Nitric Oxide’s Role In Your Fertility Health

Nathan Bryan, PhD

Well, thank you very much. It’s an honor and a pleasure to be with you and address this very interesting topic. I think, as you said, it’s missing the link. What we know about all aspects of medicine, including fertility, is that nitric oxide is a signaling molecule. It’s a gas that’s naturally produced in the human body. Then, once it’s produced, it’s grown in less than a second. But when it’s produced, it activates several different signaling cascades. It’s really how cells in the body communicate with one another. It’s involved in the regulation of circulation, blood flow, and oxygen delivery. It’s a neurotransmitter in the simple nervous system, and it’s part of our immune system and how our immune system fights off invading pathogens from bacteria and viruses. Now we’re learning, after more than 20 years, that nitric oxide is critically important in sexual medicine, reproductive medicine, and fertility. When you lose the ability to make nitric oxide, a lot of things begin to happen that aren’t conducive to normal physiology. We have to be able to, number one, understand how the human body makes nitric oxide. What goes wrong in people who can’t make it in them and how do we fix this? Once you fix this, people get better, and every organ system in the body works.

Aumatma Simmons, ND, FABNE, MS

It sounds like a pretty crucial piece of so many for fertility and other health issues. How I feel is that, at least from my medical education 17 years ago, I remember that nitric oxide was critical to blood circulation. Folds and all of that stuff. Can you remind me what else nitric oxide is doing in the body? Why is that so crucial to every piece of health?

Nathan Bryan, PhD

We know that 17 years ago, we had come a long way. The advancement of science happens so quickly now. But, when you were taught and I taught in medical schools for 10 or 12 years when I was an assistant professor of medicine at the University of Texas Medical School, it was first recognized as a vasodilator. The Nobel Prize in Medicine was awarded in 1998 for its role in the cardiovascular system as modulating vasodilation, improving blood flow, regulating blood pressure, etc. That’s still the primary role of nitric oxide in the cardiovascular system. But, 17 years ago, we thought that it was made in the lining of the blood vessels. It’s only made in neurons, and it’s activated by our immune system. But now we know that there’s nitric oxide being produced in every cell type, including sperm and eggs, and that it’s responsible for not just ovulation but also sperm motility. It’s responsible for erections in both men and women, which is the first step in fertility and getting your patient pregnant. We have to have normal functions for that to happen.

Aumatma Simmons, ND, FABNE, MS

Yes. What are the chief roles, as far as fertility and sexual health go, in terms of what nitric oxide does? 

Nathan Bryan, PhD

Let’s start with the first step in the process. As I mentioned, it’s the molecule that’s responsible for erections in both men and women. Drugs like Viagra, Cialis, and Levitra, phosphodiesterase inhibitors have been very successful over the past 25 years in the market, and they elicit vasodilation. You get engorgement in the penis and the clitoris, and that’s what’s responsible for erections. However these drugs are dependent upon nitric oxide production, and 50% of the men who are prescribed these drugs don’t respond with better erections because their bodies are not making enough nitric oxide to activate the signaling pathway,  that’s number one. If you have erectile dysfunction or sexual dysfunction in both men and women, then that’s a sign and symptom of nitric oxide deficiency. If you can’t penetrate it, you can’t have an orgasm, and then there’s no chance of conception. 

Let’s talk about it. Once we get that addressed, then what happens? If we have insemination and the egg meets the sperm, then if the sperm make their nitric oxide, it’s what regulates sperm. Patients who have decreased nitric oxide production typically have decreased sperm motility. We don’t get optimal fertilization. It’s also involved in ovulation. We know the monthly cycles of the population of women. Everything we know about conception and then the growth of the early embryo into a fetus into a live baby is dependent upon nitric oxide getting sufficient blood supply. They’re mobilizing stem cells, fully oxygenating the new embryo. All of that is dependent on nitric oxide production.

Aumatma Simmons, ND, FABNE, MS

Yes. We do need this. How do we figure out if we’re deficient?

Nathan Bryan, PhD

Years ago, that’s been a major problem for the past 20 years: how do you determine if your nitric oxide is deficient? Unfortunately, in regular medicine, you can draw blood, run labs, and figure out what your, for instance, cholesterol, vitamin B, or magnesium. If you look for nitric oxide, that’s not the case because it’s a gas. It’s produced in a stone in less than a second. It’s not anything we can detect in blood and do labs for; about 15 years ago, I developed a salivary test strip, and it’s, I tell people, a good tool to have in your toolbox, but it’s not the end all cure-allure all; it’s a biochemical test. 

The beauty of that test is that there are no false negatives. When we sample our saliva and we’re low on the test strip, it tells us that we’re proficient in nitric oxide, but what it doesn’t tell us is why we’re deficient. Now, there are some false positives that you can have because if you have an active oral infection, you’ll have a false positive reading. It’s an active immune response in any oral cavity, and it’s not reflective of systemic nitric oxide production. For that reason, I’ve gotten away from each of the test strips just because there are too many false positives. Give people a false sense of security. What do we do? We have to rely on symptoms. If your patients have an elevation in blood pressure, then that’s a sign and symptom of nitric oxide deficiency. If they have some degree of erectile dysfunction, obviously that’s a sign of nitric oxide deficiency or insulin resistance. 

We published in 2009 that nitric oxide is part of the insulin signaling pathway. Without nitric oxide, you get insulin resistance, and you don’t get glucose uptake in the circulation, fatigue, or the inability to exercise. If you get short of breath when you walk two steps, then that’s a sign of nitric oxide deficiency, vascular dementia, or mild cognitive disorders. You can’t regulate blood flow to the brain. You develop memory problems, poor cognition, dementia, and if not corrected, Alzheimer’s. We have to look at the clinical picture, the whole picture of the patient. My objective in all this, and I think the objective is to start to consider nitric oxide deficiency as part of the clinical problem and the picture of the patient, and then take steps to restore nitric oxide production. What we found over the past 20 years is that everything else you do from then on works better.

Aumatma Simmons, ND, FABNE, MS

Yes, I believe. I feel that just noticing that so many people are either deficient or have symptoms of deficiency and supporting their nitric oxide levels in the body helps fertility in so many ways.

Nathan Bryan, PhD

Well, I mean, I’m sure that in your clinical practice, fertility is probably not their only health issue. It’s a consequence of other issues. No healthy person comes to a fertility clinic, typically with the inability to conceive. They’ve got some underlying issues or problems that may have been misdiagnosed or not even diagnosed previously. This is a consequence of an underlying disorder, and you have to get to the root problem. many times we find that nitric oxide is part of the solution.

Aumatma Simmons, ND, FABNE, MS

Yes. Thank you so much for saying that, because I feel like I’m the weirdo out there. Yes, I completely agree. There are so many underlying scenarios that lead to fertility struggles, but fertility—that’s partly the misnomer—infertility is a diagnosis. It doesn’t mean anything if you don’t have it happening under the surface.

Nathan Bryan, PhD

Well, we’re the weirdos because we think differently, and it’s the people who think differently that make a difference.

Aumatma Simmons, ND, FABNE, MS

I think even for that. Cool. We talked a little bit about what it is, what nitric oxide is, what it does in the body, how it does or doesn’t support fertility, what some of the signs and symptoms are, and some ways to improve our nitric oxide production.

Nathan Bryan, PhD

It’s a very good question. It’s probably one of the most common questions I receive. I tell people it’s very simple. You only have to do two things. Stop doing the things that disrupt nitric oxide production, and then start doing the things that promote it. Let’s take those one by one. What’s disrupting nitric oxide production in this? This is a jaw-dropping moment for many physicians. You have to start asking your patients if they’re using mouthwash because mouthwash kills and destroys the oral microbiome, which is essential for producing nitric oxide. We and others have published. We published our first paper, I believe, in 2011, showing that when you use mouthwash, it kills the oral microbiome and your blood pressure goes up. Two out of three Americans use mouthwash every day, and two out of three Americans have an unsafe elevation of blood pressure. That’s not coincidental. We and others have proved that it’s causal. 

If you’re using mouthwash, when you have fertility issues, you have to go with the simple solution to just stop. I mean, that’s a cost-saving measure. Yes. The other problem is fluoride, which we use for native toothpaste, chlorides, and antiseptics. It’s a neurotoxin, and it destroys your thyroid function. People with hyperthyroidism typically have fertility issues. Fluoride is a molecule that competes with iodine binding to the thyroid hormone. As I said, it’s an anesthetic. Get rid of fluoride in your toothpaste; don’t use fluoridated mouth rinses; and then you have to get rid of fluoride in the municipal water. Fluoride is now added to municipal water systems because it’s antiseptic, antibacterial, and keeps the water supply safe. But it’s providing a neurotoxin to the human body. It’s not just the fluoride that you’re drinking; you’re bathing in it; you’re cooking in it. I encourage people to get a home filtration system to remove not just fluoride but all the other toxins and drug metabolites that are found in municipal water. Those are the big two. 

Then the other thing, or in essence, protons, inhibitors specifically shut down nitric oxide production. In 2015, there was a published study, a large-scale study showing that people who have been on PPIs, which are proton pump inhibitors, like omeprazole. All people who have been on these drugs for 3 to 5 years had a 35% increase in heart attacks and strokes. Just two weeks ago, another report came out that people who had been on these drugs for three years had a 40% increase in dementia. These drugs are not only dangerous; they’re deadly. We need stomach acid to make nitric oxide. We need stomach acid to absorb iodine and B vitamins, zinc, selenium, and iron. Without stomach acid, we can’t do any of this. We have to get people off antacids. 

Those are the big three. Stop using mouthwash; get rid of fluoride. If you’re not in acid, you have to get off. Now your body’s primed to make nitric oxide and absorb nutrients so cells can do their job. Then what do we do to promote it? Well, it’s a very simple diet and lifestyle: a balanced diet in moderation, throwing in some more green, leafy vegetables, 20 to 30 minutes of exercise per day, which is shown to clinically upregulate nitric oxide production, and then 20 to 30 minutes of sunlight. Certain wavelengths of light can stimulate or promote nitric oxide release and production. Those are the basics. I think those are the questions that most physicians fail to ask when they’ve got a chronically ill patient. We’ve proven to others that these are contributing to the underlying symptoms and progression of disease that’s been poorly managed by most so-called specialists or physicians.

Aumatma Simmons, ND, FABNE, MS

Yes, absolutely. I think I’ve heard you say the mouthwash and fluoride thing before, and I still haven’t put it into our intake form. That’s changing today. Now we do find that oral dysbiosis, or imbalance of the microflora in the oral cavity, also affects the vaginal microflora. Some studies are coming out about that connection. It has my brain going like, I wonder what else we’re doing that’s affecting the downstream impact on fertility, but it’s starting in our mouth.

Nathan Bryan, PhD

Yes. The microbiome is extremely important. After 20, to 25 years, we’ve understood the importance of the gut microbiome contributing to not just overall immunity but also the onset of systemic disease. There’s a reason we don’t take an antibiotic every day for the rest of our lives. You put on a very short regimen, a 7- to 10-day regimen, antibiotics, and then you first stop, because of the disruption and the collateral damage it’s causing to the good bacteria living in our body. The same thing happens when we use an antiseptic mouthwash every day for the rest of our lives. We’re killing the bacteria. It’s dysbiosis. Then this causes dysbiosis throughout other organ systems. We have to maintain a healthy microbiome, whether it’s in the mouth, the gut, or even in the vaginal biome.

Aumatma Simmons, ND, FABNE, MS

Yes. Are there specific foods that you love for improving nitric oxide production?

Nathan Bryan, PhD

Yes, foods have been shown to contribute to nitric oxide production. But again, diet and exercise are all dependent upon the oral microbiome, the diet, and the ability to produce stomach acid. You can exercise, and you can eat all the right foods. But if you’re using mouthwash in an acidic environment, you’re not going to get any nitric oxide benefits from diet or exercise. That’s first. But let’s just assume that you have the right oral microbiome. You have sufficient stomach acid production. Now what we’ve published is that green leafy vegetables typically have the highest amount of a molecule called nitrate, organic nitrate. Then, when we consume these green leafy vegetables, they’re absorbed in the gut. 90 minutes after we consume them, it’s concentrated in our salivary glands. Then, when we salivate, these bacteria that live in the mouth metabolize nitrate into nitrite and nitric oxide, and we swallow our saliva. We get a burst of nitric oxide gas in the stomach. These are things: spinach, kale, arugula, and beets have been hero vegetables for the past 10 or 12 years. But really, the variability of the nitrate in these foods is so variable that we really can’t make recommendations on how much you would need to eat of what vegetable. There’s a geographical difference. There’s a difference in farming practices and social conditions. All these variables determine and dictate what the nutrient density of the food is. If we look at on average, dark green leafy vegetables are typically the best.

Aumatma Simmons, ND, FABNE, MS

Okay, amazing. What you just said brought up a question for me about old Indian medicine. It’s called Ayurveda. There’s this idea that you shouldn’t brush your teeth right after you eat. What you just said is that 90 minutes after you consume these vegetables is really when that nitrite to nitrate occurs, is it?

Nathan Bryan, PhD

The nitrate to nitrite.  

Aumatma Simmons, ND, FABNE, MS

Nitrate to nitrite is happening in the oral cavity. If you brush after you eat, are you wiping out that possible reaction?

Nathan Bryan, PhD

Well, if you’re using an antiseptic fluorinated toothpaste, yes. If you’re using a mouth rinse.

Aumatma Simmons, ND, FABNE, MS

The majority of people use fluoride in their toothpaste; it’s what the dentist told us to do.

Nathan Bryan, PhD

Well, the Philistines used to use leeches to examine us, too. We don’t do that anymore because we know better. Now, I think dentists need to understand that, too, and that’s the most common answer I get from dentists. When I ask these questions, they say, Well, that’s what we’ve always done. Well, that’s not a battle excuse. Now, the advancement of science and medicine occurs so rapidly in doing things we did even 10 years ago, is not that anymore in medicine. There’s advancement, and we have to integrate these into clinical practice. The risk-benefit of mouthwash is so weighted in the risk category now that I don’t know why anybody in the world would use mouthwash or fluoridated toothpaste at all.

Aumatma Simmons, ND, FABNE, MS

That’s blowing my mind.

Nathan Bryan, PhD

That usually gets people’s attention. Things like traditional Chinese medicine and Ayurvedic medicine—these health practices and medical practices have stood the test of time. They stood the test of time because they’re effective and they work. These old principles, in Western medicine, are enforced. Fortunately, we got away from these basic principles that have been practiced for thousands of years, long before Western medicine evolved. There’s a whole concept of not brushing your teeth after a meal. They didn’t know anything about nitric oxide and nitrate-reducing bacteria in the oral microbiome back then. But obviously, they made some astute observations that allowed them to make that recommendation. Today we know mechanistically why that is because 90 minutes after you consume the meal, if you don’t have the right oral bacteria, you’re not going to get any nitric oxide benefits from eating that meal.

Aumatma Simmons, ND, FABNE, MS

Amazing. I grew up with it; my father was a believer in Ayurvedic medicine and I grew up in it. I studied it in India, but, like, just hearing these things never made sense until the science connected for me. Then I’m like, does that make sense? Because if you told us 5,000 years ago, we just aren’t doing it in real life.

Nathan Bryan, PhD

Well, this is, I mean, I think this is the basis of how I’ve been in basic science research for 20 years and, most basic science research tries to fit a square peg in a round hole and it never fits. What I want to do is take some astute observations, write clinical observations about things that are clinically meaningful, and then work backward and try to explain them. Then, once you understand mechanistically how that observation was made, we can explain that observation. Now, you better understand it. You can devise strategies or medicines based on an observation, not on the hope of an observation. That’s how nitric oxide was discovered. 

The drugs nitroglycerin, which was used for 150 years before the 1980s, were used by physicians because they didn’t have any idea how they worked. Then it was worked on by Fred Murat, who won the Nobel Prize, who discovered, well, these drugs work because they release nitric oxide, leave the coronary artery, cause nasal dilation, and cause acute symptoms of ischemia pain as an agent. Just because we didn’t understand how it works doesn’t mean that the physicians didn’t use it. But now, once we figure out how to use it, we have technology better than nitroglycerin. But you don’t develop a tolerance that has a better side of protective effects, and that’s leading to better management of patients. That’s how it should work, but it’s all based on important observations. Going back to the Ayurvedic observations, going back to traditional Chinese medicine 5 to 6,000 years ago. Now we can explain it today.

Aumatma Simmons, ND, FABNE, MS

Yes. Amazing. Is there any value, or is there space for supplementation? I know that a lot of times people want to jump to supplements. What is the thing that I can take so that you start with a foundation of, Here’s the stuff not to do, here’s the stuff to do, but is there a benefit or a specific need when supplementation would be appropriate? 

Nathan Bryan, PhD

Well, I think generally today, because of the food that’s grown here in America and because of our dietary patterns we almost have to supplement. But that’s not to say that you supplement everything. I think that’s where personalized nutrition comes in. We have to do personalized testing and macronutrient analysis, figure out what that individual patient is missing, and then supplement it. Between 1940 and 2010, the nutrient density of vegetables grown in the United States decreased by 78%. We’re deficient in things like magnesium, selenium, chromium, and iron iodide, and these things have to be supplemented sometimes, and it’s the same thing with nitric oxide. If your nitric oxide is deficient, 99% of the supplements on the market that are so-called nitric oxide supplements don’t do anything for nitric oxide. That’s the frustration with me that has been in the science for 25 years: companies out there deliberately deceiving their customers, trying to get them to buy products that they know there’s no way they can make nitric oxide. 

What we did was come to market with a productually generated nitric oxide. if your body can’t make it and our product does it for you, but more importantly, we fix the reason your body can’t make nitric oxide. We re-coupled the mast enzyme in the lining of the blood vessel. We restore the oral microbiome. Now we’re giving your body what it needs to make nitric oxide on its own. That’s the goal. We try to practice this concept of restorative physiology. The practice of medicine was supposed to be based on the principles of applied physiology. Understand disease to the extent that we can correct it. That’s basically what we’re trying to do. We understand how the body makes nitric oxide. We know what goes wrong if people can’t make it, and now we can fix it. We do this through supplements. We get the nutrition, and we also do it through some of the FDA drugs that we’re taking through clinical trials. We have approved it for the market in the next year.

Aumatma Simmons, ND, FABNE, MS

Yes, that’s awesome. I like the idea of restorative physiology. Our process is called restorative fertility. 

Nathan Bryan, PhD

I love it.

Aumatma Simmons, ND, FABNE, MS

It’s the same. It’s how we restore function. Because it’s not, we don’t have something that we need. It’s more that what we need is hidden or taken over by things that are not working well in our bodies. 

Nathan Bryan, PhD

I think that’s the only principle by which people get better. I think it goes a little bit more than that, going back to the days of Linus Pauling, who said that most chronic diseases are caused by nutrient deficiencies. We have to repeat this, but I think it goes a step beyond that. We’re also, so my perspective is that chronic disease, whether it’s infertility, cardiovascular disease, or Alzheimer’s, has two reasons only. Your body’s missing something that it needs or exposed to something it does. Now we have to consider toxins. What’s in the body that’s preventing the body from doing its job? Even if we replete all the missing nutrients, if there’s a toxin involved, whether it’s a latent virus, whether it’s a bacterial infection, whether it’s a chemical, environmental, or foodborne chemical, or even exposure to EMF now and glyphosate has been shown to inhibit a lot of these toxins that accumulate. Until we get rid of those toxins, we’re not going to be able to allow the body to do its job. But now, if we remove from the body the source of toxins and give back what’s missing, the body heals itself and does its job. It’s really that simple.

Aumatma Simmons, ND, FABNE, MS

Yes. I love this so much. This has been an awesome conversation. I appreciate your whole holistic perspective rather than supplementation. It’s this big perspective of here are all the things that are standing in the way, and here are the things that maybe you need a little bit more of to get the system back online and, in physiology, restore it in a way that’s going to support fertility and overall health, which are always related.

Nathan Bryan, PhD

Yes, that’s right. Now, what we’ve learned in 25 years in academia is that drugs and physicians don’t heal patients. The patients feel them. When we give the body what it needs, the body heals itself. There are ways to do that. I think supplements are good. I’m not saying that all drugs are bad or all supplements are bad, but we try to correct things. Then, when that doesn’t work, we supplement. When that doesn’t work, sometimes drug therapy is necessary. But I think that’s using the best medical judgment of the physician to do what’s best for that individual patient. 

Kind of my objective is to broaden the scope of the clinical picture and consider nitric oxide, and again, stop doing the things that disrupt, start doing the things that promote it; that doesn’t work, and we have product technology that does it for you, and typically that always works. I’ve been doing this for 15 years now, and I get hundreds of texts, calls, and emails every day from people saying that we’ve changed their lives, people who had been poorly managed and suffered from chronic disease for decades. Now, all of a sudden, nitric oxide comes on the radar, and they fix it. It’s amazing. It’s transformational. That’s the most gratifying thing I can do. I’m sure you’re changing people’s lives every day because procreation, conception, and bringing new life into this world are certainly life-changing. Congratulations on the great work you’re doing, and keep it up.

Aumatma Simmons, ND, FABNE, MS

Thank you. Thank you so much for joining me today. Yes, I look forward to hearing more from you. I know you’re just such a leader and educator in this space, so I appreciate you. Yes, thank you.

Nathan Bryan, PhD

Thank you for continuing to move science forward so stay tuned.