 I'd like to welcome everyone to our first in the Linus Pauling Institute webinar series. I am Alexander Michaels, a vitamin C researcher at the Linus Pauling Institute, and I'm going to be talking today about the essentials of vitamin C. And in the audience with me today, moderating your chat is Vicki Drake and Steve Lawson, and they will be reading questions at the end of the webinar. But we're going to start today with a short presentation and then questions will follow. So I'm going to start with a short journey at sea. We're going to go over vitamin C in the body. Then we'll look at vitamin C in human health, how to get your vitamin C, and then address quickly some of the common vitamin C myths. So to start, vitamin C, as most people know this, but it is a little bit of a controversy, vitamin C is a ascorbic acid. And I've actually gotten questions about this before. I've heard people ask me, is vitamin C, is it not a ascorbic acid? Somebody says it's not a ascorbic acid. I will try to address that later. But really, by definition, vitamin C is a ascorbic acid because it can prevent the deficiency of the vitamin, which is scurvy. And we'll talk about that in a minute. So the journey of vitamin C really starts, of course, with the foods you eat or the supplements you take. But the first step in that journey, after passage to the stomach, is going to the small intestine. And in the small intestine, there are villi, which are responsible for the absorption of vitamin C. And these are these finger-like projections that you see in the right-hand side of the slide. Now, on the surface of these villi, if you look closely at them, in the cells, there are transporters specifically for that recognize ascorbic acid, which is the reduced form of vitamin C, and dehydroscorbic acid, or the oxidized form of vitamin C. So when you consume vitamin C, and if it happens to get oxidized along the way, that's OK, because there are transporters that can take up either one. And these will accumulate vitamin C through the cell, and then they will get into the bloodstream. And this is the absorption process for ascorbic acid. Now, if you take too much vitamin C at one time, these transporters actually get swamped out. So you will get a maximal rate of absorption depending on how much vitamin C you take. The rest of the vitamin C that isn't absorbed by the small intestine passes on through to the large intestine and eventually exits the body. So the key thing here is to remember that there is a limit to vitamin C absorption. And vitamin C uptake will occur for a short period of time in the body, and depending on the concentration of vitamin C you're given or taking. So vitamin C, after it's absorbed, I said passes through this small intestine into the bloodstream. And from the bloodstream, it then passes to all the tissues of the body. So when we are looking at someone taking a dose of vitamin C, whether it's through supplementation or food, we actually get a slow increase in blood ascorbic acid level. And I'm showing that here on the graph on the right. It accumulates up to maybe two or three hours after you take a dose of vitamin C and then kind of plateaus. It levels off. During this part of the absorption profile, I guess is what you can call it, vitamin C is circulating to every tissue in your body and being accumulated into those tissues. So this plateau that we're seeing is the tissues and cells of the body responding to this large dose of vitamin C or this any dose of vitamin C and then accumulating it. Now, this slide is a little busier, but it does represent all the tissues in the body that we have known levels of vitamin C for, including the high accumulating tissues like the brain and the eye and the adrenal glands. But even the skin, lung, liver, every tissue in your body has vitamin C and every cell in your body has vitamin C. However, they take up vitamin C at different rates. Now, these graphs on the right are meant to demonstrate the rates of absorption. I noticed that there's no numbers on them. This is kind of just a representation of the rates of absorption. And if you take vitamin C many times, if you're deficient in vitamin C, I should say, and you take vitamin C over and over and over again, your tissues will accumulate at different rates and they'll saturate, they'll reach a maximum level at different times. So the brain tissue accumulates vitamin C very rapidly, preferentially over every other tissue in the body. White blood cells, on the other hand, kind of have a moderate absorption profile. And then other tissues, such as the liver, heart, or kidney kind of are the last to saturate with vitamin C. But again, this is after days and days of absorption and we'll talk more about what determines this, what levels of vitamin C you have in your body. Actually, I already kind of mentioned it. It's the plasma. How much vitamin C is in your blood? And we call that the steady state level of vitamin C in your blood determines what levels of vitamin C you have in your tissue. On the bottom, I've noted the brain and eye, which are kind of the highest levels of vitamin C found in the body. And then we also have the blood cells, the circulating cells. There's only one, every cell in your body actually accumulates vitamin C through the sodium dependent vitamin C transporters. That's what they're called. The acronym is SVCTs. The red blood cells is the exception to that. It does not have any SVCTs and actually has one of the lowest levels of vitamin C in the body. They accumulate vitamin C through the glucose transporters or glutes. And while every other tissue has vitamin C, what's called in the millimolar range, the red blood cells have vitamin C levels in the micromolar range. Now, what happens after you've taken a certain dose of vitamin C, after this initial absorption and distribution to all your tissues? You get, once vitamin C reaches the kidney, it actually is constantly being filtered from the blood by the glomerulus. This is a part of the kidney's nephron that's involved in filtering of the blood, urine production, and getting rid of compounds your body doesn't need. Now, there are cells within the nephron just after the glomerulus. It's a cell type in the kidney proximal tubule that is involved in the reabsorption of ascorbic acid. When you take vitamin C and it goes through your bloodstream, it will constantly be filtered by the kidneys and then the transporters take it back up again so that you don't lose vitamin C constantly. However, when these transporters in the proximal tubule get swamped out, that's when you start urinating out the excess vitamin C. And this happens when your plasma levels kinda get close to 50 to 60 micromolar. And if you look at the profile on the right, you see that vitamin C absorption occurs for a short period of time and then comes down. Sorry, I should use the pointer here. It comes down after the maximum absorption is reached. This is not only distribution to the tissues but it is excretion by the kidney. The kidney is trying hard to get vitamin C levels back down to the level that the transporters are saturated. And if you look, if you take vitamin C doses, a large dose of vitamin C, you actually see more and more of that vitamin C being excreted into the kidney. Now that doesn't mean that that vitamin C didn't have a chance to reach all your tissues and get accumulated in the process but taking multiple doses of vitamin C will result in more of that vitamin C being excreted to the kidneys as it gets filtered over time. Okay, next. So the conclusions of this journey, so this is, I mean, we've gone everywhere from ingesting vitamin C to absorption in the intestine, distribution throughout the body and the tissues and then finally we're at excretion through the urine. So the conclusions of this small journey is that vitamin C has a limited absorption in the body. There's a limited amount that can be taken up into the tissue. The blood supplies vitamin C for every other tissue in your body but the tissues take it up at different rates. And then when vitamin C reaches the kidney, it is constantly lost and re-up taken up again, re-up taken, but anything that can't be taken up by those transporters gets lost into the urine. Okay, so as vitamin C researchers, we are often concerned about what we call vitamin C status. Vitamin C status is determined and we've basically gone through all the measures of determining vitamin C status. We've realized that measuring how much vitamin C you eat is not a very good marker of vitamin C status. The best marker is actually how much vitamin C is in your blood. And this is partially because of what I was talking about before when we're saturating tissues, trying to get vitamin C to be maximal throughout your body. So we've actually categorized different plasma levels of vitamin C. I should say that this data here is kind of representative of data that was presented by Mark Levine at the NIH but it is used kind of as the benchmark for all vitamin C studies. And so we have different categories of vitamin C status, the lowest being deficiency. And of course vitamin C deficiency is when you have all the bad things happen, like scurvy, which we'll talk about in just a minute. And this is kind of really, really low intakes of vitamin C. I mean, the estimates are that scurvy can be prevented in most of the population by just taking as little as 10 milligrams of vitamin C a day. So we're talking about really low levels of vitamin C. However, it does happen, scurvy does happen, even in modern, not just in the developed world but also in, or sorry, undeveloped countries but also in the developed world. But then if you go beyond that, when plasma levels get above approximately 11 micromolar, you have what's called vitamin C inadequacy, levels of vitamin C that are saturating some tissues. For example, the brain will saturate quickly when vitamin C levels increase but other tissues won't quite reach that saturation point. They'll be at levels that could be fairly low and don't allow for optimal functioning. And speaking of optimal functioning, we still have kind of this other category, the suboptimal category of vitamin C. This is when your plasma levels haven't reached saturation. Your kidneys are still able to take all of vitamin C, you're not excreting any extra and your tissues are just about to reach that saturation point, which occurs, of course, next would be the optimal levels. The optimal levels of vitamin C that you can take are ones that will saturate your plasma and allow your tissues to accumulate vitamins or to a maximum level. Now, I should say vitamin C status is usually assessed by taking someone's fasting blood, a fasting blood sample, kind of like when you go get your cholesterol levels checked. We look at after vitamin C has cleared from the body after recent supplement use or eating an orange or whatever and this is how much is left after that elimination profile that we saw in the previous slide. And this is what we use to measure to give a judge of status in the body. Now, we'll talk a little bit about the functions of ascorbic acid and this is a little busy. This is representing the oxidation of ascorbic acid. I should mention that ascorbic acid oxidation is actually key to all of its functions in the body because oxidation is an electron donation process and those electron donation issues, or sorry, the electron donation process is how vitamin C works. Now, it doesn't always work as an antioxidant. Scavenging free radicals or getting rid of reactive oxygen species is what we consider an antioxidant function. There are actually other functions that are associated with the electron donation process. So, we'll start by looking at health effects of vitamin C when actually, when we're not really concerned with the antioxidant process, we're looking at the donation of electrons to enzymes in the body. And this happens, this is a function of vitamin C that actually reaches saturation at low levels, kind of in the inadequacy range, but really becomes a problem if you get to the deficiency range. This is when your enzymes run out of vitamin C as a cofactor. And this is a condition commonly known as scurvy. This is when these enzymes run various processes in your body, just cannot efficiently work anymore because vitamin C is no longer there in adequate levels. And scurvy is characterized by a huge cluster of symptoms. Of course, the most common are loss of teeth, bleeding gums, opening wounds. You have blood vessels rupturing under the skin so you get bruising and little blood spots perpura that appear under the skin. And corkscrew, hair growth, bone deformation, those are all symptoms of vitamin C deficiency, as well as things like poor mood and depression. And some of the hallmarks of vitamin C deficiency actually relate to those enzymes that are working at suboptimal levels. And this is the three Cs, collagen, carnitine and catecholamines. And catecholamines are a class of neurotransmitter. But these enzymes that are responsible for the production or the proper maturation of collagen, the production of carnitine and the production of norepinephrine work at slower rates when vitamin C is low. There are also other enzymes that I'm not mentioning here that are involved in other various processes in the body that become affected in the deficiency range. Now, once we get beyond the deficiency range, we look at other health effects of vitamin C. And one of them is, how does vitamin C impact your gastrointestinal tract? Actually, when you're taking vitamin C, at least initially, vitamin C in your gastrointestinal tract will be really high, or can be in high concentrations. And one of the one health effects that I often tell people about, and most people don't know about, is iron absorption. Doctors really don't talk about vitamin C in its role in iron absorption. Some doctors do, but it's becoming a little more common. But vitamin C can be part of an effective treatment for anemia, not by itself, but vitamin C can increase iron absorption. Nitrates, we talk about vitamin C and the prevention of nitrate of damage from dietary nitrate, and that can actually prevent gastrointestinal tract cancers, esophageal, stomach. And then vitamin C might also have effects on the gut health and the microbiome. That's actually, unfortunately, an undeveloped area of study right now. In any case, most of the known effects or the observed effects of vitamin C supplementation actually lie at when we go from levels of inadequacy to hopefully optimal levels. That's when we see the biggest effects, and this is actually how vitamin C studies should be conducted, looking at people that go from inadequacy to optimal, not people who are already at optimal ranges and then are taking more vitamin C on top of that. But people in the optimal range do have the lowest risks of disease when we're talking about various studies that we're looking at. And there's actually one of the limitations of vitamin C studies currently is that people don't look at plasma levels. So we don't really understand if people are progressing from inadequate suboptimal to optimal levels. However, when we're talking about vitamin C at these levels, this is really where vitamin C as an antioxidant comes into play. Vitamin C is really an outstanding antioxidant. It can react with a wide range of oxidants in the body and free radicals. When it becomes oxidized into the free radical form, it is non-toxic and doesn't cause any damage to other tissues. So it actually is good because it's taking a harmful free radical and converting it into a less harmful free radical. And it can also interact with other antioxidants in the body. I realize there's a typo here on this slide. It should say vitamin E, not vitamin C. Vitamin C can reduce vitamin E and keep it in its reduced state. And this is kind of, it has been shown if you look at plasma and you expose it to an oxidant and you look at the antioxidants present in that plasma, you can see that vitamin C, out of all other antioxidants present in plasma when exposed to oxidants, depletes first. It is the first antioxidant lost in the system. Other antioxidants, such as bilirubin, which is a breakdown product of hemoglobin, urate or uric acid, which is also a plasma antioxidant, or vitamin E are only lost once vitamin C is depleted. And on top of that, once the vitamin C is depleted, that's actually when you start seeing oxidized lipids appear in plasma. So you just have this oxidant generating system that's completely suppressed by vitamin C. But once the vitamin C is gone, then the oxidized lipid products will appear. Now, unfortunately, I don't have time to go into all the data on vitamin C as an antioxidant. And a lot of the data is a little mixed and muddled because we're looking at a lot of papers that look at dietary vitamin C levels and don't look at plasma vitamin C, papers that look at multivitamin supplement use. So it's really hard to tease out effects of vitamin C. But we do, there is some evidence, and you can see a lot of this evidence presented on the Micronutrient Information Center from the Linus Pauling Institute, where vitamin C is involved in cardiovascular disease, immune function, cancer, eye health, diabetes, and even cognitive decline. And these are just contrasting the levels of high plasma vitamin C levels with low plasma vitamin C levels and seeing effects. Now, some of the evidence is stronger than others, and of course we can go into a discussion on some of that if anyone's interested. But all this data is summarized on the Micronutrient Information Center. But, and kind of, as I just said, many of these associations are associated with fruit and vegetable intake. So fruit and vegetables are more than just vitamin C, so we could be looking at multi-component functionings here. But, and I mentioned that antioxidant function is how we presume most of these effects of vitamin C occur. But there may be other mechanisms out there. The research on vitamin C has assumed antioxidant functions are the primary route, but we haven't looked for other ways that vitamin C could be preventing or preventing the occurrence of disease. We really need more high quality trials to get this work done and to make these associations. So conclusions from this section. Vitamin C status is probably the most important marker of vitamin C levels in your body. Looking at plasma vitamin C levels is what researchers use to understand and optimizing your plasma vitamin C levels are important. And vitamin C is an electron donor. That's, it's overall, you know, throughout the body it functions as an electron donor. In tissues it can help enzymes run efficiently by donating electrons that I didn't mention it, but it donates these electrons to iron and copper in enzymes to make them run at optimal rates. And then it can contribute to antioxidant production in cells and there may be other effects that we have not yet discovered for vitamin C. In relation to these electron donating activities. In fact, I should mention that intravenous vitamin C and I'll get to that in just a minute. It has an electron donating property that's a pro-oxidant effect. It actually generates harmful free radicals, but it actually, that has been shown to have been beneficial in cancer cells. Beneficial to killing cancer cells. Okay, so now I'll talk briefly about getting vitamin C. Most people know how to get their vitamin C through fruits and vegetable intake or supplements, but understanding how much vitamin C to take and how to take it might be of interest, is actually of interest to most people when they ask me about vitamin C. So the Institute of Medicine, latest recommendations for intake are for women are adults are 75 milligrams per day. For men it's 90 milligrams per day, but these are really kind of levels of vitamin C that don't necessarily cause a optimal level of vitamin C in the body. Smokers do need more vitamin C, as I noted here, low, but this actually results in vitamin C statuses that are on the, kind of on the sharp end of this sigmoidal curve. We call this a sigmoidal curve because it has an S shape to it. And when you look at 90 milligrams per day, that actually still rests somewhere in this sharp end of the curve. So you're not reaching, you may barely be at optimal levels of vitamin C, but it's kind of iffy at that point. A lot of people actually recommend taking much more vitamin C than that. Some have recommended taking 200 milligrams per day. The Linus Pauling Institute actually recommends taking 400 milligrams per day. And that is a level that allows us to, with some level of uncertainty, because we don't know if everybody who takes vitamin C kind of rests on this curve that I displayed before. This curve is that of daily dose of vitamin C and plasma level was actually measured in young men and women at the NIH in a very small number of subjects. So we really don't know what the variation is throughout the population. Some people may have more of a demand for vitamin C. Older adults, for example, there are papers out there that show that older adults have lower plasma vitamin C levels for the same intake levels of vitamin C. So this curve may be shifted to the right and it might take more vitamin C dietary to reach that optimal level. Although once you do reach that optimal level, your body has saturated itself with ascorbic acid and you won't necessarily see any additional benefit, at least in tissues when you go beyond this. But other categories of individuals that may have shifted curves, there's some people that have genetic variants that may require more vitamin C. Haptaglobin polymorphisms is one if people know about it, Haptaglobin. Diabetics is another and smokers. We really don't know what the curve looks like for any of these populations. We've only looked at healthy young adults. And so until the studies are done, we have to assume that there's some wiggle room in this curve. So that's one of the reasons why the Lions Pauling Institute recommends 400 milligrams per day because we're going beyond this sharp point of the curve. We're not sitting at the turning point, the tipping point for the saturation, but we've actually reached safely the saturation levels. Now, like I said, most people know that vitamin C is high in fruits and vegetables. Tropical fruits especially have a lot of vitamin C. But there are some surprising sources of vitamin C that people don't know about, including potatoes. People don't really know that potatoes contain vitamin C. And often they're not a significant source of vitamin C in the diet. And the reason for that is cooking. Cooking actually will destroy vitamin C. Chopping, cooking, heating, winds up reducing vitamin C levels in your diet. So you have to be aware. I mean, obviously fresh fruits and vegetables, as I mentioned again, vitamin C supplements or supplementation is now prevalent in packaged foods. It's used as a preservative. But usually the levels of vitamin C that are found in packaged foods are low and don't really contribute highly to the dietary levels. Supplements, of course, and I'll mention supplements again in just a second, but supplements can range from all over the place, doses. And vitamin C, but you have to be aware as I just mentioned, vitamin C can react with heat, light, oxygen, metals, and high pH. So some people actually are getting less vitamin C than they think based on, say, the preparation method by which their foods are, they make their foods. One frequent cautionary note that we put out there was that don't cook your vegetables in copper pans because copper destroys vitamin C rather readily. Now, I'm sure everyone out there has heard of various vitamin C supplements that are present in the market. I've listed a few of them here. This includes, and these are many different variations on vitamin C. Usually they take vitamin C and they combine it with something or they take different forms of vitamin C and the goal here is to increase bioavailability. That is really what everyone's trying to do. But unfortunately, there's no data to support the increased bioavailability of any of these supplements. There are, I know there's some specific questions on vitamin C that we'll talk about, but no supplement to date has shown to have a greater bioavailability, at least in a peer-reviewed paper than straight ascorbic acid. Now, I should mention one thing that if you are attempting to maximize your vitamin C levels and you are taking levels of vitamin C that are suboptimal currently, it does take time to change your vitamin C status. We've known that it takes, we usually say about three to four weeks of a new supplementation regime to reach a new plasma, steady state levels is what we tend to call it. And we call this steady state because your vitamin C levels will rise after the supplementation and they'll come back down again as the kidneys kick in and try to eliminate the rise of vitamin C in the plasma. But in that process, I wish I could go back to the slide earlier, but in that process, your vitamin C levels are going up, coming back down, but your tissues are incrementally increasing vitamin C until they reach saturation. So while your plasma levels are changing over these three weeks, your tissue levels are getting higher and higher and higher and higher until you reach that new steady state. That steady state is achieved both by the combination of excreting vitamin C from your kidney but also your tissue saturating vitamin C during this process. So optimum vitamin C status is P. We really want people to achieve optimum vitamin C status. Obviously not everybody can go out and test their blood levels of vitamin C. So we try to provide a recommendation to give enough vitamin C for people on a daily basis and reach saturation in the majority of the population which is 400 milligrams per day. But some people still might need more vitamin C for optimal health and there are many options available for fruits, vegetables and supplements to achieve those levels. Okay, so quickly, since we're kind of 30 minutes or over 30 minutes into the seminar and I wanna get to all your questions, I'm gonna go over a few vitamin C myths before we get to the end. The first is vitamin C is toxic at high doses. So people who take multiple gram doses of vitamin C a day, there's often this concern that they're doing something harmful. And the upper limit for vitamin C consumption has been set by the Institute of Medicine at two grams of ascorbic acid per day. And beyond that level, you actually, the worst effect that you could see of vitamin C consumption beyond that level is diarrhea, gastrointestinal discomfort, bloating, and these actually tend to go away after you've increased your vitamin C to those levels. So as many people who've taken multiple gram doses of vitamin C know, it's a temporary thing. And there have been many studies of vitamin C, both oral and injected vitamin C, and shown that it does not have any acute toxicity or chronic toxicity over a long term. Now related to that, this is not quite a myth per se. There have been some papers out there associating high intakes of vitamin C with kidney stones. The issue here is that the oxalate that is being produced in the breakdown of vitamin C can form calcium oxalate, which is one type of kidney stone. Now the evidence out there isn't very good, but does suggest there is an increased risk in men who take large doses, but not all men. And so when we try to tell people if you have had a history of kidney stones that maybe it is good not to take large doses of vitamin C, but most people don't observe this kidney stone risk. And there are people who take multiple gram doses of vitamin C and never get a kidney stone. Now this is kind of a controversial myth because it's not quite a myth, but it's not quite truth either, or fact, vitamin C can cure the common cold. So far there's no evidence to show that once you have a cold that taking vitamin C will cure it. However, there are clinical studies out there that show that high levels of vitamin C intake over long periods of time, and maximizing vitamin C levels in your body can prevent the cold from ever occurring. However, the data on this, and I've looked at all the data on these, is not very good. We have a whole range of papers in the literature looking at vitamin C in the common cold. Now putting them all together in a meta analysis that was written not too long ago showed that there is a significant benefit, especially people who are under extreme conditions, heavy exercise or extreme cold conditions do show benefits with vitamin C supplementation. It does prevent the cold incidents. In the general population, the effect is small, but significant. So it does show that vitamin C does have a role in common cold prevention. But again, we need better studies to really definitively show this is the case. Now, this is kind of a controversial myth as well that there's no benefit to taking large mega doses of vitamin C. And this was of course supported by Linus Pauling in his recommendations. I would hesitate to tell anyone that there's no benefit in taking large doses of vitamin C. We don't recommend large doses of vitamin C because the studies that have been shown to date show that levels of 400 milligrams cause an optimal level of plasma vitamin C status. But large amounts of vitamin C have shown to have other gastrointestinal benefits and currently one of the untapped ways or not untapped but unexplored ways of which large amounts of vitamin C could have an effect on your health is in the microbiome. And these are exciting possibilities, but unfortunately none of the studies have been done at this point. Which leads me to another myth and this is kind of a research related myth. We know everything that there is to know about vitamin C and that's couldn't be farther from the truth. Vitamin C research needs to continue because we have just reached we've only just cracked the surface on vitamin C research. There's much more that needs to be done. Unfortunately, not many labs in the world today are researching vitamin C and so they kind of these new findings trickle through. We also need to increase the quality of vitamin C research. A lot of the studies that have been done before this are substandard and need to be improved. And that actually leads me to another point which is the use of animal models or cell culture. We recently wrote a paper in the Alliance Pauling Institute looking at the use of vitamin C in cell culture and animal models. And a lot of the papers that you read in the literature to date use these models. Unfortunately, there's a lot of evidence to say that the conclusions reached by these studies don't have any relation to what's going on in people. And this is mainly because cell culture, which you see a cell culture dish on the left here, has, it prevents or presents a very unique oxidizing environment in which vitamin C is lost rapidly and causes harmful reactions that aren't ever seen in the body. The other situation is when you're looking at animals like laboratory animals or even dogs, cats, pets you have at home. Every animal that is used for laboratory research with the exception of the guinea pig can synthesize its own vitamin C. But people can't. We need to get vitamin C from the diet. So how can these studies relate well to what's going on in human beings? Another myth, and I think this is my last one, that vitamin C has no role in cancer therapy. Linus Pauling wrote his book on cancer and vitamin C in the 70s with Ewan Cameron, a Scottish surgeon and they looked at supplementation of vitamin C in patients who had cancer and they showed tremendous benefits of oral supplementation vitamin C. Now some of this may have been not due to cancer killing effects, but to the fact that these patients were low in vitamin C to begin with and the supplementation actually improved their well-being on top of any other additional effects that high levels of vitamin C might have. But beyond that intravenous vitamin C, and this has kind of been revived by Mark Levine's group at the NIH, has shown beneficial effects on vitamin C research. And this is through a mechanism that as I mentioned before is a pro-oxidant, a cancer killing effect. But much more work has to be done in this arena. So that's it that I have for the webinar or the presentation part of the seminar today. And I would like to kind of get to your questions. So if you have questions that you would like to be answered, you can submit them online and we have our researchers in the back reading them off to me and I'll try to get to them. There are a couple of questions about how the body uses vitamin C and how doses should be divided daily and how long vitamin C stays in the body. Can you say how long vitamin C stays in the body and if you were interested in maintaining an optimal level of vitamin C in the blood, would it be better to take multiple doses daily? I would say that, and I may have a slide on this, let's see if I have this here. Okay, so vitamin C uptake, as we showed, if you take one supplement is what you usually show here. If you take one dose of vitamin C, your vitamin C levels go up slowly and then come back down. Now, people have theorized that if you take multiple doses, say a dose every four hours, you would get maximal levels of vitamin C. It's kind of up and down, up and down, but for approximately 12 hours after, or during this 12-hour period, I should say. So if you do divide your doses, you will likely increase plasma vitamin C levels for a longer period of time, and this will likely allow tissues that levels of vitamin C to accumulate, but only to the point that the tissues become saturated. You can't go beyond the saturation point in your tissues. They will accumulate vitamin C up until they, the mechanisms for releasing it from the tissues get overburdened, I guess you can say, and then the vitamin C comes back out again. So this is a strategy for increasing plasma vitamin C levels, but as soon as you stop taking vitamin C, your levels, as you can see on the right graph here, will start to fall and your kidneys will kick in and urinate out the rest of the vitamin C. There's actually some data to suggest that if you take large doses of vitamin C for a long period of time, that this elimination rate increases. So your body is actively trying to get rid of the excess vitamin C, not because it causes harm, but just because that is part of the tight control mechanisms that govern vitamin C levels in the body. We have a few more questions about large doses of vitamin C. One questioner writes, I take eight to 10 grams of vitamin C a day in the form of ascorbic acid. Do I have to worry about too much acid? And a related question is, is buffered vitamin C preferred? Okay, so we'll start with the, is that too much acid? It's only too much acid if it upsets your stomach or, but your body is very good at neutralizing any acid compounds you can take. For example, you could drink vinegar. That's an acid as well. That's not going to cause harm in your body. So the acid is only an issue if you feel like you're getting an acidic stomach after taking vitamin C. And this leads us into the buffered forms of vitamin C. So there are forms of vitamin C that are pH buffered. A lot of them are mixed mineral ascorbic acid or calcium ascorbic acid. And these tend to have a pH that is close to neutrality. And so when you consume them, they actually are less likely to cause heartburn. So for people who are taking large doses of vitamin C and do get heartburn after taking doses, it is advisable to take the mineral ascorbates or a buffer descorbate to reduce the incidence of heartburn. There's one more question on supplemental form of vitamin C. What can you say about liposomal vitamin C? Okay, liposomal vitamin C is actually one of the, and I'll go back to my supplement page here. Liposomal vitamin C is one of the most frequently asked questions that I get, at least in the supplement category. And it's probably because it's one of the most, the newest form. As I said before, no supplemental form of vitamin C has been shown to be more bioavailable than any other form. All these supplements that say that they have the highest bioavailability formula have not shown the clinical research data to back that up. That's basically the bottom line. Now, liposomal vitamin C is a lipid encapsulated. So there's these little lipid droplets that are supposed to bypass the tight control absorption mechanisms that I mentioned at the beginning of the talk. So they're supposed to kind of bypass the transporters, get around that limitation of absorption and increase vitamin C levels faster and higher. But unfortunately, we have no data on these. So their claims kind of will go unfounded until we have clinical peer reviewed data to really show that they do increase vitamin C levels in the body. Until that, we can make no claims about liposomal or ester C or mineral ascorbates having increased bioavailability. Even bioflavonoids, which are commonly found in vitamin C supplements, don't haven't shown to cause an increase in bioavailability. Actually, if anything, some flavonoids have been suggested to inhibit vitamin C uptake. And there are some forms like calcium ascorbic acid that have been shown to have lower bioavailability as well. Unfortunately, nowadays it's hard to find straight ascorbic acid supplements. But if you compare them across, ascorbic acid is just as good as any other form you take. Here's another online question. Glucose from corn is used to make ascorbic acid. Can you debunk the claims that using, excuse me, genetically modified organism corn as a source of glucose will in any way affect the product? Would corn-derived glucose have any effect on the product for people who are allergic to corn, for instance? No, so ascorbic acid is usually synthesized by a glucose precursor. So they just derive the glucose from some source. Now, of course, one of the cheapest and most available sources of glucose is from corn. But the starting product, the glucose, comes from the, is in a purified form. So anything that was originally coming forth from the corn is lost and it's just pure glucose. So any of the GMO products, whatever. And then it goes through several different processes in the processing to get to ascorbic acid. So there's various reactions that occur, various chemical and sometimes biological reactions that get to ascorbic acid. And these, any products that are formed, side products in this process or that came from the corn itself would get lost. They're pulled out during the process and we just get pure ascorbic acid. Now the ascorbic acid itself could be mixed with other things during the production of a pill or a supplement, but that wouldn't come from the original corn. And so therefore corn allergies don't really come into play. And also the GMO nature of the glucose doesn't affect the outcome of the product. Now, whether there's environmental or other impacts of using GMO corn I'm not going to comment on. But the ascorbic acid itself is unaltered. It's indistinguishable from non-GMO sources. Okay, the next question. Can you speculate about why IV vitamin C is not a consideration for some types of cancer treatment? Well, I'd have to say that and most doctors don't consider using IV vitamin C anyway. It's usually used by alternative medicine practitioners. However, the route in which vitamin C is thought to kill cancer cells is through, sorry, I'm gonna try to flip forward to a slide. Now this is a very busy slide, but it shows the pro-oxidant effects of vitamin C. And so when you have vitamin C levels in high doses during an intravenous injection you get the formation of hydrogen peroxide. And this hydrogen peroxide is what is considered to be the cell killing molecule. Now, but there are some cancer cells that don't respond to high doses of hydrogen peroxide and some that do. There are some cancer cells that could actually grow faster in the presence of hydrogen peroxide, but this hasn't been well clinically established. So the hydrogen peroxide killing effect has been shown usually in combination with a standard treatment like chemotherapy, but has shown clinical benefit in pancreatic cancer and lymphomas, but not every cancer cell type has been tested and we really don't know if every cell or every type of cancer will be equally susceptible to this hydrogen peroxide treatment. In addition, this hydrogen peroxide treatment or sorry, this hydrogen peroxide exposure occurs in the space between the blood vessel and the surrounding tissue, the tumor, for example. There's a little space in between them where this hydrogen peroxide is actually formed. But if you're looking, but this doesn't occur in say a brain tumor because when you're looking at brain tumors, or I'm sorry, when you're looking at vitamin C availability to the brain, you have cerebral spinal fluid that nourishes the brain and provides the vitamin C. So the hydrogen peroxide doesn't have a chance to form in the cerebral spinal fluid because there's a filtration mechanism through the blood-brain barrier that prevents these high doses of vitamin C from ever reaching the brain. We have a number of questions about the effect of vitamin C and other antioxidant exercise. Can you comment on research suggesting that antioxidants reduce some beneficial effects of exercise? The idea is that exercised induced oxidative stress actually improves insulin sensitivity and promotes endogenous antioxidant defense capacity, but taking supplemental vitamin C or other antioxidants may interfere with these benefits. That's a good question. And I'd have to say that I'm aware of those papers and there's actually, I was recently reading an article about supplemental vitamin C and E and exercise that kind of showed that the premise behind some of these papers is a little misguided. There's no plausible way by which the effects of exercise can be prevented by vitamin C and E supplements. Now, it is true that exercise does cause an oxidative stress and there are increased production of reactive oxygen species, but there have been no papers to show that vitamin C supplementation blunts the acute production, like running a marathon, for example. You still get the production of reactive oxygen species and your body still adapts. The molecular targets that have been shown in papers and some of the headlines that have been publicized about vitamin C preventing the adaptations, look at very specific markers for adaptation, usually in muscle cells, but there's really no direct correlation or at least it hasn't been shown yet to show that those muscles perform worse than they did before the supplementation. What you're actually seeing is less of an oxidative stress adaptive response, but that could be a good thing. What we really like to know is if those muscles or the tissues perform at a lower rate or if they, sorry, at a decreased capacity, then they would have before the supplementation and really that data isn't there and I don't think we're ever gonna see that data. I really think that vitamins may reduce the damage associated with exercise systemically, the inflammation, but they won't necessarily have any effects on performance. And so I think you're likely to find no effect of taking vitamin C and E on the performance during an exercise bout. We have an online question about sepsis and vitamin C. Intervenous vitamin C has been helpful in sepsis and decreased organ failure. Would oral vitamin C have similar results? One of the issues of giving someone with sepsis oral vitamin C is that they're not necessarily eating a bunch of stuff during a sepsis bout. So getting it in there might be an issue. But sepsis gets a little tricky. Vitamin C levels actually can decline pretty rapidly during a sepsis bout. Now, the reason for that is because during sepsis you have acute inflammation and sometimes you get the liberation of iron. And as actually my slide here that's still on the board shows that in the presence of iron, ascorbic acid can form superoxide and then hydrogen peroxide. It can be an iron-dependent or an iron-independent process. But the iron-independent process only occurs at high levels of vitamin C. But this can have, the iron-dependent process depends on the availability of the iron. So if you have this huge systemic inflammation like in the case of sepsis, you get liberation of iron and you can have negative effects. Now whether, it's hard to say if the intravenous vitamin C that was mentioned in the question is having an effect on killing a systemic bacterial infection which has been shown that vitamin C in high doses can have effects on bacterial cell killing. Or if it's actually preventing the oxidation responses. And so depending on the mechanism by which it's working, you'd wanna go with the high dose intravenous or the oral supplementation. If you want to get, if antioxidant mechanisms are important, you wanna go with oral. If pro-oxidant mechanisms are important and the bacterial cell killing, you would wanna go with intravenous. We just don't know which is the most important in sepsis at the moment. Here's a related online question. Does intravenous high dose vitamin C neutralize viruses and bacteria? And is there a threshold amount, say 200 grams? That's a good question. And I don't think we know if there's a threshold amount of vitamin C that will kill or sorry, neutralize viruses and bacteria. But vitamin C and optimal levels of vitamin C do support a healthy immune system. Many white blood cells use vitamin C to not only generate an oxidative burst which is normal or a normal part of the immune system to kill off invading pathogens, but it also to support the other cells and the other immune cells to give them resistance to not only the oxidative burst but any other stresses they would encounter while fighting off viruses and bacteria. So I would say that the optimal doses for neutralizing viruses and bacteria are ones that keep your immune system at optimal levels. And so far, the data suggests that any dose that saturates your plasma is good enough to keep your immune system working at optimal levels. Now, if future studies on the microbiome are done, this could also influence sepsis or other virus and bacterial immune function related. And we would love to see those studies being done because that could be another route in which vitamin C could enhance the immune system. Here's another question. Vitamin C is known to increase the body's production of oxalates which play a critical role in calcium oxalate kidney stone formation. For an individual who has already produced calcium oxalate kidney stones, what is your recommendation regarding the daily amount of vitamin C consumption in food and in supplements? So that's a good question. Yeah, so I did mention the vitamin C and kidney stones. It's not really, it is a concern. Doctors often tell people that if you have kidney stones, you should try to reduce your oxalate consumption and you do reduce your fruit and vegetables that have high oxalate. For example, rhubarb has a high amount of oxalate. You wanna avoid teas as well because they have high amount of oxalate. So levels of vitamin C though that are moderate have not shown an increased risk of kidney stone production. And by moderate, I mean under one gram per day. So if you want to supplement with vitamin C, you probably want to take less than a gram a day and you could still achieve optimal plasma levels of vitamin C and significantly reduce the risk of kidney stones, which is already low to begin with, but you would significantly reduce the oxalate production by the vitamin C. And I don't know if I mentioned this, but oxalate is a breakdown product of vitamin C. I think I mentioned that before, but this doesn't happen in high rates in people who are healthy or otherwise healthy. So fruit and vegetable intake should not be avoided as long as they don't have high amounts of oxalate that should all already be avoided in people who are taking, or sorry, who are trying to reduce their risk of kidney stones. Here's an online question. Since heat destroys vitamin C, would it be true to say that the only way to dietary vitamin C intake would be through raw vegetables and fruit? And if it is destroyed by heat, why then is there some left in the food after cooking? So not all vitamin C is destroyed by heat when you cook a vegetable or a fruit or anything else containing vitamin C. Things with low levels of vitamin C to begin with can get completely depleted, but sources that have high levels of vitamin C tend not to lose a large amount of the vitamin C. They just lose some. So you won't get the maximum level you think you would get from that fruit or vegetable. But the heat is a time and temperature dependent phenomenon. So when you increase the temperature of vitamins, or sorry, of cooking, so deep fat frying, for example, high intense heat kills vitamin C a lot faster than low heat. The time of cooking also matters. So boiling your vegetables to death would destroy more vitamin C than just a light blanching. Steaming is actually considered a way to keep vitamin C levels in fruits and vegetables high. If you still prefer cooked or microwaving. Actually, microwaving just recently was promoted on a website that I saw as a way to keep vitamin C levels high and it actually does destroy less vitamin C than any of the other cooking methods I mentioned. Raw diets, there's no reason to say that vitamin C doesn't stay around in raw diets, but you also have to realize that raw diets have another issue, one of them or two other issues. One is bioavailability. If you have a matrix that is not being broken down by cooking, your vitamin C could still be tied up in that matrix and not be liberated. This isn't usually the case for fruits. Fruits tend to have less matrix fibers, things to break down, but fruits and some vegetables do have ascorbate oxidase, which is an enzyme present in fruits and vegetables and is liberated by crushing, grinding, chopping, and that can cause specific oxidation of vitamin C. This is usually inhibited by, well, it could be inhibited by cooking for one thing because it will kill the enzyme that would destroy the vitamin C. The other thing is it can be inhibited by acid or anything that would keep vitamin C in its reduced state. Vitamin C is very happy being in acid environments. It is unlikely to oxidize in those environments. We have another online question. What health problems could low levels of vitamin C cause assuming one is not at risk for scurvy? Well, anything, so low levels of vitamin C have been associated with increased risk of cardiovascular disease. Actually, the biggest risk has been with mortality. Cancer and cardiovascular mortality rates, risk of death due to cancer, stroke, heart attack, heart disease, other types of heart disease are increased when your vitamin C levels are just above deficiency, but still in that inadequacy range. The other major, I mean, there are some immune system effects of low levels of vitamin C, but those are less clinically represented. It has been shown that increasing your vitamin C to optimal levels from levels below optimum, but above deficiency can bolster the immune system, but we don't really know if that has long-term immune system effects or not. Usually the studies that have been done are on the cardiovascular system and cancer, but things like diabetes risk has been shown to decline with plasma vitamin C levels, although the data there isn't very strong, and then the other is cognitive function. Cognitive function, again, it doesn't take a lot of vitamin C to saturate your brain with vitamin C, but there is an increased risk of cognitive decline at lower levels of vitamin C. We have two more online questions that are related to high-dose vitamin C and its antiviral effect. Since high-dose IV vitamin C would be a cheap source to cure various viruses and bacteria, including say Ebola, do you believe this would be a contributing cause to effective peer-reviewed studies of the vitamin? Billions of dollars are at stake as this idea was introduced by Dr. Clenner more than 70 years ago? True, that's actually, I think it's long overdue in travenous vitamin C as a virus or in treatment of chronic infections, whether it be virus or bacterial. There are plenty of stories, unfortunately none of them are clinical trials, but there are plenty of anecdotal stories. There was one down in New Zealand where a man was dying of a chronic lung infection. A chronic lung infection, and the family decided to give him intravenous vitamin C as kind of a last-ditch effort. Can we cure his disease? The doctor's conventional therapy has done nothing. And the man is alive today and walking around as if he never had any problems. And he attributes the intravenous vitamin C to the success in his immune system fighting off the bacterial infection. Now Ebola, HIV, name your virus, they've all been speculated to be susceptible to intravenous vitamin C, but unfortunately the studies haven't been done and finding the funding to do those studies is really hard to do. It would be a great therapy to try and get clinical evidence on, but unfortunately it's finding the interest at the higher level, say at the government or other funding agencies to support such trials. Here's a question that was submitted earlier. I am interested to know the effectiveness of topical application of vitamin C for wounds like ulcers or burns, and if there is evidence of its effectiveness, is there a special form of the vitamin and dosage level that might work best? I didn't really talk about topical application of vitamin C partially because I knew there were questions about it and I wanted to address it separately. So vitamin C levels in the skin are important in the development of healthy skin. Obviously the vitamin C in the skin comes from the, typically comes from the circulation, the lower levels of skin, the dermis, accumulate vitamin C just by the vitamin C that's passing through the bloodstream. But topical application actually is another route of getting vitamin C into the skin, and it does get accumulated. Usually you have to use ascorbic acid directly because there's a lot of other, like going back to looking at all the supplemental forms of vitamin C, there's a lot of different forms of vitamin C that have been sold to people and said use this as a skin cream, it'll work, but really few of them have shown benefit. So straight ascorbic acid actually has been shown to get into skin, but the question on whether it's effective in wound healing is a little controversial. Wound healing is a complicated process and during a wound healing, after you've cut yourself, you have different stages of the wound repair process. Some of them are oxidant in nature, oxidative stress in nature, some of them rely on collagen production, so you would think vitamin C is great, but some of them are actually crucial, the oxidants are crucial for the development of proper wound healing, in some cases it can go overboard. So knowing the timing of vitamin C in wound application, tropical application is difficult and it hasn't really been done. Most of the studies that it had done to date look at oral levels of vitamin C and have shown that in combination with other vitamins and minerals have been resulted in accelerated wound healing, like I think bed sores have been the most commonly studied and has been part of a bed sore supplementation regimen for a long time. We have another online question. You mentioned iron as a contributor to vitamin C pro-oxidant metabolism. Are there other co-factors that convert vitamin C to a pro-oxidant or antioxidant? Well, copper is another, copper and iron both kind of work in the same ways. They both contribute to the free radical, sorry, the super oxide generating mechanism that leads to hydrogen peroxide formation that is crucial to the success or is thought to be crucial to the success for intravenous vitamin C in say cancer therapy. Your body tightly regulates copper and iron in the body and so it is unlikely that this contributes to a majority of the effects seen with vitamin C. In fact, it probably only happens in very specific circumstances. Cells that are already dying or damaged in some way. But there haven't really been shown any other compounds that kind of act as an adjuvant or an accelerant for this hydrogen peroxide production. In fact, there are some who believe that the iron and copper aren't really necessary when dealing with larger doses of vitamin C and that it can spontaneously form. There is a paper out there that shows that EGCG, which is a compound found from green tea or teas in general, a flavonoid, can have a synergistic effect with high doses of vitamin C in producing hydrogen peroxide. But I think that really requires a lot more clinical study to definitively show. We have two online questions about vitamin C and food. The first is, are there any studies that show vitamin C content in vegetable or fruit produce? Winter versus summer supplies, for example. Oh, okay. Unfortunately, most researchers wind up relying on the USDA database, which has measured a bunch of different foods and fruits and vegetables for their data on how much vitamin C is in a particular commodity. Broccoli, for example, oranges, papaya. However, we do know, and I work with food scientists over at the Linus Pauling Institute, we know that vitamin C levels can vary from fruit to fruit. Even if they're one peach versus another peach from the same tree or from the same orchard, variety has a difference, growing conditions have a difference or make a difference in vitamin C content. And then, of course, preparation has a difference. Tropical fruits tend to have higher amounts of vitamin C than non-tropical fruits and vegetables. Peppers are one of the biggest sources of vitamin C in the diet and they're packed full of vitamin C. But seasonal variation, winter versus summer, I think just, I don't know if this is part of the biology of the plant, but summer fruits and vegetables tend to have higher amounts of vitamin C than winter, the winter. But during storage, there's a different situation going on here. Storage can actually impact vitamin C levels. Vitamin C is part of the ripening process. So when you have an overripe vegetable, or, sorry, fruit or vegetable, overripe fruit, I should say, you'll start to get some breakdown of the tissues and you get some oxidation occurring and that actually lowers vitamin C levels. Depending on how resistant your commodity or fruit and vegetable is to that oxidation, if they don't ripen quickly or get damaged, vitamin C levels could stay the same or vary slightly, but obviously, storage conditions impact that greatly. I know people who have done studies on vitamin C-containing products stored at high temperature, say a warm room for months and shown that vitamin C levels decline very fast. So all these factors can go into vitamin C. We tend to tell people to eat fresh fruits and vegetables, but good other sources are frozen. Frozen is a great source because when you preserve vitamin C by flash freezing, or I'm sorry, you can preserve vitamin C by flash freezing. So the vitamin C that was in that initial commodity stays there. Canning also can preserve some vitamin C depending on how the canning was done. The second question is, would the addition of vitamin C to a bottle of wheat germ oil slow down the oxidation of vitamin E in the oil? If so, would the vitamin C have to be in the form of ascorbic acid? Vitamin E, yeah, vitamin C and vitamin E definitely work together. Vitamin C is, if vitamin E gets oxidized, vitamin C or ascorbic acid will come in and reduce the tachyferol radical back to the active form of vitamin E. So it has to be in the reduced state, ascorbic acid. Any oxidized form of vitamin C will not work in this reaction. So I don't know what other forms of vitamin C you may have been talking about, but any of these other supplemental forms that have been modified in some way won't work. Any vitamin C that has been oxidized won't work. It has to be ascorbic acid. Now whether the presence of something else is also there is fine as long as the ascorbic acid is around to reduce the tachyferol radical back to its active form. They do work together not only in what you drink or eat, but also in the body. Another online question. What effect does vitamin C have on nitric oxide production? Oh, that's a good question. Actually one of the best and well-known effects of vitamin C in health has been on endothelial cells in the body and I'm trying to get to my vitamin C in health slide. I put this heart with the little blood pressure cuff here because blood pressure has actually been shown to, or reduction in blood pressure has been correlated to large amounts of, or sorry, high intakes of vitamin C. And in some people, blood pressure, you can get favorable changes in blood pressure when you take supplemental vitamin C. And that is thought to occur in because endothelial cells produce nitric oxide which contributes to blood pressure and constriction or dilation of the blood vessels. The enzyme that's involved in nitric oxide production is called nitric oxide synthase. And it has a cofactor tetrahydrobiopterin. When tetrahydrobiopterin gets oxidized accidentally due to the presence of a free radical or other oxidant, you can get what's called a trihydrobiopterin radical. And that actually can be scavenged by vitamin C. So when you restore tetrahydrobiopterin by after it gets oxidized, you contribute to nitric oxide synthase activity and therefore nitric oxide production. And that's the link between vitamin C and NO in the endothelial cell. There may be links to vitamin C to nitric oxide in other cells of the body that haven't really been explored yet. One last question relates to vitamin C and diabetes. I've been taking vitamin C and noticed it increases my blood sugar. Should I continue to take vitamin C and also a related question, would large doses of vitamin C daily manage side effects of diabetes? I'll answer, I guess the second question first. Vitamin C levels, maximizing or optimizing your vitamin C levels has actually been speculated to be very important in complications due to diabetes because diabetes tends to be systemic oxidative stress in the body. Now that being said, there are also some interesting effects of vitamin C have been speculated to impact blood glucose levels in a positive way, reducing blood glucose levels and may have some effects on acetylated hemoglobin, HB, H1AC, I think it's called. But those are really, the evidence for those impacts are scant and we need more studies to find true correlation on how vitamin C can help diabetics. But it does seem to reduce the risk of cardiovascular disease associated with the oxidative stress of diabetes. Now the blood glucose question is a really important one and anyone who's a diabetic should really know that large amounts of vitamin C can appear as glucose in glucose monitoring test strips. I have a picture of the little test, finger prick test, some of these tests, vitamin C interferes in the way the readers function. So these readers, if nobody knows how these readers work, none of them really measure glucose in your body. They measure a reaction that is dependent on glucose but vitamin C can interfere with that reaction or accelerate that reaction to appear as if it was glucose. So you can get an aberrantly high reading on your glucose test strips just by taking vitamin C. It just all depends on what the chemistry is of the testing strips that are being used. What I tell people who get these aberrant high readings is if you don't have a testing kit that uses the hexokinase method, which is very specific for glucose, you should talk to your doctor and see if you can get your blood glucose measured by the hexokinase method. And that will tell you how much of a contribution vitamin C is contributing to your apparent blood sugar. Let's see, there's, but I've actually read a couple of papers recently that show that larger amounts of vitamin C can reduce blood sugar. I don't know how profound that effect is in diabetics, but it does seem, if you do get an aberrant reading, I'd be very skeptical of that with a glucose testing kit. I don't think there's anything else I wanted to say about diabetes, but I think actually we're running out of time. So I'm going to conclude, and I would like to do that by going and telling people that we do have a few more questions that I didn't get a chance to get to. So I will try to answer them in, when we post the transcripts for this webinar, and also the slides will all be available online on our website, that's lpi.organstate.edu. But if you want more information about vitamin C, you should see our pages on the Micronutrient Information Center, the MIC or MIC, that are presented here on this slide. We have the page on vitamins at the top. We also have a very popular page on skin health that was written by me. And there's the supplemental forms of vitamin C, which is another popular article on our page, looking at how the various formulations of vitamin C may impact vitamin C levels in your body. And if you have any other questions, you can contact the lpi at organstate.edu or email me directly at alexandermichaeles at organstate.edu. And I thank you for your time and have a good day.