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,

I guess, one with bone and skeleton, and then there's another system for everything else.

Can you kind of just as simple as possible kind of explain those two systems?

Yeah, the first system, the one that was discovered decades ago, 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 that's called the paracrine and endocrine system. And that is how much vitamin D can get into these cells and be activated and then carry out in 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.

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 of it. You're not looking at the type of vitamin D that's going into the cells. And how does that relate with these two different systems?

Well, here we get, it gets pretty technical. So you have, when people refer to vitamin D, mostly when you 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. We call that 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-hydroxyvitamin D.

That's when they test in your blood, right?

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 125-dihydroxyvitamin D. And that is what drives all these gene functions in all these tissues. 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. Yes. I'll call it the reservoir.

Okay. It's the reservoir of vitamin D that's being measured.

Got it. 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?

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. Okay.

That intermediate form can also go into any cell in the body, okay, and be turned in to 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 can't, it's bound to this protein that keeps it out. That's why it lasts in the blood cell.

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. Yeah. So it needs to be replenished every day to have the full function of the vitamin present. So it's very, it's complicated. That's why a lot of physicians don't pay attention to this or scientists as well.

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. No, that's true. And because of the form that's being measured, while it's important, okay, it's the reservoir, more important for maintenance of blood calcium and skeleton. But for the other functions, the only way that you can be sure that you have adequate amounts is basically take it every day, either orally or get in the sun every day. 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. 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 versus-

Yeah, there have 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 facts as being harmful. It's idiotic.

Oh, my gosh. If someone takes a million IU's 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, right? It just kind of breaks down and then goes away or just becomes-

Yeah, it'll boost the intermediate form for a while, but it's horribly inefficient.

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.

Wow. As far as the research on this, what about, 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? 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 a vital trial where they give too little vitamin D. They give it to people in a randomized trial who 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 or randomized controlled trials, okay, where say you have a cholesterol drug and you want to test if it truly will depress 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, okay, it's impossible in this country to do a true randomized trial because the population you're dealing with has some.

Some people have very little, some people have plenty. But if you just take them at random and randomize them and give these people 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. So that's what vital in all these happens is that... 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.

Okay. And it absolutely ensures that your trial is going to fail.

So, and I'll give you some examples. And 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 one, a 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 a tremendous effect 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 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, 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 violate the intent-to-treat model, it will be rejected outright. Wow. 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. 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. Wow. Incredible. And didn't they even call the amount of vitamin D they were giving people a high dose at 2,000 IUs? Yeah, that's nothing.

To put it 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 ml.

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. Right. And I get those emails from people all the time. Wow. It's just level two.

Let's talk about the normals for a second, because I think it's a bit of an arbitrary, right? There's really no agreed upon range definitively, right? There's different ideas on it. Again, if you go back to what's the agreed upon range, it's all based on skeletal models.

Right, right. 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. You can maintain a normal skeletal level where the other system requires much higher levels in that to function in a normal fashion.

Incredible. What are the ranges for the other system other than the bone and the skeletal?

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 who take, 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. 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? Yeah, or even higher. I mean, there's an MS protocol in Brazil where this guy, I can't remember the Cambria protocol. Yeah, he, they dose with several hundred thousand. Their levels are, you know, five, 600 nanograms just for the suppression of MS. And it has basis, in fact, because vitamin D at those levels is an immune suppressor. So, excuse me, 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 those, 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. Right. So what about cancer? You mentioned one of the videos about prostate cancer. 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 he 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 the patients who have active surveillance or are watching weight. You know what that is. So 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'd 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 2005-2006 era, some back there, we wanted to give them a 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. And so 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 how it progressed. And in 64%, the tumors regressed. Wow. Wow. And we submitted this to, of course, New England Journal, and they wanted nothing to do with it. So 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. 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 a study on non-resectable colon cancer, okay, run out of Harvard and all other.

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. Yeah, 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 you're worried, they're worried about giving them, you know, a substantial. And so be that as it's 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 got to say it's, it's, it's not significant. And we'll publish the article.