9UNP0438SD Neil Binkley

- Greetings and welcome to Positive Aging Lecture Series. On behalf of UW Madison Continuing Studies, Oakwood Village, and Supporting Active Independent Lives, SAIL, we welcome you to this installment. The topic today will be "Is Vitamin D the Fountain of Youth?" And our speaker is Dr. Neil Binkley from the UW Madison Department of Medicine and Institute on Aging. Dr. Binkley earned his MD from the University of Wisconsin Medical School and subsequently received his training in internal medicine at the Marshfield Clinic. After several years in private practice, he returned to the University of Wisconsin in 1990 and completed a geriatric fellowship. He is board-certified in internal medicine and geriatrics. In 1994 he was instrumental in establishing the UW Osteoporosis Clinical Center and the Osteoporosis Clinical Research Program. 

Dr. Binkley's research efforts focused on osteoporosis diagnosis, osteoporosis in men, and the role of nutrition in bone loss. Recent studies of vitamins K and D are lending valuable data on nutritional supplementation and bone health. Dr. Binkley is past president of the International Society for Clinical Dense... Okay, I should have asked you.

- Binkley: Densitometry.

- Densitometry. We're delighted to have Dr. Binkley here today, and please join me in welcoming him. 

(applause)

- Binkley: All right, thank you for that introduction, and thanks to all of you for being here today. As you see the topic, is vitamin D the fountain of youth? And I think that all of you certainly have seen things in the press, the TV, magazines, etc, that would make you believe that maybe vitamin D really prevents aging. And I would suggest to you that common sense is a good thing. 

(laughter)

 And that when something sounds too good to be true, it probably is too good to be true. I'd also share with you that I do have a color scheme on these slides. When you see this orange or whatever color that is, I only had eight crayons in my box, I call that orange, it may be coral or peach, but when you see that, that's my opinion. And you'll see a fair amount of that here today. 

I want to start out with a little bit of history on vitamin D. And historically we were out in the sun every day. For most of the time people have been on this planet this is what we looked like. We were hunter/gatherers and I would suggest that really these people were showing us how we should still be behaving. They were exercising every day. They weren't sitting in front of their computers. They had a mixed diet that was rich in fruits and vegetables. And they had plenty of vitamin D because they were making it every day. And that's the way that we have been designed to get vitamin D is we make it in our skin, and I'm not going to go through this in any detail, but basically this is a cholesterol-like molecule that's in our skin, 70-hydrocholesterol, and when that's exposed to ultraviolet B from the sun, it changes into Vitamin D. So this is the way we're supposed to be getting vitamin D. 

And I'd also share with you that this process right here, this ultraviolet B activation or creation of vitamin D, is blocked by sunscreen. So if you're out in the sun and you're wearing sunscreen, you're not making any vitamin D. And additionally, because we're here in Wisconsin, we can't make vitamin D in the winter time. This was a study that was done by Dr. Holick's group out in Boston. The latitude of Boston is down here just south of the southern border of the State of Wisconsin. And what he did is studied graduate students, had them literally go up on the roof of the building in the winter time and try to make vitamin D and they didn't. So really from roughly October through March or so here in Wisconsin, even if you're outside in the winter time, you're not making any vitamin D. So going out and laying naked in the snow in January isn't going to be helpful. 

(laughter)

 A little more history. Vitamin D deficiency was really recognized in England in the 1700s-1800s, and it really was associated with the industrial revolution. And you can find almost anything on the internet. And what this slide depicts is the streets of London in the late 1800s. And you can see the kids are here sitting on the steps, the streets are very narrow, and what you can't see is the cloud of coal-fired pollution over the top of them. So these kids were not getting much vitamin D. And it was in England that rickets was first used, the word rickets, severe vitamin D deficiency, was first used in 1634 in the London Bill of Mortality. And interestingly enough a Dr. Whistler received his doctor of medicine in 1645. He felt that rickets was a new disease and with, I think, a fair amount of insight suggested --, probably high in vitamin D, as a potential treatment for rickets. 

It's been estimated that by the late 1800s roughly eight to nine out of ten kids in industrialized Europe had rickets. And with rickets you get soft bones, you get bowing of your legs as you're growing up. And you can see this little guy, he has bowing of his legs. And it was, in fact, so common that rickets was referred to as the English disease in the late 1800s. I'd suggest to you that maybe we've returned to the late 1800s when you see websites like this that say how to play outside. When you have to have your kids go to the internet to learn how to go out and get sun exposure, I think it is cause for concern. And when I talk to pediatric endocrinologists around the country, they are in fact seeing rickets today. So rickets is not just a historical curiosity. The kids who are having rickets today are primarily African American infants who are breastfeeding. And so the story goes that the more pigment that you have in your skin, the more sun exposure you require to make vitamin D. 

So mom is deficient, her breast milk is deficient, her child is deficient, and the kid gets rickets. So this is not just history, this is happening today. I would suggest to you that rather than thinking about these people as being cavemen, that rather we are cavemen and this is a picture of me in my usual cave. 

(laughter)

 So like most of you I wear clothing. I'm inside. We're not making vitamin D from lights like this, it requires sun exposure. When we're sitting behind glass and even if we are in the sun, we're not making vitamin D. So many of us are not getting sun exposure. Well, how about food? 

Don't we get vitamin D from our diet? And the short answer is we don't get very much. We were never supposed to have to eat vitamin D. We were supposed to make it in our skin. And I'm not going to go through the data in any great and gruesome detail but these are data from a huge study called NHANES. It's a national survey of the nutritional intake and other things in the United States. And whether you're male or female, young or old, we take in somewhere around 200 to 300 units of vitamin D in our diet per day. And we'll come back to that in a minute. Cod liver oil, some of you probably got cod liver oil when you were kids. I don't really advocate cod liver oil as a vitamin D source. 

And the reason for that is a supposition or a belief that cod liver oil probably has too much preformed vitamin A. And while it's a gross overstatement of the literature, at least one of the reasons that Scandinavia has such a high prevalence of osteoporosis and fractures is that cod liver oil or fish liver oil is still widely used in Scandinavia, and high dose vitamin A causes bone reabsorption, it causes bone loss. High does vitamin A causes rats to break their legs and rats are tough. They didn't get that place in the world by being wimpy. So it takes a lot to have rats break their legs. So you and I swim in vitamin A. We don't need more vitamin A. We don't need to be getting that from cod liver oil. Other vitamin D supplements, I think, are the way to go, and we'll get there in just a minute. If you're thinking about fish, I'd remind you that all fish are not created equal. 

You can see my friends here are very exciting about this big walleye they've caught. 

(laughter)

 And, in fact, it's often stated that salmon is a good source of vitamin D. And that may well be true, however, most of the fish, or at least many of the fish that you and I eat grew up eating Purina Fish Chow. They were not swimming off the Oregon coast. And you can see here that wild salmon has a large amount of vitamin D, whereas farm trout, farm salmon have substantially less. And maybe the way we prepare our fish also can degrade our vitamin D. You can see here that fried salmon had substantially less than baked. So I think to just say, well, I'm going to eat a serving of salmon every week and I'm going to be good as far as my vitamin D status, I don't think that you can feel confident with that. Now Wisconsin has a long tradition in the vitamin D field, going back here to Professor Steenbock. 

And many of you probably recognize Steenbock as a hall down on campus here. This is from his original publication back in --, and this is a picture of Dr. Steenbock irradiating rats. And what he discovered is that when you irradiate the animal or you irradiate their food that you create vitamin D and you prevent the development of rickets in these animals. So that discovery led to the fortification of food back in the 1930s. So a number of foods were fortified. Bread was fortified. And 1933 was a big year in Wisconsin. It was the year that Prohibition was repealed, and perhaps more importantly, vitamin D was fortified. So milk was fortified and that led largely to the eradication of rickets. 

And I think you'd expect Wisconsin to be at the cutting edge of fortification so you see that Schlitz fortified beer. 

(laughter)

 It subsequently has been felt that beer is not necessarily a health food, and so beer is no longer vitamin D fortified. So these good Green Bay Packer fans could conceivably be vitamin D deficient. 

(laughter)

 What is vitamin D fortified? Not very much. And there's not very much vitamin D in our fortified foods. So almost all milk is fortified with D, but it's only got a hundred units per serving. Some breakfast cereals have D, some milk substitutes have D, not all yogurts. 

You have to read the fine print. If you're eating yogurt and you want to use that as a vitamin D source, you have to read the fine print. Most cheeses do not have D. And, again, the dose is woefully low. As a result of that, there's lots of data out there that looks like this. These are folks who came to our research program a couple of years ago saying I'm interested in osteoporosis and we measured their vitamin D levels. And using the accepted cut point of 30 nanograms per mill, roughly two-thirds of these women were low in vitamin D. So this is an endemic problem here in Wisconsin. And it's not just here in Wisconsin, it's planet-wide. These are almost, well, what, 2600 women. 

These are women who have had the diagnosis of osteoporosis. So you would think that they had been tuned in to the importance of calcium and vitamin D and bone health. And despite that, 64% had low vitamin D. So this a planet-wide phenomenon because we're not out in the sun. We have the audacity to wear clothes. We use sunscreen widely. It's not in our diet. We don't use much supplements. And I didn't mention this but it's, I think, important to appreciate this is that our skin becomes less efficient at making vitamin D when we are out in the sun with advancing age. So because of that, it's extremely common to see low vitamin D status. 

And importantly, I think, and I'm not going to through the data in great detail, but it's getting worse. So these are data, again from NHANES back in 1990 and here in 2000. This is the percentage of folks who had adequate levels. Here it was 50%, in 2000 it was down to about 25%. And for African American individuals, almost nobody has adequate levels. Well, how can things be getting worse? Three reasons, I think, explain that. Number one, it's the super-sizing of America. So as you're well aware, many of us are getting heavier. There's more of us. 

We have a bigger body to distribute vitamin D in. And that's what this shows. The average body mass index has gone up. The proportion of folks that almost never drink milk has gone up. And the proportion of folks who always use sun screen or avoid the sun has gone up. So we're bigger, we're drinking less milk, we're having more sun avoidance, and, therefore, vitamin D deficiency is actually getting worse. How much do we need? I'd remind you that the current recommended intake is 400 to 600 IUs per day. This was back now five years ago, and these are the big names in the field. And this was just expert opinion. 

They were sitting around a table, what should we be telling people? And they recommended that we aim for 30 nanograms per mill for a blood level, and they felt that that would require about a thousand international units per day. Even a thousand is probably conservative. Dr. Robert Heaney is down at Creighton. He's been at the forefront of osteoporosis nutrition literally now for over 50 years, and he likes to create models. And he modeled how much vitamin D we should be having for a recommended intake and he suggests it should be 2600 units per day. And many of you probably have heard the name Hector DeLuca. Dr. DeLuca has literally been at the forefront of vitamin D research now for 60 years. 

He still very active in the field. And in this room a couple of years ago he stood up to a population much like you and said all of you should be taking 2,000 to 4,000 units per day. So this 400 that is our current recommended intake is probably woefully inadequate. Now, who sets the recommended intakes? That's the Institute of Medicine Food and Nutrition Board. They have not pontificated about vitamin D since the mid-1990s. They are back at the table now. And we expected the report in May of this year. Obviously May has come and gone, and they didn't get the report on time. That is not surprising. 

The word on the street is that they are going to only raise the recommended intake up to 800 or maybe a thousand. And I understand that. They're making recommendations for hundreds of millions of people. You need to be conservative, you need to stay within the data. But what I expect to see happen is that we go to 800 or a thousand and then we go up again, and we're going to see the vitamin D intake step up probably over the next decade or so to somewhere around Dr. Heaney's 2600 units per day. I think that's where we're going to be heading. Can't you get toxic? Sure. You can get toxic with anything. 

If you drink enough water you will die. Moderation. So yes, you can get too much vitamin D. I'm not going to go through the data, but I think the punch line is down here. Poisoning with vitamin D reflects misuse on an industrial scale. You've got to try. You've got to be taking a lot. Somewhere over 40,000 or 50,000 units per day. So we've got a big window of safety with these 2,000-3,000 unit recommendations. You can read that this is all you need to do. 

Walk outside with your hands and face exposed for 15 minutes and everything will be good. Amazingly enough, we're not all the same. How's that for rocket science? 

(laughter)

 And this study, I think, shows this. This is the most fun research study I've ever done. Believe it or not we went out to Honolulu and recruited surfers. 

(laughter)

 Somebody had to do it. 

(laughter)

 It was tough, but somebody had to do it. 

(laughter)

 So we put up a sign in a surf shop that said, hey, are you out in the sun more than three hours a day, five days per week? If so, come on in and give us some blood. And these kids came in, and they were folks who pretty much had no visible means of support. These were kids who were out on the surf all day, riding the waves. Their skin was dark brown. And amazingly enough, not all of them had high levels. The numbers were not big enough, but it turns out that at least the majority of the kids who were lower said, I'm Asian. Remember Hawaii's highly multiracial. 

And I think that this suggests that there's probably genetic differences in how we degrade vitamin D. We don't have that figured out yet. But I think the take home message is obvious, that we're not all the same. And another take home message is that just walking at lunch doesn't guarantee that you have optimal vitamin D status. I think that that means that we need to take vitamin D supplementation. What should we be taking? Remember there's two flavors of vitamin D. There's vitamin D2 and vitamin D3, and the structure is shown here. I think it's not important, but just recognize that there are differences and that you and I make vitamin D3 when we're out in the sun. Humans are designed to run on vitamin D3. 

It doesn't surprise us, I don't think, that we probably have a better response to vitamin D3. There's a number of easy ways to remember you want D3. It often doesn't say D3 on the bottle. You have to turn it around and get the bifocals out and read the fine print. The third letter of the alphabet is a C. Cholecalciferol starts with a C. You also can remember that chocolate ice cream is better than vanilla so you want chocolate. 

(laughter)

 These are data from our group. It basically says that both D2 and D3 work, but D3 works a little better. 

D2 is not terrible, D3 is just a little bit more potent. Most of the supplements that are out there are D3. If your healthcare provider writes you a prescription, however, for high dose vitamin D, 50,000 units, in the United States it's going to be vitamin D2. I can write a script for D3, it cannot be filled. We don't have it available. I see no evidence that pharma is going to be bringing vitamin D3 in a prescription basis, largely because there's no money to be made. Vitamin D is too cheap. So we're stuck with D2. So when your doc writes a script, don't say I want D3 because we can't get it. But if you're buying it over the counter, D3 is the way to go. 

And again, just like the sun, we're not all the same. These are data from people over age 75 who received 1600 units of vitamin D per day. And you can see that some of them have a robust increase in their levels, some of them go up a little, and some of them actually went down. So it's not a one size fits all deal where here's the right dose and everybody takes it. I see this fairly commonly where people say, I'll just take that 50,000 high dose once a month, that's got to be plenty, right? It isn't. When you just take a big blast of it, the levels go up, they promptly fall off, and at the end of a month your blood level has gone up by two nanograms per mill. So if you started low, you're probably still low. So 50,000 a month is not an assurance that you're going to be good. And unfortunately, I can't guess what your level is going to be. 

Again, I'm not going to go through the data, but this was just a simple clinical questionnaire where we said are you eating fish, are you taking supplements, do you drink milk? Something that's clinically applicable and easy and can I guess your vitamin D level? And the answer is no. And I don't find that surprising. I can't look at you and guess your cholesterol. I can't look at you and guess your bone density. I can't look at you and guess your blood pressure. And you know what? I can't look at you and guess your vitamin D. So if you want to know what a person's vitamin D level is, you need to measure the blood test. 

When you've done that, how much is too much? And here I think the highly sun-exposed folks, if you will, the naked apes are telling us what the answer is. And when you look at the published literature, here's our three highest. Surfers, farmers, construction workers in Omaha. They basically run between 65 and 80 nanograms per mill. I see no reason to push beyond that. You can find evangelical types on the internet that say we should have levels of 100, 115, 120. We can't get there by normal human physiology. I don't see reason as a physician to push people above those kind of levels. I'm certainly not concerned when I see someone with a level of 80 or even 100, but I think that to strive for that doesn't make a lot of sense. 

I won't go into this in any detail but there are approaches out there where your doctors can say we want to fix our vitamin D status, we're going to give you a large amount of vitamin D, and we're going to fix it right now. That is safe. So if you feel like someone is giving you mega doses of vitamin D for eight weeks, 12 weeks, a month, whatever, it's safe. It fills up the tank. Amazingly enough, for a vitamin or a mineral or a medication to work, it needs to be taken. Now the father of American medicine is pictured here. This is Sir William Osler and Sir William said that the desire to take medicine is the greatest feature distinguishing man from animals. 

(laughter)

 Well, when one argues with Sir William, you're probably treading on very thin ice, but I would suggest to you that vitamin D tablets on the shelf don't improve our health. 

(laughter)

 And we don't take supplements. These are data demonstrating that. The Women's Health Initiative study, this was this huge study of estrogen, most of you have probably heard of it. This was an atypical population to begin with. These were motivated women. They had an excellent calcium intake. They had an excellent vitamin D intake. And in spite of being a motivated population, only 60% of them took their calcium and vitamin D. Other data suggests that daily use of a dietary supplement happens in about half of our population, and the regular use of a multivitamin is only one out of three. So I'm not at all confident that simply attempting to supplement the population is going to fix our vitamin D status. 

And I actually like the radical concept of food fortification. This was a nice little study that Irina Haller reported recently where individuals received a cookie with 2,000-2,200 units of vitamin D in it per day. And the increase in vitamin D with food is identical to the increase of vitamin D with supplements. I'm hopeful that when the Food and Nutrition Board comes out with their increase recommendation that we'll see an increase in the amount that we can be putting in fortified foods. That's the way that we're going to have to deal with this on a population basis. And amazingly enough it does work. So we've done that. What's going to happen? Is this going to be the fountain of youth? I think it's pretty clear that vitamin D supplementation is good for bone, it reduces osteoporotic fractures, it also reduces falls risk. 

And I'd remind you that osteoporosis is still under-diagnosed and incredibly common. Roughly half of women will sustain fragility fractures in their lifetime. And while we think of this as a disease of women, it simply is not so. About one in four men will sustain an osteoporotic fracture. So this is not something that is just a disease of women. And this is just a picture, actually our last two Popes have had osteoporosis based upon fractures. I think what goes around comes around. It isn't surprising or it isn't a new idea, rather, that vitamin D is good for bones. Here's a cute little study back from 1989 documenting that high dose vitamin D, 50,000 units three times a week dramatically increased bone density. I'd love to see this study repeated, I don't believe that it's going to be. 

Now the interesting news, when I went to medical school I learned that vitamin D was important in calcium homeostasis. It was important for rickets and bone health and that was it. And now it's really clear that vitamin D has other effects outside of the bone. And that isn't surprising. We have receptors for vitamin D in virtually all of our tissues, and we have the enzymes to make active vitamin D. Those are called the 25-hydroxylase and the 1-hydroxylase, but the machinery can make active vitamin D is present virtually in all of our tissues. So what we need in each tissue is probably being made locally. It's not that it's being made by the kidneys and coming in. So our brain is probably making what it needs, our muscles are making what they need, etc. Here's a nice example of the importance in muscle. 

If you're really vitamin D deficient, you have profound weakness of the muscles. Has to be severe deficiency. It's not just this little borderline stuff that's really common. But with severe deficiency, this lady was having mal-absorption. She couldn't get out of her wheelchair. She was treated with vitamin D, and she got up and said, "Thanks, Doc," and walked away. Uncommon, but it does exist. And a lot of data out there, again, if you make muscles stronger, guess what, you don't fall down. And falling down is bad. So there's pretty good data that vitamin D reduces falls risk. 

And there's, again, people that I think perhaps are a little too evangelical that say vitamin D is important in physical performance. And these folks suggested that the level should be 50 nanograms per mill. We don't know what that level should be in older adults, and we're in the process, actually, of just starting a research study to look at that where we're going to correlate vitamin D status with physical performance. And we're going to be using a new tool called jumping mechanography where, believe it or not, we have adults over age 70 jump on a force platform. The oldest person that we've jumped so far is 92. I think it might have been this gent. And you see he's not Michael Jordan. He went about an inch. But this is a computer program that generates a measurement of force instantaneously, and I think it may be more quantitative than our current functional assessment tools. If you're interested in this study, there is a handout on the table out here and you can give us a call at that number and we'll be happy to talk to you about it. 

Now, how about cancer? This is not a map of the republicans and democrats. 

(laughter)

 The red here are higher areas of colon cancer mortality. And you can see the clusters in the Midwest and the northeast. Now there could be lots of reasons for that, but one of the potential reasons is potential ultraviolet exposure. And that's what these black lines are is how much ultraviolet you can get. And you can see areas of the west, the high plains, particularly, have a lower risk. Is that due to vitamin D? I don't think anybody really knows. 

But there is one nice perspective study that got virtually no press. And this was a study that Joan Lappe did down at Creighton and published a few years ago. It wasn't a huge study but it wasn't tiny. It was 1200 women, average age 67, and they got 1100 units of vitamin D. And at the end of four years, there was a 60% reduction in cancer risk. Why a 60% reduction in cancer risk was not newsworthy, I'm not quite sure, but our lay press did not pick up on that. And that's good enough for me. If we're doing good things for falls, fractures, muscle strength, and cancer, vitamin D doesn't have to be the fountain of youth. I think optimizing for those outcomes is adequate. I do want to share with you a study that I haven't seen yet because it hasn't been published yet. 

But it was done by some excellent investigators in South Carolina. It was reported last month in a pediatric meeting. Now, as you heard, one of my union cards says I'm a geriatrician so I don't deal with that pregnancy disease anymore. And I'm guessing that most of you don't either. 

(laughter)

 But you probably have family for whom that's an issue. And I think that these data are really pretty compelling. And so what they did was they investigated 350 women who were pregnant. At the end of their first trimester, 12 to 16 weeks, they were randomly assigned to receive the current accepted dose, 400 units of D or 2,000 units of D or 4,000, daily, and their levels went up as you'd expect. And at the end of the study, preterm labor, preterm birth, and maternal infection were reduced in the women taking 4,000 units per day. 

And so these investigators, in their abstract at least, are recommending 4,000 units per day for all pregnant women. This is preliminary but I think it's noteworthy, and it's a well-done study worth sharing. Having said that, that's, I think, about all the farther our data really allows us to go. But you can find reports in the press and in the medical literature linking vitamin D with everything from soup to nuts. I probably should alphabetize this. It doesn't quite go from A to Z but it almost gets there. And I would suggest that rather than simply believing all of this stuff, we need to be objective, we need to step back and think clearly about this. And when you see reports that vitamin D is going to prevent swine flu or that vitamin D is going to prevent aging, you probably know that that is wrong. And I feel like we've been here before. We've heard that vitamin A cured everything, we've heard that vitamin C cured everything, we've heard that vitamin E cured everything, and then we get other studies that say, "Well, wait a minute." 

And I think we should learn from that and not set ourselves up for failure because vitamin D is not going to cure everything. It might. There might be some evidence with all of these things, and I'll share that with you right now, but let's not expect it to prevent aging. I think these sort of things are fascinating and there's a fair amount of evidence out there relating low vitamin D status to a higher risk of heart attack. And there are some reasons to believe that that might be the case. It may be that vitamin D, through its role in the immune system, is involved in inflammation. And so if we're low in vitamin D, potentially we could have more inflammation in our arteries, and that might contribute to the development of heart attacks and strokes. Diabetes, huge epidemic of diabetes. Lots of good physiologic reasons to think that maybe it's the case. I just wanted to share this with you. 

This is type one diabetes, this is juvenile diabetes. And I think this smile is just a fascinating concept. This is the equator right here. So the incidence of type one diabetes near the equator is practically zero. And it goes up whether you go north or south of the equator. Could be lots of reasons but maybe it's vitamin D. And there's lots of interest in diabetes. Again, I won't go through this in detail, but animal and human study support the notion that vitamin D might decrease diabetes. It's still a notion. We need more research but maybe. 

And if so, obviously very important. How about macular degeneration. Bad problem. Most common cause of blindness in older adults. Don't really have a cure. Again, observational data suggesting that the higher your vitamin D status, the lower your risk of macular degeneration. We need more data. This one actually concerns me. And this says that low vitamin D status is associated with higher risk for death. And I think we've seen this sort of thing before, and it suggests to me that we have a marker of I'm sick. 

So if you're sick for whatever reason, maybe you're more likely to die. And if you're sick, you're probably not out on the nude beach. So you're probably vitamin D deficient. And I wonder if that's not, this association is not what we're seeing with a lot of these other diseases, and it's not clear which came first, the chicken or the egg. So I think that this is true, that it's unclear whether vitamin D is a cause or a consequence of a poor health status. And I found this quote from almost a hundred years ago now, but I think it's still just really, really true. "For every complex problem, there's a solution that's simple, neat, and wrong." 

(laughter)

 So where are we at with vitamin D today? D inadequacy is extremely common because of our lifestyle. 

We're not making it in the skin. We need at least 1,000 to 2,000 IUs per day with the caveat that we're not all the same. Not everybody needs the same dose. Clearly you can take 1,000 to 2,000 without concern. I think it makes sense to use D3 because that's what we're designed to run on, and it's a little bit more potent at maintaining our blood levels. Those doses are safe. Walking at lunch doesn't fix it. It is clearly not the fountain of youth. But it probably will reduce osteoporotic fractures, falls, maybe cancer, and potentially a multitude of other diseases. And I thank you and I'll be happy to take any questions. 

(applause)