:28] Yeah. It's helpful to have that information, because I always have to believe that some of these supplement companies, they understand a little bit of the science. I don't want to say they take advantage. That sounds pejorative. They're trying to find a solution to a problem. And so, your explanation allows a lot of the community to better understand this process.
[00:13:46] Now, there's this other production of nitric oxide that's involved. This is actually what I found so fascinating residing in the mouth, the oral microbiome is so important for nitric oxide production and how some of the things we do that we unknowingly are actually depleting or eradicating nitric oxide production or the ability to produce nitric oxide relevant to things as innocent as mouthwash.
Dr. Nathan Bryan: [00:14:13] Yeah. Well, I think what we have to start at what my approach has been much different in basic science. So, the scientific method of generating hypothesis and then testing, that doesn't work. That's why science really never translates into clinical medicine. So, what I've done a little bit differently is I take important clinical observations, what's indisputable clinical observations and then work backwards to try to figure out mechanism, why are we seeing that particular outcome with certain interventions.
[00:14:41] About 20 years ago, it was first reported that if you use mouthwash, you see an increase in blood pressure. That was a completely new paradigm to cardiologists and vascular biologists, because how is the oral microbiome connected to the second-to-second regulation of blood pressure and blood flow. So, then the question was, well, there has to be something in the mouth. Fast forward 25 years, and we now know that it's the oral bacteria. So, the human microbiome project is completely mapped. We know we understand the oral microbiome, the gut microbiome, the vaginal, the dermal microbiome.
[00:15:15] So, the bacteria that live in and on our body outnumber our human cells 10 to 1. These bacteria code for three million gene products, and the human genome only codes for 23,000 gene products. So, these bacteria, as we know, again through clinical observation, if you use antibiotic every day, what happens? People get systemic disease and they get sick because you're destroying the microbiome. Well, the same thing happens in the mouth, if you destroy the oral microbiome and it shuts down nitric oxide production, your blood pressure goes up, you lose the protective benefits of exercise, you start to develop erectile dysfunction and all the symptoms we talked about of nitric oxide deficiency.
[00:15:52] That's when we intervened. I guess, probably 20 years ago, started doing tongue scrapings, trying to figure out, number one, can we culture these bacteria? Number two, can we then ascribe some type of metabolic function to them and then start to make predictive models on? If you don't have these bacteria or you have some dysbiosis, what happens to nitric oxide production and what happens to your blood pressure? And then we published, I think, four years ago, that if you use mouthwash in patients, young, healthy patients with normal blood pressure for seven days, we can see almost a 26-millimeter increase in blood pressure. No change in diet. These are patients that are not on any drugs, drug therapy, prescription medications. We didn't change their diet. The only thing we did was give them mouthwash twice a day for seven days, and it made them clinically hypertensive.
[00:16:37] So, that's the clear association between destroying the microbiome, decreasing nitric oxide production and an increase in blood pressure. So, mechanistically, we certainly understand this. And now, we can actually predict steady state blood pressure by the presence and number of half a dozen or less bacteria in the body, in the mouth. So, it is a very powerful tool.
Cynthia Thurlow: [00:17:00]: Its really interesting, because I think that for so many of those of us that had grown up during our lifetime, we were all encouraged-- My father used Listerine every single day for his entire life. His entire life, used Listerine. Even my husband, when we first met, used Listerine breath strips. I managed to get him off of that. But how many people that are listening are unknowingly impacting such an important function in their body without even realizing it. And so, thank you so much for the work that you do.
[00:17:30] Let's talk a little bit about saliva. You mentioned that there is this complex interrelationship with the oral microbiome, how integral it is in activation of nitrate and then nitric oxide gas. How does that interplay with the digestive system overall?
Dr. Nathan Bryan: [00:17:48] Yup. Well, again, let's start with indisputable clinical observation. This comes from epidemiology. So, it's known for many decades that people who eat a really healthy diet, mainly a plant-based diet, but there's other dietary patterns, a Japanese diet, for example, the dietary approaches to stop hypertension, those have important clinical outcomes. And so, for years, people thought, "Well, it's just the vitamins and the minerals and the antioxidants that are contained in those foods that recapitulate the clinical benefits." But when you do intervention studies and you try this antioxidant cocktail or mix that's found in vegetables, you fail to recapitulate the benefits of that certain diet.
[00:18:27] Now we know that it's due to the nitrate content in certain food and dietary patterns. So, nitrate is a naturally occurring molecule. It's found in the soil. They're nitrifying bacteria that fix nitrogenous or ammonia into nitrate and then the plants that are grown in the soil assimilate this. And then when we consume it as humans, we're denitrifiers. So, we basically denitrify that whole process.
[00:18:50] So, it works like this. If you eat say 100 grams plate of spinach, when we chew that, it's taken up into the stomach-- As long as we have sufficient stomach acid production, then that food is digested, proteins are broken down into amino acids, we can absorb things like selenium, chromium, B vitamin, zinc, iodine. And then when we get that acid load into the duodenum, that promotes bicarbonate secretion. So, that's the entire acid base balance on the human body. But in that proximal gut, the duodenum, nitrate is intentionally taken up and transported and put in our salivary glands. This takes about 90 minutes. So, from the time you consume a plate of salad or spinach or green leafy vegetables, 90 minutes later, now our salivary glands are secreting this nitrate.
[00:19:39] This was first recognized in 1978, because cancer biologists were trying to understand, why would the body intentionally concentrate nitrate in our salivary glands? Because 40 years ago, it was thought, “Well, nitrate forms nitrosamines. Nitrosamines cause cancer. Therefore, nitrate causes cancer.” But now we know that the kidney reabsorbs nitrate, it's concentrated in our salivary glands. And now we know that the bacteria that live on the crypts of the tongue metabolize this nitrate into nitrite and then when we swallow our saliva, it becomes nitric oxide gas. But we're 100% dependent upon the bacteria because humans do not have this enzyme. So, again, this is another real-world example of symbiosis. The bacteria that live in and on our body are doing things essential to the human host that we cannot do otherwise without the bacteria.
[00:20:27] So, if you wake up every morning, and two out of three Americans do this and use mouthwash and kill the oral microbiome, now you've lost the protective benefits of a healthy diet, you lose the protective benefits of exercise, and your blood pressure will typically go up and bad things happen. You become nitric oxide deficient. And even more, the problem is fluoride. Fluoride is antiseptic just like Listerine. Listerine, if you look at the commercial, it says kills 99.9% of the bacteria. They flaunt that. They advertise that. That's not a good thing. [laughs] Fluoride does the same thing. It's an antiseptic. That's why they put it in municipal water, and that's why it's in your toothpaste. It's a neurotoxin, and it shuts down your thyroid function. So, you have to get rid of fluoride in your toothpaste and your drinking water, the water you bathe in, you cook in, and you have to stop using mouthwash.
Cynthia Thurlow: [00:21:20] Yeah. I think that these are practical things. I know that when my children were born and they were first seeing a pediatric dentist, one of the ways that we selected the dentist we ultimately used was someone that was open to the possibility of not doing fluoride treatments. When I presented the dentist, who is a good friend of mine, we talked about it openly, and she said, "I would say 50% of my patients at this point are not doing fluoride treatments on their children." I said, "How many others are just blindly following treatment recommendations about questioning some things that are going on?"
[00:21:51] What is the net impact of someone is taking? Because I know that I prescribed thousands and thousands of proton-pump inhibitors and H2 blockers. And so, in cardiology, we did a ton of it. Because everyone came in and they had super long, lengthy hospitalizations, or they had infarcts, heart attacks coming into the hospital. Everyone was put on PPIs, which are designed to only be used for 30 days, by the way. [crosstalk] But they're typically used for years and years and years. What is the net impact on our nitric oxide production?
Dr. Nathan Bryan: [00:22:22] Well, these drugs turns out, completely shut down nitric oxide production from both pathways. So, again, same theme here. What are the clinical observations tell us? Data came out in 2015 that revealed, that patients who have been on proton-pump inhibitors for at least three years-- I think in this cohort, it was three to five years. And then they took age match counterparts that were not on proton-pump inhibitors, accounting for all the confounders, and reported that people had been on PPIs had about a 30% to 40% higher incidence of heart attack and stroke than those who weren't same age match control groups. The only difference was the group that had 30% to 40% higher heart attack and stroke were on PPIs for three to five years.
[00:23:07] And then now, in December, I believe this latest report came out, showing that patients had been on PPIs for four years, at least four years, of 40% higher incidence of Alzheimer's. So, again, those are the outcomes. Now, what's causing this? Well, mechanistically, we know that PPIs inhibit an enzyme called DDH. It's a hydrolase that breaks down asymmetric dimethyl arginine, and that's a metabolite we call ADMA, and that inhibits nitric oxide production. So, PPIs cause an increase in ADMA, completely shuts down nitric oxide production in the lining of the blood vessel.
[00:23:41] And then the other thing, and we talked about this briefly, when we eat plant-based meals or a nitrate-rich diet, its converted to nitrite in our saliva. We need stomach acid for that nitrite in our saliva to become nitric oxide. And so, if you're inhibiting stomach acid production, then you completely inhibit nitric oxide being produced from this enterosalivary circuit, and the nitric oxide we're getting from our diet. So, again, basically, what that boils down to is this one class of drugs, proton-pump inhibitors, completely shut down endogenous nitric oxide production. They're deadly clinical consequences of this heart attack stroke and Alzheimer's.
[00:24:20] That's just part of the story. There's already warnings of, you can't absorb calcium, you can't absorb B vitamins, you can't absorb selenium, chromium. It leads to osteoporosis, bone fractures, kidney problems. These are the warnings already on these drugs. But I believe they should be taken off the market, because they're dangerous, they really provide zero benefit and they are risk. The risks are enormous. And so, they need to be informed. And if patients knew the impact of these drugs, no one in their right mind, if they were properly informed, would elect to take these drugs.
Cynthia Thurlow: [00:24:53] Yeah. It's interesting to me watching the practice patterns evolve over 25 years of being in clinical medicine. I think that, initially, they were utilized very sparingly, and now it's being given out nearly every patient in the hospital is getting a PPI on board, especially if they're in the ICU or they're in a critical care area out of concern over stress, which is just further depleting [Nathan chuckles] not only nitric oxide, but HCL production, hydrochloric acid for those that are less familiarized with that term.
[00:25:23] Let's talk a little bit about the impact of soil and farming, organic versus conventional. Because I think for many of us, we have been familiarized with the Dirty Dozen, the Clean Fifteen, The Environmental Working Group, preferentially how some organic props are improved. As I was preparing for this podcast, the things that stood out, like big tangible takeaways, I think this is a big one.
Dr. Nathan Bryan: [00:25:51] Yeah. Look, there's a whole field of agronomy that basically teaches us and informs us on what do we need to replete the soil with in order to grow a nutrient dense food. And so, for hundreds of years, it's been known that nitrogen is required in the soil to not only lead to better crop production, but to assimilate other vitamins, nutrients and minerals into that plant. Years ago, we had much different farming practices, 100 years ago than we do today. And again, if you look at the data, the food that's grown in America today has 78% less nutrients than it did in the 1940s. And so, that's just 80 years later, we've 80% reduction in the nutrient density of plants and vegetables grown in the US. So, the pressure of feeding a growing population is at the expense of nutrient density.
[00:26:43] And then, probably 20, 30 years ago, this whole organic concept came on board because most people, rightfully so, don't want herbicides, pesticides or poison on their food. So, how do you create a label that allows for that and the consumer can be confident that what they're getting is not sprayed with poisons it's going to make them sick. That's how the whole organic movement became. But I think with anything, you can go too far. And so, organic is good because there's no herbicides or pesticides. But part of the organic labeling process is you're not allowed to add nitrogen-based fertilizers to the soil, because there was fear of nitrogen runoff into streams, and lakes and well water contamination with nitrate causing infantile methemoglobinemia enteritis that was back 30 years ago. Today, we know that that's not a problem whatsoever. But you can add in organically grown vegetables, you can add compost, you can add manure. But again, there's no standardization of the nitrogenous or the potash or the phosphorus or all the other essential minerals needed for crop growth and improved yield.
[00:27:52] We published on this in 2015, conventionally grown vegetables, organically grown vegetables have on average 5 to 10 times less nitrate than conventionally grown. And so, what we found was when we tried to do calculations on how much organic celery or lettuce or spinach would I need to eat to get enough nitrate in my diet, that if you had the right oral bacteria and you had sufficient stomach acid production, that we could lead to an appreciable amount of nitric oxide to normalize your blood pressure. What we found was, it's almost impossible to eat enough organic vegetables. But two, it depends upon where you lived. What we're finding now is that lightning storms fix nitrogen in the air, because the air we breathe is 78% nitrogen.
[00:28:36] In areas where there are a lot of lightning storms along this Rust Belt, along the southern US, then that soil seems to be more concentrated in nitrate and other minerals and nutrients. Where upstate New York, even in North Carolina, there seems to be less nitrogen in the soil and as much as a 50-to-80-time variable on the nitrate content in celery in Dallas or Los Angeles compared to New York or Raleigh, North Carolina.
[00:29:04] So, the whole point of that is it's impossible to make recommendations on how much celery, broccoli, spinach, lettuce you would need to eat to get enough nitrate, because it depends on where you live, how they're grown, conventional versus organic. And so, there's no standardization. And so, that was a little bit surprising to us because-- But then when you think about it, well, it makes perfect sense. So, that's the problem. Talking with physicians like Caldwell Esselstyn and Joel Kahn, who use a plant-based diet to reverse cardiovascular disease, to their own admission, some patients get better, some patients don't. And so, why does one person respond versus other? And then when we have a conversation where I go, "Well, the ones that don't respond, ask them if they're taking mouthwash," because you completely eradicate the nitric oxide benefits of a plant-based diet by using mouthwash. Are they using fluoride toothpaste? Are they on antacids?
[00:29:57] It was like, a light went off, they go, "Holy shit. We've never asked that question.” “Why would you?” But now that you understand the mechanism of how they're getting the protection from in some patients and the regression of vascular disease and others not, then the mechanism is very well defined, then you just have to ask the right questions.
Cynthia Thurlow: [00:30:15] Well, that's where I think researchers are so critically important for clinical practice. I love that you started off the conversation saying, I re-engineer problems differently-- [Nathan laughs] solutions differently than a lot of my colleagues. And so, for anyone that's listening, that's curious, what are our nitrate needs per day anyway? That's not anything that is a clinician I was ever taught. I think this is really interesting. For people that are curious, they're like, "Well, how much am I supposed to consume in my diet on a daily basis?" Because everyone focuses in on other types of substrates. This is really important.
Dr. Nathan Bryan: [00:30:52] No, it is. But look, it's a completely change in paradigm, because, as your listeners are probably aware and some of them probably spend a lot of money on buying nitrate, nitrite-free bacon, hot dogs, no nitride cured, because, just like we were misinformed 30 years ago that cholesterol causes heart disease, we've been misinformed on nitrite cured meats, processed meats causing cancer. So, this whole concept of eliminating nitrate in our diet is to our own demise. If nitrate caused cancer, vegetarians would have a 10-time higher cancer rate than non-vegetarians or meat eaters.
[00:31:30] We know it's just the opposite, because 85% of the nitrate we get from our diet comes from green leafy vegetables. Only 5% comes from cured and processed meats. And then our cured meats, processed meats typically don't have any nitrate. It's only the cured meat products. And then the other 10% comes from swallowing our own saliva that we make from endogenous nitric oxide production. But if you look at the data, and these are standardized clinical data showing a nitric oxide benefit, you need 300 to 400 milligrams of nitrate per day. Really, that's in a single bolus. So, you need to take it all at once. So, you would need on average--
[00:32:07] Again, it's impossible to quantify how much you would need, but let's just say 150 grams plate of salad or spinach in Houston or Dallas, at least where we did some of the analysis, would give you enough nitrate that if you had the right bacteria, had stomach acid, we could normalize your blood pressure. But that's about 150 grams of spinach. Thats a whopping plate. Theres not many people who can sit down in one serving and eat that much.
Cynthia Thurlow: [00:32:32] Yeah, it's so interesting. Then the other thing that occurred to me is through the course of your research, have you seen any gender differences, life stage differences? Because I'm always viewing things in the context of women and men are very different, different life stages, menstruating women, are their needs different than non-menstruating women? Have you read any research in these areas in particular?
Dr. Nathan Bryan: [00:32:57] No. Absolutely. Estrogen is a very positive, very powerful activator and stimulator of nitric oxide production. That's why premenopausal women are a little bit protected at a decreased risk of heart attack, stroke and really all cause vascular mortality than their age matched men. But when they reach the time of menopause where they lose the production of estrogen, now you see the increased risk of ischemic heart disease, heart attack, stroke, ischemic non-obstructive coronary art disease. That's because their nitric oxide levels at that point where they start producing estrogen plummet, that leads them to an increased cardiovascular risk.
[00:33:39] Women typically eat a little bit healthier than men, from my experience. And so, I think there's probably a synergism there, a better diet along with the positive effects of estrogen that lead to a little bit more nitric oxide production and some cardio protection. But at menopause, I think we not only have to think about restoring the hormones and hormone replacement therapy, but first, we have to restore the production of nitric oxide. So, now when you do that hormone replacement therapy, you're still going to get activation and stimulation of nitric oxide, but we have to first focus on restoring the function of that enzyme. So, when we replete estrogen, it can lead to activation of nitric oxide, and basically normalize the risk in postmenopausal women.
Cynthia Thurlow: [00:34:21] Yeah. I think that we are thankfully coming full circle. The women's Health Initiative came out in 2002 when there were thousands, if not millions of women that either were taken off their HRT. Now, we're seeing a resurgence. We're coming back to this. But if you look at my mother's generation, your mother's generation, how many of those women, the trajectory of their health, has really gotten derailed by virtue of the fact that they were not even offered HRT? And so, I think and reflect on why these conversations are so important. Thank you for sharing that with the community, because I know there are many women who may not yet be at the stage that they need to replace estrogen, but helping them understand that that is certainly very important for nitric oxide production.
[00:35:04] What other types of things? We talked about fluoride, we mentioned proton pump inhibitors. What other types of medications? I'm thinking about antibiotics as a huge class of drugs. Is it duration of use? Because I'm sure everyone listening has probably at least had one or two rounds of antibiotics, hopefully appropriately. But for individuals that maybe had a long four to six weeks, maybe they had a tick-borne illness, they had Lyme disease, which is endemic in my state. I know that I had a hospitalization in 2019. I got six weeks of antibiotics and antifungals. I'm presuming at some point, if people are working to restore the vaginal, the oral and the gut microbiome, they can repopulate and refurbish the net impact on nitric oxide production. But what is the research saying specific about antibiotic therapy?
Dr. Nathan Bryan: [00:35:53] Well, as the name implies, it's antibiotic, antilife, [laughs] bacterial life. And so, there's a reason you don't take antibiotic every day, because as you mentioned, it destroys the microbiome. But look, if you have an infection and you don't want to get septic and die from this, especially when there's effective antibiotics out there to treat an infectious pathogen, but there's always collateral damage. What we found in the oral microbiome, and I think the true is in the gut microbiome or any microbiome, that these communities are extremely resilient.
[00:36:24] So, in our 2019 paper, we basically just took seven days of antiseptic mouthwash used, and then we stopped for four days. We brought these patients back after four days and then redid their tongue scrapings, reanalyzed their microbiome, reanalyzed their blood pressure. What we found was, four days off of the antiseptic, the communities had completely repopulated the blood pressure, completely normalized. So, these communities are really resilient. If you stop, shutting down their production and killing them off, then they basically repopulate. But I think it depends upon what we feed them. Obviously, the microbiome in the gut is much different than the microbiome in the mouth, which is much different than the microbiome in the vagina. So, we have to give those bugs what they need to flourish, to improve their ecology, to improve their diversity and let them do their job. Support the biome Don't eradicate it.
Cynthia Thurlow: [00:37:17] Well, and I think that's an important message for anyone that's listening that's in a panic, because maybe they are using mouthwash and fluoride toothpaste, and they're on a PPI and they have taken antacid intermittently throughout their lifetime. What is the impact of things like oil pulling? Does that have a negative net impact, or tongue scraping, which I know is ayurvedic and it's something I love doing? Does that have a negative net impact on nitric oxide production?
Dr. Nathan Bryan: [00:37:43] No, interestingly, tongue scraping, we found that the people who were doing tongue scrapings, we had to query these patients because we get different responses across these human subjects. What we found was that the people who were doing tongue scrapings once or twice a day had the best blood pressure to begin with. So, this ayurvedic practice that's been used for, what, thousands of years, and things that survived the test of time that are still around thousands of years later, they've stood the test of time because they worked. They're effective, and it selects some type of protective phenotype. So, tongue scraping is very beneficial. But what we found was that the people who tongue scraped that we gave the mouthwash to, those were the people who saw the greatest increase in blood pressure.
Cynthia Thurlow: [00:38:28] Hmm.
Dr. Nathan Bryan: [00:38:29] And it makes sense if you think about it, because tongue scraping opens up those pores, opens up those crips. And now, when you apply mouthwash, you basically you're opening up this tilling the soil to where you can get better penetration of the antiseptic and it leads to better killing. So, tongue scraping alone is extremely beneficial. It seems to have better management of blood pressure.
[00:38:50] Oil pooling, we just don't know. I think it's probably fine, because I don't think there's anything antiseptic or antimicrobial about that. But we've learned a lot on the use of antiseptics, but there's still a lot we don't know. What about some essential oils? What about oil pulling? What about some homeopathic remedies? Hydrogen peroxide, again, it's antiseptic. We find that it destroys it. Ozone, again, seems to destroy a lot of the good bacteria as well as the bad bacteria. But interestingly, this is a project we've been working on for several years now. I think we finally cracked the code, because our whole quest is how do we restore the body's ability to produce nitric oxide? That's what I've been focused on for the past 25 years. But we've created our own toothpaste and mouth rinse that, number one, it doesn't destroy the good bacteria. In fact, it promotes the diversity of the good bacteria. Because most pathogenic, non-commensal bacteria are sensitive to nitric oxide, we seem to have a way to selectively kill the gingival pathogens that carries causing bacteria while maintaining a healthy microbiome. And so, we're excited.
[00:39:57] We've just finished all the testing on that, but we should be able to launch that in the next 90 or 120 days. That's going to be a game changer, because the first study we're going to do is we're going to take people with high blood pressure and we're just going to give them our mouth rinse, with the intent of restoring the oral microbiome and leading to a better management of blood pressure. Because we've already demonstrated, if you destroy the microbiome, you see an increase in blood pressure. Now, if we give something like a mouth rinse that restores the microbiome, improves the diversity, improves nitric oxide production, can we now lower blood pressure and manage blood pressure? If that's the case, think about all the patients you can get off of antihypertensive medication. It's huge.
Cynthia Thurlow: [00:40:34] That's millions and millions and millions of patients. Not to mention the fact that when I was working in clinical cardiology, we sometimes had patients on three, four, five antihypertensives, and we would talk about refractory hypertension on so many levels. So, I love that you are doing the due diligence to help bring greater awareness to this association between buffered nitric oxide production and blood pressure.
[00:41:01] Now, when I think about digestion in general. I think maybe, perhaps, most people are familiar with hydrochloric acid, why that's so important for killing off pathogens and breaking down proteins into amino acids. Are there things that you are familiarized with in the research that are helpful for buffering the production of hydrochloric acid, specific nutrients or things that are helpful for reflux? Because inevitably, and let me be very clear, in no way are we telling anyone or instructing anyone to stop any medication. So, if you're taking a proton-pump inhibitor or an H2 blocker, continue doing so. But this is just something that I'm curious about, that hydrochloric acid is such an important component of the digestive system as well as a first line of defense in the body.
Dr. Nathan Bryan: [00:41:48] For sure. No, you have to go back to the biochemistry and understand what does a cell need to perform its metabolic function. The pyloric cells of the stomach are what secrete hydrochloric acid. So, what is this chemical reaction? And so, we understand that-- So, here's what you need for the pyloric cells to make hydrochloric acid. You need B vitamins, you need zinc, you need sodium bicarbonate, you need sodium chloride and you need iodine. But if you've been on antacids, you can't absorb B vitamins, you can't absorb zinc, you can absorb iodine. So, you become nutrient deficient. And now, these cells that are made, that are designed to secrete hydrochloric acid can't complete that chemical reaction, because it doesn't have the raw ingredients to do it.
[00:42:31] So, if you've been on antacids for a number of years, then you have to start supplementing things like zinc, and B vitamins, and iodine, and selenium and chromium, because you must have stomach acid production to absorb these base minerals and nutrients through the gastric mucosa. So, as Linus Pauling said decades ago, “Most chronic diseases caused from nutrient deficiency.” There's a physiological basis for that. Really, reflux disease to which you're prescribed antacid is a symptom of insufficient stomach acid production, because if you think about how the body's designed-- If a human body is exposed to something that it recognizes as foreign, it tries to get rid of it. So, you expectorate that. So, if you can't make sufficient stomach acid, then you can't break down proteins into amino acids, and your body sees whether it's a plant-based peptide or animal peptide, it sees it as antigen and it tries to get rid of it. So, your stomach goes, "Get this out of me." And so, you start to get a little bit of reflux in that, because your body has incomplete digestion.
[00:43:36] So, acid reflux is a symptom of insufficient stomach acid production. So, what I tell everybody is you have to acidify the lumen of the stomach before you eat a meal. Your body normally does it, but if it's been inhibited, then take a tablespoon of apple cider vinegar, which is just acetic acid, PH of around two, that'll acidify the lumen of the stomach. Now you can absorb the nutrients from your foods, break down proteins into amino acids, and now the pyloric cells have what it need to make stomach acid on its own. And so, it's really a self-correcting mechanism, but you have to get off antacids. You made a very good point, because you can't just stop taking these drugs cold turkey. This is something you have to work with your prescribing physician and slowly wean off of these over a period of time. If not, it's going to make your life miserable and you're going to have hypersecretion if you stop these cold turkey and it’s bad news.
Cynthia Thurlow: [00:44:25] No, it's really important information. In terms of the role of genetics, because selfishly I'm homozygous for MTHFR. I know that because of that genetic mutation, I am nitric oxide deficient already. What are some of the suggestions or recommendations or research surrounding these genetic polymorphisms and how they impact nitric oxide production?
Dr. Nathan Bryan: [00:44:50] Well, again, it's very well defined, mechanistically. We know that 45% to 55% of the US population has either a homozygous or heterozygous polymorphism in the MTHFR gene. That's the methylenetetrahydrofolate reductase gene. So, it's first thought, and still is it's a methylation issue. But if you look at the name of that enzyme, tetrahydrofolate reductase. That's the enzyme. So, its primary role is to reduce biopterin into tetrahydrobiopterin. Tetrahydrobiopterin is the rate limiting step in nitric oxide production. So, if you have an MTHFR SNP, especially the homozygous, then you have really reduced levels of BH4 or tetrahydrobiopterin. And that leads to NOS uncoupling, complete nitric oxide deficiency. So, that means the only nitric oxide your body is getting is from what you consume through the diet, the activity of the microbiome and the activity of the stomach acid production.
[00:45:48] So, those people that have MTHFR SNPs that use mouthwash, that use fluoride, that use antacids, they're basically creating a condition where there's completely devoid of nitric oxide. I guarantee you they're going to have ED, high blood pressure, metabolic disease, probably susceptible to heart attack, stroke, Alzheimer's. So, we have to correct them and we have to-- Number one, you have to understand your genetics, what are your deficiencies, and then employ strategies to overcome that. That's the beauty of linking personalized genetics to personalized medicine.
Cynthia Thurlow: [00:46:21] Absolutely. For people that are listening, that are curious, obviously, we talked about symptoms that can manifest, that can identify that you're probably dealing with a nitric oxide deficiency. But is there specific types of testing they should be looking for? I know that there is a blood pressure cuff test in particular that I was curious about. But what are the things that you generally recommend based on your research or people that want to determine their current levels, or what would they need to work on specifically?
Dr. Nathan Bryan: [00:46:51] Well, I think it's good just to do a genetic test. Look, let's figure out what the blueprint that you were born with to create the proteins and the metabolic machinery for that. If you get some type of single nucleotide polymorphisms, then you're going to have to compensate for that pathway that may be compromised through your genetic makeup. So, that's one.
[00:47:10] And then the other things are specifically as it relates to nitric oxide. ADMA, SDMA, these are inhibitors of nitric oxide production. Homocysteine, uric acid, triglycerides. We found that some of my patents on methods of reducing triglycerides. And then C-reactive protein as an inflammatory marker of some of my patents on the method of reducing inflammation. So, all of these are things that nitric oxide either directly or indirectly effect, and you can actually see real changes in these numbers.
Cynthia Thurlow: [00:47:40] I think it's really helpful and certainly one of those things that-- I think for many listeners, if they're trying to make sense of whether or not this is problematic. I know the role of lifestyle is certainly also very important. What are your typical high-level recommendations for individuals that are listening?
Dr. Nathan Bryan: [00:48:00] I think nitric oxide science is very complex, but the solutions are pretty simple. It's what we've known for decades. It's a physical activity. I used to say 20 to 30 minutes of light exercise a day. But now we know that just one to two minutes of high intensity interval training, once, twice, three times throughout the day. So, a total of six minutes can move the needle on stimulating nitric oxide production. So, you don't have the excuse of you don't have time anymore, because everybody, whether you're brushing your teeth or standing still in line, you can do 60-second squats or whatever and get your heart rate up and do some high intensity interval training, short duration, high intensity.
[00:48:42] Again, it's a balanced diet in moderation. I'm not a big fan of extreme diets like straight vegan, straight carnivore. I think we've evolved to get our nutrients from a diverse source of food. But I think it's moderation and elimination of sugar. Sugar is a toxin. Sugar is a poison. It's the most addictive substance we know of. And so, you've got to avoid sugar. And then don't get your nutrients or vitamins from gummies or chews. It's the most absurd thing. There are fads and supplements. There are fads that come and go. Some of these fads are dangerous. Gummies and chews completely destroy the oral microbiome. They shut down nitric oxide production. They glycate the enzyme that makes nitric oxide. It's dangerous. But yet, you see people, companies selling these gummies and chews all over the internet and TV. It's fraud.
Cynthia Thurlow: [00:49:32] I think lifestyle really is medicine. I love that the suggestions that you have discussed are certainly things that most, if not all people are able to participate in.
[00:49:43] In terms of supplementation, I know that you have some specific products. If someone is interested in trying a product or starting with something really simple, what do you typically recommend? What is your typical best recommendation? If they suspect that they're nitric oxide production is not optimized, obviously, there's lifestyle, etc., going on, but in terms of supplementation and looking at the products that your company offers.
Dr. Nathan Bryan: [00:50:07] Well, I spent 25 years in the basic sciences trying to understand how the human body makes nitric oxide, what goes wrong in people that can't make it and how do we restore it. So, we couldn't develop any product technology until we had a clear understanding of these biochemical pathways. So, our whole thought process was, "Okay, if your body can't make nitric oxide, then we have to do it for you. We have to give you nitric oxide." This all stemmed from a paper we published in 2007 showing that nitric oxide was a hormone. And so, similar to hormone replacement therapy, if you're a female and you're deficient in estrogen, we give you bioidentical estrogen. We give you that molecule. The physicians aren't giving you DHEA and hoping your body can convert it into estrogen or other precursors, because the basis for your deficiency is your body's not able to make it. It's very similar with nitric oxide. So, we have to give you this bioactive molecule.
[00:51:01] So, I'm the first and only person in the world who's ever developed a solid dose form of nitric oxide gas. So, what we do is, again, if your body can make nitric oxide, we do it for you. The only way to deliver this gas early on was through, what we call, an early disintegrating tablet. So, I make a nitric oxide lozenge, you put it in your mouth, it dissolves over five to six minutes. But as it's dissolving, it's generating about 20 to 30 parts per million nitric oxide gas. That's the same nitric oxide they give in premature babies with pulmonary hypertension or even in adults undergoing cardiopulmonary bypass to try to help improve blood oxygen saturation on the bypass machine. So, we know it's safe even in neonates, premature babies, the most highly susceptible, high risk patient population on earth. And it's therapeutic.
[00:51:48] The other thing we found was, because it's an orally disintegrating tablet, we're restoring the oral microbiome. We understand the oxidation of tetrahydrobiopterin, and we put components in there that prevent the oxidation of BH4, so now we recouple the NOS enzyme. So, if your body can make nitric oxide, we do it for you, but we improve both pathways to produce nitric oxide in the human body. So, it's the exact opposite of tolerance, or tachyphylaxis. We improve the body's ability to make it on its own. Those brand of products are called N101, and it's n101.com. Then we figured out how to make a fermented beet powder, that when you put the beets in water, they generate nitric oxide gas.
[00:52:30] But because beets are high in oxalates and they cause kidney stones in a lot of people and most people don't like the taste of beets, we remove the oxalates, we remove the beet taste, the beet pulp, the beet color. So, now we have a white clear powder. Put it in water generates nitric oxide, no oxalates, great tasting, doesn't taste like dirt. We put electrolytes in there and we put mitochondrial ATP. That product is called N.O. Beetz. It's probably the best energy. Not probably, it is the best energy product on the market, and without a doubt the best pre workout on the market.
Cynthia Thurlow: [00:53:04] I think this is all really exciting. I think my listeners know I'm a big supplement nerd. So, I was like, “I want to actually talk about these, because I think for a lot of individuals, they're looking for good solutions, but they also want to get a high-quality product.
[00:53:17] Well, I have so loved our conversation. I would love to bring you back and dive a little bit deeper into a lot of these concepts. Please let listeners know how to connect with you on social media, how to learn more about your research. We'll make sure that we link up some of your articles that you have participated in as well as access to your products.
Dr. Nathan Bryan: [00:53:34] Sure. The first thing I do is send people for proper education and the science on this. I'm not here to sell you products. I'm here to provide education, information based on real science, so your listeners can make informed, educated decisions. Because if they listen to the commercials and the ads, they're going to be misinformed or [chuckles] misdirected. But I send people to my YouTube channel. I have a dedicated YouTube channel, Dr. Nathan S. Bryan Nitric Oxide. We'll put these podcasts on there. I put lectures, some Q&As that we commonly get. I've got an educational website, drnathansbryan.com. I do a monthly blog. I just launched, called The Heartbeat Happy Hour podcast. We launch that every Thursday where we have a fun discussion on what's timely, what's topic, where the pulses are. I forget what the tagline is, but it's something like the heartbeat resonates with the pulse or something like that. Anyway, it's really cool.
[00:54:32] But again, we take timely topics, we discuss it, and put it in, and take some complex science and put it in an easily digestible form. I'm on social media, LinkedIn, Instagram, @drnathansbryan. Twitter, @drnitric. What else? PubMed, if you want to read our published papers, published over 100 peer reviewed papers in the literature. And then we've got a new book coming out, probably this fall called The Secret of Nitric Oxide, Bringing Nitric Oxide to Life. So, stay tuned for that.
Cynthia Thurlow: [00:54:57] Awesome. Thank you again for your time.
Dr. Nathan Bryan: [00:54:59] Thank you very much. I enjoyed it.
Cynthia Thurlow: [00:55:03] If you love this podcast episode, please leave a rating in review, subscribe and tell a friend.
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