YouTube made for a COVID-19 symposium
Introduction on YouTube
- Vitamin D deficiency is a global pandemic as is Covid 19. Vitamin D is a powerful immuno-modulator that is found to produce favorable responses of the innate and adaptive immune system. It can also supress the cytokine & bradykinin storm due to the hyperactivity of the renin-angiotensin system. It has action in endothelial stabilisation and prevention of thrombosis.
- When checked first time without any supplementation, very low vitamin D levels found in 90% (3 – 20 ng/ml). It is advisable to maintain serum 25-hydroxy vitamin D in the range of 40 – 60 ng/mL to minimize the risk of COVID-19 infection and its severity. Nobody has been found with the minimal desired level 40 ng/ml unless taking Vit D supplements
- We lose nothing by improving the global vitamin D status. Correcting a deficiency is our duty, responsibility & obligation as doctors. We can do more good by checking the vitamin D (25 OH D3) blood levels in Covid 19 positive patients (hospitalised and those advised tests for inflammatory markers) and raising the vitamin D levels up immediately.
- If not now, then when????
Her video was a part of Malaysian Association Of Advancement of Functional & Interdisciplinary Medicine summit April 10, 2021
Download the slides shown in the video
0:00:05.5 Dr. Mahtani: COVID-19 is a pandemic, and vitamin D deficiency is another pre-existing known pandemic, we are all aware of it. And times have changed. The thing about vitamin D to be a preventive factor for rickets and osteomalacia, it's just like a tip of an iceberg, because vitamin D has a lot of potential roles in many, many other disease prevention and good health, and we are going to focus today basically on where the viral environment we are living in with flus and colds, and today this COVID-19. So now there is enough evidence that has built up that vitamin D supplementing could reduce the risk of not only flu and influenza, but also COVID-19 infections. Well friends vitamin D is not biologically active and it comes inside us, either through sunlight, food or supplement, it gets activated as we know first in the liver, then it gets the second step of activation into 1,25 di-hydroxy cholecalciferol, and then we have the active form of vitamin D for its biological effects in the body. I can see in this slide, liver first step, second step kidneys, then the actions in the intestines and bones, and this is what our basic normal understanding is time-tested from a long time. Let's move ahead.
0:01:37.1 Dr. Mahtani: We are in 2021, and it's very important to know that vitamin D has many other mechanisms of action other than just calcium absorption from the intestine and making our bones strong and joints healthy. Every nucleus of every cell of the body has been found to have the VDR or the vitamin D receptor. It's an amazing finding to know, because it says that vitamin D actually works on every cell through every nucleus in our body, through the nuclear receptors that are present. So the activated Vitamin D binds to the receptors and carries out all its other vital functions not just on the bones, and in today's context the immune system and the regulatory mechanisms of the body, so let's have a little deeper look at the so-called vitamin D receptor. Well, 25 hydroxy form, which has been sort of made in the liver, it enters into the cells and in the cells as you can see there's this enzyme called 1 alpha hydroxylase, which is present inside the cells to convert it into the fully biological active form, and then this enters the nucleus through the nuclear receptors, through various mechanisms, transcription mechanisms, at least to production and expressions of various proteins and enzymes and does carry out the effect of the very many functions inside the body.
0:03:18.5 Dr. Mahtani: So friends, vitamin D, as we thought that it gets activated in the kidneys, then it comes in the blood and does the functions in the bones and intestines could be called as hormone-like action. The way other hormones work. Now with the knowledge of vitamin D receptors present in every cell, we have come to know about its autocrine and paracrine actions means vitamin D works inside the same cell where it has been activated, it need not just be going out in the circulation for the action, it influences the cell and the paracrine or the neighboring cells through the same mechanisms of Vitamin D receptor binding transcription mechanism and various protein synthesis, so what all actions can it do? Through this methodology, of course, we are coming to the immune system modulation, but let's at least know that it enhances entity functions, it works to suppress the hyperactivity of the renin-angiotensin system, it improves the secretion of insulin. Well, it controls cell differentiation, it does epigenetic signaling, it can induce a poses correctly, and you can see the very many functions that are possible within the domain through the help of the VDR and the vitamin D receptors. So friends, we can say that vitamin D has a big armamentarium of extra selectal actions beyond the bones.
0:04:45.9 Dr. Mahtani: Now, there is this intracellular activation of vitamin D to its biologically active form, which was not done before, we thought it's happening in the kidneys, comes through the blood, and it does the job. No the importance is that the vitamin D can be activated inside the macrophages, it can be activated inside the monocytes, which make up the immune cells for all the functions, and you can see the third one here, its a powerful genetic modulator. So it has been found to work on more than 2000 genes in our system and have an effective action suppressing some of the bad ones and enhancing some of the good ones.
0:05:36.7 Dr. Mahtani: So let's now look into vitamin D immunology in relevance to COVID-19 disease prevention and as therapy, mechanisms can be genomic, mechanisms can be non-genomic. It is not just a nutrient, it's a hormone, it's an immuno modulator, and it is also a genetic modulator. So in our immune system, we have, first, an innate immune response and then comes the recruitment of the adaptive immune response. And there is a host of cells which take part, which participate there. So the news is VDR or the Vitamin D receptors are present in the nucleus of all these cells, whether innate immune system or the adaptive immune system. And let us see now how does Vitamin D work inside the cells, inside these immune cells. So friends, the 25-hydroxyvitamin D the liver activation enters these immune cells, and then there is this local presence of the enzyme 1-alpha-hydroxylase which converts this into the final 1,25-dihydroxyvitamin D, the active form also called as calcitriol. And now this goes into the VDR into the nuclear receptors, works on various protein synthesis and has effector mechanisms. Vitamin D seems to be a very intelligent molecule.
0:07:08.6 Dr. Mahtani: There are places where it suppresses and there are places where it enhances the good arms of the immune system. So Vitamin D has its action not only at the innate immune response level, antimicrobial response, whether it's on macrophages or the antigen present in cells called as dendritic cells, it also works on the adaptive immune response, the helper cells maturing into the Th1, Th2, Th17 and the T regulatory cells.
0:07:40.5 Dr. Mahtani: So vitamin D seems to be having a very balanced response. So it's called the immune modulator, not immuno-suppressant. It modulates the immune system into to our advantage, let's put it like that. At the level of the innate immune response or what we call it as a first line of defense, Vitamin D in adequate levels, it enhances the expression of defensins and cathelicidins, which are natural antimicrobials, antivirals, and have capacity to reduce the growth of these at the level of contact when they enter. So you can see how these defensins and cathelicidins, if we have to show it in a picturesque manner, they would just go and cover the spike protein and also prevent the replication of the virus. Now moving on to the adaptive immune response which is mediated to the T-cells, the B-cells, alright. And, well, there's a phase of recognition, there's a phase of expression to control through inflammatory cells, and then there should be a mechanism to bring it down to, to bring it down, otherwise the hyperactive response will continue and lead to other category of problems. That in the adaptive immune response, the so-called T helper cell, it can mature into four possible cells, okay.
0:09:09.6 Dr. Mahtani: So Th1 is an effective mechanism to deal with and bring about the inflammatory cytokines so that things can be brought in control. Th2 could be called as production of antibodies and control of allergies and parasites. Then there is a Th17 wing of it. Well, this has a very important role to continue the process of inflammation, and, well, also in autoimmune disorders. And then there's the T regulatory mechanism which brings about the check, brings about the check and stops the process when it needs to be stopped and creates a state of immune surveillance, immune tolerance, and the body knows that, well, next time when this thing comes, I will attack but not now.
0:09:58.5 Dr. Mahtani: So friends, Vitamin D on the adaptive immune response, it's a powerful regulator. How? It promotes a timely shift from Th1 to Th2, alright. It suppresses the Th17 reaction, and it facilitates the differentiation of the T regulatory cells which are needed to bring about the correct check. So this intelligent molecule can do that. Interesting to note, this picture shows that once the vitamin D, the active form, is there, how it has a role on Th1, the cytokines it suppresses, Th17 cytokines, the ones which it suppresses, Th2 like IL-5 as mentioned used in the therapeutics as well, how it enhances the helping cytokines, and similarly for the regulatory mechanisms, how it takes up the IL-10, the interleukin the cytokine needed to bring about this action.
0:11:01.7 Dr. Mahtani: Vitamin D has a balancing role. So if we have to make it very, very simple, it reduces the replication of virus, it improves the physical barrier, it increases the cellular immune response, it improves the adaptive immune response, and it creates the perfect balance of the CD helper cells and the mechanism, and if all happens in control, it can prevent the sole cytokine storm, which is attributed to cause the ARDS and all the multiple organ failure that we see in COVID-19.
0:11:36.1 Dr. Mahtani: Now there is one more mechanism through which vitamin D works to help control the cytokine storm and the dreaded sequelae. And what is that? That is its action on the renin-angiotensin system. Well, I remember reading about it during my training of medicine that an hyperactive renin-angiotensin system can lead to vasoconstriction, high blood pressure, hypertension, and all those problems. So to simplify, in our body we have a protein called angiotensinogen and then the enzyme called renin, which activates it into angiotensin 1.
0:12:17.7 Dr. Mahtani: Then comes angiotensin-converting enzyme, which converts it into angiotensin 2. It's important to note this because this will help us understand how vitamin works here. Well, this angiotensin 2, the final effector that is made, is not only vasoconstrictor, it is supposed to be the most powerful vasoconstrictor in the body, but also a very pro-inflammatory molecule, which triggers inflammation inside the body. So this is how the renin-angiotensin system, if it is hyperactive, will not only be leading to vasoconstriction, but also a inflammatory state in the body. So uncontrolled angiotensin 2 is there behind the cytokine storm, leading to the secretion, the storm of the cytokines, the interleukins, and all the cellular hyperactivity, which makes it very, very inflammatory. So we can see here how the various interleukins are coming in, leading to a leakage, the capillary leak syndrome, and the multiple organ failure that occurs when somebody gets the CVF of COVID-19 disease.
0:13:35.1 Dr. Mahtani: So how can vitamin D play a role here? And now it's a wow moment. It was for me at least, to know that vitamin D, once it is activated, gets into the nucleus through the VDR, and through its function on the genes, it suppresses the formation of renin, right? So renin is a protein that is expressed, if you remember the slide before, I'll show you again, that renin is needed to convert angiotensinogen 2 to angiotensin 1. So if renin is not there, the entire cascade has sort of been nipped at the formative level, and the hyperactive renin-angiotensin system can be sort of controlled by reducing the production of renin. So vitamin D, it reduces the production of renin and sort of suppresses this access and suppresses the formation of the, let us say the culprit, that is angiotensin 2, the proinflammatory and the vasoconstrictor. Now, friends, there is lots been spoken about angiotensin-converting enzyme 2, right? So where does this come in this cascade should be the question?
0:14:52.8 Dr. Mahtani: So let's move to more deeper. We know by now that angiotensin 2 is, let us say not the good one, okay, and it is leading to the proinflammatory state, the pro-fibrotic state, and the culprit behind the multiple organ and the distress syndrome in the body. It converts this angiotensin 2 into another category, angiotensin 1-7, and good news, this angiotensin 1-7 is anti-inflammatory. It's not proinflammatory like angiotensin 2. If we want to prevent ARDS and all these complications, we have to sort of see that there is more ACE2 in the body as compared to AC. So, that is enough now to say that angiotensin-converting enzyme 2 protects from severe lung failure. How? What could be the mechanism? At the same time, we are also hearing that the coronavirus enters through the ACE2 receptors. Receptors, friends, okay? And once the virus is entering through the ACE2 receptors, probably it is also depleting the ACE2. Let's say that. So the spike protein sort of keys with the ACE2 and the receptor, I'm not saying ACE2, it's the ACE2 receptor and enters the cells.
0:16:21.9 Dr. Mahtani: Now, what is the hypothesis? The coronavirus through its spike protein uses the ACE2 receptor of the cell to enter and this deactivates ACE2, the protein molecule that is needed. ACE2 is the enzyme that inactivates the inflammatory angiotensin 2. So when the virus is there, it blocks the ACE2, so there's a storm of angiotensin 2 which leads to the pulmonary edema. So in order to avoid this relation well of the system is important. And there are lessons which have come up through the past SARS infection, where they found that ACE2 could be actually a potential therapy because if there is more ACE2 it will reduce the bad one that is the angiotensin 2.
0:17:14.0 Dr. Mahtani: And here there's a paper which is actually from a WHO bulletin that you can see, which says that vitamin D increases the expression of ACE2 as genetic modulator suggesting that ACE2 plays a role in protecting against, you know? The, sorry, the acute lung injury. So making it simpler, angiotensin 2, well, it's not the one we want. Can vitamin D help? Yes. And this it does by nipping at the bud level and controlling the renin production. ACE2 is a good one. Can vitamin D increase it? Yes. This intelligent molecule increases the expression of ACE2 enzyme. Spike protein that is bad. Yes, Vitamin D can prevent its attack with the help of the cathelicidins, the beta-defensins, and reducing the viral load at the level of the entry. So, friends, it's so interesting now to.
0:18:19.2 Dr. Mahtani: Try to concise the whole thing in one slide, as you can see, Vitamin D, okay, reduces Renin, it reduces ACE2, oh sorry, ACE1, but comes to ACE2, which the virus is trying to reduce, Vitamin D increases the expression of this enzyme, so that the bad one gets converted into the good end products. And at the same stage, I will also use... Or take you to the Bradykinin Storm very quickly. There's another pathway that has been spoken about as the cause behind the multiple organ failure, and that is the release of Bradykinins. And Bradykinins come... You can see in this pathway from Angiotensin one. So if Vitamin D nips the Renin, it also suppresses the progression towards the Bradykinin Storm. So you can see how in the pathway, Vitamin D is playing a crucial role, not on the immune cells, on the immune responses, but on the Renin-Angiotensin mechanisms at the same time. Very interesting. There are other mechanisms too. Vitamin D has a very powerful role on our vascular endothelium, because the cells of the endothelium also have the VDR or the Vitamin D Receptor, the smooth muscles, the heart muscles too.
0:19:45.0 Dr. Mahtani: And there it has a protective role by inhibiting the macrophage, foam cell formation, reduces the vascular smooth cell proliferation, reduces the tendency of adhesions, and reduces the cytokine released from lymphocytes, even within the endothelial cells. This probably has a role also to play in preventing the thrombotic complications that have been postulated also, and we are seeing it also pretty rampantly nowadays. Antioxidant, mitochondrial dysfunction, I will not go into the pathways, but Vitamin D also plays a role here. The mechanisms are given here, through the glutathione pathways as well. It has the capacity to reduce the oxidative stress also and the mitochondrial dysfunction as well. So friends, if I have to concise the whole thing that till now what I have spoken about, there are so many pathways, so many roles through which Vitamin D could be effective. In fact, I think we should stop calling it a vitamin because then we take it for granted, it's a pun, it's an immune modulator, it's a genetic modulator. So it works on the immune response at the innate level, adaptive level, it works on the Renin-Angiotensin system to control the cytokine storm, bradykinin storm. We just saw the mechanisms.
0:21:09.8 Dr. Mahtani: It helps to stabilize the vascular endothelium. It also has a protective role to prevent lung fibrosis and inflammation, and plus it's antioxidant, reducing the oxidative stress and has capacity to enhance mitochondrial functions as well. So friends, at this juncture, we can say that Vitamin D is not an optional supplement, it is a non-negotiable cellular necessity, it is our life health support system, and I'm sure you will agree, we all are low in Vitamin D. At least majority of us are. We lose nothing by checking it, it's possible to check it, this is how vitamin levels can be checked so easily, so we should not hesitate in doing it. And then, well, it can be so easily corrected in such an inexpensive way, such an inexpensive way that it is taken for granted. So the minimal requirement of Vitamin D, if you check through blood test, it would be 40 nanograms per ml, right? Even for preventing respiratory infections, viral infections. This was a wonderful study, and it says that it's important not to just have the level but to maintain. Maintenance of Vitamin D serum levels of at least 40 nanogram to prevent viral infections coming in. Okay, let's move ahead.
0:22:46.4 Dr. Mahtani: Now, in the present time, when the virus is getting stronger and the virus mutations are occurring, the levels recommended are about 40, 40 to 60 nanograms per ml would be optimal. So let's keep that in mind. 40 to 60 nanograms per ml would be the desired blood level. And friends, we should not be scared of these levels, huh? Even the Endocrine Society has recommended sufficiency to be 30 to 100. The upper limit is 100 nanograms per ml, it's safe. So we should not be getting satisfied with 20s and 30s when we're in an era of wearing masks, social distancing, which is important, but the physiological barrier inside us also needs to be strengthened with the right levels, right doses of Vitamin D.
0:23:45.0 Dr. Mahtani: So if not 100, friends, Chalo, let's accept 40 to 60 nanogram. Lots of studies have come, and I found this beautiful slide where they have analyzed the data on almost two lakh people through this last one year, and found that people whose Vitamin D levels were more, their chances of showing positivity became less and less and less. So lower the Vitamin D levels, higher the chances of positivity, and higher the levels of Vitamin D, well, see how it is declining. So 40 to 60 or above, aim reaching 60.
0:24:25.5 Dr. Mahtani: This is what is being implicated in this slide come study. With a very heavy heart, I'm sharing with you the reports of today's study. Less than three, 8.9, as you can see here. We have seen such pathetic reports of Vitamin D just when people come to us. Now, if somebody has such low Vitamin D levels, how do we reach the desired 40 to 60 nanogram per ml? We are in 2021, what is the starting point? And if the starting point is lesser than 20, hey, we can never even touch 40, we cannot touch 40 even with 4000 International Units taken on a daily basis.
0:25:14.3 Dr. Mahtani: So what does this paper say, that yes, 40 nanogram per ml is the desired level, and to achieve it, one needs to take at least 9000 International Units daily to contain it. When there was that influenza time in the West, they did a nice technique it is also called Ethos therapy, and they called it vitamin D hammer. To immediately boost up the level of vitamin D, 50,000 International Units were given daily for two to three days, and then the people were put on a maintenance dose and they found this a very good technique to control viral infections. So I thought, let me look at this slide here to share that how to get the target of 40 to 60 grossly dividing the category of people into two, if possible blood levels are known, 10 to 20 if they fall in this category, or if the test is not there, and they have not taken any vitamin D for more than six months. Well, friends, it's a very big category of people here who have not even done this. Without any hesitation, we can give them the Vitamin D hammer dose in today's time, 50 to 60,000 daily, because the availability is different in different countries. In India, we get 60,000 International Units. In the West, I have seen 50,000 daily for three days at least, and then they can be put on a weekly dose of the same 60,000 or 50,000 IU once a week, which would roughly equate to 9000-10,000 IUs daily for about three months.
0:26:53.6 Dr. Mahtani: Good would be to check the blood levels after that and see how it is working on that individual or alternatively one can definitely put them on a maintenance dose of half the dose at least, which would be about 4000-5000 IUs daily. So 4000 IUs cannot be a starting dose when somebody has such low blood levels. I'm sure you'll agree. The way we replace insulin when there is insulin deficiency, the way we replace thyroid hormone, why not replace vitamin D, when there is a deficiency and so many pathways are known? Now there's a second category of people who are having a vitamin D level of let us say 25 to 30 around that, and they have been taking some vitamin D ranging from let us say, a 1000 to say 4000 IUs daily. It would be fine otherwise, but in today's time when we want to see blood levels of 40 to 60 to have better protection against COVID-19 disease, we can at least give them 10,000 IUs daily. So we give them that 60k once a week for three months, or 10000 IUs daily for three months, depending upon the availability in your place, and then think of the maintenance dose.
0:28:10.8 Dr. Mahtani: A general thing that has been noticed is that if the vitamin D levels are really low in a COVID-positive patient less than 10, they have critical outcomes, they have severe outcomes. So at this juncture, is it not mandatory to check vitamin D levels for at least the people who are getting hospitalized, or who are going for blood tests for checking the D-dimer, for checking the ferritin levels. Hey, just adding a vitamin D test would be so, so... What should I say? It's so important, it's a life factor, it's a health factor, and improving the vitamin D status we lose nothing. In fact, we have been really finding good results giving vitamin D to COVID-19 patients.
0:28:57.8 Dr. Mahtani: And then they have found that as the vitamin D levels go up, the chances of death comes down. Mortality, death rate. As the vitamin D levels increase, the death rate is being found to fall down. The question may again ring in the minds of many people here, this could be toxic and all. Well friends this has been very beautifully described by Dr. John Cannell, somebody is dying of thirst but will not drink water, that "Oh, I may get drowned". This is the situation about vitamin D toxicity, they're fearing toxicity, which is actually nothing to be worried about at this juncture, and we are depriving ourselves of the benefits of this wonderful molecule.
0:29:46.8 Dr. Mahtani: So worrying about vitamin D toxicity is like worrying about drowning when we are actually dying of thirst. So to summarize, friends, in today's time, vitamin D deficiency is a global pandemic, and at the same time, we know that vitamin D is a very, very powerful immunomodulator. When checked first time without any supplementation, we see super low levels of vitamin D, 3, 20 in majority of people. Nobody has been found with the minimal desired level of 40 nanogram per ml, unless taking supplements, and friends, we lose nothing by improving the global vitamin D status. In fact, as doctors, correcting a deficiency is our duty. It's our responsibility, it's an obligation. Honestly, internally, I feel not correcting would be negligence. We must take care of the vitamin D levels and 40 to 60 nanogram would be a target level to keep our immune system strong, and by the way, it's also going to help our heart, our brain, our vascular endothelium, our kidneys. We must check the vitamin D levels, especially in those who are hospitalized or who are going for blood test for COVID positive panel. Let's include it in our protocols, and then if somebody is found to be positive, we should not hesitate in giving boluses because you can save lives.
0:31:17.7 Dr. Mahtani: If toxicity occurs, hey, it can be managed. Number one, it won't occur because the levels are so low. It's a matter of life and death. If not now, then when? So I would close my talk with full reverence to this 0:31:30.4 ?? life, that is sun. Life is not possible without the sun, and vitamin D, you could call it as the chemical expression, the chemical gift, the chemical counterpart of the solar energy. No wonder vitamin D is such an intelligent molecule. Not a single pharmaceutical agent can do all the so many functions that this one alone molecule can do.
0:31:57.5 Dr. Mahtani: So today, with all the reverence in my mind, my brain, my heart for vitamin D, I would wish you all be safe, feel confident with actually this nature's physiological protection. And do not hesitate in taking the solar energy in the form of supplements and that too in adequate doses, because doses do matter. So thank you friends, and thank you for this invitation, this opportunity to share whatever I have learnt in this journey. Once again, none of them are my studies. I'm a clinician, I deal with patients. I see the outcome of these deficiencies and how correcting can actually turn the table. And thank you once again.
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