Vitamin C for the Critically Ill with Dr Anitra Carr

Sepsis is a massive health issue worldwide. According to WHO, nearly 50 million people get sepsis every year, killing 11 million. Here in New Zealand, one in five ICU patients dies because of it. Thus, raising awareness about the role of vitamin C in sepsis can help save lives.

Dr Anitra Carr joins us in this episode to expand our understanding of the role of vitamin C in our body. She also explains how vitamin C functions not only as an antioxidant but also as a cofactor in many different mechanisms, particularly in fighting cancer and sepsis.

Everything we share in this episode will be helpful for you should you find yourself or a loved one admitted to a hospital, so tune in.

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Here are three reasons why you should listen to the full episode:

  1. Learn more about vitamin C’s antioxidant properties.
  2. Discover how vitamin C helps patients with pneumonia and sepsis.
  3. Learn about vitamin C’s role as a cofactor and how it ensures the proper functioning of different body processes.

Resources

Episode Highlights

[04:40] How Dr Carr’s Research on Vitamin C Started

  • Dr Carr’s research began in 1998, where she studied how reactive oxygen species (ROS) produced by white blood cells react with our tissues.
  • White blood cells produce ROS to help kill bacteria. However, they can also react with the tissues and create inflammation.
  • Dr Carr then began investigating how vitamin C’s antioxidant properties help decrease inflammation.
  • She also studied the benefits of vitamin C in preventing atherosclerotic plaques and the development of cardiovascular diseases (CVD).

[09:42] Vitamin C as an Antioxidant

  • Vitamin C has real antioxidant properties.
  • Metal ions produce oxidants in the body; vitamin C donates electrons to these ions, converting them to the reduced state.
  • The recommended daily dose to benefit from the antioxidant potential of vitamin C is 60 to 90 milligrammes in men and 75 milligrammes in women.
  • You need a higher dose (120 milligrammes) of the vitamin to protect yourself from CVD and cancer.

[17:57] Vitamin C in Food vs. Vitamin C Tablet

  • Dr Carr conducted a comparative dosing study between kiwi fruit and vitamin C tablets.
  • She found no difference in the vitamin C obtained from food and tablets. The body recognises the same molecule and takes up the same amount.

[21:36] Vitamin C in Sepsis and Pneumonia

  • Patients with pneumonia can develop sepsis, resulting in multi-organ failure, septic shock and, eventually, death.
  • In observational studies in patients with pneumonia, Dr Carr found that the lower the vitamin C levels, the higher the oxidative stress.
  • The body's requirement for vitamin C goes up by at least 30-fold when you get pneumonia and sepsis; it is hard to get those amounts orally.
  • ICU patients need a vitamin C dose of 100 milligrammes per day.
  • In these patients, the actual levels of vitamin C measured in the blood is lower compared to the amount they are receiving.

[25:25] Why Is Vitamin C Testing Not a Protocol in Hospitals?

  • Doctors are not familiar with the importance, recent research and mode of action of vitamin C because it is not taught in medical schools.
  • The hospital system is not set up to routinely measure vitamin C.
  • In trials, vitamin C is treated as a drug rather than a vitamin.
  • We need to know how vitamin C works to create proper and adequate study designs.

[32:27] What Are Some of the Future Vitamin C Studies We Can Conduct?

  • We need studies about the frequency, dosing and timing of its administration.
  • We need to learn about the finer details of the vitamin rather than doing the same study designs.
  • It is tough to obtain research funding due to the misinformation surrounding vitamin C.
  • We also need to educate doctors and patients alike about the science behind vitamin C.

[43:16] Vitamin C as a Cofactor

  • Our cells rely on enzymes to carry out chemical reactions. A cofactor helps enzyme function.
  • Vitamin C functions as a cofactor for the enzyme that synthesises noradrenaline and vasopressin. These hormones help in blood pressure regulation.
  • It’s better to give ICU patients vitamin C than giving them vasopressin drugs. This allows the body to naturally produce the hormone, preventing the side effects of getting vasopressin externally.
  • Vitamin C is also a cofactor of collagen, which plays a role in stopping cancer metastasis and wound healing.

[54:30] Vitamin C in Epigenetics

  • The expression of DNA may be regulated by adding or removing methyl groups.
  • Vitamin C is a cofactor for enzymes that modify DNA methylation.
  • It controls the switching on and off of genes, playing a possible role in personalised medicine.

7 Powerful Quotes from This Episode

‘I’m much more interested in the whole person and how they're feeling, not what's happening inside a single cell’.‘Don't wait until they're at death's door and at septic shock. It's hard for a vitamin to do something at this stage, even a really high-dose vitamin’.

‘A lot of these studies were designed to reproduce the first studies that came out to see if they could reproduce it also. That's why they’re using similar regimes. But now that we know more about it, each study adds another piece to the puzzle’.

‘There’s bigger issues at play with the whole pharmacological model that our whole system is built upon, and that nutrients and nutrition isn't taught in medical school. So, we're up against this big sort of brick wall’.

‘People go into a hospital setting or something, and they expect to have the latest and greatest information available, that the doctors know all that. And unfortunately, that's not always the case’.

‘Every person's life that is saved is a family that's not grieving’.

‘It’s the reason I’m doing this podcast, and it's the reason you're doing your research. And hopefully together and with many others, we can move the story along so that people get helped’.

About Dr Anitra

Dr Anitra Carr holds a PhD in Clinical Biochemistry/Pathology. She started researching vitamin C when she undertook a postdoctoral research position at the Linus Pauling Institute, Oregon State University, USA, and was also awarded an American Heart Association Postdoctoral Fellowship. Dr Carr produced a number of high-impact publications in the field of vitamin C in human health and disease.

Dr Carr is currently a Research Associate Professor at the University of Otago, Christchurch, School of Medicine. She has established her own research group, the Nutrition in Medicine Research Group, and undertakes translational bench-to-bedside research comprising observational studies and clinical trials on the role of oral and intravenous vitamin C in infection, cancer, metabolic health, mood and cognitive health.

Dr Carr endeavours to understand the underlying biochemical mechanisms of action as well as improve patient outcomes and quality of life. She also pursues various ways to improve clinician and general public understanding of the roles of vitamin C for the critically ill.

You may contact Dr Carr through anitra.carr@otago.ac.nz or call +64 3 364 0649.

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To pushing the limits,

Lisa

Full Transcript

Welcome to Pushing the Limits, the show that helps you reach your full potential with your host Lisa Tamati, brought to you by lisatamati.com

Lisa Tamati: Welcome back to the show! This week, I have another fantastic interview with another amazing scientist. But before we get there, I just want to remind you please give a rating and review to the show if you're enjoying the content and share it with your family and friends. I really appreciate that.

And if you haven't already grabbed a copy of my book Relentless, make sure you do, you won't regret it. It's an incredible story that is really about taking control of your own health and being responsible for your own health and thinking outside the box. And it's the story of bringing my mum back to health after a mess of aneurysm. And it will really make you think about those—the way our medical system works and about why you need to be proactive when it comes to health and prevention, preventative health. And it's really just a heart-warming story as well. So, you can grab that on my website at lisatamati.com. Or you can go to any bookshop in New Zealand and order that or get that and it's available also on audiobook for those people who love to listen to books rather than reading them, I know, I certainly do a lot of that. 

And just to also remind that if you have any questions around some of the topics that we've discussed on the podcast episodes, please reach out to me lisa@lisatamati.com. And if you want help with one of your health journeys or your performance journeys, or you want to work on some goal setting, on some mindset, please reach out there as well. We'd love to work with you.
So today I have the Dr Anitra Carr, who is a scientist at Otago University. She's currently a research associate professor at the University of Otago, Christchurch School of Medicine. She's established her own research group, the Nutrition in Medicine Research Group and undertakes translational bench to bedside research comprising observational studies and clinical trials on the role of oral and intravenous vitamin C in infection, cancer, metabolic health, mood, cognitive health.

And she endeavours to understand the underlying biochemical mechanisms of action as well as improve our patient outcomes. So, she's a person who loves to actually not just be in the lab and looking at petri dishes, but to actually help people in human intervention study. She currently has a study underway, which I'm really, really excited and waiting with bated breath to see what comes out. It’s a sepsis study, in the Christchurch hospital with 40 patients. And we talk a little bit about that today.

 And we talk about the role of vitamin C  today. Continuing the conversations that we've had with some of the world's best vitamin C researchers. We're looking at the antioxidant properties, we're looking at the pro-oxidant properties, we're looking at vitamin C as a cofactor in so many different mechanisms in the body. We talking about its role in the production of adrenaline and vasopressin, in hypoxia inducible factors, in relation to cancer, and especially in relation to sepsis, which is obviously a very important one for me.

One in five ICU patients in New Zealand dies of sepsis. This is a massive problem. Worldwide, between 30 and 50 million people a year get sepsis. This is something that you really need to know about. You need to understand it and Dr Anitra Carr, also shares why you may not get a doctor in a hospital situation, actually understanding all the information that we're going to be sharing with you today. So, educate yourself, learn from this and enjoy the show with Dr Anitra Carr.

Lisa: Well, hi, everybody. And welcome back to the show. Today I have Dr Anitra Carr, and today we're continuing the series around vitamin C. We've had some brilliant doctors and scientists on in the last few weeks and it's been really exciting to share some of the latest research and we have one of our own Kiwi scientists with us today, Dr Anitra Carr from Christchurch. Welcome to the show.

Dr Anitra Carr: Hi, Lisa!

Lisa: It's fantastic to have you. So, Dr Anitra, can you just tell us a little bit of your background and how you got involved with vitamin C research?

Dr Anitra: Well, I first started researching back in the late 90s. So, 1998 and I had just finished a PhD with the University of Otago and I had been studying how reactive oxygen species that are produced by white blood cells react with our own tissues, damage their own tissues because these white blood cells produce these really reactive oxidants, such as hydrogen peroxide, which is hair bleach, and hypochlorous acid, which is household bleach. So very strong oxidants and they produce these to help kill bacteria in our bodies. But these oxidants can also react with their own tissues and that's what contributes to inflammation and the processes of inflammation.

And so, I've just been studying how these oxidants react to certain components in our tissues. And when I finished that, I thought it’d be really interesting to investigate how antioxidants, such as vitamin C, which is one of the most potent antioxidants in our body, and help potentially protect against this damage. So, scavenge those oxidants before they react with our tissues, and help decrease the inflammation associated with them and features and conditions.

And so, I applied to various people in the United States, I wanted to go to continue my research in the United States. And so I applied to several people over there who are doing research in the area that I was interested in, and they'll write back and say, ‘Yes, we have postdoctoral positions available.’ And so I selected one, on the advice of my PhD supervisor, and this was Professor Balz Frei. He was at the time in Boston. And after I said, ‘Yes, I'd like to work with him.’ He wrote back and said, ‘Oh, by the way, I'm moving to the west coast to Oregon. And I'm going to be the director, the new director of the Linus Pauling Institute.’ 

Lisa: Oh, wow. 

Dr Anitra: Great opportunity it is. I like the West Coast of the United States. I've done a bit of work in California during my PhD. And so, I was quite happy with it. And so Linus Pauling had died just a few years prior to that. And so, the Linus Pauling Institute, which was in California, at the time, kind of needed a new home, I think they're in Palo Alto.

And so they ended up going to Oregon State University because that was—for a couple of reasons—that was Linus Pauling alma mater. So, he had done his undergraduate research when he was in a cultural college. And also, because the library there was going to be able to host his papers. And so he has this collection of his writings and papers, thousands and thousands of documents, because as you've stated before, he's one of the only people to have been awarded two unshared Nobel prizes. So one was in chemistry around his work on the nature of the chemical bond. And the other one was a Peace Prize for his anti-nuclear campaign.

And so the Oregon State University Library has his complete collection, it's called the Linus Pauling Special Collection. And so I spent a few years at Oregon State University researching how vitamin C can protect against oxidation of low density lipoprotein particles, which are what the body uses to export fat and cholesterol around the body, because the cells need cholesterol. But most people know low density lipoprotein protein as bad cholesterol. I mean, it's not intrinsically bad. But if it becomes oxidized, it can contribute to the development of atherosclerotic plaques and contribute to cardiovascular disease. And so I was looking at how vitamin C can protect against oxidation of this particle, and thereby potentially peak against development of atherosclerosis. And I was...

Lisa: What was the outcome of it? That would be really interesting.

Dr Anitra: Yes. So, I was particularly interested in the oxidants produced by white blood cells, because these can react with these low density lipoprotein particles and oxidized them. And vitamin C is a great scavenger in particular, and I was interested in how much do you need and how the particulars—is the real biochemical level?

And, but also during this time, so late 1990s. We were interested—Professor Balz Frei was interested in the recommended dietary intakes for vitamin C. Because in a lot of countries they are very low—these recommendations, primarily to prevent deficiency diseases, such as scurvy. Whereas, we believe you know, that the recommendations should be high to help reduce the risk of chronic diseases such as cardiovascular disease and cancer and that sort of thing. That's a bit helpful to the outcome.

So, in the late 90s, in 1998, the Food and Nutrition board of the Institutes of Medicine was re-examining the recommended dietary intake for the antioxidant vitamins, the A, C, and E in the United States.  And we write a comprehensive review around all the scientific evidence at the time for what sort of doses of vitamin C appear to protect against cardiovascular disease and cancer.

And so, we made a recommendation of 120 milligrams a day, which was, at that time twice what the recommended dietary intake in the States, it was 60 milligrams a day at the time. And so we submitted that document, and it was considered by the Food and Nutrition Board. And also another review, I'd written around vitamin C's antioxidant roles in the body versus its pro-oxidant roles. Vitamin C, referred to as pro-oxidant.

Lisa: Yes, I’ve heard that. To get hit around the antioxidant and as a pro-oxidant.

Dr Anitra: Vitamin C is an antioxidant. It's not a not oxidant, pro-oxidant. But what it does is it can reduce—so antioxidants donate electrons, and they reduce oxidized compounds. So, it reduces transition metal ions such as copper and iron. So, these are metals in our body that can read off cycles so they can produce oxidants.

Lisa: Yes, and we've talked about redox before in the podcast.

Dr Anitra: Yes, so what vitamin C does is it converts these metal ions into a reduced state and metal ions can go on and generate oxidants.

Lisa: So it gives ion and copper a longer life, does it? It sort of gives them—ion and copper away to keep going?

Dr Anitra: Regenerates them so that these metal ions can keep producing oxidants. But in our body, these metal ions are all sequestered away and protected by proteins, they're not floating around free. In the body, vitamin C doesn't seem to do that, based on the evidence, it seems to just have it’s true antioxidant roles, not this kind of prooxidant by-product, as you might call it.

So, this sort of evidence was considered by the Food and Nutrition Board and they decided, ‘Yes, it does have an antioxidant role in the body.’ And, and so they also referred to Mark Levine's seminal work to kind of work out a dose, a daily dose of vitamin C, they thought would be good to help foster this antioxidant potential on the body—potentially protect against these other chronic long-term diseases such as cardiovascular disease and cancer.

And so they did end up increasing the RDA for vitamin C instead from 50 to 90 milligrams a day for men, and 75 milligrams a day for women. So that was good, not quite as high as we would have liked to see, but still a step in the right direction.

Lisa: A very conservative, aren’t they? They are slow to respond and conservative? Because you think like being the preventative space would be a good thing, if we're trying to...

Dr Anitra: It is. Prevention is a lot cheaper, a lot easier to prevent a disease.

Lisa: Exactly. But I think New Zealand's even worse, isn't it? I think we're at 45 milligrams, which is I think it is.

Dr Anitra: One of the lowest in the world, yes.

Lisa: That’s got to change, sorry. 

Dr Anitra: So we're trying to generate the evidence to help support them increase in RDA.

Lisa: Gosh, so it's also slow, like you've been doing this for what? 20-like years. And still...

Dr Anitra: They do say that translation of science into medical research into clinical practice takes 15 to 20 years.

Lisa: Wow, that is a really interesting statement. Because this is why I think, like sharing the sort of information direct from the experts, if you like, and I sit this was Professor Margreet Vissers too, that we have to make sort of educated decisions as people in trouble now. Whether you've got cancer or whether like my case who have a dad who had sepsis, you have to make an educated decision now based on you're running out of time. And we're waiting for the research and the research will be great, but it will be another 10 to 20 years down the line before it actually…

And then in the medical world, it seems to be a very slow—Doctor Fowler said that beautifully when I had him on last week. It's like trying to shift a supertanker, Critical Care he was referring to is very, very slowly coming around. And I had Dr Ron Hunninghake on as well from the Riordan Institute, another fantastic doctor, and he talked about Medical Mavericks. Dr Hugh Riordan had written three books on people who were really ahead of their time, got in trouble for it and then actually the research and everything caught up with them later. 

So that's interesting. So, if you’re listening to this, New Zealand has got 45 milligrams as the RDA, that's just to keep you out of scurvy. Right? 

So, okay, so you've done all this antioxidant research and this with RSS and at the Linus Pauling Institute, when did you start to develop an interest in the infectious diseases, sepsis side of that, because I'd really love to...

Dr Anitra: Yes, that's, that's more recent.  So, after a few years—three years at the Institute, I decided to have our first child and move back to New Zealand. And I made the decision to quit science and just focus on bringing up our family, ended up having three children. Stayed home for nine years looking out after our children. And I made the decision that they were more important than my career 

Lisa: Wonderful. That's an interesting fact, as well as a mom and a scientist, like, an incredibly dedicated career that you'd have spent years getting there and then trying to juggle mum roles with scientist roles, and taking nine years out of your career. Has that hurt your career massively? Or I would have catch up so to speak?

Dr Anitra: It hasn't hurt my career. I mean, I'm 10 years behind my contemporaries, my colleagues because I took that time out. But that's the decision I made. And I stand by it because the first three years of a child's life are very important. So I thought I'll dedicate myself to the children in the early years. And after those nine years, right? I've done my time and really can’t get back to work.
Lisa: Mum's going to be a working mum from now on. 

Dr Anitra: But I just went back to work part time, so, within school hours, so that I'll still be there for them after school hours. And one of the things that drew me back to work—I was recruited back to run a human intervention study. What really excited me because when I was in the lab doing lead-based research, I always felt too removed from the need to be helping. And so I’m much more interested in the whole person and how they're feeling, not what's happening inside a single cell. 

Lisa: Yes. Yes, it makes sense. 

Dr Anitra: I was really excited and really grateful to be recruited back, especially after taking nine years out for my... Discoveries have been made during that time that I had no idea until I went back and I've got a bit of catching up to do. And...

Lisa: So what was that first intervention study, that human... 

Dr Anitra: This was a kiwi fruit study. So kiwi fruit is very high in vitamin C. In summary, we're interested in how many kiwi fruit do you need to eat to get adequate and optimal vitamin C level. So it's just kind of a dosing study? 

Lisa: Brilliant.

Dr Anitra: Then we went on to compare kiwi fruit with tablets. So, animal research had shown our food sources of Vitamin C seemed to be a bit better than tablet sources. And so we would—we thought we'd translate that into a human study. And what we found is there's no difference .

Lisa: There's no difference. Uptake of vitamin C from food versus tablets, the body is really good at it. Because we need vitamin C, our body has adapted ways to...  

Lisa: Take it wherever it gets it.

Dr Anitra: Take it up, regardless of the source.

Lisa: Wow, that's...

Dr Anitra: The structure of vitamin C's the same in foods as it is in tablets. So the body recognizes it the same, takes up the same amounts. I mean, the benefit of food is that you're also getting all the other vitamins and minerals and fibre. So, we still recommend food. But it is in our daily diets these days, it's very hard to get 200 milligrams a day of vitamin C.

Lisa: Just fruits and veggies. Yes.

Dr Anitra: That’s just fruit and vegetables. And as you know, different fruits and vegetables have quite different amounts of vitamin C, which a lot of people aren't aware of.

Lisa: No. No.

Dr Anitra: I mean, people know that kiwi fruit and citrus are high, but they may not realize that apples and bananas are actually quite low in vitamin C.

Lisa: Or capsicums are quite high… You wouldn’t think that broccoli… And if you decide to take a supplement, is there a bit of supplement? Like, I have heard concerns about corn-derived vitamin C because of the glyphosate discussion, and that’s a bit hard to track really, the types of vitamin C. But is there any sort of research around—I mean, I've talked previously with a couple of doctors and scientists around liposomal delivery. Have you seen anything in that department or any supplementation method that's better?

Dr Anitra: Not convincingly better. I mean, there might be trials that show that’s slightly better than just your normal chewable vitamin C. But I just go for the standard, cheap vitamin.
Lisa: Yes, doesn't have to be super special. Like it's a pretty simple molecule, isn't it? Like, the body is pretty, like you say, it needs it, it knows it.

Dr Anitra: Liposomal vitamin C kind of wrapped up in lipids, and the body doesn't need it because like you said it’s designed to recognize vitamin C in its natural form, in foods and such like.

Lisa: Yes—who was that? I think Dr Thomas Levy was saying it bypasses some of the digestive issues because with vitamin C, you can get digestive stress when you take a bigger...

Dr Anitra: When you take a higher dose. Some people, we're talking about more than four grams a day, and some people can get stress, it does but you can use that.

Lisa: Okay. So then you've moved into—and forgive me for jumping here—but very keen to talk about the role of sepsis and pneumonia and patients in ICU reasons.

Dr Anitra: So, after about five years of doing that research part time, I managed to get at Health Research Council, such as speakers Health Research Fellowship, which allowed me to move into the more clinical arena of studying infection, which was an area I was interested in.

And done some observational studies where we have recruited patients who have pneumonia, measured the vitamin C levels, and levels of oxidative stress. And found that they have very low levels of vitamin C and high levels of oxidative stress. And the more severe the condition, the worse it is, the lower the vitamin C levels, and the higher the oxidative stress.

So, if those patients with pneumonia are going to develop sepsis, and sepsis is kind of this uncontrolled inflammatory response to a severe infection. And that can develop into multi organ failure and the patient’s taken to the intensive care unit. And it can go on further to develop into septic shock due to failure of the cardiovascular system. And up to half those patients die, it’s the major cause of death in critically ill patients.

Lisa: Yes. And that's what I unfortunately experienced with my dad. And so, with the organs are starting to break down. So, when you get anything like pneumonia or sepsis, the body's requirement just goes up, a hundred-fold or more.

Dr Anitra: Yes, at least 30-fold. Yes. So, it's very hard to get those amounts into a patient orally. And so, when the patients are in the intensive care unit, they're generally sedated because they're being mechanically ventilated. And so, they're given nutrition in two different ways because they can't eat. And so, the main way is to drip feed it directly into the stomach, liquid nutrition in the stomach through nasal gastric tube. The other way is to inject it directly into the bloodstream. And so, the recommended amounts of vitamin C by these means is about 100 milligrams a day.

Lisa: That’s nothing. 

Dr Anitra: But what we did on one of our studies was we looked at how much vitamin C these patients should theoretically have in their blood based on how much vitamin C they're consuming. Because 100 milligrams a day in a healthy person is more than adequate to—provides adequate plasma, what we would consider adequate plasma levels. And so, we mapped out what it would look like in these patients based on how much they were getting. And then we compared it with what we actually measured in their blood, it’s way lower than what theoretically should have been. And so, this, this was an indication that you still need a lot more vitamin C than they're getting in the standard liquid nutrition. And that the body also has these much higher requirements, which has been shown previously by other researchers.

Lisa: And so this leading to almost a scurvy-like situation. I mean, some of these severe sepsis people—I mean, seeing one of your [unintelligible 24:53] that sort of normal community cohort of people, young people, middle aged people, and then down into the more severe pneumonia and then sepsis, and severe sepsis. And they are just over the scurvy level. So basically, their bodies are falling apart because of that, as well as the sepsis if you like. and it's...

Dr Anitra: And that’s even on top of being given a day of at least 100 milligrams a day, that's still really low.

Lisa: That's just not touching the sides. 

Dr Anitra: Yes and... 

Lisa: Why is this not like—for people going into the hospital, why is it that even though—okay, we may not know the dosages, why is not every hospital testing at least the really sick patients, what their vitamin C levels are, and then treating it the nutrient deficiency only? Even apart from the high dose intravenous stuff, but just actually—with my dad, I was unable to get a vitamin C test done to prove my case. I couldn't prove my case because I couldn't get it tested. 

Dr Anitra: Yes, no, it's so true. It's because doctors don't learn about nutrients in medical school, it’s not part of their training. 

Lisa: At all, yes. 

Dr Anitra: So they're not familiar with how important they are for the body. They're not familiar with all the recent research around all the different functions and mechanisms of action that vitamin C carries out. Over the last 10 years, all these brand-new mechanisms and functions have been discovered, and they think we know everything there is to know about it. 

Lisa: Yes, and we don't.

Dr Anitra: [unintelligible 26:34] the time. It’s basically exciting.

Lisa: Yes, it is. 

Dr Anitra: So basically, they don't understand. The hospital system isn't set up to routinely measure it. It is only ever measured if scurvy—if someone comes in with suspected scurvy. And even then, a lot of doctors aren't used to recognizing the symptoms of scurvy. It's not something they're familiar with because it doesn’t...

Lisa: They think it no longer exists because it’s what sailors had in the 1800s.

Dr Anitra: ...the parents and the wisdom. 

Lisa: It’s basically in the sick population.

Dr Anitra: It is. But I think... So when I first applied for funding to carry out these studies, in pneumonia and sepsis, there were only a couple of papers have been published at that time looking at vitamin C sepsis, and that was Berry Fowler's safety dosing study. 

Lisa: That is phase one trial.

Dr Anitra: And another one, small one in Iran. So, there was very, very little information out there at the time. And so, I put in an application for us to carry out an intervention study in our ICU at Christchurch. So just a small one, 40 people—20 placebo control of vitamin C and 20 getting intravenous vitamin C.

And not long after that, Paul Marik's study came out and that stimulated real explosion and research in this field because of the media interest. So the media picked up on it. And it hit the world. I've been talking about this for years to doctors. I see doctors and they're trying to get to talk about it. But it wasn't until it hit the media, and they heard about it through the media, they thought, ‘Okay, maybe there's something here.’ So that just goes to show how important media can be.

Lisa: Exactly why we're doing the show. I have not seen it. But you know what I mean? We've got to get this from the ground up moving.

Dr Anitra: Yes. And so since then, there's been many studies carried out around the world, all of different quality. And so we're learning more and more information, real-time clinical trials, they take a long time to run. Recruitment being the most difficult part.

The other thing is that, a lot of the clinical trials, the clinical researches are used to running drug trials and so they treat vitamin C like a drug, but it's not a drug. It's a nutrient, it’s a vitamin, that the body is specially designed to take up and use very different from drugs. And so they don't always understand how vitamin C works in the body.

And it's important to know how it's working in order to design good studies, good quality studies. So a lot of the data that's come out may be impacted by how well the study was done and thought out. So we still don't know all the important essays about the dose, how often should you give it, when should you give it?  I mean, ideally it should be given you know, as early as possible.

Lisa: Early as possible.

Dr Anitra: Don't wait until they're at death's door and septic shock. It's hard for vitamin C to do something at that stage even really high, even a really high dose vitamin. The earlier that you give it, the longer you can get it for digest.  Most of these trials have given it for four days and they stop.

Lisa: Yes, I've wondered that.

Dr Anitra: The whole time, they're in the ICU because once pharmacokinetic study showed that when you stop that vitamin C, some of those patients just drop straight back down to where they were. Now they need to keep that continued input.

Lisa: So why? Why has it been made that it's only—all of those I've seen, I think have been 4-day, 96 hour studies. And occasionally one of them is or for the latest day in ICU, but most of them have been 96 hours and most of them have been very, very conservative dosing. From what I understand conservative dosing. And I know Dr Berry Fowler said where there's some consideration about oxalate in kidney function. And I'm like, ‘Yes, but this is still a very low risk for somebody who's got sepsis.’

Dr Anitra:  If a patient has kidney dysfunction in ICU they put them on haemodialysis anyway, so which clears that excess vitamin C. So it's not such an issue for those patients. But yes, a lot of these studies were designed to reproduce the first studies that came out to see if they are reproducible. so, that's why they’re using similar regimes. But now that we know more about it, each study adds another piece to the puzzle. And so hopefully, future studies will look more into what dose we actually need and it only varies depending on the...

Lisa: The severity

Dr Anitra: Severity, etc. How long? And I believe, once they leave the ICU... So patients who survived sepsis, they can go on to have real problems, physical disabilities, cognitive issues, psychological issues, like depression, anxiety. And so, I really believe they keep taking vitamin C when they leave the hospital just orally, that might help with those conditions that hasn't been researched yet. That's a whole area of research that should be carried out to.

Lisa: So, if I was to ask you, in your dream world where your resources are unlimited, and you had lots of money, and you had lots of people to help you do all these and you have enough patience to enrol. What are some other things that you would like as a scientist and you understand some of the mechanisms and the cofactors—which I want to get on to as well—what are some of the studies that you would like to see happen? So, we can move this along faster.  What are some of the key things?  So, quality of life afterwards? Yes, like dosages, what?

Dr Anitra: Really practical things that the doctors need to know, I think, what's important, like, how much to give, how often to give it? Most of the studies are done four times a day because that's what was done in the initial studies. Is it better to give it continuously? So, when they're in the ICU, can you just use drugs continuously, rather than this kind of bolus dosing?  So, do more research around that.

So the frequency and dosing and timing like when do you administer it, how long should you administer it for? I mean, there's so many important aspects around that. And we've got the foundational research done now, we can start teasing out the finer details now, I think. Rather than just doing the same study designs over and over again.

Lisa: Yes and reproducing.

Dr Anitra: Modify their study designs to start addressing these other issues. And there's some really big studies underway at the moment. One in Canada with 800 people. I mean, they'll give us really good information, those sorts of studies, rather than the little studies. Unless you live in small countries.

Lisa: Small countries that can’t afford those things that cost millions and millions of dollars. And is there a trouble with funding because it's not a drug that we're developing here? Does it make it harder to get funding?

Dr Anitra: It's extremely hard to get funding because often on the CSUN committee, it's often medical people on these who don't believe in vitamin C. The bad press or the misinformation don't understand the importance, the relevance and so, that's why this outreach is really important. It's just educating people about the science behind it. It's not hocus pocus.

Lisa: Yes, I mean, if I can share—I mean, I've shared a little bit on the past episodes with my case with my dad. I know and I felt they just put me in that, wackery quackery caught and they paid lip service to listening to me. They didn't really and but I’m quite—well in this case, I had to be quite forceful because my dad was dying. And I didn't go away, most people would go away because—and I just wish I knew then what I know now even because I wasn't that deep into the research. And now I am deep into the research and really an advocate for this.

But I was treated like—there was one really good doctor who listened to me, who advocated, he didn't believe in it, he didn't understand the mechanisms of action or any of that sciency stuff. But he did advocate for me at the ethics committee, whereas everyone else would just roll their eyes basically.

And this is why I think it's so important to share this, to come back again and again to the science for science for science, and for them to just open up their eyes just because they didn't learn it in medical school. And it's not in the current textbook for, like you say, because it takes 20 years probably to get it to the textbook. Because it's a vitamin, they just immediately shut down, it’s how I felt. They just immediately, ‘Well, just eat an orange and you're good to go.’

I mean, the surgeon—I had a friend that was going into surgery, and she was like, ‘Should I have intravenous vitamin C, before I go into surgery to prepare my body?’ Very logical thing to do in my eyes. It’s like, ‘You don’t need that, just eat an orange,’ and it's like, ‘Oh, you don't get the whole why and how, and what happens when the body goes through a trauma and a surgery, or a sepsis or any of these things.’And I don't know, like there's a bigger issue at play with the whole pharmacological model that our whole system is built upon. And that nutrients and nutrition isn't taught in medical school. So we're up against this big sort of brick wall.

And when I tell my story to people just, sharing with friends and things, they’ll be going, ‘But where's the downside? He was dying anyway, why couldn't he have it?’ And I said, ‘Well, you're up against machinery, you're up against ethics committees, legal battles, and a system that is just very staid and conservative in its approach.’

And that's not to criticize individual people within the system. I'm not wanting to do that. I'm just trying to make people aware because people go into a hospital setting or something, and they expect to have the latest and greatest information available that the doctors know all that. And unfortunately, that's not always the case. Do you find that frustrating?

Dr Anitra: I mean, it's not the doctors’ fault as such, because they're very busy people, they don't have time to keep up with all the literature, and they're not likely to be going into the nutrition literature in the first place. Which is why we try and publish as much of that stuff and the clinical literature, they're more likely to see it then.

And they have the patient's best interests at heart. They've just heard the bad things about vitamin C and the misinformation. And so they don't want to do harm to the patient, I guess. It’s the view that they’re coming from and they don't have time to read all the latest information. And that's why just piece by piece, chip away at theirs, and educate them and hopefully it'll come into the training of the new doctors. And future hopefully, more nutrition courses will be introduced into training because it's not just vitamin C.

The body needs all the vitamins that are all vital to life. That's where the name comes from. You don't hit them, you die. It's as simple as that. So, yes, I think that it is vital that this information gets into the appropriate arenas.

Lisa: Yes. And I think that's why I'm passionate about the show is that my sort of outlook on the whole thing is, ‘Yes, I'm not a doctor, but I can give voice to doctors and researchers. And I can curate and I can investigate and I can share.’ And this is a very emotional topic for me or for obvious reasons, but I'm trying to take the emotion out of it because that doesn't help the discussion.

And it’s really hard but I understand the importance—because I know that if I share things in an emotional manner, then I'll get shut down as having mental health problems in a group being a grieving daughter. When actually I’m an intelligent person who's educated herself in this. I've got the best people, and the best researchers, and the best scientists, and the best doctors sharing the latest research. And I hope that by doing that you can get one mind after the other and just get them to understand rather than the emotional side of things. Because what I do want to also share with the story is that every person's life that is saved is a family that's not grieving. These are not statistics.

When Dr Berry Fowler's research, with Dr Merricks research and you see a drop from, I think Dr Merricks was 40%, mortality to 8% and Dr Berry’s was something like 49, down to 29. Don't quote me on the numbers, but big numbers in drops and mortality. And you go, those are just dozens, if not hundreds of lives that are saved. And those families are saved from that grief.

And worldwide, I've heard a couple of estimates between 30 and 50 million people a year who get sepsis. Of those, one in five—I've heard in your research—one in five in New Zealand ICU dies of sepsis. This is a huge problem. This is as big as cancer and actually is one of the complications often of cancer therapies. So, I don't think people understand the enormity of sepsis itself. And then pneumonia, and then we can go into the discussion of COVID, and cancer, and all those other things. It's like we're talking millions of lives every year around the world. So this research is just absolutely crucial. Sorry, I've gotten on my bandwagon a little bit. But I really want to get this information out there. And that I think it's really, really important.

And let’s change track a little bit and just talk a little bit briefly because I haven't covered this subject with the other vitamin C interviews that I've done. Around the cofactor, so vitamin C is a cofactor for so many different areas. So I remember from one of your lectures, it has epigenetic influences and hairs like with collagen synthesis, and that's not just for your skin and your and your nails, but also has implications for cancer. You've got your health, which Professor Margreet Vissers talked about your hypoxia inducible factor, tumor growth.

Can you just go and give me a little bit of information around—the vasopressin one would be very good and anything else that pops to mind there.

Dr Anitra: Yes, so the cofactor is a compound that helps enzyme function. So everything in our cells relies on the functions of enzymes to carry out reactions in ourselves or the chemical reactions require enzymes. And so a cofactor supports that function.

And so early on when I was just starting in this area of research in the field of sepsis, I was looking at the different cofactor functions of vitamin C, and one of them is a cofactor for the enzyme which synthesizes noradrenaline. And noradrenaline is one of the main drugs, as you might say, that's given to patients who are going into septic shock. So it's given to the patients to try and increase the blood pressure. And it works by making the muscles around the blood vessels contract. Makes the blood vessels a bit smaller, so it increases your blood pressure.

And so vitamin C is a cofactor for the enzyme that naturally synthesizes noradrenaline in our body. And there's another enzyme which synthesizes hormones, one of which is vasopressin.  And this is another drug that's also sometimes given to these patients to help your blood pressure. And it works by increasing the re-uptake of water by the kidney. So, that increases your blood volume and hence, your blood pressure. So, for a lot of ICU patients, they're given noradrenaline and sometimes they're given vasopressin on top of that. Really try and get the blood pressure up.

Lisa: Yes, their collapsing cardiovascular system.

Dr Anitra: And I realized, ‘Oh wait a minute vitamin C is also cofactor for this enzyme that synthesizes vasopressin.’ So here it is, a cofactor for two quite different enzymes that synthesize vasopressors naturally in our body. And so, if these patients are coming into the ICU, very low in vitamin C, and going into shock, is one of those reasons because they don't have enough vitamin C in the body to support natural vasopressor function. The doctors have to give them these drugs but if we're able to get them vitamin C, early enough that it can potentially support their own natural synthesis of these vasopressors in the body, which is a much better way to do it. Because if drugs are given from the outside, they're often given in high doses and not regulated, and so can cause side effects. There is a difference being produced in the body, the body knows what it's doing. It regulates how much and how often, all those sort of 46:07 engineering emails and so you don't get the nasty side effects.

Lisa: Can I share a bit of a story there? Because both my mom and her case was—she had an aneurysm four years ago, she was on noradrenaline, and could only be given in an ICU. And originally she was in the neurological ward. And they couldn't do it there. And I only realized like she was going into a coma. So she had massive brain damage going into a coma. That when they took her up to ICU, they could give her the noradrenaline that opened up that the vessels in the heat it a little bit, or keep the pressure up, so that the vessels were open to stop the vasospasm in her case, which was killing parts of the brain. But she'd been in the neurological ward where they couldn't give any of that earlier. And so the damage had already been done partly.

And then with the case with my dad, back then I didn't know anything about vitamin C, of course. With the case with my dad in July, this year, I got vitamin C, but it was on day 13 of his 15-day battle, because I had paid to go through ethics committees and all of that sort of jazz. So he was an absolute death's doorstep, should have been dead days ago, according to the doctors. They couldn't believe he was still going but he was one tough man. I don’t know how he was still alive but he was. And the very first infusion that we got a vitamin C, immediately we were able to take him off norad for a period of about eight hours. We needed the vitamin C again, that took me another 18 hours before I could get permission to get the second one. Unfortunately, I couldn't get it in the six-hour bolus, which was ideal.

We gave him initially 15 grams. So this was again, multiple organ failure, fecal matter, and the creatinine, desperate, desperate, desperate straits. His CRP, c-reactive protein dropped from 246 down to 115. His white blood cell count improved and his kidney function went from 27% to 33%. And I was able to take him on vasopressors and noradrenaline for about eight hours. That is incredible for someone who could die at any moment. And we eventually—we failed because I struggled to get the second and I struggled to get the third infusion and it really was too late.

But even at that point, I thought it might be interesting for your research—I have all the medical records by the way, if you want to have a look at the data exactly. But it really was a strong—he doesn't need the noradrenaline, his blood pressure was going up. And that was a really, really good sign. As the dropping of the CRP, which was still very high at 115 but it was way better than where it had been.

So goodness, what would have happened if I'd had him on day one from the surgery? Yes. And, and none of it is understood. So that's one of the cofactors that… And that brings to mind just as someone who's connecting the dots, if you have an HPA axis problem, like your adrenals aren't doing the job well. And your cortisol, vitamin C would probably be a good thing to take to support.

Dr Anitra: And sometimes it’s referred to as a stress hormone because it is involved in the adrenal response. And people who are under stress, or in animal studies who have stress animals they appear, they use more vitamin C, and they generate more vitamin C, the animals they can synthesize it themselves, they generate more vitamin C to compensate for that. We are not there anymore. So we have to take more if we're under stressful conditions.

Lisa: Exactly. And that's a really—it's just a funny thing of evolution that we've lost the ability to synthesize more as we like animals, like the goat, especially it can synthesize like a ton more when it needs that. We will give them big brains so that we can make vitamin C so we can take it.

What are some of the other cofactors? Just as we start to wrap it up, but just a couple of the other important cofactors.  And collagen? Why is collagen important apart from you want my skin and hair, and your joints? Well, I did hear in one of the lectures about collagen helping stop metastasis of cancers?

Dr Anitra: Right, yes, that's one mechanism. It's also very important in wound healing. And, interestingly, a lot of—a reasonable number of surgeons are aware of this and that they're a lot more open to people taking vitamin C around surgery before and after surgery just to help affect wound healing.

Lisa: Oh, wow. Yes.

Dr Anitra: Which is great. And

Lisa: And oncologists, are they sort of open to...

Dr Anitra: Least so.

Lisa: Least so. Yes. In fact, I've had friends who have told us, if you take intravenous vitamin C, we won't do any treatments. And this is...

Dr Anitra: And that is primarily around all the misunderstanding around those early, early trials around intravenous. What I'm seeing is when Linus Pauling showed a feat of vital intravenous vitamin C. The clinicians at the Mayo Clinic who tried to reproduce those studies, they used oral doses, so just small doses over a day.

But back in those days, they weren't aware of the different pharmacokinetics of vitamin C, they thought oral and intravenous, are just the same, like the drug. But it's quite different. Oral uptake is a lot lower, much smaller amounts are taken up versus intravenous, you can get really high doses. And very quickly.

Lisa: Up to 200 times. I heard Professor Gabi Dachs, saying that intravenous is up to 200 times for short periods, but that short periods makes a difference, because you can get that into the tumor cells and to—so that… And this is the problem. Professor Margreet Vissers was saying the original controversy around Linus Pauling’s work and because they didn't have an understanding of how can possibly this mechanism of action been working. They just pursued it, basically. And it caused this big rift, those on the side, and those on that side, and for the next—what are we? 40 something years later—we'll still actually, it's problematic.

Dr Anitra: Yes, it wasn't really till Mark Levine did his really detailed pharmacokinetic studies that people realized the big differences between oral and intravenous. And also there’s more recent discoveries of vitamin C's cofactor functions around regulating genes through herbs and through the epigenetic enzymes. These are all mechanisms, which could be involved and its anticancer mechanisms as such. And so the epigenetic area is a very, very exciting, very interesting area of research. And I think it'll enable us to personalize medicine in the future.

Lisa: Oh! I mean, I have an epigenetics program as one of my health programs. And yes, that's looking at okay, how genes being influenced by your environment, and let's optimize your environment to your genes. And the vitamin C helps serve to give people an understanding, so is vitamin C helping produce the enzymes that read the DNA? And then therefore having the reactions. Is that how it works?

Dr Anitra: It works as a code.

Lisa: The transcription

Dr Anitra: Yes, so it helps the function of the enzymes which modify the DNA. So genetics is about the DNA itself. Epigenetics is above the DNA. So it's a way to regulate the DNA as you know. Usually through adding methyl groups to the dynast DNA, adding and subtracting and that affects how the DNA is read by the enzymes that read DNA and transcribe it.

Lisa: Turning them on or off, or simplify.

Dr Anitra: So vitamin C, regulates the enzymes which modify the methyl groups and stimulates them coming off or stimulates different mechanisms happening. So switching certain genes on, switching certain genes off, now it can teach you to regulate thousands of genes in our body through stimulation of these enzymes.

Lisa: Wow. So yes, I've heard somewhere, I think it was seven or 8000 genes that are possibly affected by this. So we are really at the beginning of the vitamin C journey, as far as the epigenetics mechanisms is concerned. Yes, that's exciting.

Dr Anitra: A lot of its functions, not just in cancer, but in all areas of health and disease, these functions could be playing a role. So yes, huge areas of research possible there.

Lisa: Yes. Yes. Yes. Is there a—I remember Professor Margaret, talking about Tt? Is that one of the enzymes? The Tt one?

Dr Anitra: It is an enzyme, that's right.

Lisa: And that's important for cancer in some way?

Dr Anitra: Now, the enzyme search modifies the methylated DNA, some regulation that epigenetics. And it's definitely difficult.

Lisa: To replicate it in the cancer process. Wow. Okay, we're getting quite technical here.

Doctor Anitra, I just want to say thank you very much for your dedication because I've listened to a couple of interviews with you. And you've actually sacrificed quite a lot to do the research that you're doing because there isn't a heck of a lot of funding and things are out there. So, thank you for doing all that. It's a labour of love, I can imagine. It's a long, slow process, getting the information, getting it to be watertight—scientifically watertight, so that we can actually get people help, who need help. And that at the end of the day it’s the reason I'm doing this podcast. And it's the reason you're doing your research, and hopefully together and with many others, we can move the story along so that people get helped.

Is there anything that we haven't covered that you think would be an important message for people listening today?

Dr Anitra: Well, I think—I mean, of course, infection is very relevant these days with COVID. There’s a lot of information and misinformation floating around out there about vitamin C and COVID. And at this stage, the studies are still at the really early, early stages. Americans have done a study which shows that patients with COVID in the ICU do have low vitamin C levels, like other similar conditions. COVID is a severe respiratory infection like pneumonia and sepsis or complications with COVID. And so, I think that the key is to stay healthy, eat a good healthy...

Lisa: Boost your immune system, yes.

Dr Anitra: Yes, to support your immune system, it doesn't mean you won't get COVID. But it may decrease the severity and the duration, so it doesn't go on to become the more severe version, the pneumonia and sepsis.

So I think that's an important message and if you do get infection, your requirements, dear God, so you do need to take more vitamin C, you need to take gram amounts, rather than milligram amounts. Want you to prevent getting even more severe. So, I'm all for prevention as much as possible, not leaving it till it's too late. So, I think, yes, just look after yourself, eat well.

Lisa: Yes. And get your vitamin C. Come buy some kiwi fruit, and some oranges today, and some lemons, and capsicum. And some supplements maybe.

Just as a final thing, you yourself, have a study that's currently underway, which is really, really exciting. And this is based in the Christchurch hospital, I believe, in 40 patients and with sepsis. Can you just tell us a little bit, the parameters of that study and when you think you'll have some results from it?

Dr Anitra: So this was patients with septic shock. So once again, at the end. And they were administered either placebo control, so half the patients and the other half were given intravenous vitamin C at a dose of 100 milligrams per kilogram body tissue per day, which equates to about six to seven grams a day. The reason for that, I have wanted to use the high dose, Berry Fowler. But the ethics committee—because when I put this into the ethics committee, there were only the two studies out, which was Berry Fowler's and the small study headed by Iran. And they said, ‘Well, slightly more people have received a lot lower dose versus the higher dose. So we'd rather use the lower dose.’’ Even though there'd be no adverse events at any dose. And subsequently, no adverse events and any studies.

Lisa: No.

Dr Anitra: And so, we've used the lower dose, we've only just finished recruiting the last patients. It took a while and we had issues of lockdown. And so now we're in the process of analysing the samples that we've collected analysing the data. And so hopefully, we're about to pull that together, sometime next year and publish the results next year.

Lisa: Brilliant. I can't wait to see that. And yes, that's a little bit frustrating because I would have liked to have seen a study with the 15 to 18. And even that I thought was still very conservative compared to some of the cancer dosages. But I understand from what Dr Berry Fowler said because of the decreased kidney function often in septic patients and so on, but it's just like yes, but the dying often. And it's because that was one of the arguments that was thrown at me, I could damage my dad's kidneys. The sepsis was doing that quite nicely and he was dying anyway. So why the hell?

So, but I think even at those dosages, we’ll hopefully see some fantastic results come out of it. And hopefully, in future we'll be able to do slightly more high-powered dosages.

Dr Anitra:
Yes. Well, the key is also the size of the study, our study is very small. And we were interested in being a scientist. I'm interested in how it's working in the body because once you understand how it's working, it makes it easier to design better studies and not our future studies.

And so, our study will be too small to show a yes or no, it decreases mortality or not—that we're leaving it up to the large studies to show there. And hopefully, we can put a bit more science behind how it's working, what's happening in the body.

Lisa: And it's such a complicated thing to design a study. People don't probably realize how the parameters and the limitations and the number of variables that you can look at and the primary outcomes and the secondary outcomes and so on.

Dr Anitra: Sepsis is such a complex variable that comes in as unique in this situation. So there's huge variability in the data. And that's where the biggest studies are good, because it helps decrease...

Lisa: The statistical...

Dr Anitra: The statistical analyses of those studies. Yes, I'm looking forward to the results of the big studies coming out.

Lisa: Yes, but these, these smaller ones are really, really important. So, and it's great that we've got one going in New Zealand. So, thank you very much for your work, Dr Anitra. It’s been absolutely fascinating. And thank you for your dedication to this. I really, really appreciate you.

Dr Anitra: Thank you. Thank you for inviting me.

That's it this week for Pushing the Limits. Be sure to rate, review, and share with your friends and head over and visit Lisa and her team at lisatamati.com

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