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Beth Shirley, RPh CCN is a Registered Pharmacist and Certified Clinical Nutritionist who has developed unique expertise as both a pharmacist and certified clinical nutritionist during a distinguished 40+ year career. She has been a pioneer at the cutting edge of the evolution of what has now come to be known as “Integrative Pharmacy” …the junction between traditional pharmacy and the clinical use of nutritional supplementation.

Since 2009, Beth has worked in close collaboration with some of the world’s leading thought leaders in the field of nitric oxide research. Through this, she has developed an in- depth knowledge on the topic and its potential beneficial applications in multiple aspects of patient care. In addition, she has worked closely with the scientific community and cutting-edge companies working on innovative nutritional ingredients and approaches to their use for a variety of life’s challenges.

Beth Shirley 02:53 Her Journey:

I became a pharmacist because I thought I was going to help people. And after many years of seeing people come back sicker and sicker on more and more drugs. In 1997, I became a certified clinical nutritionist. Okay, so I became the pharmacist to go to if you wanted to get off drugs, or not go down that road to begin with. And I also started monthly Women's Health seminars, where I was teaching women, how to change their lifestyle, change their nutrition, incorporate bioidentical hormones. And I did this monthly for about 15 years.

Dr. Barrett 03:36

You know, that's, that's kind of interesting, because I've interviewed a lot of functional medicine physicians. And invariably, when I asked them that question of how they got into their space, they always have a story. Sometimes it's a personal family member story or even themselves that, you know, regular medicine wasn't working for me, and I had to find some, you know, exact better way to treat it. And so that's not that unique of a story. I think when you have very bright people that look at things and say “wait a second, it's supposed to be better than this, right?”

Beth Shirley 04:08

Yep. Yeah. And definitely it came from not finding answers for myself in the allopathic round. Right.

Dr. Barrett 04:16

What, what was the trigger that got you into the nitric oxide arena?

Beth Shirley 04:27 Her entry into the NO world

NO is very interesting, it touches every single physiological process, every single one of them.

Dr. Barrett  05:20

And that, you know, the more I read about it, the more I'm fascinated that there are there are other molecules that have this very diverse effect on multiple, biomechanical or excuse biochemical pathways. And, you know, take vitamin D, for example, that it seems to touch a lot of different enzymes and that type of thing. But, but nitric oxide, to me seems like it's really one of the most diverse molecules of human physiology from all of the different things that it does, touches

Beth Shirley 05:54

…everything like cardiovascular system, it governs circulation, and microcirculation, our brain or neurological system, our learning our memory, our kidneys, are so dependent on good microcirculation our eyes, our vision, our hormones, all of our hormones, all of our sexual hormones actually need nitric oxide. For the precursor molecules for the gonadotropin releasing hormone is how it all gets started, in essence, nitric oxide independent.

Dr. Barrett 06:31

So, if you, so let me interrupt you for a second. If for example, you thought about the fact that, you know, there's bioidentical hormone replacement therapy, we know that testosterone in males tends to decrease dramatically over, you know, the aging process, as does nitric oxide, I think there's something in some of the writings, what is it about 50% is reduced by the time you're age 40.

Beth Shirley 07:01

By the time you're 40, your ability to make nitric oxide through that nos enzyme, nitric oxide synthase, decreases to about 50%. And then by the time 60, it's only about 15%.

Dr. Barrett 07:15

So just talking about the cardioprotective benefits of nitric oxide, it's so critical, but yet it's so depleted in that timeframe, the window of cardiovascular disaster, let's call it when you know, your mid 50s. And on when you need it even more. So that's kind of interesting. But you met you mentioned something that I really, I personally need more of an explanation of, and you can help it help us out with that I'm sure as well as the audience. But you when you look at some of the literature, you'll see Inos, enos, and nnos. Can you explain to the audience some of the differences in these nitric oxide synthase enzymes?

Beth Shirley 07:58

They're all nos enzymes, only they're found and they found in different places, and they do different things…

Dr. Barrett 08:41

Are they the exact same molecular structure and that they're just produced in different areas? Or is it a little bit different molecule?

Beth Shirley 08:53

It's just a little different, but not that much. Okay. Okay. So, the inos is inducible and is not calcium dependent, the enos and the Nnos are calcium calmodulin dependent.

Dr. Barrett 09:13

So, as we get older, enos, which is the endovascular the one that resides in the endothelium of the vascular system hit brakes. What about it?

Beth Shirley 09:28

Well, the thing is oxidative stress, so any kind of free radicals oxidative stress, from EMF oxidative stress from anything, like any kind of most anything in our environment, increases free radicals that increases oxidative stress, oxidative stress, uncouples not. So, NO is a dimer. All right, and it’s held together. Okay, oxidative stress uncouples that nos and when nos is uncoupled, it becomes a superoxide generator, not a nitric oxide producer. Okay. So, under oxidative stress, you're, you're stimulating the NOS enzyme. However, you're not making nitric oxide, you're making superoxide.

Dr. Barrett 10:29

Which is something you might not want to have a bunch of, no,

Beth Shirley 10:32

no, because we the oxidative stress in this kind of environment comes everywhere.

Dr. Barrett 10:41

Just so go going back to the enos. It's the primarily the enos is the one that is depleted as we age.

Beth Shirley 10:52

Well, they all can be uncoupled. Okay.

Dr. Barrett 10:56

Okay. But when we're supplementing to replete, our depletion, we are actually probably not supplementing directly to Enos. Right? It would be more of the other structures, or would it actually be an enos? For the way you, you turned it over?

Beth Shirley 11:19

Well, nitrate, it's all of them. Okay, the nitrate can actually help increase the production of BH4, which helps couple nos. So, it makes all the NOS function better.

Dr. Barrett 12:17

Yeah, well, maybe, you know, you haven't had a knucklehead like me interview that has a primitive understanding that a question like that, but alright, so what we're going to talk about, then, the, you know, the, I guess, let's go into the supplementation process, because there's a lot of I think there's a lot of misunderstanding and what the supplementation process really is about why it's so important. I mean, we are recommending that every one of our patients over age 40 are supplemented, and that it's an ongoing thing.

Beth Shirley 12:56

But not only just over 40 anybody with any kind of chronic issue. Right, right. So pretty much anybody that's sitting in front of you,

Dr. Barrett 13:05

right? And that's what's so powerful about the testing strips, because within a matter of a few seconds, you can see whether you're depleted or not. Right?

Beth Shirley 13:14

Yeah. Because even some of the most popular medications, these uncouple, that nos enzyme, give me an example. Antibiotics, SSRI antidepressants, Azole antifungals, which are so popular now because of the mole community, right? Okay. NSAIDs, and your ibuprofen. Okay, birth control pills. That's why they don't like women over the age of 35. Taking the birth control pills and especially not smokers. That cardiovascular complication,

for sure. Strokes and stuff, right? PPIs proton pump inhibitors, right? These inhibit the production of nitric oxide through both pathways. And when these were first put on the market back in the early 90s, insurance only paid for six weeks supply. They knew that this was not a long-term type of medication people should be on. Right. But now, people have been on for decades. They're over the counter and people take them like candy. Right?

Dr. Barrett 14:27

Yeah, I think that that's one of the great myths. understandings, you at least in the patient population with proton pump inhibitors because they don't understand that okay. It changes the, the ability for your natural gastric secretions to complete a lot of these chemical reactions for lack of a better way to put it. Nitric oxide being one of them, right. I mean, if you're taking a proton pump inhibitor, that's going to decrease it You know more of the ability for you to change things with nitric oxide supplements so that then you maybe need to go to a lozenge

Beth Shirley 15:10

More than likely, or you know, work with somebody and have them change their diet and in new get off some of these foods that are inhibiting their physiological process.

Dr. Barrett 15:27

So, a lot of people are, I think, under the assumption that when you take these proton pump inhibitors, all it does is it just kind of neutralizes the, the pH to a point where they don't have the reflux symptoms, but I don't think they understand that it actually blocks your production of nitric oxide through that pathway. Both pathways?

Beth Shirley 15:59

It changes the pH of the stomach, so that with nitrate supplementation, and okay with nitrate, we consume the nitrates, they get absorbed, they circulate around, they get concentrated the salivary glands, salivary glands release a nitrate, we've got good anaerobic bacteria on our tongue that will reduce the nitrate to nitrite. Right. Okay, we know that these proton pump inhibitors actually changed pH. But then we swallow the nitrite in in the acidic environment of the stomach, some of that nitrite gets reduced further to nitric oxide. So, with PPI’s you don't have that acidity there, right?

Dr. Barrett 16:47

So, you're not going to convert it. Right? So, you talked about the other pathways the other pathway, just more of a sublingual systemic distribution of the nitrate into the I'm a little I don't understand that other pathway. I understand if you eat a nitrate you converted in your mouth with your your oral microbiome into a nitrite. The nitrate goes down into the stomach and if it's proper pH then it's converted into nitric oxide, but explain the other pathway to me. The nos pathway? Well, you said it interrupts both pathways.

Beth Shirley 17:22

The arginine nos pathway? That's where the Arginine is fed into the nitric oxide synthase enzyme to make your nitric oxide. Okay. The PPIs increase the production of what's called asymmetric dimethyl arginine. Okay. And this asymmetric dimethyl arginine inhibits that nos enzyme.

Dr. Barrett 17:52

So then when you're talking about the PPIs, messing up both pathways, that's what you're referring to. Right? Okay. Excellent. Excellent. So, I guess we can jump around a little bit. But let's talk about some of the other physiological effects. We know that nitric oxide is very important to help offload oxygen from the hemoglobin molecule, right,

Beth Shirley 18:17

Nitric oxide needs to be connected to the hemoglobin molecule in order for it to deliver oxygen, you can be super saturated with oxygen. And if you're nitric oxide deficient, you're not going to be able to deliver that oxygen to the cells and tissues.

Dr. Barrett 18:33

So that's two things that are going on in the endovascular system. If we're depleted in nitric oxide, it's going to affect the small muscle, we're not going to have as much vasodilation. And then it also affects these cells that are carrying this important oxygen to our tissues. So, there's things going on. So, it's kind of like affecting the pipe and affecting the water that's running through the pipe. Right?

Beth Shirley 18:55

Because the cells can't be more than two cells away from a functioning microcapillary. Wait, say that, again, the cells need to be like, two or less cells away from a functioning microcapillary In order to be able to affect be fed the oxygen glucose and nutrients. Okay, that microcapillary isn't functioning correctly, then you're gonna have cellular damage.

Dr. Barrett 19:24

And all tissues that are pathologic, seem to have an impairment of vascular perfusion.

Beth Shirley 19:33

only feeding the cells it's also clear in a way the cellular debris too. So, it's, it's both.

Dr. Barrett 19:41

Now, what about some of the other effects of nitric oxide that you'll read about how it seems to maybe increase the ability of us to you know, not be maybe as insulin resistant, and let's talk about that little bit.

Beth Shirley 20:00

All right, there's a, there's a glut 4 receptor on the cell. And it needs nitric oxide to be attached to it in order to translocate and bring glucose into the cell. So, when you're nitric oxide deficient, your blood sugar, well, will not be good.

Dr. Barrett 20:26

Well, and the other thing is, I would imagine, if you're impairing the glut 4, body's going to react to that and saying, Hey, I'm not getting enough glucose in for ATP production and whatnot. So, I need to produce more insulin to try to help with this, this glucose through the cell wall. And then we know that high insulin levels chronic high insulin levels are highly associated with a lot of bad things that go on in human physiology.

Beth Shirley 20:52

It increases oxidative stress tremendously, and that oxidative stress, then uncouples, that nos. So, then you've got more oxidative stress being produced less nitric oxide, so you're on this really bad vicious cycle. So that's why the insulin resistance is so connected to cardiovascular disease.

Dr. Barrett 21:17

And therefore, that might explain why the preponderance of cardiovascular disease is so much higher and significant in the type two diabetic population versus the non-diabetic population. Exactly. Same thing with cancers. Yep. So that's pretty, pretty interesting. So, I think you could make the statement, do you think this is a fair statement that anybody with type two diabetes should probably be on nitric oxide supplementation? Is that a fair statement?

Beth Shirley 21:44

That is a fair statement? Yes. So, if your body has insulin resistance, PCOS, obstructive sleep apnea? No, that makes sense, right? Because that's connected, right? cardio metabolic disease. Okay, anybody living in this EMF, crazy world.

Dr. Barrett 22:10

You know what, Beth? I don't understand EMF. You know I? I mean, at first when I heard that. It's like oh, that's just it sounds so woo woo. You know, it's like, because you can't see it. You can't feel it. You can't touch it. Right. But then as you know, hang around in the biohacking sphere for a while. More and more people are talking about what the negative effects of EMF are. Is it just that it impairs mitochondrial function and energy production? What's going on with EMF?

Beth Shirley 24:25

Increases oxidative stress? EMF stimulates this enzyme called NADPH oxidase, okay. This enzyme’s only job is to make superoxide All right. When this enzyme gets up regulated, it will preferentially steal that NADPH from other necessary processes. And one of the necessary processes that uses NADPH is that not enzyme? It’s needed to recycle your glutathione. Okay. But there's NADPH oxidase enzyme is the base of how the EMF damages it. But like you said, you can't feel it. Right, it doesn't produce heat. So, this is the way the government has been able to say there really isn't any proof that it causes damage because it's not causing heat. However, they knew in the 60s that this radiation, EMF increases cardiovascular disease, increases diabetes, they knew this.

Dr. Barrett 25:46

What's the biggest source of EMF exposure to the average day to day person? Is that their cell phone up by their head?

Beth Shirley 25:55

That's a bad one. And WiFi? It's okay. In Austin, we have 5g. Right, so you walk out the door, it's everywhere.

Dr. Barrett 26:27

Is it just power? Is it just because it's a higher power? Or what? Is it that higher frequency?

Beth Shirley 26:32

It's the energy waves. Okay. But see the beautiful thing about nitrate, though, like by supporting that nitrate to nitrite and nitric oxide pathway, nitrate down regulates that NADPH oxidase enzyme. Alright. Okay, so you're down regulating the damaging effects of the EMF by supporting that pathway.

Dr. Barrett 27:08

And when you're supplementing, I would imagine if you're supplementing with nitrates for your nitric oxide to help protect you a little bit with the EMF, I would imagine the same thing could be said with some glutathione as well, some of the other antioxidants, or do you find those? Not really a big player in that role?

Beth Shirley 27:37

And I have my own theories on the glutathione. Okay, all right. I'm a big antioxidant person. My favorite antioxidant is actually ergothianine. And it is the only antioxidant that has its own transporter to take it within the cell.

Dr. Barrett 27:57

Okay. Is it a is a constituent or a down-stream product of glutathione? Or upstream?

Beth Shirley 28:06

No, it's not. It's completely separate. And actually, there's a lot of studies showing now that melatonin is actually more critical than even glutathione.

Dr. Barrett 28:18

Wow. Because usually, a lot of people only think about melatonin for sleep, but we know that it's a pretty broad-spectrum hormone as well. There's some stuff in there that, you know, in the literature, where, and we'll probably talk about this, when we talk about methylene blue and more about my brain just went blank, I need a little bit more nitric oxide. But I guess what I was gonna say is, there's a talk, there's talk about this term called hormesis. And what is a hormetic? effect? Can you explain that to the audience, because I think that's a really important concept.

Beth Shirley 29:01

Right? And, and this is kind of the basis of the methylene blue. So, on the methylene blue, low dose, and then if you keep going higher and higher, you're actually can be causing some of the, the issues that you want to be addressing. So, it's like it's a bell curve. So, methylene blue, you always want to be kind of on, you know, the, the, the up side of the bell curve, not at the top and not on the other side. Right.

Dr. Barrett 29:38

And so, for my understanding, I always thought of hormesis as basically I mean, I guess some people even say exercise can have a hormetic effect. And I guess, is that maybe the crux of, of what some of the homeopathy foundational tenets are based on?

Beth Shirley 30:02

Somewhat Yeah, yeah, very, very like, well, with homeopathy there actually isn't even any molecules of the original. The original product is all it is, is energetic. Interesting. Oh, it's energetic signatures, or whatever, that that. And I'm, I'm really, you know, attune to homeopathy. I mean, this is something that actually helped me when I was really, really sick. Yeah,

Dr. Barrett 30:32

I think, you know, a lot of people that really throw a lot of rocks at homeopathy, one of their biggest claims is, well, it's not a drug that has any, you know, effective dosage. And so therefore, it, it's all it can't be any good. It'd be like throwing one drop of acid into a giant Olympic sized swimming pool, it's not going to change the pH of that entire pool.

Beth Shirley 30:57

They help us out with energetics, its energetic signatures.

Dr. Barrett 31:02

what is an energetic signature?

Beth Shirley 31:05

It's like, I'm kind of, I don't know, I was thinking, maybe. You know, like, those studies that show, if you speak differently to water, you have different crystals that are formed. So, it's this energetic signature. So, I got really, really sick about 10 years ago, and all of the stuff that I've learned, you know, being in functional medicine since 97, was actually making me sicker. Even the IV glutathione, and things like that. And it wasn't until we started using some homeopathy that allowed my body to start releasing some of these chemicals. So, we were not giving my we were not giving me like any, any particular there was no drug, there was no herb or anything like that. It was just energetic signals. From plants, or all kinds of things to allow the body. Like, there's so much that we don't know about energy.

Dr. Barrett 32:30

Oh, for sure. Yeah. No, I mean, if you want to talk about energy and start looking at some of the things that just they're looking at different tissues and how energy is transported through like fascia, for example, and, and some of these very interesting things, and it's so far out of our day to day understanding, and maybe even our day to day awareness that, you know, I think that's that'll be a lot of investigation ongoing kind of leads me into what I wanted to talk to you about to brown fat versus yellow fat, because I just got a a little paper that you all were kind enough to forward to me about some of the stuff that they're doing over at University of Alabama in Birmingham, talking about sustained release of nitric oxide, where they develop this liposomal, subcutaneous concoction recipe for mice, and they saw a lot of cool things that happened with that. So, let's talk about that for a second.

Beth Shirley 33:33

Well, the light fat is what, where we're storing, storing the fat storing all this energy, right? You know, the brown fat, actually, it's thermogenic, it actually can help you burn energy. And by supporting the nitric oxide, you're actually stimulating this brown fat to help you burn the energy.

Dr. Barrett 34:05

So, the brown fat plays a role in some of the stuff that you you'll read about with, like some of these cold plunges, and, you know, heat shock and cold shock proteins and that type of thing. Now, what's the understanding of the nitric oxide in the mice that they gave to well, compared to the control the mice that got the sub cutaneous liposomal recipe they seem to have on the same diet after 12 weeks, they gained about 17% less body weight and it was also a good body weight because it wasn't, you know, a muscle loss thing like you have with semaglutide where Yeah, our great guy lost 10 pounds, but eight of that was muscle. That's no good, you know? So what happened there are what's the function of the nitric oxide playing with the what? Is it just up regulating the brown fat? Or is it making more of the brown fat? What's going on there?

Beth Shirley 35:10

It's, it's making more of it. So, it's up regulating the production of the brown fat, but it's also improving the glucose, your utilization of your glucose, and instead improving your insulin utilization, so you're not so insulin resistant. So, it's all down that that cardio metabolic pathway.

Dr. Barrett 35:35

Okay, so is it converting regular adipose tissue that we wouldn't turn brown into Brown? Or is that a de novo genesis of a new type of fat?

Beth Shirley 35:49

They think it's converting to the brown fat.

Dr. Barrett 35:53

All right. Well, that's very interesting. And then they also showed in these mice that got the liposomal nitric oxide concoction, they showed that they had increased cerebral blood flow and significantly improved learning abilities. So, I think then that takes us into the neurocognitive space. You know, everybody, I think everybody gets it. Nitric oxide, peripheral arterial disease, I think that's pretty well established in the understanding of most physicians, but I don't think it is in the neurocognitive world. And in the neuronal world of how the nitric oxide is playing a role, not just necessarily from the blood flow.

Beth Shirley 36:37

In our brains, even though they're only about 2% of our body weight, they consume 20% of our oxygen that we take. You've got to have that microcirculation open in order to be able to deliver that necessary oxygen. And when we're when we're thinking when we're trying to problem solve when we're learning. This is metabolically active. Right? Right. That means there's an increased need for ATP increased need for oxygen increased need for glucose. So that microcirculation has to be open.

Dr. Barrett 37:17

Right. But in addition to the microcirculation being improved, there's also these other, I'll call them tangential metabolic benefits as well, as far as the energy production, what's going on with everything. So, it's not just this one pathway of I'm opening up the river, some more waters going down the river, or opening up the dam. I mean, there's a lot of other things at play. Is that fair to say? Yes. Okay. And then I think to think of it from a brain standpoint, because I think he made an excellent point about, you know, energy demand, that type of thing. I mean, the brain probably is not so dissimilar to skeletal muscle, because as we're exercising skeletal muscle, it requires more nutrients, molecules, all these other things, because in order for that muscle to function, it just requiring more to be delivered to it more oxygen, and that type of thing. And same thing with cognitive processes and that type of thing. And a lot of the lot of the neuro imaging that has been done today is based on that premise of how much blood flow is being taken up or increased in that area. So, it makes a lot of sense.

Beth Shirley 38:27

Like with the muscles, this is one of our biggest storage places of nitrate and nitrite. Interesting, the myoglobin can actually reduce nitrite to nitric oxide on an as needed basis. So, when you're exercising the muscles can actually make more nitric oxide, in order to open up that microcirculation.

Dr. Barrett 38:52

I'll see that's really interesting, because I, I knew that you could increase nitric oxide production with exercise, but I thought it had to do more with because of the increase in maybe the turbulence or the speed that the blood was flowing through the arteries and stimulating these cells in the end of the ileum. And then to Vascular Endothelial that that was the only mechanism but you're saying there's also a muscular effect as well. Right. That's very cool. That's the nugget worth listening to the whole show right there. So, I guess the take home message for the people is that when you're on the treadmill running or lifting weights, you should be doing some cognitive things to get all these muscles going. That's a good idea. The one between your ears and the one on your Yeah, your deltoids biceps or whatever. So, that if you are going to explain to a patient in very simple terms, maybe five bullet points of why you really need to be supplementing with nitric oxide and I will tell everybody, there's like two things that I'll never miss, and that's my fish oil and my nitric oxide supplementation because I think those two things are, like, pretty much inherent to, to being able to fight all these bad things that try to kill us so much like cardiovascular disease, but what would you tell the patient? What some of the take home points for a patient? That, here's why you need to do this? Because they may not necessarily if they start a supplement, they may not necessarily feel something discernible.

Beth Shirley 40:31

Many times, though, when you start a nitrate supplement, you actually do feel it? Because you are opening up that circulation in the brain. And cardiovascular disease is still the number one killer. Right? Okay. And diabetes, you want to keep that blood sugar healthy? How about keeping your sex life healthy? There we go. Okay, because ED is one of the first signs of cardiovascular disease.

Dr. Barrett 41:05

It's right. That's true. Okay.

Beth Shirley 41:08

But it's sexual dysfunction in both men and women, as women needed to in order to be able to have that circulation down there.

Dr. Barrett 41:22

One of the things, yeah, so one of the things, I think he made a great point that some people do feel it when you put them on it, I think there's two things that can reinforce that. One is if you don't believe that it will help you and you're doing an exercise routine on a daily basis, or three or four days a week basis, or whatever it is, if you will supplement your yourself for nitric oxide production, at some point, before that run, invariably, you will see a better a better exercise performance. And so, you don't see it tangentially right there. And then the other thing is the testing strips.

Beth Shirley 42:10

Right? Yeah. And nitric oxide actually increases the endurance. And the intensity that you can do is strokes.

Dr. Barrett  42:23

I was gonna say, is that due solely to the, the vasodilation and the offloading of the oxygen from the heme molecule? Or are there some other factors that are playing into that as well?

Beth Shirley 42:37

Well, it's also being like, clearing away the debris, like the lactate clearing away debris from these muscles that are exercising,

Dr. Barrett 42:47

You know that's a good point. Because if somebody's lifting a lot of weights or like doing lower body, and they get a lot of lactate buildup, they should try that. And they'll see because I've noticed that personally, that there's much, much less lactic acid build up after a supplement right before a session of weightlifting, etc.

Beth Shirley 43:07

Interesting. And the test strips are testing the nitrite concentration of your saliva. So, the nitrite is the immediate precursor to your nitric oxide. Right. So, if you do some, some nitrates, either with supplements or with the high nitrate foods, about an hour, hour and a half later, you know, test yourself and see how pink that got right.

Dr. Barrett 43:38

Test now and then test yourself the next morning, and see how it goes down and then how you need to reload it. And that's one of the great things about nitric oxide supplementation is the test strips really, patient patients need metrics.

Dr. Barrett 44:14

Right. Exactly. Exactly. Well Beth, I want to thank you so much for coming on. And given some of your I know, it's just a little tidbit of your expertise because your expertise in the subject matter is so huge, but I think it's one of those things where the more it gets talked about and especially when we get somebody like you with your expertise to come on and kind of distill it down I think it just makes a lot of sense. So, want to thank you for taking the time to do that. And I look forward to talking to you in the future about methylene blue and its relationship with nitric oxide. Right.

Beth Shirley 44:48

And supporting your nitric oxide will not be the only thing you do but it needs to be the base of Have everything you do. If you don't, if you have impaired circulation or micro circulation, it doesn't really matter what else you're doing what else you're taking, is not going to be able to get to where it needs to go.