Dr. Peter Attia: So I want to ask you a question about this. So what do we know about the relationship between, call it, naturally acquired vitamin D through sunlight versus supplementation of vitamin D exogenously through, you know, a supplement? Do we have any reason to believe that those are different at the same level of vitamin D?

Dr. Rhonda Patrick: In the same, like, in terms of, like, how vitamin D is acting? So the thing is, is that when you're in sunlight. Like, there's other things going on, right?

Dr. Peter Attia: That's my point. Like, if you're outside getting sunlight, you're more active. And your nitric oxide, like, there's like other things that you're getting from the sunlight. So there's a confounder there.

Dr. Rhonda Patrick: But I mean, like, with respect to, let's say, forget everything, like, let's say you finally, you convert the vitamin D3 into the 25-hydroxyvitamin D into the 1,25, you know, at that level, it is the same. Like, you know, to some degree. I mean, that's not— when it's binding to the vitamin D receptor, like the actual 1,25-hydroxyvitamin D, which is the active steroid hormone, it's the same.

Dr. Peter Attia: Yeah. Now, with respect to like, you know, your body regulates how much vitamin D3 is converted or is released in the bloodstream and converted into 25-hydroxyvitamin D at the level of sun exposure. So at a certain level, you're not making the vitamin D3 when you've gotten so much of it. That's how you avoid toxicity, right?

you're not gonna keep— Yeah, what's the highest level of vitamin D a person can ever get to naturally? Meaning, if you just, like, took an individual and put them in the sun, put, you know, shorts only, no shirt, go out there and work in the sun for all summer, like, how high were my vitamin D levels when I was in high school working construction?

Dr. Rhonda Patrick: I know there's, like, data out there where people have looked at, like, you know, people that are, like, outside. They're outside all the time, but they're honestly often looking at people like in the tropics and stuff that have more melanin.

Dr. Peter Attia: Yeah, which again, so it might depend also on that.

But that would be an interesting, at least, way to say, like, if the body has a built-in mechanism to say, I'm not gonna let you make more vitamin D than this, supplementing above that would be a bad idea.

Dr. Rhonda Patrick: And it is, yeah. And so that's why looking at measuring the vitamin D—

Dr. Peter Attia: What do you think that threshold is?

Dr. Rhonda Patrick: I think going above 60 nanograms per milliliter is probably still okay. Like going to 80, you know, like there's studies looking at 80, and it's still associated with lower all-cause mortality. And in fact, I mean, honestly, if you start to look at some of the literature, you have to take a really high dose daily for like a decade to start getting like the high calcium.

But like the problem is that when you absorb— When you have a lot of vitamin D, you absorb more dietary calcium, and you also absorb more phosphorus, and calcium plus phosphorus can precipitate, right? And so, like, there's so many factors involved, but I think most people are not supplementing. Like, there's some people that are crazily supplementing, and it's like they just think more of everything is good, but I don't think most people are doing that. Like, I don't think taking 5,000, 7,000 IUs for most people— some people have to take more than that because they have SNPs, right?

Dr. Peter Attia: Yeah.

Dr. Rhonda Patrick: And you've probably seen it in your patients where it's like they got to take a high level just to get up to 30,

Dr. Peter Attia: This, by the way, is why I think all these vitamin D trials, the mega trials, are so flawed, is they're always doing it on the basis of, A, they're taking too low a dose, and they're doing it based on dose, not level. Like, to me, the dispositive study on this would be take a whole bunch of people whose vitamin D is 30, give half of them a placebo, give half of them whatever vitamin D is necessary to get them to 60 or 80.

Dr. Rhonda Patrick: 80, yeah,

Dr. Peter Attia: get something higher.

Dr. Rhonda Patrick: Yeah, create separation.

Dr. Peter Attia: Don't go 30 to 40. But be like, do it the way you would do it in a clinical trial. Way we do blood pressure trials.

When we do a blood pressure trial, we don't say you're going to take a fixed dose of a med. We give you whatever dose of the med is necessary to change the blood pressure. So we're comparing 2 blood pressure levels, not placebo versus 10 milligrams of a drug that for one guy is too much and for one guy is too little. And yet this isn't done in vitamin D, and I find it infuriating that we have no really good reliable RCT data on what seems like a jugular question. Are you better off with a vitamin D level of 80 than you are of 30? I mean, again, we think the answer is yes, but the evidence-based medicine crowd will tell you no, because this trial that gave people 2,000 IU for 10 minutes found no difference.

Dr. Rhonda Patrick: Right, or they measured maybe, if they measured anyone's level, they measured like 10% of the population.

Dr. Peter Attia: Yes, exactly, like the most recent study. We only got a level on 10% of people.

Dr. Rhonda Patrick: With like, you know, the fact of the matter is so many people do have these And I remember having an email dialogue with JoAnn Manson. This was years ago when I was a postdoc. And I think at the time she was doing the VITAL study. It hadn't been published yet. And it was like, please, please, can you get the SNP data in there? Can you measure the levels? Like, do everything, you know? Like, it's so important. But I'm with you on that. I think what is clear is avoiding deficiency. And I do say that a lot because—

Dr. Peter Attia: And where are you drawing the line? Is 30 or 40 where you're drawing the line?

Dr. Rhonda Patrick: I say 30.

I mean, it does depend on, are you looking at what the Endocrine Society says? is more of an adequate level or inadequate? Are you looking at deficiency where you're like literally like, you know, like your bones are like, your bone health isn't, you know, good? Yeah. So, but for me, I want to know the same thing. Like I'm always kind of like hovering around 50, 60, but I'm like, should I be at 80? Yeah. You know, and I don't know. So it's always like, okay, well, I'll err on the side of caution, you know, err on the side of caution, certainly avoiding deficiency. But even with respect to like all these genes I'm talking about, you know, like what if there's some crosstalk with that?

There is crosstalk, but what if there's some way that having a level of vitamin D, you know, 50 or 60 nanograms per milliliter does help alleviate some of the effects of having no estrogen? You know, like we don't really know.

Dr. Peter Attia: That's interesting.

Dr. Rhonda Patrick: It is, especially when you look at the mechanism. And like I said, I spent a lot of time looking at these response elements and, you know, looking at the fact that estrogen can actually compensate for vitamin D deficiency in some cases, with certain genes too, and it goes both ways. So I'm like, well, I feel like that should be an important component in the equation, right?

But I'm with you on the 10, like even the studies I was talking about where there was protective effects against, you know, in the cardiovascular health, in cancer prevention with hormone replacement therapy, when initiated, like, you know, within a close range, like not greater than 6 years. So it was 6 years or less. So if you're doing it 7 years. That's not part of the study. They only did it for like 10 or 11 years and they stopped. And it's like, well, what happens then when you're 65 and you started at 55? You know, like, so we don't know the question to that, I mean, the answer to that either,

Dr. Peter Attia: but I'm happy that you're thinking about it.