332. Rejuvenate Your Immune System with Dr. Jeffrey Bland

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To learn about our courses, our community and everything we do, visit us@onecommune.com. Welcome to the Commune Podcast. My name is Jeff Krasno. Today on the podcast, I welcome the legend, the Dr. Jeffrey Bland. Jeff is widely considered the father of functional medicine. In 1991 he launched the Personalized Lifestyle Medicine Institute and the Institute for Functional Medicine, which has educated hundreds of thousands of healthcare practitioners around the world who are interested in going upstream and examining the root causes of disease. He is the author of numerous books including the New York Times bestseller the Disease Delusion and has penned hundreds of peer reviewed papers. In fact, Jeff was publishing on the Microbiome and Leaky Gut all the way back in 1985 when literally nobody was talking about it. Dr. Bland's latest project, Big Bold Health, launched in 2018 and it's on a mission to transform the way people think about one of nature's greatest innovations, the immune system. In our conversation, Dr. Bland and I deep dive on the immune system. We delineate between the innate and the adaptive immune systems and Jeff outlines the various forces that contribute to the degradation of the immune system, or what he dubs immunosenescence. And we discuss various protocols and foods for immunorejuvenation. I had the privilege of hosting Dr. Bland and Dr. Austin Perlmutter in Topanga where we filmed a new course titled Immunity Reimagined that will be released in early 2023.

So look out for that.

And if you're interested generally in functional and integrative medicine based programs with doctors like Dr. Bland and Mark Hyman, Mary Pardee, Zach Bush, Roger Schwelt and others on topics such as gut health, sleep immunity, hormone balancing, Ayurveda and nutrition. Well, you can Sign up for 14 days of free all access to Commune's entire course library, including more than 100 courses on health, personal growth and social impact. Just go to 1commune.com trial and please support this podcast by subscribing and and leaving a review on your favorite podcatcher. Now, Jeff has deeply influenced virtually every doctor that has ever been on this show, including Mark Hyman, Kara Fitzgerald, Kasey Means, David Perlmutter and many others. And he shares stories about his own mentor, the two time Nobel Prize winning Dr. Linus Pauling. It was just fascinating to be a link in the passing down of wisdom generation to generation. So without further delay, I present to you the legend, Dr. Jeffrey Bland.

Okay, Dr. Jeffrey Bland, welcome to the calming podcast. So great to be with you, man.

That's how I feel. There's just sometimes you feel like you relax into an environment and you know, you're at home. So that's how I'm feeling with this opportunity. So thank you.

Yeah. Well, thanks for taking a chance on coming up into the hills with no Internet to a place called Commune. You're, you're a brave man.

Well, no, actually this, this is Back to the Future for me because it seems like this is actually where I started was with groups of people in very remote settings talking about ideas to create a better world and doing it without the disruption of the daily life that causes interference with your best thinking. So I feel like I'm in the right home here.

Yeah, that's beautiful. This is a place for long wave thinking and long wave connection in a world of seemingly endless distraction. Right. So we get to use this place and leverage it for this kind of immersive interactions and conversations in the next two days that we'll spend together, I guarantee will be incredibly special. So again, thank you. And this is an auspicious day for me because this marks four years to the day that I started this podcast.

Oh my word.

Wow. And you know, there's been 350 some odd episodes in there. And I will say this is a monumental one because over the past four years I've interviewed functional medicine and precision medicine doctors Mark Hyman, David Perlmutter, Casey Means, Sarah Gottfried, Kara Fitzgerald. Like so many people that your colleagues and people that you know. And obviously the, the, the purpose of functional medicine is to go upstream and excavate root causes. And I feel that this conversation in and of itself goes upstream. Because all of those people that I just named owe a tremendous amount to you and your vision and all the work that you've done to synthesize around functional and precision medicine. I feel like we're at the source of the river and this is an extraordinary opportunity. Again, thank you.

Thank you.

I am really looking forward to unpacking the immune system together and immunosenescence and what we can do to rejuvenate our immune systems and just to build some general fluency around immunity in general. Because, you know, if there's a silver lining of that has emerged from the COVID epidemic, it's that people are tremendously curious right now about medical science, about physiology, about epigenetics and neuroplasticity, but particularly the immune system. So there's a lot to educate on there because we need to meet people's curiosity with stringent, high quality information now more than ever. But before we jump in there, I. I'd love for you to even go upstream from you and talk a little bit about your relationship with Linus Pauling, because I have just discovered his work, really through you, and what a marvelous, unbelievable figure in history. So I wonder if you could spend just a moment talking about how he bent the arc of your personal life and your career and everything that you've thought about to bring it to this place here.

Well, that's a real privilege to be able to honor and celebrate Dr. Pauling and you know, I'm just one of hundreds of thousands, maybe even if I was to be even probably more global and circumspect. His and his wife Eva, Helen's conceptualization as they saw their lives together and how they contributed back through their work was really global shape shifting. Most people don't understand that. And you know, I find it's. It's always somewhat sad about legacies because legacies are in the lifetime of the individual. It's hard to keep them alive in the next generation because we're all sound bit with so many different things, things that we're trying to keep in our minds. But it is really important to pause for a moment, I think, and think about the contributions that the two of them made, which I summarized in a. In a article that I wrote after he passed away at 93, that was about his legacy from kind of a higher level because some people knew of him as a unbelievable inorganic chemist. Some of them. Some people knew him as a person who started introducing quantum chemistry and quantum concepts into chemistry. Some of Him. Some people knew him as the father of the mechanism of anesthetic drugs. Some people knew him, as with Delbruck when he was at mit, the conceptualization of how the immune system works at that. Before that, there was no one who really had explained the adaptive immune system and how antibodies were selective. Because if you think just for a moment, just take a sidebar on the immune system. How is an immune system that's built out of genes that are in our body capable of recognizing substances for which they never knew they would be exposed and to have more opportunities for response than there are genes in the human genome? Our immune system can respond to millions of unknown substances from the same set of 20,000 genes. How does that work? And, you know, that's, that's a paradox or a dilemma. But he worked it out and it was, it was the foundation of how we now see mechanistically, the adaptive immune system working. So that was another. Other people would say, no, he was the father of vitamin C. There was more recent in here or more recent past in his history. Other people would say no. He was really the guy that really talked about orthomolecular psychiatry for the first time and got with Abram Hoffer to really consider the whole mental health connection. His son, actually, Linus Pauling Jr. Is a psychiatrist. And. And he really, I think, birthed that interest in his son to go on and become a psychiatrist. And so he. His article in 1968 in Science magazine was on orthomolecular psychiatry, right. And how that relates to the molecules of the mind. And then other people would say, well, no, no, actually, he and his wife, although I don't think his wife gets the credit she deserves for this, were the advocates for peace and for celebrating human equality and for opportunities of people that are disadvantaged. When I was in my two years, which were life changing though I spent working at his institute as a director of one of his research labs. This was 1981 through three. He was going to Russia to try to introduce communications between the scientific community and Russia, which is totally for boating. He was trying to have free elections in Guatemala. He was going down there and advocating free elections. I mean, I could go on and on with, with his advocacy. And of course, he is the only person to win two independent singular Nobel prizes, one in chemistry and the other in peace. And so the. The litany of things that I could talk about. Let me just, however close with a human experience, because I think it describes more than anything I could share my love for the Paulings and what he Left us all because I think it's symbolic of partnership between partners, in this case a husband and wife that creates better than either when they're synergy. So in the 50s, he was at California Institute of Technology and he was gaining world recognition for. For. He won his Nobel Prize in chemistry in the. In the middle 50s. And he was at the Krellin Laboratories and was. His opinions were very highly respected, particularly around nuclear chemistry. And if you think of Hiroshima and Nagasaki coming out of the end of World War II, more and more people were interested because nuclear power was starting and nuclear weapons were still of concern and the whole concept of radioactivity. So he was giving a lecture to the community at Caltech in which it was on nuclear chemistry. So he, as always, is eloquent lecturer, and he gave this really informative lecture trying to dumb down nuclear chemistry so the community could understand and recall. In Pasadena, where Caltech is housed is kind of the suite of the aerospace and defense industry. So there were a lot of heavy donors to Caltech as a private university that were somehow engaged in defense industry issues. So he gave this. This impassioned talk and he went off the stage and he was asked to come back and answer a few questions. And one of the women there asked the question, Dr. Pauling, you're such an authority. You speak so clearly about this. What do you think about nuclear arms and nuclear weaponry? And his response to her was, I think is a very important question, but really I'm not an expert in that area. I'm an expert in nuclear science. I'm an expert in nuclear chemistry. I can speak with authority and knowledge, but I don't think that I really can give you a competent response because that's a sociopolitical issue that's far beyond that of just the science. So he left the stage. He got in the car then with his wife Eva, Helen, who was quite an activist, and they started to drive home to their house. And she said, you know, Dr. Linus, why did, why did you say that you don't have experience? I mean, we talk about this all the time. You have very strong opinions about this. They said, well, yes, I do, but I, you know, I didn't think it was the right form to do it. I mean, I'm not being seen as an expert in that. I would just offer an opinion. And she said, hold it. How many people in the world know more about nuclear energy and nuclear processes than you? You're on that rarefied group, and you have very strong opinions about the concern you have about Nuclear weapons and proliferation. And if you're not going to speak up on it, who is? And he said, well, yeah, you've got a point. But you know, you got to remember that I am here in Pasadena and this is, you know, kind of the center of the defense industry, right? And she said, okay, fine, but I'm telling you this, that there's going to be no dinner made for you until we get this resolved. And as the story goes. He told me the story. Actually, as the story goes, a couple of weeks went by and she wasn't doing any stuff for him, right. It was like, okay, you created your island, live on it. And over the course of those couple weeks, good time to reflect. And I think was more than just the absence of having home cooked meals. I think he recognized it, that he needed to be more of an advocate. So he made a commitment to her that in every talk he gave subsequently anywhere in the world, he would have something even, no matter how hard science about the social implications as he opinionated it to have as it relates to that issue which he lived up to. If you go back and you review his subsequent speeches and ultimately those that won him the Nobel Prize in peace, which by the way, he could not go to Stockholm to receive the, the award because it was the period of McCarthy that he was not given a visa to leave because he was considered to be a communist. And so there are so many interesting stories that relate to them as a couple, their advocacy, their positions, their broad ranging nature of knowledge. And then lastly, and this is kind of my closing comment, the way I embodied all of this extraordinary work, not just Only the some 800 publications in the science literature, the multiple books and all the things they left as legacy, all the science studies, but if you were to assemble them into a kind of a sound bite and say, what did it really represent to me? And I think many, many people that have studied and admired their work would, would agree. He was, they were the first people to talk really deeply about the concept of structure and function, how they connect together. So really, if you look at the through line that connected together everything he did, from quantum chemistry up through social justice, it was tied together with the principle that if you get the structure right, the function, the good function will follow. That was my birthing those two years put in my mind, that was it put in my virus in my nervous system that I could not get away from. So when I Left there in 82, I didn't realize it quite honestly that I was speaking to. And I actually wrote when he finally passed away several years later. I wrote an article about structure function, but I didn't realize that that was so strongly embedded in me that when we hosted these meetings in my wife actually was the one that did this in Victoria, British Columbia, Vancouver island, with these 45 thought leaders that I invited to come in and do a whiteboard exercise with us that we would emerge to say that this thing that we were birthing was functional medicine that was. I have to give a lot of homage to, to the Paulings for really creating that. That concept.

Yeah. Wow, that's an amazing history. Thank you for, for sharing that. And it seems that you have followed in his footsteps in many regards, particularly in the sense of all of your multi passionate ambitions. I mean you're a business person obviously a doctor, an author, a speaker and then you're building a network of regenerative farms. Uh, you have a new venture obviously big bold health. Um, and, and I think you know this curious people.

Yeah.

End up if you're on a life path where what you're doing is not just your job. You know, you become carried by your passions and, and yeah, it's fascinating to learn more about him. Like I said, he, he's new on my radar really outside of sort of the more kind of generalities that people know about him so.

Well, let me, let me say something to you because I think you, you just introduced a concept that I believe is so centrally important and you embody that yourself and that's curiosity. You know, my grandchildren, I'm trying to do the best job I can to be the, the grandfather mentor a role now and kind of help open up ideas for them that their parents are wonderful. My sons and daughter in laws are fantastic parents but you know, the grandparents can always do it something else they can add a little bit to the, the mix. So my, my advocacy is always there to try to stimulate curiosity because I think curiosity is the nature of life experience. Once you become un. Uncurious.

Yeah.

I think you start receding as, as an organism. And our brains, I think we're put on the end of our spinal column. I call them a spinal tumor. They're put up there really to allow us the opportunity to, to be curious. And not everybody's going to invent something, not everybody's going to make some magic life changing observation. But everyone can be curious and expand their horizons by sharpening that tool. And you've done a brilliant job in doing that.

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Curiosity is so central to the method of science. You know, yes, science does produce fossil record, or it does produce particular products and goods. But really what science is at its core is a process of continually asking the question why? Continually testing new hypotheses and, and, and not being so sure of yourself that you know the answer.

All of the time.

And, and so, yeah, I'm a, I'm a subscriber to, to curiosity. And, and you know, this is just more of a general point. We'll talk about immunity, but, you know, over the last couple of years, as I've waded into the shallow end of topics that I really don't know anything about, your curiosity can carry you past that place of frustration where now, and we were talking about this a little bit earlier, you know, I will come across a new topic that will immediately seem very confusing to me, and maybe I don't. I'm not fluent with the vocabulary or the taxonomy or the nomenclature, but over time, if you stick with your curiosity, you begin to pick up every other word until you know 80% of the words and then 90% of the words, and then you begin to be able to synthesize the greater concepts. And there's nothing more gratifying in life than continually challenging yourself and pushing your horizons. And I think this speaks to a topic that we'll get to around hope and the science of hope, because I think we've been mired, as you've said, in a climate or an ecosystem of despair and certainly of fear. We can dissect how, both from a hormonal perspective, but also from an energetic perspective, how fear and the perception of despair in our nervous system actually has real physiological downstream implications on our immune system, for example, our digestive system, on and on. But I think potentially for the sake of, of our audience and just developing some core basic scaffolding around the concept of the immune system, let me kind of set it up this way, which is, without a doubt, we have, we're, we're living in an era with cresting efflorescent rates of chronic disease, cancer, heart disease, diabetes, etc. And also autoimmune diseases, psoriasis, rheumatoid arthritis, MS, et cetera. And a lot of these diseases are diagnosed and labeled by the portfolio of symptoms that they represent. And then conventional medicine for, you know, warts and all have generally then worked to manage those particular symptoms. And, and, you know, we see polypharmacology or pharmacology, people, you know, on, on multi, on different drugs. And I think, you know, at this juncture, there's half of the United States that's living with some form of chronic disease. And the last 18 years, I think, of our lives are characterized by multiple chronic diseases. Even though lifespan seems to be teetering, although receding a tiny bit, health span is suffering. Now, I think your inclination is then to Always ask the question, well, what's upstream from that? So you, you know, now a lot of people talk about, well, inflammation is upstream. You know, a lot of these diseases are characterized by chronic inflammation. But I think there's something more subtle and nuanced there where what I hear you talking about is upstream is actually a dysfunctional or imbalanced immune system, which in some cases cause is causal of chronic inflammation. But sometimes it's actually under functioning. So maybe give US A immunity 101 in terms of what is the basic function of the immune system in the human body.

Yeah, so I think you said a lot there. There was a lot of stuff in what you just said. You teed up. Let, let me, let me, if I can. This may seem a little philosophical, broad, but I promise I'll bring it really quickly back to the immune system. So when I started being a professor in medical schools back in the 70s, hard to believe. One of the questions I had asked my medical students back then, because it was around health and disease. What, what are these concepts? And so I was trying to get people to think about the majesty of a lot of being alive. You know, they said, lawn vital. What is it? Because, you know, lawn vital in traditional medical world is kind of frowned upon as a term, this life force concept. And so I, I asked the class, which I've been asking now ever since the early 70s, in all the engagements I've had, what is the probability that we sitting here today, by whatever you want to define your reality, which was, which were made out of atoms that come from stardust. We know that for sure that those atoms that make up those molecules that make those macromolecules that make up those organelles that make up those cells that make up those tissues that make up those organs that make up those organ systems that make up our whole body, what is the probability that they will self assemble from the known matter in the universe? And then the question, of course is, well, what is the density of matter in the known universe? And it's 1 atom per cubic meter. It's less actually than 1 atom per cubic meter. So what's the probability that we exist on a probabilistic, statistical, mechanical perspective that we would undergo such a coalescence process of matter from the universe that it would make us here today against all the forces of nature, which are our entropy to disorganize, not to organize.

Yeah.

Now I want to leave that just for a thought. Now, how does that relate to the immune system? The immune system is the ability of our body to resist all those things that want to tear us apart by whatever process we got to what we are. And there's a whole spiritual psychosocial kind of connotation that is meta scientific across this thing on this question is posed. But let's just go to the science side. How do we preserve the integrity of this organism against the natural tendency of the universe, which is to go to hell in a handbasket? The principal force that does that is our immune system, because it's working 24 7, 365 to sample the outside universe and to tell our body how to operate in response to that particular set of observations or stimuli. And so you say, well, hold up, isn't the nervous system do that? We have to test taste, you know, and all these kind of senses. Wouldn't that sight and hearing? Yes. The nervous system is, is the other 247 connector to the immune system. They're intimately interconnected and they're talking to one another all the time.

Yeah.

And so when we talk about immune system function, every disorder that you listed that are the diseases du jour of our time, which are not communicable diseases, they're sterile diseases. They don't associate themselves directly with viruses or bacteria infection, as contrasted to the turn of the last century, we had a lot more infectious disease, I guess, to put off, obviously SARS, COV2 and HIV. But just talk about heart disease, cancer, diabetes, arthritis, digestive disorders. Those are sterile diseases in the main. And therefore, where did they come from? They come from an imbalanced immune system. Because people say, oh no, those are associated with inflammation. And my answer is, where does inflammation come from? It comes from an imbalanced immune system. The cells that feel unrest are doing what they should do. Your immune system hasn't gone south on you. It perceives the environment in which you're living as to be hostile. And it's doing what it should do. Some people's immune system genetically are more sensitive than others, so they turn on that alarm message more quickly. Now, we call those people in medicine, the people that have immune diseases. We call them flawed. We give them, we imprint them when we talk to them in a waiting room or an exam room of a practitioner's office, you have such and such autoimmune disease. There is more than 80 different definitions. Immediately that person feels they're defective somehow. Their genes were flawed, they didn't get a full life, and they're not as good as somebody without that. No, maybe their genes are actually genetically selected to be more responsive to a suboptimal environment.

Right.

So this whole contextualization we have about the immune system today, that it's just there silently to help protect us against virus and bacteria, It's a flawed, incomplete mechanism. It doesn't actually match up with how important the immune system is, because every disorder and everything we do in our life is intimately translated through our immune system. Exercise, eating, sleep, stress, activities, social engagement, love, rage, all of those tied to the immunological function.

So fascinating. And the little light bulb went off as you were talking that, you know, closed systems are entropic, right?

Yeah.

So the immune system is perhaps the best example of an open system.

And.

That is always in dialogue with its environment. And obviously a lot of it's in the gut. Right. When we can talk about immunity in the gut. But that makes a lot of sense because that's where you're exposing it all the time, all day, everything that you put into your mouth. And so it's in a constant. Like, it's fascinating.

It's constantly upgrading its software.

It's constantly learning, which is just amazing.

And.

And there's. There's obviously numerous components of it. I mean, just on one level, and I don't think a lot of people think about this. The skin is a central part of your innate immune system. Right. It's your largest organ, and it's. And it serves, I suppose, as a barrier function. But there are the skin, there's their immune cells on the skin. Right.

The skin is a lens into the balance and function of your immune system. And if you watch any of the ads that are now appearing that are general pharmaceutical ads, they're all around new skin treatment drugs that are immune suppressant drugs to treat eczema, psoriasis, psoriatic arthritis. These are drugs that are basically designed to block the immune system, which translate its message through specific members of the immune system in the skin. So. Absolutely. And every organization is connected to our immune system. All organs have an immune system.

And this really speaks to systems biology more broadly, that western medicine has tended to look at the various systems that exist within our body as siloed entities. But particularly with the immune system, that's just antiquated project there. Now, the innate immune system, specifically, just by definition of the word innate, is the immune system that essentially we're born with. Is that a correct understanding?

Yeah, people call it the ancient, but now we've learned actually that that's a false understanding. It can be trained. It is trainable. It's interesting. The person who discovered and won a Nobel Prize in Medicine and physiology for this, to discover the innate immune system. Happened to be a Russian physiologist on the south shore of France who had made an observation when he took a starfish from the tidal pools and a sea urchin, and he set the quill of the sea urchin through the starfish's epidermis and then took his monocle, his magnifying glass, and watch. And he saw what he thought were organisms coming to the site where it had penetrated. And he said, well, what are these organisms? You can only see them with magnification. And then he started to study. They weren't organisms, they were macrophages, large parts of the immune system of the animal. And so he then termed this innate immunity. Steve, was a discovery. That person is Eli Metchnikov. Now, why is that important? Because Eli Metchnikov took over the directorship of the Pasteur Institute when Louis Pasteur died. And he wrote a book after he won his Nobel Prize called the Prolongation of Life. And what was that book talking about? The use of enemas with Lactobacillus bulgaricus to improve the microbiome of. To prolong life and to prevent premature aging. It was he that developed the gut connection to the immune system in 1902.

That is fascinating. Well, of course, and it's. We talked about the nervous system and the immune system as interactive systems with the outside world. Of course, the microbiome would be another one. Right. We're constantly repopulating our guts and other orifices and even our skin with. With trillions of bacteria.

Yeah.

And they play a huge role in the regulation of the immune system. You know, I was reading about how. Well, how prebiotic fibers, essentially, prebiotic fiber, feeds your. Your healthy bacteria and produces all of these different short chain fatty acids, one of which is butyrate, which is probably the most celebrated one. Acetate propionate, other ones. But that butyrate itself has a direct relationship with T cell regulate. With T cell reg cells essentially in the epithelium of your gut. And, you know, it's just like, my God, this is. If there. If we ever need proof that food is medicine. Oh, my God, it's right there. If we take care of these bacteria in our guts, they will actually do specific. Engage in specific mechanisms to upgrade our immune system, which is fascinating.

So let's do a freeze frame right there for a second. Jeff, what you said, that that is like exclamation three times and underline bold.

Okay.

That. That is so important. I want to make sure, we, we don't lose an ounce of the importance of what you just said, because it begs a question, right? If we keep saying, let's go upstream to find out what's going on, how is it then that feeding a prebiotic fiber would then as a food for one of the hundreds of different types of organisms or several different types of organisms in our gut, microbiome can then feed those bacteria in such a way that they will produce a secondary product from their function, their metabolism, like butyrate, and that butyrate as a molecule. And I can say from my work in early cancer therapy that I did back in the 60s, butyrate was always used in cell culture work with cancer cells to influence growth and arrest growth of cancer cells. So this molecule has a unique property. It's not the only one, but one that we studied a lot in basic science. So then it begs the question, well, how can such a simple molecule, just a 4 carbon fatty acid acid, how can it have such an effect? Because it's been found it's involved in this signaling process that it signals. And what does that mean? It means that it connects to a receptor site somewhere on the surface of a immune cell that gives it instructions. And it says through a transaction transduction process, like a wire with electricity running down it, that wire happens to run to the nucleus of those immune cells that then signal to the immune cells through transcription factors to say to the immune cell genome. You know, it's time for you to do something different. You need to now become more robust. You need to have a different personality. That personality is in you. But now I'm uncovering it by allowing those genes to be expressed. Now, that concept of expression and signaling is the basis of what upstream functionality is all about. Go to the upstream that signals downstream. What we find is that many of these central molecules, beta rate, is 1. It doesn't just have a random signaling process very specific to specific receptors on specific types of cells. Those cells that it influences generally happen to be upstream regulators of downstream several other genes. So you're talking about families of genes that are controlled by a regular regulatory function, that it's not just one gene at a time. Our body doesn't work one gene at a time. It works as clusters of genes that are expressed to form a new function of that cell. In this case, a more active immune cell, a T reg cell that then communicates to other immune cells to say, let's get our act together, guys. We have a problem here that we need to be aware of.

That's right. Or cell slow down, don't overreact, regulate. Yeah.

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Immune cells are largely leukocytes, right? They're largely white blood cells, blood cells that are produced in the bone marrow by stem cells. Is that a fair understanding?

Yeah, absolutely.

And as part of our innate immune system, there are a number of different kinds of immune cells. I think macrophages and monocytes are one of them. Neutrophils. There's these NK killer cells, dendritic cells. Dendritic cells. How does, how do these cells within our innate immune system sense and then neutralize invasive caustic pathogens? How does that process work?

So I'll try to make this simple because it is, it's fairly complex process. But to make it probably more simple than it should be, we have on the surface of our immune cells and you've already introduced the concept that in our gut we have a lot of our immune system, about 60% our immune system is clustered there. So those cells that make up what are called the mucosal immune System sometimes abbreviate the GAL to the gastrointestinal associated immune lymphoid tissue. Those cells are kind of waiting for a message to tell them what to do. Like us engineer to come in and give them instructions. And so the instructions can come through the activation of these receptor sites. The family of receptor sites that are most involved with the initiation of these processes are what are called pattern recognition receptors. These receptors are multiple family members. In fact they're well over 100 that are members of what are called the GPCR family. But the ones that we're going to focus on right here for the innate immune systems are called toll like receptors because it's like a toll gate. And so the toll gate, someone arrives at the gate and you give it a ticket and then the gate will open. And these, these toll like receptors are evolutionarily built to receive the message from the gut. That may be a message considered offensive.

Yeah.

Now what we've learned over time to make this a little bit more complicated is they probably were evolved just to see the natural things of the bugs that were in our gut that were producing bad things like bacterial cell wall debris from gram negative bacteria called lipopolysaccharides.

Right.

That's what the chemist would call those alarm substances that turn on a toll like receptor. But then we found, we started to expose people to thousands of new chemicals, some of which had mimic, they were mimicking the processes of these natural things that the body was responding to to defend us. So now we turn on excessively these processes, which by the way are processes that downstream through that signaling do what? They create inflammation.

Yeah.

So now we're in an inflammatory state.

Got it. So let me see if I can understand that properly. So for example, like in the gut, when we're, when the gut is disbalanced or in dysbiosis and you get to a place where you have intestinal permeability, where the tight junctions in the epithelial start to break down and you have endotoxins or LPSs that pass through the gut lining and into the bloodstream. The immune system all of a sudden says wait a minute, hold on, we don't recognize that. That seems like that's, that's non self. And we're about, we now we need to trigger an inflammatory response. And so they send at that juncture white blood cells, etc. Which would be fine if that was just a, you know, a finite moment in time. But now with, you know, the chronic over prescription of antibiotics or PPIs or NSAIDs or high sugar diets, or processed food diets, essentially glyphosate toxins, anything that essentially can degrade the integrity of the, of the gut, epithelial or epithelium is, is then leading to this chronic inflammation. Is that a fair depiction?

So well said. You know, it's interesting, one of my former colleagues that attended my seminars back in the 80s when I started doing doctor seminars, he sent me just recently a copy of the 1985 syllabus that I used for that seminar, which is called Got into a Toximian leaky gut syndrome. 1985, 1985, 1985.

Come on. No, there was nobody talking about that.

Well, there was, there were a few of us. And, and what happened was that as you can imagine, there were many, many criticisms of me personally, that I was making this all up or this was fantasy or there was no such thing. And I talked, even it was probably a little later, probably like 1989, I started talking about what's called postprandial endotoxemia, meaning after you eat, it induces this release into your bloodstream if you eat the wrong things.

Right.

And then I had people who are internists and pathologists really criticize me, saying, oh, hold it just a minute. If you have toxin toxic substances in your blood, endotoxemia, that's a hospital based situation, those people are critically ill and people die because of that. You're not seeing people just keel over from eating a bad meal. And I said, no, no, this is not acute endotoxia, this is chronic. Oh no, there's not such thing as chronic endotoxemia. I said there is such a thing. Well now literally hundreds of papers have been published in the top level peer reviewed literature and everybody knows there's such thing. And you can actually, by personal life experience, test it yourself, go out and have a whole pizza yourself and drink three beers and then have a big dessert with lots of frosting on it and see how your gut lining responds the next morning. And I'm telling you, you'll be in metabolic toxemia. You won't know exactly what the bio, the biological or anatomical cause, but you'll have a headache, you'll feel like you got the flu. That's endotoxic response to one meal. One meal can do that.

Yeah. Well, and of course conventional Western medicine is, is designed to deal with matters that are acute and it's very good at that generally.

Yeah.

But I think what we're talking about are conditions that are progressive, that can take hold and over decades before they become problematic or symptomatic.

That's right.

With a lot of these chronic diseases, heart disease doesn't just appear overnight. It's, it's progressive over time. So a little bit of what we're pointing to is autoimmunity here, which is essentially the body or the immune system miscalculating what is self and non self. So obviously the immune system is very good at, at identifying foreign pathogens, but from time to time, like LPSs, but also in other cases, the immune system seems to misrecognize the self and confuse it with something foreign. Why is that happening?

Well, again, I'm going to probably stir the pot. In 1999, I did a seminar series for doctors. I, I think I visited 30 cities in which I presented a concept that has a therapeutic outcome from it. It's not just theoretic, which really challenged the whole concept of autoimmunity. And it challenged the traditional rheumatological view of autoimmune diseases, of which there's over 80 different diagnoses. They certainly do exist. This is why I wrote the book the Disease Delusion. We know that there are diseases, but the delusion is to think that we know where they came from. And so why I think that we've been missed. Miss the boat. And what we're starting to learn is exactly what you were bringing up. The immune system doesn't suddenly wake up one day and say to the body, I don't like you anymore. You're not my friend, and therefore you're a hostile being relative to my presence in your body. That doesn't happen. And to even go farther than that, a lot of people say, well, it's in my genes because there are members of my family that have autoimmune disease. There is no strong linkage genetically of any single gene to any single autoimmune disease. Now, I'm not saying genes are unimportant. I'm just saying they're not the determinant. They are part of the story. So what is the story? I use one example that I think people today can understand because it's in the news as we see it on advertisements. And that's A1C. Okay, so what is A1C? A1C is we, as it a measurement of how well controlled your blood sugar is for diabetes. Right now all the drug companies saying we have the best A1C modulator. And now the people with CGM continuous glucose monitoring equipment are saying, we can help you lower your A1Cs by controlling what you eat and looking at your, your glucose levels. Because high glucose levels, even excursencies of glucose, causes your blood to have a high A1C. Now it begs the question why. Okay, here's a quick biochemistry lesson. Hang with me, please. All I mean, so what happens is when your glucose, your blood sugar is high, you have all these proteins floating around in your blood, in the red blood cells. The principal protein inside your red blood cells are, is hemoglobin, right? So when sugar gets inside your red blood cell at very high levels because you're not controlling your sugar, well, because of the way you're eating and living, that sugar doesn't have any way to be metabolized. So what does it do? It chemically reacts with the protein.

Right.

Now the example of this, the analogy I try to use is, has anyone ever baked bread? If you bake bread, you know that when you put the dough into the oven, it's all homogeneous, it all looks the same, it would taste the same. If you eat the dough before it's cooked and you put it in there and you bake it, when you take it out, does it all look the same? Of course it doesn't. You have a crust. Now what is the crust? The crust is the heat activated, a process of the reaction chemically of sugar glucose in the starch of the bread with the protein in the bread to form this new compound that forms crust on bread, A1C is crusty blood. A1C is crusty blood. It's just like cooking dough in your oven of your body. Now let me finish, let me finish here because this is kind of follow my logic. So when you then form that new form of hemoglobin where sugar is reacted chemically with it and it's never going to be the same, is it the hemoglobin that your body's immune system is familiar with? No, it's a foreigner. Now, here is the payoff from the story. If you've hung with me to this point, which I know you have, then you say, well, what about the immune system? Because we know that people that have uncontrolled diabetes have a lot of immune problems and they get more autoimmune diseases. Is it just by circumstance? Well, it turns out that those proteins that reacted with sugar, like glycohemoglobin to form A1C, the immune system recognizes them at what are called receptors of the dance. Glycosylated end products. Receptors are advanced. A glycosylated G in products E put that One together rages, your body becomes enraged. Yeah, you're now a foreigner. You're a foreigner aboard. Now. Is it just only sugar that does that? No, you can oxidize. In fact, hemoglobin is not the biggest culprit. The biggest culprit is albumin, which is the major blood protein. You have much more albumin in your blood than you do hemoglobin. It turns out we've been studying glycosylated albumin, my group, for over 25 years. You can better track aging by following glycosylated albumin than following a 1C, because it is much more indicative of this process of producing enraged immune system because you've made foreigners out of your native proteins. Now, that's not the only way this occurs. It can also occur by oxidation. So if you were to be out in the sun too long, you get a sunburn. That erythema that comes with the sunburn is in part because you've oxidatively damaged proteins. It makes your immune system see those as foreigners. And now they start reacting and you get swelling and you get infiltration of white blood cells. So all of this model I'm talking about is tied together with making you into. Not you. Now, bad diets, bad lifestyles, toxic thoughts, events of dysbiosis, all are engaged in a process of producing from you, not you.

Okay, that is fascinating. So that really helped untangle a number of things for me, particularly the relationship between, between metabolic dysfunction and the immune system, because I can understand how, you know, a high glucose diet will. Could eventually lead to insulin resistance, for example, so the cells stop receiving insulin. So you're now your blood sugar concentrations are going up. Well, where's that sugar going to go?

Yeah.

Okay. Some of it maybe to the liver with glycogen for a rainy day. Some of it gets stored as adipose tissue or triglycerides. But then what you're talking about is the formation of these glycoproteins or advanced glycation end products, which are inflammatory, I believe, in and of themselves. But what they're really doing is having an interaction with the immune system.

Yes.

That is very deleterious to, well, certainly to vascular health, for example. Right. Because, you know, there's. The source of cardiovascular disease is not just, you know, LDL sitting in the arterial walls. It's if you're going upstream from that, it's actually inflammation of the vascular system.

And how does, how does inflammation happen? Inflammation always comes back every time to immune imbalance. And let's talk about heart disease. Yeah. Because the cholesterol hypothesis, which is, you know, still being debated, I believe there's a reality to it. Cholesterol, when it becomes oxidatively injured within an LDL particle, it is in your interior cell wall of your artery. And as a consequence, when a macrophage translocates from the bloodstream to seek out foreigners that are in the vessel wall, it will find that funny. Non, non, you right. And what it does is it reacts. So now you get foam cells, right? And foam cells then produce all sorts of mischief and they produce plaque. And now you have heart disease. Heart disease, inflammation, cholesterol, it's all tied back to this inflammatory imbalance associated with immune system.

So good. This. See the, the reason why it's so under, so important to understand these mechanisms is that once you understand the mechanisms, the protocols become so much more obvious because you actually understand.

So let's take that one step farther. So is there any outcome other than intellectual kind of fodder for what I've said? So let's ask the question, how do statins work?

Yeah.

So all these years we've said, oh, the statins were selected for mold metabolites that are HMG CoA reductase inhibitors. They inhibit in the liver the manufacture of cholesterol, so they will lower your cholesterol. And that's the benefit of statins. Now I'm not saying that that is not present at all or not important, but later we found actually that the cholesterol lowering effects of different statins doesn't directly track with their ability to reduce the incidence of heart disease. That there are some statins who don't necessarily lower cholesterol as effective as others, but they seem to be better in lowering the incidence of heart disease. What are those statins? Those are ones that have the highest anti inflammatory effects because they influence the immune system. So statin therapy is actually an inflammatory therapeutic. It's not a cholesterol lowering drug by itself.

Wow.

And so when we really dig into. So then you say, well, gee whiz, if that's true, then could I get the same effect without taking a statin by reducing the inflammatory potential of my immune system through lowering the upstream factors that cause that downstream dysregulation that is the whole basis of our big bold health concept, because we're trying to get people to understand what is big and bold is our immune system that's waiting for us to treat it. Right.

So good. Okay, let's talk a little bit about the adaptive immune system because we Talked about barrier immunity, we talked a little bit about, quite a bit about innate immunity. Now let's talk about acquired immunity. T cells, B cells, et cetera. Can you opine on the adaptive immune system?

Yeah, you've already teed this up beautifully because you start off saying, well, isn't the origin of all these immune cells, no matter what their archetype, is later coming out of the hemopoietic stem cells in the bone marrow, these primordial cells that ultimately travel out of the bone marrow and into the bloodstream. Now where do they travel from? Well, they travel a lot of places, but one of their first stops that's important is the thymus gland. Right, right. And that thymus gland has the responsibility to instruct those cells that are not yet got their personality, what they're going to become. Now the thymus gland is a really important gland related to aging in animals. And we know that in humans, people that lose a lot of the thymus gland function early on have a lot of immune problems. We also know that the thymus gland and its activity is connected to a hormone that's produced in the brain through the pineal gland called melatonin. So the brain is connected and the melatonin and the pineal is connected to sleep and light, dark cycles. You see where I'm going with this? This is the functional medicine model. We keep going upstream saying, hold it. If you have a sleep disturbance, could it be because you have a deranged immune system? That's what we found so far in our work, that you get the immune system right and you wear an hour when your sleep cycling starts, or whatever use you might use for measuring sleep quality and duration. So the immune system is tied to our sleep cycles through our pineal gland, which then connects in through melatonin to our immune acquired immune cell function. So that's one feature. We also know that that particular thymus gland function is really dependent on something, an enzyme called thymosin. Thymosin is really dependent upon adequacy of zinc. So now we say, oh, could this explain why people that have zinc deficiencies because they've eaten a highly purified ultra processed diet end up with immunological problems. Yes, that's another. We can start signaling every nutrient. We can talk about vitamin D, we can talk about essential fatty acids. All of these are signaling molecules that help to orchestrate how those cells that come out of the primordial bone marrow are going to be recruited into being functioning components of our adaptive and acquired.

Immune system, specifically with the thymus gland, as I understand it, it's almost pre programmed to degrade or disappear over time. Is that an indication that our immune system essentially just is meant to degrade over time? Given the fact that these T cells mature, I suppose in the thymus, but then I don't know, by the time you're an adolescent, is it still around?

Oh, we're having fun here. I am so excited that Jeff, you bring this up because the word degrade is a value centered word. Okay, yeah, so let's think about that just for a minute. Let's, let's turn that word around for a second. So when we're young, say an infant, and we're trying to develop an immune system, we have a completely blank slate. And so we know we don't want to expose an infant to too many foreign molecules because we, they don't know how to manage that yet. But they're going to learn because their immune system has a great learning capability. And so their thymus gland is really a big schoolhouse. And so it can pick up lots of information and start instructing the immune system how it's going to fashion itself for the environment that that child is going to grow up in. Now as we grow older, we've got a lot of instructions in place and so we don't need that capacity to do all that. In fact, maybe that capacity gives us an overreaction potential. We want to attenuate that, that it's a little bit like hormones. Do you want the same growth hormone levels in your blood as a 60 year old man that you had when you were 15? Heavens no. You don't. You might think that, that you're going to get big muscles and be vital. But the data says with growth hormone supplementation in older age, individuals who produces levels that are comparable to say 15 year olds, what happens is they have increased blood sugar problems, they have increased fatty liver and they may even have increased risk of cancer. So our body has a natural instruction as to how to regulate, not degrade, but regulate. Now there's a certain point where if that function has been compromised, now suddenly you start to get a regression of function. So that is the process of immunosenescence that the immune system then, because it didn't get what it needed to be functioning. But I can tell you, having studied now enough people across different ages that there are people in their 70s and 80s who have immune system functioning that's functioning like a 30 year old. But then there are people 30 that have immune systems functioning like a 70 or 80 year old. So it's, it's, it's not directly tied to your name, your age and birthdays. It's, it's related, but it's not directly tied. What it's tied to are the processes that relate to how your immune system can rejuvenate itself. And that process is present in our body's capability if we give it the right opportunity to do so.

Okay, before we go into rejuvenation, what are the contributing components to senescence? How does that actually happen? Now obviously they're environmental toxins and diet stress, some of the things that we've talked about. But in terms of what is happening at the stem cell level and the creation of new white blood cells that might not be quite as attuned as the last round.

Yes.

Can you pick that apart for me?

Yeah. That's so. Wow, this is so much fun. I'm just really enjoying this. Thank you. I hope other people enjoying this. So it turns out that there's two processes that have been identified that are associated with that immune senescence, that aging of our immune system. Process one is directly related to what you're referring to in the bone marrow itself, that the cells that are coming out of the bone marrow are already injured and they're injured by a mutation. And it has a long name associated with it that is abbreviated chip. Chip. So I like chips because it sounds like something is in the gears. Right? Well, the word chip or the abbreviation chip has a medical name in it's clonal hematopoiesis of indeterminate potential long term. So we're not going to ask people to remember that. But what it means is that there has been injuries that the stem cells in the bone marrow have been subjected to that pick up this injury and lock it into its memory. And so when they come out of the bone marrow, they are going to reproduce that injury in other cells of their lineage. That's called clonal. They, and they survive for a long time. They live with us as clinker cells. And the problem with those mutations, those mutations occur in regions of the, of the genes of the immune cell that regulate inflammation, so called Tet2 and DMT3. Those specific genes regulate then some aspects of the cascade of inflammation. So those, those cells, those chip cells are now in a lifelong inflammatory state state. So they raise the body's residual inflammation, even if it's not out there seeking foreigners or anything. It's just in a state of hyperarousal. That's number one.

Right. But the good news that we do continually make a lot of new, a lot of new white blood cells.

Right, right.

So there is that opportunity to potentially reverse that.

Okay, now you're the science of hope. Okay, here we go.

I know you want to get into the epigenetic side of it, so no.

Let'S, let's talk about, about how this works. This is so powerful. So this, for me, this is so much fun. So, so years ago I, I read the New England Journal of Medicine, this paper that blew me away from Harvard. A Mass General Hospital lead author was Siddhartha Mukherjee. Excuse me, wasn't Siddhartha Gswal another, another Siddhartha?

Yeah.

And he and his colleagues had been studying people who have these chip cells and there are tests that you can do, research tests to evaluate the number of these cells have been locked into that state. And a surprise was that he found that the people that have increasing levels of these are people that not only have higher incidence of bloodborne cancers like leukemic cancers or what are called dysplasias that are associated with cancer, but he also found, and this was an aha. No one at first believed it in the field of hematology that it was associated with the increased risk to heart disease. Because it turns out that those immune cells that are deranged, they're not just solely working in the bloodstream, they're going into tissues as we talked about earlier, and they're causing mischief in inflammation in the vascular walls. So it's associated with, with athletes, chlorotic disease.

Right.

When I read this, I thought, oh my word. Now this is a whole new mechanism that connects the immune system to these various diseases, not just cancer. I bet you we're going to find that this is connected to dementia. I bet we're going to find this is connected to diabetes. I bet we're going to connect it this with further work to arthritis. And I've been right now we're getting sequentially increasing levels across other medical disciplines saying, oh, by the way, we found chip cells in patients with this disease too. Wow. Now here is the important thing. This is, this is why I'm excited about this. One of many things, because I'm always looking for ways how do we get out of this box. Because it always seems like this is one way street to damage and woe is us if we have that bad misfortune. But I always know the body for everything it does. One way has a way to go the other way. It's a two way street. I always thought there's a two way street I'm sure for chip cells. After Dr. Giswold gave his presentation at one of our meetings at personalized Lifestyle Medicine Institute meeting, I invited him to be a speaker. I went up to him and I said, your work is fascinating. This was probably six or seven years ago. I said, what impact do you think intervention with various tailored lifestyle diet intervention trials would have on chip cells? And he said, oh, geez, you know, I never really thought of that. We're thinking about drugs that we could find that would expunge chip cells. And I said, well, I'm sure that that's a favorable scientific endeavor to find a molecule that might do that, but I'm wondering if those molecules exist in the natural panoply of things that we do.

Sure.

And he said, well, gee, I have to give that more thought. Well, in the intervening time, he was headhunted by Stanford, and he moved his whole group to Stanford. And now he's collaborating with the old group at Mass General with Women's Health. And they just finished a very large clinical trial on postmenopausal women who collect chip cells. It's one of the connections to heart disease and postmenopausal women who, as you know, have the same incidence of heart disease in 60 as men. What they found was that by intervening in postmenopausal women who are high body mass, who are overweight, and I can connect the adipocyte tissue into this in a moment. That by intervening with lifestyle therapy, that they were able to reduce chip cells and reduce inflammation. Now, they haven't gone long enough to know if they're going to have a lowered incidence outcome of heart disease, but I will predict they will.

And so I want to try to continue to, like, disentangle some of these things. So let's say you have a good amount of like, visceral or organ fat.

Yes, that's the one we're talking about.

Okay.

And.

And those cells are communicating.

Yes.

To immune cells. Right. And I mean, from what I know about adipose tissue, it is. It is inflammatory in and of itself. It. It. You know, I think it releases some form IL6 or some one. One of these compounds.

You got it. That's right. It's one of the Adipokines, IL6.

But how are. How is excess adipose tissue communicating to the immune system? And what is the. What is the impact downstream?

Okay. For more than 30 years, I've been saying something that has not been held in high favor by some, that our whole approach towards obesity is misguided. The primacy of the calorie, I believe, has caused us to neglect the fact that we're not a calorimeter. We don't burn our food like in a fire. We metabolize our food with very, very controlled processes that is regulated by many, many different compounds in our body, hormones and things. What I've been saying for decades is that once we look very intently at all these weight loss trials that have been done saying that calorie restriction causes reduction in fat and improves health outcomes, what we will find that it is not the restriction of calories, it is the restriction of agents that activate the inflammatory potential of our immune cells that are embedded within our fat cells, our fat mass. Now, I think that there's two kinds of fat. Well, there are two kinds of fat, but I mean, phenomenologically, two types. There's happy fat and there's angry fat. Santa Claus, as a metaphor, has happy fats. And Santa Claus lives forever. He doesn't get heart disease, he doesn't get cancer, he doesn't get hypertension, he doesn't have a stroke. He has happy fat smiles and it laughs all the time. But that's not the kind of fat viscerally that most people in the Western world now have. They have angry fat. And why is it angry? It's angry because the immune system that's embedded within that fat mass, called the adipocyte, is constantly being told a message that he needs to be on guard. And it's activating in that endocrine organ, which is our fat mass. It's the largest endocrine organ in an obese person, is their fat mass. And it produces a consequence of it being alarmed by the immune system, its own alarm agents that are called adipokines, one of which you just mentioned, IL6, which travels in the bloodstream, and it says to the rest of the body, I'm fed up and I'm not going to take it anymore. That's my metaphor. I'm fed up and I'm not going to take it. And I'm fighting back. I'm telling you brain, I'm telling you heart, I'm telling you, liver that I'm not going to suck it up anymore and eat all this fat. And if you don't do something about this, I'm going to kill you. That's what causes the problem. Yeah, it's not the fat in and of itself. And in fact, well, you would say to me, well, Jeff, just a minute. Can you give me any citations from the approved medical literature that Says that people have high BMIs, high body mass index that are central obesity are people that don't get chronic disease. And yes, there's a whole literature around apparently healthy obese individuals that do not have metabolic dysfunction. And when you examine their fat mass, you find their immune system is in concert and pleasant and peaceful with their fat cells. If I take lean people that have low BMIs, but I look at their fat and I connect it into their inflammatory CRP levels, I'll find that even in low BMI people, they have angry fat that is producing a problem. So it's not just strictly fat in of itself, it's the personality of the fat and the message it's getting from the immune system. And where is that coming from? I say it starts in the gut. And it was Hippocrates that said all disease starts in the gut, right?

That's right.

So we're starting to go full circle to relearn through this, this advancing science what has been known for decades.

Yeah, Let me ask you a little bit about kind of the epigenetic dimensions of this. So I know that we talked about chip cells and, and how new white blood cells might not be functioning as well as the last generation. Are there environmental inputs that methylate DNA or gene expression such that the production of immune cells is not functioning optimally?

Yes. This is, I think, I believe in my experience of the last 40 plus years in this field is the central major paradigm shift. It is so beautiful and it is so elegant and it reminds us once again of how magic the process of life is as we piece apart this watch, this clockwork that controls our function. What has been discovered now is that there are specific nutrients that are in our foods. Nutrients that we have considered for the last 70 or 80 years as being unimportant. We take them out of foods to make them processed. Those are called phytochemicals, these plant derived substances. The reason we take them out is because they have color and they have flavor that we don't want, because we want sweet and salt and fat. So we don't want all these flavored compounds, so we take them out. Those compounds which occupy in textbooks of nutrition scientists or nutritionists that are trained dietitians constitutes a few pages in that textbook. We are now being discovered as the regulators of how our immune system and other cells actually express their function. They are signaling agents, not just antioxidants, not just coloring agents, not just flavorants. Let's talk about the flavor, taste perception. Bitter, right? So a lot of people have aversion to bitter. But it's interesting to note that children generally don't like bitter. But as people grow or they like coffee and they like red wine and they like bitter things. They like dark chocolate.

Yeah.

And why is that? Evolutionarily, I believe that it's because bitter substances from our food stimulate receptors in our intestinal tract that activate the release into our blood of glucose normalizing hormones called GLP1 and GAP. And the, the, this family of hormone, they're called the intra endocrine hormones, are produced by stimulation by specific bitter compounds in our foods. Mostly from vegetables, obviously broccoli, Brussels sprouts, cabbage, that family, even berries that have an astringent effect. Hops in hoppy beer. We studied all of these compounds and they have a unique receptor in the small intestine that's called the L cell. When they bind to that L cell, as they travel through the gut contents, they stimulate the production of the release in those cells of these hormones that regulate blood sugar, inflammation and immune function. So diet. And by the way, just to take this a step farther, if you follow any of the advertisements now from the pharmaceutical industry, there are all these ads talking about treating your A1C with this new family of drugs that normalizes your blood sugar by making your body's more sensitive to insulin. And it's your natural way that your body does that. Well, that substance that they're offering pharmaceutically is GLP1. It is the same thing that is produced naturally by your body when you eat these bitter foods like Himalayan tertiary buckwheat, which we're studying. And as a consequence, what you. And now we're seeing. Well, hold on just a minute. Isn't it true that these same drug companies that used to be saying that these drugs are useful for treatment of diabetes are now saying they're useful for weight loss and now the FDA has rebranded them as weight loss drugs as well. Why is that? Because for the reason I already mentioned that once you make your fat cells friendly and they're no longer angry fat, you will start losing weight because part of your obesity problem is connected to your inflammation potential of your body. And so what we are learning through pharmaceutical research is what nature has been trying to tell us from its wisdom through the way we live a healthy life.

And is this like metformin and berberine and stuff like that, or is it these other drugs that now are getting used for. For other.

Yeah, not metformin. It works. Actually, Metformin, which is the principal drug, first line of therapeutic for type 2 diabetes that is turning out to be likely to be affecting the gut microbiome, is that right? And it's actually influencing the microbiome in such a way as if bacteria then connect to your gut immune system to lower inflammation and improve insulin sensitivity.

So there's a lot of.

And by the way, where did metformin come from? Metformin came from French lilac.

Is that right?

This is an herbal medicine that was made into a pharmaceutical compound by derivatizing that compound that was in goats root Prince lilac that was used historically in herbal medicine for the treatment of what we now call diabetes and it works by this mechanism.

Is there a method akin to the Horvath clock for example, or some epigenetic clock that one can leverage to measure the bio age of one's immune system?

Yes, this is the frontier of immunological genomics. We're just finishing up a clinical trial actually I think we've now got everybody completed. This was a Clinical.gov approved registered trial of looking at the impact of a high polyphenol rich supplement to see if it would imprint the human immune system in such a way as to regulate its gene expression and reduce inflammation. It's the first trial I've ever seen that will then measure immune age before and after intervention. The way we do that is using a very complex AI algorithm that's been developed by several medical research institutes that are like Harvard and Emory and Mayo. We're using their algorithm, we will be able to decipher that data somewhere in October. And we're keeping our fingers crossed that we're going to find something very interesting because it would be the first trial ever with a natural food derived material that shows we could turn back the biological age clock of our immune system. But I do have to tell you, and I know this is probably end of one anecdotal, but I'm going to say it anyway because I have the fortune of working in this area for so long and I'm a biohacker and I've been studying things on myself for years. I decided that I would try our own program, our so called Immunity plus program to see what would happen when I use this algorithm on myself. So I took my blood to see what my immune age using this algorithm was before I completely committed to our program. And I was, I was 76 years age at the time and my immune age came out to be 67. I thought wow, okay, I'm feeling pretty good about that. That's, I'm younger in my immunage and my age and birthdays. I then rigorously went on our program, which is this complex program of fish oils, prebiotics, Himalayan tertiary buckwheat, exercise, sleep, stress management, regular activity, blah, blah, blah, in this, in this three month program. And then I retested using the same test. My immune age was 53. Wow. Yeah. I cut 14 years off my immune age in three months. So I know it's N of 1, so please don't over generalize.

It speaks to agency, patient empowerment.

Yes.

You know, individual responsibility, individual agency, etc. That you can see that kind of impact over really that short of a period of time. It's incredible.

So we hope to see the same thing with our 50 people that went through the program. We'll find out. Now I have to say that I'm a little bit weighted because I have a bigger, what I would call, I guess, window because of being 76. If you're 30, you're not going to reduce your age by 30 years. But.

So a lot of people are now engaging in what is known as adversity memetics or hormesis, for example, where you engage in some kind of activity that induces short term stress, short term beneficial stress, or you stress. So there's like cold hydrotherapy, for example, or I'm intermittent faster. So I do the 168 protocol where I consolidate my consumption of food into an eight hour window. And I do as well. Yeah. And one of the byproduct, there are many byproducts of this. We can talk about intermittent fasting, but. But one of them is that it stimulates a particular cellular pathway called ampk, which is associated with cell cleanup or this process called autophagy. Now I'm curious if autophagy is applicable to immune cells or if there is a mechanism like autophagy that is that serves the purpose of breaking down senescent or dysfunctional immune cells or proteins into their component amino acid parts that can then be recycled on a rainy day.

Yeah.

Is there that process?

Yeah, I think you hit it. That's one of the two ways I believe that the immune system can be rejuvenated is through this selected immune autophagy, mitophagy process. When I said mitophagy, what I'm talking about is kind of reconstruction of the energy powerhouse of immune cells, which are the mitochondria. Right. And, and these. The one thing we've learned by my deeper drilling into the polyphenols that are in Himalayan tertiary buckwheat is that they do have the Impact on enhancing selected mitophagy within immune cells. And so it's, it's selective cleansing. And you probably heard, I know you've heard of zombie cells. Yeah, just the word alone sound like, ooh, I don't want a lot of zombie cells floating around.

Probably maybe on Halloween.

Exactly. So this process that we're talking about that's associated with senescence, associated secretory phenotypes. Right. Where the cells are secreting inflammatory substances, keeping you in a constant state of what's called inflammaging. Those are resurrected by these polyphenols that are found in Himalayan tertiary buckwheat. It's one of those nutrient families that has the ability of supporting this process of cellular rejuvenation.

Yeah. So I bring up hormesis because hormesis doesn't only apply to humans.

No.

There is a concept known as xenoharmesis.

Yes.

Where that is leveraged by plants in response to stress.

Yes.

So let's just think about the Himalayas for a moment. Have you ever been there? It's a pretty harsh environment in which to grow. Right. The soil can't be particularly arable. It's very rocky, it's a lot of exposure to sun, it's very windy, probably water is very irregular. So what is the impact of that kind of environment on a plant?

Yeah, that's a really, really great question. So by a whole series of coincidence that I won't bore you with, I got introduced to this Himalayan tartary. The reason it started, it's a tartan region of, of China. And there's, there's really two varieties of Himalayan tartary buckwheat. One is the northern region, the other is southern region. The northern region has the highest level of these immune active phytochemicals. And that's the region that's most hostile in terms of the environment, the place you less likely expect the plant to grow. But it has been a major food stock for people living in that region for 2500 years. So this is a long standing food. And you say, well, how did it survive? Well, by the luck of genetic selection, it found the right combination of genes to produce the defensive substances that were necessary for it to live in bad soil. As you said, bad climate, sunburn, cold frost, bad water. And in fact it even has I found recently. And it's because it's a genome has been sequenced, it has a series of genes that are involved with aluminum detoxification. So even in bad soils that could toxic kill most plants, it can live of it has the ability, 30% of its genome is occupied by genes that produce these secondary metabolites for its immunity, these polyphenols. So it's like a little biochemical factory producing defensive substance to allow it to survive in this very hostile environment. The remarkable thing obviously for us in terms of looking at this as a planetary interconnection process is that people who eat that are in the blue zone, they're people without a lot of modern medicine. They work hard, live at very high altitude, and they are pretty darn healthy. So this is one of those examples of, of what they're eating gives them strength in their environment to be vital. Now what, when we say strength, what does that really mean? I think it can be in many levels. You can call muscular strength, you could call it, or cardiac strength. But I believe the principal thing that we would say is that if the immune system is balanced and you have a lot of immune reserve, a lot of these other organs will follow. If we're really trying to find upstream effects. And we now recognize that this particular plant food that is a principal part of their diet for all these many now thousands of years, has 50 to 100 times the level, not a percent times the level of these immune active phytochemicals that help to defend the plant against bugs, against frost, against mold, against bad weather, all these, these things, even poor quality soils.

So I think what you're saying, which is just kind of mind blowing honestly, is that the benefit of these adaptive protective measures in the plants is being transformed, preferred to human beings.

Yes.

When they consume it. Which is just.

Can I go with you one step before that?

Yeah.

This is my newest learning. So I, I owe a number of people for this, this. Aha. I've really been trying to understand it more. We have to go into the soil and say, okay, what's going on in the soil?

Yeah.

And so now we ask, even in these poor quality soils, what's the mycorrhizal look like of the soil if it's not been ag farmed and high tech farmed? Even if the soil is very rocky and it's very thin, are there living things in that soil that somehow can speak to the germinating seed to create a vital plant that has these high level of these phytochemicals? Now that is the central activity of research in Asia in plant agronomy. This last two years, over 50 papers have been published talking about soil micro rises effect upon the tartary buckwheat specifically's ability to produce these immune strengthening Phytochemicals. Now, last, let me close. I got so excited about this. I said to, to our group, I said, you know, we have these, these organic farmers in this cooperative we put together to grow this stuff for us. The first time in America for 200 years. How about if we do a field trial? So we got a plant scientist, Emily Reese, a PhD plant scientist from Cornell educated, and she is, she calls her the soil tender. She loves the soil. And so we set up test plots and we then inoculated seeds before we planted last season. In the 2021 season, we inoculated the seeds with different mycorrhizae and different soil inoculants to see if in fact the stuff that went into the ground that was going to nourish the microbiome of the soil would influence then the outcome of the phytochemicals in the plant. And much to our surprise and pleasure, we showed a very significant trend towards enhancing phytochemical activities in the plant. The way we treated the soil by inoculating it at the seed level with these friendly soil critters. So what we're saying is the microbiome of our soil connects to the microbiome of our person who eats that food that's transmitted through the whole system.

Right. And to juxtapose that against the modern industrial conventional farming that essentially uses antibiotics. I mean, glyphosate is essentially an antibiotic that is a chelator. So it essentially denudes the plant of essential micronutrients and also blocks what is known as the shikimate pathway that develops these essential amino acids which we do not create endogenously, that we have to get exogenously through diet. So when you're eating plants that are now denuded of amino acids like tryptophan or tyrosine or et cetera. Well, and then you start to, you know, well, what is tryptophan synthesize into? Well, serotonin. Well now, of course, we have a generation of or multiple generations who are on SSRIs because essentially they have some form of chronic depression or mental illness or ocd, addhd, et cetera. And so they get put on a selective serotonin reuptake inhibitor, which in some cases can stabilize someone's depression, but doesn't necessarily address the root cause is like, well, what is upstream or where. Maybe we're not getting enough B6, maybe we're not getting enough micronutrients, maybe we're not getting enough tryptophan to synthesize the serotonin that we need to, to as a neurotransmitter, to feel good, to feel tranquil, et cetera, to feel calm. So there's, you know, so many of these things and then, you know, when you start to uncover this, what is patently a superfood, essentially, and you say, no, we don't have to apply willy nilly herbicides and glyphosate, Roundup, Liberty Link now and all these other things, we can actually grow this regeneratively just the way that Himalayan Teri buckwheat actually grows. It is almost like cover crop.

That's right, it is a cover crop. And so, and it doesn't like fertilizer.

And so it's not, it's not this tilling project of rank on rank crops that's essentially degrading and desiccating the soil.

Right.

It's actually building up soil and building up water retention.

Precisely. And sequestering carbon.

And sequestering carbon, yeah. So when you start to get into the planetary impacts, you know, this is, it's just so exciting. And so I want to, want to talk about specific just a second.

Yeah.

I want to acknowledge, you continue to amaze me. So I want to go back so that it's not lost in all this stuff that you and I are talking about. I think it's quite amazing that you throughout the world, the shikimic acid pathway, that's really. Because let me say why, I think in the context of our dialogue, that is an interesting example. It turns out that now scientists, soil scientists, are studying in great detail what the mycorrhiza of the soil, the microbiome of the soil, when it's healthy does and how does it communicate to the growing germinating seed to affect its growth and, and development. And it turns out that there are a variety of substances that are secreted by healthy soil mycorrhiza, the microbiome of the soil that are chemicals that communicate with the receptors on the seed as it's growing to create this outcome of gene expression of the plant. One of those is shikimic acid, abscisic acid, indole derivatives. There's a variety of small molecules that are produced by the healthy soil mycorrhizae. That, by the way, you do not see in heavily industrialized soils, heavily industrialized soils, monocropped corn, monocryptic, you do not see these same chemical messenger substances that are regulating that. So this construct, that there is crosstalk that is occurring all the time to create a closed loop system is not just farcical it is real. It's the way that we were born into as an organism into the planet. It is our legacy of inheritance that we are despoiling. And it's a tragedy. And it can be corrected, and it can be corrected in one generation.

So what are some of the key phytochemicals that you can point to that help to rejuvenate the immune system and, you know, specifically contained by Himalayan tartary, buckwheat or otherwise?

Yeah, so we've been trying to really understand this as a symphony. And so I'm always a little apprehensive to start naming specifics because I think people might pick up a certain name and say, oh, this is the one.

Yeah, I got, I got to get quercet or whatever.

That's right. Quercet is one of them. That's right. And so, and I'm not saying quercin is not good, but I'm saying that there's a matrix. If you think of, if you think of our immune system as being responsive to an orchestra as suite, even if you had the world's best first violinist, so they were playing all by themselves, it wouldn't be the same as having the whole orchestra there. And so this is 50 different substances at that point. And then you ask a question. Why would the plant waste all of its energy making 50 different things that only needed one? It doesn't do so because it has no better things to do. It does so because it understands over the history of its own evolution that that constellation of substances actually provides a hormetic portfolio of ingredients that gives the defense against the hostile environment and improves immune function. So rutin, quercidin, hesperidin, luteolin, diosmin. I mean, I could go down the list. There are 50 different compounds of differing types, not any one of which works by itself, but by cross talking and cross communication. That's why people, when they talk to me, they say, so are you against nutritional supplementation? No, I'm not against nutritional supplementation, but I am opposed to the philosophy of let's find the single nutrient that's a green medicine against whatever drug.

Right.

I think we have to think of food as being a complex legacy of information that our body receives. Our genes get information from our food to create their function.

And that makes sense because we can be critical of the reductionist process involved in diagnosis where we try to find that one misstep and then engineer a drug to address that one misstep. Well, it would also be reductionist to say that, well, it's just quercetin and you can just supplement with quantum. Course it in.

Right, exactly.

That. We're. When we're eating whole foods, we're eating micronutrients and phytochemicals within the context of a matrix.

Yes.

And you know, and it's quantum in that way. I mean, it's. And we are perhaps not at the place where we can understand all of the interrelationships of 50 phytochemicals within one particular whole food. For example. So what about the. What about omega 3 fatty acids? What are the. What's the role of omega 3 fatty acids as it pertains to the immune system?

Well, we're more and more learning obviously that the downstream mediators of the immune system, signaling substances the immune system produces to regulate the process of immune function, inflammation, are tied to various members of the fatty acid family. I think it was a really tremendous discovery by Bang and Dyerberg some now, 40 years ago that Greenland Eskimos didn't end up with some of these western diseases, even though they ate a DIET that was 80% fat. But the fat that they were consuming was very rich in these omega 3 fatty acids. But the more that that has been studied and looked at in detail, it's not just like one fatty acid. It's not just EPA or dha. And I'm a little against this horsepower race that companies are saying, okay, then I'm going to concentrate these two principles and they're the heavy lifters. And the more I can get in the product, the better it's going to be. And the more I can charge for it, by the way too. And I don't believe that's actually biologically been proven correct. If you're doing a drug therapy for say high triglycerides, maybe, maybe under that course, if you use a purified, high potency chemicalized EPA formulation, you can use it as a drug. But for general body function of your immune system, it's the complex once again of these fatty acids that work in combination. Plus. And this is the new. Aha. There were this. There was a discovery made now about 15 years ago by an investigator at Harvard Med School that I think was frame shifting because he asked the question, okay, we know about anti inflammation, but inflammation in and of itself is not bad. We need inflammation of the right control type to repair damaged tissues. Like if you have a cutter or something. Your inflammation is an important part of the process of healing. Sure. But it's arresting inflammation. It's putting a brake on it. So it doesn't get runaway what does that. And so he started studying that and he found there were specific substance that he termed resolvins, protectins and morisons that were capable of shutting down the inflammation process. So you could upregulate and down regulators like the rheostat control. And it turns out that those what are what are called pro resolving mediators or PRMs are produced by our body's immune cells when they're healthy, but they are produced by a precursor that are certain types of fatty acid that are found in minimally processed marine oils that have names like 14, 16 related derivatives. When we started studying then the commercial oils that are being sold as supplements, we found that by the way that these are processed, they're scrubbed and distilled and high temperature treated and so forth, you don't end up with many if any at all of these PRMs that were in the natural oil. But a lot of people don't like natural oils because they're so fishy flavored and they would be considered maybe rancid. Well, what we found out in studying this more is that the rancidity and smell and taste official is not really the fish oil itself. It is the rancid byproducts of the oxidation products of fish oil. If you, if you and I know this for a fact because we are producing such a product, if you get brand new cod liver oil from cod livers that have been frozen and not exposed to, to heat at all, they go directly into processing so they come out at low temperature. That oil is colorless, tasteless and odorless. And cod liver oil, when you speak to people is like athlete, right? Oh yes, but that's not.

It's a punishment that you don't.

That's right, exactly. So but if you look at that natural oil before it's become heavily processed, what you'll find is it has very high levels of these PRMs. We made this discovery, I think that has not been well understood that the natural preservation of the integrity of the complex oils in marine organisms actually delivers a different nutrition value than these highly processed, potentized EPA DHA formulations. So again, it comes back to this concept of orchestration and the portfolio effect and that nature has this symphony. It's been speaking to us naturally that we kind of moved around for whatever reasons, commercialized reasons.

Sure, sure. Let's migrate over a bit to what I might call the biology of belief.

Yeah.

So it's been well established now that the mind and body can't be separated and we can give Very, very kind of prosaic. Examples of your sympathetic nervous system might be stimulated by a snake that might slither across this floor here, as unlikely as that might be. And that would trigger a neurological or cascade or hormonal cascade where you might get a jolt of epinephrine and jolt of cortisol, a jot of adrenaline.

All.

Of your blood would go to your extremities, your heart rate would go up, your respiratory rate would go out and you essentially would move into a fight or flight state, a sympathetic overload or amygdala hijacked state, which is absolutely fine, you know, reaction on the Serengeti or if there happened to be a snake that came through here. But I think we're. Unfortunately, what we're dealing with on the Serengeti of Facebook or social media etc and other places in our 24 hour news cycle is that we seem to be in this chronic state of fight or flight and that is having all sorts of detrimental downstream physiological impacts. We could pull on that thread for a long time of how elevated chronic cortisol rates can drive up blood sugar and degrade the immune system. Because you're moving blood away from the immune system when you're constantly in a place of sympathetic overload. And there's another side, there's the flip side of that too, which is.

What.

You might dub the science of hope. So I wonder if you could pull on that for a moment. How belief impacts our biology and what do we need to do as the human race to, to more align our, the way that we think with positive biological impacts?

Yeah, I think this is really the currency of today's important discussion. This is really, really right at the threshold of so much of what we see right now around us with despair and, and concern. And sometimes it translates into fear, which translates into rage and anger and then misunderstanding and lack of tolerance and all sorts of things brought to that. So it's very, very powerful. I think that we have crossed an interesting scientific threshold that when I was in school and now I, I can say when I was getting my advanced degrees it was in the 60s and hard to believe. The concept that we could somehow alter the way that our genes were expressed epigenetically as an adult was considered antithetical to any good scientific thought. And that concept that we adapt somehow to our environment would have, I would have been expunged from graduate school or medical school that that construct of adaptation versus genetic natural selection was just not considered to be true. We are now at a different point that just within this last 21st century, the data is now very, very convincing that even in a adult, even a late age adult, that we still have some genes, not as many as when we're an infant, but some genes in our family of genes that are still picking up information from the environment and are being epigenetically tagged with those experiences. And so if we have post traumatic stress syndrome, we've locked ourselves into a stress situation because we've actually tagged epigenetically certain regions of our immune system. That then puts us into a hyper immune state and a hyper catechol state that relates to these inflammatory potentials. And it's been thought that this is pretty much a one way street. You know, you had those experiences and too bad and there's not much you can do about it. But now we recognize through this more recent research that there are these so called metastable EPI alleles. What does that really mean in English? What it means is there are regions within our genome, maybe 100 or so loci, we don't really know specifically the number, but a number of regions within our genome that can be marked and unmarked over the course of our aging. There are processes by which we can put on marks and there are processes by which we can take off marks like methylation and demethylation, acetylation, deacetylation, things of that nature that occur at the genetic level. Now I consider this a science of hope because it then takes us from a one way street mentality that once we've been imprinted, woe is us. Too bad. But you're not going to be able to do much about it. Maybe go in psychotherapy and hope for the best. But now we recognize that actually through a comprehensive program to focus on how we epigenetically remodel. And I would say the immune system is a good place to start because the immune system is the quickest change and it can signal to all these other organs because the immune system is in every organ of the body. So here now we start saying there is a potential to turn back this sense of despair descend and to create a different set of messenger molecules. This is almost Candace Pert in some ways the molecules of emotion recast through the epigenetic lens or the, or the biology of, of the mind that create is created as a consequence of how we are sending information to it, to restructure our epigenome. And, and so it connects very intimately, mind, body, with materialistic medicine, which I've always really been in search of. Now let me close on this Because I know you are much more skillful in this area than I am. But I just want to throw a thought out for consideration. I got very, very concerned over this Covid period about what was being called social determinants of disease. Because we saw very clearly that the severity of a SARS CoV2 infection was not linear across all people. It was variations. And those individuals who had what was called the greatest social determinants of disease were the ones that seemed to have the greatest. More, more, more talent actually. And morbidity, similar, serious morbidity. And I've been hearing that term all my years being in this field, but I never really, I have to say honestly, as a male culpa, I never took it really seriously to try to dig into understanding what that term meant, social determinants of disease. And the reason I found that I didn't was I had a bias. Right. My bias was that was soft over here. This materialistic stuff that I study is hard, Right. So we have hard science here, we have soft sociology, anthropology, cultural psychology, things over here. Soft, hard. So I, I'm a scientist, I'm over here on the hard side now. Now suddenly I recognize there is actually no separation between hard and soft. Because the social determinants of disease, which are impoverishment, lack of attribution, lack of love, isolationism, deprivation, abuse, all those characteristics are those that are sending signals to our genes that mark them materialistically, not just psychologically.

This for me is just. Is the frontier.

Yes.

It's so exciting and exasperating to sometimes to, to analyze it because you know, you do have to touch things that are very, that are agonizing, that are very painful.

Yeah.

You know, gobble or mate is coming here and about a week and.

You.

Know, he has focused largely on the psychosocial side of trauma or trauma inducing events. So neglect, abuse, poverty, or if you go into communities that have no supermarket, no bank, no school, no hospital.

Yes.

So. That in response to that kind of trauma inducing event, if you do not have the ability or the resources to heal, then what's going to happen? Well, I mean if you, even if you just look at a wound, a wound can be infected, it can fester or it can scar and it can become numb and then you become alienated from that part of yourself.

Yes.

And if you continue to play that out well, then it is only natural that you are going to seek out external agents for a sense of happiness or connection. And that oftentimes turns out to be alcohol, drugs, gambling, sex addiction, instagram addiction. Fill in the blank.

Yes.

So, but, so that psychosocial side of it is, has been, I think, written about and talked about with great eloquence by Gabor and other people. I think where you're going is marrying some of that social science with some of the empirical hard science that says, okay, yeah, that's happening. But also what's happening here is that particular trigger is marking a particular gene, and that might be BDNF or the BRCA gene or whatever, you know, and that's turning on or turning off the particular expression of that gene through, potentially through methylation. It's a lollipop that sits on, on the gene. And, and that, that, that is actually hard. So you're mere hard science. So you're, you're creating this bridge.

Yes.

And I think it's fascinating. I know Kara Fitzgerald is poking at this a little bit and Sarah Godfrey is poking about at this a little bit, and I think it's right, right here we're on the precipice of this new science with actually understanding the, the physiological markings of trauma.

Yeah, I think for me. Thank you. I think that's beautifully stated. It, it's both giving kind of an understanding, but it's also giving a point of entry that gives you a therapeutic potential and a way of measuring. Because if we can identify, which I think we will over time, not today, but in the not too distant future, we will identify certain loci in the genes that you can measure by certain blood tests, probably in the immune system, because it's so easily measured by taking blood or maybe epithelial cells, but they have a longer life. I think the immune cells turn over more rapidly, so you see more temporal effects. So as we learn what genes are being marked and how they tied to function, behavioral function, we suddenly have a diagnostic probe, right. Or an assessment prognostic probe, probably better than diagnostic. So we started saying, well, that set of collected genes that are imprinted in that way trigger then that kind of a cascade downstage that can be seen phenotypically with DSM and those psychological symptomatologies. Now we intervene with whatever the treatment program that that therapist selects. It could be any number of holistic kinds of approaches. And we track in both the phenomenological improvement of the patient, but we can then see the organic changes in their imprinting of the genome that has locked them into that behavior type. I think if you can do that, you have done what Linus Pauling was talking about some now, 60 years ago, of bringing Together psychology, psychiatry, neurology and genomics all into one unified theory that gives you probes and interventions that makes all of what we call alternative medicine actually the real medicine.

So good. Jeff. Okay, as tempted as I am just to leave it right there because that was such a mic drop moment, I have one last little area to probe with you. And it's something that keeps coming up in conversations that I'm having and things that I'm thinking about. Is that how our culture has in a way, outpaced our evolution?

Yeah.

And if you look at the, you might call them technological innovations, though it's. It's unclear how. How innovative they are per se. But these things that we really sanctify in culture, which is like let's say 24 hour on demand entertainment. Okay, well that's great. Isn't it awesome to be able to log into Netflix and watch a cool documentary anytime you want? Yeah, I mean, that's pretty cool. The problem is, is that that cultural innovation is outpacing our are more adaptive human mechanisms. For example, we want to get blue light in the morning because for reasons that you touched on earlier, that sends a message through these little intrinsic ganglion receptors in the inferior part of our eye, down to the suprachiasmic nucleus, to our pineal gland to stimulate the production of melatonin at the right time of the day such that we optimize our sleep. Yes, right. And so really this idea of 24 hour on demand entertainment, it's actually undermining some of the more adaptive mechanisms that were produced by evolution. So, you know, and it's also really interesting to think about how humans actually used to sit around a fire. Well, that was amber light at night and that would be low, so it actually hit the superior part of your retina. So we evolved all these amazing things and now we're sort of on. We're moving so fast that we're not in line with nature's foundational wisdom. You know, I think about abundance and scarcity. Well, now we have 24, seven convenience, storage, food at our whim. At any moment, I mean, I really can just pick up my cell phone and order anything in season, out of season, any time of the year. And you know, really like, I think about, for example, like drinking a Big Gulp, something that I can't ever remember having done, but I'm sure I did it as a teenager. Really the. And David Perlmutter wrote a book about this essentially is fructose is a signal for you to become insulin resistant because it was A trigger to say wait a minute, scarcity is coming so we gotta store fat and. But now of course we can just. Scarcity never comes. We just pick up another Big Gulp. And I could, you know, and you know, there's example after example after example of this. So how do you think that humanity can stop this runaway train and better recognize the our evolution and more adaptive mechanisms that exist within our physiology and align with them them such that we're not producing these cascades of inflammation and chronic disease?

Yeah. So I think that's a really complicated. And the person that, that has the solution to that question, the woman who has a solution, that question, because it will come from a woman, it won't come from a man, I believe because of the nature of the mind that it requires to do the problem solving of that complex matrix. It's not, it's not watch repair, it's systems analysis and it's cooperativism and it's collaboration because it's going to require all sorts of things. But what I do know for sure is when I look today and who's making decisions for the world population about how we're going to address those is a bunch of old white men that's not going to be the people that produce a solution. I look to my granddaughters and my grandsons who have. I already see a very, very different reality about what's they see the world to be. Now they do have TikTok and they do have these other things that are a lot of screen time which is concerning. But the conversations I've had the privilege of listening to my, my granddaughters, grandsons that are now just in their teens, mid teens have conversations among their friends when they're on our boat together. And it really encourages me because they're talking about a whole different value system and a whole different way of, of assessing what they want to be as they grow up and how they will be successful as human beings. And I, I think we have to look to that because we have a lot of dead wood that new ideas are not going to come from them. Their obituaries have already been written, they just haven't been published yet. So I think that we have to look to the plasticity of this next generation who's able to see what this reality has come to. The shining object and say, well, hold up, maybe not all the shining objects are things that we really want to incorporate into our life because maybe the shiny objects are things that have been around enduring for eons.

Yeah, yeah, it's interesting. So I have three daughters, which I think I've mentioned, I've certainly mentioned them on this podcast almost too many times. But, you know, they're, they're growing up in Los Angeles with a lot of social media, a lot of social media pressure, and, and they, like everyone, have certain anxiety oriented issues. So, you know, one of them will come to me and you know, with some form of anxiety, and I'll say, listen, you know, you're not alone. I'm right there with you. I just have a few more years of building up an arsenal of modalities and tools that I use to manage that stress and anxiety. And I get the eye roll and they say, dad, don't you fucking dare say meditation. So I'm like, okay, well, you know, I'm like, breath, work, get out your.

Breath work out of here and stuff like that.

But the moral of the story is I go into my daughter's room at, and there I hear something playing on her phone and she's not in the room. And I go over and I look at the phone and she's got a meditation app on. And, you know, they'll never listen to you, but they never fail to imitate you. Right. I do share your optimism that there is a, that there is a new kind of dialogue that is happening specifically around food as medicine, around modalities such as meditation that used to be kind of castigated as this, you know, sort of hippie or Eastern thing where you had to wear a saffron robe and live in a cave and adopt some sort of monastic life. Not at all. These are becoming kind of mainstays. And that does give me, you know, a tremendous amount of hope. And, you know, Jeff, I'll just say that just over the course of sitting here with you over the last 90, 120 minutes, to be honest, I completely lost track of time because that's what happens when you're so immersed in something.

I feel it too.

And there's a whole conversation to have about sociogenomics, of how we can upregulate our, each other's epigenetics just by being focused in conversation with each other. But what you are doing, the role that you are playing to impart wisdom, is part of a tradition that goes back since the beginning of mankind. I mean, really, I look at like the way that Buddhism, for example, was passed down through generations. It was mostly oral. Eventually it got written on some palm fronds and put in these three baskets and carried around Nepal. But. And eventually there was obviously a canon developed around it. But the passing down of wisdom is so essential. And I. I feel that you have been such an integral part of that process, from Pauling to you, to folks like Mark. And, you know, I see this emergent generation of functional and precision medicine doctors out there, and it does give me a tremendous amount of hope. And, you know, there's just so much to be grateful for you about there. So just thank you so much for all of your contributions for this conversation and for everything that, you know, you're doing at Big Bold Health. Because I know that at this point in your life, that's not something you probably have to do, but you've chosen to do it. So maybe just kind of in close, you could. You could describe a little bit about the vision and mission for Big Bold Health and how you see that as a part of your overarching legacy.

Yeah. Thank you. I think that my wife and I've had many kind of very sentient discussions about this. And what does the last portion of our life look like from 76 on? And I think that we have both come to the obvious conclusion that we've been so blessed and so privileged to live the life. Do we have the 6 million miles we travel, the literally thousands of people that we've had the fortune of meeting, that we've picked up ideas and really important things from that we've included and incorporated within our lives, and we feel like we're ambassadors, kind of mosaic of all those different experiences. And so there is. If a society, as you've just said, always evolves around some tradition, some oral tradition, some passing of the bull, to use a chautauqua concept. And I think you got to pay forward somewhat. It doesn't. Nothing comes free of charge. Everything has some kind of an inherent responsibility associated with it. And for me, it's. I've had the privilege of learning a lot of things that I think of value. One of my colleagues years ago, said something to me that he was saying it very powerfully in a way that the first time he said it, I didn't fully get it. And then it took a few seconds, and I really got. He said, so, Jeff, this came after one of my seminars. He came up to me, he was a colleague that we were working together. He said, do you realize that people are dying to know what we know? And I thought, oh, my word. You know, that, like, sets a really different context. And I've had the privilege. You know, I don't have a clinical practice. I've overseen clinical research and thousands of patients that have gone through studies and so forth. But I've had an ex. Series of experiences in my life that I think I would call quintessential, in which I will be somewhere and someone will come up to me and they often, it's very intimate. They'll grab me by the shoulders or grab my hands, and they'll look me right in the eyes and they say, I want to thank you. You saved my life or my mother's life or my child's life. And I'm. I'm thinking, I never went to emergency room. I never was in terminal medicine. I was just providing ideas of opportunities for people to recontextualize their process of living and for a person to take it, take the energy to go and to communicate that to me is the greatest privilege that you'll ever get. So that comes with a responsibility. That's how I see it. So I'm. I'm trying to do all I can to pass that baton. I'm very excited working with these younger people in Big World Health. I, you know, it was Trish Erie, my colleague of 25 years that always had to endure one. Monday mornings had come back from weekend meetings, and I'd start espousing. And finally she said to me, jeff, you know, you're a pretty big guy in stature. You're always very bold. I think you need to do big, bold health and get it off your shoulders. So that's what we're up to right now.

Well, good for you. Well, I am absolutely honored and thrilled to be on your stop and on your path here and just very grateful that you come and visit us here in Topanga. So I hope this won't be the last time.

Oh, absolutely not. Thank. Thank you, Jeff. And what you're doing is it's. This is a matrix, right? We're all part of that matrix. So thank you for all your efforts.

All right, to be continued.

Right on.

Thank you for listening to my conversation with Dr. Jeffrey Bland. Check out Big Bold Health to learn how you can use the intelligence of nature to rejuvenate your immune system. And look out for the new commune course coming early in 2023 with Dr. Bland and Dr. Austin Perlmutter titled Immunity Reimagined. Now, if you enjoy this show, please subscribe on Apple Podcasts and leave us a review. If you're a regular listener, then you're likely aware of how much effort we put into the show's creation. And we really do our to keep sponsors to a minimum. So if you're looking for a way to support our efforts. The best way is to subscribe to Commune. You'll access more than 100 courses featuring the world's top authors and thought leaders and you can check it out for free for 14 days at one commune comm. Slash trial. Of course. Feel free to reach out to me directly at any time at jeff k@1commune.com. Now I'd like to thank the folks that make this show possible week after week after week, including Jake Lau, Megan Stone, Violet Augustine, Alexa Pepperman, Ruby Foster, Emma Fret, Silvana Alcala, and Ryan Tillotson. That's all from the Commune for this week. My name is Jeff Krasnow and I am here for you.

Foreign.

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