#422: Lessons from Centenarians: Immunity, Lifestyle, and Changing the Aging Game With Dr. Jeffrey Bland

Welcome to Longevity. I'm your host, Natalie Knidham. I'm a nutritionist, a human potential and epigenetic coach, and I created this podcast to bring you the latest ways to take control of your health and longevity. We cover it all, from new technology and ancestral health practices to personalized interventions and a very special interest of mine, peptides and bioregulators. Enjoy the show. Welcome back to the show, folks. I'm Natalie Knidham, your host. What if the single biggest predictor of your longevity isn't your heart, your hormones, or your genetics, but it's the age of your immune system? Today, Dr. Jeff Bland explains why immune resilience beats immune boosting, how your immune system turns over every few months, and how your diet is constantly retraining it for better or worse. We talk about a lot of interesting concepts here, and at the very end, we do talk about a product that Dr. Bland was very integral in bringing to market. 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Discount is valid on one-time purchases only. Jeffrey Bland, welcome to the podcast. It is really an honor to have you here today. Thank you. Oh, well, it's my honor. Truly, Natalie, and I think what we're going to be discussing is right at the forefront. Kind of a lot of the dimensions of change that are going on right now and how it influence people's lives going forward. And for me, this month, having my 80th birthday, it's all about, you know, pass forward, the next generation's coming up. What's on the horizon, it's really going to make a difference in the quality of our lives. So this is a great conversation. Yeah, well, happy birthday. You don't look a day over 60. Well, thank you. That's very kind. How do you feel? I feel like there's a lot more work to be done, and I hope I have the time to do it. So, yeah. Well, I'm sure you will. So let's go back in time a little bit. And then what was that moment when you first realized that the conventional medicine model just couldn't possibly explain what you were seeing? Well, you know, I think without being overly dramatic about this, I think it was with me for a very long time because my mother would, if she were still living, would say that she remembers me back even in grade school with a very strong interest in why people got sick and what was the reason that people got sick. And it was a driving force for me, obviously, all the way through high school. And, you know, I learned about infectious disease and I recognize that, okay, that's one really good kind of explanation about bugs. But then there was this other area of non-bug related illness, chronic disease that couldn't be described easily by infection. And so where did that come from? And why does that happen? And then the logic at the time, and I'm going back to the 60s, was that it's because of genes, that your genes carry this information. And so if you have family with heart disease, you get heart disease or cancer or dementia or whatever it might be. But when I started looking at the data, it wasn't so clear to me that these were inherited diseases. They didn't appear, there might be some kind of a association, but it wasn't so simple cause and effect. You say, if your father had this, and you're going to have it for sure. And so I started to really be a little bit of a skeptic as I got into college. And then I went to medical school, and because I thought in medical school, this is going to be the place where I'll be able to find an answer to that question. And for probably a variety of reasons, one of which I was probably very young to go into medical school because I graduated from high school when I was 16. So I was really in a fairly young age by the time I got into medical school. I don't think maybe I was mature enough to really handle the nature of that environment. And so I was like the constant questioner guy. And I was always asking questions. And the environment is really not set up for a lot of questioning. It's like, you just learn the stuff, you memorize it, and you recite it on demand and keep quiet, and you'll have a chance to ask questions later. That was the model. And that didn't really work for me. And so finally, at the end of my second year of medical school, my advisor, who I had a great amount of respect for, said, so Jeff, you're a smart guy, you're doing fine. But it doesn't seem like this is really jibing with your philosophy. And you're kind of a pain in the ass, actually, really, because you're asking a lot of questions and you're interrupting class. And it's not really the standard of operations that we would like. So maybe you ought to consider going over to a PhD program in the medical school, where you can ask as many questions as you want. Now, this was before the development of what are now robust MD-PhD programs. If I think I was a student today, I probably would have just gone into an MD-PhD program. But I decided then, okay, I would go across the hall and I'd start doing research and get in a PhD program, which turned out at the time this would be, let's see, what would that be? That would be 67 was the right timing for me. And so that allowed me to have free-raining opportunity to explore. And eventually, that led me into an academic position. And it was at that point where I think I had a personal life epiphany, which I would not recommend to any other human on the planet. And in fact, if I could help anybody to avoid it, I would do all I could to make that happen. My wife and I had our second son as I finished my PhD degree and was then hitting on to my academic position for the first real job I would have. And we got to the place and just sat down, didn't really even know the area yet, was supposed to start in my faculty training the next Monday. This was a Wednesday and our infant son dies. Yeah, it was, it was a, I mean, I could go on and on. But let me just say that it was an, it wasn't epiphany for for us. And it changed everything about the way I saw my career. I was really just starting at that point. But I came to recognize that if I could do anything to help anybody to avoid this happening in their lives, that it would be a life well served. So I think it opened me up to all questions. Again, I was already a questioner, but now I said, Hey, I'm going to be open to all sorts of ideas, because you can't just find ideas where they maybe are conveniently located. You got to look elsewhere in the corners and be opening discussions that at first sound and all that strange. I never heard about that before. So I think it was very good for me as my, as I started this, I started 1970 as a professor. And this was, you know, the beginning of earth year. And I was hired as a joint professor in biochemistry and environmental science to start an environmental science program. So it gave me a perfect launching pad to be an explorer. Yeah. So I think that's where it happened. Yeah, you know, what's interesting to me is by going into academia and teaching, it means that, you know, had you been a medical doctor, you might have practiced medicine completely differently than anybody else, which would have been wildly valuable to every life that you touched. But by going into academia and teaching other people, I would imagine that you wouldn't were inviting the questions you were inviting, you were inviting that those students to challenge, to think, which is not, as you aptly described, is not the model. You know, like it is not the model. I, and I can tell you that, you know, without going into any detail, recently, I've had a fairly complex medical condition come up. And when I challenged the doctor who was taking care of me, she fired me. I would say that, you know, that, that, that undercurrent of this is what we know, this is what we do, this is how we do it, don't ask any questions. Still is a very powerful current in conventional medicine. And not just, and I, and I, what I don't want to do is throw doctors under the bus, because at the end of the day, I think there are people who are trying to help other people for a living. And generally speaking, they're underpaid, overworked and, and, you know, stressed, and they worry about all the things everybody else worries about. The, the framework, both what they're taught and what they're being forced to work in, is essentially disabling their ability to be curious, to be engaged, to be, to treat every patient is like my, my analogy to treat every patient as a unique Rubik's cube that needs to, to be worked with. And, and, you know, we'll talk about functional medicine and how you kind of moved into that space and created it really, you created this universe, how that, in its best iteration is about inviting that conversation between, even between the patient and the medical doctor, hopefully. Yeah, I think you said it beautifully. And that, that really was probably the, the change in my whole focus of my career was I got an appointment then in the medical school. And so, and then later, with a colleague in 1980, we started our own medical school, the Bastier University in Seattle, Washington was started with Joe, Dr. Joe Pizorno, Les Griffith, and Bill Mitchell and I. And, and that then grew up to really open up the door to all sorts of interesting conversations with people around the world. And over my life, I've traveled six million miles, more than six million miles. And I don't think there are probably many people that have that much other than pilots, maybe, they have that much airtime. But what that gave me the opportunity to do is to visit with so many different thought leaders in different areas that were way out of what I would normally have been exposed to. And so I think what happened to me is I became a mosaic. I'm a pretty good sponge for ideas. I don't know how many unique ideas I've come up with. But I think I have been imprinted by many, many different good thinkers that had allowed me to assemble then kind of a mosaic of all these ideas. And then I in 1981 was very fortunate to be asked to take a sabbatical two years actually with Linus Pauling, two-time Nobel Prize winner at Stanford. And so I became his director of a research lab in his Institute of Science and Medicine in Palo Alto, California. And that was working with he and then his wife Eva Helen, who was a powerhouse of her own right, changed my whole philosophy is where I wanted to spend the rest of my career, how I wanted to pursue whatever my opportunities might be. And it was that then that I don't want to bore people, but I think there's a little bit of an anecdote here that's interesting. So I was finishing, finished out my two years, was going back to my tenured faculty position. And I was really had a good position at the university by that time. The president liked me, I could teach in other departments, I had the biggest research group, I was voted two years in a row as a top professor in the universe in the sciences. So I had a good thing going, a college education for my kids would ultimately be paid for. And so I got my stuff packed up in my office at the Pauling Institute. And Dr. Pauling came by and he said, Jeff, it's really nice to have you here. I hope we'll continue to collaborate. And the last question he asked me was, I just have one question to be in you, and that is, do you think your classroom as you head back is big enough? And I got in the car, and I thought I had a, you know, with my family there, we're driving 11 or miles back to our house in Washington state. And all the time I'm thinking, what the heck was that? You know, what, what was he really asking me? And then it, then it became fairly clear to me what he was asking. And so I know this sounds crazy, but it's actually true. I got home, my parents had been watching our house in the couple of years that we were gone. I had asked my dad to take early retirement from the aerospace industry. And so they were living now up in Washington state rather than Southern California. And so we're all excited to see one another, a lot of hugging and so forth. And then I say to them, so I've been giving some very deep, deep thought as to what I'm going to do. And I made a decision that I'm giving up my tenured faculty position to start some kind of an organization that's going to teach doctors how to do nutritional medicine in their practice. Now you could have heard any pin drop. And then my dad, who was, you know, an accountant by training and an engineer, he finally breaks the silence. And he says, Jeff, do you realize you do have a family like you do have a mortgage? You do have responsibilities? And I said, yeah, I do recognize that. But I, I think my passion is such that I'll find a way to make this work. I'm just not sure yet. So my, my God, my loving father, he says, after going through some angst, he then says, well, if you're going to do this, I got to come out of retirement because you know nothing about business. And at least I'm going to count, I count and buy training. So he became my business manager for the few years as we got going. So anyway, that's, that's was the transition for me in 1982. Yeah, to a whole different regime. That's incredible. So you've clearly, you spent decades help translating complex science for clinician. What's the most dangerous oversimplification that you've seen take off? I mean, the internet is rife with them right now. But in what we're seeing right now, like, you know, in a world where people are trying to grab sound bites, they're trying to grab eyeballs and ears and say the most outrageous thing to get people's attention. We're all attracted to shiny objects. And we love new stuff. And we love stuff that really sounds glamorous and sounds that we can tell other people that were first to mark and we know about this and they don't know about it. It's kind of fun. And in this field right now, I guess what's been coined biohacking, there's a huge amount of that. It's shiny object stuff. And quite honestly, I don't think we yet know if any of this stuff is going to prove to be what it's purported to be. And that is to people live to be centarians and have no disease and, and ultimately achieve their success. Because the best lesson that we can take are from things like Dan Butner's Blue Zone countries, where people are not biohackers, but other than the fact that they're living a life that has been somehow compatible with their genes and producing outcome of a century of good living, and which are still vital and active and loving and engaged. So my feeling is we got to be very sanguine about how we take on these new ideas and adopt them without fully understanding what the risk benefits are and whether they're going to return on the investment both time and money. That's not to say I'm not encouraged also always by new things and by new opportunities. But I think they have to be vetted a little bit before we totally say, Oh, this is this is the best thing since last read. Yeah, I agree with you. You know, I've often said that none of the centenarians of a live today set out to be centenarians. Yeah, you have this whole wave of people are like, I'm going to live to be 120, which now I'm going to believe to be 180 or 200 or whatever the case may be, which is which is amazing, you know, you're a living lab. Great. But the challenges, I think that there's a trail of people behind them. That's drinking the Kool-Aid. And you know, I guess we won't know otherwise. But it is. But I feel like people need to understand this is in real time, ongoing experiment. And time will tell, as you said, which I think is so powerful. Is there are there any beliefs that you held very confidently maybe 15 or 20 years ago that you're like, Yeah, no, I had that so wrong. Yeah, I think I wouldn't I want to qualify this by saying I don't think it was so wrong, but it was somewhat wrong. I think that I got into the view of the Ortho molecular medicine group. And I was certainly a principal in that group for a number of years, that more is better of certain nutrients, and that you could take, you know, super physiological doses, and it would actually do things across all people that were beneficial. And I want to be very cautious when I do this. And when I say this, because there are certain examples, absolutely were high levels of intake of nutrients are very beneficial for an individual. But to generalize it and say that every person needs mega doses of vitamins and minerals is is really an exaggeration. Because what we're actually finding out now is that it appears our body likes it best to be pulsed. It likes these kind of hormetic exposures where if you look historically at people, they went through periods of fasting, and then they went through periods of gorging. And so our body kind of has this thing built into it that it likes the synchrony of big and then small or a lot and then a little. And so just staying on regimes where we're just taking fistfuls of supplements to me is it's not intelligent. And there's really no data to say that that is beneficial. I've felt that for a long time. And even the pulsing of different nutrients at different times, right? I mean, as a nutritionist, I was taught at school, you cycle through things, you don't do the same thing. I mean, you want to maintain your vitamin D3K2 levels? Yes, like there are certain foundational elements that if they're missing, all these processes in the body don't happen. But, but especially when and I find especially in the whole longevity anti aging space, we tend to find a button and start to push it. And I'm like, yes, you know, you're going to tick somebody off in your body at some point, like it's a little bit like constantly nattering at a child, they eventually might tune you out, where if you give that signal and then step away and allow things to unfold and then come back again, I think over and over again to your point, we see that this is how our bodies work anyway. So why not kind of feed into that rhythm and allow it to do what it's going to do? Yeah, I absolutely agree with you. And you know, if you think of the way we've eaten historically, it's seasonally, we didn't have, you know, all the things all year long. So the body has these genes that have these circadian temporal rhythms built into them. And so I, I, I'm kind of now getting more and more into the what can we learn from history type of philosophy here, if we go back anthropologically and look at what people have consumed, how they consume them, where did it come from, in what season was it consumed, and what level was it consumed. So there, I'm certainly not an anti supplement person. So I want to make that very clear. But I think it's prudent use of the tools that we have that are individualized to the need of the person. That's the secret sauce. Yeah. And I've been speaking about personalization of nutrition for 40 years. And I've been criticized fairly heavily for that. I think for two reasons, one of which people said, well, there's no evidence to say that we need to do anything other than treat people with the standard daily dose of these things, and everyone's going to be fine. And then secondly, people have said, if you were to personalize, it would be impractical, because we wouldn't have the resources to be able to personalize. We need to do things in groups. And I think that that's changing dramatically with the new technologies we have now that are helping us to understand our bodies. I think of myself, you know, I have these wearable devices that I'm wearing that give me real time information about my body, we're never accessible to any other group before us. And that helps me to understand some of the things like if those of us that have worn continuous glucose monitoring to see what happens in our daily lives, you find, oh, my word, my blood sugar went way wacky. And I wasn't even eating. I just had a stressful conversation, or I just didn't get a good night's sleep, or I just used alcohol beyond that, which I should have, and look at what happened to my blood sugar. So these are real time perspectives that give us an opportunity to personalize and say, well, what's good for you may not be the best for me. And I think that's kind of where I believe the the payoff is for what we're learning to tune ourselves up based on who we are uniquely. Yeah, I agree. I think that the continuous glucose monitor is one of the most powerful tools we can put in someone's hand who's been educated and understands how to use it. It is it's even better than our rings, you know, like it's because it's more actionable, it's more immediate, it's more direct. And it gives you such powerful feedback on whether what you're doing is is working or not. So, okay, I want to move over to the immune system because we, you know, there's there's a whole where this is what we really want to talk about. And it's anyway, it's particularly near and dear to my heart right now. So when people say I want a strong, a stronger immune system, why are they missing the mark here? Like that, you know, people always and we see it in the supplement space and boost your immune system, power up your immune system, make your immune system stronger. What are they missing? Yeah, I think that's a really, really great question. So before I answer that, let me just give a really preparatory thought. If we were to look at what's knowing about longevity right now, and this is certainly not all that we're going to learn about it. But from what we know right now, and you were to ask the question, what would be the single most important thing that we know today that would help you understand your potential for longevity? It would be the age of your immune system. That is the single most important determinant of how long you're lived based on what we know today. Now that begs the question, how do you determine the age of your immune system? And unfortunately, there are new tools that are available that allow us to measure with a blood spot or a blood screen age of our immune system. So if that's true, what I just said, and I believe it to be true, then the question is, how do you get the immune system that's associated with longevity? And you get one that's the most resilient immune system. It's not the most boosted immune system. It's the most resilient. And we learned something about boosting during SARS-CoV-2 in COVID-19, and that was people who died, often died because their immune system was so boosted that it killed them. Their immune system was in hyperfunction, and they had these what are called cytokine storms, which was the immune system gone wild, and they drowned in their own fluids, basically. And so that's the extreme example of an immune system overboosted. What you want is a regulated immune system that has the intelligence to know when to turn on and when to turn off and what cell types to actually get engaged in, what cell types to maintain quiet. And that particular story is a whole different story than has been told, I believe, about immunity, coupled with the concept that our immune system is much more than just the defense against infectious organisms. It does a lot more than just virus and bacterial defense. It is rebuilding tissues, it's surveilling 24-7. There are only two systems in the body that are sensing the outside world 24-7, 365. One is the nervous system, and the other is the immune system. And they're telling the whole rest of the body how to behave. And so if we have a resilient immune system, one that has all the capabilities of knowing friend from foe and knowing when to turn on and when to turn off, and what cell type out of the hundreds of different cell types in the immune systems to activate and which ones to deactivate, that intelligence in the immune system is associated with people that are 100 years of age and still healthy. In fact, there was just a paper published of an Italian gentleman, 122 years of age, in which they, in fact, he just passed away. But when they measured his immune system age using these molecular tools, when he was 118, he had an immune system in the age of a 65-year-old. That's incredible. And so these, if you want to talk about longevity, that's where some of the secrets us lies. So when I think of how you then maintain resilience and the ability of the immune system to have this intelligence to do the right thing at the right time, whether it's allergy or arthritis or chronic pain or fatigue or cognitive dysfunction, which are all associated with immune imbalance, then you want to find ways to speak to the immune system at a fundamental upstream level. And then you say, okay, where is that? Who is the teacher that instructs the immune system how to behave? And it turns out, and I didn't know this until the last few years when I really started digging deep into this field, that 40 to 60 percent of the immune information that targets our immune system comes from our diet, 40 to 60 percent. That's a pretty remarkable figure, isn't it, when you think about it? And the thing that I think most people don't probably understand about the immune system is that our cells, our immune system that we have right now, as we sit here and have this conversation, will be different than the cells in our immune system that we'll have four months from now. Our immune system turns over about every four months. And therefore, it has a chance to learn. It can learn bad things. It can learn good things. For instance, either one of us was to have a very severe viral infection in the next week or so. Our immune system would learn from that viral infection, that information that that infection produced, and it would, for that generation of immune cells, respond and have that memory. If we ate junk food, if we did the SupersizeMe study on our own body, and we ate, say, for a month, just ultra-processed foods, our immune system would remember that, and it would imprint those cells that would stick around for as long as we continue to eat that diet, and we would have a different immune system. Now, maybe at the end of the four months, we say, oh, I've had enough of that, as Morgan Burlock did when he said, okay, now I've degenerated my health, now I need to regenerate it by getting off the SupersizeMe diet, which was the McDonald's three meals a day. And when he did that, then all of his blood parameters returned to normal. But the blood parameters returning to normal were surrogates for what was going at the immune system. Yeah, so that's, I mean, that's both frightening and exciting, right? Because it means that whatever you're doing today, if it's not optimal, you can change it. You can use your powers for good or not good. It is, and I think that that's one of the things that sometimes scares people, not in our space, not in the, you know, whether we want to call it the biohacking or longevity space, but regular folks walking around on the street, they don't want that responsibility. Because it's a little bit overwhelming. It means it's on you. But I think it's so empowering to know that you can mess it up, and then you get a do-over. I mean, it's not always that simple, obviously. But the inherent resilience in the human body that is built in can be forgiving under the right circumstances. So, you know, not to, I mean, look, there's plenty of people dealing with crazy immune system dysregulation. And we maybe we can talk about that a little bit. So, you know, like, can you think of it? I mean, I'm sure you can. Like, what would be a real life case where person symptoms look like, like they have a weak immune system, but actually the real issue is the dysregulation at a much deeper level. Well, that's a really great question. So, I think we have a cultural, almost iconic stigma. Maybe stigma is not the proper word, but some kind of a bias that women have weak immune systems, weaker than men. Because women have stronger immune systems. Well, you do. You do. But the reason I say that is that 80% of patients that have autoimmune diseases, one of the 80 different types of autoimmune diseases from thyroiditis to multiple sclerosis to rheumatoid arthritis or to systemic lupus, 80% of them are women. And so, there has been this view that somehow women must have weak or damaged immune systems, which actually is not true. And I could go through a whole narrative why that's not true. But let's just say no. What you just said Natalie is actually correct, that women have stronger, they have more robust immune systems. And for one reason is their immune systems have to accommodate a foreigner living in their body for nine months. That may even be the opposite sex from them. And I mean, just think of that. That's an immune system that's got tremendous plasticity to accommodate a foe and friend in different ways. So I think that the constructs that we carry about the immune system sometime lead us into a self fulfilling prophecy that woe is me, I just got stuck with this bad immune system. And if we look at the number of, and I'm now talking from experience of the last more than probably 30 years of individuals who complain with what we'd be called preclinical autoimmunity of these different forms like chronic fatigue syndrome related conditions or or fibromyalgia related syndrome conditions. These these are thyroiditis, I mean, I could go on and on, but I have seen countless and we have published actually numbers of papers on this intervention with diet and lifestyle, how these things resolve, because we retrained their immune system. Now there is a point where your immune system becomes so trained and so ensconced with experiencing trauma that it's very, very hard to get it back even post traumatic stress syndrome is an immunologically oriented problem. And it's hard to undo some of those trauma induced changes that occurred. You know, I always say the harder they were to put on the harder they are to take off. So if you've been really traumatized, it's harder to get them off. This may be actually where some of these hallucinogenic drugs and psychedelics are working because they're hard hitting. And they're changing epigenetically the immune system. It requires that degree of leverage to do that. So but I think a lot most of us, much more simple things can relate to the resurrection or the rejuvenation as I would call it of the immune system. And the number of symptoms that improve from that, it's always amazing to me when this occurs with a patient because they'll say, I came in wanting something to like my sore shoulder to be improved. But now I'm sleeping better, I'm waking stronger, I feel like I have more energy, my mind is more clear, how did that happen? Well, they're all interconnected, right? Our body is a network of web of things that tie together. So I think that this immune rejuvenation concept, which is what I'm spending all of our groups time trying to understand. And you know, we have now names for different immune cells, you've probably heard zombie cells. That's a really interesting name. Cells that are still sitting there in our body, carrying on functions that are kind of like fugitive cells, but they're kind of not up to par as it relates to the cells that should be doing the work that they're designed to do. And so you carry this, these cells around this baggage that are sending bad messages to your body, and if you get enough of them, now you really feel pretty bad and it creates these diseases. And it's associated with aging. And I'm reminded there is a cell type, I'm going to use a long winded term here, this is not to try to impress people just to show how this field is evolving. These cells are called members of the clonal hematopoiesis of indeterminate potential family. If I use the acronym, clonal hematopoiesis of indeterminate potential, C-H-I-P. So these are chip cells. So they sit in there as chips and they are clinkers. And it turns out that because they're hemopoietic, what means they're in the bone marrow, they're the starting point from which all the other white and blood cells are formed. So if they are already carrying bad messages, it creates a lot of hazards or chaos in everything that's going on. So it turns out that it is known, a well known, that over age, age of birthdays that people collect these chip cells. What has more recently now been found is that the number of chip cells you collect is not totally connected to your birthdays. People can be young and have a lot of chip cells, or they can be old in birthdays and have few chip cells. And it turns out that the factors that create chip cells are part of our diet lifestyle and environment that create mutations in the hemopoietic stem cells that make them into these kind of clonal nefarious cells that don't do the jobs that they're supposed to do. They're doing other things and they stimulate inflammation, the process of inflammation connected to aging. And so now we're really asking how do we get the bone marrow to be healthier, these cells that come out of the bone marrow. And so there are now a lot of work going on to look at how diet and lifestyle and other interventions can resurrect these primordial stem cells that are in the bone marrow. This is where this field is all going. It's a much more precise way of describing the immune system than we previously had. What's amazing about this is it comes full circle. On the one hand, as I said to you before we started recording, I interviewed a researcher yesterday who is working on mitochondrial transplants and they're working on actually transplanting mitochondria into stem cells, which will to your point, I mean, it could potentially rejuvenate the immune system to a degree, right? But how fascinating that our diet and our lifestyle and nutrition, that pure nutrition going back to the foundations can also play a role. And I believe that these two are not exclusive. Like both need to happen. Exactly. You can implant as many mitochondrious as you want. If you're eating, if you're super sizing every freaking day, you're going to fundamentally disable that if you're living in a stress in this state of chronic stress, that you're unable to control or mitigate the effects of on your body, that too will fundamentally affect your immune system's ability to respond. You know, I'm so I just want to say that I'm so happy that you said that about the immune system in aging, because I said that to someone recently and they said, no, well, you know, there's a cardiovascular system, there's this, there's that. And I'm sitting there going, but it's the immune system that decides everything that's happened, everything that's going sideways and all those other systems is really coming from that immune balance function, whatever the case may be, into in some way shape or form. Like, I asked the question when I'm when I'm talking to docs. And I've been amazed actually, quite honestly, maybe a little bit disillusioned when I asked this question, they say, so where does the immune system reside? And, and, you know, most people immediately say, well, it's in the blood stream, that's true, the white blood cells floating around about 10% of your blood is white blood cells. But I say, actually, the immune system is in every organ of your body. What other what other organ do you know is in every other organ? Yeah, what is the heart in the lungs? Is the kidney in the pancreas? Why is the immune system in every organ? The immune system is in your fat. It's in your brain. It's in your thyroid, your pancreas in your gut. It's everywhere because it's the universal messenger. It's the message maker. Sidebar question. Sometimes, before autoimmunity comes an overactive immune system, like how does that show up in people? And fundamentally, autoimmunity is an overactive immune system that is miss that's hitting the it's fire. It's like a gun that's been pointed in the wrong direction kind of thing. How does that show up for people? Like are there signs before the autoimmunity hits that the immune system's kind of gone offline or is overactive that people are seeing? Yeah, I think first of all, I think the term autoimmune is miss a misnomer. I want to I want to qualify this by saying I'm a heretic here. That's okay. You're allowed to be you you've earned the right sir. Okay, well, thank you. I don't think everybody will necessarily agree with me. But the reason that I say that is that autoimmunity by a term suggests that you wake up some morning and your body doesn't your immune system doesn't like you anymore. You have been you all these years. And then suddenly your immune system that's been with you says, no, hold on just a minute. I don't like something about you. And I'm going to attack you. The most pivotal thing that we share, which is you, I'm now going to make you an enemy. And I'm going to I'm not it's not only an enemy, but it's so specific. I'm going to actually even attack your DNA, your book of life. I'm going to produce a response and do war against your DNA in yourselves. Now, when I ask that question kind of rhetorically, does that sound like a logical way for the body to design itself that suddenly it wakes up and says you're an enemy of me and I'm going to attack you? Or was there something that precipitated that situation where your immune system starts attacking what appears to be you? So now you dig deeper with that question, you start to which I've spent decades now digging deeper. And what you find out is that no, normally, it's not the immune system attacking you. It's it's something that changed in you. Some molecule or some protein or something that used to be you got changed. Now, let me use an example. We all know about glycohemoglobin A1C as an association with diabetes. What is A1C? A1C is when glucose, the sugar in our body and our blood, attaches itself to the major protein in red blood cells, hemoglobin. So now when there's a chemical attachment of glucose to hemoglobin, it forms a new kind of hemoglobin, this protein hemoglobin, called glycosylated hemoglobin. Now, is that hemoglobin a natural you or not? The hemoglobin was a natural you. The sugar maybe was a natural, but you put them together, that's something foreigner. Right. Now, and what does the immune system do when it sees a foreigner? Yeah, exactly. It says, oh, I have a job to do. I got to get rid of foreigners. Now, what do we know about the correlation between autoimmune disease and diabetes? They're very correlated. Why? Because mechanistically, they share the same common theme that you form something that is not you, that your body now starts to attack. And who will be the first person to do the attack, the ones with the most sensitive immune systems? And who do they happen to be? Women. So all this stuff, when you retell the story, doesn't sound like autoimmunity. It sounds like something else that's going on. Now, let me use an example of thyroiditis, because we see a lot of autoimmune thyroiditis, Hashimoto's disease, particularly in women. And it's if suddenly their thyroid gland is said to their body, you're not a friend anymore. I'm going to kind of, the immune system is going to take care of you by reacting against you. Well, actually, if you look at this more intelligently, you find out that these antithyroidal antibodies are being produced by your immune system against things where your thyroid tissue was changed. And one of the things that causes to be changed is exposure to polynuclear aromatic hydrocarbons, organic pollutants. Organic pollutants bind with thyroid tissue, and that causes now the tissue to no longer be you. It's now a transformed tissue. And your immune system says, well, we don't want that here. That's bad. We better get rid of it. And it attacks. And the innocent bystander is you. So what do we do? Well, we detoxify. Because things turn over. Cells don't stay around. I mean, even even the neurological cells in the brain have been found to have a turnover. They're much more slow than the immune system. So the whole concept is reconstruct your body. That's, you know, this term I'm writing this book now around this concept of rejuvenation. When we look at rejuvenation as a cell biological phenomena, we've now discovered how that actually occurs. Processes of apoptosis and mitogenesis and so forth are processes of rejuvenation. The body has it. The problem is that we've overloaded the damage beyond the scope of our ability to rejuvenate. So we collect more and more junk. And we stop fasting. That's right. Exactly. We stop fasting. Right. We have to remove the inputs for the body to turn inwards to do the work. Which goes back to our initial concept of eating cyclically, eating circuitingly, nutrients in different levels in different seasons. This is all part of a natural rhythm. Yeah. So if someone's sitting there saying, okay, well, how do I know that I have balanced resilient immunity? What does that look like? Like, how do they measure that? Is there, can they tell? Yeah. So we're doing a study right now that I'm quite excited about. You're the first person I've had the chance to share this with. It's a clinical observational trial. So I don't want to call it a double line placebo control trial. But we are looking at a marker that's a very simple marker for immune resilience that most people have overlooked as a tool. And that is, it's a $6.20 test that everybody that's, everybody that's, Sign us up. We don't even need a discount code for that. Exactly. Everybody that's ever had a blood test from their doctor has had this test done. It just wasn't read in the right, in the way that I'm going to describe. So this test is called the complete blood count with differential, the CBC with differential. And the differential is to type the different types of blood cells in your blood screen. So you get lymphocytes and you get monocytes and macrophages and eosinophils. And you get a list of the different characters that are making up your blood cell population. And it turns out that the ratio of those characters in your blood personality, blood cell personality tells you some things about your immune system. This is kind of a name, this use of this algorithm. It's called the systemic inflammatory index or SII. And the SII is just a mathematical way of using the data that comes from a blood test to see what the status of your immune system is. And what we have found is that you can change your SII to make it more resilient by dietary and lifestyle intervention. So it's an easy marking tool. Now I want to emphasize that this is a surrogate marker. It's a blunt tool. It's not specific to the level that if you did cytology and you did very detailed immunological work, you get better information. But for a general first level pass for $6, it's a pretty good way to infer information. Are those values available anywhere of the ratios that people are aiming for? Yeah, they are. It's just training docs now how to use this. They just have to do a mathematical calculation they can do on a calculator very simply. You don't need a computer. Is it something we can share with the audience or maybe put a link somewhere? Oh yeah, we can certainly... There are many... I was going to say hundreds, but let's say a hundred or more clinical studies on the SII, more than a hundred. So basically we want to look for what are the values we're looking for in the SII that give us an idea that we've got immune balance. That's right. Immune balance, which is immune resilience, which is immune intelligence. That's right, which is immune age. So this is the biomarker that's going to matter when we're looking for immune aging, immune activation, immune competence. Like these ratios are going to tell us where we're at. Like many women, I'm working hard to hit my protein goals for muscle, metabolism, bone strength, but I've also learned my lesson with proteins. You really have to dig through the truth about their ingredients. I've read that two-thirds of protein powders tested had more lead in a serving than California safety limits. Not exactly the morning ritual I had in mind. Now this is why I switched to Peori PW1. I used the bourbon vanilla made with real vanilla seeds from Madagascar, and it is so smooth and naturally sweet that adding it to my yogurt bowl or shake actually feels like a treat. Plus for every scoop, I know I'm getting clean, high quality whey that supports my strength goals. 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I think you said it very well, because three months is good. It's 90 days. That's the time it takes for the immune system to start turning over. And so we have, I'm very proud to say, I think, what I'm going to say is true, we have the largest clinical trial, double-blind placebo controlled trial in humans ever done on a single food intervention over 90 days, looking at immune resilience, using molecular analysis of epigenetic sites of the immune system. It's 850 people in a double-blind randomized control in which the food we're using is the... As far as we're concerned, the most immune active food that we've ever been able to see, which is this tartaribuck wheat that we fell on to, which is a food that has a... I have some downstairs. Yeah, 2500-year history. It has the highest level of these immune active nutrients, polyphenols and flavonoids. And so we have a clinical trial. We've fully recruited now, theclinrtrials.gov, and we will have data by May. And I think it's going to be revolutionary. We'll have terabytes of data. We're doing molecular analysis using gene chip analysis plus promise questionnaires from the NIH to look at the effect on brain health, energy, sleep, and all sorts of parameters. The only intervention is that they're consuming the tartaribuck wheat? Yeah, 30 grams a day. They're doing everything us ad lib. They're normal life, whatever it was. It's not a metabolic ward study. Now, the reason that we think that we're going to have data that is meaningful is that we did a pilot trial that we published in November on 90 people, excuse me, 50 people over 90 days, in which it was not a placebo-controlled trial. We just wanted to see if there was any evidence that if we did a bigger study, it was going to be worth the effort. And we were amazed to see that without any diet control, with no placebo, that individuals who were on the tartaribuck wheat for 90 days, some of their expressions of their immune systems were changed 20-fold. So we think we are onto something here to be able to explain how diet plays such an important role. Well, it's also how a nutrient or the collection of the sweet of nutrients that is delivered by this food affects, it's got to be affecting gene expression. It's got to be affecting, like it's to be that powerful, it actually has to be going way up the chain. That's right. And we've actually can tell you the loci of the 1.2 million gene sites on our chip that we're measuring. And we can tell you what genes are having the greatest performance as a consequence of eating that food for 90 days. What made you look at that food? What got your attention? I mean, I know there's a little man with a stand at the farmer's market in the summer here who's trying to get people to drink the tea, eat the noodles, buy the flour. But what made you look at that? Well, I think it might have been the little man that you're talking about, as she was part of our story. Sam Bearan, his wife, live in Angelica, New York, and he was a former ag research professor Cornell that started growing this tartar, Himalayan tartaribuque on his little farm with his wife, who was a nurse, just for fun, and started to see some really remarkable things that when he was starting to share it with neighbors and so forth. And then I happened to run into by a coincidence, if there are such things as coincidences, when I was invited to go to China to speak to 10,000 Chinese medical doctors. My host there was a Chinese medical doc, but he had a PhD from John Hopkins. So he spoke very good English and we had a great time together. And I was asking him if he knew anything about tartaribuque because I already was kind of introduced to this farmer, farmer researcher. And he looked at me, he says, you got to be kidding me. And I said, no, why he said, he said, my research group in Wuhan are the leading researchers on tartaribuque in all of China. And we've been looking for someone in the United States to collaborate with. So we formed a collaboration agreement. And I came back and then was introduced to another investigator at Vanderbilt University that was measuring the effect on the immune system of one of the principles in tartaribuque. It's unique called two hydroxybenzylamine. And we ultimately formed a collaboration. Now I believe it or not have a consortium of tartaribuque farms in upstate New York that we are regenerative ag approved. And we're the first people in the United States ever to grow it. So wow, that's been my last few years. Gosh, that's that's insane. Kind of is what I think about it. It is so not a coincidence. Like it is so, there is nothing coincidence about any of this. I get just as I'm sorry people, you can think I'm crazy. I don't care. There this is this is energies and forces and and whatever moving people to where they need to be at the right time in the right place. Like it's just there's no coincidence. And that's just fascinating. So all right, I'm going to come back to my original kind of thread only because there's some, you know, kind of this is this was just so fascinating. There's some basic questions that I think people are going to want to hear kind of some answers that they can hang on to a little bit. But other than the fact that, you know, we all need to run around finding getting our hands on some tartary Himalayan tartary buckwheat like now. I don't need to see the results. I'll just eat it. I'm fine. I recommend the sprout powder. It's a three times higher level of the immune active nutrients over the flower. And so Himalayan tartary buckwheat sprout powder, two teaspoons a day provides the level that we did in our clinical trial. Okay, you heard it here first, and we'll we'll put a we'll put a link down below. I mean, I don't know if you sell it. I don't care. We'll just let people know where they can find it. There's this there's this whole distinction between short term inflammation signal that is adaptive that we want, we needed to survive. And then chronic inflammation that is actually degenerative. So how do we tell the difference between the two and especially because the chronic one can be much more insidious, like you're going to feel that adaptive. Yeah, that's exactly right. So that's again, comes back to this SII, because that's measuring more of the chronic states of the fire pot is the pot is boiling kind of thing over time. The as you know, Charles Sirhan at Harvard Mass General gave us a big gift about this, this inflammation that comes and goes when he discovered this class of substances in our immune system called specialized pro resolving mediators or SPMS. Yeah, and and these SPMS actually are the quenches of inflammation. So your body needs to turn it on when you need inflammation to get rid of garbage and to recreate new tissue. But then it needs to turn it off so it doesn't become a long standing chronic problem. And these SPMS that the body makes in response, if it's if you have a resilient immune system, are the things that turn the inflammation process off. And it turns out that those SPMS are derived from omega three fatty acids, icosapigenoid, chendocosahexanoid. And so there are forms of these oils commercially that have a higher levels of the pro resolving mediators that can convert it into SPMS. And those are the ones that are the minimally processed oils. That's why eating fish is different than eating a fish oil. And and so we're studying these because they're all part of this immune resolution process and getting your one inflammation at the right time at the right place at the right level, then you want to get rid of it and want to resolve it. That's what these things do. Yeah, well, otherwise, you're on basically on fire. Right. Okay, we have not mentioned the microbiome yet. We have not mentioned mitochondria yet. So I'd love to kind of spend a few minutes talking about this microbiome, mitochondria connection and and this fatigue that people just so you know, if you can help frame for the audience like gut dysbiosis and and how does end up reducing mitochondrial energy output, which is how people just then they can't get up out of their chair, they can't get out of their beds. You are so good. Wow. I'm just really impressed. That's that compressed a lot of stuff and of importance in a few words. I have a little bit of maybe pride in this area of discussion because my colleagues and I were the first people, I think, to use the term dysbiosis and leaky gut back when I did seminars in 1985 for doctors. You must have thought you were insane. They did. They still do. I mean, they still think leaky gut It's unbelievable the number of criticisms that we sustained over those early years. But with that said, we now all recognize that 70% of the immune system is clustered around the gut. You know, and people ask why was it a cosmetic reason that the great designer of the human body said, I can't think of any other place to put the immune system. So I'll just throw it around the gut. Well, remember that in the course of living, a person will eat somewhere between 10 and 15 tons of foreign molecules in our diet that our body has to decide what to do with. And so it puts the immune system right there close to the action where that stuff's coming has to make a decision as to whether it's friend or foe. So the immune system is taking messages from what's going on in the intestinal tract. And as we know, the intestinal tract has all sorts of a living organ that is not connected to the bloodstream. It's called the microbiome, literally hundreds of different species of living critters, both bacteria, viruses and protists of different types. And those organisms all have personalities and they have their own metabolic characteristics related to their genes because they are more genes of microbiome than there are genes of the human body. And so what they're doing is they're processing and creating outcome that our immune system has to determine whether that's friend or foe. Well, it turns out some of those bacteria, members of the gram-positive bacteria, that's going to gram-negative bacteria family, have in their cell walls various construction elements that when they're released can activate our immune system into inflammation. These are called lipopolysaccharides. And so if we have dysbiosis, meaning imbalanced bacteria in our gut, they can, when they die, they liberate these things that made their bodies what they were, the cells what they were. And our receptors of our immune system, so-called toluyc receptors and particularly toluyc receptor 4 picks up this information and then it signals to the whole body that we have foreigners on board that we need to fight against. And that becomes the chronic inflammation systemically. So that's the dysbiosis connection. And then you say, well, does it stop just at the gut? No, it doesn't because the blood coming out of the gut, the first place it goes is to the liver. And the liver has 10% of its construction made up of immune cells called cup for cells. So the cup for cells, which is the liver's immune system says, oh, there's a foreigner on board, I got to do something. So it sends out message that caused infatuliver disease. And then that sends out message into the blood that goes to the brain. And the brain has its immune system called the microglia. The microglia picks up that information and says, oh, Jesus, there's foreign on board, I better do fights. And it fights back to become neuro inflammation. Now we have dementia. So all these things are interwoven then as it relates to this immune relationship of the gut microbiome to the way we eat and in the things that are going on in our intestinal tract. That's incredible. So I'm going to ask you before I ask for your approach to sequencing interventions, because I do think when we're dealing with stuff like this, there's an order of operations that needs to be followed. But before I do that, what's a fatigue pattern that makes you suspect immune metabolic dysfunction rather than oh, it's a hormonal issue or it's just a sleep issue? Is there are there a couple of hints that you're like, you know what this sounds like it's it's coming out of the gut? Or I think the first symptom I'd look at it is Posteroarthostatic Hypertension Syndrome, where when a person who stands up and they get dizzy and they can't accommodate the change, people would say that's an adrenal problem. Yeah, it is related to the adrenal glands, but the adrenal glands are taking their message from this whole inflammatory cascade. And so that is kind of a whole body kind of surrogate marker for something going on that's associated with chronic fatigue, post viral fatigue syndrome, post COVID long-haul syndrome, although share that in common. So and it's also if you study the mitochondrial function at the cellular level, which we've done using various types of new tests, you'll find that the mitochondria are energetically deficient. They're not producing what they need and they're involved with reactive oxygen species. So you're now in free radical oxidative injury. So all those things are fitting together. So to me, that symptom is is and then you know, I can't go upstairs as effectively. I feel winded immediately and I don't have COPD, all those kind of things that I get lightheaded and feel like I confused, I can't clear my thoughts. All those things fit together. Yeah, like it's a total energy drain. Exactly. Okay, so what is your approach in sequencing interventions? Is it the gut first, the mitochondria, the nervous system? Like, does that depend on the person? Or is there an order of operations that really kind of you feel and you know, we started off this conversation with talking about personalization, but in a situation like this, do you feel that there's a kind of a first line of defense that has to be addressed before we move on to the next things? Well, in 1991, we developed a program that now I have to say is probably, if I look back, been the most highly adopted thing that we've ever put out in the world, we call it the 4R program. It's a sequenced program for I learned that program. I was down at school. Yeah, so 4R is our program that we developed. It was really the birthing of the Institute for Functional Medicine with that program. And it's remove, replace, reinoculate, repair, that's what the 4R stands for. And it's a sequence of tools, interventions that are easily applied, remove the foreigners and the allergic producing substances and the toxins and then replace the acid and digestive enzymes if necessary, then re-inoculate with pre-improbotics and then repair the gut lining with the various nutrients and bioactive substances that actually to better mucosal integrity. That that has probably been applied now to millions of people over the last 40 years. Yeah, 40 years or 30 years. It's foundational. Yeah, and it's easy to do and it works. And when new practitioners come into the field, they say, where should I start with my practice? They say start to be comfortable with the 4R program. Because if you do that, you're going to get such positive feedback from your patients or clients that they'll think you're a magic maker. And then you can expand your tools out into you know, hepatic detoxification or mitochondrial resuscitation. There are all sorts of other things you can do with that. That's a great place to start. Yeah. And I think what's amazing about it is it's not singling out the gut, the mitochondrial, the nervous system. What it's doing is it's addressing the foundation of where the assault is coming, if you will, and all of those things will benefit from that approach. Exactly right. That's where we got root cause. You know, it started to say, hey, you know what, what we're really trying to do is keep going upstream to root cause and this helps you get there. Yeah. In a generally, weirdly general way. Right. Exactly. Do you want to talk a little bit about motility, circadian rhythm in this whole microbiome energy conservation space? Well, I think the thing that I, and that I haven't, when there are probably many things we haven't talked about, but one that I think is, is, is very important because it cuts across a lot of therapeutic disciplines is the lymphatic system and the important role that the lymphatic system plays as a drainage system that gets things flowing in the right direction and doesn't have them sitting in the body. And we all know about lymphostasis, particularly women who've had breast surgery often or chemotherapy for breast cancer. They end up with a lymphatic injury that causes lymphostasis and then they get swelling and, and they get pain in that, in that area where the toxins don't get eliminated. Yeah. Yeah. Exactly. So the, the lymphatic system is interesting because it, it's a fluid flow system, separate set of canals to that of the blood system, but it doesn't have a pump, whereas the blood system has the heart. And so the only way you can pump lymph around the body is by mechanical force, by movement. And so this brings in all the kind of traditional therapies that go way back in history with Arivator or traditional Chinese medicine or you, you name it, every culture and Native American has had some physical method of moving things by massage or all sorts of different physical methods. Even movement, like physical movement, I think this whole idea, yeah, this idea of being a human and moving as opposed to this new found animal that sits for eight hours a day. Like, like we're doing right now. Yeah. So I'm, I'm, I'm on a meditation chair. I get to move around. So I don't know about you. Okay. Good for you. No, I'm not. I've changed my position a few times, but, but truthfully, yes. I mean, to be fair. So the theme here is the construct of when I talk about personalized lifestyle medicine, it really embodies all these tools that, you know, some people say, well, those are kind of old things, right? I like new stuff. Well, the old stuff is tried and proven for thousands of years and we shouldn't throw it out. And these things all get integrated together, just like things that we learned historically about eating and eating the right kind of foods and minimal processed. And, you know, Mark Hyman has his new edition of his book, just out of food fix, it is, I read it, it's, it's, it's revolutionary in that it takes the whole food industry and the whole agonistry on front frontal face, no prisoners. And, and, and says, you know, we have a, we have an issue, it's an existential crisis that we have to do something with because it doesn't go away by just forming more GLP one drugs. You have to make fundamental changes in the way we think about life and how we treat ourselves starting with the way we grow food. People talk about epigenetics. We talk about the genetic, the, the impact of all these different things on the expression of our genome. And one of the things that I think often doesn't get enough attention is food and how foods can trigger those genes. And I'd love to invite you to speak a little bit to how food does this, like through epigenetics, transcription factors, nuclear receptors, read, like the microbiome metabolites, like all of this whole, you know, this, this, this wealth of information. And I've, you know, I'm sure you've said it a million times, but food is not just calories and nutrition, it's information to our system. And can I invite you to speak to that a little bit? Oh boy. Yeah, you're right in my sweet spot for sure. So I'm just finishing up a book actually called the Nourish Gene. Love it. That is going to be on this topic coming out in 27 with Harper. And I'm pretty excited about this book. I think it's revolutionary in the way that I'm really talking about diet from a whole different perspective based upon the very model that you just described. I think it was 23 years ago when I know it was more than that. Now it was 1998. So that's 25 or six years ago, I guess, when I wrote a book called Genetic Nutrition Erring, which I now look back and see it was probably the first book written for the consumer public on Nutrogenomics and how genes and nutrition fit together. We have come so far since then that it's truly remarkable, but it all maps against our observation. People don't have to be a molecular geneticist or biologist to look historically at what people have eaten and how it relates to their health. And I think we all recognize that we've been involved in an uncontrolled study called the ultra-processed diet in which we are participants in that study for the last 50 or 40 years. And the results of the study are coming out and they're not good. People's health is being significantly adversely affected. Then we can say there's another observational study that's been going on and that's to go to regions in the world that are still eating their traditional diets that come out of the soil and look at their health patterns. And I'm always amazed when I take one example in Japan. If you look at the Japanese people who have stayed on a traditional Japanese diet, their level of cardiovascular disease, diabetes, arthritis was extraordinarily low. One-tenth that we see in the United States in some examples. But when those Japanese people carrying their genes with them come to the United States and are exposed to our variation on the diet, suddenly they get the same frequency of these chronic diseases that the rest of the population does. So it's not just the genes in themselves. It's something that is causing the genes to behave differently. So in the last 20 years, with the revolution in understanding our book of life, our genome that's encoded in 23 chapters that represent our 23 pairs of chromosomes, half of which come from our mother and the other half from our father, we've learned that those particular genes don't tell us exactly who we are. They tell us what we might be. Now let me stop there. I think that's a very important point, meaning there are many wheeze that are in our genes. It depends on the signals and the experience that our genes are exposed to as to how they will express themselves to become what we are in our phenotype, how we look at and feel. And that model that I've just described, which was pushed back to some extent by my medicine because medicine is there to treat us once we're broken and they don't really spend a whole lot of time thinking about how we got there, the route to get to that point where we are broken. But now it's an irrefutable fact. There are tens of thousands of studies across multiple disciplines that show that our genes in and of themselves are not the solution to how we look at and feel. It's how we express our genes. And a reminder that when I think of the two twin brothers in our space project here in the United States, one of who went to Space Lab up in this satellite for a period of about six months and his twin brother stayed on land. And they measured all sorts of things in both the brothers. In fact, it's they're probably the most expensive twins ever in the history of science. Literally millions of dollars was spent measuring all these things in them. And what they found, of course, was the twin brother up in space who had the same genes as his brother, their identical twins. As he stayed in space, he became more and more different in the way that his body was working than his twin on land. And when he came back down to Earth, it took more than a year for his physiology to re-correct itself to be more like his twin brother. So how did that happen? Well, that happened because the signals that he was getting through what he was eating, what he's exposed to, the environment of space, were signaling to his genes to express themselves in a different way. And so now we look at countries where there's longevity and historically centenarians live and have productive lives. And we ask, well, what are they doing? What they're doing is they're eating and living a lifestyle that sends signals to their genes to what I call them express their bliss genes. Their goodness genes. They're a celebration of life genes. Under a different set of circumstances where you feel continually under stress, under hostility, under threat, under not love, not a no attribution, you're eating junk, your body is responding to that, it's trying to protect you against trying to kill yourself. And so in that case, it turns out all the genes that are there to protect against the alarm. And those are inflammatory genes. And so now our major disorders in the Western world are diseases of inflammation. But what is inflammation? It's the body's attempt to try to protect itself against hostility. Because our diet is hostile, our relationships are hostile, our environment is hostile. So these things are really powerful shapeshifters of what the new medicine is going to be. The old model, which is a very deterministic model that said whatever our genes were, that's who we're going to be. That was Mendelian genetics is being replaced rapidly by this model of genetic plasticity. And it changes all of medicine changes our whole I mean, this is a seismic shift that we're undergoing right now. And then we ask, Well, how long does it take for a seismic shift to be incorporated into policy? And, you know, I think it's quicker today than it used to be because of the internet and a all kind of communication mechanisms we have today. But it doesn't happen overnight. You know, there's a lot of people that hold on to old ideas, even if they're totally wrong, they'll hold on to them because it's they're comfortable with them or it's to their advantage or they makes them look good or whatever it might be. So I think we're in this revolution in which the whole nature how our food and health system are constructed is flawed. It's built around a model that's not right. And we will as a society somehow find how the truth is going to be enacted and and and delivered to people who are not scientists, you know, they don't study all this stuff like I do. But they can be the benefit, I think of this information that can really change lives in a positive way. 100%. I mean, you know, a podcast like this, this is about this is a call out to each individual who's listening to the show right now, you have the power to do this, you have the power to change the way that you feed your body, which is going to have the power to change the way your genes express. That is huge. That is the foundation of food is medicine as a as a statement, right? But food be thy medicine is a foundational concept. It's old as time. And it, you know, it's just what's old is new. And that wisdom will never go away. So I wanted to ask you one sidebar question here, because you mentioned the people in Japan. And, you know, there's the blue zones, there's all these people. And it occurs to me that in this melting pot that is North America, how big a role do you think the loss of connection to our heritage, like our, like what it takes for like, I'm Mediterranean, somebody else will be Japanese, somebody else will be something else. To me, I've always believed that for me to get to the full express positive expression of my genome, going keto like a like an Inuit person or or or something. Actually, and it shows up in me all the time, doesn't work. It does. I don't have those genes. I don't have the genes it takes to really to respond to that. I mean, I might respond to a ketogenic diet as an intervention, if I do it properly, within a Mediterranean framework. But if I try to practice, or if I even try to adopt an Okinawan diet, it's not going to deliver the information to my genome that it needs. I think you're right on on the nature of what we're learning. And, you know, as I said earlier in our discussion, I've been a proponent for more than 30 years of this concept of personalization. And, you know, when I worked with Linus Pauling, a two-time Nobel Prize winner, you know, his whole concept about understanding the genomic uniqueness of individuals and then matching that with their nutrition need or nutrition intake was was foundational. And that that's really what spurred me on, quite honestly, to start functional medicine as a concept. And so I think what you're saying is true. I mean, we look at, let's use one example. I'd say this is probably not appropriate anymore to use this term. And that's Chinese restaurant syndrome, which is a kind of a response that people have to monosodium glutamate. Yeah. And they get reactions to it. And it turns out that there are certain genotypes that are very sensitive to MSG. And then there are other genotypes that are not sensitive to MSG at all. And so to just make a blank, blanket statement saying no one should ever have a meal with MSG may not be an accurate way of really defining it. And we could go down the list. We could talk about sulfites. I mean, there's a long list of things that are unique to a person's genetics that makes them either more or less responsive. And so I think that this intelligence that we're starting to get now about personalization based upon our genetic heritage and then how we fit, knowing that we're all not not not everyone is, but most of us are sandpiled genotypes. We have, you know, when we do our genetic evaluation, we find gee whiz, we got interesting legacy components that we didn't even know about. And I don't know. Yeah, it's it. Well, I found an interesting statistic actually that a fairly significant percentage in 23 of me of their of their database of the people that have had their genes analyzed, our individuals have found out that they're members of families that they didn't even know about because we had a lot of stuff going on that people were not talking about. So this this revelation or revolution, maybe it's the best word that we're understanding more about our genetic heritage and our uniqueness. And therefore, the the food one be could be could become the poison of another is a very, very important part of this whole story that's emerging. Yeah, for sure. All right, a couple more quick questions. What's an example of a compound in food that acts like information more than fuel? Well, I think that virtually every substance we put on our mouth can be considered an information contributor, some much more intelligent contribution, meaning very specific and how they communicate and others more general. So, you know, if I was to use a general concept, I would say what about sugar glucose? Yeah, you know, glucose is a is a energy molecule, obviously, it's broken down into energy in our body. But it has a lot of impact on how it hits on receptor sites that then create signaling that releases hormones and gets engaged with very complex network biology. And it's uniquely different from person to person. Some people are very glucose intolerant in terms of their diet, other people have the ability to manage it more effectively. So, and then we can go into more specific examples and we can say, well, there are members within the phytochemical field that may be very, very specific. Let's use sulforaphane as an example from broccoli. sulforaphane, you know, has this really remarkable effect on liver expression of enzymes that are involved with detoxification. And depending upon your genes that regulate your detox enzymes in your liver, you may have a more or less response to sulforaphane. Some, let me use another example, dienooilmethane or dim, that's another interesting compound that's found in the cruciferous vegetables like broccoli and brussel sprouts, cabbage. And in some women, you will find that taking that particular phytochemical, a couple hundred milligrams a day, has a dramatic effect on influencing their estrogen metabolism and really helps in clearing estrogen from their body. And then another woman is taking the same amount, we find that the influence is much less. So, and that activates specific enzymes that are detoxifying estrogen, which we have a whole family of those. So, I think there's many examples of specificity of specific nutrients. And then you mentioned earlier, this emerging concept of epigenetics. And, you know, we have, we should give a lot of umbrage to Randy Jertle and Robert Waterland, who is his postdoc at Duke, who really made this discovery that's birthed in 2003, the field of nutritional epigenetics. And that was the discovery in the Agouti mouse that when you gave the pregnant, in this case, rodent, you gave that gave her high doses of the methylating nutrients, folate, B12, B6, betaine, that the offspring were like they had never seen before. The osmine had a different coat color, whereas their parents got fat and diabetes and the females got breast cancer and they died young. The children lived, the offspring lived 35% longer, they were lean, their coat color was different and they didn't get diabetes. The same genes, but just epigenetically modified differently by the addition of these nutrients early on in fetal development. And that just opened up the whole door saying, whoa, just is that the case? What are we feeding kids now? What are we feeding mothers that are going to have kids? 100% and how does that influence the development of children? And does that relate to things like autism or eczema or asthma or the things that we're seeing in children? And so all these are new questions that are being legitimately raised based upon this understanding of this epigenetic remodeling of how our genes are expressed. Love it. Yeah. Wow. Wow. I love it. Love it. Love it. Love it. This is so great. All right. Let's leave our audience with a little bit of a practical roadmap if we can. So if someone wants to eat for immune balance, which by now we should all be, you know, kind of gnashing our teeth going, what do I do? How do I do it? What's the simplest structure for meals without turning this into some kind of crazy obsession? Not that it would be the worst obsession, but let's just say, what's a really simple framework we can offer people that they can start tomorrow? Yeah, you know, it's interesting to me, we've got a lot of controversy right now about plant foods. And and there, I mean, there are, there's a pretty big movement that's anti plant foods that really powerful. Yeah. That they're not healthy and they're damaging and they cause arthritis and they do bad things to our gut. I think it depends a little bit on how we talk about plant foods. If plant foods are coming from highly processed things that are ending up as white flour and a bunch of devitalized corn and soy. That's those are plants, but it'll be like saying, you're a vegetarian if you drink Coca Cola and you eat Twinkies m&ms. Exactly. We're on the same page. Yes. So, so I think that this this plant kingdom has so many messenger substances that speak to our bodies in ways that you don't get out of animal products. Now, there are certain advantages to animal products as it releases protein and amino acid levels and certain vitamins like vitamin B12 that's generally found in animal products and vegetable products. But in terms of the overall health benefits, if we were to weigh those, the plant foods, if you if you ate a diet that made sure it had a rich array of different plant foods that were minimally processed, you would be hitting a lot more success stories as it relates to how we know the body really works. And this relationship that we have with plants that goes way back in evolutionary history, you know, hundreds of millions of years is a very intimate relationship that we are seemingly still debating. It's what I find kind of fascinating. So then we say, Well, what kind of plant foods? And, and that's where I think I mentioned this concept of eating the rainbow where we eat foods that are naturally colored from the red, orange to the blue, green and yellow. Those colors are all different families of phytochemicals, all of which have different effects epigenetically on how genes are expressed and become the master regulators to a great extent of how our genes are expressed. So we could say, Oh, those foods are anti inflammatory or we could say they're antioxidants. Well, that's kind of a gross way of talking about them. But more specifically, they're actually interacting at a very specific level to turn on and turn off genes epigenetically and create a different outcome. So our body feels more at home, more friendly, and less in a hostile environment. So that's kind of where I would start, you know, you give over the ultra processed stuff, and you start introducing more of the eating by the rainbow by including vegetable products into your diet. Yeah, I love that. And eating meat and chicken and fish, like, I think that over and over again, what we see is that we do really well as omnivores when we eat the right foods. Like that's, we have the luxury of being able to access the nutrition, the nutrient density from both camps. So that doesn't mean that every once in a while, you don't have interventionally a reason to go one way or the other for a short period of time, maybe. But you know, there's a lot of wisdom in this. I just wanted to throw at the concept of inviting people to do an experiment like this on themselves, maybe for 90 days, right? If you I mean, start, start with a week if you find 90 days overwhelming. But maybe you can speak a little bit to the, to that there is a magic number at 90 days, there's, there's a magic to 90 days in impact on the human body of a certain intervention. I totally agree. And I think this is actually a major theme in my book, I have this immune rejuvenation food plan, and it's a it's a 90 day food plan. And the reason for it is the immune system, as we mentioned earlier, turns over every three to four months. And so if you want to really renew your immune information, you need to give it some time to do so. Those some cells have to leave the leave the system, and others have to replace them that are imprinted with different information. And our immune system is constantly learning. So we want to send it new information to make it friendly. And, and that takes 90 to 120 days. So you can't be impatient. It's not like taking the antibiotic for a bacterial infection that you expect in three days, you can get over the infection, we're talking about restructuring the way the body actually is working. Love it. All right, a couple rapid fire questions, Dr. Bland to finish this off, a health belief that you have changed your mind on recently. Oh, that's a good one. So I think gluten would be probably what I put as a quick that's kind of when I go quickly into my head and think about this. Now what we're finding is it by the hybridization of grains that have occurred over years with genetic inbreeding and, and crossing and so forth, that we have produced a product that is not just gluten alone. There are many other unique proteins that are in that. Yeah, that the immune system has not seen before the immune system of humans. So now it starts to look like a foreigner. And, and people often say, you know, when I go to Italy, I don't seem to have any problem with gluten. But when I'm here in the in the North America, I've got all sorts of problems. Well, it's the same supposed product, but it's actually not genetically the the the makeup of the proteins in that grain is different. So I think this is something that's very real. This whether you call it gluten sensitivity or carbohydrate intolerance, or you know, we have the FODMAP diet that is used for a lot of people with these problems. So that has been kind of one of my aha learnings over the last decade or so. Yeah. And I think what you said is so true it's it's not the gluten molecule that we maybe were exposed to 50 or 60 or 70 years ago, it's it's the we've changed it and yeah, it's changed. All right, a biomarker you think will be mainstream in five years that is not today. Oh, no, that's a good one. So I'm going to throw out an esoteric one that probably most people are not yet familiar with. But I think it's a dark horse. It's it's acronym is SUPAR, S-U-P-A-R, little s, little u, capital P, capital A, capital R. It stands for solvable, neuroplasmidogen activator inhibitor. I like super. I thought you would. Yes. It turns out that that that analyte, which you can measure in the blood fairly simply, is really, really powerfully indicative of chronic inflammatory states more than any other marker that has been studied, that's conveniently measured. And it's it's not so easily changed by the immediate environment like is HSCRP, HSCRP, a high-sensitive serocular protein that can move all over the map. If you're if you're sick or have a cold or something whereas as SUPAR is really stable because it gives you a more consistent message as to what is your inflammatory state. So that that's my insight track. And of course, I also talked earlier in our discussion about this very simple $6 test from your complete blood count, which which is the SII and SIIRI that comes from your differential. That's a that's a biomarket simple and available to everybody today. So that would be my choice. Cool. A food you personally keep coming back to for immune balance. Salmon. The question you wish every patient would ask their doctor. What does their doctor feel about the importance that diet and lifestyle play in health outcomes? Thank you. And if someone only remembers one idea from this conversation, what would you wish it to be? Each person is in charge of the orchestration of their health journey. Love it. Dr. Bland, where can listeners learn more about your work and big bold health and get their hands on that magical and other really powerful product? Actually, the the stargory buckwheat. Yeah. Yeah. So I'm really in three different places that you can find me. Actually, I my family doesn't really think this is a good idea, but I'm giving it a world. I have a virtual Jeff that is now codified. Oh, wow. My two terabytes of data that I have put into the world's literature of all my presentations, all my publications were all put into a AI program that is learned by me or taught by me. So you can you can speak to Jeff if you want to, you can either write or talk and I will either talk to you or write back to you. And so that you can find me on my own website, JeffreyBland.com. It's I'm also on the similarly with a with a virtual Jeff on the personalized lifestyle medicine Institute that I founded, which is PLMI or if you it's actually PLMinstitute.org, you know, but you can just look at PLMI if you do a Google. And then lastly is the work that we've been doing on immune rejuvenation and immune health through Big Bold Health. So BigBoldHealth.com, you'll find me and my colleagues, Dr. Ross and Pearl Mutter and others that have been working the last eight years and trying to decipher how to treat our immune system with respect. So those are the three places you can find me. Thank you. And guys, check out the show notes because we may have a Lincoln code for you guys down there to just as a listener of the podcast. Dr. Bland, this has been a total honor and pleasure. Thank you so much for taking with me. No, Natalie, you're awesome. I think your listeners get a huge value proposition by following you. You're very insightful, very sharp and also a lot of fun to be with. So that's a pretty good mix. Hey, folks, just a quick reminder that all of the information presented in this podcast is for information purposes only. No medical advice, no diagnosing, no treatments suggested here. Before you try anything that you hear about or learn about here, make sure that you check with your medical provider.