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Posted: 5/1/2014 1:51:45 PM
many of you may have read this before but I thought it was worth posting
Surprising New Vitamin D Research
By Chris Kresser May 22, 2013
So I want to talk about a couple different things today, and we’re going to start with vitamin D.
There’s a lot of new research coming out that is pretty surprising, I think, to many of us who’ve been following this issue for a while, perhaps more surprising to people who’ve been recommending really high levels of vitamin D.
For the last several years I’ve been warning against excessively high levels of vitamin D for some of the reasons we’re going to talk about today, but there’s a lot of controversy about this.
The science is definitely mixed and inconsistent, and the jury is certainly not out.
But I want to talk about some of the newer findings and go into some detail about what that might mean in terms of optimal vitamin D levels and vitamin D supplementation and sunlight versus supplements and things like that.
The stimulus for this vitamin D conversation, the most recent one at least, was a new prospective cohort study with over 1.2 million participants, so a pretty big sample size.
And this study showed that the lowest mortality or risk of death from all different causes and the lowest rates of cardiovascular disease were observed at vitamin 25D levels between 20 ng/mL and 36 ng/mL.
That may surprise some of you because as you probably know, in the US the lower end of the lab reference range is 30 ng/mL, so a big chunk of that range where the researchers found that the risk of death and heart disease was the lowest is actually in a range that would be considered deficient by current standards.
This isn’t the only study that reached this conclusion.
There are actually several other fairly large epidemiological studies that have been done in the past few years that have suggested that the optimal vitamin D level might be much lower than is currently recommended, especially by some of the vitamin D advocacy organizations, like the Vitamin D Council.
Some of the other studies, the range was 20 to 30.
I think there was one that was 20 to 35, and then one went up to, I think, as high as 40, so it’s all basically in the same range.
Now, as I’m sure many of know who have been listening to this show now for a while or have been following my blog, you understand that observational research, epidemiological data like this always has to be taken with a big grain of salt because there’s a lot of potential for confounding factors.
You know, something that we might consider right off the top of our head is that vitamin A and vitamin K2, as Chris Masterjohn has pointed out in several really great articles on his blog and in the Weston A. Price journal and that I’ve written about as well, vitamin A and K2 protect against vitamin D toxicity.
So one reason that people with higher vitamin D levels in these studies might be experiencing a higher risk of death and a higher chance of cardiovascular disease is that they’re also deficient in vitamin A and vitamin K2, which would lower the threshold for vitamin D toxicity.
And unfortunately, we have no way of knowing whether that’s the case because in these big studies of vitamin D levels, they never measure vitamin A or vitamin K2 status.
And there’s even controversy about how to accurately do that, so I don’t think that’s, unfortunately, going to happen anytime soon.
We’re left to just kind of speculate based on the biochemical mechanisms that we understand and some other studies that have shown that vitamin A protects against vitamin D toxicity and vice versa.
And then just understanding the mechanism of K2, one of the main roles of K2 is to make sure that calcium gets into the bones and the teeth and the hard tissues where it belongs and stays out of the soft tissues where it doesn’t belong.
And vitamin D, of course, regulates calcium metabolism, too. So if you have really high levels of vitamin D, which could increase soft tissue calcification, and then you have low levels of vitamin K2, which would also contribute to soft tissue calcification, that’s kind of a double whammy.
And a lot of people probably do have vitamin K2 deficiency. Vitamin K is plentiful in green vegetables and can be converted into vitamin K2..
And vitamin K2 is only found in certain foods, like grass-fed and grass-finished organ meats, and cheeses, particularly grass-fed dairy and grass-fed cheese because, as I just mentioned, vitamin K is found in green vegetables or in grass that the cows eat.
So with all those caveats in mind, let’s just talk a little bit about some of the problems with the idea that a vitamin D level of 50 or above, which I think the target for the Vitamin D Council is 50, and their suggested range is 40 ng/mL to 80 ng/mL with a target of 50, but when you look at the actual research that was done to determine the reference range for vitamin D, you’ll find that it’s pretty thin and sloppy in a lot of cases.
The earlier justification for the reference range of 30 and above, which is the one we use in the US, was looking at what level of vitamin D led to the maximum suppression of parathyroid hormone, and this was based on looking at parathyroid hormone levels in cross-sectional analysis of large populations, and there is a point where the average parathyroid hormone level bottoms out, but the range is really enormous.
There’s tons of variation in these studies.
So it’s really difficult to say this level of vitamin D is optimal for suppressing parathyroid hormone in everybody because the variation was so big.
And then the Vitamin D Council, I think, based their recommendation of 50 ng/mL on a similar type of evidence, but in this case, as Chris Masterjohn pointed out to me in a discussion we were having about this, the endpoint was the inferred storage of vitamin D in body fat and then saturation of an enzyme called 25-hydroxylase, I think that’s involved in converting 25D to the active form of vitamin D, which is 1,25D.
So there were never any obvious connections to serum vitamin D levels and any clinically significant endpoint in the Vitamin D Council’s recommendation.
And then they took two of the older studies on this issue and used one of the studies that later was found to have unreliable methods of reporting 25D levels.
I know that’s probably pretty technical and complicated, but the gist of it all is that the studies that were used to determine these ranges, 30 and above and then 50 ng/mL for the Vitamin D Council, are problematic and have been criticized by a number of different commentators in the scientific literature.
Steve Wright: Hey, Chris, you mentioned 1,25D as well as 25D.
Which one’s the active form, and do we know much about the ratio between the two?
Chris Kresser: Yeah. The inactive form is 25D, and that is converted into 1,25D, which is the active form. A lot of the effects of vitamin D toxicity that we’re talking about now happen when there’s too much of the active form in the body.
Something else that’s pretty interesting about that is that there are variations in how much of the active form, 1,25D, will be produced from a given amount of 25D, the inactive form.
And there are actually genetic polymorphisms that have been identified at this point that vary geographically that affect that conversion.
For example, we know that among Indians the level of vitamin 25D that’s required to produce a given level of 1,25D is higher than among the Inuit. That suggests that the optimal vitamin D exposure for Indians in Southeast Asia, those living in equatorial regions, is higher than for people living at northern latitudes.
And this is a fairly new finding, but it really means that one person’s optimal vitamin D level is different than another person’s, and unfortunately we’re not at the point where we can easily identify that and where you can go in and just get a test and get a piece of paper that says this is your optimal vitamin D based on your genetics and skin color and latitude and all of that stuff.
It probably isn’t that far away, but we’re not there yet.
Steve Wright: Why is all the research done on the inactive form, though, and not on the active form?
Chris Kresser: Well, that’s a very good question.
Actually in this conversation I was having with Chris Masterjohn, one of the things that he brought up is that 25D has been long used as the main marker for vitamin D status, and it’s been assumed that it’s an accurate marker of active vitamin D status, but it turns out it’s possible to have kind of a disconnect between your 25D levels and your 1,25D levels.
They’re not always what you would expect them to be, in part because of these polymorphisms and in part possibly because of disease states that cause an over-conversion of 25D to 1,25D, the active form, that happens in some autoimmune diseases.
So 25D turns out to not be a very good indicator of vitamin D status, and I believe Chris said he’s going to be writing a blog series about this in the future, which I look forward to reading, and he’s going to take on that topic specifically.
The other thing about this, too, that makes me think that the optimal level might not be as high as we thought is that in most indigenous populations that have been studies, their levels of 25D are typically lower than 50 ng/mL.
I think the highest level in any indigenous population that has been measured was 46, and that was in the Maasai.
But as Chris pointed out, that was done with modern Maasai who no longer paint themselves for war and are living a different lifestyle than their predecessors would have been, so we can’t really know necessarily that that historically would have been the typical vitamin D level in the Maasai population.
But even if it is, that’s still the highest that’s ever been identified in any traditional population.
Usually it’s significantly lower, and that’s still lower than the 50 ng/mL recommendation from the Vitamin D Council.
So when all of this is taken together, it does make me wonder what the optimal level for vitamin D is as a general recommendation, given that we can’t really identify all the individual differences yet.
Up until today I’ve been recommending a range of 35 to 50 or 60 and ensuring that vitamin A and vitamin K2 levels are adequate, and I don’t think that that’s far off, even considering everything that we’ve been talking about today.
I’m thinking about lowering the lower end of that to maybe 30 or 25, targeting 35 ng/mL as a kind of optimal number with an upper limit of maybe 50, and I think that range of 25 to 50 is pretty well supported by the current evidence, and I don’t think there’s much of a risk of toxicity at 50 if you’re getting enough vitamin A and vitamin K2.
And considering that bone density peaks usually between 20 ng/mL and something like 35 in people over 50 — in some populations it continues to increase up to 45, like in Mexican-Americans, I think — I think that’s probably a pretty good range to shoot for, 25 to 50 with a target of 35.
Steve Wright: So is there also a target range or a number that people should start tracking for the active form, the 1,25D?
You know, for a long time, the push was always to only get the inactive form tested. Now with all this new research, those of us who are testing freaks and just like to monitor this stuff on a regular basis, is it worthwhile to start getting the active form tested, too?
Chris Kresser: It may be, but I don’t know enough about it yet to make a recommendation.
I mean, there’s far less literature on that topic just because 25D has been the recognized marker for vitamin D status for so long, so that’s what’s usually used. Some studies do measure 1,25D along with 25D, but a lot don’t.
So there’s just less data to draw any conclusions from.
The data on 25D on already so unclear, so it’s going to take some time for me to dig into that a little further, but of course, as always, I’ll keep everyone posted.
There are a couple other things to point out about this. Generally, sunlight is considered to be a safer way of meeting your vitamin D needs if you can.
I mean, obviously that’s not possible for everybody, depending on where you live and your lifestyle, etc., and your skin tone, because full exposure to sunlight, midday sun exposure 15 to 20 minutes in a light-skinned person produces about 10,000 IU of vitamin D, but in a darker-skinned person, it could take up to 2 hours to produce that same amount of vitamin D.
But one reason why sunlight might be better than supplements is that the body does have some ability to put the breaks on the conversion of ultraviolet light into vitamin D when it’s had enough.
So there’s a little bit more of an inherent regulatory mechanism there, whereas when you eat vitamin D in the form of supplements of foods, although there aren’t many foods that have much vitamin D, there isn’t really a regulatory mechanism there.
You’ll just keep absorbing more and more vitamin D from the gut even when you have more than you need.
The other reason is that sunlight has been shown to have several other benefits aside from vitamin D production.
You don’t need a degree in science to know this! People feel good when they go outside and they get sun.
But it is interesting to see some of the research. For example, sunlight has been shown to increase nitric oxide production, and nitric oxide is a vasodilator, and that means it will lower blood pressure.
And blood pressure is one of the single strongest independent risk factors for heart disease.
In fact, I think I remember seeing a study that a drop in 20 mm Hg of systolic blood pressure — which is the number on the top of the equation. When they say 120/80, the 120 refers to systolic. — A drop in only 20 mm Hg cuts heart disease in half in people who are 20 to 49 years of age, so it’s a really, really significant risk factor, and anything that lowers blood pressure will have a really big impact on heart disease risk.
And sunlight increases the amounts of nitric oxide, which in turn lowers blood pressure.
There are also a lot of other studies that suggest that the incidence of autoimmune diseases is correlated with sunlight and ultraviolet light exposure. It’s been observed for some time that MS flares happen more in the winter than they do in the summer.
People are more likely to have MS that are born in northern latitudes without much sun exposure and less likely to have it in equatorial regions. And of course, you could say:
Oh, well, we don’t know where the chain of causality lies there. But interestingly enough, when people move from one place to another, they assume the risk of the new place, so that suggests that there is a causal relationship and it’s not just something to do with the genetics of people living at those different latitudes.
That said, it is still possible to experience vitamin D toxicity from only sun exposure.
There was a study done on Israeli lifeguards, and their vitamin D levels were between 50 and 60 ng/mL just from sun exposure. They weren’t supplementing at all.
And their rate of kidney stones was 20-fold higher than that of the general population, which is a pretty significant difference, and that’s probably caused by an increase of calcium.
There’s definitely a lot more to this story than is typically reported in the media. There’s no doubt that vitamin D is crucial.
It affects over 3000 genes. It plays a really important role in a lot of different processes.
Vitamin D deficiency is associated with numerous different diseases, so yes, we absolutely need to ensure adequate levels of vitamin D.
But as is the case with many other nutrients, perhaps all nutrients, there is a U-shaped curve for vitamin D, which means too little of it is not good, but too much of it is also not good.
And I think now we’re starting to see more research on the other end of that spectrum, whereas for a while it was almost exclusively dedicated towards the effects of deficiency.
Steve Wright: You know, just more anecdotal ideas, but interestingly enough, last week I asked on our SCD Lifestyle Facebook page how many people have flare-ups of their digestive issues in the summertime, and the overwhelming feedback was that people always seem to be healthier in the summertime.
And I think you hit on a great point there, Chris, that science doesn’t even understand how beneficial the sun is, but it seems like from every possible angle being out in the sun and getting adequate exposure on a daily basis seems to really help everyone.
Chris Kresser: Well, yeah, and this is once again where the evolutionary lens can be helpful.
I mean, we evolved in an environment with a lot of sunlight, in the equatorial region, and it makes sense that we would be genetically and biologically adapted to that kind of environment.
And yes, it’s true that genetic change didn’t stop in the Paleolithic, and a lot of genetic changes have occurred since that time, which we’ve discussed a lot on this show, but it doesn’t mean that our entire genetic makeup has changed.
And so we’re still kind of hardwired to have some sun exposure, and there’s definitely a lot of modern evidence that supports that as well.
OK, so we’ll come back to that. Let us know what your questions are.
This is an ongoing investigation, and it’s something that I continually discuss with Chris Masterjohn, Stephan Guyenet, and Robb Wolf, and we have a kind of little email group.
We trade studies when they come out, and we talk about them, so I’ll be curious to see how the research evolves over the next few years.
Steve Wright: Great, well, that’s like part 2 or 3 for you, so stay tuned until parts 4, 5, and 6.
Chris Kresser: Exactly. It’s a work in progress.
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