Why Nitric Oxide Production Is Super Helpful: The Key To Fight Fatigue

 

Dr. Joel Rosen: Hello, everyone and welcome back to another edition of your adrenal fix where we teach exhausted and burnt-out adults the truth about their health so that they can get their energy back quickly. And today, I’m excited to be joining forces here with Beth Shirley, who is a registered pharmacist at CCN. And she has developed expertise as a pharmacist and certified clinical nutritionist during her 40-plus-year career.

Her specialties include stress-induced hormone imbalance, intestinal dysfunction, autoimmune and chronic inflammatory issues, and detoxification, something I’m excited to talk to her about is nutrigenomics. And the supernormal oxidative stress, which I was gonna ask you what that is, Beth, after I introduce you, you’re a pioneer in the cutting edge of the evolution of what has now become the integrative pharmacy, where the junction between traditional pharmacy and the clinical use of nutritional supplements, but I could probably go on and on. But I want to get to the heart of the matter. And that’s nitric oxide. So thank you so much for being here today.

 

Beth Shirley: Thank you for having me.

 

Dr. Joel Rosen: Yeah. So why don’t you maybe I always like to ask our guests a little bit about your health journey. Maybe you didn’t have your health challenges. Or maybe you did. But what inspired you Beth to go down the firstly being trained as a pharmacist, but then getting into clinical nutrition? And then going into the world of, I guess, integrative medicine, what, what was your evolution or your Genesis for that?

 

Beth Shirley: Well, I became a pharmacist because I thought I was going to help people. And after 20 years of seeing people come back sicker, and sicker on more and more drugs. In 1997, I became a certified clinical nutritionist. And I became the pharmacist to go to if you wanted to get off meds or not go down a road, to begin with.

And along that same route to what would steer me into that is, when I was 37, I was depressed, and I went to the doctors and all they had was depressants, and I thought that for a couple of years, and then I thought, you know, then I went on him. And then after I hit 40, I was gone. You know, there’s something else going on here. And so that’s when I read the book, what your doctor may not tell you about menopause by Dr. John Lee. And it taught me about bioidentical progesterone. And I started using that.

And notice within like, nine months, I was off the antidepressants, and I had a progesterone deficiency, not Paxil deficiency. So that all happened kind of at the same time, you know, about 1996. And so since then, I’ve been just taking care of the physiological process, supporting physiological processes, not doing anti this and anti that, because the body wants us to be healthy.

And since 2009, I’ve been in the nitric oxide space. And once you start learning about the power of circulation in microcirculation, you will, you will know that this is the base of everything. If you’ve got impaired circulation and microcirculation, it doesn’t matter what else you’re doing, nothing’s gonna get to where it needs to go.

 

Dr. Joel Rosen: Yeah. And I’ve talked about to my audience before in terms of, if you’re in a room that doesn’t have very much oxygen, water, food, or I guess exposure to the cold, the one that you want the most is the oxygen. And if you’re not using oxygen for energy production, you’re using oxygen for oxidation. It’s almost like you’re instead of getting an income, you have an expense and it can create a Demand and supply problem in your body.

Just an aside, though curious, in your wanting to help people become a pharmacist. I’m just kind of curious, when was it along the way that you were realizing how deep and like how long into your practice that you realize that This isn’t helping people with what you were doing?

 

Beth Shirley: Well, I was a pharmacist for 20 years before I figured out that this just I mean, it that that was all combined with my health issues, where all they had was pharmaceuticals to treat me and that’s not what was going on. So I wasn’t being helped myself. And neither were all these people that are coming into the pharmacy. They weren’t being helped.

 

Dr. Joel Rosen: Right. And so as far as you alluded to the fact that typically the paradigm for pharmaceuticals is to block The mode of action whereas potentially hormone support or understanding the physiology and and looking at endogenous production of nitric oxide for signaling and blood flow and oxygen delivery, is more supportive. So let’s maybe springboard off of that Beth and talk about what we know about nitric oxide for the person that doesn’t know what it is. What is it? And why is it so important?

 

Beth Shirley: Well, nitric oxide is a basic gas along with oxygen and carbon dioxide for the body, it’s nitrogen and oxygen, it’s just two molecules, and oh, so it governs circulation microcirculation, which is important because cells can’t be more than two cells away from a functioning microcapillary.

If they’re more than two cells away from a functioning microcapillary, they or that microcapillary is not open and delivering oxygen, glucose, and nutrients the tissue and cell will die. So nitric oxide is important for our immune response, which is so critical in today’s environment, it’s important for mitochondrial biogenesis. It’s important for mitochondrial health.

And this is where your cholesterol gets metabolized into pregnenolone. It’s important for your neurotransmitter balance, it’s important for sexual function in both men and women. It’s important to decrease inflammation and oxidative stress. To like it increases telomerase, which has everything to do with aging.

It just touches every single physiological process, it’s important for your kidneys, for your ears for hearing for your hormone balance nitric oxide, it is essential in the brain to make your LH RH luteinizing hormone-releasing hormone, which then goes on to produce your LH which goes down to your testes for your testosterone, your ovaries for your progesterone and your estrogen. So nitric oxide is involved with every single physiological function needed for the glute four receptors to translocate and bring glucose into the cell.

 

Dr. Joel Rosen: Wherever oxygen is needed for ATP production, it plays an important role, which is pretty much every physiological function in the body.

 

Beth Shirley: Well, actually, the hemoglobin has to have nitric oxide hooked onto it to be able to deliver oxygen to the cells. You could even be supersaturated with oxygen. And if you don’t, if you’re nitric oxide deficient, you’re not being able to deliver that oxygen to the cells. Right.

 

Dr. Joel Rosen: So as far as why, and I’ve had Nathan, as I mentioned, Nathan Brian on a podcast before but explain to our listener why this such an important compound or is not being taught or they haven’t heard about or potentially their doctor hasn’t mentioned it. Why is that?

 

Beth Shirley: I am thinking that actually because it touches so many physiological processes it does so much, that it’s too overwhelming, an idea to even understand because it does touch everything. And people don’t understand. I mean, cardiovascular disease is still the number one killer in the United States. Nitric oxide deficiency. Diabetes, number two, is nitric oxide deficiency. You know, I, I? You know, I don’t know. I don’t know why people don’t want to understand what is at the base of all of these physiological processes.

 

Dr. Joel Rosen: I mean, I don’t I mean, I know that the Nobel Prize for toffee G was recently awarded in 217. And we say that the time that it takes for the ivory towers to sort of hit the street can be something of a 17-year cycle. And I know that the Nobel Prize for nitric oxide discovery wasn’t 99 its?

 

Beth Shirley:  It was 98 almost 200 That wasn’t studied A lot. Yeah. The patient is there.

 

Dr. Joel Rosen: It’s there. It’s there. And it’s interesting because you would think now and it’s a slippery slope in terms of the subject with the pandemic and virals and low lows that nitric oxide would be the first line of defense. So I guess the question would be so. Right, right, whether we know it or not.

 

Beth Shirley: But talking about it for the last two and a half years, right, when this whole thing started, there is the nitric oxide connection. And I’ve been, I’ve been posting about it on LinkedIn, and Facebook.

 

Dr. Joel Rosen: Right, so So I guess the question would be, why would nitric oxide be depleted or low? Or why would we not have enough and what makes it problematic for being able to make it in the first place?

 

Beth Shirley: Well, we make nitric oxide through two different pathways. One is the arginine nos, nitric oxide synthase. enzyme. This enzyme is really sensitive, its pH-dependent is oxygen dependent. Hypoxia shuts down a lot of things shut it down.

And I’ll talk about that in just a second. And the other is the nitrate to nitrite to nitric oxide pathway, where we consume the nitrates that get absorbed, circulate, and get concentrated in the salivary glands. salivary glands release the nitrate and we’ve got good anaerobic bacteria on our tongue, that will reduce that nitrate to nitrite.

Nitrate is the immediate precursor to nitric oxide. So this pathway, only to I mean, it’s not so dependent on all of these other environmental factors like the NOS enzyme pathway. So what affects that is age by the time we’re 40 the nos pathway is only functioning about 50%. By the time we’re 60, It’s only functioning about 15%. Diet, the standard American diet devoid of nitrate-rich veggies and essential cofactors and nutrients, lack of exercise, medications, antibiotics, antifungals, and depressant birth control pills and Said’s PPIs PPIs interfere with the production of nitric oxide through both pathways EMFs EMFs increase oxidative stress, oxidative stress uncouples the NOS enzyme and when nos are uncoupled, it becomes a superoxide generator, not a nitric oxide generator, pollution, glyphosate, genetic snips, and not just your nos snips, anything that might increase oxidative stress, like your so D snips, catalase snips, anything that interferes with the production of BH for your QD PR, your DHFR. If you have any MTHFR snips, you are by definition nitric oxide deficient, because you’re not making your BH four BH fours that couple that nos enzyme.

And the big one is stress, stress interferes with the production of nitric oxide. So it didn’t stress interferes like with Sonos, your inducible nos that’s why when we’re stressed we get sick easier. And it interferes with the e nos endothelial nos. That’s why when we’re stressed we have more cardiovascular issues, hypertension, strokes, and mice. So there are a lot of things that go into the production of nitric oxide.

And that nos enzyme, but the nitrate to nitrite to nitric oxide pathway can pick up the slack. So I’m gonna say we’ve got a good oral microbiome. And the beautiful thing about nitrate supplementation is it helps rebuild microbiomes in the gut, in the oral cavity on the skin, in the vagina, and everywhere you’ve done an oral microbiome nitrate supplementation helps rebuild that.

 

Dr. Joel Rosen: Yeah, I mean, you had a lot there. And there are so many things My head’s thinking of what I want to ask you, but one of the things that stick out with someone probably has heard if they’re aware of nitric oxide is the nitric oxide uncoupling. And I think that’s an important springboard to talk about. So you mentioned BH two or BH four is the, I guess the nutrient or the compound that helps to make the nitric oxide from endogenously or from the de novo pathway with a combination, of proteins to be able to do that?

Yeah. to write and having the genetic susceptibilities of potentially MTHFR or DHFR, or QTP, the other types of genetic snips, I guess the question for you would be, why if someone because I’ve heard this a lot anecdotally with clients is, well, I take mth I take methyl folate, and I still have cold hands and extremities, I have brain fog, I have lack of libido and desire and motivation. I guess the question is, why does it not necessarily translate nitric oxide uncoupling a little bit more in detail, and then why does just not taking methyl folate at high doses create more nitric oxide reductionistic well?

 

Beth Shirley: Just addressing VH four isn’t going to address all those other factors that I talked about, like diet, stress, pollution, EMF, and glyphosate. So just addressing the BH four isn’t going to address all of those other things too. But the beautiful thing about nitrate supplementation is it increases your production of BH four, which helps couple that nos, decreasing the superoxide production. So the three main ways we make superoxide in our body is nos uncoupling.

And the NADPH oxidase enzyme and uncoupled electron transport chain. But supporting the nitrate to nitrite nitric oxide pathway addresses all of those issues. So nitrate helps increase the BH which helps recover nos, decreasing superoxide production nitrite and nitric oxide downregulate, your NADPH oxidase enzyme that gets upregulated by all so many things.

And then nitrided nitric oxide help where we couple that electron transport chain without interfering with the production of ATP. So you’ve got to address a lot of things. I know we talked a little bit about that NADPH oxidase enzyme, this enzyme gets upregulated with so many environmental factors, iron mTOR, sulfites, inflammatory cytokines, mold, I mean, you name it, it gets upregulated by it.

But what happens when there’s NADPH oxidase enzyme gets upregulated? What it does is preferentially steal that NADPH from all these other necessary processes, like fatty acid synthesis, hormone synthesis, and phase one detoxification, you can’t regenerate your oxidized glutathione plus you don’t like it’s the electron donor for the NOS enzyme. So you want, like there’s just so many environmental factors that are upregulated NADPH oxidase EMF, we’re swimming in the sea of EMF. And that’s how EMF does its damage, it stimulates that NADPH oxidase enzyme. So we’ve got down-regulate.

 

Dr. Joel Rosen: Right. Yeah. And I thank you for sharing that as a very elaborate, but yet succinct way of explaining what happens with that NADPH oxidase upregulation. Another one, which I’m sure you know very well is in terms of the H MOX and recycling heme so that you’re able to reuse that iron, which ultimately, it’s like an all or none, right? It’s, it’s like a domino effect where I use the analogy, if you’re only making interest payments, you’re never cutting into the debt, and you keep falling further and further behind. And if you’re not having that NADPH to do its day job and recycle glutathione and BH four, and H MOX and everything else in between, you’re increasing even further than NADPH steel and creating a perfect storm.

 

Beth Shirley: So that’s inflammation. Oxidative.

 

Dr. Joel Rosen: Right exactly. Which then goes on with from what I’ve learned through Bob it goes on to stimulate mast cells, which then ultimately stimulates your HPA axis which creates cytokines which create histamine which causes core so many domino effects for sure.

 

Beth Shirley: Well, guess what down regulates mast cell degranulation nitrite and enteric oxide.

 

Dr. Joel Rosen: Right, right. Yeah, yes. And it gets depleted when it’s upregulated I guess as well, right? So so as far as well What is it about the well that I mean? The foods that are rich in nitrates and supplementation, can you maybe get into how what we can do for that?

 

Beth Shirley: So the high nitrate foods your arugula, spinach, butter, lettuce, celery, Bok choi, beets, and all of them have the all of them except for arugula have the potential to have to oxalate issues in your sensitive population. However, rubellite is the highest nitrate veggie without the oxalate issue, or the Berkeley life professional.

Two capsules will give you about the same nitrate concentration as five ounces of spin eight or seven ounces of beets. And this will give three to 400 milligrams of nitrates which the study shows that it takes to make the physiological changes, like the changes in blood pressure, or the changes in exercise endurance and, and decrease in recovery time. And that’s what you get with two capsules of the Berkeley.

So I usually recommend having those capsules or Berkeley and then high nitrate and veggies at lunch and dinner to help sustain that level. And you can check your levels with a test trip. This test drip is a saliva test drip, it tests the nitrite concentration of your saliva. So it’s testing your ability to take that nitrate and reduce it to nitrite. So it’s dependent on your oral microbiome.

So usually, you can do two capsules, and then within an hour, an hour and a half, test your saliva. And you should be able to start seeing that test strip term. If you don’t see it turn that’s telling me you’ve got something going on with your oral microbiome. So you start asking questions. Are you using mouthwash? Are you using fluoride toothpaste? Fluoride is anti-microbial. Are you using whitening toothpaste with hydrogen peroxide? Are you on any antibiotics? Are you on any PPIs?

Do you maybe have an infection somewhere in that the oral cavity? But the beautiful thing about nitrate supplementation is you are going to be rebuilding that oral microbiome which then helps rebuild your intestinal microbiome.

 

Dr. Joel Rosen: Right? Hey, you know, as far as a couple of questions that came out of that, I’m glad that you brought up the oxalates because they’re yet another NADPH oxidase stimulator that further decreases your nitric oxide. But as far as a lot of people will ask, Well, what about the beets in the formula? Are their oxalates in there, maybe you can assure them that there are.

 

Beth Shirley: There are only about 10 milligrams of fermented beetroot in there, you’re not going to get oxalates out of 10 milligrams of fermented beetroot. Right.

 

Dr. Joel Rosen: Right. I think that’s an important point to add. And then the other one is, as far as which is great. Thank you for sharing in terms of if you’re not holding that positive marker that’s indicating with the test strips that you’re producing, you’re producing nitric oxide, that you have to look at the terrain, which is the mouth which by itself, even that is very helpful for the gateway being breached into the immune system, which so many people miss, right?

 

Beth Shirley: The immune system, the cardiovascular system, diabetes, this oral microbiome is connected with everything.

 

Dr. Joel Rosen: Right? Do you ever just as an aside, because you also mentioned how important pH is for being able to make that nitric oxide and is a measure of tissue oxygenation. And I guess if we have a lot of oxidative stress and free radical production, our pH levels are going to be lower.

We’re not going to have as much tissue oxygenation. One of the things that I’ve advocated for is at-home pH testing as a pharmacist because I got a lot of backlash on when I posted that on social media from kidney nephrologist Dr. Saying I don’t know what I’m talking about because that isn’t helpful.

 

Beth Shirley: Yeah, yeah. Yeah. So So like any kind of chronic issue any diabetes or any kind of chronic inflammatory issue, you’re going to be more acidic. And this uncouples that nos in time, there’s less oxygen, being able to be carried to tissue Right, you knew what you’re talking about.

 

Dr. Joel Rosen: So thank you. So that means a lot coming from you. So as far as the other thing that Nathan talked about when we interviewed him, was with the de novo pathway which does implicate more of our genetic susceptibilities or challenges to be able to make nitric oxide, a lot of farms. Pharmaceuticals, a lot of supplement companies will tell you the benefits of arginine and mention that Arginine is never that weight-limiting step.

 

Beth Shirley: Because we get enough in our diet, maybe you can explain a little bit of arginine, there’s very, very rarely an arginine deficiency. You know, the COA, the binding coefficient for arginine to the NOS enzyme is low, it doesn’t take much to saturate that enzyme. And the cell doesn’t even take in arginine to feed that nos pathway.

The cell will take up citrulline to make its arginine to feed that pathway. But giving excess arginine to somebody with their nos being uncoupled, increases oxidative stress. It arginine has many pathways that can go down not just your nos pathway, it can increase your hDmA a symmetric dimethyl arginine, which is connected to all-cause mortality, and it can increase ammonia, which is connected with you know, kidney function. So there are more pathways arginine can go down than just your nos pathway. And there’s rarely a deficiency of IT. And especially if somebody’s over 40, or if somebody’s got any kind of chronic issue, I do not recommend arginine supplementation.

 

Dr. Joel Rosen: Right? Because this is gonna be uncoupled. And then you’re gonna make it.

 

Beth Shirley: Yeah, it can’t, it can’t use it. So it’s gonna be on other pathways. And those pathways aren’t necessarily healthy.

 

Dr. Joel Rosen: Right? I mean, I’ve had clients that have done there, you know, their research and tried to do arginine supplementation for my more nitric oxide. And I think Bob Miller even talked about some of the bad press that arginine gets in the research is that you have, they never really, I guess, controlled for which subjects have uncoupled nitric oxide and is that arginine driving superoxide instead of nitric oxide production, one of the things we talked about before we got on which I think it’s important for maybe a little more of a sophisticated listener, but also for myself to kit understand a little bit more.

Because the next question and some people’s teaching has been, then that nitric oxide when it’s uncoupled, and you’ll take arginine will produce superoxide, and then that superoxide will turn into peroxy nitrite. Maybe you can dispel that and why that’s not a thing.

 

Beth Shirley: Yeah, the peroxynitrite nonissue is one of my favorite subjects. So nitric oxide, when combined with superoxide, makes a molecule they call peroxy nitrite. However, when you’re making superoxide, you’re not making as much nitric oxide because superoxide shuts down nitric oxide production. So by optimizing nitric oxide, you’re down-regulating the production of superoxide.

So you’re decreasing peroxynitrite production. So remember, those three main ways that our body makes superoxide nos uncoupling NADPH oxidase and uncoupled electron transport chain, and supporting the nitrate to nitrite nitric oxide pathway down-regulates all of those ways we make superoxide.

And if you’re downregulated superoxide production, you’re down-regulating peroxynitrite production. However, peroxy nitrite is on a will there. There’s a new paradigm emerging in the nitric oxide research community, showing that 90 to 95% of that peroxy nitrite, ISON rises to an O three, which is nitrate and inert. And then in some of my other talks, I talk about all of actually the beneficial actions of peroxynitrite.

So, I want you like when you read these studies about peroxy nitrite, I want you to understand they’re not measuring peroxy nitrite they’re measuring nitrotyrosine and they’re assuming peroxy nitrite was there. And that assumption keeps getting repeated and repeated and repeated like it’s its truth now. However, just because you see nitric oxide as metabolites around tissue damage, and cellular damage, does that mean That is what’s causing the damage? Just because there are always cops around a crime scene doesn’t mean the cops are there doing the damage. They’re there to help clean it up. Nitric oxide can scavenge all these free radicals, they’re there to help clean up that damage.

 

Dr. Joel Rosen: Right. So as far as back to the canary in the coal mine in the sense that when you do the nitric oxide test strips, and you’re seeing that you’re not holding, or you’re not making that nitric oxide, or that nitrate, the nitrate and as far as the health of the mouth, once you say you, you, you disinfect it, you look at some of the things that may have been depleting the ability to to make that nitric oxide and you continue to support it with getting the nitrates with the supplementation, do you see that start holding longer even if you don’t do it an hour and a half after I’m curious on that.

 

Beth Shirley: Next bait has a half-life of six to eight hours. Okay, right. And so I like doing a couple of capsules in the morning and then adding some high nitrate veggies at lunch and dinner to help sustain that level. But in people with a lot of oxidative stress, you may need more. If you’re trying to do something like get somebody off blood pressure meds or not go down that route, you might need two capsules twice a day, in addition to some high nitrate virtues, for sexual function in both men and women, I recommend two capsules in the morning and another two capsules on our before the activity.

So you know, use the strip and you can tell whether you need more. And then, you know, like during different environmental challenges, you might need more likes, if everybody around you is sick, you might need more. Right?

 

Dr. Joel Rosen: Well, I think it’s I mean, I love that you brought it up in terms of that wasn’t aware of necessarily when you test and you’re not holding that it’s more of the ecology of the oral biome. And I was extrapolating that too, yeah.

 

Beth Shirley: Dependent on your microbiome. which is a good subset

 

Dr. Joel Rosen: Of the whole body of everything that up-regulates your NADPH and EMFs and glutamates and sulfates and everything molds and iron dysregulation and histamine and stress and viral loads and il six, I mean, everything that that does that. So as far as the topic that we were talking a little bit about which is not necessarily understood is the different kinds of nitric oxide.

So you have inducible and endothelial and two and no three, maybe talk a little bit about that because what I had maybe learned was that no two might be upregulated and it might suppress nos three like what are they why do we need to know about them? How do they work? What is the deal with them?

 

Beth Shirley: Yeah, well nos one neuronal no is mainly concentrated in the CNS and the brain. Nos two inducible nos, this is your immune response. And nos three your endothelial Nasus is with the nitric oxide produced in the endothelial cells. And when I nos does get upregulated when you’re when you’re trying to fight something it does downregulate your Enos and your handoffs. But another beautiful thing about nitrate supplementation, it down-regulates and up-regulated Imams. However, there’s this same kind of uncoupling issue here too.

So, a lot of times when you see that they start talking about too much nitric oxide because I nos is upregulated. Read carefully those studies. Because if there is a lot of oxidative stress and inflammation going on, that I nos is uncoupled to. So this damaged tissue and cellular damage might not be due to that upregulated nitric oxide is more than likely due to upregulated, uncoupled Sonos which is producing superoxide. That can’t be quenched.

 

Dr. Joel Rosen: Yeah, it makes sense. So, what question Can I have you to know the methodology or at least the biochemistry of the NADPH steel? And things like iron oxidation and mTOR that up-regulate that and steal away the NADPH that doesn’t allow the nitric oxide to be made and make more superoxide? As far as where do you find the antioxidant response elements come into play there?

Because I think it’s kind of confusing for people where, you know, with Denon Harmon and the whole free radical theory of aging, and understanding that okay, I know I need antioxidants, but at the same time, I do need a certain amount of oxidative stress to signal and create some kind of immune response. I guess the question is, where does the signaling of the antioxidant response elements come into play with nitric oxide? Do you find that there’s a Goldilocks zone of doing it this way? Or do it that way? Is your insight on that?

 

Beth Shirley: Well, in today’s environmental challenges, the idea of too much in oxidants is pretty nonexistent. Because everything is up-regulating that NADPH oxidase I mean, everything. And so too many antioxidants just haven’t been the case for quite some time.

But nitric oxide like supporting that nitrate to nitrite and nitric oxide, you know it, scavenges the use of free radicals. It can scavenge the free radicals from the Fenton reaction, your LH, and your Fe three plus, it can down-regulate Myeloperoxidase, which decreases your hydrogen peroxide production down-regulates xanthine oxidase which decreases superoxide production. So supporting that nitrate to nitrite and nitric oxide pathway actually, helps get all of these inflammatory processes under control, and not so out of control.

 

Dr. Joel Rosen: Right, that’s a good answer. So as far as just to recap, being able to get rid of the things that would reduce the nitrate-reducing capacity in the body such as PPIs, mouthwash, and antibiotic use, being able to supplement with something like Berkeley life that’s going to supply the nitrates to be able to be produced in the first place. That diet that’s rich with nitrates, although being aware of the Oxalic consumption, and a lot of them, the only one being arugula that doesn’t have that.

But at the same time, when you take the Berkeley life, you’re not getting the oxalates out of the small percentage of beetroots. The question I have to you which I find it being more and more a catch 22 When people are exhausted and burnt out, and all of this is going haywire, and they’re not making energy, and the electron transport chain is uncoupled and you’re producing way more superoxides, is the ability to do movements and high-intensity movements, even if it’s for short periods.

I’d be curious to know what you think the role of that is, and or, you know, blood flow restriction type things I used to see those be effective for nitric oxide production or even getting some kind of muscle contraction and even for the most challenged person that has some issues with all of this, is that something else that you’re advocating?

 

Beth Shirley: Yes, because supporting that nitrate known to peroxide pathway, our muscles or myoglobin in our muscles can reduce that nitrite to nitric oxide on an as-needed basis. And that’s what we need when we’re exercising we need more oxygen and glucose nutrients being delivered. And just as importantly, we need the debris to be carried away.

So supporting that pathway, you know, gives the raw material to the myoglobin that can reduce it further. The electron transport chain can reduce nitrite to nitric oxide when oxidative stress gets so far out of hand. It helps re-couple it. But most studies show it can recover out couple it without interfering with the production of ATP. So by even just supporting that pathway, you allow people to even do more movement than they were able to do before.

 

Dr. Joel Rosen: Right. Right. And I think it’s important though To not resolve yourself have the responsibility of even if it’s, you know, just moving your arms to be able to get that blood flow, blood flow going. So, yeah, I know those are great insights as far as the superoxide.

Because I think that’s a charged conversation now because of EMF and the stimulation of superoxides and how that ultimately will lead to NADPH oxidase overstimulation and then not being able to recycle your BH four, and then creating even more superoxide. Do you feel that with the minerals being so devoid in our soils, we’re ever going to be able to just supplement our take foods enough to rebuild the prerequisites for nitrates and nitric oxide production? Or do you feel that it’s something that we ultimately have to agree that we got to get it elsewhere? Exogenous Lee?

 

Beth Shirley: Well, the DASH diet, the Dietary Approaches to Stop hypertension, has about 12 to 1500 milligrams of nitrate per day. So the DASH diet has been used as medicine for cardiovascular disease very successfully. But it is quite a challenging diet to follow. I mean, you have to pay attention to the number of vegetables you’re eating. So as far as supplements, I think that there’s a, there’s a big place for what we write.

 

Dr. Joel Rosen: I’d be curious as to when was that study done. Because I’d be curious to know how much more the stress and NADPH oxidase confounding stimulation would deplete that nitric oxide at a like I guess, commence a rating, the amount that you would need that you’re getting out of the DASH diet for taking into consideration how much more stressed our life is with social media and with what’s going on in the world and what information we’re given or not given. And I don’t even know if it’s even possible to say, you know, to have a food that would be high enough, even if the dash studies show that it was

 

Beth Shirley: No, I agree, because we’re just overloaded, totally overloaded with oxidative stress, capacity. Capacity to increase.

 

Dr. Joel Rosen: Yeah. You know, one question actually, which wasn’t on my question list, which is sort of off the CUSP is. And I don’t know if I’m pronouncing it correctly, but ag Monte or ag totally product? Yes. Can you can you tell? I’m glad that I remembered it during this conversation. Could you tell me a little bit about what it used to be, I guess an ergogenic aid is used for exercisers and bodybuilders. Can you tell me a little bit about it?

 

Beth Shirley: human studies using it? There are no human studies. I mean, there are some animal and rodent studies. But I’m just I’m not a fan because it’s supposed to be stimulating. You’re not in time, along with the arginine and citrulline. I mean, there’s, you know, supplements that have the arginine citrulline and agmatine in it, that I’m just I’m not a fan. You’re still trying to make a dysfunctional uncoupled nos work and it’s just not going to.

 

Dr. Joel Rosen: Right, right. So I guess the takeaway for genomic practitioners like myself, especially with peroxy, and nitrite not being an issue is that genomic Lee speaking when you look when you do see these major nos one, two and three polymorphisms the de novo pathway isn’t necessarily even though we’re addressing it from lifestyle management and stress management and decreasing the NADPH oxidase stimulation isn’t the area that a practitioner is going to have the most bang for their buck implementation wise, it’s going to be more of the being able to produce it through the nitrate nitric pathway correct.

 

Beth Shirley: But then also know that that nitrate is going to help re-couple that nos. Right.

 

Dr. Joel Rosen: So would help that pathway after all

 

Beth Shirley: Right, so you’re going to be decreasing oxidative stress. Right?

 

Dr. Joel Rosen: I’m curious to know as far as what you’re seeing is when someone takes Viagra and they don’t notice any improvement because you can’t save something that’s not there, meaning if your nitric oxide is uncoupled and taking something to keep the nitric oxide around longer, but it’s not there, is that still happening from a prescriptive point of view, doctors are still doing it scratching their head wondering, oh, I don’t know why that didn’t work.

 

Beth Shirley: And those drugs, the Viagra, the CLS, don’t work at about 50% of the men, precisely because you got to have enough nitric oxide to get the erection to begin with those drugs a PDE five inhibitors allow the nitric oxide to hang around a lot longer. But if you don’t have enough nitric oxide, to begin with, you’re not going to get an erection. And, you know, they’re not asking questions.

 

Dr. Joel Rosen: I mean, listen, it’s the reason you switch to your nutritional background to realize you’re making a difference because I, I see what I see harmful anecdotally with some of my toughest clients. And this is just an aside from the ones that have been taking benzodiazepines for so long. And all that oxidative stress that slows down that glutamate to GABA conversion is not allowing any of that excitatory neurotransmitter to get there.

And then you’re trying to keep it around something around longer. That’s not being produced. It’s analogous to somewhat of the hope that Viagra is a magic wand and is going to fix all processes that inflammation and stress are causing in the first place. I think there are so many different types of meds that are ineffective that way and they’re just throwing it at the wall and hoping to see what sticks. I mean, is that sort of what you got out of that way of practicing?

 

Beth Shirley: Yeah, when nitric oxide is involved with anxiety and depression, anxiety and depression are and are modulated by BDNF. Nitric oxide modulates BDNF, increasing neuronal neurogenesis, and synaptic plasticity, nitric oxide actually can increase GABA in the brain. So a lot of times when people start doing nitrate supplementation, they start feeling calmer. They’re not so anxious, or not so depressed.

 

Dr. Joel Rosen: Right? Yeah. And once again, you know, the biggest stress in the world is not having enough oxygen. Right? And if you’re not having enough.

 

Beth Shirley: Yeah, nitric oxide hooks onto that hemoglobin to release the oxygen to the cells and tissues. Right? Well, that’s what.

 

Dr. Joel Rosen: I mean. Like I’m saying like, if you’re not respiring, at the cellular level, which is dependent on that nitric oxide, being able to be there to do that, then you’re going to be more in a, a, I guess, a glycolytic. Stress excitatory neurotransmitters for the short term is not a problem.

But when you’re keeping that button stuck in the on position forever, it just becomes, you know, so I guess impactful at the autonomic level where you start to see people not be able to regulate their blood pressure and they’re and their heart rate and their temperature.

And now that’s when you know that it’s gotten so so bad. So I guess the question would be if someone just like if you can hold that nitric oxide level an hour and a half later, and we know that that that oral bio meets a dressing, same thing in terms of a check if you take Viagra or Cialis that helps to keep nitric oxide around longer and it doesn’t work then you have a challenge there to know that okay, something’s not being done that you need to address is that correct?

 

Beth Shirley: Eisley? You exactly you know, like, erectile dysfunction is endothelial dysfunction. And it’s usually one of the first signs of an underlying cardiovascular complication. So you need to address it. There are a lot of things going on. It’s not just because you can’t get interaction. Okay, your whole cardiovascular system is impaired.

 

Dr. Joel Rosen: Interesting. Yeah. And then I guess just one, thank you. I’m using your brain here as things start coming into my head. So one of the other things that I see a lot too is the coenzymes and NAD NADH NADP, NADPH, acetyl, CO a, and Koay. As far as NAD, it seems to be sort of the nutrient your use is there any correlation between nitric oxide and those and those coenzymes especially in terms of NAD or NADPH, or not? NADPH but NADH.

 

Beth Shirley: Yeah, I’ve got a lot of people that are on the Berkeley and add some NADH or NADPH. to that. Okay, you know, because the nitrates help recover the NOS. And then he or NADPH is what donates the electron. I have a lot of people that are in that combination.

 

Dr. Joel Rosen: Stacking it, you know, because what the reason I asked that question is that I’ve found it that NADPH oxidase is just super like not only upregulated but as you mentioned, super upregulated right there in a major crisis. And they take NAD, it a lot of the times will feed a lot more of that. superoxide. And so I use that as a gotta-be.

 

Beth Shirley: Careful. You’ve got to be gotta be careful. Yeah. Especially on all these people that are doing the IV and EDS. Right, right. Oh, really? Look into, okay, why did this person get so sick? Right? Oh, yeah, right. Well, you just better come back and get more you need more, you know, you need to down-regulate that NADPH oxidase. Right. Right.

 

Dr. Joel Rosen: But so the follow-up question is, there could be a challenge with just going super dosing on the NAD because that NADPH is upregulated takes that nutrient spills out more free radicals. But is there a problem ever taking too much of the nitrates to produce nitric oxide? Is there an upper limit on that as well?

 

Beth Shirley: Well, as I said, the DASH diet has 12 to 1500 milligrams, and that’s like taking two capsules four to five times a day. So you’re not Odeon it with the DASH diet. So I don’t have anybody that has taken more than two capsules three times a day. It’s just not necessary when you start checking your levels. You know so yeah.

 

Dr. Joel Rosen: Yeah, I mean, I have a client that I’m thinking of specifically who’s having a tough time. And I feel like I’d love to be able to push that titration up to as much as we can, with the nitric oxide boosting nutrients to see what kind of results we can get with that. But it’s always, you know, somewhat of a trial, right?

Because you want to see how, like the oral biome, you can’t just expect the nitrate nutrient to get that nitric oxide produced. If all those other expenses are draining the account in the first place, I would imagine it’s the same thing with just doing that with someone who’s super challenged with upregulation of these stressors that are depleting it and uncoupling it or making more superoxide in the first place as well. Right.

 

Beth Shirley: So yeah, but the beautiful thing about nitrate supplementation is how you rebuild that moral microbiome. Right? which when coupled, you know, don’t give up if it’s not changing right away, don’t give up just hang in there. It will change. I’ve had a couple of people telling me that, that we would never get their strip to change because it had never changed before with anything else. And then it was never going to change. Well. It did. Right. Right.

 

Dr. Joel Rosen: Mean, and also to, just from what I see is, they’re so close yet so far, it’s like they got a tumbler lock, and there’s seven out of the eight things and they’re just missing that one thing if you’re doing a lot of really good foundational work, but you layer in that nitrate.

Now it’s missing that eight tumblers and now everything is synergistically getting better. But if you weren’t doing that legwork beforehand, you can expect just that nitrate to be the magic wand if you’re not addressing stressors and diet.

 

Beth Shirley: Yeah, it’s not, it’s not the magic wand however it is the base. If you don’t have good circulation and microcirculation and doesn’t matter what else you’re doing, it’s not going to get to where it needs to go. So it’s the base of everything else that you’re going to be doing. You want anything else that you’re taking or doing to be able to get to where it needs about right.

 

Dr. Joel Rosen: So and then we talked a little bit before we got started in terms of if you listen you know morally at Robins with the root cause and bioavailable copper Ansarullah plasm and being able to move iron out of tissues, I guess what is this a chicken or the egg thing or is this more of the nitric oxide is dependent on the copper is dependent on the nitric oxide or the Surulere plasm. Where do you see that relationship tying into all of this?

 

Beth Shirley: Well, nitric oxide deficiency increases the Fenton reaction. And when you replenish the nitric oxide you’re been able to scavenge Euro H and your Fe three bluffs. So sometimes when people have this iron just regulation and it’s not just the iron dysregulation, it’s also the nitric oxide deficiency too.

 

Dr. Joel Rosen: Could you say, though, at the same time, it’s a two-way street where the Fenton reactions deplete the nitric oxide?

 

Beth Shirley: Availability? Yeah, it is. It’s depleting it because the nitric oxide is scavenged and that Fe is three plus. Right, so takes it out of being bioavailable. Right.

 

Dr. Joel Rosen: Okay. So I mean, I’ve talked to Morley, which I’ve talked to before, and he would say, Well, that’s because you don’t have the bioavailable copper to move the iron that creates the Fenton reactions that deplete the nitric oxide.

 

Beth Shirley: Yeah, I can’t go into that right now.

 

Dr. Joel Rosen: That’s fine. I appreciate it. So as far as the bottom line is, is that you need to address the entire picture, right, and you need to rebuild the ability to make nitric oxide. And you need to get enough nutrients in your soils and your foods to be able to get your minerals up to drive up your pH so that you’re getting oxygenation. And you’re you have good life purposes and belonging and purpose. And all of the above. I don’t think there’s a free lunch anywhere out of there in that regard.

 

Beth Shirley: No, it takes work. It takes work.

 

Dr. Joel Rosen: So as far as the question that I always ask people at the end of the podcast interview, Beth, there’s knowing what you know, now and you certainly know, a super, super amount of information. And I’m probably sure along the way, you always have new information.

But what discoveries or what you’ve learned over the years that you would have told the best that didn’t understand this that would have made a bigger difference or a better improvement in your health? I’m always curious to know what my interviewee’s answers are to that.

 

Beth Shirley: Well, the pharmacy I worked at. So the last one I was there for 15 years, was right next door to dry cleaners, and my office shared are all with the dry cleaners. And that’s when they were using all these perks. So everything that I had known, in functional medicine allowed me to stay there way years longer than I should have.

So by the time I left there in 2012, I was, really, really sick. Those chemicals are solvents, they dissolve fat. And they tore my brain. So I couldn’t even work for a few years. So I would tell myself to get the hell out of there, like yours before I did. Because it just totally changed my life.

 

Dr. Joel Rosen: Wow, I’m glad you identified that and were able to overcome that. I think it’s just an epitome of what it is in our world that we have to be super vigilant of the water. We drink the food we eat the air we breathe.

 

Beth Shirley: Yeah. I mean, everything. I mean, I always do an IV, vitamin C IV, glutathione, I, vol. Everything was making me sicker. And I’m the one on one of those that got sicker on glutathione. Then without but has to do with that nitric oxide deficiency. Right.

 

Dr. Joel Rosen: Right. And that NADPH not being available for recycling glutathione makes more superoxide Oh, interesting. Well, listen, Beth, I appreciate your time. You know, and I wish I would have listened to and I will listen to more of your recordings.

And I know you’re doing your job of spreading the news on this important compound. What if people haven’t heard of you, Beth? And where did they go to learn more about what you do and where they could listen to the information you’ve put out already?

 

Beth Shirley: On LinkedIn, I post a lot of recent studies and I’ve been posting for the last two and a half years about the nitric oxide deficiency and this viral environment that we’re in on the Berkeley life professional page on YouTube. I have a lot of my webinars.

And I go deep into the EMF. It’s, you know, I spent a lot of time and energy on that because that’s information they don’t want us to have. They don’t want that information out there. So that’s a good one. But there are quite a few pretty good ones on there.

 

Dr. Joel Rosen: Excellent. All right, well, good. I’ll make sure that I’ll post links in the thread to where they can get access to you and we talked before we got started on how I could create a discount link so that we could pass savings onto the listener to try this out. I certainly think that they should get as their tools I always say tools in your toolkit, the nitric oxide testing kit to be able to see that and then also the nitric oxide boosting nutrients. And then maybe we didn’t get into it, but maybe you could just give me a quick little rundown. I know, there’s also serum and lotions. What are some of the other products that Berkeley life puts out to help boost nitric oxide levels?

 

Beth Shirley: Well, the nitric oxide serum is it’s a topical nitric oxide. So it’s increasing circulation and microcirculation just right at the skin level. So it’s good for wrinkles and is good for acne for discoloration for healing. And Dr. Brian made this specifically for his dad who’s a paraplegic who had some sores that his allopathic doctors told him that would never heal, ever.

You know, and using this nitric oxide serum healed the sores. So it’s pretty cool stuff. So it’s one side of the serum is nitrite. The other side is vitamin C. And when you mix them, you’re making nitric oxide gas.

 

Dr. Joel Rosen: Interesting. Cool. Well, it’s, you know, I would say, as bad as the environment depletes our NADPH and uncouples, nitric oxide, we have all these cool new developments as well to combat a lot of these challenges. So there’s still hope out there.

So anyways, Beth, I appreciate your time. And I’ll make sure I put the post where they can learn more about you and get some of the products from Berkeley life and I will make sure that I start listening more to the research you put out and or talk about and I want to thank you for your time today and wish you nothing but further success in the future.

 

Beth Shirley: Thank you so much. Appreciate it. Thank you.

 

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