Vitamin D and COVID-19 Prevention
April 7, 2021
New research indicates that Vitamin D may protect against COVID-19, especially in Black people. Today, on At the Forefront Live, we'll talk with investigators about that research study, hear more about the importance of adequate Vitamin D in preventing disease, and find out how you can participate in a clinical research trial to see if Vitamin D is protective against COVID-19. That's coming up right now on, At the Forefront Live.
And we want to remind our viewers that today's program is not designed to take the place of a visit with your physician. Let's start off with having each of our investigators introduce themselves and tell us what you do here at UChicago Medicine. And Dr. Meltzer, you're actually on set with me, so we're going to start with you and then we'll go to Dr. Lee in just a moment.
Great. I'm David Meltzer. I'm a Fanny Pritzker Professor of Medicine and I'm Chief of the section of Hospital Medicine here. In addition, I run the Center for Health in the Social Sciences, which we call CHeSS.
Fantastic. And Dr. Lee?
I'm Raphael Lee. I'm a Paul and Aileen Russel Distinguished Service Professor at the University in Surgery and in Medicine and at Pritzker School of Medical Engineering I'm a Plastic Surgeon and a Biomedical Engineer who has spent most of his career focusing on trauma and trauma-related problems, such as wound healing and scarring.
Fantastic. And we'll talk a little bit about Vitamin D in wound healing here in just a moment, which is a fascinating connection that I think people will be interested in. But let's start off with just kind of some of the basics. And Dr. Lee, I'm going to start with you. Talk to us a little bit about Vitamin D-- what exactly does it do for the body, why is it important, and why do we need to make sure we have enough of it?
So vitamin D is an extremely important, fundamentally important biological molecule that functions much like the Secretary of Defense for the cell. And it regulates the immune system. It regulates and controls the ability of cells to respond to stress and injury, attacked by offending organisms like viruses and bacteria, and it really has an ancient history in the biological system dating back over 500 million years. And so it's still, even today, in our complex systems, no longer single cells like yeast and fungi, but now complex organismal systems such as a person-- the immune system has several different components and Vitamin D continues to play the central role in regulating the body's response to stress and injury.
So its ability as the single cells in the body to protect itself with antimicrobial proteins and repair molecules and controlling inflammation. And then, modifying the part of the immune system that actually learns from an offending organism so that it develops antibodies and get the delayed response. We call that adaptive immunity. So Vitamin D is really essential, in terms of body function.
So how do we get Vitamin D? I think that's the big question everybody would ask. We think about it, I think about going out in the sun, but there are other ways. And I don't know, is that the primary way to get Vitamin D?
So the term vitamin implies that all the vitamin that the source is through a nutrient. But in fact, we can make-- our bodies can make Vitamin D with the aid of sunlight. The sunlight, cholesterol is converted in the skin to an active molecule that then gets converted into Vitamin D. And that happens with the influence of the ultraviolet component of the sunlight. And so our skin plays an important role in regulating how much vitamin D we make, and also that means that sunlight exposure is really important and therein lies where there are differences in the color of skin and also the changes in human habitat over the last 100,000 years that human society existed on Earth.
In the last couple of hundred, we've moved increasingly indoors and we get less sunlight exposure. There's some advantages to that, but the disadvantage is that Vitamin D production is low. Now, the other source of Vitamin D is dietary. And so plants make a form of Vitamin D called D2, and then animal systems like fish make Vitamin D by getting their precursor from the plants that grow on the surface of the ocean, which are the main source of Vitamin D and then they convert that to a vitamin D3.
So today, our primary source of Vitamin D, particularly for those of us who live up above the level like St. Louis and north of that, we don't-- can't get enough sunlight, so we have to have the dietary intake and fish and certain kinds of plants-- mushrooms and so forth. And then, of course, we have Vitamin D fortified milk, and so forth, in the modern society. Those are really our dietary sources of Vitamin D.
And I was going to say, you brought up where we live. Chicago is kind of a difficult place in the winter because it is gray a lot and so I would imagine you don't get nearly the Vitamin D levels you would want from the sun. But skin color is also an important factor in this. People of color tend to get a little less Vitamin D, is that correct?
Yeah. So that's the reason why-- one of the main reasons why there is variation in skin color. The people that normally have emerged from parts of the world that's more equatorial than in the temperate zone, they need color in their skin, so not to make too much Vitamin D. But those who have come from the more northern or more southern regions of the globe where there's less sunlight and there's more overcast, they don't have very much pigment in the skin because they need as much sunlight as they possibly can to make Vitamin D, and they've adapted other mechanisms to control the immune response.
Now, I also-- when we talk about Vitamin D and its function, calcium and bone metabolism is the thing that comes to mind first, but calcium plays a key role in regulating the immune system. And of course, by regulating calcium, Vitamin D continues to have this fundamental role in regulating skeletal growth. So in order to have normal skeletal growth in the more regions of the Earth that's closer to the equator and regulate the immune system properly, skin color has to-- more pigment is needed in the skin.
Interesting. So Dr. Meltzer, I know that you've been studying the relationship between COVID and Vitamin D and that's been taking over the news lately, it seems like. We were talking before the program about just all of the attention that you've received for the study. Tell us how you got interested in that and what are you seeing so far?
Yeah, yeah. So I had a general awareness of the importance of Vitamin D for bone health and that it was important for immune function, but what really got me interested in this topic was an article that I saw that had been published about two years ago that showed that patients who were randomly assigned to get Vitamin D supplements had about a 70% reduction in viral respiratory tract infections. And this-- I saw this article back in March. At that point, COVID was brand new. We knew it was caused by a coronavirus, knew that was a viral respiratory tract infection. I knew that coronaviruses are common causes of viral respiratory tract infections and thought, boy, maybe Vitamin D would work.
And so what I did was I went into the records that we have here in the hospital for the patients that we've cared for over the years and I knew that we had a large group of patients who had Vitamin D levels that we'd seen in the past and that they were coming in and getting tested. And so I looked to see whether those patients who had Vitamin D deficiency and weren't adequately-- had not adequately been supplemented were more likely to test positive for COVID. And what I discovered is that those patients who were, indeed, Vitamin D deficient and hadn't been treated were almost twice as likely to test positive for COVID. And that's the basis of the article that we published in JAMA Network Open.
That's fascinating. We will take questions from the viewers. We're going to try to hold some of those towards the latter part of the program because we have quite a few questions to get through that we've already talked through with our researchers, first. But we will take your questions. So just type them in the comments section. We'll get to as many as possible as we can.
So talk to us about differences in race, because we touched on that with Dr. Lee a little bit just a moment ago, but you're seeing some pretty marked differences, I would imagine in the study?
Yeah. I knew when I started this that Vitamin D deficiency was much more common in people with darker skin, and much more common in areas like Chicago where we don't get much sun. In our original sample, the majority of patients who were coming in and getting tested for COVID were African-Americans, so we knew we had a sample that was heavily African-American and thought that that might be the group where we were seeing the biggest effects. But we didn't have enough cases at that point to really study it.
So over time, we collected more cases. Our original study was with only 600 cases and most recently, we published the second study with 3,000 cases. And with the larger sample size we were able to break things down by race, and also by level of Vitamin D. And what we found was that the effects, the association of Vitamin D deficiency with COVID was much stronger for African-Americans. And moreover, what we found was that the risk of testing positive for COVID was actually increased, even with levels that were above what is considered adequate. So normally, 30 or above-- 30 nanograms per milliliter or above is considered an adequate level. And we found that patients who had levels of 30 to 40 nanograms per milliliter of Vitamin D actually had a two to three full times increased risk of COVID compared to patients who had 40 nanograms per milliliter or more.
So that made us think that African-Americans may benefit in terms of immune function of having even higher levels. We suspect there may be similar relations for individuals who are not African-American, as well, and that's something we're continuing to study. But for now, we see this strong association for African-Americans.
So explain to us how this works. You've done the research as far as just looking at the association, and now we're starting a clinical trial, is that correct?
Yeah, that's right. So what we observe is an association and we control for lots of other variables that might explain both the Vitamin D level and why people get COVID so that we don't think it's confounding, but we don't know for sure. And so a randomized trial allows us to take a bunch of individuals who meet certain eligibility criteria and then consent them. And then allow them to randomly receive either a low dose or a medium or a high dose, for example, and then understand whether they are less likely, indeed, to get COVID, depending on the dose that they get.
Interesting. So how-- you were telling me a little bit before the program, we do have some folks already involved, but you would like to get more, too, so I want to promote that throughout the program so we can make sure we get that.
Sure. Let me tell you a little bit about the studies.
We're doing we're doing two of them. The first one is funded by NIH, and that's a study we're doing jointly with Roche. And there, people come in, they sign a consent form, they get some labs done to test their calcium levels and other sorts of blood levels that might indicate what the right dose safety for Vitamin D would be. And then, assuming they meet the eligibility criteria, they're then randomly assigned to either a low dose of Vitamin D or a medium or high dose of Vitamin D. And this allows us to tell whether that medium or high dose is affecting them, compared to the low dose, in terms of whether they test positive for COVID over time. And we call them every few months to see how they're doing and checking in.
So that's a study that's just in the Chicago area and requires that people come in either to us or to Roche. The other study we're doing is completely on the internet. And there, people sign up, they can go to the website, they type in answers to questions to make sure that they're eligible. If they're eligible, we simply mail them some Vitamin D and then we follow up with them through surveys over the course of a year and see what their outcomes are. And that's open to people anywhere in the US.
So that probably answers my next question, which would be, do I need to be a patient of UChicago Medicine or Roche to participate?
No. Absolutely not. We have had many of our own patients sign up and of course, that's wonderful. But we've had lots of people show interest from elsewhere. And one thing we've seen is actually people signing up in groups some time. They see the study, they get interested in it, they tell their friends, and they kind of do it together. So we welcome people of course, who are our own patients, but really anyone from the Chicago area, and for the internet-based study-- anyone in the country.
Perfect. It's just-- it's fascinating to me, and it's got to be really interesting work and very rewarding from your standpoint.
Oh, I mean, this has been fascinating. There are people who've spent their entire career studying Vitamin D and I had not, but now that I learn what there is in Vitamin D, I really think it's a fascinating area. And I think potentially really important in understanding how we're going to address COVID.
Great. And let's bring Dr. Lee back into the conversation for a moment, as well. And Dr. Lee, you touched on this a little bit earlier in the program, but can you talk to us about the best sources for Vitamin D, because those are the questions that are coming in from viewers. People want to know what are the best sources and how much should they take?
Well, so today, in modern society, Vitamin D is quite available in pharmacies and the over-the-counter preparations that are usually based on fish oil. You can get them in various doses. The dosage is in units because it's not a pure compound, but it is measured in terms of activity. So if one is-- a typical dose of Vitamin D traditionally had been somewhere between 400 and 2,000. And now we know that's pretty inadequate. You can get pills up to 5,000 or 10,000 units at pharmacy. And of course, as you-- over-the-counter-- and the amount that you should take, you should really have a physician's advice because some people have medical problems that could influence the amount of Vitamin D they should take.
You know, it's interesting because I know from some folks standpoint, and I'm in this category, too much sun exposure is a bad thing. I've had some significant challenges with that over the years. So the supplement probably is the way to go for people like that, I would imagine, and probably dietary changes. But the tricky part of this, and again a little bit of a discussion before the program is, it's really kind of difficult to tell how much you actually need to take. Is that-- would that be accurate?
Yeah. I think it's really hard to know. The guidelines that led to the recommendations of 400 to 600 to 800 international units a day as the recommended daily allowance were based almost completely on bone health. They really didn't have any data on how much you need for the immune system. And then, the paper that we studied or published recently is one of the few that really ties blood levels of Vitamin D to immune function. But even then, we don't know for sure that the blood levels are the right measure. There are theories that emphasize what's called free Vitamin D-- vitamin D that's circulating in the body but not bound to Vitamin D binding proteins, which is most of what's measured, and strong reasons to believe that simply taking a supplement, even if your levels don't necessarily go up that much, may be of independent value.
So one of the reasons in our studies that the basic comparison is between 400 international units a day and 4,000 international units a day is that we really don't know, for sure, what the right level is. Nor do we know, frankly, that the level is the perfect measure. It may be that getting daily sunlight, that taking a supplement daily, makes such a big difference. I can't help but resist pointing out that COVID got so much worse when it got to the winter. And now, it's getting much worse in South America as they're approaching winter.
So sunlight and the production of Vitamin D really does seem like it's quite possible could make a difference. And so that daily supplementation or daily sunlight, which unfortunately isn't possible in Chicago in the winter, at least, unless you're a very robust person-- getting something daily is probably a really good idea. And that's one of the reasons why, in our studies, the control group with low Vitamin D is actually getting the recommended daily allowance. It's not that they're getting no Vitamin D.
Interesting. So if somebody had their COVID-19 vaccine, should they still take Vitamin D? I imagine there's-- I mean, there's a lot of other benefits, obviously.
Yeah. The truth is we don't know. Obviously, you get a lot of protection from the vaccine and people should be getting the vaccine and wearing their masks and social distancing and all of that. But we know the vaccine isn't completely protective. And we don't know how long it will continue to be protective, or what will happen with some of the new variants that are coming around. To the extent that Vitamin D is important for enhancing the immune system, I think there's good reason to believe that it may be useful in this. And so the eligibility criteria for our study include people who've gotten the vaccine.
We think we will learn the most, probably, from the people who haven't gotten the vaccine because they're at higher risk, but we welcome the participation of people, even if they've gotten the vaccine, because we think the risk is still there and the potential for benefit is still there.
And so, Dr. Lee, I know you're extolling the benefits-- you're both extolling the benefits of Vitamin D and that's certainly evident, but can you take too much? Is there an issue if you go overboard with it?
Well, it's certainly-- it's certainly possible. But as Dr. Meltzer just pointed out, we are just beginning to get an insight into what the dose response is and also at what point the system is overloaded or gets to the point where there might be a toxic effect. And so these answers are not there yet. There have been a lot of concerns about raising serum blood calcium levels with Vitamin D supplementation. And we found a lot of those concerns-- in fact, not just we, but the entire medical community that that's a very unusual problem unless one has other endocrine issues. So it absolutely is possible to take too much, but with the doses that we're talking about here, it's very unlikely that it is too much.
I mean, after all, a lifeguard working on the beach makes about 20,000 units per hour.
So until we-- the doses we're talking about are small, compared to what a person 5,000 years ago working in the field would make on an hourly basis.
So we're just learning.
Yeah, yeah. That's fascinating. I had no idea. We are getting some questions from viewers and I want to get to as many of those as we've got about nine minutes left. So this one is from YouTube. Thanks for viewing on YouTube. Can people with high Vitamin D have low antibodies as T cells have already taken care of infection with the help of Vitamin D? Dr. Meltzer, I don't know if you want to--
I don't know, or Dr. Lee, would you like to answer that one?
Well, so you know, it really-- so first of all, the precise answer to that really depends on the individual. I mean, they have different effects. I mean, the Vitamin D turns on the function of certain kinds of immune cells like the white blood cells and the cells that are on the surface of the intestines and in the bronchials. These are eosinophils that have sort of a generalized, predetermined response. But it down regulates a bit the other type of immunity. Together, it's orchestrated. And you know, this is an area of expertise where new results are coming out every year. We don't know the entire story yet.
And I think that's a great answer. And I'll just add that one of the things we know about Vitamin D is it's an immunomodulatory. It doesn't just activate the immune system, but it prevents it from becoming over-reactive--
--which we know is a problem in COVID. And there's some evidence that it also increases the specificity of response to the immune system. So better targeting the pathogen without leading to too much inflammation.
Interesting. Here's another good question. Does a Vitamin D lamp help or does it need to be a supplement? I have heard about people that buy the specific lamps that they put on themselves when they're at their desk at home all day.
Yeah. I think we know that sunlight works very well. I know that there are Vitamin D lamps that have been shown to increase Vitamin D levels. I think there are a variety of brands out there. How well they work, I can't speak to any specific brand. But you do have to be careful, of course, because that's ultraviolet radiation and there are risks associated with that. So it's definitely something that's in the realm of things worth thinking about, but we are studying supplementation because it's much cheaper and doesn't have some of the same exposure risks.
But as Dr. Lee said very rightly, there's a lot we don't know about Vitamin D. And there may be some hidden advantages to lamps in doing things like breaking down Vitamin D once it's already been activated and that needs to be gotten rid of.
Great. Dr. Lee, another question from a viewer. I'm going to throw this one to you. Does Vitamin D need to be combined with other vitamins like K to be effective?
No. I mean Vitamin D has-- I mean does require certain action of other vitamins like Vitamin A to activate the receptor. But that I think clearly these things are what's really fundamentally is required is part of the normal diet. So there's no other co-factor that's required to take with Vitamin D for Vitamin D to be effective in a normal person with a balanced-- on a balanced diet.
Interesting. Another question from a viewer. Dr. Meltzer, I'm in your study with Roche. I'm concerned that I have to decrease my Vitamin D3 in order to go on your low dose study. I've been on 6,000 IU for 14 years. What effect, if any, will this have on my levels?
Yeah. So in general, if people are on a dose of Vitamin D that they have been recommended by a doctor, we recommend that they stay on that dose. We don't want to disrupt a plan of care that has worked for someone. On the other hand, if people are taking a dose on their own and don't know for sure whether that's a dose that they really need for any reason or don't have a doctor who's told them that, I think we're all guessing, in some sense, and being randomized to a different dose could be a very reasonable thing to do.
As I mentioned earlier, the level that you measure is informative but it's not necessarily the key driver of this. We do not know whether they're taking 400 or 4,000 or 10,000 units will change outcomes, nor do we know whether it will change outcomes depending on what your blood levels are. The blood levels are heavily reflective of the amount of Vitamin D that's bound to Vitamin D binding protein, and what may be most active and affecting your immune system is what's called Free Vitamin D. And although those are correlated, they are not perfectly correlated and they may vary across people according to the Vitamin D binding proteins.
And the Vitamin D binding proteins I'll say, differ a lot among people independent of race, but they also differ quite a lot across races. And so that may be one of the important reasons why we're seeing these different effects in our studies are different associations with Vitamin D levels by race.
So we have about 2 and 1/2 minutes left in the program and I want to talk just a little bit more about the study so we can really emphasize that you need more people to join you in your studies. So you're putting out that call and asking for some help there.
Yeah. We are really eager. Ideally, we would enroll 2000 people in each of our studies. In total, across the two, we've enrolled about 700 so far. So we have a ways to go. They're easy to sign up. There's information available on the internet. I think there'll be a URL put up and there's a phone number available, as well, for people who want to call the phone number. If you're telling your friends and don't have the URL with you can simply Google Vitamin D or a Vit D and UChicago and it'll pop right up on your website browser and you can find information there.
There's actually a page that will guide you through thinking about whether the in-person study or the internet study might be preferred for you. And you can do that based on whether you're really eager to have a very higher dose like 10,000, or you're happy with the 400 or 4,000 and how practical it is for you to come in to U of C or Roche to get labs or whether you prefer to just do it on the internet and let us mail you some Vitamin D.
Great. Well, John, who is our Producer Director, Executive Director, pretty much wear many hats and runs the thing, he's been putting that graphic up a lot. So hopefully we'll get some folks signed up. And I do want to let people know, remind people, that the program actually will live on Facebook so you can always refer back. And if you want to talk to one of your friends and in your social circle, you can even send him the link from Facebook or YouTube, as well. So we'll make sure that we get that information out to as many people as possible. This it's really interesting.
Oh, great. Thanks. It's been fascinating to study and I really hope it makes a difference in COVID and beyond, because I think Vitamin D is of fundamental importance for our immune systems, in general. And we're going to need those even when COVID is gone.
And I got a message that somebody watching just signed up.
Oh, that's great. I'm thrilled.
We've got at least one. So that's good.
That's a big success. I'll take it.
That's awesome. Thank you so much for doing this. And Dr. Lee, thank you so much for taking time out of your day today to do this. We really appreciate both of you coming in here.
Thank you so much. So we are out of time. Special thanks to our physicians, obviously, for being with us today and researchers. And a big thank you to those of you who watched and participated in today's program. You had some really wonderful questions.
Please remember to check out our Facebook page for our schedule of programs that are coming up in the future. And to make an appointment with one of our doctors you can go at UChicagoMedicine.org or you can give us a call at 888-824-0200. Thanks, again, for being with us today. And I hope everyone has a great week.
New research indicates that vitamin D may protect against COVID-19, especially in Black people.
University of Chicago Medicine researchers Raphael C. Lee, MD, ScD, and David Meltzer, MD, PhD, discuss the importance of adequate vitamin D in preventing disease, and how you can participate in a clinical research trial