Nutrition to Improve Immunity - with Dr. James DiNicolantonio | The Empowering Neurologist EP. 116

Well, hello everyone. Welcome back to the show. I'm Dr. David Perlmutter, and you are watching The Empowering Neurologist. You know, one topic that's in the front of everybody's minds right now is immunity. Obviously, we want to have a good immune system. We want to have an immune system. that is balanced, and we want to do everything we can from a lifestyle perspective to keep our immunity functioning tip-top. And we have a great book that we're going to be looking at today by Dr. James DiNicolantonio. He's been on the program before, called The Immunity Fix. Let me tell you about Dr. DiNicolantonio. He is a doctor of pharmacy as well as a researcher in the field of cardiovascular science. He's well respected internationally. He's known throughout the world as an expert in the areas of the interaction between nutrition and health. He has been involved in actually forming health policy. He has testified in front of the Canadian Senate regarding how added sugars are harmful to health. He serves as the associate editor of the British Medical Journal's Open Heart, a journal published in partnership with the British. Cardiovascular Society, and he's on the editorial advisory board of several other important medical journals. Dr. DiNicolantonio is the author or co-author of over 250 really terrific publications that we would find in the medical literature. He's also the author of 4 bestselling health books, several of which we've actually talked about on this program before, including The Salt Fix, Super Fuel, The Longevity Solution, and his newest book that we're talking about today again, The Immunity Fix. We're going to learn a lot about what we can be doing to help our immune systems today, so here we go. Well, Dr. D'Nicolantonio, you're back on the show. You're a repeat offender. Welcome.

Thanks for having me, David.

Your book is certainly very timely. As I mentioned in the introduction, people are really focused on immunity right now, and I think, you know, as an overview, what your book talks about is not necessarily that we want to expand our immune function, but it's really, I think, much more about balance of the immune system. These days, why should we care? Why should we worry? What do we need to be doing?

I think what's interesting is beyond just immunity, I think it's brought a lot of things up to the forefront, how sick, metabolically sick we are in the United States. I think people with metabolic syndrome, which is essentially having 3 or more of 5 different conditions, high blood pressure, high glucose, You know, elevated waist circumference, high triglycerides, low HDL. If you have 3 or more of those, you are considered to have metabolic syndrome. And essentially, that's been shown to increase the risk of dying from COVID-19 by about 3-fold and increase the risk of ending up in the ICU by 4.5-fold. And so people are now kind of saying to themselves, well, geez, if I can fix this condition, maybe I'll have a better, you know, COVID outcome if I do get this. I think that's really the goal that I had with writing the book, The Immunity Fix, was to mesh metabolic health with immune health.

You said an awful lot. Early on, it was very clear that bad outcome was associated with exactly what you just talked about, individuals with metabolic issues, which are a— with all due respect— reflection, by and large, of lifestyle choices. And having said that, I'm hopeful that our viewers will recognize that as a statement of empowerment. In other words, you can choose then not to have these metabolic problems if you do various things that I'm sure you and I are going to talk about today. But that said, it was noted earlier— early on in the COVID experience that the people who had the worst outcomes or risk of bad outcome were those who were so-called immunocompromised. And I think what you've just said is that you have now thrown a wider net into who are those that we consider to be immunocompromised, and you've brought in the notion that having any of the components of metabolic syndrome, importantly obesity and insulin resistance, diabetes, etc., that these are markers of being immunocompromised, that those issues, getting back to my original statement, which are pretty much related to lifestyle choices compromise our immune system— systems. That is a pretty powerful statement.

Right. And I think what's really scary too is that you don't have to be outwardly obese to have metabolic syndrome, right? A lot of people actually are skinny on the outside but fat on the inside, which essentially they have this visceral fat accumulation and insulin resistance. So you can't even tell by looking at someone If they're immunocompromised?

Well, I will say that recently in November, in Medical Hypothesis, was a really interesting article, from my perspective anyway, and I think you do get to this later on in your book. I hate to jump the gun, but it's in my mind right now. And this was a study— no, it was a hypothesis indicating that one of the mechanisms that may be related to bad outcome in these individuals is that their NAD levels are low. And I know you cover NAD and NAD boosters and nicotinamide riboside, nicotinamide mononucleotide, and maybe we could just segue there for a moment. And it said perhaps the bad outcome in COVID in people with these metabolic issues is related to their reduction that is seen with these underlying conditions in their NAD levels. We know that NAD is important for sirtuin activation and functionality, which helps to reduce inflammation. So, I mean, that's about 3/4 of the way through your book, but let's just go there because we get a lot of requests these days for people wanting to know what's up with NAD+.

Right. I think, you know, NAD+ is sort of like one of those biomarkers of underlying inflammation. Essentially, if you have low NAD+, You have high inflammation. It's taxing those levels. And so really, the goal isn't necessarily to supplement with NAD or NAD precursors. The goal is to fix the inflammation that's driving NAD down. And I will say there are SIRT1 activators, like melatonin, for example, that drive NAD levels up through both SIRT1, but also melatonin, and this is— Linked with good sleep, obviously, is, is an NRF2 activator as well. It actually increases the transcription of NRF2, which then upregulates our overall antioxidant defense enzymes. So really, the book is about how do you increase your resilience, your own antioxidant defenses, and that in turn is going to boost your own NAD levels but have a multitude of other benefits.

So then our listeners are on the edge of their seat recognizing that NAD is so important. What can they do right now if boosting NAD might be a good thing to do?

I would say the first thing would be to cut out the omega-6 seed oils. That is probably the biggest driver of inflammation in the human body. If you don't burn them right away and you store them in your cell membranes, the half-life for linoleic acid when it's stored is up to 680 days. These fats really sit with you for a long time if they get stored and they cause tremendous damage, as you know, to the brain as well, forming these aldehydes. 4-HNE being a very powerful, sort of something that increases neurofibrillary tangles in the brain and all these other damaging effects. So, that would be the first step. Get rid of those corn oil, safflower, soybean oil, these things that we've been told, these vegetable oils that we've been told are healthy to cook with, they're actually probably the worst things for our health.

Well, you have just sent to me an abstract of a article that you, I guess, will publish soon. I'm not sure. I'm going to read the title: Boosting Temperature, Heat Shock Proteins, and Nitric Oxide as Potential Strategies Against RNA Viruses. We know that coronaviruses are RNA viruses, so we know that exposure to heat, exposure to cold, one of the things that they do is, aside from their effect on heat shock protein, nitric oxide, is they dramatically increase the availability of NAD, possibly through this activation of this nicotinamide phosphoribosyltransferase enzyme. But the point is that— so you're looking at thermal challenges, either cold or hot, possibly as an antiviral strategy.

Yeah, absolutely. And so, well, originally what sort of drove the interest is an expert came on the Joe Rogan podcast and was saying that sauna therapy won't work because The WHO had said that SARS, not SARS-CoV-2, but SARS can be killed at 133 degrees Fahrenheit very rapidly, within 10 to 15 minutes, a very high cycle killing. And what this expert on Joe Rogan was saying, well, the lungs will never get to 133 degrees Fahrenheit, so saunas aren't going to have any benefit. And then I was probably one of the first people to say, well, that's not how saunas work. Saunas boost core body temperature. which activate heat shock proteins, and those heat shock proteins can dock onto the viral ribonucleoprotein complex, preventing its export and essentially inhibiting viral replication. And we see if you heat shock animals prior to infecting them with lethal bird flu, there's a significant reduction in death and lung pathology and viral replication. So I think even— there's dozens of prospective studies that if you go into the sauna 3 to 4 times a week, you're at a lower risk of pneumonia, influenza, the common cold. And there's even clinical studies, David, where people, they split 2 groups into— one group got 3 to 4 sessions of sauna per week, the other group did not for several months, and it cut the risk of getting the common cold in half. And that was a clinical study. It was only in 50 patients, but I think it's pretty eye-opening when you look at the animal data, the prospective data, and the clinical studies that heat shocking yourself consistently increases the resilience of your own cells. And has these antiviral effects if you do get RNA viral infections.

Yeah, and I would say that, you know, the research, the publications that demonstrate reduced risk of cardiovascular disease and even dementia that have been described in individuals who spend a reasonable amount of time in the sauna, a lot of that study, a lot of that research, of course, comes out of Scandinavia because that's, you know, fairly common practice there. But getting back to the notion that, well, it doesn't translate to humans because we don't heat our bodies up to 138 degrees, I wish I could have been in the audience on that one because what you're saying is true. I mean, it really isn't dependent upon a massive increase of our body temperature or a massive reduction of our body temperature. A couple of degrees is a hormetic stress activating a variety of pathways. We had the opportunity several weeks ago to interview Wim Hof, the Iceman, and we had— it was a great interview. We had a really, really great time. And we've been doing the cold plunge ever since, which is hard to do in Florida. I might— I would fill in the swimming pool with ice, not really. But I think that it brings up just the notion, as I think you characterized quite well, that stressing your body, in this case with thermal stress, ends up doing some good things. And, you know, you talk in your book, getting back to the NAD story, about other things that we can do to increase NAD. You talk about nicotinamide riboside. Yeah. Nicotinamide mononucleotide as supplements. But the most powerful things, I think, at least demonstrable changes in raising our NAD levels, are exactly what you're getting at, these thermal challenges, and also the value of aerobic exercise. I mean, I think that's often underrepresented in the lifestyle recommendations, as is sleep for that matter, but what a neat and nifty way to augment your body's availability of NAD+, so that it can do all the great things that you just described, like reduce inflammation and play a role in sirtuin functionality. So, you know, really very important. Where would we go right now if we wanted to kind of define a program? And I'm saying this, I'm asking this question because last night I took my wife's mother to get her first Moderna COVID immunization. Oh, wow. And it occurred to me that, you know, an immunization is— requires a pretty good immune system to develop antibodies. That's how it works. At least that's how the mRNA— well, and the adenovirus DNA vector as well. They work by harvesting a good immune system, hopefully, that then generates these memory cells, T memory cells, as well as cranks out antibodies. So What might you say to somebody who's planning, let's say, to get an immunization in the future? What should people be doing nowadays prior to that immunization to really get the most out of it?

That's a great question. I think it almost comes always back to metabolic health because we've seen that people who have metabolic syndrome and obesity do not respond as well to these vaccines compared to people who are healthy.

We've known that for a long, long time.

We certainly have. And what's actually even more scary is that if you have these conditions, metabolic syndrome or obesity, you're actually more likely to shed the virus longer. And it may give the virus more time to mutate inside of you as it's replicating. And so essentially, if you have a population that is sicker, more overweight, you're potentially shedding a more virulent strain of viruses for a longer period of time. And I think that's something that we need to focus on, that if we can fix the population's health, That literally that might actually improve and reduce the spread of RNA viruses.

Well, you mentioned that there are some nutrient deficiencies that are kind of characteristic with respect to bad outcome. Maybe we could talk about a few of those.

Sure. What was really interesting, and this is kind of a story I like to tell, is that there are certain selenium-deficient areas in China that if you get infected with something called Coxsackievirus, typically it causes something like hand, foot, and mouth in children and doesn't really cause much of an issue in adults. But if you are selenium deficient, it takes this nonvirulent virus and it leads to something called Kishan disease, which essentially leads to cardiomyopathy. And you treat those patients by simply giving them selenium supplementation. And so, so that just highlights the fact that being depleted or deficient in a single nutrient can take a non-virulent RNA virus and actually make it fatal potentially. And we see this with selenium as well, even with COVID-19, and people who are deficient in selenium are at a 3 to 5-fold higher risk of dying and same, you know, a 3-fold higher risk of having a poor outcome. And so, and that's just one of many nutrients that we see being depleted leading to You know, were associated with worse COVID outcomes.

Well, you dedicated a whole section in your book to magnesium. That certainly plays a fundamental role. Where is magnesium fitting into the program and why?

Yeah, it's so interesting because magnesium has completely taken this backseat to vitamin D. But the compelling story is that in order to activate vitamin D to its, you know, active hormone form called calcitriol, There's these enzymes that depend on magnesium, and so if you're deficient in those enzymes to convert vitamin D3 to calcidiol and then to calcitriol, it needs magnesium throughout these pathways. And we have immune cells that can actually form active vitamin D themselves, but they also require magnesium to do this. And so I had a really cool graphic on how magnesium deficiency leads essentially to immunosuppression. And the levels of magnesium within the cell, the actual ionized magnesium, which is the active free form, when that is low inside your CD8 T killer cells or your natural killer cells, that actually reduces their cytotoxicity. And so we see diabetic patients, they actually have low levels of intracellular free magnesium and this immunosuppression.

So these days, not everybody's going to run out to their doctor's office and have a magnesium level done, or perhaps better, an erythrocyte or red blood cell magnesium level done. Is there any general recommendation that you might make to people so they can be at least assured that they have adequate amounts of magnesium on board?

What's really interesting is that we've always demonized blood levels as being poor markers and the fact that you can have tissues that are deficient in numerous minerals, but the blood levels typically stay normal. But the key is that in almost every single case, blood levels will become suboptimal. They'll still be in the normal range, but if you are on the low end of normal for numerous nutrients, including magnesium, that is highly indicative of deficiency because the blood will maintain a quote-unquote normal level, but it'll shift to the lower end of the range. And if you match that too by checking your urinary magnesium and that is also low, That's very highly suggestive of magnesium deficiency.

Beyond supplementation, things that people can get their hands on, there is the notion of medications that people think, you know, they want to ask their doctors for, and you talk about things like ivermectin, hydroxychloroquine, azithromycin, and others. So why don't we just go through that list? Let's start with hydroxychloroquine, and I think you ended up in the book coming out I think in favor. So why so?

So the key with hydroxychloroquine is that you have to give it early enough for it to have any chance of working. It doesn't work later on because it doesn't have anti-inflammatory effects. How hydroxychloroquine works is by essentially reducing the replication in the body. But once that becomes too much, it's not Very beneficial. And so, if you break out the studies between those that gave hydroxychloroquine early on and those that did not, you consistently see benefit if it's given early enough, particularly if you add azithromycin to it.

Well, I will say that the early reports that did come in on hydroxychloroquine, I did not find compelling. But nonetheless, I did— because I was out in the wilderness this summer, I did have a bottle with me in case something were to happen. I'm not sure I would have taken it. Mm-hmm. You know, the cardiac dysrhythmia part of that story, I know it's not huge, but having had an event in the past of a cardiac dysrhythmia, so I felt it was not a good idea. Nonetheless, I wanted to have it with me. But I think that there is some literature that is suggesting right now that early use of hydroxychloroquine may be effective. What about ivermectin? And first, Why don't we talk about ivermectin in terms of its global distribution and availability for decades, and then how it came to be looked upon as— I think the literature is quite supportive of ivermectin, but how did we get to that place?

Well, like you said, yeah, that's a good point. So ivermectin is— its availability is, you know, throughout the global world. You can get it pretty easily, and it's cheap. And so there's when you have a cheap substance that you can get fairly easily, that competes with pharmaceutical branded medications, so to speak. And we actually published a paper on ivermectin and its potential use in COVID-19, but it was not for early on. It was for late stage, its anti-inflammatory effects. And really the divide came because the levels that were needed to have its antiviral effects were too high to ever be obtained Orally on a physiological level through actual ingestion. And then we had— we came out and said, well, that's not how really ivermectin works. It's these anti-inflammatory effects. But you do need to get the dose right. And we think around 20 milligrams per day for an average adult human, 20 to 28 grams seems to be sort of the magic number. But as you said, there's been meta-analyses published on ivermectin indicating significant benefit. The thing is, is that the quality of the studies aren't— they're sort of mediocre. And so we do still need that really nice 2,000-patient randomized double-blind controlled trial to truly know, but all the data is pointed to the right direction that there is some benefit likely.

Well, I will say that whenever I go live and talk about ivermectin, there are always plenty of comments from people saying, well, should I take my dog's heart worming pill, or we've eaten horses, on and on. To be clear, so there's no misunderstanding, we are not making medical recommendations here, and by all means, this is not a recommendation to go out and find some ivermectin. This is a pharmaceutical that needs to be used, if it is used, under the direction of a healthcare provider, of a physician. You spend a lot— an entire chapter in the book talking about beta-glucans. And I would bet that our viewers may not be up to speed on beta-glucans. So what's the role of beta-glucans in immunity in general, but specifically also in COVID?

Right. So beta-glucans sort of work similarly to going outside and exposing yourself to dirt or foreign substances. So essentially, you're taking the cell wall of baker's yeast, which contains these yeast beta-glucans, and they have a unique structure. So we're not talking about beta-glucans from oats. This is from baker's yeast, and it has these 1,3,1,6 unique branches that activate our own immune system. Essentially, you're tricking your body into thinking that it has an infection by taking these cell wall components of baker's yeast, and your dendritic cells will break those particles up, and essentially, it'll increase immunosurveillance throughout the body. The key with that is it's more of a chronic— you take this during the cold and flu season for several months, and there have been several clinical studies, probably at least a dozen, that daily use of yeast beta-glucan significantly reduces the occurrence and the severity of upper respiratory tract infections.

And I think there's an anti-inflammatory effect, too, through activation, as you mentioned, of the dendritic cells to the Formation of Tregs, then production of IL-17. So let's then, for our viewers, talk about what does a COVID risk reduction lifestyle look like. Why don't we first talk about diet? What should people be eating?

We actually had a pyramid in our book, and it focused on both animal foods and some plant foods as well. I think it's important that people understand though that you can't get all the active forms of vitamins through solely eating plant foods. So, while plant foods are— I almost consider them medicine, there are certain nutrients that you almost have to source through animal foods, right? Like active vitamin A, D3, B12, all of these nutrients are extremely important for immune health. So, we do focus on organ meats like liver, which is high in copper and Choline and all these other nutrients that are difficult to get if you're just eating plant foods. And then focusing on things like pastured eggs for their omegas, the cholines, things like that. So a healthy whole food diet that I do think contains some animal foods is essentially what we recommend in the book.

Yeah. I would say though, plenty of our viewers do not eat animal products. So where are the areas then that they— you mentioned B12. DHA would be certainly another area. What are the things, Colleen, that they need to be thinking about that because they have elected to completely avoid animal products, let's just say, we'll talk about that group, what should they be really thinking about in terms of making sure through supplementation that they're getting so that they don't get into trouble?

Right. People who consume plant foods seem to do fairly well on things like magnesium, copper, But they failed on zinc, B12, iron typically as well, and like you said, DHA, choline. And you can take supplements to get those nutrients, and I think most people who are on a heavily plant-based diet or a vegan diet will have to do

that. Would you say that eating iron-rich plants, whatever it may be, spinach, etc., Is not as good a source for iron in terms of delivering that iron as it would be in relation to eating red meat.

Right. Yeah, that is 100% true. And so I think especially for women who haven't gone through menopause yet, which need 18 milligrams of iron per day, they'll be hard-pressed to get that amount on a plant-based diet from a bioavailability standpoint. As you're alluding to, the bioavailability of iron from spinach, I think, is only about 3%, whereas the bioavailability of iron from animal foods is more of the— I want to say 20% range.

Okay, but again, we're trying to throw the largest inclusivity net that we can, and that will work for everybody. Those are good things to know. B12 as well, certainly something that vegans will want to be thinking about in terms of trying to supplement because they're not eating animal products. No judgment here. Right. I do eat some animal products. I am certainly more plant-based than ever, and— but with those things in mind that you just mentioned, there is a situation now moving beyond COVID— doesn't mean we can't come back to it— but where the immune system is dysregulated to the extent that it's actually reacting against our own bodies. which is not something that we want. We call that auto-self-immunity, autoimmunity. So what— I know you covered in the book quite a bit— what's going on with the immune system that would cause it to react against our own bodies?

Oh, that's a great question. I think a lot is going on. The most simplistic answer would be, in my opinion, 2 different things. One is you have damage to the— you have intestinal permeability of leaky gut, damage to the lining In your intestine, and now you have foreign particles that essentially can hit the bloodstream and activate the immune system. And then the second factor would be a depletion in vitamin D and vitamin A, which control your T regulatory cells. So as you had alluded to, your, your dendritic cells are sort of your first line of defense. They sort of take foreign particles and then deliver messages to the T regulatory cells, and they handle everything else. They calm everything down or they ramp everything up. If you are depleted in vitamin A or vitamin D, your T regulatory cells are sort of dysfunctional now, and you can have that ramp up of your immune system, which can lead to autoimmune diseases. So those 2 vitamins, A and D, are extremely important, and unfortunately, most people are deficient in those 2 vitamins.

Well, beyond that, let's— you mentioned that things are getting through the gut lining that shouldn't, that we have a permeability issue that really seems to be playing a central role here in hyperinflammatory conditions, autoimmunity being one of the hyperinflammatory conditions. You know, interestingly, the go-to treatment has been, you know, before the monoclonal antibodies, and even still the go-to first line of treatment seems to be to give people steroids. And it's an interesting choice because, yes, symptoms might improve in the short run, But you're destabilizing, you're making changes to the microbiome, which can actually enhance gut permeability, making the problem in the longer term worse. So, you know, it's interesting how the mainstay approach to treating the problem is actually likely contributing to that problem being more continuous, more pervasive. So— I guess maybe there should be an approach that deals with these situations right off the bat. With monoclonal antibodies, I think in your world and my world, it would be to be focused on reestablishing gut wall integrity. That said, what are some of the strategies that people could look to for focusing on where the breakdown may be? Why do we have this gut wall integrity issue, leaky gut, if you will, and what can we then do about it?

Right. I think some of the main contributors of leaky gut or increased intestinal permeability is obviously being driven through refined carbohydrates, Right. Fructose, sugars, omega-6 seed oils. I mean, when your intestinal cell metabolizes fructose, it legitimately increases oxidative stress and inflammation and can damage the lining. And there's animal studies indicating that as such. And I think with seed oils, it's probably even much worse. So people, if you can eliminate those ingredients, reduce the amount of foods that you eat from takeout and from restaurants, which typically use those inflammatory omega-6 Seed oils, and really cooking whole foods at home, whole plant foods, whole animal foods, is going to be the first step to fixing the gut lining.

Well, it's interesting you mentioned fructose because there does seem to be this messaging in the world that because fructose has a very low so-called glycemic index, doesn't spike our glucose, nor should you expect that it would, and because of that, therefore, it doesn't cause insulin spikes, therefore, it won't as readily lead to insulin resistance, that therefore fructose is a good sugar. Good sugar in the same sentence, to me, sounds like a bit of an oxymoron. Having said that, glad I said it, what's then— what's the downside? You mentioned that we should be avoiding fructose.

Yeah, that's a great point that you bring up, is sort of the glycemic index and how Fructose sort of flies under the radar and you would— a lot of people consider it a good sugar because it has a low glycemic index. But the problem is, is it forms advanced glycation end products 10 times more than glucose. And when you combine glucose with fructose, that's a huge problem because the fructose can lead to a condition and activate the polyol pathway, which actually converts more glucose into fructose. And then when your intestinal cells metabolize that, and the kidneys too, when you reach a certain threshold, that leads to dramatic inflammation. So I try to tell people you can't outrun a bad diet because you can't outrun oxidized tissue damage, right? And so it's not just about calories too. It's about, are these foods and calories damaging to the body?

I have to say, last night I was reviewing a study on fructose. And it said that there was absolutely no effect on blood glucose or insulin resistance or sensitivity during the entire time of the study, which lasted 7 days. And that's the messaging I think that sugar— I mean, the sugar industry has latched onto. They've done studies whereby people will consume a can of soda that's high in high fructose corn syrup, high fructose, And measure their blood sugars all day long, and maybe even the next day, and lo and behold, there isn't really much change. Therefore, we should be sucking down high fructose corn syrup because it doesn't do that. But, you know, what you just mentioned is these pathways whereby inflammation is augmented, which then may have an effect on the activity of the insulin receptor, for example, these don't happen overnight. The nonalcoholic fatty liver disease that ensues and its downstream effects, and the effects of increased intracellular fat, and importantly, as we're learning now, the effect that fructose has on augmenting uric acid, and how that may filter down to all components of what you talked about earlier, the metabolic syndrome. Therefore, we should not be consuming soda with high fructose corn syrup. And therefore, maybe we should be drinking fruit juice. No, I don't think so. I mean, people think, well, it's fruit juice. What's wrong with a big glass of orange juice or apple juice? Well, there's an awful lot of fructose in there. And you know this notion of agave nectar. Well, how could you argue with something that's called nectar? That's you know could be up to 90% fructose, and it's super sweet. And when we recognize that yes, there may not be a change in your blood sugar today or tomorrow. But in the long run, this stuff is nasty. I think that's an important bit of messaging. In our last discussion that we covered today, I'd like to just turn our attention to what is the role of immunity in cancer, and maybe we can morph that into then what should we be doing?

Yeah. Well, when I was researching for the book, I was actually really shocked at how interconnected the immune system is with cancer. And essentially, we have these precancerous cells that are constantly forming in the body, and the reason why they don't turn into cancer is we have something called immunosurveillance. Our own immune cells seek out these precancerous lesions or cellular formations and essentially take care of them. And really, that's controlled partly through the levels of magnesium in those cells. So there's actually a condition, it's called X-Men disease, where these people have genetically low magnesium levels in their immune immune cells, and they have chronic activation of Epstein-Barr virus and a significant increased risk of lymphoma. So we know that there's many viruses that actually cause cancer, and your immune system will determine if these viruses are chronically activated, which 95% of us are infected with Epstein-Barr and don't even realize it. And so it's just— it's interesting to think how the— how your own immune system Is on the surveillance for viruses that just could potentially become activated that you are just chronically suppressing through your own immune system and through activation of your own viruses that you already have, that you've had for years, could actually lead to cancer.

Interesting. Well, there's this whole thing where people believe that they're suffering from Epstein-Barr syndrome because now the doctor has found elevated levels of antibodies against Epstein-Barr virus in their blood. And like you say, you know, most people, almost everyone, has been exposed to Epstein-Barr, and, you know, it probably is residing in our bodies, as is herpes simplex virus type 1. Mm-hmm. There are multiple organisms living within us. There are bacteriophages that are living within the brain that are regulating the viability of bacteria and even the functionality of bacteria, for example, in the gut. And the number of bacteriophages probably outnumbers our gut bacteria by 1,000 to 1. We have viruses throughout our bodies. Our bodies are anything but sterile. You know, we used to think that there's no bugs in our body, then we sort of embraced the notion that we had this whole group of organisms living in the gut. Okay, I can believe that, but the brain has viruses, may well have chlamydia pneumoniae in many people. Mm-hmm. The placenta is not sterile. We have this notion that, you know, various parts of the body are pristine as it relates to organisms, but the truth is that we are living in this relationship with organisms, and then when our immune systems are perturbed in one way or another, then things can become more of an issue, as is the case with Epstein-Barr, EBV, that it may then become more fulminant and become an issue. is the case with certain bacteria within the gut. Many people harbor Clostridial species, first of all, that are actually very good for us in terms of maintaining the mucus, but even C. difficile is found in many of us. Right. It's just suddenly the host changes, we change, and then something like C. diff can become an issue. So whether the EBV or Clostridia or other species are issues really is kind of a contextual issue depending upon the host. And, you know, getting back to COVID, I think that you've brought to our attention that the host and the health of that individual is really very, very important in determining outcome. And what was so empowering about our discussion is that we can change that dynamic. Right. We can make the lifestyle choices that you just recommended, paying attention to our selenium levels, our magnesium levels, vitamin D, vitamin A, getting exercise, heat and cold. I mean, who would— you know, I'm really looking forward— all you sent me was the abstract. Who would have thought that heat and cold or cold exposure might be so powerful in terms of our immune systems that it even should be considered on the therapeutic table as it might relate to COVID? Before we go, there was a question in your book that was raised, and I want— I'm not sure I fully understand the answer, and it's getting back to our discussion of NAD+, Raising NAD using supplements. And you asked a question, the heading was, should we take NAD once we are already sick? And I didn't fully get the answer, so what should we be doing? NAD precursors?

I think there is some data that if the pool of NAD is depleted and it's an acute situation, that there may be some benefit in that particular situation. But once you're out of that situation, it's always best to fix the underlying cause of low NAD. And ultimately, like you and I had just said, it comes down to poor lifestyle that's really causing those NAD pools to become depleted.

You also just touched upon— I can't let this go because it's front of mind— that we should do what we can to activate the NRF2 pathway. So maybe you can just tell our viewers what is that pathway and then how do we activate it?

Sure. Yeah, so NRF2 is Nrf2 is a transcription factor, and it allows the activation of all of our endogenous antioxidant systems. I've actually published several papers on different strategies how to activate Nrf2. The best way to do that is to get good sleep and essentially melatonin supplementation at night, 10 to 20 milligrams. This is higher doses than what you typically see. are very potent NRF2 activators. Broccoli sprout powder, that provides something called sulforaphane, at a dose of about 20 to 40 milligrams per day seems to be the optimal dose for activating NRF2. Things like lipoic acid can also do this, as can ferulic acid. There are ferulic acid supplements, but we can actually increase those through drinking things like coffee. which our body takes the chlorogenic acid and converts it eventually to ferulic acid. Those are some of the acids.

I'm so happy that you mentioned that.

Good. Yeah, all you java junkies out there.

Everybody I interview, any of the books where they talk about coffee, I've said to all of them, this is absolutely confirmation bias that you seek out this research because you know darn well that you love your coffee. Right here, if it's Dr. David Sinclair and his new longevity book, or James Clement talking about the mTOR versus AMP kinase pathway to switch, you know, there, there are plenty of people who just want to justify their coffee, and I'm all in, believe me, I'm all in. To be sure, we're not talking about a frappuccino, we're talking about black coffee. But anyway,

right, exactly. That's an important differentiation for sure.

Well, listen, thank you. And this is your wonderful, wonderful book. Yet another to your expanding list of accomplishments. So I'm really encouraging our viewers to get that book, to read. There's some terrific information in there. So, James, thank you for spending time with us today.

Thanks, David.

We'll talk soon. Bye-bye.

Okay, take care.

Well, thank you to Dr. DiNicolantonio for that amazingly helpful information. You know, basically that is empowerment. We want balance of the immune system. We don't need hyperactivity of the immune system. That's what happens, for example, in the so-called cytokine storm. But on the other hand, we want to do what we can to improve our innate immune function and our adaptive immune function, which we did talk about today. A lot of good information. Thanks for joining me. I'm Dr. David Perlmutter, and we will see you all soon.