 How does the food you eat contribute to your overall health? Do supplements help prevent disease? For the past 25 years, the Linus Pauling Institute has served as a trusted research hub for Oregon State University. Our mission is to promote optimal health through cutting-edge nutrition research and trusted public outreach. Our work bridges multiple disciplines to understand the connection between dietary components and optimal health. Welcome to the Linus Pauling Institute's webinar series. Hi everyone, good afternoon or good evening or good morning depending where you are in the world. My name is Emily Ho and I'm the director of the Linus Pauling Institute and I want to welcome you to the Linus Pauling Institute's second webcast of 2021. This year marks the 25th anniversary of the Institute at Oregon State University and we've kicked off this celebratory year in February with our vitamin C and health new frontiers webinar that was presented in honor of Linus Pauling's birthday. If you missed it, the recording is still available online and the link is on our website. There are going to be more webinars coming later this year. One will come up early this summer in July and they'll continue into the fall. So today we're continuing our webinar series with the latest research with vitamins. Today we're highlighting vitamin D. This webinar is why a healthy immune system needs vitamin D with our presenter, Dr. Adrienne Gompart. As a note, this entire webinar will also have auto closed captioning for you for those who need it. So as usual, our turnout for today's event is really impressive. We have over 1200 people registered for this webcast and we're thrilled to see such an incredible interest in this topic. So without further ado, but before we get to the main event, I'd like to take a moment here and let our moderator Dr. Alexander Michaels take the stage. Hi, everyone. I'm back. Hi. Thank you, Emily, for that introduction. My name is Dr. Alexander Michaels, as Emily said, and I'm a researcher and communications officer at the Linus Pauling Institute. And I'm going to serve as the moderator for today's webinar. The last webinar I did was our webinar on vitamin C, as Emily mentioned, and that was a really fun webinar to do. Getting four vitamin C experts in a room together just to talk about the latest research was just amazing. I'm still working through all the questions from that event. So today's webinar is focused on vitamin D, hot topic in the world today. The webinar is going to consist of two parts. The first part will be a presentation by Dr. Gompart, followed by a Q&A session. And we hope to have everything wrapped up by 5 p.m., so we will have to get going quickly. Before I get started, I'm going to do a quick rundown of how our Q&A system works. If you look below me here, there's a Q&A button. If you have a question for the speaker, you can submit it in the Q&A section, and we will try to get to it during the talk. Sorry, after the talk. But we do have 200 questions submitted already before the event. So I'm going to apologize in advance if I can't get to all of them in time. So at this point, I'm going to ask Dr. Gompart to turn on his camera, and we can get to an introduction here. It is my pleasure to introduce Dr. Adrian Fritz Gompart. I will be referring to him as Fritz during most of this talk as our speaker today. Dr. Gompart came to the Linus Pauling Institute in 2008 when he also joined the biochemistry and biophysics department at Oregon State University. And before coming to OSU, Dr. Gompart completed his postdoctoral research in hematology and oncology at the Cedars Cyanide Medical Center and the David Geffen School of Medicine at UCLA in Los Angeles. He obtained his PhD in microbiology at the University of Washington in Seattle. Fritz has several research projects going throughout the years, and most of them funded by different agencies within the National Institutes of Health. He also conducted research trials, including a recent trial that I was happy to help with, a clinical trial with funding from the supplement industry. His research focuses on the understanding the impact of vitamin D and other micronutrients in the immune system, which has been an unbelievably important topic in recent years and months. And I think at that, I'm just going to let Fritz take it from here. Thank you very much for that introduction, Alex. It's a real pleasure to be here, and perhaps we should just go ahead and get to the talk and then let people ask questions. Okay. I'm going to talk about why a healthy immune system needs vitamin D. Overview the talk that shown here on the slide will be covering key questions. One is what is vitamin D and how do we get it? Is it vitamin D3 or vitamin D2? Which one is a preferred vitamin form? What is the difference? And who would benefit from additional vitamin D? How much does one need? And why does the immune system need vitamin D? So vitamin D is a fat-soluble sequestering hormone, and it's stored in the liver and the fat. It's an enhancing calcium and phosphorus uptake in the small intestine because it increases the expression of transporter proteins in this area, and this improves the absorption of these minerals. The primary benefit is maintaining adequate calcium levels for strong bones and preventing rickets. Of course, calcium is involved in other important cellular functions. If we continue discussing vitamin D, it's important to understand how it is made by the body and how we obtain it from the diet. In humans and other animals, ultraviolet B rays in the form of sunshine, cleave the 7-dehydrocholesterol, which is in the skin, and this becomes pre-vitamin D3. This form undergoes a structural change, which then converts it to vitamin D3. We can also paint this from the diet in certain fortified foods and foods like fishes or in a supplement. It's also known that a molecule called agasterol in the fruiting body of mushrooms can be converted to vitamin D2 by exposure to sunshine or ultraviolet B rays, and this can be obtained in the diet from eating by eating mushrooms. That course has been exposed to sunlight. The difference between D2 and D3 is a methyl group that's highlighted here on a carbon that's highlighted in this circle. So both of these forms can be carried in the blood to the liver. And there they're converted to the 25-hydroxy vitamin D3 or D2. Or D3, it's also known as calcifidyle or calcidyle. This form is generally inactive, and it's the form that's measured in your blood by your physician to determine your vitamin D status. So when the body needs the active form of vitamin D, that's the 1-alpha-25 dihydroxy vitamin D3, also known as calcetrile, this conversion occurs primarily in the kidney with regards to maintaining calcium levels. However, there are other cells that can carry out this conversion, including immune cells. So just briefly, there's some discussion as to whether vitamin D3 is preferred over vitamin D2 as a supplement. And there are differences in how the body handles these two forms. So if you take the same dose, say 50,000 IU, that the serum levels of your 25-hydroxid will increase similarly. However, as you go, as you watch over time what happens, you can see that the D2 form clears from the blood more rapidly than the D3 form, which tends to stay at high levels for at least a month after this large intake. So while taking large doses and waiting for a long time may not be ideal for D2, if you take it daily, it should be one way to maintain levels of vitamin D, and this may be something that's preferred by individuals who do not want to consume animal products. So how does vitamin D work in the body? Well, vitamin D mediates its effects on the cell via the vitamin D receptor. And this is a transcription factor that is activated upon binding of the active form of vitamin D. So you have synthesis of 25-hydroxid and in the body, an enzyme converts that 25 to 125 as we discussed. And this 125-dihydroxy vitamin D then interacts with its receptor, and this receptor can turn on the expression of genes in the nucleus. And so many of these genes are involved in classical functions such as calcium uptake and bone health. And then they're also genes involved in non-classical functions such as cancer chemo prevention, antibacterial responses and anti-inflammatory responses, and perhaps anti-hypertensive responses. So these are generally considered non-classical functions. And the reason that vitamin D has the vitamin D pathway has such an effect on numerous systems is that most, the vitamin D receptor is expressed in most cells and most tissues of the body. And over a thousand genes are regulated by the vitamin D receptor, and it's ligand the active form of vitamin D. So it's the fact that so many genes are regulated by vitamin D highlights that adequate levels of the 25-hydroxid D are important. And so inadequate levels are still an ongoing health concern worldwide. And in this study by Hilger and colleagues, they looked at almost 168,000 participants from the general population, measured mean serum, and they basically aggregated studies that were looking at mean serum 25-hydroxy D levels. And they found that if you use the endocrinology cutoffs of 75 nanomole per liter or 30 nanogram per mil serum 25, that 88% of people were insufficient. And if you use the cutoff of the Institute of Medicine, which was 20 nanogram per mil or 50 nanomole per liter, 37% of individuals had insufficient levels of serum 25B. And 6.7% of the population was deficient. And this just arrow points out the U.S. here. You can see the circle size is how many participants were in the study. The greens is sufficient adequate levels. Yellow and orange and red would be inadequate deficient levels. So you can still see that there are a number of people worldwide that don't get enough vitamin D. So what factors affect 25-hydroxy D levels? What is the climate and weather? So seasons in the winter, we don't synthesize vitamin D when we are north of 35 degrees latitude or south in the winter in the south. Skin pigmentation or clothing, darker skinned individuals make less vitamin D on sun exposure. Clothing and sunscreen block the production of vitamin D by the skin. Age is important. So cholesterol content to the skin decreases. So that component, the 7-dhydrocholesterol is present at the lower levels in the skin of older people. Also mobility, if you're not getting outside, you're not able to synthesize vitamin D. Obesity, obese individuals tend to have low circulating levels of serum 25-hydroxy D. And then diet and supplement usage. So depending on your diet, you may have very little vitamin D content in your food. This is particularly an issue for vegans, vegetarians and so forth. So considering the factors that affect serum 25, then it stands to reason that older individuals are going to benefit from increased vitamin D intake. Individuals with darker skin or those who cover their bodies with clothing or avoid sun exposure. Nursing, air, home, residents, vegetarians and vegans and hospitalized patients for all individuals who could benefit. With regards to vegetarians and vegans, it's interesting to note I found this on a vitamin D website. And when you look at this, you realize there's very little vitamin D present here and possibly with the exception of mushrooms. So if you are able to find these in the store, you can get mushrooms that have been exposed to ultraviolet B-rays and they are actually a good source of vitamin D. But when you look at the foods that are actually rich in vitamin D, they're fatty fishes like tuna, mackerel, salmon or fortified foods like dairy products, orange juice, soy milk and cereals. And then there's beef liver cheese and egg yolks that also have vitamin D. So these are generally not probably consumed in large quantities by vegetarians and vegans except for some of the fortified soy milk perhaps cereals. So how much does one need? LPI recommendations are for a daily intake of vitamin D and healthy adults of 2,000 IU per day, infants 400 to 1,000 IU per day, children and adolescents to 600 to 1,000 IU per day. The upper limit that's been set by the IOM is 4,000 IU per day. Our recommendations are higher than the current IOM recommendations, which are 600 for healthy adults and 800 for those older than 70 and I believe 400 for children. So we are recommending a bit higher and we feel that this is important in making sure that most people can reach serum levels that are say 30 to 60 nanogram per mil. At least reaching 30 and we recommend that people maintain their serum 25 hydroxy concentrations at this level. So we've gone through some introductory material. Now it's time to consider why does the immune system need vitamin D. Well historically sources of vitamin D were used to treat tuberculosis and this was some of the first earlier clues that sources of vitamin D were important in immune function. So it was known that cod liver oil could effectively or could help a number of patients with tuberculosis. You also are probably where the cod liver oil is considered healthy because it does have vitamin D in it. Also has vitamin A. And sanatoriums were used quite a bit in the late 1800s and early 1900s to treat patients with tuberculosis and they found that people's health improved quite a bit. But at the time they didn't actually know what the benefit was from. And in the 1940s by the 1940s they had already been isolating vitamin D in the form of vitamin D2 from yeast that was irradiated with light. And they could give purified forms of vitamin D2 to patients. And a physician found that he could, named Sharpie, found that he could use a 600,000 IU dose of vitamin D2 and alcohol to treat patients who had lupus vulgaris which is a mycobacterium tuberculosis infection of the skin. And here's a patient, an example of a patient who had been living with this condition that disfigures the face quite terribly. And they put them on a treatment where in the first week they got three doses of this 600,000 IU, then for the second through fourth weeks, two doses per week, and then once per month indefinitely. And you can see that there was quite a dramatic improvement in the condition of this patient. This was seen in a lot of patients, but it eventually fell out of use once antibiotics to treat this bacterial infection were discovered. However, this was also a very strong indicator that vitamin D was having a major effect on immune response. In the ensuing decades, it was noted that vitamin D deficiency or insufficiency correlated with increased susceptibility to mycobacterium infection, bacterial infections, but in particular mycobacterium tuberculosis infections. This was discovered back in the 80s that activated macrophages which are really important innate immune cell for fighting infection, particularly not surprisingly mycobacterium tuberculosis infection could metabolize the 25-hydroxyd to the 125-hydroxyd. And that active form needed to turn on genes. And it was also found that if you provided this active form of vitamin D to immune cells like macrophages, you could increase their ability to basically engulf and kill bacteria, including mycobacterial pathogens. But in the early 2000s, my group and others discovered that this also led to increased expression of an antimicrobial peptide in these cells. This is just a western blot that allows us to detect protein and this was something my group did. We found that if we took these macrophage-like cells and we gave them vitamin D, shown the active form of vitamin D, shown by the plus, compared cells that did not receive the vitamin D, there was a dramatic increase in the expression of this protein. And this is the capillicide and antimicrobial peptide. So these were all very interesting findings and there was a lot of renewed interest, but not only does vitamin D regulate the antimicrobial peptide, it also has a major effect on the differentiation of immune cells in the innate immune system, which would be monocytes and macrophages and dendritic cells, and it also has major effects on the function of T cells and B cells. And so this table is not meant to mean a whole lot to you as far as all these different names, but these are all genes that are involved in immune response. And vitamin D is either directly or indirectly regulating expression of these genes, and that can be through binding to their promoters or by affecting the cells that express them. But in monocytes and macrophages and dendritic cells, we see increased expression of antimicrobial peptides. We see in macrophages increased phagocytosis, which is the engulfing of pathogen. We see effects on T cell differentiation, so increased T regs, which are good as far as the receding inflammation, and we see a decrease in inflammatory T cells like TH1 and TH17. We see decreased cytokine, inflammatory cytokine expression in monocytes and macrophages, and in T cells, we see increased T reg cell differentiation and operations in homing to skin and other inflamed tissues. And we also see decreases in inflammatory cytokine. So these findings with vitamin D show that there's a major impact of vitamin D on immune cell function and activity. So is vitamin D good for your immune system? Well, these findings, of course, together with the epidemiological studies that have been done, show that there's a connection of vitamin D to reducing the risk of autoimmune diseases, reducing inflammatory properties, such as the potential risk of cytokine storm. And this is particularly an issue with acute respiratory distress syndrome, which can occur with viral infections, and we're quite familiar with that with COVID. It can reduce the risk from infectious disease. So vitamin D supplementation has been shown to reduce the risk of acute respiratory tract infection from a very large meta-analysis study that was done by Martino et al. in 2017. What they did was they collected all of the data from individuals who participated in clinical trials, and these were randomized double-blind placebo RCTs of supplementation with vitamin D3 or D2. And the study had to be looking at the incidence of acute respiratory tract infection, and this had to be part of the study design so that it was collected prospectively and it was pre-specified as an efficacy outcome. They found 25 eligible studies, and they obtained the data for almost 11,000 participants. They found that when they analyzed this data, that vitamin D supplementation reduced the risk of acute respiratory infection among all participants by 12%. That doesn't seem like very much, but when they did a subgroup analysis, they found that the protective effects were seen in those receiving daily or weekly doses rather than large doses of once every month or several months. And they found that the protective effects were stronger in those with a baseline 25 hydroxy-vitamin D level below 10 nanogram per mil. And they saw a 70% reduced risk of acute respiratory infection, so that's quite dramatic. And even those who had higher than 10 nanogram per mil showed a 25% reduced risk for infection. So clearly there were some very important effects of vitamin D supplementation that were uncovered in this analysis. The good thing was vitamin D did not have any influence on serious adverse events, so it was safe and it protected against acute respiratory infections overall. So what does that mean with respect to COVID-19 and the SARS-CoV-2 pandemic? Well, there's been a lot of interest in vitamin D and COVID because of the reasons that we've been discussing. And what studies are finding is that a number of studies, observational studies, and not all of them, but they are finding that vitamin D deficiency or insufficiency correlates with the increased risk of infection. So a number of retrospective cohort studies, looking at one case, 190,000 U.S. residents, showed that increasing serum concentrations of 25-hydroxy-D lowered the risk of a patient being SARS-CoV-2 positive. In Israel, 7,800 patients were looked at and those with less than 30 nanogram per mil serum 25-hydroxy-D had a 50% or higher risk of infection. And a number of small case control studies and meta-analyses have supported these findings here. Small number of studies show that COVID-19 severity is associated with low vitamin D status and one case control found no link and three studies found a link to mortality, but two did not. So this has raised a lot of interest and a number of random control trials are now underway to address vitamin D supplementation and COVID-19 prevention and treatment. But what we would conclude is that the currently available data indicate improving vitamin D status through supplementation represents a modifiable risk factor of COVID-19. So I'd like to thank you for your attention. If you have any questions, I'm happy to take those. Thanks, Fritz, for that talk. I know a couple of people were having audio problems during the presentation, so hopefully we've got some of those addressed. I'll try to speak up and project as much as I can. And so I think for the benefit of the people who were having some audio issues and hopefully they can hear us better now. Maybe we should just go over some of the major effects of vitamin D in the immune system. I mean, you talked about vitamin D having a myriad of effects on B cells and T cells that has antimicrobial functions. Can you go a little further into the work with the acute respiratory infections? These infections that you were talking about, they're kind of undefined, right? I mean, the interest in vitamin D as far as the development of acute respiratory distress syndrome would be based on the findings that vitamin D has an impact on the expression of these inflammatory cytokines. So it tends to have a dampening effect on the expression of these inflammatory cytokines, which are what are out of control when this situation develops. So the thought is, if you have deficient levels of vitamin D, 25 hydroxyd, that you don't have a sufficient substrate for production of 125 dihydroxy vitamin D3, which is going to then activate the vitamin D receptor, turn on expression of genes or even turn down the expression of genes and have the effect that the 125 has on these immune cells like T cells and macrophages and so forth in the site of the infection. So whether vitamin D actually, if you supplement, will actually affect these outcomes is not as clear, but based on a lot of in vitro work and work in animals, this is sort of what the thought is as far as vitamin D goes. And the studies that have been done in people, there's some support for that, not all studies support that. A lot of it is correlating deficiency with outcomes. Sure, sure. I think I was specifically talking about the AI meta-analysis that you went over. These infections, I mean, they came from various sources, right? They weren't really defined. Right, the infections weren't necessarily defined. It was sort of a broad classification of acute respiratory tract. So you could be talking about any different sources. That could be influenza infections, cold, yes, different types of. I know everyone's going to be interested and I've already saw a request for the last slide, your slide deck again. We will make these slides available to everyone after the presentation is over, but we'll go over the COVID information again in just a moment. But I kind of go to a little bit of the basics of your talk, some of the questions that we received in pre-registration. A lot of people are interested in knowing where the cutoffs for vitamin D levels, blood levels are. What is considered good? What is considered bad? Is there a level that's considered too much? Right, so there's probably not surprising that there's confusion. So in 2010, the Institute of Medicine decided that sufficiency would be set at 20 nanogram per mil or 75 or 59 molar per liter. And that was based on requirements for bone health. And so because of the other potential effects of vitamin D on other health outcomes, the American Endocrinology Society set it at 30 nanogram per mil, which is what it was before the IOM changed it to 20. So that's Boston confusion. At the LPI, we are going with the Endocrin Society guidelines at 30. And we're recommending keeping it between 30 to 60. There's probably not any benefit going over 60 nanogram per mil. And as you get higher and higher levels, there's always a potential for perhaps unwanted side effects. So it's generally thought that you could probably reach up close to 150 nanogram per mil and still not suffer any ill effects. But it's not clear that having levels that high are necessarily any more beneficial. So basically we recommend between 30 to 60 nanograms per mil. So, but if an individual got their vitamin D level tested or blood vitamin D level tested and came back with something close to 100, you wouldn't necessarily be concerned, but wouldn't necessarily ask them to continue supplement. Yeah, I don't know if I'd be concerned, but then that's that's a pretty, pretty good level there. You may not need to take as much of the sub if you are so taking a supplement you may not need to take as much as you're taking because it's probably not necessary to be that high. Although, you know, the studies and lifeguards have shown that when they spend their time out in the sun during the summer they get levels that approach, approach that or go higher. So, a lot of people have asked, they're having difficulty raising their blood vitamin D. I mean we focus on blood vitamin D as a marker. Right. But what about the people who are in trouble getting to that level that threshold. Right, so they're measuring 25 hydroxy vitamin D in your blood to determine your status. And it's a frequent question to get from folks saying I'm taking a supplement but my levels are not increasing. And I've even I'm not an endocrinologist but I've spoken to my colleagues who are endocrinologists and work on vitamin D. And they say that this this this question is not uncommon and it's not entirely clear why why that's happening. But there are a number of studies that are done genome that they're basically these genome wide studies that are done with these nucleotide polymorphisms that are in genes that are involved in vitamin D metabolism and so some of those genes were on that slide, where we went over the chemical structures and synthesis of vitamin D so genes like the sip to our or the sip 20 sip 24 a one wasn't on there. That's a gene that makes a protein that breaks down vitamin D. And there's also a gene that regulates the production of the seven to hydro cholesterol, and there are variants in these genes that do seem to have an impact on serum levels of 25 D so it's possible individuals that have a for traveling a little it's it's not clear really clear what is happening there. I think we just had a little hiccup in your internet right there. Yeah, yeah, I cut out there. Yeah. So maybe that there's various genes, variants in these genes that metabolize vitamin D that are responsible for some individuals not reaching having increases in their levels. Sorry about that. So snips or individual gene variation may be one influencing factor. How about people have asked about say obesity, or maybe other vitamins and minerals or maybe drugs. Yeah, there you know those possible like interactions between drugs that people are taking as possible way of There's some some drugs like anti convulsions have been attributed to increasing the production of the enzyme that breaks down vitamin D. There's also possibility that you may be magnesium deficient. So there's there's there's work showing that magnesium increasing your magnesium levels and improve your vitamin D serum levels because magnesium is important co factor for these enzymes that regulate regulate metabolism of vitamin D. So I think in general there are a lot of things that can go into why your vitamin D levels aren't going up there could be magnesium deficiency is one that now is his there's a lot of interest in right yes and and I heard about that one quite a while ago and that personally helped me with my vitamin D levels, but I know other people who who have not seen the same effect so it's it's kind of got to be careful with with what works for one person may not work for you. Well let's let's go with let's turn our attention to vitamin D forms people a lot of people have asked even today about D2 and D3 is there any for I guess first of all is there any reason to supplement with both D2 and D3. To supplement with both. I don't or get a source I don't I don't think I did necessarily us you know supplement with both and just pick one there. There. I know there are people who don't want to take a an animal form of vitamin D which would be the vitamin D3. There's interest in something that's an option there and vitamin D2 is is the one that is probably the best option there it's derived from a fungal source. And I think if you take it daily that it keeps your your serum levels of vitamin D where you want them. It's maybe not good for bolus dosing bolus dosing refers to taking large doses say once a month or maybe once a week and actually one thing that came out of the acute respiratory tract infection study that I mentioned by Adrian Martin was that people who benefited the best were taking a daily dose of vitamin D supplement and not bolus doses and they did say also weekly but in speaking with him recently. I think he believes that daily supplementation is probably best even better than taking weekly doses so there seems to be something important about getting vitamin D each day versus large doses intermittently. So that was that actually answers one of our questions that we received which was you know which is the best regimen for vitamin D supplementation if you choose to supplement right night. We recommend taking it daily daily people do ask about injections though or or the large bolus oral supplementation are those considered safe or are there any side effects to do large amounts like that. There are sometimes there are large doses given by physicians to people who have really low serum levels of 25 D3. That's quickly raise the levels because it does take some time for your levels to come up if they're low. I don't believe that's been shown to be unsafe generally for people. I wouldn't recommend taking those doses every day for long periods of time. But the there is a there is there are concerns about large bolus dosing to maintain your levels and say 100,000 IU per month or you know several hundred thousand for the for three months. And that's that you might actually activates metabolism in your your body that that affects vitamin D in a way that perhaps you don't want want to have occur. So that's why it might be better to get it in sort of a daily regimen rather than really large doses that then activate certain metabolic pathways. That makes sense I guess you know at that point your body may be seeing it as more of not a toxin exactly but just something to be getting rid of because there's too much of it around and so that. Sorry I got out again so. No it's okay I was just I was just kind of say it's your taking large bolus doses may activate certain metabolic pathways that can have a negative effect on vitamin D. So. Let's see there's actually I'll ask this question. A lot of people have also asked about this. What about vitamin D combined with vitamin K is is there benefits to taking both together are there synergies are there additive effects of vitamin D and K. It's it's it's it's not that getting adequate levels of vitamin K are probably important in the function of vitamin D and also adequate vitamin D levels in the function of K. Overall the effect would be to improve bone strength by getting adequate levels of both and to reduce the possibility of calcification and soft tissues like the heart. I'm not a vitamin K expert but from what I understand generally you can get enough in your diet if you eat a diet was rich and leafy green vegetables and. What else is good for K. Nato fermented foods and things like that so there are there are ways to get vitamin K and most and from what I understand most people do get enough of you to a varied diet. So you I don't know if supplementing is necessarily needed. But you do want to have it's probably good to have adequate K adequate magnesium as well which you can get from leafy green vegetables and some other foods. But as far as I don't think there's enough data out there yet to to make decisions about. You know basically combining D and K and so forth but basically if you're eating a healthy diet and you're getting adequate you should just make sure you're getting adequate levels of the different micronutrients because definitely they don't act in a vacuum vitamin D is not acting alone. It's it's probably their interactions with K interactions with magnesium perhaps some other micronutrients that are important so. And certainly people have been concerned and some of our questions are along these lines is taking D in the absence of calcium bad is taking D with too much calcium bad is you know do you have to worry about calcium at the same time that you're worried about your D supplementation. Yeah and again not a calcium expert but but I would say that trying to get make sure you get enough you know adequate levels of calcium in your diet and but and then many of these micronutrients we can get in our diet vitamin D is one of those rare ones where it's it's fairly difficult to get enough vitamin D in your diet and that's why we recommend us and a stand alone. And supplement to make up for any inadequate inadequacies in diet because as I mentioned there's just a few foods that have significant levels of vitamin D otherwise you'd have to you know you'd have to eat a whole lot of eggs or a whole lot of drink a lot of milk to get to to the international unit numbers that we talk about. Yeah that's true dietary sources should be pretty low for most dietary sources. So, so let's turn then to sunlight, you know, people have been asking some questions about sunlight and understanding is the vitamin D from sunlight, somehow different from the vitamin D that we're taking in the D three that we're getting in supplements. Is there any benefit to getting it from sunlight. Well the vitamin D that you synthesizing your, your skin and ultimately in the metabolism that goes on after at least the skin is going to be identical to to the supplement that you and buy and consume. Am I still there. Yeah, yeah, yeah. Okay. Sorry, sometimes I don't know today has been a problem. So, the vitamin D three that you buy as a supplement is going to be identical to what you synthesize in your body. Okay. But as far as sun exposure there's a whole lot of other things that happen in your skin with sun exposure and there are other there are other compounds that are synthesized and there's a lot of interest in what those are and and the benefits of those so sun exposure is going to be different from just say taking a supplement because of the the usually other added benefits from that. But then of course there's the opposite, which is staying the sun too long. Right. The negative effects of being right so you don't want to get, you don't want to get a sunburn. Yeah. And so if you want to use the sun to make vitamin D, you may want to go out for a few minutes, synthesize some vitamin D and then put on your sunscreen. Actually that that that's a great or brings up a great question right there is like how long does it take. Obviously it depends on your latitude. Right. So there are there I don't I don't have the website remembered or memorized but there are links to websites you can go to and calculate how long you need to be exposed to the sun to synthesize a certain number of international units of vitamin D. You can check those out and put in the numbers and they take in latitude time a year and even the surface that you might be standing on whether it's concrete or sand or grass. And also how much your body is how much of your body is exposed and you can you can calculate how much vitamin D you can synthesize somebody like myself, say in the noon day sun. In the middle of summer might be able to synthesize 1000 IU in about seven to 10 minutes. Okay. Before, you know, before any kind of sunburn would occur. But in a nice Oregon winter. Right. Yes. And so if you're living between 35 degrees north or south latitude during the winter months you there should be enough UVB rays in the sun to synthesize vitamin D it's just when you go beyond those north or south during the winter months for about four or five months from November to March. There's not enough UVB rays to synthesize vitamin D so some sort of other sources, such as a supplement or foods that are rich in vitamin D would be the best option. So, a couple of a couple of people have asked about vitamin D as nature is a hormone. Why is it called a vitamin if it's a hormone, steroid, you know, it's steroid hormone. Right. It's a steroid hormone, which means that one of the rings is cleaved. Is it. I mean, the reason it's a it is it is a hormone it was, it's the reasons called vitamin D is it was discovered in food sources initially when researchers were studying, studying the vitamin. They found that they could feed certain things to rats that they made deficient by feeding them a diet that was low in vitamin D they could feed them. Let's say oatmeal, the rats would for a long period of time they would not be getting any vitamin D they'd keep them in the dark basically and these rats would get problems like bone bone problems and so forth. They found they could then feed, feed them things that were irradiated and or just feed them things from rats that were not in the dark and like bedding material and this would reverse it so it was initially found through consumption that they could correct the deficiency. So it was called a vitamin essentially that's sort of how it came about. And then what I'll tell you that they determined that it was actually being synthesized in the skin with sun exposure. So another way of, I mean, we define vitamins I guess in two different ways, one of which is something that comes from our diet but also as something that corrects a new deficiency in the diet and so the name still sticks, you know, you can use dietary vitamin D to correct deficiency. Yes, you could. So okay, let's let's turn our attention back to COVID-19 because I know a lot of people are going to be interested in that information. You showed some of the synopsis of vitamin D and COVID but I know there's a lot of papers showing up all the time about vitamin D and COVID. And do you have any word of caution on viewing these articles I mean there's there's a lot of different designs out there. A word of caution. I think you think we want to focus on peer reviewed papers, there are a lot of, there are a number of, you know, now papers are being deposited in pre pre prints pre print servers, those pre prints aren't necessarily peer reviewed. And we've had there have been examples of papers that have not not been able to get through the peer review process have been issues with them. There's been examples of papers have gone through the peer review process it's not it's not bullet proof but then issues arise. And so it's it's kind of the Wild West out there with this, what I would say about vitamin D and immunity in immunity is there's clearly a role for vitamin D in the immune immune system. And that comes from a sort of a preponderance of a lot of in vitro work which is you know not necessarily ideal but, and then combining that with clinical studies, epidemiological studies the associations with deficiency and so forth. Taking all this evidence together and then of course observational studies. We know that it's important in the immune system. And what we want to make sure people do is make sure they're getting enough vitamin D so that their immune system can function properly. Whether I don't think you should think about. Oh, COVID's coming through a better just start loading up. When you get sick, what you want to do is you want to keep your levels, you want to keep your levels up all the time so that when you do encounter something, your body will respond properly the immune system can function properly. I think the best example of why we think vitamin D so important is macrophages, which I mentioned, they're important in fighting infection, and particularly mycobacterium tuberculosis is one where the macrophages really important and I think this is why this, why this came out. In the years, many years ago, that there was an association of vitamin D with mycobacterium tuberculosis infection and that's when the macrophage encounters a pathogen, it activates the production of 125 from 25. So if you have really low circulating 25 in your system, you won't have enough present to convert to 125 and the 125 is turning on these genes that we know fight infection like the antimicrobial peptide. So with COVID these and this peptide as well as other genes that are regularly by vitamin D are important in fighting viral infections as well as bacterial infections. So does vitamin D help you with COVID I would say vitamin D helps you with probably many types of infection and the coronavirus infection and the development of the COVID disease are going to probably be impacted by your vitamin D status. These studies are again, suggesting there's importance and I would agree that there's probably something important there, whether you can treat with high doses of MD I'm not sure, but I do think at least maintaining adequate levels goes a long way and perhaps reducing your risk of infection and perhaps reducing the severity. And of course there are studies now being designed and started that are going to be looking at the use of supplementation in patients who get infected and become developed COVID. And I think we'll have to wait and see how that turns out. I think, I mean, some important notes are, you know, the, the, the, a lot of the studies that we're seeing on vitamin D are in patients, right people are already shown up at a hospital for some severe. They're not really looking at people who are necessarily living at home. And so we've already got a subset of a group that kind of self selected group they've already got some sort of problem. And also those study designs are very different. I mean, I looked at some today that used large oral bolus doses, as you mentioned, and some use daily supplementation. Some even used calcidil. Can you talk about calcidil a little bit? There's interest in calcidil because calcidil refers to the 25 hydroxy vitamin D. That's the form that circulates in your blood. If there's interest in that as a supplement because it raises your serum 25 hydroxy vitamin D levels more, much more rapidly than taking the vitamin D supplement because it bypasses the metabolism that has to occur in the liver. So there's interest in using that to raise levels very, very quickly. There was a study on that where that was used in some patients in the, in Spain. I've heard that there may be some questions about the study. Yep. As far as the validity of the results, there were some problems being pointed out in design and so forth. So I think it remains to be seen whether that's also going to be useful, but it clearly does raise levels more quickly. And if that's important in certain conditions, it might be a viable option. Submentation, but it's considered, at this point, I think it's considered a drug in the United States. Yeah, the FDA is still regulating instead of drugs. Even though you find 25 hydroxyd in food sources like eggs and certain meats and livers and so forth, but it's at much lower levels than say the vitamin D itself. So I think the bottom line for the Linus Pauling Institute at least was, you know, after the pandemic started, and all these papers appeared for vitamin D. Our recommendations really haven't changed. We still recommending people take vitamin D supplements to get their levels up, regardless of what the current infectious disease circulating the planet is. And I think, again, if your levels are really, you know, if you get a measurement and your levels are low, you may want to work with your physician to raise those levels quickly. And you can do that by taking higher doses than say 2,000 IU, you know, the upper limit is 4,000 IU, but it's not uncommon to take 10,000 or 20,000 or even 50,000 depending on how rapidly you want to increase those levels. And then you can back down to a lower level and maintain your serum levels. And I'm going to probably have to close it on this question here, but that raises kind of a logistical concern during the pandemic is, you know, you can't always get out and get your blood levels checked in the middle of a public health crisis. And people want to know if you should check your levels regularly. I mean, what can you do if you can't, for some reason, check your levels? So is it just continue on at a normal dose and keep taking your supplement? It's not that difficult to check. There are companies that will do those blood spot tests. Mail order companies, yeah. Basically, you can contact them and they'll send you the kit. You can do your blood spot test. And those are pretty good for getting a number. And they're not terribly expensive from what I remember. Somewhere around 50 to $95. Okay. Well, I think I'm going to have to leave it there. We're kind of at time and but I'd like to thank you for it's for all of your time today and that presentation answering all our questions. It was great having you here. Thanks everybody for participating. And so now I'm just going to ask Emily Ho to come back on to kind of lead us out for this webinar. Emily. Yes, great. Thank you. Thank you all. Thank you for all your time with us today. Hopefully in the spirit of Linus Pauling, we hope you learned a little bit more about how to live better longer using the science nutrition. Don't forget to check out our website. We'll have the PowerPoint presentation, this webinar and all of our previous webinars there. And I encourage you to check out our micronutrient information center, which is also on our website for even more information. And many of the answers to your questions are all about vitamin D are there as well and our vitamin D article so please check that out. I'd like to present it here and all the resources that the Institute has for you are provided and funded by many of our generous supporters so people like you who have a passion for nutrition science so love to hear from you if you have more ideas on webinar topics or topics you'd like to hear about we'd love to hear about it. I encourage you to consider donating to the Linus Pauling Institute. No gift is too small. Every little bit makes a big difference in helping us produce content like we have here today. So for more information, you can always send us an email, check out our website for ways to support and give. Lastly, want to give a big shout out. Thank you to Dr. Gombard for sharing his research and lending his expertise. I also want to thank Dr. Michaels for being a great moderator. Thank you for behind the scenes Isabel Misson and Nancy Shanks from the OC Foundation for all their help with the webinar as well and as well as Dr. Drake, who is the director of the Micronutrient Information Center. Thank you just big thanks to all of you for being here and caring about your health. Looking forward to seeing you next time. Thank you.