162 | Miracle Molecules: Nitric Oxide (Part 3)

Embark on an enthralling voyage through the maze of your own body, discovering how the humble molecule nitric oxide orchestrates a symphony of health within us. Our latest episode peels back the layers on the oral nitrate-to-nitric oxide conversion, revealing the unexpected heroes and villains in this biochemical saga. From the leafy greens on your plate to the bacteria in your mouth, we piece together the puzzle of how your everyday habits, including your mouthwash routine, could be quietly influencing your health. You'll be surprised to learn about the delicate dance between stomach acid and oral bacteria, and why a diet rich in certain vegetables isn't the straightforward solution it seems for boosting nitric oxide.

Imagine a world where taking an extra supplement is the answer to our health woes. Now, let's shatter that illusion. We dive into the intricacies of nitric oxide synthesis in the body, uncovering the truth behind arginine supplements and their effect on our health. The episode features expert insights on how our bodies utilize the amino acid arginine and nitric oxide synthase enzymes to maintain the balance of this critical molecule. We explore the murky waters of septic shock and reveal why arginine surplus is no panacea for such severe conditions. Instead, we chart the complexities of our internal chemistry and how it defies the simple fixes often peddled by health trends.

Strap in for a deep-dive into the paradoxical force of nitric oxide in autoimmunity, where too much or too little can tip the scales toward disease. We discuss the fine line tread by nitric oxide synthase enzymes in our immune system and the role they play in conditions like Hashimoto's and rheumatoid arthritis. Assessing nitric oxide imbalances isn't just for the labs; we'll share telltale signs that your levels might be off-kilter. With expert commentary shedding light on the nuances of this molecule's impact on our well-being, this conversation doesn't just scratch the surface; it goes to the heart of the matter, equipping you with the insight to navigate the tides of health influenced by nitric oxide.

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Transcript

Speaker 1 0:01

One of the greatest obstacles to crafting health and wellness is identifying and controlling inflammation. It's at the core of all complex and chronic diseases and is the driving mechanism that underlies the most common symptoms that people like you struggle to overcome. Join us as we explore cutting-edge science and research to give you the information and tools you need to create the quality of life you want and deserve. And now here is the host of Inflammation Nation, dr Stephen Noseworthy.

Speaker 2 0:30

Hey guys, we're back with the Inflammation Nation podcast. This is part three and probably the final aspect or final part of our talk about nitric oxide as one of the miracle molecules that are in your body, in everybody's body. So in the last episode I went through the highlights of what this first miracle molecule does for us, ranging from how nitric oxide relaxes your blood vessels to control your blood pressure, to protecting the neurons in your brain, to all the functions in controlling the exchange of oxygen and carbon dioxide, and we talked very briefly about how nitric oxide has a role in the gut, also was involved in controlling all of your hormonal systems, and you know a lot more. Then we went into the first of two different pathways or two different ways that your body makes nitric oxide, both of which account for roughly 50% of the picture. So 50% of your nitric oxide that you have in circulation is made from one pathway, the other 50% by the other one, and that first one we went through was what we call the oral pathway.

Speaker 2 1:42

And again, very quickly, when we consume food that has dietary nitrates and nitrites, things like green vegetables or even foods that have been preserved with nitrates and nitrites. As long as we have two things in place. Then we can take these dietary sources of raw materials again nitrates and nitrites and we can convert them into nitric oxide. And the first of those two things is a healthy oral microbiome where certain classes of bacteria that live on the back of your tongue can take those nitrates and nitrates and use specific enzymes that they have. That we don't have. That's why we rely on them. But they have these enzymes that convert these raw materials from our diet into nitric oxide and then we swallow that in our saliva, gets into our gut and then gets into circulation. And the second thing that has to be in place is that once we swallow some of these nitrates and nitrites from our diet things that don't get converted in the mouth itself we have to have enough stomach acid in the gut to make nitric oxide from those precursors. Now I cautioned you not to use mouthwash because that kills your oral microbiome and it reduces your ability to make nitric oxide through this pathway. And I also suggested that you do some self-evaluation to see if you've got low stomach acid symptomatology, which happens a lot. If you've got a thyroid problem including, of course, hashimoto's disease, it can happen a lot with gut infections, particularly with H pylori. But there are other things that can lead to low stomach acid and poor nitric oxide, things like chronic stresses or changes in cortisol, and you know we could build the list out, but pretty much any major metabolic disturbance can do that. So one of the big takeaways, or the big clues that you've got low hydrochloric acid, is protein maldigestion protein maldigestion.

Speaker 2 3:48

Now, the logical thought here is that if you want to increase your nitric oxide levels, the easiest thing to do is to simply eat more food that has nitrates and nitrites in it, and most people are going to gravitate towards. Well, I guess that just means I need to eat more salad, I need to eat more leafy greens, and there might be a couple of problems with that, just as a simple strategy. First of all, not all greens contain the same amount of nitrates and nitrites, so a lot of it just depends on which greens you choose to use. Now, with respect to the studies that show how nitric oxide can control blood pressure, studies show that you need to have about 300 to 400 milligrams of dietary nitrates as a single dose to affect your blood pressure, and most americans get less than 150 milligrams of dietary nitrites throughout the entire day, and it's even lower in scandinavian countries. And so you might be thinking well, all I need is a list of the higher nitrate greens and I'll just eat more of those. And again, it sounds like sound thinking on the surface. Yes, you could eat more beets or beetroots or spinach and lettuce and radish and celery and chard. Those are the foods that we know of that have the highest nitrate content.

Speaker 2 5:03

But if you look at the math, how much do you need to affect something like your blood pressure and how much is, in, say, a standard two-cup salad or two cups of green salad? You'd, honestly, you'd have to eat probably three to five cups of greens every day to have a positive and certainly an immediate effect on your blood pressure. And you know, some people are going to be able to pull that off and a lot of people are not. And for some of you, eating that much vegetable matter is going to tear up your gut, especially if you have things like IBS or SIBO, if you're particularly sensitive to fermentable foods or what we call FODMAP foods, and it might be an issue also if you're sensitive to oxalates. It just so happens that a lot of the foods that contain a lot of the nitrates that we would like to use from our diet also contain high amounts of oxalates, which then can promote the formation of oxalic acid crystals, and it's not a problem for everyone, but certainly for those of you who it is. You know exactly what I'm talking about.

Speaker 2 6:07

But this approach of just saying like, well, I'm just going to eat more greens and I'm going to stick to the list of foods that have more nitrates in it assumes that the nitrate content of these greens and other foods is the same everywhere, which we know is not true. In fact. Fact, a friend of mine, who just happens to be one of the top nitric oxide researchers in the world, did a study on the nitrate content of greens leafy greens in different regions of the country, and he found that there was significant variation in the nitrate content, say, of lettuce and kale, across different parts of the USS. It was higher in some areas, it was lower in others, and so you can't just automatically say, oh, I'm just going to eat more greens and trust that you're getting everything that you need. And the main reason for this why it varies from country, or actually does vary from country to country, but even within a single country like the US. The reason why we see such a wide variety of nitrate content from region to region is because of differences in growing conditions, the condition of the soil, the fertilizers that are used, even light exposure patterns, and we can add to that list even how these greens are processed and they're stored right. Different processing methods and different storage methods can alter the nitrate content, even assuming that the soil and the fertilizer used is appropriate.

Speaker 2 7:34

How you clean and how you prepare your foods in your home, whether you boil them or bake them all of this can change the nitrate content. So I hate to say it, but it's not as simple as just saying I'm going to eat more leafy greens, right? So the nitrate content in greens and vegetables is just simply not predictable, not necessarily reliable, certainly not homogenous, and boosting your nitric oxide level simply by eating more greens is it's not effective and, in many cases, not even efficient. And don't forget, on top of that, you have to have a healthy mouth, you have to have the oral microbiome that would allow you to do that, and so if you have dental issues, periodontal disease, you could have compromised that and you can eat all the greens you want. It's not going to affect your nitric oxide, and then we throw in the next step, which is adequate stomach acid as well as a good, healthy microbiome, and that's the way that you optimize the system. So that's the first pathway, and I know I threw a couple of extra things in there that we didn't talk about in the first episode.

Nitric Oxide Synthase Enzymes and Arginine

Speaker 2 8:36

Now what about the second pathway? So we have the oral pathway that involves bacteria in the mouth, stomach acid and so on, but in the body you have a family of enzymes called nitric oxide synthases, nitric oxide synthase. It's a family of enzymes. There's three different versions, and these enzymes use an amino acid called arginine as the raw material to make nitric oxide. So on one hand, we have the bacteria in our mouth feeding off the nitrates in our diet and on another hand, we have amino acids like arginine in our body all the time, and then we have a family of enzymes that takes that arginine and makes nitric oxide.

Speaker 2 9:20

Now, just for clarity nitric oxide is nitric oxide, which is nitric oxide. There's only one kind, but we have different ways to make it. So the nitric oxide is nitric oxide, which is nitric oxide. There's only one kind, but we have different ways to make it. So the nitric oxide made by the bacteria in your mouth or through the cooperative effort of hydrochloric acid in your microbiome, for example, is the same as the nitric oxide that's made by this nitric oxide synthase enzyme system. It's all the same. Furthermore, the nitric oxide that's made by your brain or by your immune system or inside the lining of your blood vessels is the same that's made everywhere else. Like I said, nitric oxide is nitric oxide is nitric oxide.

Speaker 2 10:01

Now let's get back to this enzyme family and using arginine as the raw material to make it. There are a lot of nutritional companies these days and have been around for a while that are making nitric oxide boosters, and the main ingredient is arginine, for the simple reason that, with this enzyme family of nitric oxide synthases, arginine is the raw material, it's the precursor to nitric oxide. So these companies make nitric oxide boosters, main ingredient is arginine, and these products are sold to people who want to enhance blood flow for different reasons. They might be, you know, someone who exercises and they're chasing that fabled pump of muscle building and bodybuilding. Or it might be marketed to people as a solution for cardiovascular disease or high blood pressure. And it might also be marketed to people men, obviously who suffer from erectile dysfunction and once again, this sounds reasonable on the surface, that if my body uses arginine to make nitric oxide, then if I take arginine as a supplement, then I will automatically make more nitric oxide. And that's not the case, for a couple of different reasons. First of all, if someone is deficient in arginine and nitric oxide, or, let me say it this way, if they're deficient in arginine or their nitric oxide is low because they lack the raw material to make it from, then yes, taking an arginine supplement in that case can probably help.

Speaker 2 11:36

But humans typically consume plenty of arginine in their diet, even a standard American diet and on top of that, arginine is not an essential amino acid. And what that means is that even if you didn't consume plenty of arginine and I promise you probably are then your body would take other things to make arginine. So the difference between an essential amino acid and a non-essential amino acid is that you can't make essential amino acids and you have to get them from their diet. Same thing with essential fatty acids you can't make them, you have to get them from your diet, say from fish or fish oil, but you can make these non-essential amino acids, among which is one of which is arginine. So you can make these from other things in your diet and also in your body, and therefore you don't really need to supplement with more arginine above what you're already getting through the foods that you're consuming.

Speaker 2 12:33

And to drive this point home, that arginine deficiency is really not a problem, is that we have studies on people who die from septic shock, or what we call septicemia, where at some point their organs begin to shut down. But these studies show that all of these people have plenty of arginine in their body. And so what's the link between septicemia and organ shutdown and arginine availability? Well, research isn't entirely clear here, but there are two possible explanations as to the role of nitric oxide in septic shock and organ failure. Number one, organ failure in septic shock, could be in part due to a lack of nitric oxide, which prevents oxygen from getting to your organs. Remember, one of the fundamental rules of nitric oxide is controlling how your red blood cells drop off oxygen to your organs. Remember, one of the fundamental rules of nitric oxide is controlling how your red blood cells drop off oxygen to your organs and cells and then pick up carbon dioxide to get rid of it. So one explanation is in septic shock and organ failure. You have an acute lack of nitric oxide. You can't give oxygen to your organs and because the organs have no oxygen to make energy and to function, the organs begin to shut down. The second explanation is actually the opposite, wherein, during septicemia, there is a massive increase in nitric oxide produced by the system, which can drop blood pressure way too low and people die from hypoperfusion of their entire organ system. The end result is the same is you can't oxygenate your cells.

Speaker 2 14:15

But there's two theories as to the role that nitric oxide can potentially play in these septic shock. Either way, whichever mechanism turns out to be the right mechanism or the true mechanism in septic shock, studies are very clear that there is not a problem with arginine deficiency. Let me say it another way, and just to reiterate this In studies on septic shock, where people die of organ failure and we suspect nitric oxide is a problem, if the answer turns out to be they don't have, suspect nitric oxide is a problem. If the answer turns out to be they don't have enough nitric oxide, the problem is never that they've run out of arginine. And so in these cases of severe metabolic dysfunction like septicemia, arginine deficiency isn't the problem, so there has to be another reason why nitric oxide might be deficient. It's not the lack of arginine availability. So the same thing holds true for you and I that if we're concerned about nitric oxide levels and you probably should be, especially if you're over 30, 40 years old that list of things we have to be concerned about when we start getting older starts getting longer and longer every day, it seems. But let's assume for the moment that low arginine could be a problem, which it really never is. But let's assume for the moment that it could be a problem.

Speaker 2 15:34

Simply taking more arginine to get more nitric oxide assumes that arginine availability is the rate limiting factor in nitric oxide synthesis, which it isn't. What do I mean by that? What do I mean by the rate-limiting factor? Well, pretty much every chemical reaction in your body has a rate-limiting factor, something that controls how fast or how efficiently a chemical reaction runs, and sometimes it is the lack of raw material. I just, you know, think about building I don't know, building a chimney out of bricks. Well, if you run out of bricks and the chimney's not done, you can't finish the job. So sometimes, yes, a lack of raw material can derail some kind of a chemical reaction.

Speaker 2 16:22

Sometimes it's a nutritional co-factor that needs to be present, and it could be anything from vitamins or minerals or enzymes or other things, so these are called nutritional cofactors, and other times it's a specific catalyst in the form of an enzyme, like these nitric oxide synthase enzymes. Now, in the case of these special purpose nitric oxide producing enzymes called nitric oxide synthases, they are unique in a couple of ways. First of all, they require more nutritional cofactors than any other enzyme in the human body that we know of. My last count and understanding is that there are eight different nutritional cofactors that nitric oxide synthase requires. One of those is vitamin C, another one is something called tetrahydrobiopterin, and it just so turns out that the rate-limiting enzyme, or the rate-limiting aspect in this nitric oxide synthase system that controls how much nitric oxide we can make inside our body, is this compound called tetrahydrobiopterin, or we usually call it BH4, b, as in Bob or boy, bh4 for short.

Speaker 2 17:40

But let me hold on to that moment, that thought for a moment, so that we can talk about the three different types of nitric oxide synthase. That's used by the brain, the immune system and the blood vessels, and that's the order in which these things were discovered. Nitric oxide synthase was first discovered in the brain, then in the immune system and then eventually in the blood vessel or the vascular system. So these again, these three forms of nitric oxide synthase enzymes that takes arginine and makes nitric oxide. They are present inside different tissues, so in the brain and in neurons. The version is called neuronal nitric oxide synthase, or we might say N-N-O-S, and that first N stands for neurological, so neurological nitric oxide synthase, so that enzyme takes arginine and converts it to nitric oxide in the brain, in the nervous system, including the peripheral nervous system, including even the nervous system in your gut. And, as we talked about last time when it comes to the brain and the production of nitric oxide, it enhances blood flow to the brain, that's oxygen delivery, nutrient delivery. It improves waste removal, that's important. But it also is used to help control the balance between excitation and inhibition and it's involved in the processes of plasticity and the formation of new synaptic connections. It does more, but those are probably the big things that most of us would be concerned about. So that is N-NOS, or neuronal nitric oxide synthase, that's the production of nitric oxide in your brain.

Speaker 2 19:21

The next one is I'm going to skip to the third one, which is the blood vessel one. I'm going to skip to the third one, which is the blood vessel one. This is called E-N-O-S and the E stands for endothelium and that stands for the vascular endothelium. So this is nitric oxide made or I should say nitric oxide synthase that's generated in the cells that line your blood vessels and your heart. And it's the same nitric oxide made by the NNOS system in your brain. It's the same compound, it's the same properties, but when we make it in our vascular system it protects our blood vessels from damage and inflammation that can lead to cardiovascular disease and plaquing and clogged arteries. It controls the immune cells that really kind of want to crash into the lining of the blood vessels, that vascular endothelium, and cause inflammation in your blood vessels. And, as we've mentioned several times, the nitric oxide made by this endothelial nitric oxide synthase enzyme can relax your blood vessels and it improves blood flow, reduces your blood pressure, and again, there's more to it. But that's the main things that we're concerned about.

Speaker 2 20:30

And then the third, nos, or nitric oxide synthase variant, which is the second one. What was discovered has to do with the immune system, and this is called INOS. So we have N-N-O-S, which is in the brain. We have E-N-O-OS, which is in the brain, we have ENOS, which is in the blood vessels, and we have INOS, which is related to your immune system, and this is where we can get into trouble. Under normal conditions, nitric oxide made from this INOS, or immune system pathway, is actually part of how we destroy infectious organisms like viruses and bacteria. I think I mentioned in the last episode this immune strategy called the respiratory burst right, which is where an immune cell, like a macrophage, for example, will poke a hole in the cell wall of, say, a a bacteria and it will inject a ton of nitric oxide which destroys the bacteria from the inside.

Speaker 2 21:33

Now the problem is that sometimes this INOS system, this immune-related nitric oxide synthase system, gets hyperactivated and it goes crazy. And when it does so, it produces nitric oxide in quantities that are up to a thousand times more than what we typically see with normal function. And it's this massive increase in nitric oxide from the immune system, through this INOS system, that can actually destroy not just pathogens and foreign invaders but, in the context of things like autoimmune disease, can actually destroy our own cells in a problem of collateral damage. And so if you're listening to this and you're like well, hey, I've got Hashimoto's disease or I have rheumatoid arthritis, or I have multiple sclerosis or any other autoimmune condition where your immune system is attacking and destroying your own tissues. Part of the problem is this inappropriate activation or upregulation of nitric oxide production in those tissues through this INOS pathway. So the situation we have with nitric oxide as a miracle molecule is a little bit more complicated than you know. Hey, your nitric oxide is too low, let's bring that up.

Speaker 2 22:55

Sometimes it's a problem of nitric oxide being dysregulated as part of your autoimmune or your inflammatory state, and again, it's not uncommon. We see this with a lot of people who have Hashimoto's, any other autoimmunity. They're making nitric oxide, but they're making way too much in the wrong place. Right, they have nitric oxide going wild from the immune system, but it actually in those cases quite often is at the expense of the nitric oxide going wild from the immune system, but it actually, in those cases quite often is at the expense of the nitric oxide that's being produced in the brain as well as the blood vessels. So as a general rule and I'm not saying this happens all the time, but it's a pattern that we look for, especially with autoimmunity is that we suspect based on the literature and based on our observations in clinical practice.

Speaker 2 23:45

We suspect that in cases of autoimmunity and progressive tissue destruction and loss of functionality, that the INOS, or the immune-mediated production of nitric oxide, is way too high and that happens at the expense of nitric oxide being produced in healthy amounts in the brain and in the blood vessels. And that mixture is not cool. I don't know how else to say it and there's no scientific way of saying it other than you know that sucks for whoever has that problem. And this has to do again with how metabolic imbalances and immune activation and immune dysfunction, with autoimmunity, can skew or deviate the relative activation of these three different enzyme pathways, these three different nitric oxide synthase systems. And again, there's a tendency under inflammatory states, autoimmune conditions, that the nitric oxide levels in the brain and the blood vessels go down and therefore you lose a degree of protection of those things and at the same time the immune system is pumping out crazy amounts of nitric oxide in the target tissues of the autoimmunity and that just contributes to more inflammation, more tissue stress and more damage. So here's a trick that we use in clinical practice to try to assess if someone has a problem with nitric oxide deficiency or perhaps more commonly, dysregulation.

Speaker 2 25:10

Number one we check for symptoms of poor blood flow in different systems, so we look for a combination of symptoms as part of their presentation. We might look for things like brain fog or mental fatigability. Like you know, I can use my brain for a while but then my brain gets tired. That's quite often a sign of poor blood flow and or inflammation. So brain fog and brain fatigability. We also check for things like cold hands and cold feet. Right, that's easy to pick up on when someone has poor blood flow. We also check for fungal infections, mostly in the toenails, because it's harder to perfuse these tissues and a lot of times we'll see hair loss. Now I'm one to talk I don't have much here these days but nonetheless, particularly if you're a woman, particularly if you're a woman with Hashimoto's and you are experiencing hair loss, it might not be your thyroid, it might not be the Hashimoto's, it might be the background lack or change in nitric oxide production leading to poor blood flow. And the reality is is that your hair follicles are living cells, living tissue that need blood flow just like everything else does. And I'll remind you that there's no specific lab test that measures nitric oxide directly, but you can do things like look for elevated homocysteine levels and think about potential problems with methylation, potential problems with methylation.

Impact of Nitric Oxide on Health

Speaker 2 26:45

Now this is a good time to jump back to the concept of this thing called BH4 or tetrahydrobiopterin, as being the rate-limiting factor or the rate-limiting step in nitric oxide production when we make it using one or all of these different nitric oxide synthase enzymes, and this applies to all three, not just one of them. So this character called BH4, as I mentioned before, is one of eight nutritional cofactors we need to make nitric oxide through this pathway. Vitamin C is a very critical part, but it doesn't limit nitric oxide production in the same way that BH4 does. But when we have low BH4, we can have it for several reasons. We can have a problem with not producing enough BH4, or we can have a problem with not recycling and reusing the BH4 that we already have in our system. So let's talk quickly about BH4 production. If we can't make enough nitric oxide, not if we can't make enough nitric oxide, if we don't have enough B4. And so that begs the question where does BH4 come from? Well, in short, it comes from the purines in our diet, but, more specifically, we make BH4 as a byproduct of energy metabolism.

Speaker 2 28:05

Now, that may sound familiar to you. This phrase or this idea brings us right back to the mitochondria that we spent so much time talking about when I brought you guys through that entire series on exercise. Remember that the mitochondria is an organelle that lives in your cells and this is where we make energy from glucose, fats or ketones, even amino acids. And I'll just remind you that your cells don't have just one. They can have a couple of hundred to a couple of thousand different mitochondria.

Speaker 2 28:37

Now, this is going to get too geeky very quickly. I'm going to try to hold myself back here, but purines are carbon and nitrogen compounds in our foods that we use as building blocks to make DNA and RNA, and one of these purines is called guanosine. Now, aside from being used to make DNA and RNA, guanosine is also used to make something called GTP, gtp, and GTP is a chemical cousin of ATP, which by now you should know ATP is the currency of energy. It is pretty much energy, right? So when you eat and you can run dietary energy sources through your mitochondria, like fats, proteins and ketones, you are making energy in the form of ATP that's called adenosine triphosphate. That's what ATP stands for, and adenosine is another purine, just like guanosine.

Speaker 2 29:35

So the only difference between ATP and GTP is that in GTP the guanosine replaces adenosine. Like I said, they're chemical cousins. There's just one difference, and what that means is that GTP can also function as a source of energy, just like ATP, and that energy is used to make proteins and to make glucose through things like gluconeogenesis, but the GTP it's a source of BH4. So it goes like this we eat foods that contain purines like guanosine, and you'll find that through many different foods, but mostly in meats, very high density in organ meats. So we eat foods that contain purines, particularly guanosine, and the guanosine gets incorporated into GTP as part of how our mitochondria make energy again as we burn things like fats, carbs and ketones, and the guanosine of the GTP can be used to make BH4, and that BH4 controls the rate at which we make nitric oxide through these three different enzymes. So there's a production possibility there. We can have a deficiency in GTP because we're not eating enough food, we're not consuming enough foods that contain purines, or there's a problem with our mitochondria and we're not making GTP as a byproduct of that.

Speaker 2 30:56

There's a lot of different places where this system can go wrong, but that's only one of two places. Remember, we make BH4 or we have BH4 available, either because we're making new stuff all the time as we produce energy, or we can recapture and recycle BH4 that we've just used, right. So it's not making new BH4, it's just recycling stuff that we already have. And this is where things like homocysteine levels and poor methylation capacity comes into play. Now, methylation itself is just a big discussion and I'm sure that some of you guys have probably been tested for methylation defects these gene tests that are available. But suffice it to say that one part of the methylation cycle involves the interconversion of BH4 into BH2 and then back again. So we use BH4 as part of the methylation and urea cycles and then we convert it into BH2. But then we can take the BH2 and make BH4 from it again and we can just start all over, and that's what we call BH4 recycling. So, again, we have the ability to make BH4 directly from the mitochondria as part of energy production, but we can also recycle and use it over and over again.

Speaker 2 32:15

So just to stop here and think clinically and how do you apply this to yourself. Well, if you have fatigue, we might theorize that your mitochondria are not making ATP that you want, and if they're not making ATP, they're not making GTP. If you are avoiding animal products in your diet, maybe we have a raw material deficiency right, that doesn't really happen with arginine, but it certainly can happen with BH4. Or maybe you have a problem in your methylation cycle. Maybe you're not recapturing or capturing and recycling BH4, adding to the total pool that's available to help these nitric oxide synthase enzyme systems do their job, which is to make nitric oxide. And that's apart from the pathway that's using the oral microbiome.

Speaker 2 33:02

Now, on top of that, on top of us making it through our mitochondria because of our diet and energy production, apart from being able to recapture and recycle it as part of the methylation cycle, there are some studies that show that we have certain probiotic species in the gut that can generate BH4 in their own metabolism, which we then can use in our metabolism. This is one of the big things that the microbiome does for us is that it makes stuff that we can use. It makes vitamins and minerals, it makes anti-inflammatory compounds, they can make some short-chain fatty acids that are essentially ketones, but they also make BH4. And that means that we can add one more thing to our growing list of how we can see changes in nitric oxide production is by having an unhealthy gut, having a poor microbiome, having dysbiotic overgrowth, having infections, having intestinal permeability or what we call leaky gut. So just track with me here for a second gut. So just track with me here for a second.

Speaker 2 34:07

Bh4 is the rate limiting factor in nitric oxide production through this nitric oxide synthase enzyme system. If we have mitochondrial issues and energy production issues, we can interfere with how much BH4 we make, which limits how much nitric oxide we make, and if we have issues with the methylation process and we can't recycle our BH4, we can't make enough to control nitric oxide production. So we want to look for things like high homocysteine. And listen, if you can't control homocysteine levels without always being on some kind of methylation support, like methylated B vitamins, methylcobalamin or B12 or methylfolate, or taking things like betaine or trimethylglycine, if every time you come off those your homocysteine levels pop up, you probably have an active MTHFR gene or maybe a CBS gene mutation and you just need to be on those supplements all the time. And then, finally, if our microbiome is not where we want it to be, we lose the contribution of BH4 made by our microbiome. So it's a lot of stuff right.

Speaker 2 35:12

But I think that what we've gone through over the last three episodes even though it got a little bit sciencey there and just at the end, maybe throughout, but it's incumbent on you. If you are over the age of 30, certainly by the time I said, you know, by the time we're 50, we have about 50 percent of the normal um or of the nitric oxide levels that we had when we're, say, in our 20s. So if we're, if we're middle-aged and beyond, if we have fatigue and energy production problems, if our oral microbiome and oral health isn't good, if we can't acidify our stomach and our hydrochloric acid is down and we can't digest proteins, if our microbiome is off and we have infections or dysbiosis or leaky gut, all of these things compound to potentially affect your nitric oxide production. And I'll just give you a sneak peek right now I'm working with a company to make probably the premier nitric oxide boosting supplements available to you guys, my listeners, my loyal listeners, thank you very much. Um available to you uh, hopefully at a discount, and we'll have some news coming out about that probably in the next couple of weeks or so. But I believe so strongly that number one.

Speaker 2 36:37

As a clinician, whenever I take on a new client in my one-on-one coaching program and I am taking new clients I always think about the potential for nitric oxide being a problem, particularly if they're fatigued, if they have gut problems, if they have thyroid issues, if they have Hashimoto's disease, if they have any autoimmunity, if they've got really bad brains, gut issues. I think I may have already said that Nitric oxide is always on the table as something that could be a problem. I'm not saying it is a problem with every person who has those complaints, but we know enough about these nitric oxide systems, how we make it, where it comes from, what it does and how to generally assess the potential for it to be a problem. We know enough that if we don't ask the question is nitric oxide a problem and can we do something to fix that, then I wouldn't be doing my job as a clinician, as someone who is trying to help somebody get their health back and get back to the person that they used to be and improve their quality of life and their longevity.

Speaker 2 37:41

All right. So we're going to leave it right there for today. We'll call the first segment, if you will, of the miracle molecules discussion. We'll call that complete, and next time we'll move on to the second miracle molecule, and that will be glutathione. All right, guys, thanks for listening. If you haven't already hit the subscribe button, make sure you get notified when new episodes drop. Follow me on social media All the links should be in the episode descriptions and we'll see you next time on the Inflammation Nation podcast.

Speaker 1 38:14

Thanks for listening to Inflammation Nation. If you enjoyed this episode, make sure you subscribe to our podcast. Be the first to know when a new episode drops, so you can stay on top of your game. It also helps others like you find the answers they need. You can use the links in the episode description to check out Dr Nosworthy's self-learning programs for thyroid detox and gut health, or you can submit a question for the podcast and even reach out to Dr Nosworthy directly.