COVID-19 and Vitamin D | Association Between Vitamin D Deficiency and COVID-19

[Music] all right ninja nerds in this video today we are going to be talking about vitamin d and its effect in covid19 before we get started though please make sure you hit that like button comment down in the comment section and please subscribe also down in the description box web links our facebook instagram patreon account as well as all of the articles and all the references that we're going to be referring to throughout this video all right let's get started all right engineers so what we're going to do is is i'm going to basically give you guys the take home messages or basically summarize all the different kind of articles that i went through basically involving vitamin d and covid19 there was a lot of articles that i comb through i'm going to have all of those down in the description box if you guys want to go click them and really kind of dig in through all the the details of it but i want to just kind of give you guys the take home message so there was eight things that i wanted to talk about and we're going to really kind of dig into how vitamin d is involved in these processes and a lot of detail over here we're going to really get into the immunology the nitty-gritty stuff first thing that we kind of see with these articles is that whenever there is lower vitamin d levels it is associated with an increase in mortality particularly in covidinite cova-19 patients that are hospitalized that's one big thing and we're going to talk about why that is the second thing that we see is that vitamin d low levels of it actually are associated with longer days of people being on the vent mechanically ventilated because of the cardiopulmonary complications associated with cova-19 the other thing which is really interesting is there may be something with this viral clearance and so we may see lower vitamin d levels associated with higher sars cov2 positive pcrs related to infectivity in that sense here's something i really found that was interesting in one of the articles is that lower vitamin d levels are associated with elevated crp fibrinogen d dimer levels and covid19 patients these are all things that are those acute phase reactive proteins massive kind of inflammation cytokine storm so we'll talk about some relationships with that the next thing is that we see that low vitamin d levels are associated with a decreased clearance of that sars cov2 virus the next is that low vitamin d levels are associated with elderly african-american race hispanic race and particularly common in obese individuals or metabolic syndrome kind of conditions next one is that low vitamin d levels are associated with an increased risk of developing or progressing of chf coronary artery disease diabetes and hypertension and then finally one of the big things is that we don't have a lot of data on like the actual mechanism of how vitamin d is particularly helping in respiratory tract infections with covid19 or starscov2 but we do see that vitamin d has been shown to be effective against viral respiratory tract infections like rsv influenza and rhinovirus and we'll talk about all those mechanisms these are the take home messages that we can basically ascertain from all of these different articles now what i really want to spend most of the time doing is going over how this is theoretically possible all right so now what we're going to do is in order for us to really understand how vitamin d is we're kind of basically helping us to modulate our immune system and play roles and particularly prevention or maybe even particularly treatment in covid19 we have to kind of go through the basics like the metabolic pathways of vitamin d build our foundation and then we'll dig into like the immunomodulation some of the other cascades that it's involved in so big thing to remember is that vitamin d actually can come from you know exogenous sources foods that we eat or the actual medication like the capsules or liquid solutions that it comes in what are some of these actual sources just so that you guys know you can find this in milk particularly if it's like it can be fortified in milk it could be an egg yolks that's another big one yogurts cereals an interesting one is liver okay so liver and another one is mushrooms okay so these are just some of the types of things where you can find vitamin d in now if we take vitamin d whether to actually be through an actual like source like the actual vitamin d capsules or whether we get it from this type of food source we're going to intake that and it's going to get basically ingested and moved down our gi tract right so this green tube here is representing your gi tract and here is going to be our cute little vitamin d ready to try to help our body now this vitamin d is actually a fat soluble hormone that's very important so in order for it to actually be absorbed it actually has to be bound with fat and cholesterol into these things called me cells i don't want to get too deep in that but i just want you to understand that you need fat or some type of cholesterol source in order for the vitamin d to properly be absorbed across the gut tube and into the bloodstream and here we're going to represent our vitamin d now vitamin d when we're actually taking it it's usually in the form of a particular name i'm going to abbreviate it because it's one heck of a name i'm going to abbreviate it as cholecalciferol so usually it's in the form of what's called cholecalciferol we're going to abbreviate that as ccf so if we and we actually ingest these substances we can get vitamin d need fat in order to absorb it across the gi tract into the bloodstream the type that we're actually absorbing into the bloodstream is ccf cholecalciferol in this form of vitamin d now that's one way that we can get vitamin d the second way that we can get vitamin d is from the skin so you know within the skin we actually store a particular type of cholesterol here called seven i'm going to abbreviate this one as well seven actually i'll write it dehydro cholesterol okay 7d hydrocholesterol and what happens is if we are exposed to sunlight what that does is is it helps to be able to convert that 7d hydrocholesterol into this cholecalciferol if you will so what do you need in order for this process to occur you need sunlight or uv light right or uv rays if you will and what that does is those uv rays hit the skin and help to convert the 7d hydrocholesterol into what particular molecule again the cholecalciferol or the vitamin d now big thing to remember here is that this is actually a fat soluble type of hormone it's actually a steroid hormone if you look at its structure it actually resembles that of asteroid because it's derived from cholesterol in order for things like that to move throughout our bloodstream it can't just go willy-nilly everywhere on its own it has to be bound to something to move it around so we have these proteins in our bloodstream called vitamin d binding proteins and these vitamin d binding proteins help to bind onto the vitamin d pretty straightforward and then help it to move to the particular organs that it needs to go to so again what are these proteins that we actually have here we're going to abbreviate these as well these are needed to transport the vitamin d it's called vitamin d binding proteins now we've taken the cholesterol i mean we've taken the vitamin d whether it come through food source or whether it came from the skin from exposure to uv light we have this cholecalciferol it's being transported via the vitamin d binding protein then what happens is it travels through the bloodstream and goes to a beautiful organ that we all should be very thankful for and that is that good old liver okay what happens is in the liver there is a particular enzyme that is very integral to vitamin d metabolism this enzyme is called 25 hydroxylase and what this enzyme does is it helps to be able to add a hydroxy group onto the 25th carbon of colic calciferol so now if we have that process happen here we're going to take the cholecalciferol and we're going to help this enzyme to stimulate it and this is going to convert the actual cholecalciferol into 25 hydroxy cholecalciferol so we'll put like a little hydroxy group onto that now what is the name of this now this is called 25 hydroxy cholecalciferol now the next thing that has to happen is we got to take that 25 hydroxycolic calciferol and send it to another organ in physiology we are pretty aware of what happens here it has to go to the kidney and you know in the kidney and though it's called the proximal convoluted tubules there's a particular enzyme there called one alpha hydroxylase again what is it called one alpha hydroxylase and all this enzyme does is it puts a hydroxyl group an oh group on the first carbon of the cholecalciferol so now if this guy does that it helps to catalyze this step here what is this going to look like now well now you're going to have this 25 hydroxycholecalciferol turn into the active form which is called one comma 25 dihydroxycholicalciferol and this is the active form of vitamin d okay we'll write that down active form of vitamin d this is the form of vitamin d where it exerts a lot of its actual effects it's hormonal effects one of the things that we do know about this enzyme i'm sorry about this actual hormone is that it has the ability to work on the actual gi tract particularly in the duodenum and when it acts in the duodenum it helps to be able to increase the calcium absorption and what that does is that increases the calcium levels in the blood so we're going to have increased calcium levels in the blood but this is actually one of the things that we commonly know about it but there's something else about the vitamin d that's very interesting when it comes to the immune system action so let's take this 25 hydroxycholecalciferol and now we're not going to just take it to the kidney we're going to take it somewhere else we're going to take it to our immune system cells because guess what our immune system cells can do these immune system cells can do a couple things one is they have a particular enzyme guess what enzyme they have within them if we take an immune system cell let's just say that we pick this as our macrophage okay this is our macrophage right one of the white blood cells it has a particular enzyme here called one alpha hydroxylase that should sound familiar right and what that one alpha hydroxylase can do is do what it helps to convert the 25 hydroxy cholecalciferol into what into one comma 25 dihydroxycholi calciferol so now this actual macrophage can actually express this molecule therefore converting the 25 hydroxycolicocephal into one comma 25 dihydroxylic dihydroxycholic calciferol which is the active form of vitamin d at once we probably only thought oh this is the only way that we can get that activated vitamin d but our immune system cells can also help with forming active vitamin d so we understand how we're able to get the active form of vitamin d right we could either take it via the absorption right from the skin from the gi tract to the liver get the 25 hydroxy go to the kidney make one come 25 dihydroxy which is the active form or take it to our immune system cells in this case we're picking macrophages and they can also help to convert the 25 hydroxy into the active form one comma 25 dihydroxy now here's the cool thing when you take a look at this hormone it's a steroid hormone that means that they don't need proteins on the cell membrane for them to bind to and exert their effect they can pass right through the cell membrane when they pass through the cell membrane there's a particular protein located inside of the cell that loves to bind to and this is the vitamin d receptor so inside that actual vitamin d we're going to represent it as a circle now a little pink circle here that vitamin d that one come 25 dihydroxycholine calcified the active form is going to bind onto this little receptor inside of the cell and this is called a vitamin d receptor protein so it's going to have a vitamin d receptor protein once it binds to that protein guess what happens it gets taken into the nucleus of this macrophage when it gets taken into the nucleus of this macrophage it activates particular genes in the actual dna that dna when it's actually going to be stimulated particular genes are stimulated it'll then make mrna you know mrna and then mrna will then go to ribosomes you know ribosomes help to do with the mrna make proteins so then we're going to make proteins what is this process here called we're actually going to do what you're going to have gene expression make mrna that is called transcription then you're going to actually translate that into proteins now these proteins that are made are very very interesting and that's what we got to talk about what are some of these proteins that it's actually going to make here so it's going to make a couple different proteins one of those proteins that we really want to talk about here is going to be what's called catholicitans catholicitans one heck of a name but this is a really cool antimicrobial protein the other one that we're going to talk about here is called beta defenses called beta divincins so already we're able to see that vitamin d has the ability to work on our macrophages increase the proteins synthesis particularly what types of proteins beta defensins and catholicitans these are antimicrobial proteins that's what i want you to take away from this let's focus on beta defense first because it's a shorter action catholicisms have one heck of an action so what beta defensins do is they love to just fist these viruses cell membrane okay they look just punch holes into the cell membrane now actually what we should be very specific here is a virus is not a cell but it has in this case some viruses especially sars cov2 it has an envelope so a viral envelope is basically made up of a phospholipid bilayer and what happens is is these beta defensins they love to come and just poke holes into that actual viral envelope which is basically a phospholipid bilayer similar to that of a cell membrane in actual like host cells or bacterial cells so now once it starts actually kind of punching all these holes let's actually write that down that's a funny thing right it's called it's going to be punching holes in the actual viral envelope when it's punching these holes into the viral envelope this basically is going to lead to the destruction of the virus this will lead to destruction of the virus so already we're able to see how vitamin d is able to potentially work on viruses in a simple way one of them is by increasing the expression of beta defenses increasing the expression of beta defensiveness now remember what i told you there's not a ton of data looking at this mechanism in sars kovi 2. but what we do see this this actual mechanism in and some of the research is we see this in rsv the respiratory syncytial virus we also see this in the rhino virus and we see this in the influenza virus okay and so we can us in some way make an association that vitamin d maybe has the ability to do this via affecting that virus via the sars cov2 virus that causes cova-19 so that's one way that we're able to get to this process the next way is actually the more intense but very very cool way all right the next thing here the catholicitans right these are antimicrobial peptides one of the things that they can do okay is they have the ability to act on these viral particles right and you know viruses they have particular proteins that are basically incorporated into like the viral envelope it can cleave some of these viral proteins so one of the things one of the quick easy dirty things that it does is it helps to act on viruses and actually helps to cleave or another kind of term that we like to use is it undergo it causes proteolysis right in other words as breaking down the proteins cleaves are undergoes proteolysis of viral peptides that are basically making up the virus and by doing that if you cleave some of these actual viral peptides guess which are going to induce destruction of the virus so one way we can actually do this is by increasing catholicity and expression now here's the next thing that catholicisms do which is even cooler they act on macrophages you see this here this is our macrophage so it's going to come here and it's going to stimulate this macrophage our immune system cells so these catholicisms have the ability to activate macrophages so they can stimulate the activity of macrophages there's something else that they help to do they act on small capillaries so let's say that the virus is actually infected some part of the tissue right let's say it's the respiratory tissue one of the things that these viruses will do is trigger you know this immune response let's say the catholicism response catholicitans will actually cause the vessels in that actual vicinity of where the pathogen is to become more permeable so it's going to increase the vascular permeability so that's another thing it's going to do it's going to increase vascular permeability why is that important because you know what's running through the blood white blood cells like macrophages so catholicisms are going to increase the permeability of the vessels where the pathogen is and cause more macrophages to leak out into this area where that pathogen is and then it's going to activate more of the macrophages and then it's going to do one more thing it's going to tell the macrophages where to come where is that virus or that pathogen and this is called chemotaxis so it has the ability to induce taxes increase vascular permeability and activate more macrophages now when we activate more of these macrophages here's why this is so interesting these macrophages start then release uh basically whenever they're activated they come and they engulf what does that call whenever a macrophages takes in particle matter phagocytosis so what's going to happen is this macrophage is going to undergo phagocytosis what is this called here let's do it in a different color make it purty right this is called phagocytosis phagocytosis so it's going to undergo phagocytosis of this actual virus viral particle okay once it takes it in it takes it into what's called a phagosome combines it with a lysosome makes a phagolysosome breaks down that actual virus like a shiatsu and then does what expresses a piece of that viral peptide in this case one of the peptides on the virus and the one big one that we know about is the s peptide and sars cov2 expresses a piece of that virus on a very particular protein in this case this purple protein what is this purple protein here called this purple protein is called an mhc2 molecule and again what is that red molecule there that's indicating an antigen okay so this is indicating a antigen in this case that's one of the viral peptides okay then a particular cell is good just kind of come running around running around the area where the pathogen is and all these immune system cells and it just so happens to click in with this actual mhc2 molecule in the antigen what is this cell here that comes into this area this is called a naive t cell okay so it really doesn't know who it is like most of us right and what happens is this naive t cell has to have a particular protein that recognizes the antigen and that is called a t cell receptor then it needs a particular protein to recognize the mhc2 molecule that is called what that's represented here in pink since we have that pink this is called a cd4 molecule so it's called a cd molecule once this interaction happens this naive t cell depending upon cytokines that are released has the opportunity or the decision to go two ways if it's like giving it options if the naive t cell decides to go this way we need particular cytokines to stimulate it to go in that direction and if we want it to go this way we need particular cytokines to push it in this direction what are the cytokines that push it in this direction which is what vitamin d actually helps to do which is very interesting we need a particular molecule here called interleukin 4. so what happens is that interleukin 4 is present what it does is is it stimulates this naive t cell to become a particular type of t cell very specialized t cell and we call this a th2 cell so it's a t helper type 2 cell this t helper type 2 cell once it's stimulated by interleukin 4 to go from naive to t helper 2 then guess what it does it then starts releasing more cytokines that are going to activate this next cell what are these cytokines this is interleukin 4 and interleukin 5. and what these cytokines are going to do is they're going to stimulate this next cell here this purple cell and this is called a b cell or a b lymphocyte and what b cells do when they're stimulated by interleukin 4 5 is they proliferate and then they convert or differentiate into another type of cell this is called a plasma cell and then what happens is this plasma cell once it's primed by these cytokines it starts blasting out very important little antibodies and these antibodies are now primed to bind to the particular antigen that our macrophage phagocytosed and what is that actual antigen well in the sars cov2 virus we know what it is it is the s-peptide but again we're talking about this with other types of viruses rhinovirus influenza rsv but we can try to make maybe an association with the s-peptide now once these antibodies bind to the s-peptide what does it do i guess that's the big question right it can enhance what's called your complement system and without getting into tons of detail here is your complement system is basically a part of your innate immune system and they basically help to put holes and really damage and enhance the immune system reaction to come and destroy more of that virus the other thing it's going to do is it's going to increase like your phagocytosis process so you're going to basically have that macrophage come in and gulf more of the virus and the last thing it's going to do is that it helps to neutralize the virus so in other words if you had a virus and we actually produce these antibodies let's say here is the virus and we produce antibodies against it if i have antibodies bind to every single one of these points here guess what happens that has no ability now to bind to the actual host cell and cause damage in this case and the sars cov2 virus is the s-peptide binding with the ace2 receptors if we theoretically produce these antibodies and bind to it then we can actually inhibit the actual insertion of the virus into the host cells so that's pretty cool right to see how our immune system helps in this process here's the other thing though this pathway is good that's what i want you to associate with if you will and you know i know this kind of sounds a little bit crazy but this is the good pathway so i want you to kind of just in a really simple sense think about this as the good pathway or the uh anti-inflammatory pathway if you will this other pathway is where we run into a lot of issues with potentially sarge v2 so this pathway is actually going to be dependent upon two things one is dependent upon an interleukin that's released but guess what this th2 cell whenever it goes in this direction it doesn't want this pathway to occur so this th2 cell this is crazy cool it releases a particular cytokine and this cytokine is called interleukin-10 and what interleukin-10 does is it tries to inhibit this pathway to make sure that most of the naive t cells are going the good pathway or the anti-inflammatory pathway well that begs the question what the heck is this bad pathway i guess if you would or this pro-inflammatory pathway and why is it bad and we've got to get back to the question here how in the heck does vitamin d help with this we've kind of seen some sense here where it comes from that catholicitans the beta defenses and we're going to talk about the next part we know that vitamin d is trying to drive the catholicity in production drive the beta defense and production but guess what else it's trying to do it's trying to drive this anti-inflammatory pathway so what it does is is i want you to remember here is insert vitamin d here in your diagram where it also has the ability to stimulate this pathway the anti-inflammatory pathway so it wants to drive it this direction and if it drives it this direction what happens then via this th2 induced interleukin tent it inhibits or suppresses the pro-inflammatory are bad pathway if you will now that begs the question what in the heck is this pro-inflammatory pathway all right here we go in order for the naive t-cell to go this next direction we obviously need this interaction here but we need another cytokine and this cytokine is called interleukin 12 interleukin-12 and what interleukin-12 does is it converts the naive t cell from this interaction into another type of t cell and this t cell here we're going to write it here in blue this is called your t h 1 cells or your t helper type 1 cells when it stimulates this process the t helper 1 cells start releasing a ton of a particular molecule that's really going to ramp up inflammation and this molecule that it's releasing is called gamma interferon now what gamma interferon does is it activates macrophages now you might be like oh that's going to activate macrophages and cause this process to occur well remember if it activates macrophages they phagocytose the virus and it comes down to this pathway it's going to drive it this direction why am i saying that this is the bad pathway here we go these macrophages when stimulated by the gamma interferons they start releasing a ton of cytokines cytokines that you guys might remember from our first covid19 video that we did interleukin one and tumor necrotic factor alpha and interleukin 6 and interleukin 8 and you know what else lots of other small little inflammatory molecules called chemokines and there's so many of these i'm just going to put cxcl that's what they stand for chemokines there's tons of these so we're going to make a lot of these molecules and if you guys remember one of the big ones that was pretty much responsible for a lot of the things that we see with the stars cov2 is which one interleukin-6 this is the big one now regardless these inflammatory cytokines this is going to produce a massive amount of inflammation okay so i'm going to remember we gave it a particular name what was that called when you had this massive amount of inflammation due to all these cytokines cytokine storm so it's gonna cause this massive cytokine storm and what that's gonna do is it's going to act on a bunch of different organs and if you guys remember we said that it kind of induced multi-system organ failure how did it do that do you guys remember remember it had the ability to act on the heart and we said that when it acted on the heart it did what it had the ability to induce what particular type of things it maybe had the ability to induce heart failure or worsen already present heart failure it had the ability to produce myocardial infarctions right so these are some of the things that we saw with respect to the actual kind of the cytokine storm related to the multisystem organ failure if you remember we actually kind of talked about what type of molecule that you kind of trend whenever somebody is having this kind of cytochrome storm you're you're kind of tracking those troponin levels and that's one of the reasons why the other thing is it's acting on the lungs all of these cytokines and when it's acting on the lungs what was that doing to the lungs that was inducing the acute respiratory distress syndrome ards so that could potentially induce ards acute respiratory distress syndrome then it was acting on the kidneys and you guys remember what it was doing to the kidneys it was damaging the kidneys and inducing a severe aki so it could also cause acute kidney injury man this is kind of starting to make sense right all right what else here's where i found it very very interesting what particular interleukin did we say again interleukin 6 was the big kind of like problematic one well one of the things that we see here is that it also can act on the liver and you know when these act on the liver particularly interleukin-6 but even a little bit of interleukin 1 and tnf alpha it triggers the production of a lot of different types of acute phase reactant proteins what were some of the ones that i mentioned over there with vitamin d crp light bulb should start coming off fibrinogen ferritin right and there's other different types of molecules over there you know what uh the breakdown product of the actual fibrinogen is you get like the d dimers too so that's also another relationship over there but again it's producing a lot of these what we call acute phase reactive proteins now the big thing with these is that these also enhance the inflammatory response and one of the things that we see from one of the articles here particularly pertaining to crp specifically is that crp as well some of these acute phase reactive proteins would promote a lot of inflammation of our blood vessels how the mechanism is pretty in depth and and it's simply put that crp binds on to cells particularly what's called phosphocholine on the cells our endothelial cells of our blood vessels and induces a lot of inflammation a lot of reactive oxygen species but the whole entire end product here is that it starts increasing atherosclerotic plaques right so atherosclerosis endothelial cell dysfunction and you know what happens whenever you have lots of plaques and endothelial cell dysfunction and a lot of inflammation within the blood vessels it increases the risk of thrombosis so with a lot of these this cytokine storm and the related acute phase reactive proteins particularly one of the big ones crp what are some of the things that we're seeing with this we're seeing increased inflammation but pertaining to the blood vessels right so it's increasing inflammation causing cellular dysfunction particularly that phosphocholine molecule that it binds to and it's increasing thrombotic states thrombotic states and it's increasing reactive oxygen species whenever these pro-thrombotic states occur what do we see from this you can start seeing emboli or thrombus form isn't that one of the interesting things about the actual covid19 is that we see of this high coagulability of this hypercoagulability scene with this disease maybe related to the cytokine storm so this is one big thing now here's where i got to add in this next part here let's say that someone has a heart failure or a coronary artery disease or they have diabetes or hypertension what do you think that these plaques in these thrombi are going to do to those conditions it's going to worsen them and what patients do we see higher fatality rates with kelcovid19 patients with cardiovascular types of comorbidities like which ones this is going to increase the risk of worsening so this can particularly worsen what kinds of conditions chf hypertension coronary artery disease and what else diabetes mellitus oh man so now we have an idea of what why this pathways is so dang bad right but here's the cool thing let's follow this now let's come back and see how potentially vitamin d can reduce the risk of worsening chf hypertension cad diabetes mellitus decrease these actual acute phase reactive proteins and potentially decrease thrombotic states and inflammation and decrease this actual high mortality rate associated with all these complications for multi-system organ failure wasn't that what we talked about over there we're decreasing the time required on the vent let's go back and see how the heck it does that all right so now that we've kind of gone through this here's what i want us to do let's take for example we have decreased vitamin d kind of follow this process then let's come back really quickly and see what happens if we normalize or increase our vitamin d how it's going to affect this process ready you have low vitamin d low vitamin d will lead to less proteins like beta defenses and less catholicitants decreased beta defenses is going to lead to what decrease fisting those actual viral envelopes right that's going to lead to decreased destruction of the virus also you're going to decrease catholicism decreased catholicism leads to decreased macrophage activation decrease chemotaxis decrease movement of the macrophages into that area where the pathogen is it's also going to decrease the proteolysis or cleavage of the viral peptides which decreases the destruction of the virus so now the virus is building up next thing if you have decreased vitamin d you have decreased follow this pathway decrease phagocytosis of the virus then that means that if you have decreased vitamin d where else does it act in this anti-inflammatory pathway if you have less vitamin d trying to stimulate this immune system reaction this direction which way are you getting what happens then let's kind of follow this decreased vitamin d leads to decrease interleukin 4 converting the naive t cell into the th2 so we end up decreased th2 cells decrease b cell activation decrease plasma cell activation decrease antibody production decrease neutralizing of the virus decrease complement system activation of the virus and decrease phagocytosis of the virus then on the other fact if there's decreased vitamin d you're having decreased stimulation of this pathway right if there's decreased stimulation of this pathway what else is happening there's decreased interleukin 10 that means that you're no longer suppressing this pathway where are you going to drive the pathway in the pro-inflammatory or how do we define it pro-inflammatory or bad not bad bad pathway now if you're not suppressing this this is going to have more of these t cells turn into th1 cells more th1 cells release more gamma interferons more cytokines more multi-system organ failure more acute phase reactive proteins more inflammation more thrombotic states and worsening of chf hypertension cad and diabetes mellitus it makes sense that we can kind of understand those assumptions that we made so we talked about the deficiency of vitamin d in this pathway now what if we have increased vitamin d or normalized vitamin d or upper limit of normal vitamin d how does that help it increased vitamin d increases expression of the beta defense inc and catholicitans that means that we're going to increase the destruction of the virus by proteolysis or punching holes in the viral envelope we're going to make more catalysis more macrophage activity more phagocytosis more expression of the actual virus on the mhc2 complex if there's more vitamin d which pathway are we going to try to stimulate this pathway the anti-inflammatory pathway increasing antibody production to neutralize enhanced complement system activity and phagocytosis as well as increased vitamin d is going to increase the th2 cell production of interleukin 10 suppressing the bad pathway decreasing the cytokine storm decreasing the multi-system organ failure type of effect decreasing the actual acute phase reactive proteins decreasing inflammation thrombotic states and decreasing the worsening of these comorbid states in kova 19. that's amazing how that actually makes sense right we got to do one last thing that i thought was also really cool going back to this ace 2 angiotensin cascade so the next thing that you guys got to remember we kind of talked about this a little bit back in our cova 19 kind of pathophys video but if you guys remember your renin angiotensin aldosterone kind of cascade right the liver produces a particular molecule called angiotensinogen tensinogen angiotensinogen is a precursor because we know that it actually has to get converted into what's called angiotensin type one and it's done that happens via particular enzyme made by the kidney which is called renin so renin helps to stimulate this process then angiotensin 1 is has to be converted into the next important molecule and this next important molecule is called angiotensin ii and angiotensin ii in order for that to happen we need a particular enzyme in the lungs which is called ace now let's be very careful because we're going to kind of type this one as ace one because ace2 is a different molecule and that is going to help to stimulate the conversion of angiotensin 1 into angiotensin 2. now here's what we know about angiotensin ii we know that high levels of angiotensin ii particularly can increase lung injury how one of the things that we know is that if angiotensin ii levels are high it binds on to an angiotensin receptor when it binds onto that angiotensin receptor it increases vasoconstriction to kind of increase pressure it actually increases inflammation and it increases like fibrosis and a lot of like remodeling processes and all of these things basically increase lung injury now what we know that's really cool vitamin d inhibits renin so let's kind of a little smash in here our little vitamin d okay that one comma 25 dihydroxy cholecalciferol it inhibits renin follow along with me then if you have decreased renin that means less angiotensinogen is converted into angiotensin one so there's going to be decreased angiotensin one less angiotensin one means that you'll have less angiotensin too that means less activity acting on the angiotensin receptor less vasoconstriction less inflammation less fibrosis less lung injury how does it get any cooler than that guess what it does angiotensin ii can move a different pathway angiotensin ii has in order for it to move to this next molecule okay it needs a particular enzyme that we are all aware of in this cova 19 pandemic and it's ace2 right ace two it's designed to stimulate this pathway what does ace2 stimulate angiotensin ii to become i'd never heard of this molecule until this but it is called angiotensin one seven and what angiotensin one seven does is is it increases your vasodilation effects that's gonna decrease the pressure right in your cardiopulmonary circuits it's also going to decrease the inflammation it's going to decrease the remodeling via that fibrosis and that is going to decrease the lung injury one of the theories behind this decreased a decreased movement into this pathway is what sars cov2 right what we are assuming here is that sars kobe 2 there's an association that whenever you have lots of sars cov2 right it is doing what to this enzyme it's decreasing the concentration of this enzyme right because it's binding to it causing it to get taken and it's just decreasing the amount of ace2 so that means less angiotensin ii goes to this pathway more of it goes to this pathway guess what vitamin d does what we're potentially seeing vitamin d may actually and again when i say may we need to kind of do a little bit more studies into this but vitamin d can potentially stimulate and increase the activity of ace2 if you increase the activity of ace2 you increase the conversion of angiotensin to wear to angiotensin 1-7 you increase vasodilation decrease inflammation decrease fibrosis and the big bare bones thing here is that you decrease lung injury so vitamin d has the potential to increase this pathway and decrease this pathway that's amazing and then the one last thing that i read and just to finish it off is like there you know as if there isn't enough that we've covered is that we've also seen that vitamin d can stabilize so vitamin d also can stabilize those pulmonary capillaries so the epithelial cells are the endothelial cells of the pulmonary capillaries it's been shown to stabilize the cell membranes okay of the pulmonary capillary endothelium and again that is quite interesting when it comes to this actual disease we've done a lot so far but we're almost there and this is very interesting what we've been able to kind of see from this the next thing that we have to talk about is the people that are like what are the causes of vitamin d deficiency and let's make sense of that and what's very very very interesting is the people that are more likely to be vitamin d deficient if you look at the if you kind of like take and compare put them right next to each other those that are vitamin d deficient are usually when you look at covid19 fatality rate in covid19 they're almost like identical and kind of vitamin d deficient and severity or higher fatality of cova 19 kind of the demographics and risk factors and all that stuff it's really interesting pretty much make it simple what if your liver is failing so if you have liver failure or like severe like chronic liver disease right that decreased function of the liver is going to lead to decreased vitamin d kind of like activation right so we could really say activation because it has to go through that whole kind of hydroxylase pathway and then from there we obviously could see what that could potentially do the other thing which is pretty straightforward is what is another pathway that you have to go through you have to go through the kidney right we said that that was one of the other pathways so when someone has a chronic kidney disease or some type of renal failure that also leads to decreased vitamin d kind of activation and decreases the kind of amount of activated vitamin d to carry out those functions and again we can see what that would do here's the really interesting one obesity right and you're probably wondering what the heck i was too until i kind of looked into the mechanism here with obesity you have more fat cells theoretically right and what how do we define obesity like you use bmi right greater than 30 which means i'm obese but and i am but the whole point here is that whenever there's high obesity that means higher fat cells what do we say about vitamin d it's as fat soluble hormone guess where it actually does get stored sometimes and fat cells if you have more fat cells guess what you do to that vitamin d you sequester it you suck it in and if you sequester lots of that vitamin d how much vitamin d is actually in the blood circulating and available to carry out these functions not a lot and so that can decrease the vitamin d in the kind of the actual the the circulating vitamin d we'll just say in the blood in this case and we can kind of see how that is effective right that's it that's very interesting the other thing here is with elderly i don't know how many helps to represent them except with someone with a cane no disrespect but you know an elderly and those that are elderly they have decreased production of vitamin d from the skin the elderly is a very um pretty straightforward one and in elderly individuals 70s 80s right so we could say like 70s you know to 80s their skin has less vitamin d production right so they have also just less vitamin d production and here's the thing go back to this what patients do you see higher fatality rates in with covid19 elderly could it be some association rather than exact correlation i don't know but again that's a very interesting thing to look at elderly have higher fatality rates and one of the things here is that they also have low vitamin d production again could just be an association but the other thing here which is also pretty interesting is go back to your skin remember your skin is important for producing vitamin d so in those individuals who have lots of melanin right which actually kind of like decreases your vitamin d production and absorption that also would lead to decreased vitamin d what individuals have darker type of melanin african american and hispanic okay it's actually very very common in general for this population to have low vitamin d because of the high amounts of melanin in the skin also those would decrease sun exposure you could add that in there as well if they have decreased sun exposure with relation to like the 35th parallel when you look at like the map and stuff like that whenever there's decreased uv exposure or kind of sunlight exposure that also could potentially decrease that vitamin d production and again which population do we see higher fatality rates with covid19 african american and hispanics they also have low vitamin d is this association is it actually kind of a correlation again interesting facts here and again the other thing that we know about vitamin d is that whenever there's uh lower levels we already kind of wrote this down there but it's been known for a long time that low vitamin d is associated with higher rates of chf hypertension coronary artery disease and diabetes mellitus when you look at the population that is a higher fatality rates with covet 19 what are those conditions these conditions again it's pretty interesting we can't obviously just assume oh it's vitamin d but it's pretty interesting to kind of see some of these kind of relationships here that covers pretty much everything about that vitamin d pathway the risk factors and all of that stuff kind of really tying in everything we talked about with the take-home messages of all those articles all right so the question is is that that i would like to know and i know that i hope that you guys would be asking is what is a low vitamin d right it's a level that basically potentially you know increase the risk for a lot of these potential possibilities with any viral infection whether that be stars cov22 or any respiratory infection and the other thing is you know what also is really interesting is that vitamin d um has also been associated with decreasing the risk of colorectal cancer so again you just can't go wrong with taking it you know and we'll talk about one of the big things is vitamin d toxicity is crazy rare we'll go over that a little bit but again there's so many more benefits than there is risk to taking vitamin d and that's one of the big things that i kind of wanted to say on my part when it comes to vitamin d there again there is way more benefit to vitamin d than there is risk associated with it okay especially like toxicity all right so the first thing that i want to talk about is what is a low vitamin d level again there's a different units for our uk and engineered fam i kind of went and tried to find out what it was but generally that in the uk i know that they use nanomoles uh per liter so in the uk it's less than 30 nanomoles per liter right is what we kind of say when you're checking like the serum vitamin d levels in america we use nanograms per milliliter and generally anything less than 12 nanograms per milliliter in the u.s is considered to be kind of a low vitamin d level there is other numbers um and then what they kind of say is the other numbers that i read in one of the articles was they actually said less than 75 and less than 30. but again this is kind of like the really lower limits you get below this you should probably consider taking vitamin d what is the goal vitamin d level really and what we see is that from a lot of these articles is that whenever you try to achieve a a vitamin d concentration within the blood that is greater than 75 nanomoles per liter you see a decent benefit from the vitamin d okay and then whenever you see levels within the u.s of greater than 30 nanograms per milliliter you see that a decent benefit with that when it comes to vitamin d for those of you that are curious i was looking it up and there is a conversion factor between this and it's it's generally if you take nanograms per milliliter and you multiply that number by two that's going to give you the number in the actual nanomoles per liter in case you were curious i wanted to kind of learn that as well so that was interesting but again low vitamin d levels are generally somewhere on this your goal to anything to take away from this is to you know try to achieve something higher than this amount that leads that begs the question then what dosage should i take to try to keep my vitamin d levels above that range and there's a lot of different numbers so the next thing is dosage of vitamin d what dosage do we need to be taking a vitamin d to get us to around that goal and before i mention that because i i went into the um the endocrine societies kind of recommend recommendations but one of the things that i thought was really interesting and this kind of answers a little bit of this question is what if you're taking these large bolus doses right so really large bolus doses is versus kind of like the prophylactic like doses and generally those are like daily or weekly you know what was interesting they were like in one study they gave like high bolus dosages like um 20 000 international units all the way up to like about over even over 100 000 international units and when they compared that to those who were just taking like a prophylactic dose daily or weekly the daily or weekly dose was shown to be more effective and superior than these large bolus doses so that's really interesting and so one of the things that we should take away from that is it's better to receive these kind of daily weekly prophylactic doses than it is to get these large large boluses okay so the next thing is what is this dose well if we went kind of off of the endocrine society and what they kind of looked at was generally okay if you're a adult an average is somewhere around 2 000 international units per day that begs the question though what's kind of like the upper limit you can go 2000 international units generally what they say is the upper limit is going kind of around 4 000 international units per day some people take higher than that you know and that is okay and i'll explain why it's okay it's just that some research has shown that it's not super effective it is a little bit more effective it does increase those vitamin d levels when you go above 4000 but it just doesn't do it that much so it's not super super effective but it is still effective if you go above that 4 000 international units per day the other one is for pediatric patients so for for little kids they say a thousand international units per day and that is pretty decent and then there is a microgram conversion if you guys look that up um there is kind of like in case you look at your your medicine you're like whoa this is like micrograms there is kind of microgram conversions between international units and micrograms but generally this is kind of that like recommended dosage is 2 000 international units for adults you can go up to 4 000 but there's just not a lot more tons of benefit beyond 4 000. all right so before we move on to the toxicity of vitamin d there's one other thing that i want to mention because we talked about these dosages that are recommended by the endocrine society they added one other thing for fatties like me so obesity right when you're taking vitamin d and people who are obese they obviously sequester more of that vitamin d so guess what you have to do the dosage that they actually kind of set out for obese patients okay so for obesity you have to take that recommended daily allowance dose and multiply it by 1.5 for overweight but for obese greater than 30 bmi you have to multiply it by three and that will give you the actual dose that you should be taking to keep those vitamin d levels closer to goal okay the last thing that i want to mention here because this obviously should be a question with anything you take is there adverse effects or risks or anything that come with it and believe it or not according to the endocrine society toxicity of vitamin d is very very rare you would have to get levels greater than so normal goal is greater than 30 nanograms or greater than 75 nanomoles per liter you'd have to get greater than 150 nanograms per ml of vitamin d plus you'd also have to have hypercalcemia to really see some of the uh toxic effects of vitamin d and to even add on to this fact that obviously this is a very high level when you look at it in comparison to greater than 30 and greater than 150 okay well let's take the person that would say okay what if i take lots and lots of vitamin d i could potentially get to that level there was a study in 2018 and what they did is they gave i think it was like 20 000 international units per day to like a patient group and whenever they check that over time they check the serum levels of vitamin d at that at that at that amount of prophylactic dose the actual level of vitamin d was only around 60 nanograms per ml and they were taking large dosages where generally we're only going to be you know maybe up to 4 000 if you want to go a little bit higher so that just kind of shows you that there is a really really slim chance of having vitamin d toxicity but let me add on one last thing that could potentially increase the risk of vitamin toxicity vitamin d toxicity and this is in patients particularly who have sarcoidosis you know in sarcoidosis are other granulomatous diseases but this is the big one they produce lots of vitamin d and if you take large doses of vitamin d and your body because of this disease is producing large amounts of vitamin d there is a potentially higher chance to reach beyond that level and start experiencing the toxic effects but with all of this kind of said and seeing the benefits of this and the very little minimal risks the benefit of taking vitamin d extremely outweighs the risk of any toxic effects of vitamin d especially in particular particularly prevention of coping 19. iron ninja so this covers everything that we need to know about vitamin d and covid19 again if you guys want to dig through all of these kind of studies again i'm going to have all those links in the description box so you guys can go check out those studies and what i've talked about here in this video but i hope it made sense i hope it helped and i hope it answered your questions about the effect of vitamin d in covet 19. iron engineers as always until next time [Music] you

Channel: Ninja Nerd Lectures

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Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science, coronavirus, covid-19, vitamin d and covid 19, covid, covid and vitamin d, vitamin d, health, news, vitamin d deficiency, vitamin d coronavirus, covid 19 and vitamin d, vitamin d and covid, coronavirus vitamin d, covid 19, vitamin d3, SARS CoV2, SARS, corona

Id: cT1CaTv5-e4

Length: 62min 1sec (3721 seconds)

Published: Sun Jan 31 2021