Debunking Misinformation About Vitamin D - Dr. Hoffman interviewing Dr. Grant
Recently, headlines have proclaimed that vitamin D is ineffective, that we shouldn’t bother testing for it, and that most people shouldn’t bother taking it. Pushing back on those assertions is Dr. William Grant, one of the world’s foremost vitamin D researchers with over 60 published studies. His latest paper explains why research on vitamin D is plagued by methodological errors and colored by bias against nutritional supplements that might supplant pharmaceutical drugs. Dr. Grant explains how vitamin D, far from being just a “bone vitamin”, can impact a wide range of conditions ranging from dementia and Alzheimer’s, cardiovascular disease, diabetes, mood disorders, and cancer; studies have shown it improves pregnancy outcomes and extends life; the latest research suggests a benefit for respiratory infections and Covid. We also discuss the important role sunlight exposure plays in vitamin D synthesis, and how wrong-headed health authorities have stigmatized sun exposure to great detriment. What levels are best? How much to take? Is there an upper limit? Dr. Grant is currently the director of the Sunlight, Nutrition, and Health Resource Center.
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0:01:15.3 Hoffman: Welcome to today's Intelligent Medicine podcast. I'm your host, Dr. Ronald Hoffman. I think you'll find this a fascinating podcast because it's on the subject of vitamin D. Paraphrasing Rodney Dangerfield, vitamin D don't get no respect these days because in light of a recent study, the VITAL study a lot of negative publicity was generated. The VITAL study was in the New England Journal of Medicine originally intended to assess the effects of fish oil and vitamin D on cancer and heart disease. But they did a subsidiary analysis for the effects of vitamin D on osteoporosis and it drew a blank. It did not show in this particular study a robust, beneficial effect.
0:02:03.4 Hoffman: Yet on the slim basis of this evidence alone, vitamin D's impact on osteoporosis, they drew some pretty drastic conclusions. The results of the VITAL study are being leveraged to undermine public confidence in vitamin D supplementation and even to put the kibosh on vitamin D testing. Accompanying the original article in the New England Journal of Medicine, there was an editorial which is highly unusual. They opined, "VITAL and this ancillary study show that vitamin supplements do not have important health benefits in the general population of older adults. Thus, there is no justification for measuring vitamin D in the general populace or treating vitamin D to a target serum level." And worse yet the editorial proclaims, and this is astonishing, and I'm quoting, "People should stop taking vitamin D supplements to prevent major diseases or extend life."
0:03:06.0 Hoffman: And so, [chuckle] today we've invited one of the world's experts on the subject of vitamin D. He's published or co-authored over 60 papers on subjects related to vitamin D and nutrition in general. His background is that he's a PhD in Physics at UC Berkeley. And among his accomplishments in... He published a landmark paper in 1997, linking diet to Alzheimer's disease. Huh, that certainly been born out by years and years of subsequent research, and more and more critical papers. But he's also focused on the role that vitamin D might play, not just on osteoporosis, because that's what we're taught in medical schools, vitamin D was good for your bones, but its other benefits, its benefits for a wide range of disorders.
0:04:04.7 Hoffman: So without further ado, here's Dr. William Grant. It's a pleasure having you on the program. It's really a privilege to share with you on this auspicious day, because today is the day when one of your landmark papers has been published. Comparing the evidence from observational studies and randomized control trials for non-skeletal health effects of vitamin D. So, tell us a little bit about how you got involved in vitamin D research and tell us about the latest paper.
0:04:36.2 Grant: Okay. Thanks for having me.
0:04:38.3 Hoffman: My pleasure.
0:04:38.7 Grant: It's a pleasure to be here. I got involved with vitamin D starting in 1999 when the Institute of... National Cancer Institute published the maps of cancer mortality rate by county in the United States. And it was interesting that in the Northeast United States cancer rates are very high and in the Southwest, they're very low. And I was referred to the work by Cedric and Frank Garland, who in 1980, published a paper saying that, "Sunlight... Higher sunlight in the Southwest, lower in the Northeast seemed to be correlated with the risk of colon cancer. And because the most important benefit of sunlight exposure was vitamin D production, vitamin D must reduce the risk of cancer." And that was 1980 and still in 1999 there was no traction. Well, I looked at these maps, and I was working for NASA at the time as an atmospheric scientist, so I got the NASA satellite image for surface solar UVB doses for the United States. And...
0:05:52.8 Hoffman: In fact it would be called these days, it would be called a heat map for vitamin D exposure. I mean, now it's like a familiar graphing technique to spot trends.
0:06:05.7 Grant: Okay. Okay. Okay. And, so I compared that with the cancer maps in what are called ecological studies, geographical ecological studies, and I showed that for about 13 types of cancer there was a strong inverse correlation between solar UVB and cancer mortality rates. I published that in the Journal of Cancer, in 2002. And it then spawned a lot of research in universities. Although, when it was first published, I had not included other risk modifying factors and I got criticized for that. For example, I left off the states along the boarder with Mexico because they had high rates of stomach cancer. I later learned it was because of Mexican Americans there who had a lot of H. Pylori infection and had a lot of stomach cancer. Anyway, I was able to add a lot of the confounding factors like alcohol, smoking and that sort of thing. And it took submission to 10 journals before it was accepted. See, the mainstream journals do not like vitamin D. The mainstream journals work for Big Pharma.
0:07:09.1 Hoffman: Right.
0:07:09.5 Grant: And Big Pharma sees vitamin D as competition for profit and income. And so they kept saying, "Oh, we just don't wanna publish it." Finally, got published at a conference proceedings for a conference held in Germany and published in a Greek journal. And now, it has a lot of citations, but back then it was pretty much ignored. So that was how I got involved, and then kept going from there.
0:07:36.0 Hoffman: Right. So in this... In the latest article, which is just published... And by the way let's mention also that your current position is Director of the Sunlight, Nutrition and Health Research Center and the website for them is sunarc.org. And you can learn more about your research and you can learn more about the benefits of vitamin D there. So it seems like there's such an astonishing array of conditions for which vitamin D might have a critical impact. And you cite in your article and it's a long list, Alzheimer's disease and dementia, autoimmune diseases, cancers, cardiovascular disease, COVID 19, major depressive disorder, type 2 diabetes, arterial hypertension, all-cause mortality, which I guess is... That's the name of the game, whether you're gonna live or die. Respiratory tract infections and pregnancy outcomes. So how is it that vitamin D, which we were taught in medical school, that was the dogma then, was... It was the bone vitamin. If you don't have enough, you get rickets. How is it that vitamin D has such a plethora of benefits.
0:08:50.5 Grant: Well, it actually... Okay, there's the vitamin D that you take in supplements or make in the sun, that's then converted and delivered at 25-hydroxyvitamin D, which then circulates around and then any organ or any cell that all of a sudden needs the effects of vitamin D can convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D or calcitriol, which is a hormonal version of vitamin D, which can go to vitamin D receptors in almost every cell in the body. And there it can affect gene expression, upregulating some, and downregulating others. So they've shown that thousands of genes can be regulated by vitamin D. So it's primarily through this gene regulation, it's a hormone just like estrogen and progesterone, testosterone, et cetera. And that's often overlooked. And when they try to say, "Well, vitamin D is like vitamin C or vitamin E, which haven't shown many benefits," but no, it's really a hormone.
0:09:52.6 Hoffman: Indeed. And so there seem to be vitamin D receptors throughout the body. It is ubiquitous. And so, let's tackle some of the major impacts that it has, system by system. And let's start with the brain. You wrote a pioneering paper in 1997 that linked diet to risk of Alzheimer's disease. Now that's well accepted, but what role does vitamin D play?
0:10:24.9 Grant: Well, one of the main roles of vitamin D is to reduce inflammation. It affects the production of pro-inflammatory and anti-inflammatory cytokines. So if you raise the vitamin D levels, you're gonna reduce the production of pro-inflammatory cytokines, and that's gonna reduce the inflammation and oxidative stress. And almost all the major diseases are linked to inflammation. So that's one of the primary things. I think that they've also found that for Alzheimer's disease, it can help clear the plaque that forms in the brain. Vitamin D also reduces the risk of hypertension and high... I think, hypertension is involved in dementia and Alzheimer's, so it is just a number of factors.
0:11:17.2 Hoffman: Okay. And then there's autoimmune diseases. And lately, it's become trendy for rheumatologists to measure vitamin D because of recognition that vitamin D may play a role in conditions like rheumatoid arthritis, lupus, and so on. What's up with that? What's going on there?
0:11:36.5 Grant: Well, I think inflammation, I'm not really the expert on that. I'm an expert on cancer though, and I can tell what's happening there. Okay. In cancer, the... First of all, vitamin D sort of interrogates all the cells in the body and ask, "Does this cell really belong in the organ it is?" And if so, it will let it proliferate and differentiate and so on, but if it doesn't belong there, it'll help the cell commit suicide or apoptosis. Then if you... Now, if a tumor starts growing, if... As long as it stays in that... Where it is, that's okay. But if it starts growing too fast, which requires the formation of blood cells, blood vessels around the tumor, then it can grow faster and vitamin D can reduce the risk of... Reduce the formation of these blood vessels.
0:12:25.6 Grant: But... And more importantly, cancer only kills, if it gets... If it can metastasize into the body and vitamin D reduces risk of metastasis as well. So it turns out that since there are many factor... Risk factors for cancer, smoking, toxins, inflammation, et cetera, et cetera, vitamin D is only one of the players in the field. And it turns out that in the VITAL Study and other studies, they find it's hard to show that giving a little bit of vitamin D supplementation reduces the risk of cancer formation. But even VITAL showed that the 2000 IU per day they were giving to people who had above average vitamin D levels, reduced the risk of cancer mortality rate. So... Yeah. If it's... You gotta look carefully at the studies and understand the mechanisms to try to figure out these, what's happening.
0:13:18.3 Hoffman: Yeah, and it takes someone like you who's an expert on studies to do a deep dive and actually look at the data, but sometimes they draw the conclusions that there was no "Statistically significant benefit." And yet impressive trends are sometimes seen towards benefit. It's just that they don't reach whatever, 95% confidence levels, right?
0:13:42.3 Grant: Well, also The New England Journal of Medicine only allows one conclusion from the study in the abstract. And they totally ignored the secondary findings, which show some benefits for those with low BMI and almost a significant benefit for Black Americans. But then the spokespeople for the VITAL study in all the press releases also ignored the secondary findings. Now what the VITAL did find recently that they did find a beneficial reduction of autoimmune disease. Again, I don't know the details but it was a significant finding.
0:14:20.8 Hoffman: Has that been published yet because I haven't heard that.
0:14:23.7 Grant: Oh, yes.
0:14:24.3 Hoffman: Oh, okay.
0:14:24.4 Grant: Yes. Hahn, H-A-H-N was the author.
0:14:27.0 Hoffman: Yeah. And it didn't get as much ballyhoo as this study in the New England Journal of Medicine, which generated all kinds of headlines in the conventional press. Like these, "Study finds... " Here, let me just read some of these. "Study finds another condition that vitamin D pills do not help." "Study finds vitamin D supplements do not reduce risk of broken bones." "Stop taking vitamin D already," shouts Forbes magazine. And on and on and on.
0:14:52.3 Grant: Well, there's a mass media blockade on vitamin D instituted by the FDA and accentuated during the COVID era. I published a paper in April 2nd, 2020, suggesting that vitamin D reduced the risk of COVID as far as infection in COVID incidents mortality and so on. And I said over 1,800 citations in scholar at google.com, but that's not... You don't see that anywhere in the press because the Big Pharma wants to sell vaccines and they don't want you to think that there's a simple way to prevent or treat COVID.
0:15:32.5 Hoffman: Well. Okay. So what is often cited in the criticisms of vitamin D is that there are observational studies. Studies would show that people who are replete with vitamin D seem to do better, but that's not enough for science. They have to demonstrate that giving vitamin D and that's a different story. They say sometimes that, "Okay, well, people who have low vitamin D maybe they're impoverished, maybe they're ill health anyway, maybe inflammation saps their vitamin D level or perhaps they're obese. And we know that obesity tends to lower vitamin D levels. And there maybe even are racial differences in vitamin D levels. So it may be that African Americans have low vitamin D levels, but that doesn't explain that vitamin D is beneficial.
0:16:28.0 Grant: Okay. So what we showed in this latest paper was that most of the RCTs on vitamin D have been poorly designed, conducted, and analyzed. The problem is like VITAL enrolled people that averaged 25-hydroxyvitamin D of 31 ng/ml, which is relatively high. It's maybe... It's high. Then they gave a very low dose, 2,000 IU per day.
0:16:49.3 Hoffman: So let me just summarize. What you're just saying is that they started with people who had pretty good levels of vitamin D anyway, right? So maybe giving vitamin D to people who have pretty good levels is not gonna show such a dramatic difference. Is that what you're saying?
0:17:02.9 Grant: Right.
0:17:03.9 Hoffman: Okay.
0:17:04.5 Grant: That's one thing. Yeah. And it's probably the main thing, but the second thing is Michael Holick showed decades ago that a person can make between 10 and 25,000 International Units of vitamin D per day in a simulated sunlight. Well, 2000 IDEU is only 20% or 10%-20% of what you can make in a day. And our ancient ancestors were out in the sun all the time and so they were making much more vitamin D than we are now. But the third thing is, when they do the analysis of the results, they generally just look at the results in terms of intention to treat, in other words, they have the vitamin D supplementations group and the placebo group. And they look at the results for all the... Each arm separately. Well, everybody has a different response to vitamin D, and everybody starts...
0:17:55.8 Hoffman: It's like a one size fits all. In other words, to make... I mean, for scientific studies, in a way... They have a way they have to design it. That's what they do with medications. They give maybe two or three levels, but most, but they just... It's everyone gets the same thing. And you're saying that people need tailored vitamin D dosing.
0:18:13.1 Grant: Well, in a drug trial, there's no other source of the agent in the RC and vitamin D, you've got sunlight diet supplements.
0:18:20.8 Hoffman: Yes.
0:18:21.3 Grant: So, plus genetics. So there was a study from Tufts University called D2d. It was for looking at, going from pre-diabetes to diabetes. They gave them 4,000 IU per day. And when they looked at the placebo versus vitamin D group, there was no statistical significance between those outcome in terms of going to diabetes. But when they finally looked at the vitamin D levels for those in the treatment arm, they found that as they rose above 30 ng/ml that for every 10 ng, they got 25% reduction in progression to diabetes. And all the way up to over 100 ng/ml I think, well, it's 50ng/ml or 60ng/ml. So, I mean that was probably sort of a secondary finding, but they consider that an observational study rather than a result of a clinical trial. So it didn't get much play.
0:19:26.5 Hoffman: And just for reference, how many Americans have those levels, 30, 40, 50, 60, people who were... Just the unwashed multitude, who, I don't know, maybe they're not taking any vitamin D or perhaps they're taking a paltry amount in a Centrum or something. I mean, how likely is it that the vitamin D is gonna be that high?
0:19:45.2 Grant: Well, according to a study of 2015 using Quest Diagnostics data from several million people, about a third of the population has above 30 ng/ml.
0:19:56.1 Hoffman: Only one third?
0:19:56.5 Grant: About a third has below... The third has below 20 and got a little less than a third in between 20 and 30. And of course in winter, levels go down quite a bit by 60... By 30 or 40%. And mortality rate goes up by about 25%, overall mortality rate.
0:20:17.3 Hoffman: So what we're saying is that there's a vast number of Americans who have less than 20 is consider deficiency; It's frank deficiency. Up around 20 to 30 is maybe insufficiency in other words, not adequate but not frank deficiency, and a very small fraction of Americans have vitamin D's above 40, 50, or even 60.
0:20:43.6 Grant: Right.
0:20:44.3 Hoffman: So the other thing that lately they've launched is a campaign against sunlight because sunlight, [laughter] being a source of vitamin D that vitamin D... I'm sorry sunlight has been now classified as a carcinogen by, I guess it's the World Health Organization. Am I correct in saying that?
0:21:03.3 Grant: Right. Right.
0:21:03.4 Hoffman: Wow, it's like stay out of the sun because you know, just like it's like cigarette smoking, you know, you gotta avoid it.
0:21:10.2 Grant: On the other hand, a study from Sweden... It was actually a melanoma study, but an enterprising scientist looked at the data and found that those, the one third that had the greatest sun exposure had a 30% lower mortality rate than the lower third that more or less avoided sun. And said that sun avoidance was about, gave about the same magnitude of risk of death as cigarette smoking.
0:21:36.2 Hoffman: Well, there you go. So it kind of sounds like a two-edged sword. Okay. Good point at which to pause, because we're talking about vitamin D and we're pushing back against some alarmist headlines, which suggest that we should stop taking vitamin D; It's a waste of money and waste of time. And in fact, even testing for vitamin D is kind of a waste of time. I'm sure the insurance companies would love that because that's part of their cost containment strategy. [laughter] Fewer people will be asking for vitamin D tests and, you know, can save some bucks. Our guest is one of the world's experts on vitamin D and especially it's non-skeletal health effects. In other words, pervasive effects that go beyond building strong bones but extending to things like brain, autoimmune disease, cancer, cardiovascular disease, mood disorders, and immunity or for COVID and respiratory tract infections, and pregnancy. And of course, all-cause mortality. We'll do a little deeper dive on some of those subjects and more in part two. I'm Dr. Ronald Hoffman, and this is The Intelligent Medicine Podcast.
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