 So I'm going to start out today by talking for a few minutes about vitamins A, D, and K, and where we get them in food. And probably for a lot of you that will be reviewed, but I think it's good not only to get everyone on the same page, but also to start out that way so that we stay from the get-go grounded in what are the practical realities of how we can use this information as people who are interested in diet and lifestyle. So vitamin A comes depending on how you use the word, it can come in two forms. The form of vitamin A that we need in our bodies for all of the functions that I'm talking about today is called retinol. It's only found in animal foods. And by far and away the best source of vitamin A is liver. That's because all other animals like we do store the main vitamin A storage in our liver. And that's true for fish as well. So the livers of fish are rich in vitamin A and one way to get vitamin A is to consume cauliflower oil. There are smaller amounts that are found in butter and egg yolks and other animal fats as well. But if you think about butter and egg yolks these are the fats that are really important to the reproduction of animals. And so if you think about an egg, that egg has an enormous task in front of it which is that inside it is incubating what's going to become a chick and that developing chick has no opportunity to eat anything until the shell hatches. So the egg has to contain a very rich supply of nutrients that's going to support that entire development. And if you think about milk products, milk products are really the only food on the planet that's actually designed to be a food in the sense that the mother cow or whatever species it is is making that milk specifically to nourish a young calf through development. And for the same reason, this is much more reliably going to have vitamin A as well. Now that of course all depends on the diet of the animal. So if you have animals that are raised on pasture and have greater access to vitamin A precursors in their own diets they will also be richer in vitamin A. We all are familiar with carotenoids from carrots. In general red, orange, yellow and green vegetables are very rich in carotenoids that can be about 10% of the carotenoids that are known can be converted into retinol. In general if the plant is any of those colors that's a reliable source that it contains pro vitamin A carotenoids. However the ability to use carotenoids as sources of vitamin A is highly variable and it's not really reliable because as you can see on the screen there are a large number of not only circumstantial health related factors or factors related to how you use the food but also factors like genetics that are pretty much out of our control. So if you look at the different types of foods they all have different matrices and that affects our ability to convert carotenoids to retinol. And so that range tends to be three to 25%. If you take something like vegetables it's gonna be closer to 3%. If you take something like red palm oil it's gonna be closer to 25%. And if you take fruits it's gonna be somewhere in between. Now we can control the bioavailability for example by cooking those fruits and vegetables or by pureeing them and that will allow a greater conversion of those carotenoids to retinol. However there's a bunch of things that are more or less beyond our control or are very difficult to control. So if you look in the bottom few bullet points you can see that dietary fiber, parasites, toxic metals, oxidative stress and deficiencies of iron, zinc or protein or hypothyroidism can all decrease the conversion. And then conversely you can increase the conversion with dietary fat, vitamin E or a deficiency of vitamin A. And this last point is what many people refer to when they say that carotenoids are the preferred form of vitamin A because you only make as much into retinol as you need. And that's true because if you're deficient in vitamin A your body's gonna say, oh, we need a lot more vitamin A let's make more of this enzyme that makes that conversion. But what if you're deficient in vitamin A and you're also deficient in iron, zinc and protein and you also have intestinal parasites and so on and so forth then that's not gonna be an adequate source for you. And if you look at, it's not that relevant to us most of us but if you look in for example the developing world you actually see a profile of protein, energy, zinc and gastrointestinal parasites that makes it very difficult to obtain vitamin A from those foods. And then finally, the genetics is the factor that's totally beyond our control. Our knowledge of this has been increasing rapidly over the last few years but what we see so far is that if you take for example people with European ancestry about half of those people will have their ability to convert carotenoids to retinol cut in half compared to the other half. And within that half, the majority of them being about one third of the total have that ability cut fourfold. So you take half of people with European ancestry and you give them a certain amount of carotenoids and they'll make a certain amount. And then you take a third of people with European ancestry that same amount of carotenoids they'll make four times less. So that's a huge difference that's well beyond our control. And the groups that are discovering these polymorphisms are always publishing new data about new polymorphisms. So we're really not at all at a point where we can definitively say oh you're a good converter, you're a bad converter and so on. And of course regardless of your genetics they're operating in the context of all these other things. So in my opinion it makes the most sense to at least get basic adequacy of retinol and then also eat a diet that's rich in red, yellow, orange and green vegetables. But if you are trying to get all of your vitamin A from colorful vegetables then it's kind of a lottery. You may be getting that and you may not be. Vitamin D is we all know we make from sunshine. It's also in cod liver oil, fatty fish and smaller amounts in butter and egg yolks. I would say the data is not very rigorous at this point but there are some cases where farmers have been sending in pastured egg yolks to I believe the magazine was called Mother Earth News that did some analyses of pastured egg yolks and the amount of vitamin D that's in the egg yolks actually makes them competitive with fatty fish. So if these foods at the bottom are from animals that are raised on pasture it may be the case that that term smaller is less significant and they're actually competitive with these other foods. If you look at vitamin K we can break it into two forms, vitamin K one and vitamin K two. Vitamin K two is further broken down into many sub forms and it's not necessary to go into great detail about the sub forms but it will come up as relevant when I talk about the mechanisms by which fat-soluble vitamins affect sex hormones. So I will talk about it a little bit here and if you take leafy greens as an example because vitamin K one plays an essential role in photosynthesis, the greener the plant the more the K one and then animals will eat that vitamin K one and they'll convert a portion of it to vitamin K two and so you can again connect this to animals raised on pasture. If cows are eating grass they're getting a lot more K one in the diet than if they're eating corn for example. Now the conversion to vitamin K two is also like carotenoids it's highly variable and somewhat unreliable. I would be really surprised if there was a lot of genetic variation in cows because cows tend to rely almost exclusively on plants for this. I don't know if there is but if you look at humans and you look at rodents and you look at birds you see an enormous variation in the ability to convert vitamin K one to vitamin K two. So this introduces kind of a confounding because I'll talk about the importance of getting K two specifically but it's sort of like vitamin A like you may sort of win that lottery and maybe you're a good converter of K one to K two so maybe you can get by with mostly leafy greens supporting those systems but based on what we've seen you probably can't and I'll go into a little bit more detail about why I'm saying that later. But vitamin K two is also made by bacteria and that means it also comes up in fermented foods and it also is produced in the intestines. Now it's really unclear whether the microbiome in humans actually contributes to nutritional vitamin K two supply. I would say the evidence on the whole is that it does not and that's partly because when the bacteria make it they make it inside their own membranes and you would actually have to digest and destroy those bacteria to release it and then absorb it and they're also doing that mostly in the colon beyond where we would absorb vitamin K in the diet so I really doubt that that's relevant. However it's super relevant if you're an animal that's copper phagic for example if you're a rat that poops and then eats it or it's super relevant if you, I don't want to like detract from the palatability of your sauerkraut for lunch but it's kind of an analog right? When we take a food and then we ferment it with bacteria and then we eat it that's kind of an analogy there. Anyway that will add vitamin K two and then the fermented food will be rich in vitamin K two and sort of the grand example of that is natto which is a food in eastern Japan that the most people in here probably wouldn't want to eat more than a little tiny bit of if that because of its gooey texture and it's a very strong taste and smell but it is the highest known source of vitamin K two that there is. But if you look at what most people are eating most people are getting their vitamin K two from egg yolks and cheese and cheese is a really interesting example because it synthesizes all of this information. So when the cow eats vitamin K one in the grass some of that vitamin K one gets into the milk. Some of it is converted to vitamin K two and the K two goes into the milk. Then we take that milk and we ferment it into cheese and the bacteria make more vitamin K two and then the cheese winds up having that all that diversity of vitamin K forms. Now egg yolks just happen to be rich in it and people eat a lot of eggs and so that's why they're important and you won't see that. In eggs you will see that the vitamin K two is basically exclusively a form called MK four, menaquin on four and that's really important because that represents the fact that all animals including humans to the extent we convert K one to K two we convert it exclusively as MK four. Whereas if you look at fermented foods you'll see a lot of other different types of vitamin K two and the predominant one is generally MK seven that you're seeing in those fermented foods. And if you look at supplements in the market you'll see MK four, you'll see MK seven and so on and so forth. And the reason that this is interesting is because there's some pretty convincing evidence that although what we most understand about vitamin K those forms all overlap in their function to a certain degree. There are some specific functions of vitamin K that are only emerging now that seem to be exclusively dependent on MK four and that would explain why animals including us when we turn K one to K two exclusively make MK four. And in fact it's not just K one but we could also consume MK seven and convert a portion of it to MK four. We could consume any of the other meniquinones that are in fermented foods and convert a portion of it to MK four. So basically any vitamin K can be converted to MK four and MK four is the only form of vitamin K that humans will synthesize. It's the only form of vitamin K that chickens will synthesize and on down the line. So we'll come back to vitamin K related mechanisms and it'll become clearer momentarily why that's important. So there are actually a number of different mechanisms that can be involved here. And one thing that's known and that's been known for a long time is that the active hormonal forms of vitamin A and D which are retinoic acid and calcitriol both of those independently will act on gonadal cells to increase sex hormone output. And that's known from inducing deficiencies in animals and repleting those deficiencies and it's known from just taking gonadal cells and dropping the active hormonal forms of those vitamins on them and seeing what happens. Now, it's my guess that these mechanisms are not relevant to most of us in this room. And so I'm not gonna go into detail about what they are. But I'll mention briefly that if you take the animal experiments of the vitamin D deficiency, most of the evidence indicates that you have to make the animals hypocalcemic to compromise their sex hormone production through that specific mechanism. Hypocalcemic is a profound deficiency of vitamin D. If you take someone with early rickets, their serum calcium levels will be within the reference range but towards the bottom of it. They will have to progress to severe rickets before serum calcium drops below the bottom of the reference range. So when we're talking about these experiments, we're talking about animals that were made really, really, really deficient in vitamin D. Vitamin A, I'll show you momentarily a study that demonstrates how this is very compelling when you have someone who's deficient and when we view that study, you'll see why you probably have to be really deficient for that mechanism to be important. Before doing that, I want to review a few of the other important mechanisms. So I alluded to the fact earlier that Mediquinone 4 has some specific physiological roles in our metabolism and one of those is to increase the expression of the enzyme CIP11A, which is the enzyme that converts cholesterol to pregnenolone. And that is the first step that's involved in the committed synthesis of all the steroid hormones, including the sex hormones. And so this can be relevant, clearly relevant to producing enough hormones and probably relevant to contributing to the right balance of hormones as well, because, let me skip that thought. Okay. Moving on, there's one other mechanism that's important. And I'm gonna tell you the clean story and then I'm gonna explain why this clean story is actually the dirt on another dirty story. So if I were to ignore everything that everyone else had ever said about osteocalcin until Gerard Carcenty's lab started discovering what I'm showing you on this slide over the last decade or so, the story looks like this. Actually, his story starts over here and I'm adding this part. Okay, so what I would add to this story is that vitamins A and D synergistically cooperate to increase the expression of a protein called osteocalcin that's primarily made by bone cells and thus the name osteo. And it binds to the extracellular matrix in bone, which is mostly calcium, thus the term osteocalcin. And if you take cells and you just put a little bit of A on them, you just get a tiny bit of osteocalcin, same thing if you put a lot of A. If you just put a little bit of D, same thing. But if you put A and D together, you get a massive increase in osteocalcin. So this is a synergistic response. The osteocalcin that you get from the combination is far greater than what you get from adding the effect of A alone to the effect of D alone. Now, if you don't have vitamin K, you won't carboxylate, which we could often think of as an activation process. You won't carboxylate that osteocalcin. And carboxylation in this particular case is what it allows it to bind to the bone matrix. Once it's in the bone matrix, during the process of bone resorption, it gets released and it gets D carboxylated to form under carboxylated osteocalcin. And under carboxylated osteocalcin acts on the testes in males to produce testosterone. And it acts on various tissues in the pancreas to increase insulin production and other tissues, especially adipose tissue, to increase insulin sensitivity. And so although you get higher insulin levels, you are extraordinarily sensitive to that insulin and you have an overall strong improvement in the metabolic profile. Now, I will say that you can make a strong case that this is relevant to a lot of us in this room. And that's because if you look at the general population, you'll find a lot of under carboxylated osteocalcin in their blood. And you'll also be able to correlate that, for example in men, the amount of under carboxylated osteocalcin correlates with testosterone levels. And in women, it correlates with adiponectin levels, which are part of what creates this insulin sensitivity response. And so that makes it seem really relevant. Now, I will back up and I'll explain why this story is a little bit dirtier, but actually this is the dirt on top of the old story. So the old story was that osteocalcin needed to be activated by vitamin K and that was good for the bones. And how it was good for the bones was sort of vague because if you took mice and you deleted their osteocalcin gene, their bones didn't look that bad. So this was sort of a puzzle for a really long time. And there were always these studies coming out that were using this as a marker of vitamin K adequacy. So if people had higher under carboxylated osteocalcin, we would say, hey, wait a second. No, we wouldn't say, hey, wait a second. We would just jump right in and say, oh, they must not have adequate vitamin K reaching the bone because vitamin K isn't carboxylating it. This really, now there's truth to that story because if you don't have vitamin K there, the osteocalcin will just spill out into the blood without being carboxylated. But that's far from the whole story because the under carboxylated osteocalcin when it's released during bone resorption is good and is necessary for all these positive metabolic effects. And in fact, one of the most recent studies found that under carboxylated osteocalcin is actually a critical part of the adaptive response to endurance exercise. So there's a lot coming out about why we actually need this in the blood and it really muddies the waters of trying to use that in the blood to say that person doesn't have enough vitamin K. But here's the deal. If this is supposed to come out of the bone during bone resorption to provoke these responses, it's gotta be in the bone first. And if you are not making enough A and D, you're not gonna have enough osteocalcin. If you don't have vitamin K, it's not gonna go where it's supposed to go. And it's not gonna get released at the right time to create that response to the right thing. So I would argue that this is a mechanism that's probably relevant. It's gonna be really hard to do studies about how it's relevant because you can interpret under carboxylated osteocalcin in opposite ways when you see it in the blood. But it implies that you have to have all these things together. And if you just put D in, you're probably not gonna get a robust response. Or if you just put A in, you're probably not gonna get a robust response. And I did some research in my laboratory that I haven't published yet, but I found that vitamin D alone could increase under carboxylated osteocalcin, but only when it was a massive dose that causes hypercalcemia. So you're not just gonna take 3,000 IU a day or 4,000 or even 5,000 probably and actually get this response. But maybe you would if you combined that with A and K to get the coordinated mechanism. All right, so let's shift gears now and look at a few human studies. This study is the most compelling study I've ever seen on vitamin A and testosterone in humans. And what they did was they took boys who were not undergoing puberty and they gave them either testosterone or oxandrolone, which is a synthetic testosterone-like molecule that provides a similar response. And what I'm showing you here is the proportion of the sample who had their testicles increased to the size that we would say that puberty had been induced. So if you look at six months, every column is zero except the columns where they provided vitamin A and iron, which is called nutrition. And if you look at 12 months, everything is 100% that received any kind of treatment except the control is still at zero. So vitamin A and iron not only are as effective as testosterone replacement therapy and inducing puberty, but it works faster. So on the one hand, this is absolutely remarkable because that means that in most cases where people are being treated with anabolic hormones, you may be able to just fix their nutrition. On the other hand, look at the dose that they're using. This was 6,000 IU per week of vitamin A. If that is what's providing that response in that study, then it's probably totally irrelevant to most of us in this room because that means you're only gonna get that benefit if you're not already consuming a lot more vitamin A than that. And most people who are nutritionally adequate are consuming a lot more vitamin A than that because even the RDA for most of us is gonna be around 3,000 IU per day, which is a lot more than 6,000 IU per week. So this is an incredible response in what looks like it's probably a very deficient population. Vitamin D, we know observationally that if you look at men, as 250 HD increases, so does testosterone. And it peaks at about 35 nanograms per milliliter. And then it kinda starts to go down after that. And as you see this increasing gray area, that's the variation. And so it gets more variable and we don't have as many people up here, so the increase in gray area indicates lower statistical precision. But if you look here, it looks like the main benefit that you get is 35 nanograms per milliliter. Keep in mind that the numbers on the x-axis are nanomoles per liter, so I converted it down here. Now there's also evidence that from one small trial that vitamin D alone will increase testosterone in males who have poor vitamin D status and poor testosterone status. This is really complicated, so I'm gonna draw your attention to a couple things that are on here. And one of that is that their 250 HD is increasing from 13 nanograms per milliliter to 35 nanograms per milliliter. 35 should sound familiar from the previous slide. PTH is the signal of the body's perception that the body is deficient in vitamin D and calcium. It went down from 39 to 34, so this was in the range that suppresses PTH. And so I would look at this and I would say, okay, maybe if you're very deficient in vitamin D, that works. Now the problem with this is that after this study was done, there were 12 other studies where people went back to trials of vitamin D. Yeah, I did that on purpose, yeah, thanks though. There were 12 other studies where people went back to the data from previous RCTs with vitamin D supplementation and they found that there were no effects in any of the 12 trials. So I tried to look at this and I said, okay, wait a second, probably they weren't as deficient in vitamin D. Looked at some of them, no, that's not the case. I said, okay, wait a second, maybe they didn't have low testosterone. No, that's not the case. So this is disconcerting because one of the things that you would expect from a pool of small studies is that if there's no effect, some of the studies are gonna show that there is one. And that's because if we say that, when we talk about statistical significance, we say that if a p-value is 0.05 or less, it's significant. What that means is that in less than 5% of the cases, we would expect to see that result if there isn't one. That means that if we ran 100 trials, we should see five trials where we did see that result when there really isn't one. So if there's one trial that shows an effect and there's 12 that shows there and does not, the collective evidence, unless you can find something very unique about that one trial, suggests that there's no effect. But this gets even worse. So look at the total testosterone in the first red box. The reference range for total testosterone is nine to 58. And you can see there that it went up from 11 to 13. So these guys were at the total bottom of the reference range and they moved up in a statistically significant manner to the total bottom of the reference range. So even if that's statistically significant, how clinically significant is it? And if you look at their free testosterone, which is generally thought to be the index of bioavailability, there's no statistical difference, but it's slightly higher in the placebo group. Now, I went through and I looked, okay, what about in females? And there's a significant body of literature, again, showing observational studies that aren't borne out in clinical trials. But I did find this one study that was very recent. And this was women with polycystic ovarian syndrome, 54 women, and they gave them 400 IU vitamin D, 1,000 milligrams calcium and 180 micrograms of vitamin K2. This was in the MK7 form, which like I said before, a portion of could be theoretically converted into MK4. And what you can see is that if you look at free testosterone and DHEA sulfate, which are androgens that are too high in this case, I can't see these numbers very well, but they are decreasing from 3.7 to 1.6, 1.9 to 1.1. They're basically being cut in half. That looks like a meaningful improvement in the high androgens in women with polycystic ovarian syndrome. Now, is this because they use the combination instead of one nutrient? Or is it just that the vitamin K2 is the only factor that matters here? Or is this an anomaly? And if we did 20 other studies and would find they all have no result? I don't know the answer to that question, but it looks hopeful, not only because this is the only study where they're actually putting vitamin K into the mix and actually using a mix, but also because we could worry, well, if fat-slable vitamins increase sex hormones, does that mean that it's gonna make polycystic ovarian syndrome worse since some of the sex hormones are too high? And this suggests that when you're dealing with nutrition, what you're dealing with is not to try to manipulate something up or down, but provide the body with the raw materials it needs to regulate itself. And I think that's what we should be trying to do. So I would conclude that the principle that fat-slable vitamins help increase and optimize sex hormones has very strong mechanistic support. But there's no human trial that's provided definitive evidence that a particular dose of a single vitamin in a particular context will do that in humans. And context is too variable and too important to expect any such RCT to ever do that. The likelihood that fat-slable vitamins will help in any context depends on number one, what is the specific inadequacy? Number two, are the relevant synergists present? So if you take someone who is deficient in vitamin D and not K, why would you expect K to work and not D? But if you take someone who has the opposite profile, why would you not expect the total opposite of that result to happen? So yes, I think we can get good RCTs if we're able to hypothesize and take specific samples that we say fit a context where a specific treatment will help. But if we just take random samples of people and throw vitamins at them in different combinations, I think we should get really confusing results because that shouldn't be the approach that should work if we just think about what's happening in the body with common sense. So I would say we can all try to get some midday unprotected sun exposure, not enough to burn, use fatty fish, egg yolks, preferably pastured, get calcium from dairy products, bones, leafy greens. I don't think we need a lot of data or RCTs to do that. For vitamin A, I think we should all try to eat liver once a week or maybe take clout of oil daily if you can't do that and eat a lot of colorful vegetables. I don't think we need a lot of data or blood tests to do that. For vitamin K, I think if we combine leafy greens and animal fats and fermented foods to get the diversity of vitamin K forms, especially egg yolks and aged cheese, which are the easiest ways to get it or natto, which is the most potent way to get it. I don't think we need a lot of data or blood tests or RCTs to do that. And we should keep in mind that we always want to obtain the fat soluble vitamins with a fat-inclusive meal because it's needed for their absorption. For going beyond that, I would say that I'm a big advocate of measuring PTH for vitamin D status. I don't have time to go into it now, but there's a lot of diversity in individual vitamin D needs. And the parathyroid gland is reacting to the body's own perception that vitamin D is deficient. So I think if you keep it below 30, which is the lower half of the reference range or at least around 30, that's a good idea. I would keep serum retinol towards the middle of the reference range rather than within it. I think that's a pretty good idea. I don't like any vitamin K tests that are available, but if you follow my work at chrismasterjohnphd.com or the Daily Lipid podcast and your favorite podcast app or on Facebook, Twitter, Instagram, or Snapchat, whatever your favorite, I will let you know when I approve of an available vitamin K test. With that, I'll open it up for five minutes of questions. Hi, Chris, that was really terrific. I'm from San Francisco and we've, where it's really foggy a lot of the year, then it's cold and people generally tend to not go out in the sun a lot and wear covers up. And we've started measuring 25 vitamin D levels. And it turns out that everybody is extremely deficient like levels below 10. So do you think that there's a geographic or a seasonal variability to what you're seeing or does anybody know the answer to that? Well, I think it's very well known that there are seasonal and geographic correlates of vitamin D status. One of the questions become how strong are those compared to the local pollution and the local weather patterns? And probably the latter is more significant as your case seems to illustrate. But we used to say that, you know, if you're at this latitude, it's available at this time and et cetera, et cetera. And then we started modeling like ozone and things like that. And we said, oh, actually you can get zero vitamin D synthesis at the equator sometimes. And when we take Inuit and we watch them go out side in March, all of a sudden their 250 HD increases. So maybe you can get it up there. So I really think that it has, I mean, especially in urban environments, I think the local environment is a lot more potent. So like if you're walking around in Manhattan, I don't really care what season it is. Like there's giant buildings that are upstairs Hong Kong or whatever there's, you know, tall buildings affect vitamin D status and so on. So yeah, I think that's definitely true. And if you have someone who's below 10 nanograms per milliliter, you know, maybe that's in the range where just vitamin D is gonna help. But I think that if you start with the idea that what you wanna do is a comprehensive diet and lifestyle analysis to try to find what the weakest links are, you will find the vitamin D in that sense. And you may find that in those many cases that is what you wanna work on. Yeah. Hi, Erin, I'm Kate Shanahan. I think we've met before. Thank you so much for that fascinating data stream that I downloaded from the talk. I'm glad it's in the morning when caffeine is still working. I'm dying. I thought my upload speed was working. I'm dying to know why you didn't mention anything about vitamin E, especially since, at least according to the West Indie Price Foundation, it's like the fertility vitamin. And that's the gonad. Yeah, that's a good point. So it was, so actually vitamin E is named after its role in fertility. So it comes from the Greek words, literally it means an alcohol, all that allows you to bear from the Greek word tokos and ferro to carry, so to carry and bear a child to birth. But I don't think anyone in 2016 would really say that it should be called the fertility vitamin because the reason it was named that was because when they gave animals severe deficiencies of vitamin E, they became infertile and that was the clearest link that it had. But then everything after that in the 20th century laid down the fact that actually it's the antioxidant vitamin and what it's really doing is protecting against oxidative stress. And so I think it's possible that there are people who have infertility because they're low in vitamin E. If that's the case, it's because they have oxidative stress going on and not because vitamin E plays a direct role in increasing sex hormones. More likely than not, people are gonna have relatively maybe suboptimal status of vitamin E combined with a whole host of other factors that are increasing the reactive oxygen species burden that's gonna contribute to long-term degenerative disease. Certainly I would pay attention to looking at that in infertility, but I don't think that vitamin E really follows into the same category of having these direct effects on sex hormones and that's why it didn't include it. So it's not so much like a DNA activator the way D is and doesn't affect enzymes the way K is. It's really just an antioxidant in the membranes as far as we know. I mean, it's complicated. So there's a school of thought of people who look at all these studies showing that vitamin E deficiency changes all these genes and then there's the school of thought who point out that's because oxidative stress causes gene expression changes and you actually haven't shown anything other than that vitamin E is an antioxidant. I kind of fall more into the latter camp as do most people who have like, I won't go into it. I kind of fall into the latter camp, yeah. For people who... For that came right out of the animal and either, I don't know, if you know the animal has no parasites, eat it raw or lightly cook it or something like that. So I eat liverwurst that has a blend of different organ meats with beef and makes the taste very mild and it's really easy to just take out of my fridge and eat it without doing anything to it. Other people cut up liver and freeze it to make liver pills and they eat that. Other people take desiccated liver. I think any of those things are beneficial but it really comes down to what is the form, what is the form of eating liver that you will actually do on a daily basis and consistently getting organ meats in some form and is more important than the specific way in which you do that. Okay. I have another question. So for people who... We have one minute in fairness if we could take the next one and then you and I can speak afterwards, yeah. Hey, Chris. Thank you. Hey, gotta be quick. What is... Do you know if there is any specific genetic tests that one would look at if you were mentioning carotenoid to retinol conversion and also vitamin K1 to vitamin K2 conversion? Yeah. I don't think, to be honest, I don't think even that vitamin K experts don't have a very clear idea about... I mean, we're learning now...