Read the full transcript of Professor Bruce Hollis on Dr. Eric Berg Guest Interview on “Your Body Is Begging for Vitamin D”, July 14, 2024. Professor Bruce Hollis is a pioneer in vitamin D research and an expert on vitamin D deficiency.
DR. ERIC BERG: Today we’re going to be talking to Professor Bruce Hollis, the pioneer in vitamin D research. You’re going to find this extremely fascinating. Let’s dive right in.
So, Dr. Hollis, I watched one of your videos and I literally had to put it on pause because you said something that blew me away. I’ve never heard this before in my life. And I had to spend the next eight hours trying to validate what you said, which is absolutely 100% true.
And this little piece of information will explain a lot of, I think, the confusions that people observe when they see negative research on vitamin D and a lot of other things. So that piece of information was related to: There’s actually two different systems in the body that deal with vitamin D. There’s one with bone and skeleton, and then there’s another system for everything else. Can you kind of, as simple as possible, explain those two systems?
The Two Vitamin D Systems in Your Body
BRUCE HOLLIS: Yeah, the first system, the one that was discovered decades ago, is that vitamin D was associated with skeletal integrity and maintaining blood calcium levels in a strict fashion, and it’s very important and it has to be maintained all the time. And so that system involves vitamin D and parathyroid hormone, kidneys, and that’s basically referred to as the endocrine function of vitamin D. And that’s what everybody always identified vitamin D with.
And then as time went on, molecular biology came into focus. They started finding cells that had the ability to respond to vitamin D that had nothing to do with the skeleton. Immune cells, cancer cells, placental cells, and the list goes on and on. And it turns out that that’s the second system, and it’s called the paracrine and endocrine system.
And that is how much vitamin D can get into these cells and activate it and then carry on their function. I mean, just in the human body, give or take, there are 20,000 different genes that are controlled for various functions. Vitamin D has the ability to control 10% or 2,000 of those genes in one fashion or another. And so to basically brush that aside, as a lot of my colleagues did, just saying it’s an artifact never made any sense to me.
Understanding Vitamin D Blood Tests
DR. ERIC BERG: So if we take a look at these two systems, when you get your blood test done in vitamin D, you’re looking at the inactive version. You’re not looking at the type of vitamin D that’s going in the cells. And how does that relate with these two different systems?
BRUCE HOLLIS: Well, here it gets pretty technical. So when people refer to vitamin D, mostly when they refer to vitamin D, it’s the form you get when you take a supplement or when you make it in your skin when the sun hits your skin. That’s what we call the vitamin D or the parent compound.
And then that compound goes into the circulation. It doesn’t stay there very long, but it gets turned into another compound called 25-hydroxy vitamin D. That’s what they…
DR. ERIC BERG: Test in your blood, right?
BRUCE HOLLIS: The intermediate form. That stays in your blood for weeks. And that’s a good and a bad thing because it stays around for a long time, but it’s not very accessible to these tissues that need it. It’s accessible to the kidney that maintains blood calcium.
And then finally, that compound is turned into another compound, which is really one of the most potent hormones known. And that’s the 1,25-dihydroxy vitamin D. And that is what drives all these gene functions and all these tissues.
DR. ERIC BERG: So the one when you go to the doctor and get your blood test, you’re looking at not the active form, it’s an inactive form that can stay around in the blood for several weeks.
BRUCE HOLLIS: Yes. I’ll call it the reservoir. It’s the reservoir of vitamin D that’s being measured. Got it.
DR. ERIC BERG: And then it turns into the active form, or a certain amount will turn into the active form. But then how does that relate to these two different systems?
How Vitamin D Works in Different Body Systems
BRUCE HOLLIS: Well, so that intermediate form, the reservoir form, can turn into the active form in the kidney. That’s highly regulated, and that’s what regulates blood calcium.
That intermediate form can also go into any cell in the body and be turned into the active form and function in that given cell, whether it be a cancer cell to stop cancer from progressing, or immune cells to make them function in the appropriate fashion.
And also the problem with that intermediate form is it’s not very accessible to these cells. It’s bound to this protein. It keeps it out. That’s why it lasts in the blood so long.
So the parent compound, the one that you take in the supplement, turns out it’s really important because that form can get into any of these cells and be activated all the way down the chain to the active form. The problem is that form disappears within a day. So it needs to be replenished every day to have the full function of the vitamin presence. It’s complicated. That’s why a lot of physicians don’t pay attention to this or scientists as well.
DR. ERIC BERG: So this is kind of what I want to get into, this point that you just mentioned, because you have the different types. And then when people get their blood tested, they’re assuming that there’s one system. “Oh, I have enough in the blood, so everything’s going to be satisfied.” But that’s not necessarily true.
BRUCE HOLLIS: No, that’s true because of the form that’s being measured.
And of course that’s really not feasible for a lot of reasons. So the oral consumption of vitamin D on a daily or at a minimum on a weekly basis is important because that’s the base form and that form comes and goes very quickly.
DR. ERIC BERG: Wow. So this has to do with like half-life and breaking down. Some of it goes down quick, some stays in there. So now in one of your videos, you went through a bunch of studies and you showed people step by step, like a number of studies that failed, that showed no response with vitamin D, and you correlated that with, “Well, that’s because they only let people take it once a week or once a month.”
Why Many Vitamin D Studies Fail
BRUCE HOLLIS: Yeah, there’s even been one study on skeleton where they took it once a year, like a million units once a year. And then they said, “Well, this didn’t work out very well.” And that continues to be cited in some circles as being harmful. It’s idiotic.
DR. ERIC BERG: Oh my gosh. If someone takes a million IUs of vitamin D just one time, I think after a day it goes down to half and then the day later it goes down to a quarter. It just kind of breaks down and then goes away or just becomes…
BRUCE HOLLIS: Yeah, it’ll boost the intermediate form for a while, but it’s a horribly inefficient way of doing it. And it becomes more so. If you do it once a day, it’s efficient. Once a week, it’s less efficient. Once a month, even less efficient.
DR. ERIC BERG: So wow, as far as the research on this, what about, you know, you have all these, most of the researchers out there, they kind of look at vitamin D just related to bone and calcium. They’re kind of just almost pretending like this other system doesn’t exist. Is that true?
BRUCE HOLLIS: Yeah, basically, yes. I mean, first you have to accept the fact that vitamin D has functions beyond calcium. And I mean, the data are all over. But what ends up happening is things are run like the Vital trial where they give too little vitamin D, they give it to people who, in a randomized trial, don’t need it.
You know, it’s like in the Townsend newsletter I mentioned to you when I was discussing it with the author of that paper. So the gold standard for all drug trials are randomized control trials, where say you have a cholesterol drug and you want to test if it truly will lower serum cholesterol if you take it.
So the drug company assembles a population of people and they administer half of those people the drug and half of those people get placebo. And then they analyze the data and look at it. Of course, in most cases it’s successful. And this is how drug trials are run.
But the drug that you’re giving those people, the body has never seen it. They don’t have a base level of it, unlike nutrients. Not just vitamin D, but any nutrient trial. It’s impossible in this country to do a true randomized trial because the population you’re dealing with, some people have very little, some people have plenty.
But when you, if you just take them at random and randomize them and give half of them a level of vitamin D, oftentimes not even enough, and this other half only get placebo, and placebo in this country means they have to get the standard daily dose. So they’re not even getting zero. And what happens is that it’s a horribly compromised study.
The Problem with Current Research Standards
So that’s what Vital and all these… And the other thing is when you end it and you do your data analysis, wouldn’t you think that you might take the basal level into effect when you do the analysis of the data? Well, that’s illegal. You can’t do that. That violates the intent-to-treat model. And it absolutely ensures that your trial is going to fail.
So, and I’ll give you some examples. I’ve worked primarily in pregnancy. We did pregnancy studies and found out that vitamin D decreased complications of birth. But the best trials were actually done overseas and the best couple were done actually in Iran, where the population is generally vitamin D deficient across the board.
And they had a fairly large patient population. Half of those women got a substantial dose of vitamin D and half of those people got nothing, which is how you can’t run a trial like that in the US because you’d be violating standard of care. But that’s truly how vitamin D trials should be run.
And in those trials we saw tremendous effects on decrease in birth complications like preterm birth and preeclampsia and diabetes and everything else fell into the treatment group.
If you do the same trial in the US, you can’t do it where our nutrition is better. People have better vitamin D levels. But when you randomize them, like I said, everybody has some. And so it’s not like you’re given a drug that has none. And when you look at the results, it’s totally blurred.
And it’s even, you know, you can overcome that to some degree. When the statisticians would take the basal level upon study entry into effect, and then you analyze it like that, you can see effects.
And in fact, that’s why observational studies, you know, when they have these big groups of people and they look at vitamin D levels and outcomes via cancer, via pregnancy and things, and it’s based on a lifestyle. And uniformly those studies, and there’s thousands of them, would show really big effects of vitamin D.
But then when you went to do these randomized trials and you had all these complications and you can’t adjust for the base level, all of that disappears and you get no effect at all.
But if you submit your paper to New England Journal or JAMA or British Medical Journal, and you analyze the data and want to take into account basal levels, that violates the intent-to-treat model. It will be rejected outright.
DR. ERIC BERG: Wow. So the Vital study is definitely the study that certain groups are using to tell people, “Well, see, it doesn’t really work. Yeah, we did the study. It’s definitive.”
BRUCE HOLLIS: I’ve challenged the authors of that study to reanalyze their data, taking baseline levels into account of their patients, and they won’t do it.
DR. ERIC BERG: Wow. Incredible. And didn’t they even call the amount of vitamin D they were giving people a high dose at 2,000 IUs?
What Are Optimal Vitamin D Levels?
BRUCE HOLLIS: Yeah, that’s nothing. To put in perspective, I’m 73 years old. I take 10,000 units of vitamin D a day, and I have for years. And my level of vitamin D levels are between 80 and 90 nanograms per milliliter.
And my personal care physician is pretty progressive. She’s all for that, not just with me, but for her entire clinical group of patients that she follows. And so she wants her patients to have a minimum level of 60. That’s really out there compared to most family care physicians or primary care docs.
In fact, they’ll get a level back from, be it the Mayo Clinic or Cleveland Clinic or whatever. And those levels like mine, which are 80 or 90, will be flagged as too high. And I get those emails from people all the time. It’s just level two.
DR. ERIC BERG: Let’s talk about the normals for a second because I think it’s a bit arbitrary. There’s really no agreed upon range definitively. There’s different ideas on it.
BRUCE HOLLIS: And again, if you go back to what’s the agreed upon range, it’s all based on skeletal models, right?
DR. ERIC BERG: Right.
Skeletal vs. Cellular Vitamin D Requirements
BRUCE HOLLIS: And the skeletal models, that’s something that we haven’t talked about. The ranges on those two systems are different. You can maintain a skeletal model on a relatively low amount of, say, 25 or 30 nanograms or maybe even lower, where you can maintain a normal skeletal level, where the other system requires much higher levels than that to function in a normal fashion.
DR. ERIC BERG: Incredible. What are the ranges for the other system other than the bone in the skeletal?
BRUCE HOLLIS: Oh, I’m saying if you want to have cancer prevention or cancer treatment. So if you’re trying to prevent cancer, that’s one thing. If you have active neoplasia, that’s a different ballgame. That’s pharmacology. So your levels would be higher, but for prevention and optimal functions, to me, a minimum level would be 50. So 50 to 100.
And that’s well within the normal physiologic range in sun-repleted populations. So if you spend a lot of time, and we’ve looked at this over the years, and people, lifeguards or athletes who are outside in the sun in the summer months, or people who live in the tropics, their levels are routinely 80, 90, 100 nanograms. That is not an abnormal level from human physiology. In fact, that’s what we all were at one time.
Therapeutic Doses for Chronic Conditions
DR. ERIC BERG: This is incredible data. So you do have prevention, then you have the therapeutic dose. When someone has a chronic inflammatory condition, autoimmune or cancer, those levels I would imagine need to be a bit over 100, right?
BRUCE HOLLIS: Yeah, or even higher. I mean, there’s an MS protocol in Brazil where this guy, I can’t remember, the Coimbra protocol.
DR. ERIC BERG: Yeah, Coimbra.
BRUCE HOLLIS: Yeah, they dose with several hundred thousand. Their levels are, you know, 5, 600 nanograms, just for the suppression of MS. And it has basis in fact because vitamin D at those levels is an immune suppressor. It will alter the T cells in the favor of T2 away from T1. T1 are the ones that cause autoimmune attack.
And so vitamin D at those levels, and some of those people show that vitamin D at those levels are more effective than the drugs that are prescribed. Of course, vitamin D is free, essentially. And those drugs are enormously expensive to take every month with severe side effects.
Vitamin D and Prostate Cancer
DR. ERIC BERG: So what about cancer? You mentioned one of the videos about prostate cancer.
BRUCE HOLLIS: So, you know, with prostate cancer, we did a study more than 10 years ago now where we looked at—I went to, at the time, I went into the chief of our urology department at the Medical University of South Carolina, where I was on faculty and another fellow, and I went in and talked to him, and it was a friend of mine, and I said to him, I said, look, we want to do a study in your group of patients on this, patients who have active surveillance or watch and wait, you know what that is.
So we—you go in to have your prostate, your PSA is going up, they do a biopsy, and your prostate cancer is low grade, say at least in six. So the doctor says to you, well, we prefer to really do nothing. You know, we want to watch and wait, which means we’ll check back with you in a year, see if it’s worse. Okay?
So we said, we want to do a study on these guys. And what we want to do is we, at the time, every time we did these studies, you had to propose how much you were going to give the patient. And so if you go back to this period of time, which is in the 2005, 06 era, some back there, we wanted to give them really modest dose of 4,000 units a day. I would have liked to give more, but at the time, you have to go through an institutional review board and they have to okay it.
Most of this, unfortunately, where we are and stuff, most of the prostate cancer occurs in the African American population, which are really deficient in vitamin D. So we approached them and we said, we want to do this, and we want to give them 4,000 units of vitamin D a day. And it was an interventional trial, it wasn’t a randomized trial, but we had historical data on patients that were in that practice.
And so we put them on 4,000 units a day and we monitored their levels. And then at the end of the year, they got a repeat rectal biopsy like you get for prostate cancer. And we looked at the cell grade and the recurrence or how it progressed. And in 64%, the tumors regressed.
DR. ERIC BERG: Wow.
BRUCE HOLLIS: And we submitted this to, of course, New England Journal, and they wanted nothing to do with it. So we submitted it, finally got published in the Journal of Clinical Endocrinology and Metabolism, which is a respectable endocrine journal. And it really went nowhere. I mean, if it would have been a drug that a drug company had, it would have been worth billions.
DR. ERIC BERG: Yeah.
Higher Doses for Cancer Treatment
BRUCE HOLLIS: So when people treat cancer like that, like prostate cancer, 4,000 is nothing. I’m saying take 20,000 or more because you got cancer, you’re not dealing in normal physiology here. You’re in pharmacology.
And the pushback you get if you try to put these trials—well, I’ll give you an example of a study called the Sunshine Study, which is study on non-resectable colon cancer. Okay. Run out of Harvard and several others. And in those studies, they were giving vitamin D prior to giving chemotherapy and to see if priming these people with a level of vitamin D prior to giving them chemotherapy had an effect.
And so, sure enough, I mean, the final study is being done. But the initial study that was published a couple of years ago, after the data was looked at, it basically extended the patient’s lives by two months if you primed them with vitamin D. And it was only like 8,000, maybe 10,000 units a day, which at the time I said to the primary investigator on this study, I said, why don’t we really go for like 50,000?
And the response I got back is, we can’t get that through the IRB. I said, these people are dying. You’re giving them really potent chemotherapeutic drugs and you’re worried about giving them vitamin D. Yeah, right. They’re dying. They’re not going to survive. You’re trying to prolong their life. You can’t even operate on them because they’re too far along. And they’re worried about giving them a substantial—
Be that as it may, even if the doses they gave in conjunction with the chemotherapy extended their lives by about two months. And in cancer chemotherapy, that’s a big deal. Okay? Drugs are approved on that basis.
But it was funny because it was sent to JAMA and it was the initial data, the way it was analyzed by the School of Public Health at Harvard, showed significance at like 0.035. And then JAMA comes back and says, well, we want you to do it this way, so do it that way. And it comes back with 0.045 or something. And no, no, now we want you to do it this way. So then it comes back at 0.051.
And then they say, okay, that’s good, but you’ve got to say it’s not significant. And we’ll publish the article. The only thing that shows up in the news was that vitamin D was not significant in progressing and treating the cancer.
DR. ERIC BERG: That’s completely false.
BRUCE HOLLIS: Well, it’s not. It’s—if you look at, if you look at your level of significance, like point difference between 0.05 and 0.051. So that’s, that’s 50 patients in 1,000 versus 51 patients. I mean, it’s just to get the, it’s just to get the term “not significant” into the article.
DR. ERIC BERG: Holy macro.
BRUCE HOLLIS: So what happens all the time.
DR. ERIC BERG: So what you’re saying is there is some slight resistance by these journals, and—
BRUCE HOLLIS: I’m being very sarcastic. In the major medical journals, there is huge resistance to it. There was an article that just came out in Science magazine that showed that vitamin D and the mechanism of how through the microbiome, it regulates colon cancer. And that actually got published. It’s very technical. Okay, it’s very technical, but it shows the mechanism, how vitamin D works not at the endocrine level, but the cellular level to regulate cancer immunity in these patients.
DR. ERIC BERG: Wow.
Vitamin D Storage Myths
DR. ERIC BERG: So as far as the storage, I was under the assumption that all this vitamin D gets stored in your fat and then when you need it, the body pulls it out. But that’s—
BRUCE HOLLIS: No, that’s not true either. Yeah, fat soluble vitamin goes into your fat when you need it. And I’ve even heard people in the old days say, well, what happens when you have bariatric surgery and you have a lot of vitamin D and it pours in, you get vitamin D toxic. Well, that was totally ridiculous. I mean, it doesn’t. It just, you know, it might supply a little bit, but it’s not, I mean, maybe enough to supply the endocrine portion for a while, but it definitely isn’t enough to supply the cellular portion.
DR. ERIC BERG: Because I think you even studied, you tried to find vitamin D stored and you couldn’t find it or—
BRUCE HOLLIS: Yeah, we looked at, we looked at levels in fat. So other things are stored as esters, like fatty acid esters and fat tissue. So we would dose even humans and take fat samples and look for it. And there was nothing special about fat tissue, about vitamin D being in there. I mean, there was some in there because it just distributes in tissues in general. But it wasn’t anything against a gradient where you had this high level of vitamin D and fat tissue.
DR. ERIC BERG: Wow.
Vitamin D and Vascular Health
DR. ERIC BERG: You also mentioned the relationship between vitamin D and even the endothelial layer on the inside of your arteries becoming a bit leaky.
BRUCE HOLLIS: Yes. You know, if you go back several—this wasn’t my work, but it happened. It was done by a group of biochemists in Utah. And what they had, I believe it’s called cavernous malformation syndrome, where you have these leaky vessels in your brain. It’s a metabolic defect, and they leak fluid.
And these guys were looking for compounds that would avert or be more therapeutic so these endothelial vessels wouldn’t leak. So anyway, they had this system where they ran thousands of compounds through this test for this leakage. And what they found was they found two compounds, one of which was vitamin D, which they were really disappointed by, because good old vitamin D was a stabilizer of endothelial function, meaning it stopped the leakage.
The interesting thing there was the parent compound. Vitamin D itself was the most potent.
DR. ERIC BERG: Wow.
BRUCE HOLLIS: Not the other forms, but vitamin D itself.
DR. ERIC BERG: You talk about the ones in supplements or getting it from the sun.
BRUCE HOLLIS: Yeah, the one we’re getting from the sun in your vitamin supplement was the most potent at overcoming this endothelial function.
Vitamin D and Breastfeeding
BRUCE HOLLIS: One of the other things that we did in our pediatric work was it has to do with human lactation. Yeah. You know, when I go back to my graduate school days, and I was, you know, not the best student because I always questioned my mentors, you know, and so we were taught—and I was a nutritional biochemist by training.
And in the training, they would teach, well, you know, human milk is the perfect food for the nursing infant, except for one thing. They could get rickets if they take it. So you got to give them a supplement. I thought, that makes no sense whatsoever.
DR. ERIC BERG: Right.
BRUCE HOLLIS: How could that be? And so, you know, time goes on, and we do research, and it goes for decades. And finally we figured out that to overcome this problem, the mothers were taking too little vitamin D by the recommendations that were being made by the different organizations.
So once we could measure the stuff in milk and blood and look at how much was passed into the milk from the blood, and it turned out that a woman who’s lactating needs to take about 6,000 units a day to pass enough vitamin D into her milk to satisfy her infant. And then the infant doesn’t need any. She doesn’t need drops every day. She’s getting enough from the mother. The mother’s taking 6,000 units a day.
And actually, that has been implemented in pediatric practice to some degree on progressive pediatricians who actually pay attention. So it’s an option now instead of giving—instead of giving the nursing infant 400 units drops because mother’s vitamin D is enough because she deficient herself.
DR. ERIC BERG: I wonder if this postpartum depression is related to this vitamin D, because low vitamin D—
BRUCE HOLLIS: It’s possible. We looked at some of that, but in our studies that we ran in pregnancy. But, you know, it’s possible. But our numbers, we didn’t have enough to really make an assessment if that’s true or not. But it’s possible because vitamin D definitely has neural effects.
Vitamin D Resistance
DR. ERIC BERG: How does this idea of vitamin D resistance on top of all these other issues? We have vitamin D resistance. You have the vitamin D receptor. You have certain microbes like that are involved in Lyme disease. You have Epstein Barr virus that competitively downgrade receptors on top of everything else. Have you looked into that?
The Challenges of Vitamin D Research Funding
BRUCE HOLLIS: I haven’t. I mean, they’re hereditary. They’re people who have hereditary resistance because their receptors are metabolically inactive. You know, again, it’s possible, but to look at those kinds of studies or to run… First of all, at this point in time, nobody’s getting any money to run any more vitamin D trials. It’s over. Okay?
DR. ERIC BERG: Really?
BRUCE HOLLIS: Yeah, it’s over. You can’t even find a student who would go into somebody’s lab to study vitamin D. Metabolism is committing career suicide. And this isn’t just in the U.S., it’s in Britain too.
The vital study in these articles, like Scientific American, had totally decimated vitamin D research and trials are expensive to run. The government won’t fund them. Drug companies don’t want them. They don’t even want them run because they compete with drugs that they have in development, such as the drugs for prostate cancer.
You have one that’s free, that is pretty good at suppressing prostate cancer and it doesn’t cost anything. You think the pharmaceutical companies want that knowledge out there?
DR. ERIC BERG: It’s criminal. Totally criminal.
The Case of Makena and Preterm Birth Prevention
BRUCE HOLLIS: Or vitamin D in preventing preterm birth or complications. There was a drug called Makena that was 17 hydroxyprogesterone. Remember that one?
DR. ERIC BERG: Isn’t that for cancer? That’s for cancer.
BRUCE HOLLIS: No, no. This was for prevention of preterm birth. It was injectable. I don’t know what company made it. It was a small biotech company back in 2010. This company was bought out by a bigger company and they had this one drug, 17 hydroxy progesterone, which was called Makena.
It was approved as a speedy approval by the FDA. There was only one problem. It never worked. It was expensive and it was an absolute abject failure. Two years ago, the FDA made them pull it from the market.
DR. ERIC BERG: Was it a progesterone or was it…
BRUCE HOLLIS: It was 17 hydroxyprogesterone. You can look it up. You can look at the history of it. And so it was doing… They were proposing it did something that vitamin D actually does, which was appropriate. Vitamin D levels can reduce preterm birth, but it’s free.
DR. ERIC BERG: Wow. There’s no money in it.
BRUCE HOLLIS: No. And it’s… Yeah.
Magnesium: A Critical Cofactor for Vitamin D
DR. ERIC BERG: So you also mentioned in one of your videos, it’s important to also realize that vitamin D needs magnesium as the cofactor.
BRUCE HOLLIS: It does, yeah. I reviewed a lot of papers years ago and I remember reviewing this one that clearly showed that magnesium status was a potentiator of improving metabolism of vitamin D within the cells, meaning it was a simple thing.
So people who had better magnesium status also had higher levels of the intermediate form of vitamin D, the 25D form, to get measured. And so I myself was taking a fair amount of vitamin D, but I really wasn’t that satisfied with what my blood levels were.
I mentioned that what people take is very individualistic of how you respond. Some people are really good metabolizers, some people aren’t as good. They need to take a lot more to get their blood levels. You only know what it is if you haven’t tested.
And so I started taking magnesium and instantly increased my blood levels by about 40%. And there’s really no way to know if you’re magnesium depleted because blood measures don’t really tell. So the only way to know it is I take, I think, 400 milligrams a day of magnesium oxide, just a supplement every day. And then, you know you’re magnesium replete for other reasons just besides vitamin D. So it’s a key…
DR. ERIC BERG: It’s a what?
BRUCE HOLLIS: Key cofactor. Yeah, in the metabolism of vitamin D. So it interacts with the enzyme that activates vitamin D. There’s two or three of them that need that magnesium as a cofactor.
Vitamin D and Mitochondrial Function
DR. ERIC BERG: Absolutely. Have you ever done any research on vitamin D in mitochondria?
BRUCE HOLLIS: I haven’t. So vitamin D, there’s two different enzymes. One of them is located in the mitochondria and one of them is located in the microsomes, different cellular components. So that’s where these enzymes that activate vitamin D are within the cell. One in the mitochondria and one in the microsomes.
DR. ERIC BERG: Oh, wow. That’s kind of important. The mitochondria, as far as… I’ll have to look where that’s… what that does or how it influences the mitochondria, which is…
BRUCE HOLLIS: Yeah.
DR. ERIC BERG: So much of a problem with so many people. If someone takes a higher dose, like a large dose of vitamin D3, isn’t there some mechanism that it does turn into inert compounds? I think it was one that was called tachosterol or lumisterol.
Sun Exposure and Vitamin D Regulation
BRUCE HOLLIS: Well, those are things. Those compounds are made in the skin by sun exposure. It’s probably one of the ways that the body regulates how much vitamin D.
So if you’re pale as a ghost and you go out in the summer sun and expose yourself to 20 minutes or so of intense sunlight on the initial exposure, you’ll make about 20,000 units of vitamin D that will be released into your blood over the next day.
But then you start tanning, that exposure becomes less. You know, the next day you’ll make less and less and less. And that’s where the production of these tachisterols and lumisterols and all these things probably assist in blunting the effect of vitamin D made by the sun.
But in the body, once you take vitamin D, I’m not sure it’s metabolizing to those things. I think it just disappears. You know, the body will just excrete it through the bile acid functions and then activate it. But those, what you’re mentioning is a control point for the sun, solar production of vitamin D in your skin.
Debunking Vitamin D Toxicity Myths
DR. ERIC BERG: Okay. And then as far as the, you know, you have hypercalcemia, I think they have exaggerated that a bit. But what’s your take on toxic doses? In the research on the toxic, you’re going to, you know, even people are saying, “Oh, you’re taking 10,000, you’re going to get kidney stones.” Like, really?
BRUCE HOLLIS: Well, vitamin D’s never been associated in studies with getting kidney stones.
DR. ERIC BERG: Wow.
BRUCE HOLLIS: I mean, most kidney stones are oxalates. I mean, it can… I mean, so if you’re taking, if you’re worried about kidney stones and vitamin D, and if people are taking high doses, say they’re taking 30, 40, 50,000 units for cancer, my first recommendation would be limit your dairy intake.
The other thing is that before anything happens in the blood, it happens in the urine first. If you’re worried about high blood calcium or too much vitamin D, you would have your urinary calcium monitored. As long as there’s no calcium being dumped into your urine, you don’t have a problem.
And at 20,000 units, I mean, there are rare genetic defects that would cause vitamin D to become toxic. And one of those is an enzyme that inactivates vitamin D called the 24 hydroxylase in the kidney and other tissues. And if you have a defect in that enzyme, then it’s potential you could become toxic. But those are really rare defects.
DR. ERIC BERG: So if we take those out of the picture, how many people really end up getting hypercalcemia from…
Safety Studies in Pregnancy
BRUCE HOLLIS: We never saw one. And in our studies that we did in pregnancy and lactation, when I proposed to do these studies back then, you could get… this is in the early 2000s. So when we proposed to do these studies in pregnancy, pregnancy is the most sensitive group you can do studies in.
So we were proposing in these studies that we were going to give pregnant women 4,000 units a day because that’s what we calculated they would need to become sufficient. It’s probably low, but you have to start somewhere. And at the time, 2,000 units was the upper limit of safety. So we proposed 4,000.
And so the granting agency saw, “Yeah, this grant’s great, but you can’t do this, you’ll kill people.” So we said, “No, we won’t.” And so the funding agency said, “We’ll conditionally approve this grant if you go to the FDA and get an IND number, investigational drug number.” That’s what drug companies have to do when they come up with new drugs. We had to do it for vitamin D. Okay.
And we did it. We submitted an IND, it delayed the study by a year and the FDA granted our IND application. And as a consequence we had massive monitoring, we had monitoring committees, we had to report to the FDA every month. And we never saw an adverse event due to vitamin D supplementation.
And a lot of other people used our IND for other things. Other, you know, there are all kinds of studies going on. Never once did we see hypercalcemia. If we saw that, usually it was due to something like dehydration, but it was never due to vitamin D supplementation.
The Journey Into Vitamin D Research
DR. ERIC BERG: Incredible. Knowing the importance of vitamin D… I, it’s one of the most important vitamins. How did you stumble on, start doing research on vitamin D? Did you know this in advance how important vitamin D was to the body and you were just so interested in it?
BRUCE HOLLIS: Well, it started when I was a graduate student at Ohio State University. And at the time I was in agriculture and my advisor at the time, they were looking at, in cattle there’s a disease called milk fever. It’s called parturient paresis.
And what happens is these dairy cattle are bred to make massive amounts of milk. Physiologically, it’s not sustainable. And what happens in those cattle is they go through more and more lactations. They can’t maintain serum calcium once lactation is initiated because their blood levels of calcium plummet.
It turns out why that happens is they need to mobilize bone calcium. And as they get older and into more and more lactation cycles, it becomes impossible for them to do it. So once they initiate lactation, their blood calcium would drop to four or five and they just keel over and lay there because they’re paralyzed.
And then the farmer would have to dose them with high doses of calcium and then the cow would stand right up and then it would fall again. The cow would fall down. So, and when this happens, it’s a big economic loss because, you know, they got to get… The cow can’t breed anymore and the cow can’t make milk.
And so they looked at ways to make it better for the cow not to go into this condition. And one of the ways was to give them really huge levels of vitamin D to make it stop. And it was successful to some degree, but there were other things that were better. But that’s how I got into it.
And then, of course, I went more towards human nutrition and I was interested in the milk issue and I was interacting with people in pediatrics and, you know, the first grant we came up with, it’s interesting. So the first grant back in… I was telling you about the FDA, it was basically a safety study that we were designing to look at and based around skeletons.
At that time, we didn’t even know to ask the questions about does vitamin D prevent preterm birth and preeclampsia, gestational diabetes and all this other stuff. So we ran a study and when the data were analyzed, this is where it’s frowned upon. We analyzed the data and we said, “Look at this. Vitamin D is preventing preterm birth and it’s preventing complications of birth.”
And I presented it at a meeting, it was in 2009, and the audience went crazy in the wrong way. I mean, I was attacked. “How dare you say this? You know, this is heresy. This can’t be true.” You know, I mean, it was incredible. So when you present data like that, you better be prepared to be hammered.
DR. ERIC BERG: Wow.
Groundbreaking Findings on Childhood Asthma
BRUCE HOLLIS: And then, you know, since that time it’s been basically… it’s shown. There was an article that’s in that… that was… We did called the VDART study at Harvard. It was done with Scott Weiss, who was a world renowned asthma specialist.
And we found out that vitamin D… If you give enough vitamin D, especially like preconception, you could basically eliminate childhood asthma. But no one will, you know, the data are clear if you analyze them in the appropriate fashion like is discussed in this Townsend newsletter article.
And even Weiss chimes in and we learned a lot from that study like we do from all these studies that you needed to give more, you needed to correct baseline levels and you could, you know, there would hardly ever be another childhood asthma child born if mothers were replete when they conceived or even started taking it early when they found out they’re pregnant.
You know, most of our studies were in the first trimester because that’s when they walk in and they figure out they’re pregnant. You can’t… to do preterm or preconception studies is hugely… But that’s when it would be most effective. Because the vitamin D deficiency in the trials that we run is mostly missed in first trimester because you don’t even know they’re pregnant. So you’re only getting a hold of them at 12 weeks or so or maybe later than that.
DR. ERIC BERG: I think it’s probably the most important time to eat healthy and get enough nutrition is when you’re not born, before you’re born.
BRUCE HOLLIS: Yeah.
DR. ERIC BERG: Incredible. So wow.
BRUCE HOLLIS: I’m just, I mean it leaves you speechless because you have this knowledge and you know, and it’s going away because you can’t. Nobody else can do follow-up grants on this anymore because when it goes to this, first of all, the government won’t. You know, these studies that we did, they cost millions.
The Vital study was 30, 35 million, maybe more. To me, it was totally wasted money because our studies that we did in pregnancy were probably over. The terms of the grants were five or six million dollars to do these clinical studies, and government isn’t going to shell out that kind of money anymore. The drug companies will pay them not to do it.
DR. ERIC BERG: Incredible. Incredible.
BRUCE HOLLIS: So you either accept the data that we have now, and I think that people should also not only look at the randomized trial data that we did and the things that were done overseas where you had true vitamin D deficiency, you could do a real randomized trial and not have it compromised by what levels of indies went in the beginning.
And the other thing in our country is non-compliance of the patients is a serious issue. They don’t comply. “Oh yeah doc, I took the vitamin one.” In fact, they never took it at all. And you know, here’s the other thing in intent to treat: if you know that those people aren’t complying, you can’t eliminate them for the data analysis.
DR. ERIC BERG: What?
BRUCE HOLLIS: No, it violates the intent to treat model. Wow.
DR. ERIC BERG: These are, this is stuff that people don’t know. They have no clue unless you’re in the research field. So I guess in certain parts of other countries around the world, there’s probably maybe places where hopefully they’ll continue doing vitamin D research. I don’t know.
Vitamin D Research in Other Countries
BRUCE HOLLIS: Yeah, I mean, you know, like I said, there’s stuff still going on in Iran, you know, where most countries really have a really big vitamin D deficiency problem because of lifestyle. Women are in burkas and they’re not allowed to be in the sun. And so you have in places in India the same way.
DR. ERIC BERG: What about Saudi Arabia?
BRUCE HOLLIS: Yeah, Saudi Arabia too. Any of the Muslim countries where the females are restricted have a horrible vitamin D deficiency problem.
DR. ERIC BERG: Well, you got me thinking about that because you have compounded by all the diabetes. They have no sun, no vitamin D. Yeah. Incredible. Is there anything else that you want to end off with that you want people to know about? This has just been mind-blowing and I’m going to…
The Challenge of Getting Proper Medical Recommendations
BRUCE HOLLIS: I think that the only… You’re never going to get… Well, I can’t say never because my physician is pretty progressive on all this stuff. So there are physicians that are. But the ones who depend on their professional organizations for recommendations like the Geriatric Society, like OBGYN, even in Pediatrics.
And if they’re only looking at the recommendations coming out of those professional societies which are solely based on reports like the Endocrine Society, which just came out with revised recommendations, which are ridiculous again, they decreased everything that people should be taking, going back to the Institute of Medicine 2010, which has never been redone.
You know, you have to look at programs like your own to educate people. And fortification is only done to highly motivated individuals, or supplementation. Fortification is a different matter. But until the government would change it, never. You know, we always sought to get fortification of product higher, like milk for vitamin D. But they don’t want to do it.
DR. ERIC BERG: No.
BRUCE HOLLIS: So supplementation is only done by highly motivated individuals. And how do you prove prevention? Right. You can look at that. You can look at observational retrospective data.
The Physicians Health Study
And a lot of the data that came out of the… Are you familiar with the Physicians Health Study at Harvard run by the Walter Willett Group? I mean it’s been going since the mid-80s, health professional studies. Basically it was physicians or nurses participated in this study. And every year they give a blood sample. And every year they’d fill a questionnaire. “What happened to you this year? Did you have a heart attack? Did you get cancer?”
And then they had blood samples, banked millions of these samples. And what they do is then they say, “Okay, we want to look at this disease related to this compound.” And there’s been a number of those studies done on vitamin D, mostly all positive.
And those data are really valuable, okay, because those look at lifestyle over a long period of change. But they’re discarded when studies like Vital say other BS.
DR. ERIC BERG: Are they still doing that study now or are they…
BRUCE HOLLIS: Yes. Health professional study still ongoing.
DR. ERIC BERG: Okay. Yeah. I think he was involved in what? The Planetary Health Diet. The new Planetary Health Diet.
BRUCE HOLLIS: Willett. Yeah.
DR. ERIC BERG: Oh, yeah, Willett.
BRUCE HOLLIS: He’s involved in everything. The most cited scientist in the history of science.
DR. ERIC BERG: Incredible.
BRUCE HOLLIS: And I know Walter Willett. I’ve interacted with him in the past quite a bit on this stuff.
DR. ERIC BERG: He definitely gets a lot of funding.
BRUCE HOLLIS: But that study, those health professional studies were a gold mine. I mean, extraordinary value. You know, not a randomized trial, but there’s a lot of data in there that should be paid attention to. Should be paid attention to.
DR. ERIC BERG: Well, I’m sure it’ll get published if vitamin D is not favorable.
BRUCE HOLLIS: Wow.
DR. ERIC BERG: This has been incredible. Thank you so much for taking your time to do this.
BRUCE HOLLIS: You’re welcome.
DR. ERIC BERG: I’m going to put that link down below of that article from the Townsend Report so everyone can check it out, but thank you so much.
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