Vitamin D: The Trillion Dollar Drug? with Dr. Michael Holick: Rational Wellness Podcast 395
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Dr. Michael Holick discusses Vitamin D: The Trillion Dollar Drug? with Dr. Ben Weitz.
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Podcast Highlights
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Dr. Michael Holick is the world’s leading expert on vitamin D research. He is a Professor of Medicine, Physiology and Biophysics, the Director of the General Clinical Research Unit, and Director of the Bone Health Care Clinic and the Heliotherapy, Light, and Skin Research Center at Boston University Medical Center. As a graduate student he was the first to identify the major circulating form of vitamin D in human blood as 25-hydroxyvitamin D3. He then isolated and identified the active form of vitamin D as 1,25-dihydroxyvitamin D3. He determined the mechanism for how vitamin D is synthesized in the skin, demonstrated the effects of aging, obesity, latitude, seasonal change, sunscreen use, skin pigmentation, and clothing on this vital cutaneous process. His website is DrMichaelHolick.org.
Dr. Ben Weitz is available for Functional Nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure. Dr. Weitz has also successfully helped many patients with managing their weight and improving their athletic performance, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111.
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Podcast Transcript
Dr. Michael Holick on Vitamin D
Dr. Weitz: Hey, this is Dr. Ben Weitz, host of the Rational Wellness Podcast. I talk to the leading health and nutrition experts and researchers in the field to bring you the latest in cutting edge health information. Subscribe to the Rational Wellness Podcast for weekly updates, and to learn more, check out my website, drweitz.com. Thanks for joining me, and let’s jump into the podcast. Hello, Rational Wellness Podcasters. Our topic for today is Vitamin D with Dr. Michael Holick. Michael F. Holick is a Professor of Medicine, Physiology, and Biophysics. He’s a Director of the Bone Health Care Clinic and a Director of the Heliotherapy Light and Skin Research Center at Boston University Medical Center. Dr. Holick is the world’s leading expert on vitamin D. As a graduate student, he was the first to identify the major circulating form of vitamin D in human blood as 25 hydroxyd3. He then isolated and identified the active form of vitamin D as 1, D. He determined the mechanism for how vitamin D is synthesized in the skin, demonstrated the effects of aging, obesity, latitude, seasonal change, sunscreen use, skin pigmentation, and clothing on this vital cutaneous process.
Vitamin D production. I wanted to start this discussion by reading a section from Dr. Holick’s recent article, Revisiting Vitamin D Guidelines, Critical Appraisal of the Literature. If the pharmaceutical industry had developed a single drug capable of reducing cancer mortality by more than 25%, Incidents of metastatic and fatal cancer by 38%, reduced autoimmune diseases by 39%, Including type 1 diabetes by 88%, preventing the advancement of prediabetes to type 2 diabetes by 76%, peripheral vascular disease by 88%, lowering risk of respiratory tract infections by 58%, Thank you. and COVID 19 infections, hospitalizations, and mortality by 74%, 22%, and 45%, and accelerating COVID positive patients to COVID negative by 66%, reducing risk of preterm birth by 62%, and preeclampsia and the need for a c section by more than 50%, the drug would be heralded as a miracle drug. With patent protection, this single drug sold worldwide would be the first trillion dollar drug.
Thank you so much for joining us, Dr. Holick.
Dr. Holick: My pleasure, Ben. Just one correction, and that is because of my other activities, I’m no longer associated with Boston Medical Center. Oh, okay. Yeah, and you can go to my website drmichaelhollick.org, and read about all the reasons why.
Dr. Weitz: Oh, okay, great. So let’s talk about how you first got involved with vitamin D.
Dr. Holick: Sure. So you know, just like any other student that you, you want to have education and, and background and do research in the hottest area. And so I started my career back in 1968. and was eager at this time when DNA was first [00:04:00] discovered that I would wanted to have my career in this area. So I went to the professors at the University of Wisconsin. I had been admitted to the graduate program at University of Wisconsin in 1969. I went to Dr. Lardy and many other really well known biochemists, and They had lots of postdocs, so they don’t need a graduate student. And so they sent me off to Dr. DeLuca, saying that he’s working in vitamin D. And you should talk to him. And I said, I have no interest in vitamin D. And they said, it doesn’t matter what your interest is, because it’s likely that’s where you’re going to be working. And sure enough, I lucked out. I mean, I made Sal’s ear basically into a golden purse, because back then, vitamin D was considered to be a boring subject, right? Prevents rickets in children, right? And end of story. But we But we [00:05:00] began to realize that vitamin D was metabolized, and my master’s degree was to identify the major circulating form of vitamin D in human blood, and to see if it was the same as was found in pigs a couple of years before, and I did, and not only Did I do that?
But I realized something when I was doing the research. There was a contaminant in human blood that wasn’t in pig blood, so that following that procedure didn’t work. So I wound up developing a whole new system of separation techniques and started the research in July of 1969, and on Thanksgiving Day of 1969, I found this new method for separation and had basically completed my master’s degree in three months and identified the major circulating form of [00:06:00] vitamin D as 25 hydroxyvitamin D3. And then the hunt was on for the active form of vitamin D. And at the time, we didn’t really have very much information. We just knew that if you gave radioactive 25 hydroxyvitamin D to a vitamin D deficient animal, rat. In, in the intestine, it appeared very quickly as this new polar form. And so the thinking was that the intestine is the major source of this.
And so everybody started hunting and trying to figure this out. I decided The only way to really know is that you can’t just simply take intestines from chickens and think you’re going to find it because it’s the active form that you needed to have a deficient animal to give in a 10 international units with radioactivity.
And so we grew up 1500 chickens and collected their intestines and I [00:07:00] developed new chromatography techniques and. In 19 71 reported the first identification of the active form of vitamin D is 1-25 Di-hydroxyvitamin D. Now, why was that important? Two reasons. The first is we knew that vitamin D is being activated, but the real question is where?
And the group in Cambridge, England figured that out. It turns out it’s the kidneys, not the intestine. So now we began to realize why patients with kidney failure had severe bone disease and did not react to vitamin D. So I’m an organic chemist, and my roommate and I were the first to chemically make the active form of vitamin D.
And that was my introduction into the excitement of translational research. We gave what we made in the test tube to kidney failure patients that were wheelchair bound, had severe bone disease, and they [00:08:00] began walking again and had dramatic improvement in their bone health. There was also a rare disease called vitamin D dependent rickets type one that we now recognize was caused by the defect in the enzyme in the kidney, and we gave this active form of vitamin D to them, and these children had severe rickets, all of a sudden, which we cured them of their disease. So that’s my introduction into vitamin D. And then I became fascinated by the fact, why would Mother Nature have all of us depend on sun for our vitamin D requirements? And then I spent the next decade after getting my PhD and MD to begin answering the questions that you had suggested. What is the effect of season, latitude, degree of skin pigmentation on the cutaneous production of vitamin D?
Dr. Weitz: So is getting vitamin D from the sun, better than ingesting it from food or supplements?
Dr. Holick: People ask this question all the time. And so the answer is, we did a study and we showed that if you’re exposed to stimulated sunlight in a tanning bed that we had in our clinical research center, compared to taking an oral dose of vitamin D, that the vitamin D lasted about two to three times longer in your bloodstream. So there may be some advantage to that. And we can talk about that later on as to why. Not only should you, in my opinion, maintain your blood level of 25 Hydroxy D, but you should also maintain your blood level of vitamin D, which may have its own distinct biologic function. We also believe, Dr. Slominski has done a lot of this work looking at photoproducts and metabolism within the skin, and it could be that when you’re exposed to sunlight, yes, you increase your risk of non melanoma skin cancer, but it looks like the [00:10:00] vitamin D itself gets activated in your skin and helps to reduce that risk. So that there may be a very important role in this it’s just beginning to be looked at in some detail, so we don’t have the complete answer to it, but there may be some additional benefit by making vitamin D and photoproducts in your skin compared to taking it as a supplement, and then Separately, we know that when you’re exposed to sunlight, you feel better, and you make beta endorphin, you, you are more relaxed, your blood pressure goes down, you make and release nitric oxide and a whole bunch of other photochemicals that seem to be very important for your health.
Dr. Weitz: But it’s not as easy to make vitamin D from the sun as we think. And if you don’t get exposed, if you’re not living at the right part of the globe you know, close to the equator, if you’re if it’s wrong time of the day, if it’s the wrong time of the year, you may be getting a lot of sun exposure and not really making that much vitamin D apart from your own physiology and the fact that we’re all trying to get our cholesterol levels as low as possible.
Dr. Holick: So, you get an A plus for your understanding of the complications associated. And so the simple answer, believe it or not, is that if the zenith angle of the sun is less than 35 degrees, you will not essentially make any vitamin D. None. None. Essentially none. And so, that’s why Even at the equator, we’ve done studies like in Panama, and showed that at 8 o’clock in the morning when the sun is shining brightly, or at 5 o’clock in the afternoon when the sun is shining brightly, in June, you make essentially no vitamin D. Because the zenith angle of the sun is too oblique, [00:12:00] and what’s happening is that the radiation, the ultraviolet B radiation that makes vitamin D is absorbed by the ozone layer. So it never gets to the Earth’s surface. So that’s why time of day is very important. It’s between about 10 a.m. and 2 p.m. is the, is the time that you are able to make a significant amount of vitamin D. Season is also an important part because the zenith angle changes. And so in Boston, we know that by the 10th, end of October, you basically can’t make any vitamin D from sun exposure until next October.
end of March, early April. If you live up in Canada, six months of the year, in Edmonton, Canada, we did a study to show basically by the end of September until the end of April, they basically are not making any vitamin D. So, time of day, season, latitude. We also did a study of altitude. I had a good friend that went to base camp in Mount Everest. And so I gave him my ampoules and he put them as he was going up the mountain, and we showed him nicely that in Agra, right, the Taj Mahal, right, November, zero vitamin D is being made. Wow. Partly because of air pollution and whatnot, but it’s, but when he went up to 5, 000 meters, which I think is where base camp is you efficiently can make vitamin D, right?
Mm hmm. Skin pigment, right, was designed for us to prevent damaging effects from excessive exposure to sunlight, and as a result, the melanin is very efficient in absorbing UVB radiation, and so people of color are more likely to be vitamin D deficient because of it. They cannot as efficiently make vitamin D.
They can make the same amount of vitamin D. They just need a much longer time. Sometimes as much as four to ten times longer [00:14:00] outside to make vitamin D, say compared to me, who’s very fair skinned. Sunscreen use. Sunscreens, by definition, right, an SPF of 30 decreases the amount of UVB getting into your skin by about 97.5%. And if you use it properly, right, it will absorb 97. 5 percent of the vitamin D producing rays and therefore reduces your ability to make vitamin D in your skin by about 98%, right? So, there are a lot of factors involved and obvious question is what to do. And so, what to do in this day and age is develop an app.
Which we did, working with Ontometrics out of California, because we had collected data from around the globe for how efficient the sunlight is in making vitamin D. And the app takes into account the [00:15:00] Ability to, for satellites to measure how much UVB is coming into you, into the Earth’s surface at any place on the planet. So we put all the information together. It’s called dminder. info, d m i n d e r dot i n f o. It’s free on your Android or on your iPhone. It’ll tell you basically anywhere on this planet when you can make vitamin D, How much vitamin D you’re making based on area of exposure and it warns you to get out of the sun so you don’t get a sunburn.
Dr. Weitz: You mentioned UVB as the key factor. So, people who are lying in a sunbed that’s basically giving them UVA are not going to be making vitamin D then?
Dr. Holick: So, most sunbeds, most tanning beds, definitely contain UVB radiation.
Dr. Weitz: Oh,
Dr. Holick: they
Dr. Weitz: do?
Dr. Holick: Okay. So, decades ago, they had what was called a safe [00:16:00] tan, they thought. Okay. Okay. Blast you with UVA because you were not damaging your DNA. Well, it turns out that’s not true, number one. Number two is that UVA gets deeper into your skin, so it increases wrinkling, alters your immune system, increases risk for melanoma, and increases risk for skin cancer. So, most part, most, 95 percent or so of tanning beds, or maybe now it’s 100%, all have a couple of percent UVB as part of that exposure.
Dr. Weitz: Okay, last time I was in a tanning bed was like 30, 40 years ago when I was doing body UVA back then.
Dr. Holick: That’s exactly right. Yeah, because they thought it was a safe way to tan. And, and what was happening is that, that, and it’s actually not good for you, is that you have your melanocytes are at this, at the basal layer of your epidermis, [00:17:00] between the dermis and epidermis and as a result, when you’re exposed to UVB, you’re hitting those melanocytes and they’re making mulla melanosomes and, and going northward up into the epidermis. They cover the nuclei to prevent DNA damage. Ah, interesting. But, when you’re exposed to UVA, it’s a different story, because now, all of a sudden, the UVA is going through your epidermis, into your dermis, and the melanocytes are not sure what to do, so what they actually do, is they start making melanosomes, and they send them into your dermis. Ah! Not! protect your epidermis, and as a result, increases your risk potentially for skin cancer.
Dr. Weitz: Oh, wow. Fascinating. Fascinating. It’s the first time I’ve heard that. So some people don’t want to take supplements, and can you get the vitamin D you need from eating food without supplementation? [00:18:00]
Dr. Holick: How’s that for an answer?
Dr. Weitz: I love it! Let’s get right
Dr. Holick: down to the truth. There you go. Because, at least based on the Endocrine Society guidelines of 2011, and we can talk a little bit about the 2024 in a minute, is we recommend that adults beyond 1, 500 to 2, 000 units a day. So there’s 100 units in an eight ounce serving of milk, skim milk, right? And in yogurt, and there’s about 500 to 1, 000 units, but only in wild caught salmon, right? And in wild caught oily fish, right? And if you’re, if you eat a lot of mushrooms, it exposes sunlight, okay? Or, Drink cotton oil every day, right? You cannot get enough vitamin D from your diet. We did a study back in 2000, in the early 2000s with Carolyn Moore and Minute Maid, and we showed that no [00:19:00] child or adult in the United States could get enough vitamin D from dietary sources based on earlier recommendations of only 400 units of vitamin D a day.
Dr. Weitz: When it comes to vitamin D supplements, does it matter if you’re taking a capsule filled with vitamin D in a powder form or vitamin D in an oil form? And is it important to consume it when you’re eating a meal containing fat?
Dr. Holick: Yep, they ask this question again all the time. So we did the study. And what we were interested in was, the thinking had been that vitamin D was added to milk because the fat in the milk helped you absorb the vitamin D, right? But we knew vitamin D was being fortified in skim milk. And there is no fat. So we did a study, not only to look at whether vitamin D absorption is different in skim milk versus whole milk, but [00:20:00] we also added vitamin D to orange juice, a micronized form in orange juice. And we demonstrated they’re equally the same. In fact, believe it or not, because you don’t Absorb 100 percent of your fat, right? And vitamin D is fat soluble. Actually, on whole milk, you’re less efficient in absorbing vitamin D. And so this concept that you have to have a fatty meal in order to absorb vitamin D is incorrect. In fact, it probably decreases your efficiency as opposed to increasing your efficiency.
Dr. Weitz: We’ve, we’ve, I thought it was because of the, the fat. breaking down enzymes that are going to be secreted when you consume fat, the lipase?
Dr. Holick: And the answer is no. So what’s happening is that when, when you absorb vitamin, when you ingest vitamin D, it gets to your to your duodenum. [00:21:00] And now both pancreatic and bile are all coming together. They form these micelles, right, chylomicrons, and then they get absorbed into your lymphatic system, right, and then it goes all the way up into your sapenovena cava, gets dumped into your venous system, right? So it has nothing to do with any enzymes or anything else. It’s simply Vitamin D being fat soluble has to get incorporated into my cells. It cannot be absorbed directly from the gut into the portal system to the liver, which is where most things go.
Dr. Weitz: Interesting. I think one of the reasons why some in the functional medicine community like myself think about this is because we’ll have a patient whose vitamin D level is what I would consider sub optimal, let’s say it’s 30, and give them 5, 000 units of vitamin D. It barely gets to 40 in other patients, it’ll go to 90. So then [00:22:00] what’s wrong with that patient? How do we get that patient’s level up? And so maybe we just, the answer is we just have to give a more, rather than, you know, I sometimes look for a different form of vitamin D. Let’s take one in, in a, in a capsule with oil in it.
Dr. Holick: Right. And so, and we’ve done those studies, by the way, as well. So, we’ve, we’ve done studies looking at vitamin D absorption in oil, or putting it on a piece of toast, right? And, and all of it seems to be bioavailable. Okay. Formulation is important. Because some formulations may prevent it from even being available to be formed into polymicrons, but the more likely cause for this is you have what’s called a 24 hydroxylase that’s principally in your kidneys, and it is initiated by the active form of vitamin D.
And what it does is it, it, it metabolizes [00:23:00] the side chain, cuts it off and makes it water soluble. So it’s biologically inactive for the active form of vitamin D. That enzyme recognizes 25 hydroxy D. And so there are people out there that have high Metabolism, and they have people out there that have a mutation in that gene, and as a result, they have low breakdown, and so as a result, or have much higher blood levels of 25 hydroxy D for the same amount of vitamin D, but for the most part, we’ve done the studies with Bob Haney many years ago, We showed that for every 100 units of vitamin D that you ingest, if your blood level of 25 hydroxy D is at around 15 to 20 nanograms per ml, will rise by about 0.
6 to 1 nanogram per ml. But for those that are much lower, that’s what we recommend. And then the other issue, which you guys deal with all the time, right, [00:24:00] is celiac disease. Sometimes the first time you pick it up is when you give your patient. The 50,000 unit vitamin D and all of a sudden they come back and, and, and they don’t see any change.
So you work ’em up for celiac disease. ’cause about 10% of the population, I believe Right. Has this genetic, this genetic disorder, autoimmune disorder. Right, right. Finally, something that is often unappreciated by the medical community is that the only pharmaceutical available for vitamin D, right, is vitamin D2.
And even though vitamin D2 has gotten a bad reputation, it turns out, at least from studies that we’ve done, at physiologic doses and even at pharmacologic doses, it works perfectly fine, right? There’s a problem. And that problem is that if you stand out a blood level The 25 Hydroxy D, and it’s done by a platform antibody assay, [00:25:00] we reported sometimes that antibody cannot recognize 25 Hydroxy Vitamin D2 as much as 50 80%.
Dr. Justin Marchegiani Oh, wow. Dr. Bernd Friedlander Right. And so youso if you’re on Vitamin D2, the only way to know the Vitamin D status is you have to get liquid chromatography tandem mass spectroscopy assay, right? And that’s specifically Ordered through Quest and through LabCorp and others, but you need to specifically order that if your patient is on vitamin D2.
Dr. Weitz: Okay. Is it better to take 10, 000 units of vitamin D a day than to take a 50, 000, 50, 000 unit injection?
Dr. Holick: So, A, I don’t, we don’t usually recommend injection if you don’t have to.
Dr. Weitz: Okay.
Dr. Holick: For a variety of reasons. And It can have complications, it can be very uncomfortable, and it’s [00:26:00] not always bioavailable. And you’re probably aware that the FDA took it off the market a long time ago, and no one has gotten approval for it. But I know That, you know, specialty pharmacies will make it, and if you are kind of obese, right, and you can’t absorb it very well, or you have bypass surgery, right, or if you have Crohn’s disease, for example, it may be your only option, but use, right, the recommendation that I like to have for my patients is to take it daily, right, If you can’t, it’s better than to take it once every two weeks. It’s okay, right? But something’s better than nothing,
Dr. Weitz: right? Yeah. Well, I consider 5, 000 units of vitamin D along with vitamin K sort of baseline nutrition for pretty much all my patients.
Dr. Holick: Yep. I mean, I take seven to 8,000 units a day and my blood level’s around 81 nanograms per ml. The end. cited back in 2011 that I chaired that committee, we recommended should be around 40 up to 60 is a really good preferred range and up to 100 is perfectly safe.
Dr. Weitz: Yeah, I usually use 50 to 70 and one of the reasons why is especially for women, I saw this study that showed that at 60 the risk, decreased risk of breast cancer was really significantly lower and so I thought 60 was a good target.
Dr. Holick: Yeah, I mean, that was one of our studies. We showed that, that on average women that had a blood level of around 40 reduced risk of breast cancer by about 50%. And that’s from the Nurses Health Study out of Harvard.
Dr. Weitz: Right. So, vitamin D it’s purpose is really to help the body to utilize calcium, correct? Correct.
Dr. Holick: That is its major function in evolution, is to maintain [00:28:00] your blood calcium in a normal range, because as you know, your ionized calcium is critically important for neuromuscular function, right, and most metabolic activities, signal transduction, right, and so, And each of us have a set point for our serum calcium, and even though the range is 8.6 to 10. 2 or so, depending upon the laboratory, right, each of us is very specific and, and it’s for that reason, and so vitamin D, therefore, has two major functions. The first, the only source of calcium is from your diet, right, and vitamin D, through its active form, is the only hormone that regulates calcium absorption. But if you can’t get enough calcium from your diet, and then, and you can’t conserve it with parathyroid hormone in your kidneys, for example, it will go to your bone [00:29:00] to remove calcium. It will take monocytes that are the precursors of osteoclasts and induce them to become osteoclasts. And
Dr. Weitz: so contrary Even in the presence of osteoporosis, if your body needs to normalize your blood pH, it’ll pull calcium from your bones.
Dr. Holick: Right. Normal calcium in your, in your blood. That’s exactly right. And that vitamin D deficiency will precipitate and exacerbate osteopenia, low bone mass, and osteoporosis.
Dr. Weitz: And, and part of that purpose of calcium is to make sure your blood stays at the right pH, correct? That helps,
Dr. Holick: yes.
Dr. Weitz: Yeah.
Dr. Holick: Yeah. I mean, if you have low pH, your ionized calcium goes up. If you have high pH, your ionized calcium goes down, and it’s ultimately your ionized calcium, the free calcium that’s important in getting into cells and having biologic functions.
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Dr. Weitz: Now you emphasize the importance of calcium for all different functions of the body, including cardiovascular health. But these days A lot of people are afraid of taking calcium because they’ve been told that calcium increases your risk of heart disease.
Dr. Holick: Right. And then they also, they get these CAT scans, right, where they’re looking at your calcium content in blood vessels, for example, right, to give you some idea.
Dr. Weitz: I just, I just had a patient come from her [00:32:00] cardiologist and say, Oh no, don’t take vitamin D. You have atherosclerosis. That’s going to make it worse.
Dr. Holick: And the answer is, that’s not true. And there was a paper actually published on this looking again, I think, at the National Health Survey data. They showed that if you maintain a normal calcium intake, it reduces risk of cardiovascular disease by about 29%.
And the other issue of kidneys is kidney stones, right? Right. And so it turns out, right, that, that the thinking was one is one is equal to two, i. e., if you have kidney stones, which are mainly calcium oxalate, that the cause is you’re taking too much calcium. But the answer is no. It turns out, population studies show that if you maintain a good calcium intake with your diet, you’re You reduce your risk of kidney stones.
Well, how is that possible? Well, the reason is that kidney stone formers are mainly absorbing too much [00:33:00] oxalate. And oxalate then in getting into your ultrafiltrate in your kidneys, binding calcium will cause kidney stones. But if you take calcium with your meal, it binds the oxalate in your diet. Ah. And prevents you from absorbing it. And therefore, it decreases your risk for kidney stones.
Dr. Weitz: Boy, we are busting some myths today, Dr. Hollick.
Dr. Holick: We recommend, or at least what I recommended, for patients with kidney stones, is that you be on calcium citrate, right, as opposed to calcium carbonate. Because now, you also citrify the urine, it chelates the calcium in your kidneys, and helps to release it, reducing risk for kidney stones.
Dr. Weitz: Fascinating. Fascinating. Is it important to take vitamin K with vitamin D to decrease the potential for the calcium that vitamin D is helping to move around to make sure that it doesn’t end up [00:34:00] in the arteries?
Dr. Holick: So you’re not going to like my answer.
Dr. Weitz: I, I, I know your answer is different than my opinion, but
Dr. Holick: And so, but, but I actually, I mean, you may be aware that I edited a book with Jerry Neves on nutrition and bone health. And we had Sarah Booth, who’s one of the world’s leading experts of vitamin K, wrote the chapter. And she had concluded, and also for me reading all the literature concluded, it’s mainly based on that study, right, in Holland, right, where they showed that taking, you know, lots of information on diet from a large group of people, that they said that those that had a higher intake of vitamin K reduce their risk of cardiovascular calcification. It’s true, vitamin K, right, gamma carboxylates, right, a couple of [00:35:00] proteins like osteocalcin and osteonectin, and it does bind calcium. But there is zero evidence, in my opinion, zero evidence, that that binding of calcium to those proteins have anything to do with bone mineralization, right, and I don’t believe that vitamin K It’s so intelligent that it’s gonna tell your calcium where to go.
Dr. Weitz: I think the, the data is strongest that I’ve seen is on the MK four, especially studies in Japan. Yeah. But like I said,
Dr. Holick: yeah, I, I have no problem people taking vitamin K. Right. And so, and so I tell my patients, you wanna do it, it’s perfectly fine. But if you have a healthy diet, right, you should be able to get, I think, all the vitamin K that you need.
Dr. Weitz: Right. Vitamin D stores in fat, which is why obese patients [00:36:00] often have lower levels of vitamin D. Now, the most popular drugs in the country are the GLP 1 agonist drugs like Ozembic, and a lot of people are losing weight. Are they potentially going to be liberating all this vitamin D from their fat stores?
I’ve heard you say that if people get surgery to lose weight, that that won’t work because of decreased absorption, but these patients are not getting surgery. They’re just taking these medications.
Dr. Holick: Right, so you’re correct. So we did the study in patients with gastric bypass surgery that they will lose as much as 50 kilograms of fat within a year. And we did the blood levels of 25 hydroxy D. So it turns out that it has nothing to do with absorption. It has to do with the fact that the vitamin D is destroyed as the fat is being destroyed. And so same [00:37:00] thing likely with ozempic. I see. I’m very surprised that you’re going to see any alteration in blood levels of 25 Hydroxy D. I think anything that may go down. Interesting.
Dr. Weitz: Let’s bring up your recent paper on the Endocrine Society’s 2024 Clinical Guidelines, which you vociferously disagree with.
Dr. Holick: So, the 2024 guidelines, in my opinion, were really not guidelines. I mean, they make it very clear in the introduction that this is not related in any way to disease processes associated with vitamin D, Calcium or Parathyroid Hormone Metabolism. But you would have thought that the endocrine society whose members are endocrinologists and healthcare professionals interested in endocrinology, that they’re going to be seeing patients with various disorders, that, that, that information would be [00:38:00] very important to them. I mean, in 2011, that I chaired that, those guideline committee, is that we provided that information.
So it’s still available to endocrinologists. End. What to me was really interesting and very important observation by the 2024 guidelines is that they recognized that at least in children, that if you increase their vitamin D intake, potentially reduces risk of upper respiratory tract infections. And so they made that recommendation that children maybe should receive empiric vitamin D.
They also suggested that. Type 2 diabetes may be prevented from type 1 diabetes based again on the literature. They also said during pregnancy that they appreciated the literature and suggested that pregnant women probably should be on vitamin D supplementation. So the good news [00:39:00] is that they at least appreciated the non calcemic effects of vitamin D, which have been published now for more than 50 years.
Bye. In the end, they said, children and adults only need 600 units of vitamin D a day. They did, even though they, they pointed out that children could benefit from more vitamin D, they didn’t make that recommendation. They kind of left it up to whoever, was reading it as to what they wanted to do. And they didn’t even give a specific amount.
They said, this is the average number, right, that it came from, from 500 to maybe 10, 000 units. So we recommend this dose. But they don’t say it. They don’t tell you that children should all be on. And I pointed out that, look, we know, at least from our studies and other studies, that it reduces risk of COVID infection, for example, substantially in adults. So if you believe that it inhibits respiratory tract infections in children, why wouldn’t you say the same thing in adults? But they did not. Okay, during pregnancy, right, reduces risk. of preeclampsia, and needing a c section, and type 1 diabetes, potentially, wheezing disorders in infants. I mean, the list goes on. Decrease in dental calories, right? But yet, they did not recommend And pregnant women unequivocally should be on more vitamin D.
Dr. Weitz: And all these diseases are diseases that we seem to be completely unable to prevent that cost our medical system just hundreds of billions of dollars a year.
Dr. Holick: Yeah, and that’s why, to me, you know, I think that they had a golden opportunity to really make a difference. And another area is autoimmune disorders, right? The [00:41:00] vital study, which, which we could talk about if you wish, regarding the effect that it, didn’t have on reducing risk of fractures, when they went back and looked at their data, clearly demonstrated a 22 percent statistically significant decreased risk of autoimmune disorders, including psoriasis and rheumatoid arthritis to name a few.
Just that alone, you would think, would have been a recommendation for the FDA. because the vital study gave 2, 000 units a day, right, to those individuals that you would have recommended 2, 000 units a day.
Dr. Weitz: I
Dr. Holick: mean,
Dr. Weitz: why not, right? It’s, it’s insane. It’s such a simple intervention. It’s so safe. It’s so inexpensive. And yet, you know, significant They have to get tortured before they could even [00:42:00] consider recommending a vitamin, even in 2024.
Dr. Holick: Yeah, and it’s very unfortunate. And, you know, and there was that other study that I pointed out in my Why
Dr. Weitz: do you think they’re so just philosophically opposed to ever recommending vitamins?
Dr. Holick: Well, part of it has to do with the so called meta analyses and randomized controlled trials that they consider to be the gold standard for what, how you recommend. And I pointed out in my commentary review, right, you should not be using RCTs for gold standard when looking at a nutrient for two reasons. The first is that that they do not permit any longer for an absent of a nutrient. So, all studies, or most studies, require placebo group get at least [00:43:00] 600 and up to 800 units of vitamin D a day. We know supplement manufacturers put on at least 20 percent up to 50 percent more in their, in their product, right?
So the 800 could very well be 1, 200 units a day. And now they’re comparing that to 2, 000 units a day. How do you expect to see? any difference, right? And then the other problem is, right, that if you’re looking at vitamin D, well what about calcium, or vitamin K, or magnesium, right? And how are all those related to the outcome measure that you’re looking only for vitamin D?
Why would the placebo group have to be given vitamin D? So the argument is that you can’t have a person vitamin D deficient. It’s guaranteeing that their vitamin It has
Dr. Weitz: no benefit? Are you worried about them being deficient?
Dr. Holick: Exactly right. So that you have to be, you’re obligated to give those individuals the amount recommended by the Institute of Medicine.[00:44:00] And for those over 70, it was 800 units. So therefore, everyone could take up to 800 units a day in the placebo group.
Dr. Weitz: Wow. Okay. I, I’ve not heard your opinion about this. I’m pretty sure I can guess what it is. But when it comes to autoimmune diseases, there’s this Dr. Trevor Marshall who has this theory that certain autoimmune diseases encourage the body to have lower vitamin D levels in order to lower inflammation. And so therefore the body just converts all the vitamin D to one, two, five. So therefore you have somebody with low vitamin D and if they have certain type of autoimmune disease, if you give them the vitamin D, it’s going to make their autoimmune disease worse. And the only way you can find out about this is to measure their one, two,
Dr. Holick: So I’m very familiar [00:45:00] with this. I’m sure
Dr. Weitz: you must be.
Dr. Holick: Yeah. And and he, my understanding is that he was doing studies in China. I saw it. I don’t think he’s ever published anything that demonstrated disaffected. This is kind of his concept on his head, right? But the vital study, right? That everybody accepts, right? 2,000 units of vitamin D a day reduced risk of autoimmune disorders by 22%. Right?
Dr. Weitz: End of story.
Dr. Holick: Right. And Kalimbra, right, down in Brazil, right, he gives a thousand units per kilogram body weight, right, to treat autoimmune diseases, very effectively. And we recently published a paper of a guy that showed up young man, and he, he had optic neuritis. He had a clear lesion in his head. It was clear that likely he had MS, and he refused [00:46:00] standard treatment, and came to me, and he wanted to be on the Carenbo protocol, and I put him on it. And so he was on 50 to 60 to 70, 000 units of vitamin D a day. He continues that even to today, so more than five years. He’s had no progression of his MS. Wow.
Dr. Weitz: So the one autoimmune disease that Marshall really highlighted was sarcoidosis. So, in sarcoidosis, is there any reason to be concerned about vitamin D? And also, a second question is, do we want to measure the 1,25 level? So,
Dr. Holick: in sarcoid, You’re probably aware of this, that 90 percent of sarcoid patients have hypercalciuria, and about 10 15 percent have hypercalcemia, and the reason is that the sarcoid have activated macrophages that convert [00:47:00] 25 hydroxy D to 1,25 D. And why macrophages do that, we think, is because it induces them to make cathalosidin to help fight infectious diseases, right? But in a granuloma, it’s having a different function, whatever that might be. And the problem is that if you give too much vitamin D, It’s enough substrate for that hydroxylase to now raise your blood levels to 1,25 hydroxy D, which will now cause hypercalciuria and hypercalcemia. So typically, for my patients with sarcoid, I would always maintain their 25 hydroxy D at around 20 to 25 nanograms per ml, because it was published. 40 years ago showing that sarcoid patients in the wintertime had a perfectly normal serum calcium and in the summertime they were hypercalcemic. And the reason was that they were making vitamin D, their 25 hydroxyl D was [00:48:00] going higher and now that one hydroxylase was being very active. Yeah, you have to be careful with vitamin D and sarcoid patients, or patients with TB, or other granulomatous disorders, even fungal granulomatous disorders, all associated with hypercalciuria and hypercalcemia.
Dr. Weitz: Is there any benefit to measuring the 1,25?
Dr. Holick: Well, the only benefit is, to make you feel better, right, is that if the patient is hypercalcemic, right, and has sarcoid, that’s the reason, right? And so, you want to measure it? To convince yourself that’s perfectly fine.
Dr. Weitz: Well, the reason why it started becoming popular in the functional medicine world is I remember going to seminars and doctors saying, look, you’re giving the patient the vitamin D3 and you’re not seeing the levels go up. Measure the one, two, five, maybe they’re over converting and you don’t need to give them more.
Dr. Holick: Yeah, that’s not true. [00:49:00] So we did a study and we showed that when you give a thousand units of vitamin D a day that the 1,25 D levels don’t change at all, even 2, 000 units a day, right? The body cares about your 1,25 D level very much. And, and only when you’re vitamin D deficient, right? You can’t efficiently absorb dietary calcium. PTH goes up. And as a result, it stimulates the kidneys to make more 1, 25 Dihydroxyvitamin D. So as a result, people will see the elevated levels of 1,25 D, thinking that, aha, if you give more vitamin D, you’re going to see more 1,25 D. Only when you have Secondary hyperparathyroidism, right? And so, but otherwise, no. And, and we never, I never recommend measuring 1,25D, except if you have granulomatous disorders, you have a hypercalcemic patient. So, for example, we published, and it’s [00:50:00] very sad, actually, is that these men go on the internet. And they want to bulk up, so they wind up injecting themselves with mineral oil or some kind of, of methacrylate or whatever, right?
Dr. Weitz: Oh, you mean what they put directly into the muscles? Okay.
Dr. Holick: And it excuses them to have granulomas. And they start making that 125D. And I had one poor guy, he had, he had injected his pecs, he injected everything in his body. He was rock solid. And he died, unfortunately, at a very young age of hypercalcemia because his, we could not control his calcium. Wow. Because he had such
Dr. Weitz: Was he a well known bodybuilder?
Dr. Holick: No, he wasn’t. No, he was depressed and so started weightlifting, didn’t see much of an effect. So therefore, when on the internet, they said, here’s a non steroidal way of being able to improve your muscles. And so he bulked up by doing that and he lost, he lost his family and he lost his life. Wow. There’s a recent publication, by the way, of another group. What they did, which is really good, is that they showed that surgically they go back in and take out a lot of the stuff, and that can actually save their lives.
Dr. Weitz: That’s crazy. Vitamin D has crucial benefits for the cardiovascular system. Can you talk about that a little bit?
Dr. Holick: So there’s really good evidence that it plays a role in the renal angiotensin system, right? Dr. Lee many years ago showed in rat model that or a mouse model that, that, Alteration in the renal energy of tension is very much regulated by vitamin D. We think actually that’s maybe one of the reasons why vitamin D may be also helpful in COVID, right? Because because of the receptor, right? That, that it was being recognized by. [00:52:00] So, there is evidence that it reduces risk for hypertension. We did a study many years ago and showed just exposure in a tanning bed that raised 25 hydroxy vitamin D levels had a significant impact, but we also know that it increases nitric oxide, right, and so all of that, you know, may be combined, but there is reasonably good evidence that it reduces foam cell formation. There’s another study that was done, right? And foam cells are the ones that collect cholesterol and they esterify it and they deposit it, right? Vitamin D helps in that process. So, there is, in my opinion, no evidence that maintaining an adequate vitamin D status will increase risk for cardiovascular disease and there’s no reason to stop taking vitamin D if you have cardiovascular disease.
Dr. Weitz: And in fact it potentially could prevent it. I’ve seen some of your papers where you’re describing how it [00:53:00] reduces not only atherosclerosis, but the stiffness in the vascular system.
Dr. Holick: And so, we did a study with Dr. Dong down in Georgia, and took teenagers black teenagers, and they were all vitamin D deficient. They had a 20 and we either gave them the recommendation of 400 units at the time, or 2, 000 units of vitamin D, and showed, that raising the blood load up to 34 nanograms per ml reduced the vascular kind of constriction it relaxed the, the major blood vessels showing that they’re likely decreasing blood pressure and therefore long term decreasing risk for atherosclerosis and heart disease due to hypertension.
Dr. Weitz: Vitamin D also has benefits in reducing risk of cancer.
Dr. Holick: Correct. And so what was really interesting is in 2019, a Japanese group reported that when they gave, again, about 2, 000 units of vitamin D a day to patients with digestive cancers and looking at relapse free disease. They reported 2019 in JAMA, no effect. And so that was kind of like one of the last nails in the coffin for vitamin D.
Dr. Weitz: By the way, there could be 99 papers showing benefits to vitamin D, and then the one that shows no benefit, that’s the one that gets printed in JAMA.
Dr. Holick: But then, happily, happily. group realized something, which was that when they looked at their data more carefully, that those that had higher 25 hydroxy D at baseline getting the vitamin D seemed to benefit. So they went one step [00:55:00] further, and they asked a fundamental question, which was, What about if your patient was developing antibodies to p53? And as you know, p53 is a major hormone that regulates cell growth, right? And cancers are very clever. So what they do is that they will mutate your gene. and have a mutated p53. The mutated p53 now actually enhances the cancer cell growth and it prevents 125D from interacting with its receptor to have the anti proliferative activity that it normally has. So they looked at this and they showed that those patients that developed antibody to p53, meaning that they’re now fighting the mutant p53, they were Those that took vitamin D, the 2, 000 units, improved survival by 150%.
Dr. Weitz: Improved survival by 50%. Right. Wow. Name a form of chemo that does that.
Dr. Holick: Got it. And so, and they published in JAMA, right? And JAMA contacted me and I did the editorial for it. So to me, it gives you a whole new perspective about vitamin D and cancer, because now we’re beginning to recognize that if you don’t have The desired benefit, because that’s what everybody wants to see. It could be that there are other things that need to be taken into account. And, and this study, I thought, was really kind of earth shattering in, in revealing that if you take vitamin D and your body’s fighting your cancer by making antibodies that you can have significant benefit.
Dr. Weitz: So preventing type 1 diabetes, type 1 diabetes, it’s, it’s, you know, much less common, obviously, than type 2, but patients [00:57:00] who have type 1 diabetes are, it’s a horrible disease, and they have to be on lifelong insulin, and we, we really have not been able to make much progress on trying to prevent it, but yet, Vitamin D seems to be a very beneficial way in preventing this and a really high statistical lowering of the risk. How, how does it do that?
Dr. Holick: So we think it has two functions. The first is, we don’t really know what the cause for type 1 diabetes is, right? It’s an autoimmune disease. Some people believe it could be a viral infection and that the body is overreacting, causing this autoimmune effect. But the other possibility is that, but we know that vitamin D receptor exists in your beta. In your T, B lymphocytes that make antibodies. And what vitamin D does, the active form, [00:58:00] modulates the production of antibodies. And we believe that what it may be really doing is modulating the production of auto antibodies and decreasing their production. Ultimately, therefore, decreasing risk for developing type 1 diabetes.
Dr. Weitz: And can it, sometimes adults get a type 1 diabetes. Right, right. Can it also prevent that?
Dr. Holick: We don’t know. I mean, we don’t have those studies, but we do have the study, again, where the D2D study, where they gave vitamin D supplementation, and they looked at the progression of pre diabetes to diabetes, and originally concluded that there was no benefit. But then when they go back and look at it more carefully, they realize that actually it does in a very significant way.
Dr. Weitz: Great. This has been a great interview. We could talk for hours [00:59:00] on vitamin D, but I know your time is very valuable. So thank you so much for joining us today, Dr. Holick. It’s my pleasure and have happy holidays. Happy Holidays to you, and people want to know more about your research. How can they find out more about you?
Dr. Holick: Yeah, so they can go to my website, which is just Dr. Holick.org. So, Dr. Michael Holick dot org It’s probably the best place, but you can go to my Facebook, which again is just Dr. Michael Holick.
Dr. Weitz: And you’re still doing ongoing research?
Dr. Holick: Yes, and so we continue to be very active. I mean, you may want to have a separate discussion about this, but we figured out a way of controlling hot flashes in menopausal women. What? Breast cancer. Yeah a device that you wear on your wrist, and it reduces the intensity of a hot flash by almost 50 to 75 percent. Wow. Yeah, quite dramatic. And then we’re also doing studies in EDS right now, and we’re identifying genes that are responsible for mast cell hypersensitivity.
Dr. Weitz: Yeah. Interesting, yeah. I see a lot of patients for gastrointestinal disorders, and mast cell activation is a big issue.
Dr. Holick: Yep, and so we just published a paper on this.
Dr. Weitz: Oh, really? Interesting.
Dr. Holick: Send me an email and I’ll send you the paper.
Dr. Weitz: That’d be great. Thank you so much, Dr. Holick.
Dr. Holick: Happy Holidays. Happy Holidays. Take care, Ben.
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Thank you for making it all the way through this episode of the Rational Wellness Podcast. For those of you who enjoy listening to the Rational Wellness Podcast, I would very much appreciate it if you would subscribe. If you could go to Apple Podcasts or Spotify and give us a five star ratings and review. As you may know, I continue to accept a limited number of new patients per month for functional medicine. If you would like help overcoming a gut or other chronic health condition and want to prevent chronic problems and want to promote longevity, please call my Santa Monica Weitz Sports Chiropractic and Nutrition office at 310-395-3111. And we can set you up for a consultation for functional medicine. And I will talk to everybody next week.
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