 Hello everyone and welcome to the Linus Pauling Institute's first webcast of 2021. My name is Alexander Michaels and I'm a research research associate at the Linus Pauling Institute where I've been involved in vitamin C research in for the last 20 years or so, and I will be your host for today's talk. We have an amazing turnout today for today's event. This is vitamin C and health new frontiers registrations went off the charts as soon as this webcast was announced has been increasing steadily every day. I think the last numbers we have is more than 1200 people are registered for this webcast, and I can see down below that more people are filing in at the moment as I'm talking so I'll give everybody a moment to get in. But I think this is just a testament to how amazing vitamin C research is and how much people really want to know about this molecule. So big welcome to everyone. I'm glad you made it out here this Saturday to hear about the latest in vitamin C research. This virtual formats great for us because we can reach so many people around the world, who just want to know what we have to say and and hear from our speakers. We have four vitamin C experts with us today. That's going to they're going to just be answering your questions for the most part. Let me start by acknowledging that this talk on this day was no coincidence we are only one day away from Linus Pauling Day in the state of Oregon, February 28 2021 will be the 120th birthday 120th anniversary of Linus Pauling's birthday in Portland, Oregon. And the names take behind the institution and his mission for helping everywhere, everyone everywhere achieve optimum health. So in honor of Dr. Pauling's work with vitamin C, we've pulled together vitamin C experts to give an update on the latest research on this amazing molecule as I said, but before I start introducing the speakers. I'd like to start by introducing our director of the Linus Pauling Institute, Dr. Emily Ho, whose camera is on with me right here. This is Dr. Ho's first Linus Pauling Day as director, but she's definitely been at the Institute through many aligns Pauling Day before this. And I think Emily you gave a you gave a talk for our Linus Pauling Day event last year, if I remember correctly and that was great. And so, without further ado, I'll just let Emily take over and give us some perspective on today's event. Well, welcome everybody to the Linus Pauling Institute annual Linus Pauling Day. Again, my name is Emily Ho and I'm the current director of the Linus Pauling Institute and as Alex mentioned this is my first Linus Pauling Day and we are doing things a little bit differently. We are the day before Linus's birthday, and we're doing things remotely. But, as was already mentioned, I'm really thrilled that we're able to reach so many of you with this important message and this important information, and really help share with you the inspiration of Dr. Pauling, who's one of one of OSU's most famous alumni. He's won two unshared Nobel Prizes, one in chemistry and one in peace. Pauling didn't win his Nobel Prizes for his work in vitamin C, but he certainly has had a huge and lasting impact on how the world views vitamin C and its impact on health. And Linus Pauling really was a true innovator and not afraid to go against the norms and very early on began to research how high doses of vitamin C had dramatic effects on human health. In 1970, he published the vitamin C and the common cold, and then updated it in 1976 where he published this vitamin C, the common cold and the flu. Pauling is well known for coining the term ortho molecular medicine, and to summarize that concept really talks about the right molecule in the right concentration in the right place in the body. And vitamin C is one of the perfect example of this concept. In the late, mid to late 70s, working with a surgeon in Scotland, even Cameron, Pauling really envisioned new potentials for vitamin C to treat a whole host of different diseases and maladies, including cancer, skin disease, schizophrenia, common cold and infections. And we're going to talk a little bit more about some modern updates with you today. So later on in 1986, his New York Times bestseller on how to live longer and feel better was first published that really helps outline Pauling's concepts of taking vitamins and minerals, and how they are key to preventing disease and live a long life. This work really helped revolutionize the way that many of us think about nutrition and health. And again, we're going to bring you more of these updates of these concepts with our international panel of experts who will be introduced to you shortly. So Linus Pauling was born in Portland, Oregon on February 28, 1901. So again, tomorrow he'll be he would have been 120 years old. He went to the Oregon agriculture, which is now known as Oregon State University where he met his wife, Eva Helen. And after his death in 1994, Oregon's governor, who at the time Barbara Roberts, recognized his remarkable achievements and named February 28, the first ever Linus Pauling Day. And today at the Institute, we celebrate this every year, as we are doing today. It's also the 25th anniversary of the LPI at OSU. We celebrate. But in today's celebration specifically we're going to honor the spirit of Linus Pauling, his spirit of innovation and his love for vitamin C by bringing you some of the world's experts on vitamin C and health. So now I'm going to turn it back to Dr. Alex Michaels, one of our own vitamin C lovers at the Institute, and he'll be moderating our session for today. Thank you, Emily. And that was a great and excellent background for why we're doing this all today. And we just love to talk about Dr. Pauling but of course this is not, this is not a webinar about Dr. Pauling, this is a webinar about vitamin C. And what I'm going to do right now is actually introduce one of our speakers to give us some background and kind of a little vitamin C primer. We don't have time to go into a full background primer on vitamin C that would probably take a whole another webinar to do so and if you are interested in webinars about the basics about vitamin C you can find those kind of webinars on our homepage, lpi.organstate.edu or our YouTube page. Right now I'm going to introduce our first speaker, Anitra Carr. Anitra and I have known each other for more than 20 years now. We met in the Linus Pauling Institute when I was a graduate student, she was a postdoc. She and Balds Fry had just written some of the seminal review articles about vitamin C and health that helps set the newest or the latest RDAs in the United States. After leaving the Institute, she went back home to New Zealand where she's now an associate professor at the University of Otago in Christchurch. But I'll let Anitra tell you the rest. Anitra. Thanks, Alex. So today, as Alex mentioned, I'll just give a very brief overview of vitamin C and health, but specifically focus on its roles and cancer and infection because of Linus Pauling's interest in those areas. And also as a way to introduce the areas of expertise about panel members. So as Alex mentioned, after I finished my PhD in New Zealand, I obtained an American Heart Association postdoctoral fellowship, which I carried out with Professor Balds Fry when he not long after he had been made the new director of the Linus Pauling Institute at Oregon State University. So my research focus at the time was looking at the role of vitamin C and potentially protecting against the development of cardiovascular disease. And as Alex also mentioned, we wrote a number of high impact papers around the role of vitamin C and human health and disease. One was submitted to the Institute of the Food and Nutrition Board of the Institute's Medicine during their review of the dietary intake recommendations for the antioxidant vitamins. And the recommended dietary intake of vitamin C was increased one and a half fold from 60 to 90 milligrams a day in 2001. That year I also had our first child and then took the next nine years out of my career to help raise her and her two siblings and all now teenagers. So in 2010 I returned to work at the University of Otago in Christchurch, New Zealand, and I carried out human intervention studies investigating vitamin C by availability and health effects including around immunity and mood. And more recently I set up my own research group and I've been investigating the use of intravenous vitamin C in patients with cancer, pneumonia and sepsis. I'm also interested in the role of vitamin C in metabolic conditions such as diabetes and metabolic syndrome which is also known as pre-diabetes. So why do we need vitamin C? So normally vitamin C is synthesized from glucose and plants and the livers of most animals except humans and a handful of other animal species. And this is due to random genetic mutations that have occurred over our evolution that have resulted in a key enzyme in the biosynthetic pathway being knocked out. So we can no longer make vitamin C or synthesize it in our livers. So what this means is that vitamin C is now vital for life and we must get it through our diet in order to survive. And the best sources of vitamin C are fresh fruit and vegetables. Vitamin C has numerous functions in the body. It's a cofactor for a family of metalloenzymes which have numerous important biosynthetic and regulatory roles in the body. For example it's required for collagen protein structure, cellular energy production, hormone and neurotransmitter synthesis and metabolic regulation. And recent research is indicating a role for vitamin C in epigenetic regulation and this is a very exciting new area of research because it's indicating that vitamin C can help up and down regulate thousands of genes in our bodies. So as Emily mentioned Linus Pauling is well known for his work around vitamin C and cancer having published the popular book Cancer and Vitamin C in the late 1970s. In the mid 1970s he carried out a study in 100 terminal cancer patients who had been treated with 10 grams a day intravenous vitamin C for at least 10 days and then 10 grams a day of oral vitamin C thereafter. And he reported that the patients who received vitamin C had much better survival than the control patients who didn't receive any vitamin C. And this was true for all cancer types but in particular colon and breast cancer. So after he published this study doctors at the Mayo Clinic in Arizona decided to carry out a couple of clinical trials to see if they could reproduce these findings. So in these studies patients with advanced cancer were treated with 10 grams a day of oral vitamin C or a placebo tablet which contains no vitamin C. In both of these studies there was no differences in survival between the vitamin C and the placebo group. But has anyone noticed the differences between these studies and the original Pauling study? These studies used oral vitamin C only the original Pauling study used intravenous vitamin C initially followed by oral. So this is where a lot of the controversy around the use of vitamin C and in cancer has come from. A lack of understanding of the differences between oral intravenous vitamin C because we now know there are large differences between the two. So this figure shows you the blood levels of vitamin C after oral or intravenous vitamin administration. You can see after oral administration you just get this little blip in your blood. Whereas intravenous vitamin C bypasses the regulated intestinal uptake of oral vitamin C which means you can get much higher blood levels following intravenous administration. However you can see that this high peak is still quite transient and that's because vitamin C is water soluble and so any excess that the body doesn't need is excreted quite rapidly by the kidneys. So it has a half life and blood of only you know less than two hours. Anyway to put this into perspective an infusion bag of vitamin C. It typically contains about 70 grams of vitamin C for patients with cancer these days is equivalent to a thousand orange oranges and that's why it needs to be administered intravenously. High dose intravenous vitamin C is likely required or facilitates penetration of the vitamin into the core of solid tumours. So we've recently shown that the core of colorectal tumours is very low in vitamin C as you can see by this red area here. Following intravenous vitamin C administration to these patients you can see much higher levels of vitamin C in the tumour and this likely facilitates its anti-cancer activities. Other research has shown that people who have higher vitamin C levels in their tumours have much better survival than people who have low levels of vitamin C in their tumours. This data here is from patients with breast cancer but similar trends are also observed with patients with colorectal cancer. So Jenny Driscoe who's on our panel has had many years experience administering intravenous vitamin C to patients with cancer. She's also been involved with a number of clinical trials so she'll better answer many of your questions around these areas. So what is the connection between vitamin C and respiratory infection? It turns out that serious respiratory infections such as pneumonia are a major complication of the vitamin C deficiency disease scurvy. And pneumonia is one of the major causes of death for people with scurvy. So this indicates a strong link between vitamin C insufficiency and infection. And we now know that vitamin C has numerous roles that support healthy immune function including improving the ability of white blood cells to eliminate pathogens from the body. Once again it was Linus Pauling who stimulated an interest in the use of vitamin C for respiratory infections. You can see that not long after Pauling published his book vitamin C in the common cold in the early 1970s there was a huge upsurge in clinical trials investigating the use of vitamin C in the common cold. This figure shows vitamin C levels in patients with severe infections such as pneumonia and sepsis shown in the orange head. Normally their vitamin C levels are much lower than community dwelling cohorts which are shown in the green bars. And if the patients go on to develop severe sepsis and enough in the intensive care unit their levels are the lowest of all with many in the deficiency range. Critically ill patients also have much higher requirements for vitamin C than the general population. Normally 300 milligrams a day of vitamin C would be more than enough to saturate the blood of a healthy person. However 10 times this amount or three grams a day is required to saturate the blood of critically ill people. And this is equivalent to 40 oranges a day. And so this is why Trivenus root is often chosen for these patients as well. What about vitamin C and COVID? So the World Health Organization has highlighted vitamin C as a potential adjunctive therapy with biologic plausibility for the patients with severe COVID-19. So sepsis is a major complication of severe COVID. And this recent clinical trial carried out by Dr Fowler has shown that septic patients who receive intravenous vitamin C have significantly decreased mortality compared to the patients who receive placebo. And he can talk more about this trial in a minute. Another recent trial carried out in Wuhan China and patients with severe COVID has shown that the patients in the high dose intravenous vitamin C group also had significantly lower mortality. And those in the placebo group. And there are now numerous trials running up and running around the world investigating vitamin C use for COVID-19. Dr Fowler is an experienced intensive care physician and he'll be able to answer new questions you have about administration of intravenous vitamin C to patients with sepsis and COVID-19. So with respect to prevention of disease, you can see from this figure that there are a number of diseases that can be partially or almost fully avoided by healthy diet and lifestyle. These include colon cancer, stroke, coronary heart disease, type 2 diabetes. And this is why the US government now recommends that half your plate should be fruit and vegetables. And this is because they contain numerous healthy nutrients such as vitamin C. With regard to vitamin C and diabetes, we found that people with pre, both pre-diabetes and diabetes, much higher proportion of them have inadequate vitamin C status, which is shown by these yellow, orange and red bars. And this was despite them having a similar dietary intake of the vitamin as the healthy controls. And what this means is that the elevated oxidative stress and inflammation that's observed in diabetes is depleting the vitamin C levels in these people. And we know that diabetes is a major risk factor for cardiovascular disease. And there have been a number of large epidemiological studies that have shown that higher levels of vitamin C are associated with lower mortality from cardiovascular disease. This figure just shows data from a large study of 20,000 British adults. The people who had the highest levels of vitamin C in their blood, shown here, had a 60% decreased risk of mortality from cardiovascular disease. Compared to the people who had the lowest levels of vitamin C in their blood. But this trend could just indicate vitamin C is acting as a marker for a healthy diet. But it does also have a lot of functions that help support healthy cardiovascular functioning. And Retraba has recently published a review around the roles of vitamin C and E and metabolic syndrome, which is a major risk factor for both diabetes and cardiovascular disease. So she'll better answer any questions you may have around this. And now I'm going to hand back to Alex, who will introduce the speakers in more detail. Thanks, Alex. Thank you, Anitra, for that background. Actually, I'm going to try to do this quickly so we can actually get to the questions. The questions, you know, we've already gotten plenty of questions from you guys during the registration process. You're still typing questions in as we speak. I'm going to. And, but if you haven't seen the question and answer button, you look below and Q&A and you can type your question in there and we are monitoring that during the talk. But I'm going to ask the rest of the speakers to turn on their cameras for the moment. I'm going to let each one of them talk about their work for just a brief second before we get to the questions. Starting with Dr. Jeannie Driscoe from Professor Emeritus from the University of Kentucky Medical Center. Jeannie, if you want to. Well, I'd like to thank the Linus Pauling Institute and the webinar planners for including me in this seminal gathering. I mean, it's really, really wonderful. But I'd like to give a special shout out to Dr. Emily Ho and Dr. Alex Michaels for putting together this gathering you've done a wonderful job with this. As Alex said, I'm Jeannie Driscoe. I'm currently a professor emeritus at the University of Kansas Medical Center, and the former endowed professor, interestingly of orthomolecular medicine, and administrator of KU integrated medicine. So academic institutions like to see you have the four pillars of academic medicine. And that is education, service, research and clinic practice. Well, at KU integrated medicine, we fulfilled this mandate by providing education and integrative medicine to all types of students, a fellowship and integrative medicine, and education of postdocs and integrative medicine basic science. So, KU integrated medicine also served both of our academic communities through committee work, but also the state of Kansas at the Board of Healing Arts around the topic of integrative medicine, and the nation by sitting on various committees and review boards. We also had a very robust clinic practice, and you'd probably not be surprised to know we included IV vitamin C in our treatment of patients with chronic complex illness. So we used IV vitamin C in cancer patients, acute and chronic viral infections, acute and chronic bacterial infections, chronic fatigue, fibromyalgia, and environmental toxicity, including mold and mold mycotoxin toxicity. And here's a picture of my colleague and scientific partner Dr. K Chin in the front, and she's with her students and her postdoc in this picture. Dr. Chin was a postdoc under Mark Levine in his lab at the NIH who many of you have heard of. And at this, during her time as a postdoc she conducted basic science research in high dose IV vitamin C. Dr. Chin and I are most known for is our translational research, and that is the combination of basic science research with research and patients in the clinic. And most people think of us as translational researchers around the topic of cancer. And of course we are currently we have a study in patients with bladder cancer using IV vitamin C. But important for this discussion, we're now looking at IVC, intravenous vitamin C for SARS-CoV-2, the virus that causes COVID-19 by studying it in a viral cell tissue model, and an animal model, and this research is ongoing. We are excited to provide this basic science research information and coronavirus that will certainly extend to other viral infections as well. I can't give you really results as of yet, but I can tell you that the current IV doses used in recent clinical trials are likely not adequate as an antiviral agent. So more information to follow. Next slide now, Alex, thanks. Today we're going to be discussing both oral and intravenous vitamin C, and I want to make it very clear that they act very differently in the body. As Dr. Carr has shown with her work, oral vitamin C, excuse me, is a very powerful vitamin with many important properties. Different people during different stages of health need different doses of oral vitamin C, as she's shown. Healthy adults on the left with a good diet are in the green zone, requiring only minimal supplementation of vitamin C. But with aging, illness, and or poor diets are requirements for oral vitamin C increase, as I will know as now moving into my retirement phase. We then come to the primary divide that red bolt down the middle. And that's when we cross over from oral vitamin C to intravenous vitamin C. This is a big divide and no amount of oral vitamin C can be given to be equivalent to intravenous vitamin C. Oral vitamin C gives us blood levels in the micro molar ranges, while intravenous vitamin C gives us blood levels in the millimolar ranges. This is a thousand fold greater concentration in the blood. It's like trying to jump from one side of the Grand Canyon to the other, for example, it's impossible. So something happens when vitamin C is given in the vein, and it bypasses the gut absorption as Dr. Carr showed you. And vitamin C becomes a drug. And though it may retain its vitamin properties, it now becomes a pro oxidant when it enters the space around the cells. And through a chemical reaction called fentanyl chemistry, it reacts to become hydrogen peroxide. So hydrogen peroxide is the end drug, and vitamin C is the pro drug in this case. And we have shown this in our research and it's now been replicated multiple times around the world. It is the production of hydrogen peroxide that makes the secondary divide. So if you see off to the right, you start looking at patients that become ill and maybe come to the clinic, like our patients, or hospitalized or at worst in the ICU. So that second divide is a division between the low dose IV vitamin C and the high dose IV vitamin C. And this is where it really becomes, it really is doing its job as an antiviral or antibacterial drug when it crosses the secondary divide. So significant hydro peroxide is not formed under approximately 10 grams. So IV doses under 10 grams are low dose IV vitamin C, not high dose IV vitamin C. Well, doses above this range, even up to 100 grams produce significant hydrogen peroxide. And again, our research has shown that increasing doses of IVC result in increasing blood levels that will become hydrogen peroxide in that space around the cells. It's a linear response. The higher the dose of IVC, the higher the production of hydrogen peroxide. I guess an analogy would be to think of it like vancomycin antibiotic. So let's say you need to give a gram of vancomycin every eight hours for methicillin resistant staff areas or MRSA. If you only give one milligram, for example, you will not be able to get an adequate blood level to fight MRSA. Given that the vancomycin is an ineffective antibiotic, it only means that the wrong dose was given. Therefore, you can think of IV vitamin C in the same way. The dose is critical, and it has to be given on that right side of the secondary divide, or it is an ineffective anti-infective agent. We've also shown in our research that the infusion rate is critical, and it should be given at 0.5 to one gram per minute. That means a 50 gram dose could be given over one to two hours. And we also have shown in our research this is very safe, given the fact that a patient has a normal G6PD enzyme, adequate kidney function, and no history of oxalate kidney stones. And we have given thousands of doses safely both in research project and in our clinical practice. So while IV vitamin C fixes scurvy in these ill patients, it is our hypothesis that the higher dose produces hydrogen peroxide, which results in an anti-infective and anti-cancer agent. Next slide. Thank you very much. Thank you, Jeannie, for that introduction. Actually, you've pretty much set up our next speaker pretty well. So I'm going to invite Dr. Fowler, Barry Fowler to take the stage and talk about his work with Sepsis. Okay, thank you very much. Can you hear me? Yep. You can hear me. Okay. Thank you all. I want to tell you how excited I am to be part of this webinar today and also honored to have been asked to present here today. As Dr. Carr and Dr. Drisco mentioned, during critical illness, plasma vitamin C levels dropped to very, very low levels. And in our initial clinical research, we found that patients with severe sepsis had near scurvy levels of plasma ascorbic acid. And in the years of basic research that we did with a animal model of sepsis, we found that vitamin C could be very effective when administered intravenously, as Dr. Carr and Dr. Drisco have mentioned. And so we put together an application to the NIH. The NIH sponsored us for a phase two group of concept trial that we entitled vitamin C infusion for treatment in sepsis-induced acute lung injury or the Citrus ALI trial. And we had seven medical centers between VCU Cleveland Clinic Medical College of Wisconsin University of Kentucky and Emory University in Atlanta, Georgia, participating and enrolling patients in this trial. We screened 1,262 subjects because of our elimination criteria. We eliminated and excluded 1,092 subjects and randomized 170 patients for this trial. We found and we enrolled 83 placebo patients who were receiving standard of care for sepsis and acute respiratory failure by mechanical ventilation. One patient was excluded prior to receiving vitamin C, who had a problem called acute eosinophilic pneumonia that presents very similar to ARDS, which is acute respiratory distress syndrome, and that patient was excluded. And on the vitamin C group, which was 84 patients, we excluded two patients who were leukemic patients that were suffering from diffuse alveolar hemorrhage, which also looks very exactly like sepsis-induced acute lung injury or acute respiratory distress syndrome. And that was 84 patients who received vitamin C and the same standard of care that the placebo patients got. Next slide. The vitamin C group received 50 milligrams per kilogram of body weight every six hours for 96 hours. This was close to what Dr. Disco was mentioning. Each patient received approximately 15 grams of intravenous vitamin C over the course of 24 hours, but they received it somewhere around 3,500 to 5,000 milligrams every six hours infused 50 mls of dextrose 5% in water over a 30 minute period. Next slide. We were very interested to determine how vitamin C could protect the organs that fail, especially in sepsis. And we used what is called the SOFA score, which allows a broad assessment of organ failure. The SOFA score is an abbreviation for sequential organ failure assessment score, and it allows us to look at the organs that I've listed here. Next slide. The, over the course of the five years that we were conducting this, we found that the clinicians who were caring for the ICU patients in the trial did not often order hepatic function studies. So we had to eliminate liver function in the trial. And so what we published was a modified SOFA score, which in the literature has been found to be legitimate, the modified SOFA score. Next slide. And as Dr. Carr mentioned, over the course of the time that we were infusing these patients every six hours for 96 hours, if you look at the orange column on the left, the blue line represents the placebo patients. In over 96 hours, 19 placebo patients died versus only four patients who were receiving vitamin C died. And when we looked at the cross section between the patients who were placebo patients and the patients who received vitamin C, there was no difference in the male-female ratio or the age. But interestingly, however, if you look at what occurred after the vitamin C treatment, you saw the mortality that we were reducing over 96 hours in the vitamin C treatment group began to rise and essentially parallel that that was gotten in the placebo. Next slide. In the placebo patients, we found that 46% of those patients, these were septic individuals who were in acute respiratory failure, had died versus next slide. So 30% of patients receiving vitamin C, and this was significant at 28 days, and you can see the level of significance of P equals 0.01. The important thing to mention here, and Dr. Carr and Dr. Drisco mentioned this, by giving patients who are critically ill, 50 milligrams per kilogram of body weight every six hours. We looked at the plasma vitamin C levels as high as five or six millimolar versus at the onset of the vitamin C treatment, which were patients that were approximately 18 micromolar. And so we were able to increase the vitamin C levels by over 6000 micrograms per mil. Next slide. The important piece of this research, and what every critical care doctor has been anxious to find is a therapy that can reduce mortality and organ failure is directly related to mortality. What you have in this graphic shows you that vitamin C effectively and significantly reduced organ failure of the sequential organ failure assessment score. Next slide. We published this as you can see below in JAMA in 2020 and feel that it's important for clinicians around the world to consider this. We are now working with the prevention and early treatment of acute lung injury network, the so called pedal network to perform a much larger trial using vitamin C in patients with sepsis. As has been mentioned by the previous two speakers vitamin C is being actively investigated around the world in patients with sepsis. And also I might add we at Virginia Commonwealth University are also conducting a randomized double bond trial using the same dosage the VCU protocol we call it in patients with COVID pneumonia. It's ongoing and we are enrolling as we speak at Virginia Commonwealth University we now have over 140 COVID positive pneumonia patients in the hospital at Virginia Commonwealth University Medical Center. Thank you very much for inviting me to be part of this. Yeah, and when I heard about your enrolling COVID patients I knew I had to get you on the panel. Thank you for that for the intro and I'm going to I'm going to quickly turn it over to Dr. Marat Traber who's actually from the Linus Pauling Institute and while her work doesn't always focus on vitamin C. She definitely has vitamin C peppered in there every once in a while. Marat. Thank you very much Alex. It's a real pleasure to be on the stage with such illustrious vitamin C investigators. I want to emphasize that I'm so pleased to be named the Eva Helen Pauling chair. And so this is a real honor for me to speak at a Linus Pauling day. What I'd like to talk about is healthy people. And you might all be wondering what is metabolic syndrome. Well, it is a disorder of healthy people who are perhaps you've heard of obese, have hypertension, have hyperlipidemia, maybe even the beginnings of type two diabetes. It's a formula that says, Well, maybe you were edging yourself into danger. And I'd like to emphasize this because if you think about all of those risk factors that are what are likely to make you more likely to have very severe reactions to COVID-19. It really speaks to diet is important not only for chronic disease, but also your immune function and your resistance to disease. And I was very taken with Dr. Drisco's picture that the green to the red zone. And if you're over there in the green zone. Does that really protect you. Are you prevented from getting sick. And if you look at chronic chronic disease numbers, the answers are yes, eating huge amounts and literally five to nine servings of fruits and vegetables every day is what I as a nutritionist would like to encourage you to do. So, what am I talking about metabolic syndrome for Alex, if I can have the next slide. It turns out that my favorite vitamin vitamin E, when it does its job protecting you from lipid peroxidation. And you may remember that vitamin E is a fat soluble vitamin that fat soluble vitamin sits in membranes, not where vitamin C is, but the radical pushes vitamin E out there into that aqueous phase where vitamin C is necessary to reduce it. When you have an infection and increase oxidative damage, you are creating more radicals, excuse me, creating more radicals that you need these two antioxidant vitamins to work hand in hand to protect you. And if we go to the next slide. What it turns out is metabolic syndrome, probably is afflicting more than 35% of American adults. It increases the risk of life threatening diseases. These are mostly chronic diseases, but I think we're going to probably see in the upcoming years that probably also increasing the risk of serious coven. So, we've been interested in metabolic syndrome and collaboration with rich Bruno at the Ohio State University, we studied people with metabolic syndrome. What we found is they have low vitamin C status. So exactly what Dr. Drisco was talking about, they've slipped out of the green zone into the yellow zone. Is that because they have more oxidative stress is that because they eat fewer fruits and vegetables. They have poor vitamin C intake, probably so. But what we also found is they have increased endotoxemia. So they are already on the way and primed for getting sepsis. We've heard how dangerous sepsis is, and how those patients come into the hospital with exceedingly low vitamin C levels. Well, we found out that that low vitamin C also makes low vitamin E. And so this whole idea of these interactions is demonstrable. And we'd like to encourage everybody. You don't need IV vitamin C if you are a normal healthy person. What you need is lots of fruits and vegetables. Maybe you should skip that steak and red meat and salami and go for fish. Go for fiber, and especially go for exercise. So on that message for healthy people. I'd like to turn it back over to Alex. Okay. Thank you, Meret. So at this point, we're actually going to start the question and answer session after. And I think what I'm going to do is follow up with with our number one question actually is as a vitamin C researchers the first question I'm always asked is, how much should I be taking, and I'm going to start with an e-tron that I think, Anitra, do you want to try tackling the how much should I be taking question? Very good question. And as the speakers have pointed out, the amount to take depends on your state of health. So healthy people. Mark Levine has done pharmacokinetic studies where he's given increasing doses of vitamin C to healthy people and shown that doses of 200 milligrams a day upwards will saturate the blood of healthy people. So I would recommend taking at least 200 milligrams a day. Most of us take more than that because it's very hard to get supplements that are less than 500 milligrams a day. So those of us who take supplements for generally taking at least 500 a day, that is fine because you know where our bodies will take what they need and excrete the rest. So at least 200 a day, you can get that from five to nine servings of fruit and vegetables. As long as at least one or two of those are high vitamin C foods because fruit and vegetables actually can have quite different levels of vitamin C in them. Bananas and apples are low in vitamin C. And oranges and kiwi fruit are high in vitamin C. So try and include high vitamin C foods in your diet if possible. And of course, if you're cooking those sources of vitamin C, it reduces the amount of vitamin C in them. The Lyons Pauling Institute does recommend 400 milligrams of vitamin C a day and it's partially because of that wiggle room we don't really know about. We've seen Dr. Levine studies and healthy people. And so we don't know what's going on in people who are sick. I'm going to actually just push the question on to Dr. Driscoe, if you would like to make a comment, what do you say when people ask you how much vitamin C you should be taking to be able. You're good. Yeah. I was fortunate to be able to measure vitamin levels in patients. And I do want to mention that measuring vitamin C levels in patients is really, really difficult. If you have a doctor that or a practitioner is going to measure your vitamin C level, and they send you to the lab to do it or they draw the blood in their clinic and send it over to the lab. It's probably not going to be done correctly. It's something that's called a critical frozen. And this doesn't go for the other vitamins. This goes for vitamin C. It's a critical frozen. As soon as you draw that sample, it has to be immediately processed because vitamin C degrades so quickly in liquids in lab specimens, whatever. So it has to be measured immediately. So if we were able to measure vitamin C, we were able to give advice based on the patient's need. And again, as it's been clearly shown today, different people at different stages need different amounts. So personally, because I'm aging and I take a little bit more vitamin C. And I think the good recommendation is to go up to bowel tolerance. So whatever you can take without upsetting your GI tract is probably a good dose for you at that time. And of course, it changes day to day and illness to illness. As Alex, you said we often need more when we're ill. And so that's how I usually respond. It's fair. Dr. Fowler, do you have a standard answer when someone asks you how much vitamin C? Well, I always and I think I have to agree with a nitra. I have a huge respiratory clinic. And I'm always dealing with infection, especially in people with underlying lung disease, especially during cold weather, even outside of the coronavirus. So I always advise them to take 500 milligrams twice daily of a product called ester C and ester C is formulated so that it does not upset your stomach. There are other preparations out there on the market of buffered vitamin C, but I have and personally take 500 milligrams twice a day. Jeannie just mentioned, we have measured vitamin C and our laboratory personnel. And exactly what she said, we take vitamin C immediately and plunge it, plunge a little purple top tube into ice water. And then directly into the laboratory centrifuged and we add a reducing agent that prevents it from being oxidized. And when we did that, we showed those high levels that I mentioned earlier. And when we did this on a laboratory personnel taking those levels of vitamin C 500 twice a day, we routinely got 250 micrograms of plasma vitamin C. Yeah, definitely know the challenges to accurately measuring vitamin C levels in anything. As I've been doing that for about 20 years now myself. But I know you say, you know, you should be getting vitamin C from the fruits and vegetables that you eat. When we get to about 400 milligrams or so it does get a little harder though to get that, that that amount of fruits and vegetables unless you're eating a lot of tropical fruits. Well, and I would like to emphasize I'm talking about normal healthy people. So we're talking about people who don't have current disease, who want to improve their health by improving their diet. And I think the idea of we're not that smart in nutrition yet. We're still waffling over saturated fat and cholesterol. And what is absolutely clear is you live longer. If you eat the diet I'm talking about lots of fruits and vegetables should fish fiber. And for God's sakes, if exercise were a pill. We would be so rich recommending taking 30 minutes of exercise every day. So being a COVID captive in my house. That's what I've done in. Hey, I feel healthier because of it. And of course, you know, there's so much more in fruits and vegetables than just vitamin C as you mentioned I mean all the vitamins all the minerals fiber. So you know, if you're going to take supplemental vitamin C just do it on top of all those fruits and vegetables. So, so okay I'm going to switch topics slightly. Dr. Fowler mentioned it just a moment ago, supplemental forms is something that we talk about a lot. It is of course one that's that's a little buffered helps with stomach, but one we get a question about a lot is liposomal vitamin C. And so, if for anyone who doesn't know liposomal is is lipid encapsulated vitamin C, kind of lipid droplets with with vitamin C in the center. And I'm going to start with Dr. Drisco on this one. What do you think about life is almost see why I have a very passionate answer about this because if you read some of the, the late books, it'll tell you that you can take liposomal vitamin C, and it'll be equivalent to getting IV vitamin C, and that is not accurate. So liposomal vitamin C perhaps is absorbed a bit better out of the GI tract, and gives you a little bit better blood level than, let's say, a typical tablet of L ascorbic acid of vitamin C, but it's still in the micro molar ranges. So it's that jumping over the one edge of the Grand Canyon to the next you can't do it with liposomal vitamin C. It's a good form. It does increase your blood level somewhat, but it's not the answer to replacing IV vitamin C. Perfectly fair. Dr. Carr, you have a follow up on that. Yes, I agree with Dr. Drisco. There's not huge differences between the two forms. And I think the thing to remember is that the body, because we absolutely need vitamin C in our diet, our body is very well designed at taking vitamin C up from food or tablets, whatever the source, it will get the vitamin C that it needs. So we've done studies where we've directly compared food sources of vitamin C with tablets and we've found exactly the same bioavailability, which means we're taking up the vitamin C the same amount regardless of whether it's with food and food as a tablet. So I think just trust the body. You give it, you know, give it enough and the body will take what it needs regardless of the source. I totally remember your studies with the kiwi kiwi fruit studies. Those are great. I love those. So I'm going to just pause for a moment here we were at the top of the hour. It's now noon. We don't want to terminate the broadcast now but we understand if people need to go. We only really scheduled this for an hour but we'd like to extend out another 20 minutes or so just to give more time for questions and answers from our panelists. Yeah, I'm going to continue. I think I might as well just go for the elephant in the room at this point. Let's talk about COVID-19. So, I'm going to start with Dr. Fowler again on this one. What do you think about, I mean, obviously you've got a trial going on right now. What do you think the role of vitamin C is going to be in COVID-19. Thank you very much for asking that. Can you hear me. Yep. Okay. COVID pneumonia, which is viral infection of the airways produces an inflammatory response. In fact, a very severe inflammatory response that is similar to sepsis. And in my experience, working with critical care doctors here at VCU, viral sepsis prevents presents very much like bacterial sepsis. And the extent of inflammation in the lung of patients suffering from viral pneumonia from the coronavirus. It's very similar to bacterial ARDS induced acute respiratory failure. And in our work, and I'm sure many of the panelists are familiar with the work we've done in the past 10 years. We showed that vitamin C very effectively, once you get these high blood levels acts as an interventional anti inflammatory drug. And in our studies of sepsis induced ARDS, we showed that vitamin C is successful, because first of all, it lowers the explosion of cell free DNA and the circulation, which is characteristic of acute inflammation. And the other thing we have shown is that vitamin C in these high plasma levels actually prevents vascular injury. And that is what is happening in COVID pneumonia is intense vascular injury of the lawn. And by giving high doses of vitamin C, we have shown that it's anti inflammatory and bacterial sepsis. And we have some sneaking suspicion that patients that are getting vitamin C in our trial, even though we're blinded, we have interestingly some patients who are recovering quickly, and other patients who are going on to die. And so I think for COVID pneumonia, vitamin C in these high blood levels and I'm talking blood levels that are in the five to six millimolar range, as Dr. Drisco mentioned, is effectively anti inflammatory. And that it, it calms down the inflammation, which unfortunately in many of these patients is leading to early pulmonary fibrosis in patients who do survive mechanical ventilation of 20 days or so. Same question to you, Dr. Drisco. I, you and I chatted briefly at the beginning of the pandemic about the stories coming out of China IV vitamin C and and and COVID-19 cases. Any, any follow up on that. Well, we had, we were able to help in another hospital in Wuhan with several of their patients in the ICU, and it's a case report, and we're getting this published now. And these patients were severely infected and not expected to survive. And when we used intravenous vitamin C at doses between 25 and 50 grams infused over a very short period of time, as I mentioned, maybe an hour, excuse me, the patients actually survived and were able to be discharged. So that intrigued us significantly. And when we heard Dr. Zang's reports about his patient, his trial that he treated patients with higher doses as well. We decided that what we needed now were the viral cell tissue work and the animal studies. So that's why we got funding to start those studies and they're underway now. I'm going to, I'm going to turn this over to Anika just for a moment, but, but kind of change the question just a little bit, because I know you've written a lot or a good review on the possible roles of vitamin C and COVID-19. There's a recent paper on oral dosing of vitamin C during COVID and it didn't look good. Do you have any comments on that one? Yes, this was a study carried out in Cleveland Clinic. I believe that's the one you're talking about. And they also had an arm where the patients were given zinc and zinc and vitamin C combination. And the dose of vitamin C they used in that study was eight grams a day oral. And they said to divide it into two or three doses a day, so potentially four grams twice a day. And we know that, you know, large doses like that aren't very, you know, adequately taken up into the body because the transporters in our gut are saturable. So they can only take up a certain amount of vitamin C, you know, over a certain time period. And earlier trials carried out in the common cold were more effective if the vitamin C was given more regularly. So on an hourly basis, for example, smaller doses spread out over the whole day. In this trial, Neva Lesh did show a shortening of the symptoms. So there was about 1.2 days shorter symptoms in the patients who received vitamin C versus the patients who just received standard of care. This wasn't statistically significant because they actually stopped the trial early because they thought it wasn't, you know, they said it's not effective. In reality, you know, it did show an effect. So I think if the trial had been designed better, there are a number of design issues with that trial. We might have seen, you know, even more dramatic results. And that's a typical problem we see with vitamin C studies in general. I mean, just poor study design or studies that are terminated early just because of various, but ways to, from our perspective, those would be very statistically underpowered studies. And so you can't really say anything. Yet they get big headlines saying vitamin C doesn't do anything in COVID-19. And I think that's a mistake to some degree. So some of it is like setting yourself up for success before the infection. Marat, you kind of talked about that, you know, getting your immune system primed. I mean, I don't know if you've been following the vitamin C and COVID literature, but, you know, it does make sense, right? Well, it makes sense to me. I think Mark Levine's name has already been mentioned a couple of times in this little symposium, but I'd like to remind everybody that the RDA for vitamin C was actually set based on Mark Levine's data showing that vitamin C can saturate white blood cells. And remember, white blood cells kill bacteria by spitting out bleach. And we all heard the horror story from the Trump administration. But the idea is that it actually works in vivo. I really wonder how much vitamin C is actually protecting white blood cells. And that's where I think it's a reasonable assumption that if you eat a good diet, if you have these tendencies towards having more difficulties, if you got an infection, taking vitamin C makes sense to me to protect yourself. Yeah, I mean, the immune system works through free radical mechanisms and nothing better to help you resist those free radicals than antioxidants like vitamin C and vitamin E, of course, don't want to forget that. And I guess that brings up another question that somebody asked in the crowd. What are the interactions? I mean, you know, we got vitamin C and vitamin E. Are there any other interactions that we should be paying attention to the body? Well, I think I've become the goddess of interactions. We are interested in vitamin C, vitamin E, glutathione, the production of energy metabolism, so the mitochondria. I'll throw in phosphatidylcholine, phospholipids, the membrane. So I can trace that to folic acid and we've been studying those kinds of interactions in the developing zebrafish embryo. And it seems like vitamin E is key to making all of those interactions feasible and possible. So if we had another week or so, I could explain the whole thing to you, but thanks for asking. We'll get you in a webinar sometime soon, right? And of course, as Dr. Carr mentioned, you know, zinc, there's a zinc, zinc is in support for the antioxidant network as well. So we can't forget that. You know, we also know that vitamin C has interactions with iron and copper, especially if you're talking about bioavailability iron. Vitamin C helps the bioavailability of iron. And so a lot of people take them together when they need more iron. I think it's a caution that if you don't need the iron, it might not be a great idea. So I think I'm actually going to turn back to recent headlines again because just the other day and just as we were planning this webinar, a new article came out on sepsis. And so I'm going to, I'm going to open the mic up for Dr. Fowler. Did you see that, that recent result with vitamin C and sepsis? No, what, which one are you? Oh, it is another JAMA article that basically said that. Oh, I know what you're talking about. All right, so let me let me address that. That was the Victus trial, which, which studied intravenous vitamin C at 1.5 grams given four times a day, way less than what we gave. Also, thiamine 200 milligrams per day, combined with hydrocortisone at 50 milligrams, four times a day. And that would be 200 milligrams. And I was part of this trial. And so I'm an author on the paper and that low level of vitamin C did not save lives, did not reduce organ failure, did not reduce the time of vasopressor support or time on ventilator, or time in ICU. And there was some criticism because the trial was privately funded. And after 500 patients had been enrolled, the funder pulled support that had been targeting 2000 patients. And so some of the argument was that statistically, we didn't see our outcomes because we weren't able to enroll the number of patients. And I think what we have learned today in this conversation, when you're treating critically ill patients, the, all of the biological reactions that are so relevant up that are injuring organs, it can't be treated by 1.5 grams of vitamin C. And it has to be treated with large doses, and it probably starts at about 15 grams intravenously. And Dr. Disco has much more experience in giving higher doses of intravenous vitamin C. And I think that's where studying sepsis needs to go. The study that I mentioned that's probably coming up within the next year on the petal network will use the VCU protocol for giving vitamin C. It's good to know, dose matters. Dr. Disco, I see you nodding your head. Let's get your take on this. I mean, definitely dose matters when it comes to sepsis, but also cancer. Yes, absolutely. I think probably what people need to understand in all of this is that there really is not a negative effect that occurs at these higher doses. We've done a pharmacokinetic study with increasing doses of intravenous vitamin C that we were getting ready for publication. And we started at 1 gram to 100 grams IV in patient healthy patients. And then we studied 2550 75 and 100 grams in cancer patients no longer getting therapy. And what we found was there isn't a maximal tolerated dose 100 grams was well tolerated and it still had an effect so likely we could even go higher. And we saw no organ damage. There's often a medical myth is what I call it that there's increased bleeding with these high doses of IV vitamin C. There was no change in bleeding factors and we measured three or four different bleeding factors, no change, no bleeding. There was not kidney damage, the kidney function remained normal from baseline to the following day. And some of those patients came back for four repeated doses weeks a week apart to confirm what we found. So there was and there's no injury to the red blood cell. And the calcium levels may have shifted a little bit at the high. What happens is when the higher doses of IV vitamin C when you even put it in plain water. It has what's called a high osmolality it's like a salt water to salty water for example. And at those high osmolar doses, we found there was a little bit of calcium shift, but not significant significant calcium drop. So that's another medical myth that's been out there that you can't give high dose IV vitamin C without putting calcium in the bag. Well that's not accurate. There's a lot of misunderstanding and misuse of IV vitamin C and some of the people that are not giving the proper doses as Dr. Fowler mentioned are poisoning our research agenda is essentially that so before you mentioned, you know, you were screening for kidney stone, you know, people with kidney stone problems before giving IV, how a lot of people have asked how real is this kidney stone risk. It's only in people and so what I want to back up we screen patients for this pharmacokinetic study with a 24 hour urine to look for oxalate production in the urine. And those patients that had very high oxalate levels that were excluded from our trial had had oxalate kidney stones. So we never in our clinic practice ever gave IV vitamin C to anyone that had a history of oxalate kidney stones. And if a patient didn't know they what kind of stone they had we aired on the side of caution. Sure, sure. I'll throw that to Dr. Carr actually when it comes to oral vitamin C is that you know, a concern that most people should have I mean if they're if they haven't had a history of kidney stone formation. No, I personally don't think it's a concern. I haven't done oral vitamin C research but Dr. Carr has but it should not it would be like eating your fruits and vegetables. And you may there may be some people. There's many reasons why kidney stones form but the oral vitamin C would be no different than eating a healthy plate full of fruits and vegetables. There's another thing I want to mention I'm sorry I have to say this. Recently in the literature there was a paper by Dr. Merrick, who is running who really run the victim's trial, and was using the 1.5 gram IV dose. I'd like to say that he's mentioned that you don't need to check g6 PD enzyme he has that in the literature, and the g6 PD enzyme, maybe at one gram dose is not an important enzyme to check. As you get higher in your doses of vitamin C but in the vein, you're going if you don't have that g6 PD enzyme, you're going to have a risk of breaking down red blood cells, and I have seen this I have actually helped several boards of healing people look at patients that have had massive homolysis lost blood, because they had g6 PD deficiency and got high dose IV vitamin C. So it has to be checked before high dose IV vitamin C is given. So I'll be quiet now. You know, anyone who's giving you intravenous vitamin C should be screening you for risks before doing this. I mean you don't trust a medical practitioner who doesn't do the screenings. I'll throw the question to you about, you know, safety. You know, when it comes to oral, do people have to be concerned? I don't believe so. If you have healthy kidney function, there should be no issues regardless of your oral type intake. Yeah, I haven't heard of any issues with oral, it's mostly just the high dose intravenous if you already have a pre-existing risk. Yeah, there were a few papers that looked, but they were kind of weak, you know. A lot of these are just association papers. So they look at someone's vitamin C intake and look at their later oxalate stone function and seen association. This does not prove a cause and effect. There's so many other factors that can increase someone's risk for these stones such as dehydration, you can get it to get it from other foods and vegetables cause high oxalate as well. It's not just vitamin C breakdown. So as you say, those papers are very weak, but they are the ones that are picked up by the media and the doctors, unfortunately. And my last question, unfortunately, we're running out of time, you know, so many questions, not enough time to answer them all. But I think what I'm going to ask is something that Barry touched on briefly, which was funding, you know, funding for trials is difficult. Do you have any trial start with you since you're on screen? How hard is it to get money for vitamin C research right now? That's very hard. Always has been. That hasn't changed. Although, you know, with with every trial that's published, this helps to help see our argument for doing, you know, vitamin C research. In the past, you know, there's been a lot of misunderstanding around the importance of vitamin C and its roles and functions in the body. But all the recent research showing these new mechanisms that are acting in the body, the epigenetic mechanisms, the regulation of gene transcription. This is all pointing towards mechanistic rationales for how vitamin C can work in different diseases. And so we can target our trials better based on all the information that we're gathering every, you know, every study is a piece in the puzzle. But it is still extremely difficult because still on a lot of these funding committees sit doctors who haven't learned about vitamin C and their medical training and don't understand its functions or its importance. So it's up to us to, you know, educate people, educate the doctors, publish and speak about it. And, you know, you know, it helps, but it is very difficult. Last, I'm just going to push that to Dr. Traver. I mean, how, how hard is it to give people to care about vitamins? It's very difficult. I think there's a certain cache about what is the latest fad, whether it's microbiome or even COVID-19. And I think to do basic studies that ask what is the best, what is the reason why we need vitamins. We're still working on that. And the mechanisms are just amazing. You heard epigenetics just mentioned. I think people thought, well, that's only important for cell division. Well, it turns out all of regulation of cells is dependent on epigenetics. And vitamins are in there supporting how well does this work and to not be able to get funding because somebody says, oh, we already know everything we need to know. And nobody is deficient in vitamin E or vitamin C or even zinc. So it's not true. And I'm, I'm worried about everybody's health. So I'll stop there and agree. We're going to have to stop there too. So I'm going to actually ask, I think every speaker for, for, for everything you said and all the questions that you've answered, this has been a great talk, which we could go on for another hour. But now I'm going to bring on Dr. Hope one last time to close this out. Great. Thank you. A huge thank you to our expert panel, Dr. Carr, Driscoe Fowler, Dr. Traver and our moderator, Dr. Michaels, a big thank you also goes out to OC foundation, Andrew Norwood and OC media services Nancy shanks and Eric who have been helping us on the back end. Again, thank you for all of you as well. Your passion for health is really apparent and trying to help answer your questions is something what the LPI is really all about. I know we weren't able to get to all the questions we're still learning how to, how to interact in this virtual world but please reach out to our email for more questions and we'll manage. We'll send out some communications around recording of this and additional venues to be able to answer your questions. If you liked our presentation today and vitamin C and appreciate our research that really helps uncover all these keys to optimal health, please consider making a donation and honor of Linus Pauling's birthday and Linus Pauling day. The links are here for you as well. We really appreciate your support in any way that you can, even if it's just, you know, we just want to hear from you and reach out to you as well so have a great weekend. And remember to eat your fruits and vegetables and think about vitamin C. See you soon.