Regenerative Health with Max Gulhane, MD
I speak with world leaders on circadian & quantum biology, metabolic medicine & regenerative farming in search of the most effective ways of optimising health and reversing chronic disease.
Regenerative Health with Max Gulhane, MD
95. Critical role of the Vitamin D system in Infection and Immunity | Prof Sunil Wimalawansa
Expert physician researcher Sunil Wimalawansa explains why Vitamin D plays a critical role in immune system function, the physiology various forms of vitamin D and how to ensure you keep a level compatible with optimal health.
Dr Sunil J. Wimalawansa, MD, PhD is a globally respected clinician-scientist, educator, over three decades of leadership in endocrinology, osteoporosis, metabolic bone disease, and nutrition. He served as professor and chief of endocrinology at leading U.S. medical institutions, including the Robert Wood Johnson Medical School/Rutgers University.
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TIMESTAMPS
3:30 Vitamin D Metabolism Made Clear
9:30 Sunlight Timing And Skin Production
15:20 Peripheral Activation And Inactivation
21:40 Immune Cells Depend On Daily Supply
27:00 D3 vs Calcifediol vs Calcitriol
33:20 Acute Illness, ICU, And Rapid Repletion
39:30 Safety, Toxicity, And Hypercalcemia
45:10 Disease Thresholds And Target Levels
51:30 MS, Autoimmunity, And Latitude Clues
58:00 Dosing Rules And Obesity Adjustments
1:04:00 Frequency Matters More Than Mega Doses
1:09:00 K2, Magnesium, And Cofactors
1:14:00 Study Design Pitfalls And Bias
1:21:00 Practical Takeaways And Resources
REFERENCED PAPERS
Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study PMID: 34064175 https://pubmed.ncbi.nlm.nih.gov/34064175/
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Okay, welcome back to the Regenerative Health Podcast. Today I'm sitting down and speaking with Professor Sunil Wimalawanta. Now, he is a professor of medicine, of endocrinology, and human nutrition. He has had an extensive career treating patients in clinical medicine, and he is a world expert in the vitamin D system and the effects of vitamin D deficiency on health. So uh, Professor, welcome to the podcast.
SPEAKER_01:Hello, Max. Thanks for getting me involved in this discussion. I'm looking forward to having a fruitful discussion for benefiting the public.
SPEAKER_00:Great. Well, tell us a little bit about your career and your obviously academic interest mixed with clinical work to kind of get you to this place of being an authority on vitamin D.
SPEAKER_01:Yeah, I originate originally from Sri Lanka, it's a small island in uh Indian Ocean. Then I I moved to United Kingdom for my postgraduate studies and my PhD and all this basic stuff. And but 10 years later, I moved to US. Now I'm in the US uh for 30 plus years and engaged in the both research and clinical medicine, academic clinical medicine all this all these years, 40 plus years. I never done private practice. So throughout my career, uh I've been in academia and uh I'd like to continue that, but one more important thing actually, but 30 years ago I switched my interest from acute medicine to disease prevention using holistic approaches, the patient as a whole, and rather than looking at a compartmentalized medicine that we have been taught over the years in the Western medicine. Thank you.
SPEAKER_00:And and how how did you get interested in the vitamin D system?
SPEAKER_01:Originally, I uh we in I have a had a lab in back in Hammersmith Hospital Royal Post-Keeping Medical School back in the 1980s. So we used to do some the biochemical studies and mostly cell culture studies using uh active moiety or vitamin D, which is calci triol. And uh that time we were interested about uh mostly about the cancer cell line to control their growth and reversing them back to a normal normal cell. They are very impressively, we could do that, but using higher doses of calcitriol. But that amount of doses or the concentration will not achieve is possible in human beings. So we are worried uh what's going on, and now we know that it's really the circulatory concentration is uh irrelevant of calci triol. What matters is the intracellular generation of calcitriol from vitamin D3 as well as 25 hydroxy D, because this peripheral uh target cell like immune cells, cardiovascular cells, the brain cells, all has both enzymes to convert D3 and 25 hydroxy D, so calci triol, into calcifidiol into calci triol active moid. So these cells basically depending on the circulatory blood concentration of D3 and calcifidiol. So that's the reason we are measuring the 25 hydroxide D as a vitamin D status.
SPEAKER_00:Yeah, that's a and it's a great opportunity to talk about uh the metabolism and the physiology of vitamin D. And and as you mentioned, and a lot of my uh listeners who followed my work up till now know that the the vitamin D that is generated in the skin and that we take orally actually has to go through a stepwise process of enzymatic transformation and activation before it gets to that the active form, which is as you mentioned, is uh is is calcitriol. So the to talk to us through the this process, how do you how do you see the most important ways that the body is actually generating or intaking vitamin D?
SPEAKER_01:The vitamin D is in historic historically we're supposed to get at least 80-90 percent of the amount through sun exposure. Unfortunately, because our the new lifestyles and indoor uh work mostly, and some air pollution in places like India and other countries, the amount of UVB risk getting on to the earth's surface is much limited. So indoors we get nothing, and the winters we get nothing. Even if you get a full sun exposure during winter period, the amount of vitamin D generated in skin is zero. So let me make it easier by sharing the slide with you. Hopefully. This basically is a summarized the whole uh metabolism of vitamin D from UV exposure to diet and supplements, irrespective whether we get a D2 or D3 from the diet, because some most of the mushrooms and things have got a D2, whereas if you the salmon and other uh animal ones have a D3. Irrespective of that, a D D2 and D through get a conversion in the liver to form 25 hydroxyl vitamin D, which is called calcific diol, through the hormone or an enzyme called 25 hydroxylase. But as we discussed later, I hope that we can also, there's a very important process of this happening in the target cell, which is not present in this slide. So this 25 hydroxyl D get further hydroxylate at one position here in front of that through one hydroxylase enzyme, which is present ubiquitously every almost every cell in the body. But until about 10-15 years ago, we are only knew of the concentrating of the renal cells, genal tubular cells, which converting this uh 25 hydroxy D to calcetriole, which is the actually the hormonal form of vitamin D, which is difficult to quantitate, but we think that it's not no more than the 20-25% entire activity of the vitamin D. So remainder is very important, which is 75% of the activity to vitamin D from non-hormonal vitamin D. This is crucially important as most healthcare workers uh still doesn't seem to be get that uh concept. So this non-homal form is generated at the peripheral target cell within them. So, because the circulatory concentration of calci triol is about 900-fold lower than what they can get into the target cell. So they have to parensitize locally, that depending on the circulatory concentration of both uh 25 hydrogase D and D3. So, anyway, it's from there, then the the this it will involve with uh the through the hormonal path, it will the serum calcium maintenance uh through parathyroid and bone cells, and also feedback increase the calcium absorption from the intestine and also renal tubular absorption. So, again, that we are clearly talking about a part of the uh 20%, 25% part of the vitamin D activity. So it's also important to realize that there's a built-in mechanism in the body from skin to liver to all the peripheral cells with a 24-hydroxylase activity. So when a 24-hydroxylase enzyme activated, it neutralized okay, or catabolized the activity of 25D, D3, as well as uh more importantly, the casid trio. So that is a major inactivation step to control the feedback mechanisms of these uh complex pathway.
SPEAKER_00:Yeah, it's it's an extremely uh intricate system that the body has developed. And I'm I'm trying to think of a really good analogy again to get people to understand this this concept. But essentially what we've got is this circulating form, and that is the form that you get measured if you go to your primary care doctor or you you get measured on a serum, a venous blood drawer, but it it needs to be activated. And what um what uh Sunal said is that historically or canonically this has occurred only in in the renal cells in the in the kidneys, but what we know now as it relates and is important for immune system function is that all these critical immune cells, macrophages, neutrophils, I'm guessing, um, and lymphocytes, they also activate the precursor vitamin D on site, and that helps them to have their function. So it's almost like uh in uh in a war zone, you've got artillery shells uh in the all over the front, but they actually have to be put into the howitzer to before they can be fired off and be activated. Otherwise, you'd have the you know everything going exploding. So um the the other interesting point that you made was this inactivation step. And more recently, uh I uh there was a review released uh regarding the formation of these uh other secosteroid compounds, which uh seem to have related effects to vitamin D like uh lumesterol and and tachisterol as well. Yes.
SPEAKER_01:But the concentration of those uh metabolites are very small. So even though they have it can be demonstrated a biological effect in vitro, very difficult to show that in vivo because for a number of reasons. I mean, firstly, you cannot give this kind of uh unauthorized metabolites to human. Secondly, even if you do that, there's no way of uh controlling it. So the other point I uh I forgot to mention that to activation of the 7D hydroxy cholesterol, which is natural is a basically uh uh endogenous compound on the skin, it needs is activated by the UVB in the range from about 280, 280 to 305, it's a median about 300 nanometers. So this is a crucial thing because um second thing actually in the day of the and the time of the day, because the if the if you get the UVB race and the uh the the broader angle, and that will not penetrate the system and also reach uh not reach getting inside the uh into the skin as well. For example, uh the the the best time to be in the sun to get vitamin D is from about 1030 to 130, 10:30 a.m to 130 pm, because that's a time what you call the zenith angle, because the angle between the vertical and the sun rays coming this way is the shortest. Shorter the angle, the higher the penetration of UVBs coming into us and also through the skin. So the extension of that actually to contrary to the previous myths, and if you uh you recommended by to go to the sun, get the sun exposure in the early in the morning and afternoon. But we need to be mindful that the amount of vitamin D generated in the morning and in the evening is negligible, maybe zero, close to zero. Similar thing happened in the winter time in the period from about October, end of October to up to about end of April. The vitamin UVB race does not reach us. So that's the reason. Basically, no matter how many hours you stay on the sunshine during this period, you you do not increase your serum vitamin D levels.
SPEAKER_00:Yeah, very uh interesting point. And and look, the the uh other times of the day are important for a circadian rhythm point of view, um, and have all kinds of other health benefits that I've talked about previously. But yes, the the midday the prime is prime time for for vitamin D generation because of the the essential penetration, as you said, of short wavelength flight through the atmosphere. Do you do you have any comment about the sulfation and the the process of sulfation of skin-generated vitamin D versus perhaps uh an oral supplement?
SPEAKER_01:Um not much really, because my understanding is not deep enough to make uh definitive comments, but it these are important areas both for activation and inactivation of vitamin D. Excuse me, and the uh the the skin itself is a unique thing because uh excess sun exposure will never cause too much vitamin D in the blood. There is a built-in mechanism within the skin, it the the the uh the vitamin D3 get or the precursor itself get destroyed or 25 hydroxylated, and therefore it prevented getting into the circulation through binding to vitamin D binding protein. So this is an inherent protective mechanism we we have. It's very important to overexposure to sun, of course, can harm the skin and the DNA, all this stuff you stay too long, especially one needs to absolutely avoid the sunburns, which can have a long-term consequence, negative consequences. But irrespective of the time, you you will never get vitamin D toxicity or higher level of vitamin D in the circulation.
SPEAKER_00:Yeah, that that's a point I make clearly to people, which is it's it's not physiological possible to get hypervitaminosis D from overexposure. And as you said, there's other issues we we push past the hormetic benefit of UV light um if if you're gonna cook yourself, but uh hypervenovinvitaminosis D isn't one of those. Let's let's talk about your specialty and your expert domain, which is the role of this uh system in immunity, because uh you're gonna show a slide us, uh show us a slide later on, but it feels like um clinical medicine is essentially mired or trapped in a paradigm of which is essentially exclusively interested in the bone complications of vitamin D. But what your work and others have showed is that uh there's a profound role of this compound, this psychostoroid hormone in immune function.
SPEAKER_01:Um thank you so thank you for the question. Uh so it's complicated, but I let me to summarize uh or the presenter in the fairly straightforward manner. So as we discussed a few minutes ago, immune cells functions, activation is almost primarily 80% of the activity is dependent on the availability of intracellular calciol within the immune cells, not in the circulation. So by giving calci triol as an agent orally or intravenously, very few, or if if at all, none will none of them will get into immune cells or the cardiovascular cells, because there's no mechanism for active absorption of calciol. So, and also I mentioned that the level of you can achieve with the calciol in the circulation is about 900 fold less than that needed to diffuse into immune cells. So that's not going to happen. So immune cells are primarily depending on the circulatory D and 25 hydroxy vitamin D, uh, cancer B diode. So level of this achieving and maintaining in the circulation is crucial for all the peripheral target cells to for vitamin D from brain to immune cells. So if you have an intermittent intake of vitamin D, for example, say if you take a once a month or once every other month, or once in two weeks, even, the level becomes insufficient to get into the immune cells in between the nails. So therefore, why even if you have uh immune issues or getting infection, during those periods immune cells are in unable to get activated. That's the importance of getting daily vitamin D3 intake or at least once a week, because the half-life uh uh as shown. Let me show you a slide on the half-life so we can oh okay. So the this slide summarizes the half-lives and the normal ranges of three uh two metabolites and vitamin D itself. So 25 hydroxy D is the longest because partly because it's bound to vitamin D binding protein and lasts longer. And the vitamin D is 24 hours. That's the reason why need why need to the physiological rationale of a daily doses are better than intermittent doses. Because, as I said minutes ago, vitamin D3 intake and the circulatory level, which you which you routinely we know we do not measure, is not available, that has a highest probability of getting into the immune cell compared to 25 hydrox vitamin D because of the concentration gradient and the affinity to vitamin D receptors. So this is more tightly bound compared to vitamin D. So it's more vitamin D get absorbed. So intermittently, if you give vitamin D, this level would be go down intermittently. So that's one of the also the reason for some people get adverse effects, so-called adverse effects, like in prosthetic carcinoma and pancreatic carcinoma, the circulating big fluctuations are not physiological for human beings. Because we are supposed to get vitamin D from the sun daily exposure historically. Short active, they do the job. In contrast, 125 hydroxide vitamin D, which is calciol, is very short-active. It gets the DNA deactivated very quickly. Plus, the concentration is here, it's picograms per milliliter. It's almost a thousand fold less than D3 and 25 hydroxy. So you can see that why this amount, a small amount, is unable to get into the immune cell. So giving calciole to expecting results is insane. It doesn't happen. It can only cause adverse effect. Because one 125 hydroxy is very active. If you raise a level to 100 plus, here you will get a hypercalcemic syndrome. So that's you're not helping patients by. Giving this thing. So instead of you should give the vitamin D or 25 hydroxy D in certain circumstances, we can discuss it appropriately. Major difference is if you give vitamin D, it takes about three days to appear in the blood as a 24 hydroxyl vitamin D, which is also necessary for renal function, renal activity to the hormone. Whereas if you give calcific diol, which is less hydrophilic, therefore it does not depending on the intestinal lipid mechanism to get it absorbed. Otherwise, it has to go to get absorbed into the input and ultimately end up in the thoracic duct into the blood system. And then they have to be converted to 25 hydrox D in the liver is uh the rate limiting step as well. So this process of vitamin D taken into convert it into 25 D and appear in this circulation take about three days, anything from two to five days. But in in sick patient like ICU, this will take seven to ten days. So here's the point in sick patient in ICU, giving vitamin D you can give 600,000, it's not going to help them. Because it will not get into the circulation as a 25 to D that is necessary for some additional function because it takes too long. These circumstances, specifically in acute circumstances like COVID, for example, acute infection. So you can give available calcific diol, very small doses, about one milligram calcifiol, will do the job. And when orally given 25 hydroxy D, calcific diol, within about four to six hours, it appears in the circulation. Compared to take three days in the vitamin D. Eventually, the actions of between two are the same. So if it's in the acute situation, giving this vitamin D and expected results is not right. So we have to, depending on the 25 hydroxidines, things like ICU situation, they should be available for this patient. So what one more thing on that.
SPEAKER_00:So if we look yeah, so I was just gonna, if you go back to the slide, I would just gonna quickly summarize for people uh that what what what you said, and what essentially is uh um Professor is saying is that there's these three different forms of of vitamin D, and the progression from vitamin D to 25 hydroxyvitamin D, which is the storage form and the measured form, and then the final uh form of 125 dihydroxyvitamin D, uh, these are all separate forms. And the way that they are existing in the blood or the range that they're existing in the blood is is different and uh specifically um managed. And the point being that uh if you're taking um oral vitamin D, then that can uh that will have a half-life of 24 hours, it it will it it will actually peak and go back down. But if you're having vitamin D generated cutaneously, then the half-life is longer because it's binding to the vitamin D binding protein and therefore keep potentially slowly dripping into the system. And and I believe that was uh uh a study done by Hollick showing um irradiation with uh one minimal erythemal dose of UV light uh led to 10,000 unit um kind of equivalent, but it was a much slower release compared to uh the an orally dosed preparation. Um the point being that ideally, as you said, in a we'd have daily UVB exposure such that we have a slow drip of of uh vitamin D into the system and therefore a slow drip of uh of 25 hydroxy vitamin D into conversion into 125 hydroxy vitamin D at the end target cell, whether that's the kidney organ, whether that's the brain, whether that's the immune system, uh it it it's etc.
SPEAKER_01:Yes, uh thank thank you for summarizing. So you did very well. So this slide's uh this is the last one on this series to show that again, the more important the concentration in the blood that can see the nanomoles, whereas a pico moles in with cancetrioles. It's very important to understand that so the difference between what you can achieve and the half-lives of uh uh D3 molecules. So preferably what we recommend is to take D3 routinely, but there are specific instances where you can uh take 25 hydroxide calcific diode. One, as we said, is uh the acute infections because that will act within 46 hours. The second one is that somebody with the liver failure, which does not produce 25 hydroxide, clearly, given that it will be beneficial, you can bypass the liver. So on the other cases, calcifidiol is not a replacement for vitamin D. It's just 20 times more expensive, and it's unnecessary to give calcifidiol when there's no rush, then you can get all the benefit by giving D3.
SPEAKER_00:Can you speak to the clinical evidence for the the use of calcifidiol in uh acute illness, say ICU, ICU admission? What what and the this other idea that um potentially we're we're trying to assess our patient's vitamin D status. So we take a 25 hydroxy serum measurement. Is is that a negative acute phase reactant? Is that going down because the patient is is so unwell, and because the they're they're essentially consuming up uh that that um that's one point max.
SPEAKER_01:I mean, this again we learned during the last just a few years really, and there are convincing evidence that any acute illnesses, even the trauma, infections, autoimmune exacerbation, consume significant amount of uh cassit triol within those immune cells. So this is one way things intracellularly generated calciol does not come back to or secreted back to the circulation, they get destroyed within the uh active cells, immune cells. So what is necessary is actually in even those circumstances, unless you give them enough substrate D3O calcifidiol, your immune cell activity continue to go down. For example, if somebody with acute infection admitted and the level could be normal, uh the the the the D3 D 25 hydroxy D could be normal, but the consumption of vitamin 25 hydroxy D and D3 tremendously increased during infection. So, unless you give a supply of vitamin from the day one, if you measure the level in day four, day five, it could be actually going back to the deficiency level. So, this is another principle very few people understand and difficult to grasp. So it's part of the not necessarily part of the the acute phase reaction, but the consumption within the immune cells, because they use so much to get it activated and and they get uh they're deactivated with the 25 hydroxide enzyme. So to replace that, you need to have a daily supply of vitamin D3 and 25 hydroxide D coming into the circulation and then moving in inside the cells.
SPEAKER_00:And do we have some do we have some randomized controlled trials come look double blinded or placebo controlled showing that patients treated with with calcifidiol have a better outcome and say in acute respiratory distress syndrome compared to a placebo? Is that data that we have or not not really?
SPEAKER_01:Another good question, uh Max. I mean, during the COVID, there had been at least 10 different randomized controlled trials from different groups that clearly shown that if you give classified diol, it has a tremendous benefit in the prevention of complications and deaths. About 50% reduction in hospital setup and ICU. But again, the sick patient giving vitamin D, people have shown that even randomized controlled trials, they're basically no effect. The reason is, uh, as I said before, the vitamin D might not even get converted to 25 hydroxy G to be benefited because their system, whole enzymatic system in the body is not functioning well. So this is the classical example of where people need to be given some very small doses, just one milligram for uh loading dose of calcium triol, and you can actually repeat that in every third day. That will maintain the 24 hydrox 25 hydroxy levels within the normal range of about 40 nanograms per meal.
SPEAKER_00:Yeah, excellent. And I again, I mean, we we've we're it's a little bit um technical, but I think this is extremely important for us to talk about, um, especially for the doctors who listen to the podcast, which is um we we we obviously use or you as an endocrinologist and uh um renal renal physicians, they use calcifer trial uh for their kidney failure patients because that those patients lack because of chronic kidney disease, they lack the ability to convert 25 hydroxy D to calcive trial. So they're obviously giving them that uh that hormone uh directly.
SPEAKER_01:Yeah, it's absolutely right. So uh we haven't spoken about the calcetriole specific uh indication. So as you said, Max, uh, is uh the renal failure is the commonest thing, and everybody knows for the last many decades. So the renal tubular failure will lead to inability to convert vitamin D precursors into calcitriol, the hormonal form. So therefore, when the hormonal form goes down, the uh the musculoselic system, parataryl glands, bones all get deranged. So, because they cannot function normally without the level of uh without having a calcitriole, 125 hydrose vitamin D available to them. So having said that up to about 15, 18 years ago, that's the only treatment uh nephrologists used to give to uh the renally impaired patients, like stage four, stage five uh renal failure. Since then, there were many studies shown that if you combine the calciol with vitamin D, the complication and the survival is significantly increased. That shows the other beneficial actions of what these precursors in these patients, that means also in every other patient which we are missing. So now the current treatment is actually not only provided the casset triol, but also provided them with a reasonable dose, something like 5,000 to 8,000 international units of vitamin D on a daily basis, because we know that categorically through randomized controlled trials, their survival and the quality of life both improve. The same thinking, uh, the measurement of 125 hydroxy D is redundant, should not do it because you cannot interpret that data. The only reason for doing the 125 hydroxy assays is in real failure, or there are very rare genetic disorders of failure of production of 125 due to enzymatic failure in the hepatite mostly. So there is no routine reason for measuring 125 hydroxy D3.
SPEAKER_00:I'm I'm very glad you brought that up because in some uh holistic health circles, um people are advocating for measurement of 125 hydroxyvitamin D. But I think as you've really uh comprehensively shown, it's it's not really giving us a very good idea about uh anything except in the case of severe um renal failure because of its tiny circulation, uh tiny uh in the circulatory system, and the and the fact that, as you mentioned mentioned earlier, that uh most of this enzyme and of this hormone is actually being converted on site in the cells when it's being uh needed. I I would be curious myself about a trial of whole body uh you know heliotherapy for these coronic renal uh failure patients and whether um in addition to if we could um help them generate massive amounts of solar cutaneous uh vitamin D and and uh and secosteroids, maybe that could even uh help um improve function and potentially reduce the amount of supplement needed.
SPEAKER_01:So before addressing that one, I think we're going to go back to the previous one, which is uh not not only that 125 hydroxyl level is uninterpretable, it's actually misleading. So if you could recall that the first second slide I mentioned, I showed that let's take a step back. So different tissues need different thresholds of vitamin D in human, not the diseases, it doesn't affect with the age, but different tissues have a different threshold. For example, uh muscular skeletal tissues, 15 to 20 nanograms per milliliter is more than sufficient to full functioning of the of the uh for the human. If you take back, take a step back and then think why is that happening evolutionary? This is the evolutionary mechanism for saving our human lives. So imagine that you are back to undergathering at the stages. If you don't have a musculoskeletal system to go after animals and eat and kill, and also running away from them, you are dead in no time. So, priority in the body is to provide the necessary circulatory calcetral hormone compromising the all the other other systems which are not priorities for survival at that time. Therefore, whatever the available 25 hydroxy D is taken up actively. There's a positive mechanism of extracting 25 hydroxy D into renal tubular cells, it's called a mechanin-cubuline mechanism. So even the little of 24 hydroxy D available will be extracted from the circulation to renal tissues to convert it to the hormonal form of calcium triol. That's one do this job. So in those circumstances, if you measure the 25 hydroxy D, or if one measure the 125 hydroxy D level could be absolutely normal, but the 25d hydroxy D could be very low because of that active mechanism of extracting 25D into the renal tubular cells. So coming back to the heliotherapy and things, there are a lot of studies going on even now. So this is showing uh some initial studies show the controversial data, but I think that things are getting better once if people understand what exactly the wavelengths and prevent the harmful wavelength provided to patients and the duration of uh exposure, that kind of thing, uh things are getting better. You have to remember that no matter how much exposure we have, heliotherapy or sun exposure, we will not get hyper level of vitamin D or 25 head with D in circulation. So this safety mechanism overrate everything.
SPEAKER_00:Yeah, thank thanks for re-emphasizing that. And uh a previous podcast guest and uh founder of MedCram, Dr. Roger Schwelt, who's a intensive care uh physician in Loma Linda, California, he's had some great results with uh acute viral respiratory illnesses and with simply just taking his patients outside. And uh he's got some great videos that on on that, the why that is working and uh and and factors not only related to the vitamin D system, but also to near infrared, which is which is very interesting. Uh, I want you to talk about the hypercalcemic syndrome, and I and and I think it's relevant because the the threat or the worry about inducing uh hypercalcemic hypervitaminosis D is probably one of the biggest things that is uh factors that is preventing my colleagues and probably your colleagues from helping people to uh get to a healthier vitamin D level. So so can you can you talk about this diagnosis and what it actually means to have too much vitamin D in in our system and what that leads to?
SPEAKER_01:If you want my add one more thing on the previous one. So historically, going back to 100 years now, the tuberculosis and leprosy patients they were segregated. So the people who were taken into the sunshine or the onto the sunshine on the daily basis survive, whereas the rest demise. So they didn't know what what curing this uh this patient who exposed to sunshine. So that concept has been there for nearly a hundred years, and of course, over the past uh few decades we really we got to know that that's because the conversion of uh your generation of vitamin D in the skin, which does that uh uh uh therapy for these patients, it's similarly uh as you said, that it uh it is very important in infection control. So let's come back to the toxicity. Vitamin D toxicity, I would say that's as rare as a hen's t. Extremely rare. Only 100 twenty cases have been reported in the literature. Almost all of them are due to mistakenly taking very high amount of vitamin D. For example, in Canada, there was the dropped droplets of vitamin D, and uh they had one million units per ml. So instead of drop taking, those who take one ml per day, they had multiple millions of vitamin D coming into their bodies in short period, and they develop uh hypercalcemic syndrome. Secondly, to diagnose hyperclasmic syndrome due to toxicity, you need to have at least three specific things. Number one, EC circulatory level of 25 hydroxy D should be above 150 nanograms per meth. Most cases above 200-250 nanograms per meter when you get a toxicity. Secondly, there must be a hyperclasmic symptoms. The dry eyes, uh, cardiac arrhythmias, and uh various other hyperclasmic syndrome. And third one is hypercalciuria. So once you get all three variables, you can categorically say that okay, this is probably most likely due to vitamin D. Let's stop vitamin D and almost always cases with time, it will come back to normal. Very few patients needing dialysis, short, short-term dialysis to remove the ionized calcium. But that's true with any hypercalci syndrome. The most commonly is secondary to cancer, head and neck cancers and squamous cell carcinoma. That's not due to vitamin D, but is due to PTH related peptide, PTHRP, uh peptide released from the squamous cell carcinomas. So that's a complete difference. But it's the paranoia life-threatening conditions. Yeah.
SPEAKER_00:Yeah, exactly. Yeah, yeah. The the the point is, and I'm going to convert to Australian units, uh, 150 nanograms per mil is uh going to be above 300, 350 uh nanomoles per liter again as this threshold for toxicity. And and I'm not advocating that people uh are using you know ultra-high dose supplementation. Like my my preference is always that people build their serum vitamin D naturally. But uh, you know, even on our reference ranges, uh I've I've heard of lots of people who've naturally had levels of 180, even over 200 just from solar exposure. And their doctors have said, you know, hey, what are you doing? Stop doing whatever you're doing. And as you've you've you've you've clearly laid out for us, Sunil, this patient is so far away from uh a hypocalcemic syndrome. One is because they're not even supplementing. So no matter what that level is, it's not they're not at risk of hypercalcemia because it's cutaneously generated. And two, even if they were without high serum calcium, without hypercalciuria, without uh symptoms of hypercalcemia, then this patient doesn't meet the criteria and is therefore not at risk of uh of complication of having too much vitamin D in the system.
SPEAKER_01:Yeah, I mean, in in general, there's no reason to get alarm with that kind of numbers. I mean, even the normal range from in US is uh the upper limit is in 100 nanograms per milliliter, which is uh 250 nanomoles per liter. So the uh there's only one or two exceptions uh with a sensitivity to um um vitamin D. One is a Williams syndrome, for example, is a generating disorder. So those with the Williams syndrome and uh they have a hyperactivity to on generating and maintaining high level of vitamin D, which is an extremely small uh number, number of patients. So the the I I think it's it's a hypercalcemic syndrome, secondly to whole vitamin D toxicity itself is hyped due to a number of uh reasons, mostly political, and big pharma have been amplifying the stories just like happening with uh I was McKean during during the COVID period.
SPEAKER_00:Let's let's talk about the breadth of uh issues that are potentially ameliorated or prevented by vitamin D repletion. So we've we've we've briefly we've obviously uh and you've got a very good slide on this. Um at the base level, you've we've talked about bone complications. And um, in children, that severe vitamin D deficiency uh causes rickets. And people people might have seen pictures of children with bowed legs, bowed femur, and uh tibia fibia, and that's through uh having a lack of vitamin uh D. And then in the adult, we get dysplasure of bone formation, which is called osteobalasia, uh, and long-term contributes to osteoporosis or thinning of bones. But as you as you alluded to, Sonil, this is really just the tip of the iceberg. Um, above that, we've got these muscle functions, and it's it's very interesting to me that you can prevent falls in the elderly by simply just raising their vitamin D level. And uh how many athletes out there could optimize their musculoskeletal function with with by raising their serum vitamin D levels? But um talk talk us through the next steps incrementally as we raise the serum vitamin D level and what disease processes that is preventing or ameliorating.
SPEAKER_01:Right. So interestingly, over the over the few decades of uh my clinical practice, I have seen many patient patients brought to me for various reasons. And when we treat them with a high dose vitamin D, we regenerate at least 200,000 as a uh uh bonus bonus dose and 50,000 a week. Within about a week, two weeks, many of these patients starting walking. It's not a miracle. All they most of them had a severe osteomalacia with the pelvic and the girdle weaknesses, so they cannot comb their hair or eat, they're very weak shoulders, they cannot get from the bed or chair because of uh the pelvic pelvic muscle weakness. So these will get rectified within days of adequate supply or what I mean. When I say adequate supply, not given by 5,000 or 10,000, they need the starting dose by 200,000 or 100,000 at least to begin with to replenish their stores, and they'll have remarkable uh recovery from their illness, illnesses. So let's see and similarly, I as I as we said, the most uh of the of the the diseases as I mentioned here, this this slide basically is showed that this is a serum level of vitamin D, 25 hydroxy D in nanograms of mil. For Austrian levels, you need to multiply by two and a half times. So 15 to here is above 80. That's a separate category. You just forget about for the time being. And here on this x-axis on the right side, I showed is a reported percentage risk reduction or improvement or getting rid of the symptom. You can see that in calcium metabolism, skeletal issues like ricote and osteomalacia, there's a 90% recovery within weeks of getting the level up to 20 nanograms per mil. For example, others, osteoporosis, fracture prevention, inflammatory bowel disease, which is immunological disorder, they need a little bit higher. So obesity, diabetes, some of the cardiovascular disease, they need 40 nanograms per mil. These are tissue threshold, the vitamin D can get into the relative responsive peripheral target cell. And autoimmune disorders like multiple sclerosis as well as uh acute infection, they need a lot more higher, minimum of 50 nanograms per mil. So these are the categories we are talking about one person or less of the population who has a vitamin D resistant syndromes, generally preferable to treat by the experts who can handle higher dose of vitamin D, like Coimbra Protocol, and there are two or three very high dose vitamin D protocols, but it must be administered by somebody in a center or somebody who knows how to handle this and prevent adverse effects. But these disorders like uh plaster headache, migraine, some uh will respond dramatically when the level were raised higher than 80 nanograms per milk. Some of them actually to up to about 150 nanograms. But this is not for routine practice for primary care for the GPs. Please don't try to do that because that you can get into issues. So basically, the slide shows that there are different thresholds for vitamin D for different tissues. However, it's also important noted that there's no differences in threshold for male, female, or young versus old, or sick versus healthy. That doesn't change. So what we need is uh to have a white uh the minimum level to accompany or actually to take care of at least 90, 95 percent, 98 percent of the disorder, which is 50 nanograms a meal. 40 nanograms will also okay, that covers about 80 percent of the disorders. Whereas calcium metabolism, 15 nanograms will only take care of the calcium and sorry, the the skeletal muscular cancer disorder, which is about 25 percent of the issue. So people asking what is the what should be the normal range? So depending on the interest of the group or conflict of interest, they say, okay, 20 is enough, like Institute of Medicine did, because they were only focusing on the records and and and Austrian Malaysia. Even then, they made a huge blunder, uh statistical mistake by missing a decimal point, and instead of 600 milligrams of calcium, instead of 6,000, they actually recommended 600. They made a huge issue. That causes really problem for the subsequent the all the guidelines because they were all relying on the Institute of Medicine guidelines, which are therefore every possible every other guideline came after that to a completely screwed because they are all catering for musculoskeletal only. Only now people are beginning to realize that that's to be the mistake. We need to get out of it, and we need to revise the muscular the guideline to cover these disorders, otherwise, they'll be not not even touched.
SPEAKER_00:Yeah, and 40 nanograms per mil again to for the uh UK and uh Australian listeners, that's uh 100 nanomoles per liter. So that's that's commonly one that I just say to my patients, like, I mean, at least let's try and get you over a hundred and let's get you at least over 40, again, ideally through natural sunlight exposure and as a as a as a first line, because we're gonna hope we'll prevent so many uh issues. And you know, I would I was uh talking to a clinician and uh the rheumatologists or the uh immunologists who are treating sorry, the neurologists who are treating multiple sclerosis, they as a rule, they want their patients over 100. So it's almost like certain specialties within medicine have have realized that if their patients go beyond, go below these levels or above certain levels, they do better. Yet for some reason it's not uh universally acknowledged because of siloing and medicine. And, you know, I'm I'm interested to hear your your thoughts on that. But uh the the truth of the matter is that if we get above some of these thresholds of 25 hydroxy D, uh ideally through natural exposure, then we're gonna prevent so many of the chronic diseases that are affecting us as uh today in society.
SPEAKER_01:I'll give one example of um so this is about uh two or three decades ago in our clinic, my clinic, we had uh something like a 70 plus multiple sterosis patients coming to us on various issues, and uniformly their level were about 5, 10, 20 is the max. So in my clinic, we opted to change that and uh to want to keep the less the level above 80. Within months, you'll be surprised that recurrence rate of my multiple sclerosis reduced by 80 percent. So instead of coming every three months of various ailments, now they're coming once a year. You don't need to. All because we are now providing the enough vitamin D to immune cells so that that autoimmunity can be controlled within themselves.
SPEAKER_00:And you in one of your review articles, you really eloquently described what is actually going on when we're we're vitamin D replete versus deficient. And I've explained it to my patients as uh in a in a simplistic way is that when you're vitamin D deficient, your immune system has its fists up and it's ready to fight, uh, essentially ready to fight itself, and therefore put putting you at risk of autoimmune conditions. Um, and that is also the latitude gradient, the UV latitude gradient that we see in autoimmune disease because of the lack of availability of vitamin D generation or um sun exposure, sun-seeking behavior, the further down away from the equator you go, the higher MS and type 1 diabetes and these diseases rise. But uh you put it really eloquently in your review article when you describe this vitamin D system as almost a switch that's turning the immune system from pro-inflammatory uh if you're deficient to uh essentially immune tolerant and anti-inflammatory when when you're when the patient's vitamin D replete.
SPEAKER_01:Yeah, it has been now described over the last 10 years by many research groups. Uh the phenomena what you mentioned is for example, TH1 cell to TH2 cells, that transfer will not happen unless there is a sufficient vitamin D, active vitamin D within cell. Same with the TH17 cells. So in in the vitamin D deficient status, these active immune cells will remain in the inflammatory setup. So produce, continue to produce inflammatory cytokine rather than anti-inflammatory cytokine. So in the presence of sufficient vitamin D, so TH cells, TH1 converted to TH2 cells, then that alone will prevent the generation of inflammatory cytokine and start to generate more protective anti-inflammatory cyclotriin. So this thing happened on multiple sites or the mechanism within the immune cells. So this is another one area, the switching necessary from vitamin D to immune cell to do what it's supposed to do rather than harming us by generating autoantibodies.
SPEAKER_00:Yes. Well, let's talk about dosing now and uh how how do you approach the the topic of dosing and talk about perhaps some of these cofactors that are necessary or or required in in the metabolism of uh vitamin D as well.
SPEAKER_01:Yeah, so the the recommended doses by the government and most societies is 400 to 600 uh milligrams, sorry, international units on a daily basis, which barely change the serum level of vitamin D. So I told you the reason because they fork they'd mess up with the conversion from statistical error. So generally, what we do is if there's a no emergency or the patient is not sick, you can start the normal replacement therapy of vitamin D. What we recommend is actually this is after analyzing about over 500 publication, published data on uh 25 hydroxy D and how it affects the various systems. So we we come up with the formula to give between 70 to 90 international units per kilogram body weight for non-obese person as a replacement dose. Very easy to calculate, very easy to remember. You don't need charts anything, even though in but two, three years ago we have we published a detailed tables how to calculate on an individual basis. That's cumbersome, but helpful. But if you remember to use uh mentally calculator 70 to 90 international per kilogram basis, that is the amount necessary for maintenance. However, people with obese overweight and those who are with um the other disorder, well, comorbidities, or taking uh medication that increase uh hepatic catabolism of vitamin D, like reptilal drug drugs, or anti-epileptic drugs, they are going to need about three, maybe four times higher than these doses to maintain the serum level of 22 hydroxyD between 40 and 80 nanograms a mil. So it's it's it's a concept that sometimes going to take a little while to understand, but it works and very easy to remember and use in in clinical setups.
SPEAKER_00:And in terms of the the dosing, we've we talked briefly about how we essentially want to maintain a constant supply, like a drip of uh vitamin D into the system so it can be readily and and accessibly converted to calcitriol. I I think of this like uh and I and I think it also about this during um gestation and and pregnancy with respect to all micronutrients, is that you want it's like you want the shelf on the supermarket to always be full. You don't want to you don't want there to be a period where you've you've got an empty shelf where you can't restock. You always want there to be enough. And uh so so what is the the daily recommendation? Again, I'm gonna preface this with uh I I recommend people get solar generated D if they can as a first uh port of call, and they can use an app like uh uh DMinder to to kind of track that or estimate the amount that they're making. But if if say that they're supplementing and say they've got a critical illness or they've got a severe autoimmune disease, um what what would you recommend in terms of dosing frequency?
SPEAKER_01:Yeah, I I as I'm I'm totally agree with you. Whatever it is, is a daily is the best option. If you can remember to take daily or is it combustant, then once a week is the second best option. Both works pretty well. But if you increase the frequency beyond twice a month, it's actually not helping. There are studies done with uh the the giving a very large dose of vitamin D on every six monthly, three monthly, or annually, none of them showed any benefit. In fact, uh annual treatment has shown actually significant negative effects, like increased force and fractures. That's understandable when you because when you Give the large doses to somebody deficient, transiently that person becomes vitamin D sufficient. So their function becomes good. So they started walking straight away, and they are going to have falls because they don't have the balance enough. So that's the reason for increased uh fractures and falls, not because the vitamin D toxicity, because they do they try to run before they can stand up. So that that way. Let me also mention uh before I forget that uh the dose of uh calcifidiol, which we have published uh in about three years ago. So again, very easy to calculate. And if you remember to 0.014 milligrams per kilogram body weight, an average person has come to about one milligram basically. So 0.014 milligrams per kilogram body weight is a standard dose you can give to anybody to raise their serum-25 hydroxy levels within four to six hours to a given condition. So it will power them.
SPEAKER_00:Amazing. And and maybe that's one for the general medicine physicians, the internal medicine physicians who are treating their impatients. Uh, get your pharmacy to stock calcifidiol. And if you're having someone coming in with a low-barne pneumonia or another sepsis, I mean it's it's it's a it sounds like a very cheap and safe intervention to yes, treat them with intravenous antibiotics, uh, but why not treat them as well with uh with calcifidiol if you can't, which most people can't put them out on the porch uh on in the sunlight.
SPEAKER_01:In this regard, so so the the calculate very detailed calculation we have made on different models, and the cost benefits of vitamin D prophylactic will using is about one to ten thousand. So if you spend one dollar in uh to to treat with vitamin D, you get close to ten thousand dollars worth of uh prevention. Because these patients are getting into vitamin D deficient patients are getting into various complications, diabetes, asthma, GI, neurological. So if you look at the test needed to these patients, like MRIs, etc., hospitalization, those if you do the detailed analysis, it's a huge cost-benefit of providing vitamin D. In addition, the recent work we have done uh on occupation point of view, it shows that it significantly reduced the absentees and improve the work efficiencies. So I suggest that uh the companies and the directors and owners of these large businesses think think carefully and see whether they they what benefit they can get by the making their uh working population vitamin D sufficient, which costs virtually nothing. And we even without without the testing 25 hydroxy D. Testing is recommended but not essential. By doing so, they can see that the difference within six months of productivity and absent reduction of absent disease so that in other words the opportunity costs reduce dramatically in these patients or in these circumstances.
SPEAKER_00:That makes that that would make uh sense to me. Can you speak to the use or the co-supplementation with vitamin K2 and this idea that uh potentially if we are supplementing in isolation uh vitamin D, the possibility of adverse cardiac calcification um effect.
SPEAKER_01:Yes, uh sure. The vitamin K is the one you you you're now you're referring to, although vitamin K has no direct effect or enhanced activity of vitamin D, it's supposed to divert that excess calcium, if any. I'm talking about the ionized calcium in the blood towards the bones. So just like uh osteocalcien, then that kind of thing to absorb the calm serum excess calcium into that. But generally, uh unless you're taking anything more than 7,000 international units per day, you are not needed to have white on K2. But taking K2 is no harm. The amount of K2 we recommend is about uh 100, 150 micrograms per day, or there are once a week capsules, come up comes up with 800 micrograms per capsule. So, for example, if you're taking 50,000 unit capsules together with one capsule of K2 of 800, that will 100% protect you from any possible potential of calcification issue. So the second most important nutrient or the supplement you need for activity with uh vitamin D, and it's particularly the receptor interaction as well as in cerebral coinsular activity is magnesium. So in the in the magnesium deficiency, vitamin D, know the many of those hormones work properly. If you look at the thyroid hormones to insulin to test hormones, their release is depending on the availability of a certain intracellular amount of magnesium. So as a vitamin D interaction with the VDR, vitamin D receptors, as well as a chromatin interaction need um magnesium. So just by increasing the vitamin D dose, say if you give about 50,000 once a week or six thousand a day, if the patient if the person is magnesium deficient, you may not see the benefit as you expected. So in addition, there are other things like a whole bunch of other things like omega-3 fatty acids, zinc. They are all cofactors that facilitate the activity of most of the enzyme, but not necessarily vitamin D. But holistically, for a person to function well, all these core factors are going to be necessary as well.
SPEAKER_00:Yeah, and very interesting point. And anecdotally, I've heard of people who have supplemented or they they've commenced high dose vitamin D supplementation and then found them themselves getting cramps. And uh, I think that speaks to the the need to uh ingest uh the magnesium potentially with that. Do you have any recommendations on preparation or dose or route of uh administration of that magnesium?
SPEAKER_01:My best recommendation is take a banana a day, maybe a two a day. But that will provide about 200 micromilligrams of vitamin D s or magnesium necessary. If you can, or if you don't like banana, you can take all the count of magnesium, 200 to 300 milligrams on a daily basis, or even every other day, that definitely is going to be helpful rather than taking nothing. Because most of the Western diets are deficient in magnesium.
SPEAKER_00:Yes. Are you are you aware of any um and again this is a question uh related to the fat-soluble hormone nature of vitamin D. Are you aware in the literature of any interaction with the vitamin A system and whether supplementing uh higher doses of vitamin D perhaps in uh might be uh unyoking or or disturbing a relationship between uh vitamin A and vitamin D.
SPEAKER_01:Only literature I have seen and um understood is actually high vitamin A intake, it definitely can interfere with the vitamin D metabolism. So that's the balance between the vitamin D and vitamin A are necessary. But when if one someone getting a super super high dose of vitamin A, you need to be careful because uh not only the vitamin D interaction, it also can interfere with the bone mineral mineralization and indirectly increase the like uh the increase the the likelihood of duolyping occur malasia and other bone disorders.
SPEAKER_00:Yeah, and and that I mean no one is recommending high dose vitamin A supplementation, so that's uh I think we should make that clear that uh synthetic vitamin A uh, you know, retinoid supplementation is not anything that that I'm advocating for. And and we know that these retinoid medications like isotretinoin are uh potently teratogenic. So uh you make that we'll make that uh uh abundantly clear. So um that's uh that's a very good kind of summary of uh of of the topic. And do you do you have any uh other quote uh points that you would like to raise um about about the topic?
SPEAKER_01:Um yes, I know. I mean you have to be careful on what's happening in some countries, actually in in Australia also. The government's trying to regulate uh minerals and supplements, uh nutrients basically. So that is showing that it's a control mechanism for politicians or whoever the people who want and uh shouldn't. Natural food or minerals and supplements should never be regulated by the government. That can always cause problems rather than help it. As I said before, the there are a very small category of people who are going through very high doses of vitamin D. They are mostly either vitamin D resistant disorders or disresistant to other drugs, like asthma, for example, or migraine headache does not respond to the standard therapy, they'll have a plastic headache. They will get a remarkable response if you raise the level. But that needs to be done by the experts, not endocrinologists generally, but somebody who have expertise of handling how high doses of vitamin D. Secondly, uh the those who are taking vitamin D, there's no reason to take calcium supplements. Because vitamin D itself, if you're having a sufficient amount of dose and level between 30, 40, and 50, that should increase the fractional absorption of calcium from the intestine and automatically get adjusted to the appropriate level of absorption. Therefore, you don't need to. In fact, we should not take excess calcium, extra calcium when you're taking a sufficient vitamin D. So it's not a routine or we generally discourage to taking calcium supplement the people who are taking vitamin D, except in the case of pregnancy and lactation, because the the requirement of calcium goes up tremendously for fetal transfer and calcification of their fetal bones. So other than that, uh there's nothing specific for to restrict the taking vitamin D. Finally, the the effect of vitamin D through the immune system not only uh the both adaptive and supreme immune system, and they generate a lot of anti-antimicrobial peptides like the uh LL22 and things to protect the human being. So need to think about the optimizing vitamin D on people who are coming with any infection or autoimmune disease, because that might really helpful rather than getting into the the the high-end in the auto auto um antibody therapies and that kind of thing. It's just usually unnecessary.
SPEAKER_00:Yeah, I mean what that's such an important point. And the way that medicine is going now is that there's a new monoclonal antibody flavor for you know every single new cytokine under the sun. And yet these the basics aren't being done. The patient isn't getting basic advice about uh ideally full body sun exposure, generating and maintaining a high serum vitamin D level, supplementation if that's not possible, um, maintaining an aligned circadian rhythm. I I know it's not your uh area of research, but we we know that the the circadian clocks are regulating uh immune system function as well. So if people are exposed to artificial light at night, they're suppressing melatonin, um, then they are also uh going to be hamstringing their immune system function. Yet uh no no none of uh very few of our colleagues are are discussing this in terms of giving their patients the full uh advice to to optimize their immune system and their health.
SPEAKER_01:I 100% agree with that. The the natural therapy and uh immune regulation using the supplement or the diet itself is is the best way to do that rather than getting injection and all the other cocktails uh available or recommended by various pharmaceutical organizations.
SPEAKER_00:Uh and and maybe a final question, because I really enjoyed what this in one of your research articles was this idea of uh study design, designing a study to to essentially have a null finding. And what I mean by that is that uh there's this there's in this immense pressure from the pharmaceutical industry towards the generation of novel therapies. And the reason for that is because what if it's novel, then it can be patentable, and if it's patentable, it's a profit-generating source. So uh the the corollary is that if there's an effective generic medication or supplement or hormone, uh then it's in the interests to uh essentially reduce or denigrate it the efficacy of of that compound. And one of the ways that you describe in one of your review articles that uh this can be done is by simply uh if say we're testing the role of vitamin D in a disease outcome, is simply recruiting a whole bunch of people that aren't vitamin D deficient. So you give them vitamin D, nothing happens. Well, was it because the vitamin D didn't work or because they weren't they were vitamin D replete?
SPEAKER_01:You're absolutely right again. I mean, the the if you look at the last six major, what I call the mega vitamin D studies, sponsored by governments and the industry together, like uh the the the vital study, for example, and there are several of them, seven of them. So if you look at the recruitment, the more than half of the patients have vitamin D sufficient on their own guidelines. So, what can you expect to give vitamin interactions?
SPEAKER_00:And this idea that is sufficient in vitamin population to anything. Uh essentially, so that's one way of showing that vitamin has no effect. During winter they would have significantly less or non-vitamin D spinnings. And are you aware of literature or the phenomenon? There are many examples melatonin kind of in on vitamin D receptors to potentially compensate and during winter time for an absence of UV.
SPEAKER_01:And also multivitamin max. And there are a lot of uh vitamin D that came up over the last what three, four years in a few groups, melatonin, a few of your C G now and this biprotector. So how do you interact? The different metabolic pathways and human ingredients. So so the things going on. I'm just already summarized. And the X band is T and the interaction with the volume. The baseline as well as other and on to bring them together that you only should reprove the other side by the circuit rhythm. Again, um because you could bring a study harmonizing supposed to work. Yeah, vitamin D.
SPEAKER_00:And maybe a final question is I really enjoyed put this in one of your research articles. This idea of thousand units study design. Designing is study to have a null finding. And what I mean by that is one should never this immense pressure from the pharmaceutical industry towards the generation of novel. Normal normal. And the reason for that is because what if it's novel, then it can be patentable.
SPEAKER_01:And if it's patentable to profit, just like maybe other nutrients.
SPEAKER_00:Uh essentially reduced or denigrated the efficacy of that compound. So there are one of the ways that you describe in one of your review articles that can be done is by simply instead of testing the role of vitamin D. It's simply recruiting a whole bunch of people that have a target. So you give them vitamin D, nothing happens. Or was it because the vitamin D didn't work?
SPEAKER_01:Because they worked in the vitamin D didn't happen. So if you were to do that again to make sure if you look at the last and at least six to four months later, that they are all the backup and level of vitamin D. Like without that, just simply to correlate the dose of vitamin D to vital study, for example, and there are several of them. Seven of the patient is different. If you look at the group, metabolism is different than two patients. Even if they are weight to give five thousand UDs, they have different what can you expect to give vitamin D 2000 unit?
SPEAKER_00:It's just such poor science, and somebody to me it's sufficient in vitamin. I mean, in any industry is anti-competitive behaviour. But what essentially it appears that the farms would design to simply weaponizes uh the randomized control while it weaponizes fire to essentially knock off competitors over the community. There's a whole bunch of uh generic label of painting or multiple that we're not we won't discuss here, but uh some people will will you can read between the lines. Uh you have two groups, don't find the group. You've got a null finding and then come up with you you try and you say people who don't read into the the depths of the study designate the two, and then you can therefore write everyone off as a quack or uh anti-science there are several things. So I'm just saying, you know, that's my two two sense of cynicism.
SPEAKER_01:Next one is actually measuring the baseline vitamin D. A couple more points to add when you do that. You wonder how if we could be able to vitamin how the efficient twenty and twenty twenty five on our recent uh new paper by generating people type vitamin D by studies, otherwise two agents are severely deficient that efficacy is more than percent reduction in fertilization. It takes one year for them to raise their patented two patented drugs unless you give a train to a thousand units. And you only have the reduction of the daily utilization. They will respond very well. They do not have the certainly reduction should never use the slow end of the tattoo. Here's there are 100 plus norms after no proteins by 30 plus randomized controlled use trials showing every study. Propaganda is why is it like reduction by 50% cost nothing? And finally saturable groups that we saturated by the which we most rejected the reaction Rosities for example has no nutrients side effects. Different between the nutrient and the pharmaceutical agent poorly designed studies many different and nutrients the serum 25 the pharmaceutical agent have a target level to be achieved. So if you can give a V and I mean multiple sections showing that it is not going to happen. So if you were to random is the wrong use and at least show efficacy of the money to make sure that they are all their old requirements above the target level they use that to discredit without that just simply to randomize the design specifically by the industry in in the approval because every patient is different medication. And yes and vaccine is different people regulatory approved even it's the same rate anything else 5,000 units. Whereas nutrient differently pharmacokinetics are different it's it's just such poor science to me it it it evokes or useful anti-competitive behavior.
SPEAKER_00:I mean in any industry there's anti-competitive behavior but what essentially appears as the pharmacologist simply weaponizes the randomized control trial it weaponizes science to essentially knock off competitors in this case any beneficial say item desupplementation or let's there's a whole bunch of other cheap generic off pay off label I mean isn't it just a call to we're not we won't discuss here but uh patient in front of some people will get the back between the lines uh and you'll do this junk science and then do the out of finding again written off by this you've you've you're trying you know I would say a uh to people who bring to the breed into the church of that randomized control that good but this doesn't work and then you can therefore write everyone off as a common sense or intervention science and if we've stable even that in a clinical two too simple improving with um with the same your case of MS patients that we've raised their vitamin D's use that in our clinical judgment during the COVID period we've got to help our patients rather than discounting or discrediting uh potential beneficial safe treatment options because of vitamin D I mean XYZ uh conflicted study said uh that it was clinical trial efficacious but it was again a flawed and the showing that the efficacy is more than 50% reduction of hospitalization and the death so maybe we could finish with drugs the summary like the vaccine slide that you've that you've prepared and to viral and they only had the reduction of hospitalization.
SPEAKER_01:They did not have the death reduction of any of those studies getting the approval. So this like this vitamin D summarizes the vitamin D plus vitamins with about 30 plus randomized control plus trials showing affects virtually everything properly designed in development pregnancy trade about about 50% complications go infants then finally IQ with the kids get affected by vitamin musculoskeletal disorders getting a mistake and all the case the nutrients is gave bad nutrients and comes back in certain countries to define those transfers curves are different policies. Nutrient chronic dose are going to work in the presence of vitamin gains whereas some chronic pharmaceutical can manifest as a results of vitamin deficiency. So and non-traumatic and other publish multiple reviews and autoimmune diseases are randomized control efficacy of any obvious metabolic disorders like discredit what worse in the randomized metabolis by the industry other side is the coinists who have these medications medication if you treat them properly supplement them properly get the heliotherapy increase the serum levels anything else they all whereas nutrients behave differently in their pharmacologist and demonstratable RCTs are the circumstances least important or the useful well uh let's wrap up and I really like to end with some actionable advice for nutrients so as actually the based on what you said not being targeting seven to nine days because we have to natural units per kilogram of the cut body weight way too far.
SPEAKER_00:And I will say preferably you can demonstrate and if not you can do supplementation and essentially to use K2 if you I mean isn't it just a call to get back to day patient in front if you're obese get back to then you need an N equals one experiment and triple that anecdotes speakwise again written off by this deal and it's also into the internal physician mice control trial we need to treat patients to consider practically putting your patients out common sense not intervention supplementing the style as a clinical 0.01 proving with uh saying your case kilograms the the host of MS patients that we've raised their vitamin D level. That's fantastic. Anything else to add and if not let us know to help our patients rather people can follow your work discounting or discrediting potential beneficial safe treatment options because of XYZ uh conflicted studies and articles and the suggestion in our not efficacious but it was again a flawed uh investigation as well as uh X and uh Facebook so so maybe we can finish with well just as a summary slide also in the site and yeah we'll we can wrap up a Google scholar we can also pull them up okay I'll I'll include them in the YouTube show notes so people can click on those research papers and read them for themselves.
SPEAKER_01:So uh Professor Wimbledon wants to thank you very much for time we what happened in I think uh a lot of people can get some very interesting and useful information so thank you in deficiency it harm pregnancy thank you pregnancy complication goes up infants they are even IQ IQ the kids get affected when the mother is vitamin D deficient then musculoskeletal disorders we knew that for decades and uh is again coming back the record is coming back in certain countries due to different different OT policies then all the chronic diseases are getting worse in the presence of vitamin D. And some chronic disease actually can manifest as a result of vitamin D deficiency and non-traumatic acute illnesses mostly the infections and autoimmune diseases things are get initiated and as well as aggravated in vitamin D deficiency.
SPEAKER_00:Again these two uh the obvious ones the metabolic disorders like obesity diabetes all get worsened in the presence of metabolic uh the vitamin D deficiency the other side of the coin is when you have these deficiencies and if you treat them properly or supplement them properly or get a heliotherapy to increase the serum level they all get better and virtually has virtually most effective demonstrable in these circumstances yeah fantastic well uh let let's wrap up and I really like to end with some actionable advice for for people for people and I think um based on what you said uh targeting 70 to 90 international units per kilogram uh of of body weight uh and I will say preferably if you can do that through solar exposure and and if not through supplementation and potentially to use K2 if you if you're supplementing over 7,000 units uh per day and if you're obese um then you need maybe double or even uh triple that and likewise if you are uh on you know severely unwell and also for uh internal physicians and people who are treating sick patients to consider uh obviously putting your patients outside but if not uh supplementing with calcifidiol at uh a dose of 0.014 uh is it milligrams um per kilokilogram yeah fantastic anything else to to add and if not let let us know sort of where um people can follow your work and uh what yeah yeah we have a we publish um useful uh articles and the suggestions in our LinkedIn as well as uh X and uh Facebook okay well uh our articles are actually articles are actually published also also in the research gate site and uh and Google Scholar you can also pull them up okay I'll I'll include them in the YouTube show notes so people can click on those research papers and read them for themselves. So uh Professor Wimalawanda thank you very much for your time we we are very much appreciated and I think uh a lot of people are gonna get some very interesting and useful information out of the discussion so thank you. You're welcome Max thank you okay what did you think of that episode? I was very grateful for pre Professor Wimalawanda for explaining some of the core biochemistry underlying vitamin D physiology and how it affects uh immune system function. As I mentioned in the interview I really believe humans should be getting and striving to get uh all their or almost all their vitamin D from UVB light and not rely on either supplementation or food for vitamin D uh sufficiency. And as I've talked about extensively in previous uh interviews and videos this is because sunlight has so many other collateral benefits in especially in in in other wavelengths um that we can't really ignore or just hyper focus on uh on uh supplements to to kind of get our level up I think the position on the in-hospital treatment of acutely ill patients and particularly those with acute respiratory illnesses and and viral illnesses is really timely and and relevant um using calcifidiol as it was discussed and and really measuring vitamin D status on admission and then correcting it could could be a very cheap and effective way of of reducing in hospital mortality so that that is something that I'd encourage any physicians or internal medical uh intensive care physicians who might be listening to consider. Um thanks for your support and stay tuned over the next couple months as I recommence the regular podcast cadence. So thank you for your support.
