Rhonda: Hello everyone, and welcome back to another episode of the "FoundMyFitness" podcast. I am very excited. Today we're going to be talking about COVID-19. And it's a topic that's on all of our minds right now and has been for the last almost a year, pretty much.

And my guest today is someone that, in my opinion, has been a real important voice throughout the COVID-19 pandemic. His name is Dr. Roger Seheult. And he is a quadruple board-certified physician. He is certified in internal medicine, in critical care medicine, in pulmonary diseases, as well as sleep medicine. But in addition to treating patients and also teaching medical students in the classical setting, like a classroom, he also runs a popular and very, very informative YouTube channel where he educates not only medical students but the broader public in general. And his YouTube channel is called MedCram videos. And this is where I discovered Dr. Seheult. He has been covering the COVID-19 pandemic pretty much since the beginning. And he has been someone that has really done a fantastic job diving into the scientific literature, being very comprehensive, and uncovering just a wide array of very important topics related to this pandemic.

So I'm very excited to have Roger on the show today, and to discuss, you know, all things COVID-19. Roger and I share a few passions. In addition to educating the public, we also share passions about, you know, scholarly work and diving into the literature and trying to, you know, answer important questions and find good data to, you know, support hypotheses.

So, Roger, can you tell us a little bit about, I mean, you know, you've been covering COVID-19 since March, you know, 2020. How have things evolved for you in terms of covering this pandemic? And you and I were chatting, actually a little bit on the phone a few days ago, and you were telling me sort of what got you into this. How you, you know, were in the trenches out there and decided to sort of dive into the literature for certain reasons. Maybe we could talk a little bit about that.

Dr. Seheult: Yeah. So thanks very much, Dr. Patrick, for having me on the show.

So, this all started back when I was, well, I mean, I could go for far back. But I've always had a passion for teaching and taking things that are complicated and making them easy and understandable. And all through my college, medical school, residency, and now as an assistant professor at a couple of medical schools, that's what I do. And one day, I had the honor of having a PA student, a physician, assistant student that would change my life. It's not every day that a student changes your life. It's usually a teacher that changes your life. And Kyle Allred who is the other half of MedCram. And he happened to be my PA student for a month. And he, he said, "Dr. Seheult, students don't go to the library, check out articles." Like, you know, I used to do. "They go to YouTube, they go to Google, and they Google the question they have, and they look for the shortest video they can find."

And so he saw a real need there. Because as they go through the PA program, which is a two-year program, you know, sometimes they don't get all of the education that they feel that they need to get. They have to do a lot of studying on their own and it's very time constraining to go and check all of these things out.

Long story short is we started making videos about medical topics. So COPD, congestive heart failure, pneumonia, asthma, and we started posting them on our YouTube channel. And we'd gotten up to, you know, few 100,000 subscriptions. We were doing some videos that were very helpful. And then Coronavirus hit. And one day we decided to do a Coronavirus video. This was probably in late February, early March. And it just exploded because here was this virus that was basically taking over in China and people wanted to know about it. People were concerned about it. And people wanted to know more. And so instead of the world looking at, you know movie stars or sports stars, they were now for the first time looking at people like you and me, Rhonda, people who had been working in medicine and nutrition and medicine and science.

And really, there was a lack of communication. I mean, we have whole TV shows on sports, about how to communicate what's happening in the world of sports, and we have a whole infrastructure for that. We don't have that for medicine and science. And so it really put a lot of people like myself and a number of other people like myself and you on the hot seat to describe this to millions and millions of people. What is it that's really going on? And really, the question was begs is what do we do about it? And that sort of changed our lives.

Rhonda: And do you feel like earlier on, your thoughts about, you know, the pandemic have changed since, you know, everything that's, you know, happened since, you know, eight or nine months ago in terms of prevention and treatment and, you know, what the data out there suggests? Like, how has that evolved for you in terms of you're also in the hospital treating patients as well?

Dr. Seheult: Yeah, you know, I grew up in the scientific world of, you know, the hierarchy of evidence. So you've got epidemiological evidence, case-control studies, but really the thing that you need to have to be able to look a patient in the face and say, This is going to help you is a randomized control trial. And those types of trials take a long time, they take a long time. And the problem in this is that the system that we've set up of randomized controlled trials, applications to the FDA, these are great for diseases and conditions that are with us chronically. And that moves slowly. But they're not adequately designed to really help the majority of people in a worldwide pandemic, because people are dying very, very quickly. And you want to come up with answers very, very fast. And these things take time.

So that's one thing that I learned very, very quickly, is that if you want to try to save lives, and, you know, all of us look at this, from a different point of view. I guess I'm coming from the point of view of Yeah, I understand the ivory towers, I understand the people at the FDA, I understand the people that people are relying on them to say, here's something that we've tested, that looks good, and it works. But on the other hand, I'm working in the trenches too. So I'm looking family members in the face. And they're looking at me and it's like, "What can I do for our loved one? What is going to work?" And what we have to do is marry those two concepts together and come up with things, I believe that may have plausibility to work. But if we're going to institute something, if we're going to do something, it's got to have very, very low risk.

And so what you've seen, is you've seen a wide variety of things now that have gone through the FDA that probably never would have been approved under a normal situation. But because of the pandemic and the flexibility that we need to have, we need to move quickly because as things get out of hand, more and more people are dying. So for instance, convalescent plasma was approved using emergency use authorization through the FDA. And there was no controls in that study. So that's just an example of the type of things that we're doing. We're moving quickly here, we're in a pandemic, and we have to be creative. And we have to be understanding that this is not business as usual.

Rhonda: Have you looked back in history to see... I mean, this isn't the first time the world has dealt with a pandemic, and there's always lessons to be learned when looking back in history, you know, things repeat themselves, right? And you're not always starting, you know, from scratch, basically, there's a lot you can learn from the past.

Dr. Seheult: Oh, absolutely. I'm hoping we were going to go there in this topic because there is so much that I have studied. Not to say that I'm an expert in this, but just looking back at where we were just 100 years ago, is very informative, in that. And I think if we want to get into that what we've got to do is look at the disease itself. So COVID-19. And I think probably one of the first things that somebody needs to understand when you think about COVID is it's all about timing. It's very important that you understand that there is an early portion of the disease and there's a late portion of the disease. And the timeline that separates those two is really when you get pneumonia. I think that's probably the best way to make that demarcation. Early in the phase of COVID-19, before you have pneumonia, there's a certain set of factors that are going on in the body, we can get into detail what those are, that makes certain interventions more plausible and more efficacious. And then there's the later phase of COVID-19 where patients generally are hospitalized or on oxygen. And we see other types of interventions to be much more effective.

To give you an example of that. Steroids. So dexamethasone, that was a UK recovery trial that came out, showed without a doubt that steroids improve. Well, what they found was that patients who were not on oxygen, so in other words, early in the course of the disease did not benefit from steroids, it was equivocal, whereas those that were the sickest patients on the ventilator requiring high doses of oxygen seemed to be the ones that benefited the most from dexamethasone or steroids. The flip of that was remdesivir. So whereas steroids were very beneficial late in the course of the disease, medications like Remdesivir, it's not an anti-inflammatory, but rather an antiviral, it prevents the viral replication. The opposite was found. Remdesivir was much more efficacious early in the course of the disease, and not so much so for those patients on the ventilator.

So it's not just like this disease is a one-fits-all thing. You've got COVID. No. Is it early or late COVID?

So taking that into consideration, we can then go back and look and see what people did 100 years ago, for these diseases, because what people did in the hospitals 100 years ago, is nothing like what we're doing today. I mean, they did not have oxygen, they did not have ventilators. They had some medications which we can talk about. But what I started to realize is that in a pandemic situation, it's very, very difficult to scale up production of any pharmacological agents, as we're finding out now. Let's look at vaccination. Let's look at medications. Fortunately, dexamethasone is dirt cheap and we've had it for a long time. And we can manufacture the stuff pretty quickly. But if you find any kind of pharmacological intervention, be it hydroxychloroquine, be it ivermectin, and we can talk about those things. Those things have to be scaled so rapidly, and to such a high degree that as soon as you say, this medication is efficacious, you can't find it in the pharmacy, it's gone.

And so, what this has done, to me as an individual, has really looked at plausible, biochemically plausible, rational, efficacious remedies that are not a cure-They're not going to fix you or protect you 100%, but may in a population type of setting swing things enough so that we can deaden [SP] the blow of the pandemic.

Rhonda: And are you talking in a sense about lifestyle factors? Things that are low-hanging fruit?

Dr. Seheult: Oh, yeah, absolutely. Absolutely. So lifestyle factors. But not just lifestyle factors. Because what are you going to do to somebody who has not been practicing the proper lifestyle and now they get COVID-19? What do they do? It's too late for them to institute lifestyle changes that are really long-lasting, but what do they do? And I think there is a science behind some of the things that we can do. And, you know, vitamin D, we talked about vitamin D in the past, and now in the future. Vitamin D has been a long story. You've been talking about vitamin D longer than I have. And there are other things as well. Things that actually have some scientific plausibility, which I love to talk about.

You know, so again, like what we've been talking about Rhonda, it's an all of the above type of thing. It's not just any one thing that's going to help. It's like, for instance, when you go to the operating room, right, we want to prevent infections. And so we don't think that just the doctor or the surgeon wearing the mask is going to solve everything. We also have a negative pressure or a positive pressure operating room, and we make sure that we use betadine or ChloraPrep on the incision. We're doing multiple things because nothing, particularly by itself is going to be effective. And so some of the stuff we've been talking about today, like hydrotherapy, or we're talking about vitamin D, none of those things by themselves is going to, you know, wipe out the pandemic. We have to do all of the other things that we know work like wearing masks, you know, over our nose and our face.

And that's the other issue too, is we're seeing a lot of this. People are in homes, and maybe it's their eight-year-old that's positive for COVID. What do they do? They can't just send their eight-year-old down the street and have them go to a motel. So what do you do in the home? And that just made me think of something else because the CDC has just come out now with updated information about what to do in terms of ventilation. So the key in preventing yourself from getting COVID-19 is to make sure that, you know, you're not getting it from somebody directly from like large sputum or droplets.

So you want to make sure that you're wearing a mask, that they're wearing a mask, that you're distanced. But also realize that if you're in a room that's stagnant, wearing a mask is not going to be 100% effective because it's kind of like smoking, right? If somebody is smoking on the other side of the room, you may not smell it. But if you're in there for long enough, that smoke is going to fill up the room. And so what's really important is ventilation. Now, you know, that may be difficult to do in the wintertime when it's cold outside, but as much as possible, even just cracking the window a few inches, if you can do it, and maybe dressing more warmly, having ventilation in closed spaces can really do a lot.

So it's all of the above. It's the mask-wearing, it's the distancing, it's to make sure that you're not in an enclosed space for a long period of time with other people. You know, interestingly, you might wonder why people don't get the virus when they're on a plane. That's a closed space and people are wearing masks. Well, you may not know this, but they do air changes, like tenfold, every hour, and all of that air is going through HEPA filters, and so the virus gets trapped. And that's why it works as people are on planes for five, six hours, you know, going across the continent, they're wearing masks, but they're not getting COVID-19. You might find a few examples where people might get it. But generally speaking, it's very successful. And why is that? It's because of ventilation.

And so all of these things put together is really what the answer is. So following the recommendations, following what the CDC says. But here's some other things that we've talked about today that may also be beneficial. So I just want to make sure that everyone's clear on that.

Rhonda: Absolutely. I think it's super important to keep that in mind that wearing a mask and social distancing, and, you know, washing your hands, of course, as well, and ventilation are really important. And definitely, there's been so many studies now with mask-wearing too, right? I mean, you know, it doesn't have to be an N95 mask, I mean, even, you know, someone wearing a cloth mask, it can both protect you from infecting others, and also can actually filter out some to some degree, some particles that are, you know, you won't be exposed to as many viral particles as if there were no mask, even if it's not a super high-quality N95 mask, you know, filtering out particles. So I found some of those studies to be reassuring, at least where it's like, Okay, well, even, you know, people wearing any kind of masks, you know, helps.

So, yeah, thank you again, for bringing that up again, Dr. Seheult. Let's dive into vitamin D. You know, it's definitely a passion of mine. I'm a bit of an enthusiast, you know, but I've published a couple of peer-reviewed studies back in 2014, and '15. And so, you know, I've been very familiar with the vitamin D literature for many years. And, you know, so when this pandemic first started, I was already familiar with the role of vitamin D in the immune system, and also in preventing respiratory diseases and randomized controlled trials showing that. But maybe you can kind of, you've done a fantastic job covering the role of vitamin D in COVID-19. And early on as well, you were out there championing, you know, the vitamin D may play an important role. And you looked at, you know, maybe we can talk about some of the observational studies and what the limitations are of those and also some of the very, very preliminary, you know, pilot randomized controlled trials that have been done. But maybe just start with some of the basics. Not everyone realizes that vitamin D, the name can be a little deceiving.

Dr. Seheult: You're absolutely right. And this is one of the first things that, and I know I'm preaching to the choir here, those that have watched you know that vitamin D is so much more than just a vitamin. But I would encourage anybody who is interested in this. Just Google vitamin D structure. And look at the actual chemical structure of vitamin D. You know, I got my bachelor's in chemistry. So that's the first thing that I naturally do is you can tell a lot. Yeah. Good. Yeah. So yeah. So yeah, exactly.

So you know that if you look at the structure of vitamin D, it is very similar to the structure of cortisol, of the structure of testosterone, of estrogen, of progesterone. And what do we know about all of these other steroid hormones? They go directly into the nucleus of the cell where they affect transcription of protein factors. And depending on the cell type, it's going to have a different effect. So already, right off the bat, you can see that vitamin D is doing something very different than what we would think of as just a vitamin where you need a cofactor to have an enzyme do A to B. It's much more nuanced than that.

And very early on, the studies on vitamin D were involving calcium, bone metabolism. And so they came up with all of these things because they didn't know what else vitamin D did, really. I mean, they had some idea, but they came up with these standards, oh, you need so much vitamin D for your bones to do whatever it needs to do and the calcium.

And so, the analogy I like to use is, like, you know, you're baking something right, and you put so much flour into the recipe. It's as if to say that's the only thing that flour is good for is this one recipe and that if you use flour for anything else, that's exactly the amount of flour that you'd have to use for any other recipe. Well, that's nonsense, of course. I mean, we know that we need a certain amount of vitamin D for proper bone metabolism. But why does that carry that that's the amount of vitamin D we need for a proper immune function? I mean, none of those things are there. And we have all of these standards about how much we need.

We'll talk a little bit about the observational studies, but vitamin D is not just a vitamin, it literally falls more into hormonal...I mean, think about Addison's disease. Addison's disease is where you have antibodies that attack the adrenal glands, this tiny little gland that sits on top of your kidneys. The purpose of that adrenal gland is to make cortisol, aldosterone, androgens. These things are essential. In fact, if people lose their adrenal glands they will die because they don't have enough cortisol. Cortisol is essential for just the regular running of the body.

And here we have this thing called vitamin D. The problem is we don't have a gland that makes vitamin D. We have the skin. So the skin through the sun, and ultraviolet radiation, which barely penetrates through the epidermis, it gets down to the dermis, where the actual starting product is. And so if you don't get enough of this, you are going to be lacking in a whole host of things. So let's talk a little bit about what we found. And, you know, prior to COVID-19, we had some very good data on vitamin D. There was a wonderful meta-analysis? What's in a meta-analysis? Where they take a bunch of studies, they, sort of, chop them up, put it through a grinder, and they look and see what the overall is so they can get a much bigger and much bigger subject number.

And Martineau who was the lead author on that British Medical Journal, meta-analysis, that was done a number of years ago now, showed that supplementation with vitamin D decreased acute chest infections by 50% significantly in that study, and also in the long aging health study called TILDA in Ireland showed that vitamin D supplementation was beneficial. So we knew that there was immune properties. They found vitamin D receptors in the immune cells. And so all of this stuff is emerging.

And then and then we get to COVID. And we start to see some really interesting studies coming out showing an association. Now that's an association not necessarily causation between a lot of the same things that we see in COVID we see in vitamin D deficiency. So what do we see? The older you are, the more apt you are to get vitamin D deficiencies because your skin is not as effective at making vitamin D. And we saw there was an age predilection in COVID-19. What about race? We saw that race, particularly darker-skinned people were affected more in COVID-19. And you could say, well, there's some confounders there, right? Because people who are ethnically darker may not have access to health care. Well, this cared even in those countries where there were socialized medicine, where everybody had access to health care, which doesn't erase that completely. But it was still a very strong association. We also saw it not only in gender but also big-time in BMI. So the more obese you were, the less the vitamin D, also, there was more morbidity in terms of COVID-19.

But all of that got fleshed out in I think in a beautiful study that was done here in the United States that looked at 191,000 people. And it was published in "PLoS ONE," the journal, an article titled SARS-CoV-2 positivity rates associated with circulating 25-hydroxyvitamin D levels.

So let's back up right there and talk a little bit about metabolism. You've got these cholesterol derivatives that get converted into vitamin D in the skin. Well, then that has to go to the liver for a 25-hydroxy group to be put on one of the carbons. Now you've got 25-hydroxy vitamin D. This is what we measure in your blood. And then it gets converted into 1,25-dihydroxyvitamin D in the kidneys for metabolism, or in the white blood cells where they're needed there. So we're looking at 25-hydroxyvitamin D. That's the storage form of vitamin D.

And what they found was as your levels started to drop below 50 nanograms per milliliter, we started to see an increase in SARS-CoV-2 positivity rate. And it didn't matter based on race, gender, geography, or age, all groups saw an increase in SARS COVID 2 infections associated with a lower level of 25-hydroxyvitamin D. The lower these levels went, the higher the positivity rate.

And that was just the beginning. I mean, this went on and on and on. No matter how you slice it or dice it, there was this very strong association of vitamin D deficiency with higher rates of COVID. Higher SARS-CoV-2 positivity rates and higher admissions. We see people being admitted to the hospital who had lower rates than those that had similar symptoms but we're not SARS-CoV-2 positive.

And, you know, as you know, just because you have an association doesn't tell you that you have causation. The only way you could really find that out is by doing randomized controlled trials that we've talked about.

Rhonda: And so you mentioned admissions, but also mortality. Weren't there some studies also showing that patients that were more vitamin D deficient were more likely to have a severe case and even die, versus ones that had higher vitamin D levels?

Dr. Seheult: Absolutely. Yeah. So they showed that there was a difference in mortality, that there was a difference in which ones went on to need ventilators. And so all of this. So the question wasn't, was the vitamin D involved in this somehow? The question was vitamin D, the causative role, or vitamin D deficiency the causative role?

Rhonda: Right. And as you mentioned, because these are observational studies one could argue, well, maybe low vitamin D is just biomarking unhealthy, in general, right. And this is where, as you mentioned, randomized control trials are really key. But there's another type of study that I love to cite and talk about, because as you had mentioned, previously, randomized controlled trials are very, very expensive to do, they're very difficult, you know, they take a long time. It's a challenge.

So another way of measuring more of a causative role, you know, of certain factors, and particularly, in this case, lifestyle factors or something that, you know, I call vitamin D lifestyle, because you're making it you know, from the sun, they're called Mendelian randomization studies. And essentially what they do is they measure, so everyone has, you know, different variations in their sequence of DNA in their genes. And these variations often are just a change in one DNA nucleotide, which is called the single-nucleotide polymorphism, or SNP for short, as you know. But for people listening and watching, there are many different variations in genes that convert, for example, 25-hydroxyvitamin D, the major circulating metabolite of vitamin D, into 1,25-hydroxyvitamin D, which is the active steroid hormone. And these changes in just one nucleotide of DNA in these genes are associated with lower circulating levels of 25-hydroxyvitamin D, because, you know, it's just, you know, different genes are doing different things. And sometimes genes get less active. And sometimes they're more active based on this, you know, sequence change.

So it's well known that these certain SNPs are associated with lower circulating 25-hydroxyvitamin D levels. And so there have been meta-analyses looking at people that have the SNP, didn't measure vitamin D levels at all, it's already known, they have lower circulating levels. So you can't say, Oh, you know, you're just measuring their low vitamin D. That's bio marketing and other health status. This is just genetics. We're just looking at a gene that's known to cause that. And these people have a much higher mortality from respiratory tract infections. They have a higher all-cause mortality, they have a higher cancer mortality. Cardiovascular-related mortalities is unchanged. But respiratory tract infections are much higher.

And so, that Mendelian randomization study, I love to cite that because it really is establishing causation because, you know, you're not just measuring vitamin D levels and then saying, well, maybe they're low in vitamin D because they don't go out and exercise or maybe they're low in vitamin D because they're, you know, obese and, you know, vitamin D is less bioavailable, which it is in obese individuals, as you mentioned.

So, the Medallia randomization studies, in addition to the randomized controlled trials, I think another piece of evidence that hints towards possible causation of vitamin D being important for preventing respiratory tract mortality as well.

Dr. Seheult: Oh, that's amazing. I wasn't even aware of that. That's a great way of showing causation. And of course, they are working on some pilot studies that are trying to show randomization, but how big of a study was that?

Rhonda: It was quite large. I don't recall off the top of my head, I do have it linked in my notes, I can get up and send you. But yeah, there's been other SNPs in, like, the vitamin D receptor, for example. So children that have a single nucleotide polymorphism in the vitamin D receptor, they also have a higher mortality from respiratory tract infections as well, you know. So vitamin D, as you mentioned, you know, it's a steroid hormone, it's going into the nucleus, you know, it binds to the vitamin D receptor, which then heterodimerizes with another receptor called the retinoid receptor. And that complex, you know, goes into the nucleus where your DNA is and it recognizes a very specific sequence of DNA called a vitamin D response element. And these are in more than 5% of the protein-encoding human genome. I mean, that's a lot of genes vitamin D is regulating in all sorts of tissues. You know, brain in the immune cells, you know, and other organs as well.

So, I do think like, you know, thinking about mechanism, and I know, you've talked about, you know, the role looking, you know, underlying mechanisms, how does vitamin D regulate the immune system? I mean, there's a variety of ways. And specifically, it's really interesting. And I'm getting off topic here. I want to get to the pilot randomized controlled trials, but are you aware of the role vitamin D plays in the ACE2 and renin-angiotensin system?

Dr. Seheult: I know there is a connection. I was actually reading that just briefly. I think you're the one that sent me the article. But I need to remind myself.

Rhonda: We covered it back in March or April. I did a short little Q&A podcast on it. And it's really interesting, you know much more about the renin-angiotensin system than I do as a medical practitioner, which, you know, it obviously plays an important role in regulating blood pressure and fluid homeostasis, and, you know, I think even in the lungs too. But what's interesting about the vitamin D renin-angiotensin system kind of it converges on the ACE2 receptor, which, as you know, and probably most of the world has heard by now is how the SARS-CoV-2 virus enters into ourselves, it binds that receptor. Well, what's been shown with SARS-CoV-1 is when the virus which also binds to the same receptor to get inside of the cell, it binds to the receptor and it internalizes the receptor and down-regulates ACE2, which is not good because that is really important for this renin-angiotensin regulation, as you know, Dr. Seheult. So that's been shown with SARS-CoV-1.

And what happens when the ACE2 gets down-regulated, acute lung injury gets really bad. And so there's been some animal studies that have found, for example, if you high-dose with the active form of vitamin D, the animals, and then you cause acute lung injury, ACE2 goes down, acute lung injury goes up in the placebo group, but the vitamin D group, it normalizes the ACE2 levels.

So if you think about it, you know, this is a hypothesis, of course, another potential way vitamin D could be playing an important role in this specific virus is through regulating ACE2 levels. And what's interesting is that there was just a very recent study that came out. ACE2, the gene, it's located on the X chromosome. And women have two X chromosomes most of the time. One of those X chromosomes, the gene is inactivated. But there are genes that escape that. And ACE2 is one of those. And so women have much higher levels of ACE2. And so researchers are thinking this is protecting them from a more severe COVID-19 outcome because they're getting that ACE2 levels, like, you know, higher in terms of, you'd think, Oh, well, more ACE2, that means the virus is getting in and, but actually, biology always tricks you. You know, you always think one thing, and then it's like this beautiful, you know, sort of complex scenario.

But I'm digressing. And I just, kind of, wanted to bounce it off you because you're such a scholar, and I thought you probably would find that interesting, and I certainly hope scientists are testing that hypothesis because it seems very relevant.

Dr. Seheult: Yeah, it does. Not only that, the human body is so complex as you say that there's so many connections. The other aspect of angiotensin or ACE2 I should say is that it gets rid of pro-oxidative products and it increases antioxidant products. So for instance, angiotensin II, and angiotensin (1-7), those are in balance and ACE2 tries to keep those in balance. But when ACE2 is knocked out by other SARS-CoV-2 or SARS 1, the amount of oxidative stress goes up dramatically. And what we see that that may play a role in terms of thrombosis. So you have oxidative stress in the ACE2 receptors at the endothelium of the vasculature that causes inflammatory stress, oxidative stress, that causes thrombosis. And that's where that happens as well. So all of these things, it seems as though we've got the dots, connecting them requires very good randomized controlled trials. But again, like you said, hypothesis driving type of studies that may answer that question.

Rhonda: That was very enlightening. I do remember reading about that. And, wow, I didn't realize it played the role in the thrombosis as well. So that's super interesting. But as you mentioned, yes. randomized controlled trials are key. And there have been, I've seen, you know, one stronger, but small trial that was published, was it back in September, that found... I think it was in, was it Spain, perhaps?

Dr. Seheult: Yes. Yep. It was October, I've got it pulled up here, October of 2020. And it was Marta Castillo who was the lead author on this one out of Spain. There was a little issues with the randomization. So probably the effect was overemphasized. But if you look at the effects, they were quite dramatic. In the calcifediol group. Lets us back up a little bit, what's calcifediol? That's the name that we give the 25-hydroxyvitamin D.

So in this study, they didn't give just vitamin D, they gave the product of the metabolism in the liver of vitamin D.

Rhonda: Now, do you think that's important for someone that is undergoing, let's say, I mean, if you're so sick, and maybe your liver's not working properly, your kidneys aren't working? I mean, how are you going to convert these vitamin D metabolites into this steroid hormone? Right? So, do you think it's important to give someone that, you know, more downstream, like an active form versus vitamin D3, for example?

Dr. Seheult: Exactly. And so that's the question is whether, because it takes some time for the vitamin D to be metabolized in the liver. I've seen some people say up to, you know, seven days. It probably is a little bit less than that. But when you're giving vitamin D in the acute situation, it doesn't really matter if you're just supplementing over a long period of time and you're hoping to prevent yourself from having bad outcome with COVID-19. But if you've already got COVID-19, what they may be saying here is that supplementing not with vitamin D, the product prior to liver metabolism, but in fact, calcifediol 25-hydroxyvitamin D, might be a more efficacious intervention. And that's what they did in this study.

Rhonda: And you know another thing this sort of brings to my mind, you'd mentioned the pre-pandemic randomized controlled trials looking at the role of vitamin D supplementation in preventing respiratory tract infections. I believe it was Martineau that was the senior author on that.

Dr. Seheult: Yes.

Rhonda: And what was so interesting about those meta-analyses was that they found weekly doses, daily doses, worked, but monthly doses did not in terms of protecting against key respiratory tract infections. And to me, it's like we can't learn from the past. Like, there's something wrong, you know. So when you're designing a clinical trial, you need to be familiar with literature and see, oh, there's these meta-analyses showing that monthly doses don't work. Maybe we shouldn't design the trial that way. Maybe we shouldn't just do one large dose which I think I've seen a preprint floating around for COVID-19 where there was one large dose and there was no effect.

Dr. Seheult: Yes. Yeah. You're referring to the Brazilian study where they gave 200,000 international units at the very beginning.

Rhonda: Yes, I don't believe it's peer-reviewed yet. Am I correct for saying that?

Dr. Seheult: You're correct. At least I haven't seen it yet.

Rhonda: Okay.

Dr. Seheult: This study though, this Spanish study where they gave something called calcifediol which is, again, 25-hydroxy. This is not an over the counter medication. This is a prescription-only. It's usually prescribed by nephrologists in patients with renal disease that have very high, you know, parathyroid hormone levels. And they gave it on day one, they gave it on day, I believe three, and then again at day seven. And what they found was in the calcifediol group, there was only 2% that went to the intensive care unit, whereas in the placebo group, 50% of those went to the intensive care units. That's a very, very marked number. Again, there was, I think, the British recently got together and looked at all of the data. And you may have known they made a recommendation that there still was not enough evidence to cause supplementation to prevent COVID-19. Interestingly, they discounted this Spanish study because they felt that the randomization was not good enough. But there's been some mathematicians that have looked at this study and said that it would be impossible for that randomization to fully describe what happened in this study. In other words, they believe that there was an effect of calcifediol in the study.

Rhonda: And it seems very likely, if we have, as you mentioned, meta-analyses of many, many, many, you know, over 25, different randomized controlled trials, showing vitamin D supplementation prevents respiratory tract infections, you know, in people that are vitamin D deficient between 50% to 70%, and even still had an effect and people that had normal, sufficient levels of vitamin D, maybe we can talk about what those are. But what would make, I mean, of course, you know, viruses are different, but I mean, a respiratory tract infection, you know, to some degree, there's got to be some common denominators, right? I mean, so, to me, it would seem, you know, logical that something like vitamin D, where, in the United States, you know, 70% of the U.S. population is categorized as vitamin D insufficient, which defined by the endocrine society is less than 30 nanograms per milliliter. And 30% of the U.S. population is what is called vitamin D deficient, so they have less than 20 nanograms per milliliter of blood levels of 25-hydroxyvitamin D, which is the major, you know, circulating metabolite of vitamin D.

So, I mean, you know, the question becomes, and maybe we can talk a little bit about vitamin D supplementation and safety. But is it really, I mean, you don't have to make a bold statement that it's going to prevent COVID-19. I mean, absolutely, we should be following the CDC guidelines on social distancing, on wearing masks, on washing our hands. And also, you know, as soon as they become available vaccinations, but in addition to following the CDC guidelines, it might be prudent to say, it's probably important to become vitamin D sufficient. In other words, if we already have data that, you know, 70% of the U.S. population, you know, has insufficient levels of vitamin D, then clearly, people need to take a vitamin D supplement, and, you know, I think or maybe need to get their levels measured. I mean, the best way is to go to a doctor, get your vitamin D levels measured, you know, and then see what those are, and then take a supplement to bring them up.

And the reason I say that is because, as you mentioned, you know, we make vitamin D in our skin. But depending on where you live, you know, you said UVB radiation is how we make it in the skin, depending on where you live, many parts of the year, UVB radiation is not even hitting the atmosphere. Right? So.

Dr. Seheult: Exactly. And so if you live above the 35th parallel, which, if you're in the United States, that would be the southern border of Tennessee or just a few miles north of us here in Southern California. You know, most of the country lives above the 35th parallel, which means that you're not going to get enough UVB radiation in the winter months to supplement or to keep elevated your vitamin D levels sufficiently. And so you've got to take supplementation.

Rhonda: And sunscreen blocks UVB radiation and most people are wearing sunscreen. Most people are indoors now. You know, we're on our computers, we're not in agrarian society like we used to be. You know, people aren't out in the sun all the time. People are inside. I mean, if you look at, you know, enhanced data over the past couple of decades, you see vitamin D levels are steadily just going down, down, down, down. And I think that's because most people are now spending more time indoors. Also, as you mentioned, people like African Americans, people with darker skin have much lower levels of vitamin D. In fact, African Americans, the most recent enhanced data that was published, they're 30 times more likely to be vitamin D deficient than Caucasians.

And the reason for that is because melanin is a natural sunscreen, I mean, it protects you from the burning rays of the sun. So if you live in, you know, Australia or closer to the equator, you know, Somalia, for example. That's great because you're getting a lot of UVB exposure year round. But when you take a person and they migrate, say they move from Africa to New York City to Chicago, well, it becomes a problem because you're much further from the equator. And now you've got this natural sunscreen that helps you, you know, protect you from the burning rays of the sun. And now you're living in a place where you're not getting as much sun. And so there was a study that came out of the University of Chicago A few years ago that found African Americans in Chicago have to stay in the sun six times as long as a Caucasian to make the same amount of vitamin D in the skin.

Dr. Seheult: Yeah, I believe it. And you know, the other thing people say, Well, if that's the case, then how come people are getting COVID-19 in sunny places, in hot places? For instance, if you remember back in the early part of summer, there was a huge epidemic in Arizona, and also in Florida, in Texas. Well, I mean, if you think about it, yeah, there's a lot of sun. But if you're inside, you're not going to get exposed to the sun.

Rhonda: Right. You think people in Arizona are going out in the sun in the summer, dude, it's like living in winter in summer. I lived in Tennessee for six years, and I'm from Southern California. So summers, I was used to spending on the beach. When I went to graduate school summers became like winter because I did not want to be outside. It was like 95 degrees, humidity, hot. I mean, so I spent way more time inside in the summer in Tennessee than I did in the winter in [Southern California.

Dr. Seheult: Right. And here's the other thing, too is that UVB barely gets through the atmosphere down to us, and it does hit us when we're outside. And the sun's got to be pretty high up in the sky. You go behind a piece of glass, there's almost no UVB at all, the only thing that's coming through is UVA, which is, you know, nasty ultraviolet radiation that makes your furniture, you know, fade, your carpet fade, and it gives you aging wrinkles on your skin. So if you think that you're sitting by the window is going to give you some nice vitamin D, think again.

Rhonda: And clothing, right? Clothing also blocks it, you know. So, you know, the question becomes why vitamin D insufficiency and deficiency is so prevalent in our country. And also, you know, in places like the UK where you said, you know, they're not finding enough evidence to recommend vitamin D to prevent COVID. Well, maybe that's a strong statement, and you need more randomized control trials to make an extraordinary claim like that. But you can still make a claim that it's probably in your best health interest to maintain good levels of vitamin D. And that because we know vitamin D deficiency is so prevalent that it's probably best to get a vitamin D test and measure your levels and take a vitamin D supplement.

Dr. Seheult: Exactly. And the thing that's a little confusing too, is that a lot of these levels that we've come up with are based on the endocrinological function of vitamin D with bone metabolism. We don't know if that's the value that we need for immunological functioning or COVID. But we do have some associative studies that seem to show at least in those studies that we talked about earlier where looked at 191,000 people that SARS-CoV-2 rates started to go up once levels dropped below 50. So that's an interesting number.

Rhonda: That's interesting. Back in 2013, there was a meta-analysis published, I don't know the author's name, but the studies dated back from the 1960s to the 2013. And it was looking at all-cause mortality in association with vitamin D blood levels. And it was found that you know, levels, somewhere between 40 to 60, or 70, like was the lowest all-cause mortality. Like, there was this sweet spot. You know, and of course, it's one of those things where, you know, associative studies, there's always the problems that people try to, you know, correct for confounding factors. But the idea is to look.

And this is what you've done such a fantastic job, you know, with your scholarly work at MedCram videos is looking at the whole body of evidence. The observational data, the mechanistic data, the case studies, and you know, if there are randomized controlled trials, the animal studies as well, you know, because that helps give us some insight on mechanism, and of course, you can't translate an animal study to humans, but if you take the whole body of data, right, everything together, then you can begin to tell a story as well. So, in terms of supplementation, though, you know, the upper tolerable intake that's been set by the Institute of Medicine has been 4000 IUs a day. And, you know, vitamin D is a fat-soluble vitamin, what about toxicity? [inaudible 00:50:30]

Dr. Seheult: Toxicity, there was a statement that I read that said that vitamin D is probably the least toxic fat-soluble vitamin. So there was a study where these Polish scientists looked at the Mayo Clinic's database, and they looked at 20,000 people. And we've talked about this in our in their video that we recently published, one person had hypercalcemia, out of those 20,000. And they had ranges, people supplementing anywhere from 0 to 55,000 units a day. And really just one person. And that person's vitamin D level, if I recall correctly, was up in the 200, 300 range. That's nanograms per milliliter. And that's [inaudible 00:51:14]

Rhonda: That's hard to do. Wow.

Dr. Seheult: Yeah, it's massive.

Rhonda: Yeah, I remember reading a study, and I'm sure you've seen this one where there was the long-term supplementation with 10,000 IUs a day and it was really no toxic effect. And that was, I forgot how long term it was. But...

Dr. Seheult: Yeah. The other thing that I've seen is that, you know, it's not a linear-response curve. So as you go up in supplementation, it's not like your nanograms per milliliter are going to go up linearly. What we notice actually, is that the first 1000 units that you supplement causes an increase of about 4.8 to 5 nanograms per milliliter. Whereas, when you get up to about 15,000, 20,000, 30,000 that each additional 1000 goes up by about a 10th of that. So it's a nonlinear relationship. It's exponential, but the reverse of exponential. As you go up higher and higher, the increment becomes less and less. It's almost like you're saturating receptors, if you will, it's probably not the case but that's what it seems to be like.

Rhonda: Do you measure vitamin D levels in your patients? Or is that something that's common in the hospitals you work in?

Dr. Seheult: Yes, so we have been doing it. It's problematic if you don't have a lab that does it quickly. So you get the result back in two to three days, which you kind of want to know that upfront. So we will supplement and then wait for those levels to come back. But most of them are low. And there's been studies on this too that have showed that most of these patients, specifically with COVID, are coming back with low vitamin D levels. What they did in one study, they wanted to see whether or not it was the symptoms that were causing the low vitamin D. So they took these patients and they said, okay, anybody that has X, Y, and Z symptoms we're going to look at. And then they figured out which ones were COVID and which ones were COVID-negative. Well, the ones that were positive for COVID and had the same symptoms had lower vitamin D levels than those people that had similar symptoms but were negative for COVID. So it's not just the symptoms of COVID that's causing the low vitamin D levels. It's something about COVID itself that seems to be doing it.

Rhonda: Wow. So in the ICU where you're treating patients, you guys are giving patients vitamin D?

Dr. Seheult: Oh, yeah.

Rhonda: That's great. Is that something that's being spread amongst hospitals? Do you know?

Dr. Seheult: I hope so. I'll tell you what we're doing based on the SHADE study. This is another randomized controlled trial that came out of India. And it showed basically, when they supplemented patients in the hospital with 60,000 units a day for 7 days, that there was an improvement by day 21 in the number of COVID-negative patients on testing. Now, that's probably not the best surrogate because you know, PCR picks up any little detectable fragment of RNA and gives you a positivity. It's a surrogate. But it was like 60% versus 20%, at week 3, were negative by just supplementing with vitamin D.

The other thing that they looked at was fibrinogen, which was a marker of inflammation that was significantly lower as well. So based on that study, we don't have 60,000 units typically here in the hospital, we have 50,000. So I figured the 50 versus 60 is going to be very small difference. And so that's currently what I'm doing in my patients and I'm recommending to my colleagues to do the same. We haven't seen any toxicity. There was no toxicity in that randomized controlled trial either.

Rhonda: So you're kind of just assuming right off the bat that most likely patients are low in vitamin D. I mean, which I think is a reasonable assumption considering NHANES data showing that 70% of the U.S. population's insufficient...

Dr. Seheult: Correct. And if they're not, it's probably not going to hurt them if we do it for just seven days.

Rhonda: Right. Right. Well, I'm looking forward to more, you know, data on vitamin D in terms of randomized controlled trials. I only hope these randomized controlled trials are designed properly. And, you know, there's so many factors when it comes to something that's nutrition related or something that you know you can make from the sun. You know, it's not like a drug. When you do a randomized controlled trial with a drug, a pharmaceutical, you know, drug, people have zero levels of that in their body to start with. You know, you give them that drug or the placebo, and it's obviously, you know, they're going from zero to something. Whereas, with something like vitamin D, and also with nutrition in general, that you have to measure things at baseline, you have to quantify it. You know, you have to have something quantifiable. And I've seen randomized controlled trials, believe it or not with vitamin D where they don't measure vitamin D levels. They just give them the supplement. And it blows my mind that that can even get past peer review, or how do you design a trial that way? I mean, you know, it's adding to the confusion, in my opinion. So I'm hoping that because of the seriousness of this pandemic, that you know, people designing these trials are doing so carefully.

You know, like the fact that we know from previous data that one high monthly dose of vitamin D may not be enough and may not do the job, right. And as you mentioned, maybe that's because it doesn't bring their levels up because it's not happening in a linear way. Right?

Dr. Seheult: Right. So there was a great study that looked at that in France. You know, apparently, the practice was that every nursing home patient would get 80,000 international units of vitamin D every 3 months. And when COVID hit, these patients were being admitted to the hospital, they asked a very interesting question. It was kind of a quasi-randomized study. As they were being admitted, they would ask the question, so how long has it been since you got your 80,000 international units of vitamin D? And when they sorted them to those that had gotten it within the last 30 days to those that had gotten it past 30 days, there was a clinically significant difference between those that had gotten it recently and those that had gotten it more than a month out.

Rhonda: Wow. And do you ever have people just tell you, well just go out in the sun more or, you know, eat some food that's high in vitamin D? I mean, what do you say to people that might say such a thing?

Dr. Seheult: Well, you don't know if it's working. So I was taking too, and I mean, I'm not living at the North Pole here, I'm in Southern California like you, and I was taking 2000 units a day. And I wanted to get up above 50, because of some of that data that I showed. So when my levels were tested...so, me, I work outside. I don't like working inside a lot. So I go outside too. I do gardening, I, you know, like working around the garden and stuff. That, plus 2000 units in the middle of summer and I was at 48. So that tells you that you may have to work a little bit harder than you think at getting your vitamin D levels up.

Rhonda: Yeah. And I think again, depending on how much melanin you have in your skin, depending on your age, you know, you're anywhere between two or four times less likely to make as much as you were when you were younger. You know, depending on all that stuff. Are you wearing sunscreen, where you live, what time of year it is all those factors. I mean, so just to say go out in the sun more. You know like, what if you're an African American living in Chicago and it's November, what are you going to do?

Dr. Seheult: Right. And in the middle of winter, the sun's pretty low. So it's probably there's not a lot of UVB probably that's coming through, ultraviolet B radiation. It's got to go through a lot more atmosphere to hit you when the sun is that low in the sky.

Rhonda: Right, exactly. And the other thing is people think you can just get it from your diet. And this is another sort of factor that I really would like to address. Because, you know, the reality is, first of all, the food that's been fortified with vitamin D the most is milk. And unfortunately, you know, there's a lot of people that are lactose intolerant. And 75% of African Americans are lactose intolerant. And there have been studies that have shown that, for example, African American women that have a single nucleotide polymorphism in the lactase gene that allows them to, you know, tolerate lactose, they have much higher levels of vitamin D because they're drinking milk.

So fatty fish, salmon, you know, like four ounces have close to 400 IUs maybe. But you know, people aren't eating fish in the United States. They're not. I mean, maybe in Norway or Japan, you know. And, of course, Omega 3, I mean, is also very important. And I also think it's very important to get enough Omega 3, particularly now because of the role of Omega 3 in inflammation. And, you know, there's been a meta-analysis showing that supplementation in hospitals, like, prevents ICU stay, or lowers ICU stay, prevents mortality, like, by up to 60%. I think they were this was parenteral. How they're giving it?

Dr. Seheult: IV?

Rhonda: Yeah, they're giving it through the IV. As well as there's been other studies showing it helps prevent, as I mentioned to you, it was venous thrombosis. But my point is vitamin G's in the fish, most people aren't eating fish. So a supplement, it's really the easiest low hanging fruit. I mean, as you mentioned, it's really hard to get people to change their lifestyle. You know, we know for example that people with metabolic syndrome with type 2 diabetes, that are obese, high blood pressure have much, you know, higher risk of a severe COVID-19 outcome, right? But to get someone to completely reverse your type 2 diabetes is a lot of work. You know, we know things that can do it in diet, you know, cut out the refined sugars and exercise and there are things that can reverse type 2 diabetes. But that takes, you know, motivation, you have to want to do that. It takes a lot of effort. And it takes some time.

Whereas, you know, I think most people can take a vitamin D supplement. It's one of the cheapest, I mean, it's literally like a penny a pill. It's one of the most affordable supplements ever. And, in my opinion, one of the most important, you know, because of the widespread deficiency, because of the way our society is now where we have migrated to other places, you know, where we're indoors much of the time, and it's just a very different world that we live in, you know, compared to, you know, 1000 years ago, you know, or maybe that's too far back, but you get my point. So.

Dr. Seheult: Yeah. There's so many things that are involved with it. And I'm of the opinion too, just because of some of my sleep background as well, that I do believe that there is a benefit from actually getting out into the sun. So I don't say that going out to the sun is the only way you can do it or should be the only way. I believe in supplementation, I supplement as well. But there is something to be said for getting outside into the fresh air and sunlight and allowing that light to hit the back of your retina. It has wonderful effects in terms of getting your circadian rhythm on sync. So yeah, I think one of the things that we need to learn about is it's not an or, it's an and, it's an all of the above type of thing. And just because you supplement doesn't mean you shouldn't go in the sun, just because you go in the sun doesn't mean you shouldn't supplement.

Rhonda: Oh, I 100% agree. Thank you for bringing the circadian rhythm up. I mean, it's one of the things that I've noticed having early bright light exposure and setting my circadian clock is one of the most important things that has helped me sleep better at night because my clock is set early. And you know, my body starts to produce melatonin under reasonable time as long as I don't have bright lights or blue light on in my house all night. But so you also are in the sleep medicine. Do you run a sleep clinic or you're involved in the sleep clinic?

Dr. Seheult: Yeah, I have a sleep clinic and I also I'm a medical director of a sleep lab as well.

Rhonda: So what are some of the things... I mean, sleep is also very important for immune function, and what are some of the things that you're you're helping your patients do with in terms of sleeping better and helping...?

Dr. Seheult: Yeah, so sleep is a very complicated topic because everybody may have problems sleeping, but it's for a myriad of different reasons. It could be medical reasons, it could be just, you know, maladaptive behaviors. But the point I want to make is that sleep and the immune system are intimately connected. We know for a fact that people who get more sleep before they get an immunization have a better immune response with higher antibody titers to, for instance, the flu vaccine. We know that when people are challenged with a virus, they actually did this study where they put rhinovirus into subjects' noses on purpose. You know, living on a college campus people will do any study for very little money, so it's easy to get those kind of students.

But this is what they did. They subjected them to rhinovirus, and they put it into their nose, and they waited to see how many people came down with the common cold. And when they will look back and saw what their sleep habits were, it was a five to seven-fold difference. If you looked at those people that got seven or more hours of sleep per night versus those that got less, and whether or not they had a good sleep efficiency. So sleep efficiency is how many hours you're actually sleeping, divided by the number of hours that you're in bed. And so you have good sleep efficiency, you've got good hours of sleep, so good quality, good quantity, your risk of getting any kind of virus, like rhinovirus, adenovirus, those sorts of things, is cut by five to seven-fold.

That's a massive number when you consider what we're trying to do to reduce the incidence of COVID-19 right now with vaccinations and things of that nature. That just a good night's sleep can have that much of an impact. It's not a cure, but it's certainly somewhere to start.

Rhonda: That's a very robust difference. I mean, I know I probably speak for many other people. I know from personal experience, absolutely 100% If I get a bad night's sleep and I've been exposed to a virus, it'll take me down, aou know. And this seems very relevant right now with vaccinations that, you know, sleep plays such an important role in the antibody titer and how many antibodies you're producing. But even in a more general sense, I mean, you know, the fact that that sleep is so important for just immune function.

So do we know that some of the mechanisms? I mean [inaudible 01:06:41]

Dr. Seheult: So one of the mechanisms that's involved has to do with the stickiness with how those immune cells stick to each other. And that's regulated by, you would probably not be surprised, by G proteins and cyclic AMP and second messenger systems. And what we notice is that when you sleep more, your cortisol levels are lower. And cortisol, of course, is cortisol and epinephrine, and all of these other beta-adrenergic systems affect the G protein. Stimulate the G protein causes increasing cyclic AMP in these immune cells. And they make those proteins like the major histocompatibility complex 1 and 11, less sticky, and so it impairs your immune system when you have higher levels of cortisol, higher levels of stress.

Rhonda: And really interesting study, since you just mentioned the light exposure and helping with sleep. I saw there was one study where people were exposed to 10,000 lux of light, and I believe it was for, like, a significant period, like 6 hours. You know, where, like, it's a weekend, you're just you're outside at the beach or something you're, you know, outdoors. And it lowered their cortisol levels by 25%, I think, during the phase where it's not supposed to be high or something. Because cortisol obviously wakes you up. I mean, your cortisol is regulated in a circadian manner and, you know, it's important for waking you up. But the problem is, is that people are having higher cortisol from, you know, psychological stress, you know, from... What are some other things that raise people's cortisol?

Dr. Seheult: Yeah. Oh, so other things like sleep apnea? That's a big one.

Rhonda: Sleep apnea. Basically just a lack of sleep.

Dr. Seheult: Yes, sleep apnea which is, you know, tied to obesity. So.

Rhonda: What are some of the main practices that you tell your patients? Like, what have you found some of the most robust practices for improving sleep? Like even the lowest hanging fruit too. So things that are the lowest hanging fruit and things that are more robust.

Dr. Seheult: So the most important time of sleep is the sleep that you get at the beginning of the night. There's really two types of sleep that are the best at making you feel healthy. And they are slow-wave sleep, which is right at the beginning of the night. In fact, this is the type of sleep that is associated with growth hormone secretion, especially in children. If there was ever the fountain of youth, this would be it. Growth hormone makes you feel younger, makes you look younger. In fact, we were giving growth hormone injections many years ago until we realized that it can cause problems because of where they were getting it from. But that's another story. But growth hormone and slow-wave sleep at the beginning of the night is very, very important. Yeah, REM sleep is toward the end of the night. That's when you dream, and that's also a good part of sleep as well, but nothing beats slow-wave sleep with these large delta waves if you were to look at this on a polysomnography. So the most important time to sleep is really that time before midnight. And there's a lot of research in the last four or five years that has been going into this holy grail of slow-wave sleep and what happens at the beginning of the night.

So with that being said, think about what's going on in the United States right now. Okay? And over the last 50 years. We've essentially turned night into day, right? If you've ever seen those satellite pictures of what the United States looks like at night, it's lit up on both coasts. And if you look at our area here in Southern California, it's very bright. It's probably one of the brightest in the nation, probably only second to New York, and the DC, New York, you know, area. But here's what's happening, people are coming home later, they're, you know, eating later, staying up later, they've got a lot of work to do. And they're putting their faces in front of screens, which is emitting light.

Now, what does that light do at that hour, what that light does at that hour in just about everybody is it shifts the circadian rhythm and delays it. So whereas you would feel sleepy normally at let's say, 9 or 10 at night, you're now going to start to feel sleepy at 11 or 12 at night. And so you don't go to bed until later. So you would normally be waking up 7, 8, 9 hours later because that's how much sleep you're really supposed to get. But unfortunately, that goes into 8,9 in the morning, and you're supposed to be already at work at your desk, or you know, now with COVID, you're at home working somewhere. Or because of the fact that there's so much density, you've got to get up at 4 in the morning, 5 in the morning to get in your car to do your two-hour commutes to beat the traffic to get at your desk.

And so what we've done, essentially, over the last 50 years, is we have sandwiched the amount of available hours that we have for sleep. And what's been cut off is that first part of the night before 12 where the best, most restful part of the night is going to happen. You know, it's been said many times, and from people hundreds of years ago, I don't know how they knew this, but over 100 years ago, they said that that two hours of sleep before midnight is worth more than four hours of sleep after midnight. And the science is actually showing that to be true. It's amazing.

Rhonda: So the two things I found to be most effective, or maybe three, in making sure that I am not a night owl. I mean, there are genes that do control this. And there are some people that, genetically, they're night owls. And there are some genes that actually allow people to get less sleep, but those are sort of a lot more rare, right. But what I have found for me is bright light exposure. So you wake up in the morning and what most people do, they want coffee because they're sleepy and they didn't get enough sleep. And so they're trying to counter that with some caffeine, right? Maybe they should step outside for 30 minutes, maybe drink your coffee outside, go for a walk, you know, if it's cold out, you know, drink your hot coffee and, you know, do some stretches or yoga or something. But go outside and set that clock so that your circadian rhythm sets earlier so that you start making melatonin earlier.

However, in order to make melatonin earlier, previously around our house, we had these Philips Hue lights, which basically, you can program them to turn red at a certain time. So red would be something that isn't as disruptive to melatonin production. Because as you know, blue light is what disrupts it. And so you can program them to like let's say come on at 5 p.m. And so now all the lights in your house are red rather than bright light. Now I have dimmers. And dimmers also really help because I just dim them so low that, you know, at night it's like, you know, any light that's on our house is very, very, very dim.

And the other thing is that well now, I try not to like work and get on my laptop and... Anything that gives me emotional stimulation. Whether or not it's bad or like don't look at social media like I don't want to see a bad comment or like, you know, anything like that, that'll get me upset that'll completely throw off my sleep. But there are apps that you can put on your computers and phones that like blackout some of the blue light or you can wear orange glasses. I personally find that even watching TV that'll stimulate me and so that you know, I actually prefer to just chill out, you know, and maybe read a book, or you just kind of decompress. But avoiding blue light at night and getting the bright light exposure I think those are the really main things that have gotten to me. You know, I go to bed, I'm like in bed and asleep by 9:30.

Dr. Seheult: Yeah, that is. You asked me the question, what's the low hanging fruit? And you just answered it. That's exactly what I would recommend. And that's what I do recommend.

Now, from there, people have different problems. People have sleep fragmentation where they wake up a lot. Some people can't fall asleep, some people can't stay asleep. We could come back and do another two hours on recommendations for each one of those things. And each one's an individual. So it's hard to say but the kinds of sleep hygiene stuff that we've just talked about can go a long way in getting you started on finding your fitness, basically.

Rhonda: Yeah. Yeah, there's other things. Exercise. Some people think the sauna, which, sauna is something that you've recently developed a passion for. So you tell me. It's something I've been passionate about for many years and public-speaking about. And you've dove into a little bit about the effects of heat stress in terms of sauna use on the immune system and lung function, respiratory tract infections, which is also very relevant now.

Dr. Seheult: Yes, exactly. So vitamin D gets me excited, talking about sleep gets me excited, but nothing gets me more excited than talking about this. This is really amazing stuff. Because I have a feeling that it could be helpful in COVID-19. It makes plausible sense. Let me tell you the evidence for that just sort of offhand. Okay.

So I said at the beginning that you've got to look at COVID-19 as a timing issue. Early on, in the disease we've got good evidence now, from immunologists, that SARS-CoV-1, SARS-CoV-2, and MERS, all three of those, they kind of act the same way in that early on in the disease, they suppress the innate immune system. So there's two parts to your immune system. There's the innate immune system that's sort of the garbage collector that goes around looking for stuff that shouldn't be there and eating it up. What are the tools of that innate immune system? Fever is a big tool of that innate immune system. Interferon, the substance called interferon, there's gamma-interferon, beta-interferon, and alpha-interferon, all of these things are the tools of that innate immune system. The other part of the immune system is the adaptive immune system, that's B cells, T cells. That's what we're using with the vaccination.

What I'm talking about is the innate immune system. And early on, this virus suppresses the body's ability to mount that response. The thing about the innate immune system is it's very robust in children. But as you get older, its efficacy diminishes with time. So that's why we see fevers all the time in pediatric populations. They get a virus, they get a fever. But we're not seeing the fever so much in the adult population, and certainly not as much as we would expect to see in SARS-CoV-2.

Now, that being said, as the virus, using various techniques, proteins, things that it does, as it suppresses that immune system, you get this low-level of viral infection that goes on for days. And then finally, the adaptive immune system kicks in and you get this cytokine explosion that ends people up in the hospital with pneumonia. So again, it's a timing issue. The question is in COVID-19, do you want to suppress the immune system or do you want to elevate the immune system? And the answer is yes. Because you want to enhance the immune system at the beginning so that it gets rid of the virus. But notice that all the things that work late, like steroids suppress the immune system. So you got to be very careful about which phase you're looking at.

Okay, so what they've done, there's a couple of papers that were published in Science about a month or two ago. They could explain 14% of all of the severe cases in their cohort, based on two findings. One was a bunch of genetic mutations that basically left the subjects hamstrung in terms of secreting and producing interferon. So interferon production is a complicated system, there's many genes involved with it. And in many points along that pathway, there were mutations that basically caused the interferon secretion levels to be nil. All of those mutations were found only in the severe COVID-19 patients. Okay? Did not find any of these in the mild patience. So again, there is some causation there, like you were talking about before with the SNPs in vitamin D.

The other one that made up about 10% was older patients that had developed antibodies to interferon. So essentially, their interferon levels, even though they're being produced, they were being inactivated. All of these patients that had antibodies against SARS, or against interferon were in the severe, non in the mild to moderate group.

So what they determined was, and other studies have borne this out, that in order to predict a mild to moderate course of the disease, you have to have an adequate interferon response early on in the course. And you wanted to have that to lead to a mild to moderate. If you did not have a good interferon response early on, that would lead to severe disease in almost all of those cases.

With that in mind, what I started to do was look at a number of things. Number one, looking at heat. So there was a number of studies, actually, that have been produced, some at the University of Toronto, some also in other centers as well, that showed that if you take human beings and heat them up in a hot water bath, 39 degrees centigrade, the purpose of this is not to kill the virus, the purpose of this is to enhance the immunity. And what they found was that they were able to, independently of these potential mutations that fever or temperature itself was able to cause a secretion in elevation in interferon, tumor necrosis factor, those sorts of things.

There's one study that they did, where they took subjects, put them in hot water baths at various degrees, so 38.5, 39, 39.5, etc. And when they took the monocytes out of their body and put them on the petri dish and exposed it at various temperatures to LPs, which is lipopolysaccharide, which is a universal activator of the immune system, that interferon levels were 10 times higher once they got up to about 39 degrees centigrade, or celsius, which is around where you start to have a fever. So lots of plausibility there.

Okay. So now what we did is I looked back in history and I thought, well, maybe if we started to heat up their bodies, maybe there could be some immunity. Think again about the fact that 80% of all symptomatic COVID-19 patients, 80% never need to go to the hospital. Why? Because their innate immune system does the job. It takes care of the virus. Twenty percent end up going to the hospital. If we could somehow increase that 80% to 85% ,90%, that would have a huge impact on the number of people that are seeking medical attention right now in the hospitals.

So I decided to look back. So there was the flu epidemic of 1918 and 181 in the United States. Now, remember, this is before oxygen. This is before randomized placebo-controlled trials. This is before the discovery of penicillin even. There was sort of two thoughts about how to treat this pandemic or this epidemic of the flu. And as these soldiers were coming back from World War 1 and bringing the flu with them, there was a lot of Army hospitals that were treating these patients. And the thought was that it was the symptoms of the flu that was killing these patients. Well, we knew how to treat fever by giving aspirin. Aspirin had just been discovered in 1899 by the German company Bayer. And so a lot of Bayer aspirin was being used to get rid of fever, to get rid of symptoms. And we knew exactly how that went in the army camps. That was the one way of treating it. The other way of treating it was by doing what we've just been talking about, which was rest, sunlight, fresh air, and hydrotherapy. And this was the type of pattern that was being used in a number of sanitariums in the northeast of the United States.

Well, I stumbled across an article that was published in 1919 By Dr. Ruble [SP]. Now Dr. Ruble was the medical director at the Boston New England sanitarium. And what he wrote was he said, you know, this epidemic has given us a fine opportunity to see if there is a difference in terms of our therapies. He called these rational therapies. And so that's exactly what he set out to do.

And what he did was he collected the data from all of the 10 sanitariums that he knew about in the northeast of the United States, and compared them to what was going on in the sanitariums or in the army hospitals at the time. So what he did was basically say, which one is better? Is it the treatment in the army hospitals with the aspirin where we're trying to kill the fever? Or is it in the sanitariums where we're trying to basically increase the body temperature with hot towels and hot foot baths and things of that nature? And just a point, the things that they were doing in the sanitariums. There's nothing there that we couldn't do in our own homes today. I mean, we've got hot water, we've got all of these sorts of things.

So he did that. And what he found was a couple of things. Number one, he found that there was two phases. There was the early phase and the late phase, just like we have with COVID. He found the same thing with the flu. And the thing that demarcated that was exactly what we have with the COVID-19 and that is pneumonia. So the practice in the sanitarium was if anybody came down with any kind of symptoms, period, there's no need to test. You just immediately start hydrotherapy, you immediately start sunlight, you immediately start fresh air, and bed rest. That was the key for the sanitariums.

When they did that, and this was a number of about 446 subjects, only 2% of those subjects went on to develop pneumonia. Only 2%. He was able to get the data from the army hospitals. And in the army hospitals, about 20% of the camp came down with the flu. How many of those patients with the flu went on to develop pneumonia when they got aspirin, and they got all of these other things? Sixteen percent. So eight times the number of people in these army hospitals had pneumonia.

Now, when you looked at pneumonia in both the army hospitals and the sanitariums, the mortality from there was about 40% to 50%, in both. So it didn't matter. Once you had pneumonia, the damage had already been done. And so when you look at the infection fatality rate in the sanitariums, it was about 1.1%, whereas, the infection fatality rate in the army camps was about 6.4%. So it was a fraction of that.

So obviously, this is a different time. This is a different practice. This is a different disease. But it's the same immune system. And the very fact that hydrotherapy and heat can cause potentially an increase of the very thing that's lacking that we're seeing early on in the COVID-19 course gives me pause that there is biological plausibility that hydrotherapy, early on, while you're supposed to be sitting home and waiting for you to get sick enough to go to the hospital may impact and change the course of the disease so that you don't have to go to the hospital.

The reason why I find this particularly attractive is because there's no company that has to make hydrotherapy. There's no rationing of hydrotherapy. You don't have to leave your home for hydrotherapy. You practicing hydrotherapy doesn't take away the ability from somebody else to do that. All of those things are the same problems though that you have with ivermectin or hydroxy, or any other medication that might have to be produced and be distributed. This is something that everybody can do. And it's also got very, very low risk.

So I, I think, and actually, I am working currently with an institution up in Northern California called Del Mar that is looking into this. And we have actually done a pilot project with students on the campus to do hydrotherapy to see if it will... We're measuring markers, we're measuring inflammatory, it is not a randomized controlled trial in any sense. But we're trying to get more data to see if this is a plausible way of dealing with this. And, of course, this would not be affected by the viral mutations or anything like that. It's a way of teaching the immune system or revving up or enhancing the immune system to deal with an infection that is suppressing the innate immune system.

So I've said a lot there. But, you know, ask away, see what you think.

Rhonda: That is a really phenomenal, scholarly work that you did there, Roger, diving deep into history. And that is just so informative. And I really enjoyed listening to all of that research that you that you've dug into. Fascinating. I do have a few questions for you. And I hope I don't forget them all, because there's quite a few that lined up.

First of all, with the interferon response that occurs when you elevate the core body temperature, whether that's through a hot bath, or a sauna, or steam or steam shower, or perhaps even hot towels, you were mentioning. How long does that increased interferon response last? Is that something, for example, that's 24 hours? Like you can still measure, or is it just very, very acute, or is it even known?

Dr. Seheult: I don't know if it's known. I do know that in those sanitariums it's very labor-intensive. It's actually the reason why this went out of favor. I mean, you can imagine that here you have this practice of doing hydrotherapy, which is very labor-intensive. And then you have the discovery of penicillin in 1928 and you can just give a tablet.

So because of its labor intensity, it was generally done maybe once a day. And so if it lasted 24 hours, then that was probably enough. The protocol that we're doing right now where we're testing it out is maybe two or three times a week, but it's it is very labor-intensive. We don't know how long it would last.

Rhonda: In your protocol that you're doing, are you giving your students hot baths, are they taking a hot bath, and if so, how hot, how long, and how much of their body is submerged under the water?

Dr. Seheult: Okay, so this is a very good question. The protocols are based on the historical protocols that have been published. And you can actually find his book. It's called "Rational Hydrotherapy." It's written by John Harvey Kellogg. It's about 1000 pages long. It's a massive book. I think it's in Google Scholar. You've got to, sort of, find the book. But there's a number of resources that people are interested in. And if you were to talk to me about a year ago, I wouldn't have known anything about it. I've researched it. But the body of information that has kept this alive are really the physiotherapist or the physical therapists, we call them in the United States, because of hydrotherapy helping in physical ailments, muscles, things of that nature. And so they're the ones that have kept this information for a long time.

And so the protocol that I'm going to tell you is based on what they have seen and what they have done and used. And typically, what is this is you basically have the patient lie down on a surface. And there's various ways of doing it. But you can use towels that are wet, and you can heat them up either in a microwave or in a stove. But that's basically boiling hot water with a towel. And you basically sandwich that between other towels, you place it on their back, and you place it on their chest. So they're basically being sandwiched. They're the meat, and the bread is two very hot towels. And you also place a very cold towel on their head and on their neck. And what you're trying to do there is you're trying to heat up the body as much as you possibly can, and not heat up the thermostat, which is in the brain, which is going to sweat and try to get rid of that heat as much as possible. So what you have here is you've got peripheral vasodilation that occurs trying to give off the heat. But actually what's happening is it's picking up the heat, heating up the core body temperature, and you do this for about 20 minutes. Now, those towels will not remain hot for 20 minutes. So sometimes you have to recycle them and have more ready to go. So you heat them up, you cover them up. And if they're sweating, then you know that you're doing what you need to be doing.

At the end of this 20 minutes of heat, something we do that's kind of paradoxical and it's also probably the most uncomfortable portion of this treatment is you then basically put a very ice-cold towel and replace the hot with an ice-cold towel and you do friction rub. Basically, friction is the best way to explain it. This is something that's come along for 100 years, they've done this. When we look at the data and we try to see why they would do this, we believe that this seems to work because the cold causes vasoconstriction and it locks the heat in. So after you're done, it's not easy for the heat to dissipate through those vasodilated vasculature. But the other thing that it does is, just like we know when you take a cold shower, that vasoconstriction causes demargination of leukocytes, and that causes the amount of leukocytes in the solution if you will, or in the vasculature to go through, find the viral particles and report to their lymph nodes through that increased circulation. And that sort of jumpstarts the innate immune system in finding those epitopes and presenting them to the antigen-presenting cells. After that's done, the protocol is for them to lie down and to really not move for the next hour and to just completely rest.

And so this is what we're doing. And I don't believe any of the students, now this is a student population. So they're young. I wouldn't expect these patients to need to go to the hospital. And I don't believe that in any of our cohort they've progressed or gotten worse.

Rhonda: Do you measure their temperature? Is there a rectal thermometer in there somewhere?

Dr. Seheult: Yeah, they're not doing rectal thermometers. We are measuring temperature. We're also measuring a number of cytokines as well in that. And we've just finished the preliminary aspects so we haven't had a chance to look at the data as yet. But it'll be very interesting to see.

Rhonda: It's fascinating that you're adding the cold shock, and I don't know how much the friction plays a role, because, you know, in Finland, where saunas are ubiquitous, it's also very quite common to jump in a cold water, freezing, like the Baltic Sea or something. You know, a lot of people are jumping into the cold water after their sauna and they go back and forth as well.

Dr. Seheult: You know, it's funny you say that. How long has the human race been on this planet? We could debate that. But it's probably been at least 1000s and 1000s of years. And do we believe that we've only discovered immunity and what works in the last 100 years? I think not. I think a lot of learning has been passed down, generation to generation, and probably in multiple cultures. And one thing that's really, I found very interesting is no matter who I've talked to, and I've talked to a number of people that are interested in this, whether they are of Asian descent, whether they are of Middle Eastern descent, whether they are from South America, or as you mentioned, in Nordic countries, all of them seem to have this memory, whether it's their grandmother that did it, or whether they look back 100 years ago, they all seem to do the same thing. They come down with an illness, a virus, and they... For instance, in the Middle East, I was talking to someone from Iran, he said, "You know, my grandmother, when we got sick, they would put us in the hot sands. They would use whatever was hot around them, and they would use it to improve their current situation, whether it was a viral infection, or what have you. And I think there may be something there. And maybe we've forgotten what we needed to do. And what I'd like to say is this is that, you know, here we are in this pandemic, and we don't have all the medications to treat all these patients.

Instead of saying, you know what? You're just going to have to wait at home and wait for you to be sick enough to go to the hospital. That's kind of like turning back the clock 1000s of years. Why don't we just turn back the clock 100 years and see what we did 100 years ago when we didn't have these things and see if they work. I 100% believe that we need to do randomized controlled trials to really see whether they work. I want to see if they work.

But the question is, is in the meantime, while we're waiting for them to work, if there's something that has biological plausibility, and it has very little risk, you know, what's the risk of hydrotherapy? Well, number one, burning yourself, you have to be very careful that you don't burn yourself. And number two, if you've got a predilection for cardiac arrhythmias, or tachycardia, or atrial fibrillation, it's probably not a wise thing to be exposing yourself to temperature extremes. So barring that, I think this has got pretty low risk and may be beneficial.

Rhonda: So I 100% agree with you. And, you know, there have been quite a few studies looking at the health benefits of using the sauna, there have been a lot of observational studies from a friend of mine, Dr. Jari Laukkanen, he's an M.D., Ph.D. And he is the senior author on the paper that showed, I believe it was men and women in that study that used the sauna two to three times a week, had a 20% lower pneumonia risk than if they did four to seven times a week. It was maybe up to 40% lower or something like that. Where it's dose-dependent, and they had corrected for a whole host of factors, all types of different respiratory diseases, had corrected for asthma, lipid levels, I mean, just many different things. And so that was something that was quite surprising to me, you know, because I was so familiar with the literature on, you know, the benefits of using the sauna on cardiovascular health and how, you know, heat stress itself, it is elevating your core body temperature. In a way it's mimicking exercise, your heart rate elevates. They've done a side by side, head to head comparison on a stationary bicycle and comparing it to 20 minutes in a sauna.

And all the same physiological changes happen while you're exercising, your blood pressure actually goes up, your heart rate goes up, you sweat, your core body temperature elevates. While you're in the sauna, your blood pressure goes up while you're in there, your heart rate goes up, you're sweating, your core body temperature goes up, but then when you're done with the exercise, or you're done with the sauna, blood pressure goes down even lower than baseline. You know, your heart rate improves. And, you know, so it's very comparable to cardiovascular exercise. And there's many, many benefits in terms of, you know, chronic sauna use, and I think to some degree, hot baths, you know, and perhaps, you know, this hydrotherapy, I think that falls in that category where you're elevating your core body temperature, whether it's through a hot bath, or these you know, hot towels, or if it's in a steam room or you know, a sauna, which is what I have. You know, I try to do it four times a week. But it's fascinating that that could actually be helping my innate immune system.

And I think there's other studies that have shown effects as well my common cold.

Dr. Seheult: Yep, that's exactly right. I mean, not just on cardiovascular but also on immunity and also on, like, real-world cold. So they've done multiple studies on these and they've shown there to be a benefit in that. And so, because it's because it seems as though the benefit that we get from hydrotherapy or thermal hydrotherapy, however you want to call it seems to be the one part of the immune system that's crippled early on with this Coronavirus. There's biological plausibility again there that I think, Wow, this piece seems to fit. The only thing we're missing here is a randomized controlled trial. Boy, somebody should do that. I mean, that would be amazing.

[Dr. Patrick]:.Yeah, absolutely. Do you take hot baths at home? Is that something you're...

Dr. Seheult: Yeah. So I have a spa outside. Actually, believe it or not. I live at about a mile up here in Southern California. So we just got about six to eight feet of snow. I'm looking out the window right now because we've got about, well, it's melting right now, but it's about six to eight inches of snow.

And so, just the other day, we all went into our spa and heated that thing up to the max and got out and ran around in the snow, rolled around in the snow. And then we jumped back in. And it was invigorating. So I do that every day. My wife is also a internist. She works at the hospital. And so every day we've made it a point that when we come home from work and we go through our rigmarole where we, you know, basically disrobe in the garage and put the Coronavirus in this basket and that goes into that. We basically go directly to the spa. And hopefully, the chlorine and the hot water kills the Coronavirus. But even more importantly, hopefully, if we happen to be exposed that day, and we just don't know it yet, that treatment in the sauna or spa I should say, helps our innate immune system to find that virus and to kill that virus before it has a chance to do its dirty work.

Rhonda: Absolutely. My husband, he's been really big on getting in the jacuzzi and then hopping into the 56-degree pool. I'm having to adapt. Cold showers are a little easier for me, but they're not...I mean, although they're colder now, I was i was actually doing a lot of cold showers in the summer. So I've been doing that sauna. And the summertime, it's warmer, the cold shower is warmer, so it's not really as cold as it should be. So I'm trying to get into the cold a little bit more.

What are your thoughts on, you know, for example, like, people that are getting vaccines? You've gotten the mRNA vaccine.

Dr. Seheult: Yeah. I got the Pfizer vaccine, oh, probably a little over a week ago. And I didn't change what I was doing. I was still doing it. The way that the mRNA is delivered to the cells so that they can make the protein is in these very small little micelles or these bilipid layers that shouldn't have an effect. That shouldn't be immunogenic. So I don't think it should affect the efficacy of the vaccine.

Rhonda: Using the sauna or... Yeah. Can you talk a little bit about just briefly, I know we've been chatting a while, I promise to round it up, but mRNA vaccines are a new technology. I mean, they're not a new technology. They've definitely been around for a few years. But it's new to humans. You know, use in humans, basically.

Dr. Seheult: Yeah. So, if you think about mRNA vaccines, it's like an envelope with a message in it. And that message is going to tell the cell what kind of proteins to make. This is exactly what happens, by the way, when you get a viral infection. When you get Coronavirus or any other Coronavirus, or any other RNA virus that comes along is that virus fuses with your cell, whether it's in the cells in your nasal mucosa or anywhere else. And it basically tells those cells to make foreign proteins. And so, in that sense, this is no different. We're just doing it in a way that doesn't cause more viruses to be made. When you get infected with a virus, the virus tells the cells to make more of everything. Make more RNA, make more viral proteins, so your cell can make more virus. In this sense, the mRNA vaccine is only telling your cell to make a portion of the protein which we want the immune system to recognize so that if it ever comes around again, the immune system is ready to attack it and to prevent it from invading your body. So in that sense, this is, sort of, a dead-end virus that we're putting in. But it's not even that, it's not even a virus. It's just a portion of the mRNA.

So what about mRNA? mRNA is in the cytoplasm of the cell. It's not in the nucleus of the cell. And if you can imagine, you know, we had a professor from San Diego, Dr. Crotty, who, I love this analogy, it's like a post-it note, mRNAs are like post-it notes. They're here today, maybe a few days later, they're gone. You crumple it up and you throw it away. They are not like your marriage certificate or your social security card that you put away in a filing cabinet that you never take out. It's like the original. That's like your DNA. That's like in the nucleus. So that is not what an mRNA is. mRNA is like your post-it notes that you post in your room and they're here today and gone tomorrow.

So there's really not a danger that this mRNA is going to hang around. And even if it were to hang around, the purpose of the immune system is to find these cells with this foreign mRNA in it because it makes proteins that are foreign and to destroy those cells. That's why you get an immunogenic response when you get the flu vaccine or in this case, the mRNA vaccine, you get pain at the site, you get a little bit of a fever, perhaps, you might have some muscle aches, body aches, it'll feel like you actually have a viral infection because that's your interferon that's responding to it. That's your adaptive immune system, eventually, that's responding to it.

So that would explain Moderna's vaccine and also Pfizer's vaccine. The other one that's coming out is the AstraZeneca, Oxford one. Does the very same thing, except instead of using mRNA in a little, like, a lipid droplet, like a butter droplet, if you like, it's using a different vector, it's actually using a chimpanzee adenovirus that you're like, why would you use a chimpanzee adenovirus? Well, it's because humans haven't seen chimpanzee adenovirus. And so we don't want to have a vector used in that situation that could be recognized by the immune system and destroy the vector before the message gets into the cell. In this case, the message is not an mRNA, it's actually a DNA. And so the DNA goes into the nucleus in the AstraZeneca, Oxford version, where it is transcribed into an mRNA. And then the rest is the same from there.

So that's basically the three types of vaccines currently available, except for the Oxford. The Oxford one, I believe, was just approved a couple of days ago in Great Britain. So that'll be coming out. There's a whole bunch of other vaccinations, even sort of the conventional type where they actually have the protein and they inject that. Those are in process still, they have not come out. The reason why they're probably taking longer is because it takes a long time to make the protein. And there is a lot of regulation that goes along in making the protein. And that's why these vaccine companies who choose not to use mRNA, who choose to do the conventional way, are taking a long time. And that's why in the past, it took a long time to make a vaccine because there's a lot of regulation that goes involved, there's a lot of making sure that everything is purified.

What Moderna and what Pfizer, and what AstraZeneca are doing is they're moving that factory production points out of their realm and they're putting it into your body. So it's your body that's now making the protein, it's your body that's doing this, they don't have to do that. And therefore they can get a product faster.

And the other advantage with it, by the way, is we've talked about a little bit about these mutations or variants of the virus, and we're worried whether or not the immune system is going to be able to track this and actually be effective against it. Well, the nice thing about the information, the mRNA is that if this mutation, or if this variant is significant, they can always change the information on the mRNA so that it matches the variant. And so the immune system can respond to that. And they can do that actually, fairly quickly. So these are all sort of interesting advances.

I could completely understand how people would say, Well, I don't know, this is kind of new, let's see how this works. That's a perfectly rational response to have to see. Because obviously, there's a lot of things that we don't know about, and we're not going to know about it until we actually immunize and vaccinate a large population of people, but so far, it seems to be very safe, and it seems to be effective.

Rhonda: With vaccines, you know, there obviously are potential side effects that may or may not happen in an individual. I mean, you can go on the CDC website and look at the variety of vaccines and look at the potential side effects for a variety of vaccines that are available. It seems, at least looking at, you know, the list that those side effects typically are acute. They're not like a long-term thing that you're looking at, you know, a year from now all of a sudden appearing. Or is that something to worry about, in general with vaccines? Has it ever really been documented?

Dr. Seheult: Yeah. So yeah, so there are there can be long-term effects that can happen. Generally speaking, though, 90% of those long term effects usually pop up within the first month or two. And so, we're going to know pretty quickly whether or not there's going to be long term effects into postmarketing. Probably the worst-case scenario that we've seen so far was a flu vaccine that was, it was a regular flu vaccine, it was not an mRNA, it was not a DNA, it was just a regular flu vaccine that was administered in Europe a number of years ago. This is back in 2009, 2010. And they did find an increased risk of narcolepsy in patients that were vaccinated with that type of vaccine. And the thought process there was that perhaps there was an immune response that cross-reacted with the portion of the brain that produces hypocretin, which is the basis for narcolepsy. And so that didn't happen in all of those patients, but it was substantially increased in the general population.

So those are the types of things that we would be looking for. It's usually an autoimmune response. But I would just say at this point that right now, right now, what we're seeing in terms of COVID infections and vaccinations, your risk of getting a post-infective autoimmune condition is probably higher in COVID if you were to get infected with COVID versus getting the vaccine. Remember, you're going to make antibodies against multiple portions of the Coronavirus. And so your chances of getting an antibody that might be directed against something in your body is higher when you have more epitopes, like you would with a natural infection with COVID-19, than you would against a very specific portion of a very specific protein of SARS-CoV-2, which is the spike protein.

So, for instance, Guillain-Barre syndrome. It's very well-known that people who come down with viral infections can get this thing called Guillain-Barre syndrome, which is an autoimmune condition where your antibodies attack your nerves. And it's, sort of, called ascending paralysis where you can't walk at first, then you can't breathe. It's very rare, but it's definitely known to happen after a natural infection. Well, does it also happen after immunizations? Yes, it can. But we believe it's probably higher in a natural infection than it would be in immunization. And when we're talking about a pandemic situation, we see the weigh the risks and the benefits and I believe that the benefits of getting the vaccine outweigh the risks, at least at this point, given the information that we have.

Rhonda: I'm 100% with you, and I also am excited about this new mRNA technology that's being used. As you mentioned, I think there's actually benefits to, you know, having this technology as well. So I'm actually excited that it's actually a new technology that we're using for vaccines.

You know, with COVID-19, you read all these horror stories of, you know, obviously, there's the risk of being hospitalized and going to the ICU and needing oxygen and, you know, progressing into this severe case. But there's a lot of people, as you mentioned, 80% of people that don't have to go to the hospital. That their immune system takes care of it. You know, they don't have a real severe case. But then you start to read about these other long-term effects that are cropping up, like heart palpitations and all sorts of funny stuff.

Dr. Seheult: Yeah, so there's one study that showed that 60% a month out still had myocarditis or inflammation of heart tissue. That's pretty scary. You know, what are the long term effects that we're going to see from this pandemic? Because there's millions and millions that are being infected with this virus. And so even if it's just 1% of the people getting something, but we're seeing actually higher than that. That could really change the landscape in terms of what we see out there in terms of disease and population. So it's not this binary thing about they live, they died, it's they live but they've got, the term is long haulers, of course, and more and more people are becoming long haulers. Unfortunately, we don't know how long this stuff is going to last. But I've seen studies. One recent study that showed that one rare side effect was psychosis. People actually hearing things and seeing things. It's very rare, but it's certainly something that's well documented in people that have been completely healthy until they came down with the virus.

Rhonda: Wow. Yeah, I'm certainly more afraid of long term effects with getting COVID-19 versus getting an mRNA vaccine.

So, you know, is this autoantibodies, like that you mentioned that is a common thing with getting any viral illness, has that been looked at or studied or linked to this long term?

Dr. Seheult: Yeah. So they're looking at this. We saw in kids, there was this Kawasaki-like illness that was occurring, we just don't know if that's similar to what we're seeing. I anticipate that we're going to be doing a lot more research in terms of the immunity and post-immunity as we go.

Rhonda: Well, I am, for one, extremely excited about the vaccine, you know, that has now been, you know, making its way to the population.

And I've really, really enjoyed this conversation, Roger. What are some of, like, the top five things that you're doing in your lifestyle right now to keep yourself healthy? And your friends and your family? And perhaps patients? I'm not sure. Obviously, this is not medical advice, but what you're doing?

Dr. Seheult: So, I think probably one of the biggest things that I'm doing is making sure that I get enough sleep. That's number one, and we talked about that. Number two is I am making sure that we're doing contrast showers. So what is a contrast shower? Hot and then cold, hot and then cold, hot and then cold. So five minutes hot, one minute, cold, five minutes hot or three minutes hot, one minute cold, and another three minutes hot, one minute cold, hot as you can tolerate, as cold as you can tolerate. And as we get toward the winter months, cold becomes even colder. So those cold water in the pipes can really do it. So I do that. I'm also, obviously, taking a supplement with vitamin D, that's probably one of the most important ones I'm doing.

For others, there's not as much data on, but I'm still making sure I get a nice big bowl of every antioxidant fruit I can possibly get hold of. You know, blackberries, strawberries, raspberries, pineapple. That's what I have for breakfast. I'm also taking NAC, N-acetyl cysteine. There's a study that showed that it improves symptoms in the flu virus, we don't know if it helps in COVID-19. But and as we talked about earlier with ACE2 and the fact that there's oxidative stress, you know, NAC is a great antioxidants. It's packed with antioxidants. And recycles the glutathione peroxidase system, which is helpful in dealing with oxidative stress. So I'm taking that. I'm also taking zinc, but you want to make sure that you don't take too much zinc. Zinc, you don't want to take more than 40 milligrams of zinc a day. That's elemental zinc, otherwise, you're going to have...

You know, we see a lot of people at the hospital dying and it could really weigh on you. You've got to have your faith placed in something higher than just yourself. And it's not just a matter of what macromolecules you can take into your system, but you've to be grounded and know what you're doing.

Rhonda: Absolutely.

Thank you so much, Roger, for this conversation, for your amazing coverage of the COVID-19 pandemic on your YouTube channel and MedCram videos, has been by far, like, my, if I want to know about anything going on with COVID-19, I go to MedCram. I tell everyone about it. I mean, it's just been very scientific analysis, very well explained to people that don't have a science or medical background. Just phenomenal job with these videos on COVID-19.

If people want to continue to find out more about what you're doing, where's the best places they can find you?

Dr. Seheult: Yes, so if they go to YouTube and just type in MedCram, go to our channel and sort the videos by chronology. They'll see the latest of what we're doing. medcram.com and Facebook. And also Twitter. We tweet as well.

Rhonda: @medcramvideos.

Dr. Seheult: Yeah.

Rhonda: Great. So everything is @medcramvideos, basically, on all the platforms. Instagram, Facebook, YouTube, and the website.

All right, Roger. Well, thank you so much. Again, I really appreciate everything that you've been doing, and look forward to more information that you put out. And I just enjoyed this conversation a tremendous amount. So, thank you.

Dr. Seheult: Thank you so much, Rhonda. It was a pleasure to be on. And yeah, I hope we can continue this.