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RHR: Immune Rejuvenation and the Roots of Functional Medicine, with Dr. Jeffrey Bland

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Chris is joined on this episode by the father of Functional Medicine, Dr. Jeffrey Bland. They discuss the history of Functional Medicine, how it has impacted current medical approaches to health, and the process of immuno-rejuvenation. Dr. Bland dives into how the immune system and the gut microbiome are linked, how diet impacts more than just your digestive health, the role of epigenetics in immune health, zombie cells and what role they play in the aging of the immune system, and the immunity superfood Himalayan Tartary Buckwheat.

In this episode, we discuss: 

  • Dr. Bland’s history and what led to him to coin the term functional medicine and co-found the Institute for Functional Medicine
  • What developments Dr. Bland feels most encouraged by, in terms of where Functional Medicine stands today in our medical paradigm
  • How Functional Medicine embraces the concepts of systems theory
  • Conventional medicine’s failure to properly acknowledge the role that nutrition and nutritional intervention plays in healthcare
  • How conventional research protocol has a limited focus on population risk and why other study designs could lead us to a better understanding of functional individuality
  • What immuno-rejuvenation is and why it’s important for overall health
  • Himalayan Tartary Buckwheat, a new superfood and immunity accelerator 
  • Three primary nutritional drivers of immuno-rejuvenation – phytochemicals, omega-3s, and pre- and probiotics

Show notes:

Hey, everybody, Chris Kresser here. Welcome to another episode of Revolution Health Radio. This week, I am thrilled and honored to welcome Dr. Jeffrey Bland as my guest.

If you’re familiar with Functional Medicine, it is largely due to Dr. Bland’s efforts. He coined the term “functional medicine” in 1991, when he co-founded the Institute for Functional Medicine (IFM) with his wife, Susan Bland. IFM has gone on to train over 100,000 clinicians around the world in Functional Medicine. Dr. Bland began his career as a professor of biochemistry at the University of Puget Sound where he studied vitamin E and its effects on cellular aging. He is also a best-selling author, thought leader, educator, entrepreneur, and consultant. I’ve had the privilege of encountering Dr. Bland’s work over the years and have always been impressed by his rigor and scientific acumen and his ability to do very deep dives on a wide range of scientific topics and then translate [the] insights that he has into practical and actionable steps that practitioners and the general public can take toward improving their health.

One of his areas of expertise is the immune system, so that’s what we’re going to focus on in the conversation today. But since I’ve never had the opportunity to interview Dr. Bland, I couldn’t resist taking the chance to ask him about his history with Functional Medicine, what led to the fundamental insights that inspired him to coin the term functional medicine and to co-found the Institute for Functional Medicine, what he’s most proud of, what developments have most surprised him over the years, and what some of his disappointments have been, in terms of where we stand today in our medical paradigm. This is one of my favorite podcast interviews. I consider Dr. Bland to be an inspiration and a mentor, and I was so grateful to be able to spend this time with him. I hope you enjoy the conversation. Let’s dive in.

Chris Kresser:  Dr. Jeffrey Bland, welcome to the show. It’s such a pleasure to have you as a guest.

Jeffrey Bland:  I can’t tell you how much I am looking forward to this discussion. You’re a master, and I’m really looking forward to our repartee.

Chris Kresser:  Well, I owe a lot of my work to you. We wouldn’t be sitting here having this conversation about this thing called Functional Medicine were it not for your pioneering work. I believe you coined the term back in 1991 when you started the Institute for Functional Medicine with your wife, Susan Bland, which has now trained over 100,000 clinicians in this incredible body of work we call Functional Medicine. So I have to ask, before we dive into the immune system, which I’m really looking forward to, just a little bit about the origin story. How did you come to this concept of Functional Medicine? What led you to that and then [to] the founding of the Institute for Functional Medicine as we know it today?

Dr. Bland’s Background and the Inception of Functional Medicine

Jeffrey Bland:  Well, as we both know, life is not a linear path. As I say, life happens in between our plans. So, for me, if you would have asked me when I was in college, at the University of California, Irvine back in the 1960s, would I ultimately somehow end up with this concept of Functional Medicine and this extraordinary community of people like yourself that I’ve had the privilege of working with these last 50 years, actually going on almost 60 years, I would have said the probability would have been approaching zero. But as a consequence of a number of events, and I think one of the most seminal events was as a university professor back in the 1970s and early ‘80s, I had the pleasure and privilege of meeting Dr. Linus Pauling, [the] two-time Nobel Prize winning laureate, who was gracious and asked me if I would come and spend two years of a sabbatical period in 1981 to [19]83 running a research lab at his Institute of Science and Medicine in Stanford, Palo Alto, California.

That was a life change for me because it really opened my eyes to the much broader world that I hope to provide some contributions to. He was such a luminary. We had all these people from all over the world come [to] visit us at the institute, previous Nobel Prize winners and discoverers of all sorts of different things. And what I found was [that] he and his wife, Ava Helen, were much more than just great scientists. They were just great people. They embodied the concepts of freedom of enterprise, freedom of ideas, respect for individuals, cultural tolerance, all sorts of things that were really important for me at that young age, as an aspiring academic, to learn about. When I left the Pauling Institute in [19]83 to go back to my university position, the last thing Dr. Pauling said as I was carrying my stuff to my car with my kids packed up [and] ready to head back to the Seattle area, he said, “So Jeff, it’s wonderful to have had you here the last couple of years, and I hope we’ll continue to be able to collaborate and work together. But my question is, ‘Do you think your classroom is big enough, as you go back to your university position?’” It was then, 1100 miles of driving back with my kids [and my wife] in the car, that I had a chance to really think about what he was saying. What was the meaning of that question? I finally came to the conclusion that what he was asking me is, was this a time in my career where I really needed to consider where I could make my best contribution?

By that time, I had done quite a bit of traveling, I had met people around the world, I was starting to do quite a bit of education for practitioners, and I came to the conclusion that where I should put my energy going forward was trying to help practitioners learn how to do both nutritional medicine and preventive medicine in their practices. That was really my calling. So I gave up my tenured faculty position and decided to start off on this new venture, which when I think back now was a little bit crazy because my kids were in high school and I had a mortgage and a family and had the reality of life, [and] I was giving up all that security as a professor. But it was the right decision, in retrospect, because that opened up my ability to meet so many other people. I’ve traveled over 6 million miles now in my career, all over the world, meeting extraordinary thought leaders. I’m kind of a mosaic of them, and that ultimately led me to recognize that the most important feature of the precedent to disease was how we’re functioning. No one was really focusing on function. Of course, Linus Pauling was a big believer and actually published many papers around structure and function as one of his principal concepts, going from some molecular all the way to social enterprise. Get the structure right and function will follow. So I thought, “Well, maybe this is a time that we really need to bring together thought leaders in our field.” I [was] fortunate to meet many of these [people, like] Leo Galland, Sid Baker, David Jones, [and] later, Mark Hyman, [who] were really committed to looking at, what is the best way we can deliver service to people in need, particularly across the chronic disease area, and get away from being tethered to disease and [instead] function?

We broke down function into four categories: physical function, metabolic function, cognitive function, and behavioral function. My wife decided that we should put together a whiteboard meeting in Victoria, British Columbia, and invite 40 of our top friends from around the world to come hang out to talk on [the] whiteboard for three days about what a healthcare system [would] look like if we [were] to idealize it and not be set within the concepts of reimbursement or licensure, but just how we [would] construct the right kind of system. It was out of the second year we did that meeting, again back in Victoria [in] 1990, that I came up with this idea that maybe what we should call this is Functional Medicine and codify the Institute for Functional Medicine.

I have to say, at first, my colleagues [and] my good friends [who] were coming to these meetings said, “Well, Jeff, that’s a great idea. But I don’t think that’s the right term.” Because back then, the term Functional Medicine [had] two different connotations. One was geriatric medicine, older people or disabled, and the other was psychiatric medicine, meaning psychosomatic illness. That it was all in your mind. It didn’t have a high reputation.

But I had been reading the literature extensively and I saw there were many new papers that were coming out that were talking about functional cardiology, functional radiology, [and] functional endocrinology with a recontextualization of the word function. So I said, “Hey, maybe we ought to skate to where the puck is going, to use an old metaphor, and we then started [the] Institute for Functional Medicine in 1991, with our first meeting. But I have to give, in closure, a little bit of a mea culpa because it was some eight years later, after we had started the Institute for Functional Medicine, that one of the colleagues in this Institute said, “Jeff, did you realize that Willoughby Wade, a professor and dean of medicine at a British medical school, published in 1872 in The Lancet magazine [the term] functional medicine?” And I was very embarrassed because I consider myself a pretty good sleuth of literature and I could not find that article, initially. It was present, we did find it, and lo and behold, when he talked in his old English about his thoughts of Functional Medicine, it really synced up with what we were trying to do.

So I cannot claim any credit for this. I have to give Willoughby Wade credit because he first wrote of this concept in The Lancet in 1872. We just recapitulated it and brought more modern concepts into the 21st century.

Chris Kresser:  Well, certainly, there’s that saying, “there are no new ideas,” but you certainly played a huge role in codifying and organizing and communicating this concept to a larger audience, and I’m forever grateful for that. I know I can speak for so many other Functional Medicine practitioners who say that we literally wouldn’t be here doing this work without you.  So, much appreciation for you, Dr. Bland, in that.

The Influence of Functional Medicine

When you look at medicine today and how Functional Medicine may have influenced medicine and the way things are going now, what are you most surprised and encouraged by? And what are your biggest disappointments?

Jeffrey Bland:  Thank you. That’s a really, really insightful question. Let’s talk about where I really feel encouraged first. I started lecturing extensively trying to get this concept across in the mid ‘80s, and, in fact, one of my attendees at one of those seminars in 1985 sent me just recently a syllabus that I put together for that seminar. It was on gut dysbiosis and the gut–immune system and the relationship to leaky gut. We came up with that term and started using it in the early to mid ‘80s. And [there] was a lot of pushback. People [wondered] what was wrong with us [and thought] we should either have a prefrontal lobotomy or be excised from trying to be an educator in health science, because there was no such thing as postprandial endotoxemia or leaky gut. As far as they were concerned, it didn’t exist. But I’d have to say that now, if you go to the medical literature today, 2022, you’ll find that there are literally hundreds of papers being published on these topics using these terms in traditional, peer-reviewed scientific literature.

So I think that there has been a staying power and a growth [in] acceptance of what we’ve been doing, because what we were talking about and the terms that we were using to language our model were not trying to tread on the disease model. The disease model is what it is. You have the [diagnosis-related groups] (DRGs) and you have the ICD-10 [codes], and [they handle] a specific kind of condition related to a kind of terminal illness or more late stage pathology. But there was no one really focusing on how we describe the earlier stages of this function, of health that is chronic in its disease, before it becomes more acute. That was where we were landing and we were trying to use a new emerging science called systems biology that tied things together into network thinking in a way that was not used in traditional disease-focused medicine, [which] was all, “Can you name the diagnosis? Get to the diagnosis.” The sine qua non in medicine was the diagnosis in the pathology-based model. For us, it was going upstream and trying to understand, “What are the origins that have confluence that come downstream ultimately to give rise early on to dysfunction that later may become a disease?”

That required a whole different strategy of thinking, a whole different set of research tools, [and] a whole different clinical approach to the problem. As with any new paradigm, you get a lot of pushback from people who say, “Well, I already have the answers; don’t confuse me with new information.” So, I think [we] have made really great strides in progress that the concept of systems biology and healthcare, and the concepts of function have both started to gain a landing spot in changing [the] curriculum of healthcare institutions around the globe.

Chris Kresser:  Dr. Bland, could we just linger on this for a moment? Because I think it’s a profound paradigm shift that you’re talking about. So profound that maybe listeners aren’t [even] fully aware of it. In systems theory, the sum of the parts is more than the whole. You don’t just add up the parts and get the whole. The whole is the emergent interactions between all the parts and is so much more complex and so much more profound than the old allopathic paradigm, which is just looking at the body as a disparate collection of parts. [Where] if you have a doctor for every different part, that’s fine because we’re not really thinking about how these parts interact and inform the health of the whole. To me, that’s one of the most fundamental insights that [you] and your colleagues had, and that Functional Medicine as a whole offers. Because it really changes the whole perspective and the way that we might approach somebody who walks into the clinic door. We’re thinking of them as a whole person with all these emergent interactions going on, rather than just a collection of parts. So can you talk a little bit about any insights you’ve had along the way with that? Or just how that came about? How did you start to apply these concepts of systems theory to Functional Medicine?

The Concept of Systems Biology in Functional Medicine

Jeffrey Bland:  Well, thank you. And again, I want to give credit to Linus Pauling, to guide my thinking in this area, because he was already talking about this concept of function and its relationship to structure, and I was heavily impacted by that [and] my couple of years spent there at the Institute. But I think what [part of that lesson] I maybe took to the next level was when I started to look at the literature through this different lens, and I started to recognize [that] when you look at people in the clinic, or people out in the world at large, who had chronic health problems, and you started to examine what their problems were and how they were trying to find solutions to their problems, they would often be seeing, as you just mentioned, Chris, several different subspecialists in different medicines for their different ailments.

Let’s use a classic example, one that I used to talk about a lot in the early days of the development of Functional Medicine. A woman who had osteoporosis, who had early stage cardiovascular disease, and had rheumatoid arthritis. This is an actual patient, by the way.

Chris Kresser:  Yeah, that’s not an uncommon cluster of conditions. We can see that in thousands of patients.

Jeffrey Bland:  In speaking with this woman, and this is going back in my experience to the ‘80s, it became very clear that she was going to Stanford Medical School and Medical Center for treatment. That’s a very high center of excellence for pathology-focused medicine, and she had [a] top rheumatologist, cardiologist, orthopedist, and endocrinologist dealing with her bone problems. So she was getting good medicine, based upon the model that was segmenting, as you said, into the different organ systems [and] treating them independently. The explanation that was offered to her as to why she had these three conditions simultaneously was comorbidities. These were comorbidities. That’s the way they were described to her. Comorbidity, meaning occasionally, these things occur simultaneously in an individual.

Chris Kresser:  That’s a fancy word for coincidence, right?

Jeffrey Bland:  That’s right. Exactly. Thank you. So that was a head scratcher, right? Like, why? It’s not just her alone, as you mentioned. There are many other people [who] have those three things coming together. So I and my colleagues [started] looking at, “What are the points of attachment upstream, the biological connections that give, downstream, into the experience of the person [and] those three different ‘diseases,’ which are separated across those specialties of medicine?” And we found that there were specific characteristics, [that] we call fundamental biological processes, that were dysfunctional that then gave rise, ultimately, to those three different diseases. They were all interconnected. It was part of a system. So rather than treat each individual disease with its own collection of drugs, why don’t we go upstream and ask the question, “What are the agents that are imbalanced out of these fundamental physiological processes? And can we manage those so that, downstream, all three of those conditions are improved?”

Starting from that logic tree, it built out the whole architecture of the Functional Medicine model. Because we found, lo and behold, that when we did that, a lot of these conditions that were comorbidities started resolving, all of them simultaneously. Whereby treating cause with an effect, we ended up with a whole different outcome. That was really the birth, I think, in the mid to late ‘80s, of what later in the ‘90s became Functional Medicine for me.

Chris Kresser:  Wonderful. Making the roots of the tree healthy, so that the trunk and the branches and the leaves are healthy. It makes so much sense, I think, when we explain it to people in simple terms, like you have.

So tracking back to the original question, you’ve seen, and I’ve seen, as well, even in my own, much shorter career, where talking about intestinal permeability or leaky gut would get you eye rolls, or perhaps laughed out of the room in a scientific conference. Now, if you go into PubMed, like you said, you’ll see thousands of references linking intestinal permeability to not just gastrointestinal problems, but virtually any of the modern chronic diseases that we suffer from today. And that’s just one example. There’s so many other examples of things that Functional Medicine pioneers like yourself discovered early on and were talking about early on that were anathema to the current theory at the time, but then later became, not only accepted, but sort of the default paradigm. So that’s the good news.

The Role of Nutrition and Nutritional Intervention

When you look at the landscape, was there something that you expected to change or make more progress by now that hasn’t changed or that’s come up against more resistance? Perhaps things like the conventional medical model, with the infrastructure of insurance and licensing and everything that you mentioned? Or something else? Is there anything that stands out as something you wish would have progressed faster than it has?

Jeffrey Bland:  I think there are a number of answers to that question I could provide. But let me focus on one that’s contemporary right now, and that is the role that nutrition and nutritional intervention plays in this whole schema. I would have thought [that with] this model of systems biology and the concepts of looking upstream and how that influences downstream effects, that the variable that everyone engages in at some level, which is eating and food, and nutrients within food, would have a more dominant impact upon the training of practitioners. Because it’s inescapable that the things that we eat have [a] significant impact upon the genes that represent our book of life, that then express our function into how we look, act, and feel. So, the construct that a fundamental principle of this whole thing has to be nutrition and personalization of nutrient intervention seems so obvious to me that it would come along for the ride and be a major tool that would be accessed by health practitioners across different disciplines. Of course, that’s not happening. Even today, gastroenterology has not really embraced nutrition as a major core concept. The one subspecialty of medicine that has to do with the plumbing that associates itself with use of our food, [when] 70 percent of our immune system is clustered around the intestinal tract, still does very little in understanding and applying nutritional concepts that, for those of us [in] our field, [are] just so obvious.

That’s a little disappointing. No, it’s more than a little, it’s very disappointing to me. And it begs the question, why? Why the pushback? Why not the acceptance? And I think there are many answers to that question, having to do with medical politics, medical economics, medical education, convention, standards of care, hospital medicine versus ambulatory medicine. All sorts of things play a role as to why nutrition doesn’t play a more significant role in training of practitioners about how to remediate and prevent the unnecessary burden of disease.

The immune system shouldn’t be strengthened, but rather, balanced. Tune in to this episode with Functional Medicine pioneer Jeffrey Bland and learn why the difference is crucial and how you can turn back your ‘immunity age’. #chriskresser #functionalmedicine #immuno-rejuvenation

Using the Correct Type of Study Design to Evaluate the Effectiveness of Therapies

With that stated, let me give one recent example and that’s dietary supplementation. I was activated within the last month when I read in the New England Journal of Medicine and the Journal of the American Medical Association (JAMA), in separate issues of the journal all coming at the same [time] in late July and August, articles that were criticizing dietary supplements and saying there’s no reason for dietary supplements. It was going back to the old expensive urine arguments from, in my case, over 40 years ago. Why take a supplement if you just excrete it away? It doesn’t do you any good. The JAMA had two papers that were describing large, community-based research on taking vitamin and mineral supplements, looking at the incidence of cancer and heart disease, [and] showing no effect in reduction of either of those by people who took vitamin supplements over a long period of time. There was an editorial accompanying those research papers saying, “See, this is just once again another example of why taking supplements is a waste of money and could be potentially dangerous.”

Then the New England Journal of Medicine, [in] the same period of time, has this article on vitamin D intervention and bone loss and bone fracture, showing no effective vitamin D supplementation on bone loss or bone fracture in this large study. Then an editorial followed that, saying, “See, once again, this is why nutritional supplements are overhyped, and they’re of low value, and maybe even potentially dangerous if you took too much of certain things.” So these things [have] come back periodically in my last 40-plus years in this field to be revisited, and they’re fallacious based upon the very principle that you and I have already started to talk about. Let me quickly state why I believe they’re fallacious. These are studies that are done in community-based, population-based structures that are really designed to do drug treatment studies, in which you take a very highly active compound that’s a new-to-nature molecule developed by a pharmaceutical company [and] that has very strong potency to its way that it acts in the body. You test it against a thousand people who have [the] condition that you want to see its effect [on], and you see what the results are in that placebo, blinded trial against people who don’t take that molecule. And because it’s such a potent molecule, if it shows a statistically significant difference among the placebo takers, you call that an active drug, and if it’s safe enough, then it can be approved. That’s a pharmaceutical model.

Now put a nutrient into that specific testing protocol, that same research protocol. Community-based, population-based study. We have everybody, unwashed America, take a vitamin supplement over the period of some years, and then you look at the aggregate outcome and the statistical outcome and say, “Did it statistically reach significance of value?” And they would say, “Well, no, it didn’t reach statistical significance.” Now, does that mean that everybody out of those thousand people [who were] studied over the course of years of taking a vitamin supplement had no benefit? No, of course it doesn’t. There are people within that study who probably had very significant value because they had unique personal needs that were different [from] the group at large. But they were lost in the noise of the study design and the statistics, so the conclusion is [that] vitamin supplements don’t work. But for those people [who it] did work [for], it was hugely valuable. And people do not take vitamin supplements for the group; they take vitamin supplements for themselves.

We know that a great percentage of our population invests in life insurance. Of those people [who] invest in life insurance, how many people ultimately get value from the premiums that they have paid if they’re investing in term insurance? How many people actually use their benefits because they had something for which the insurance policy would have paid in a life insurance policy? The majority do not. Therefore, why do people invest in life insurance? Because they want the security of thinking [that] if they were one of those people [who] needed it, they would have it. And they’re willing to pay on that risk equation to have the backstop of they may be one of those in need. That relates to taking vitamin supplements because you don’t know unless you’re doing exhaustive functional testing and starting to look at your personalized nutritional needs, which fortunately, is starting to [be] much more readily available. But as an inexpensive, safe way of filling gaps for which you may not know exactly what your gaps are, it’s like an insurance policy.

So it’s the same logic. And you cannot get the answer to that by doing a large, population-based study to look for statistical significance. That’s an entirely different question for drugs alone. So to me, this argument continues to be fallacious about why dietary supplements are not valuable.

Chris Kresser:  Yeah, there’s so much to unpack there. I mean, as you said, from the beginning, the game is rigged against supplements in the way that those studies are designed. And for that matter, that’s also what makes it very difficult to study Functional Medicine interventions because the whole research paradigm is based on the concept of isolating the impact of a single variable. Whereas we acknowledge that [the] human body functions as a system. It’s closer to systems theory, and you’re looking at emergent properties across all these different interactions that can’t possibly be captured in [a] randomized, controlled trial study design.

Jeffrey Bland:  Yeah, and that’s why we’re starting to see studies like what are called n-of-1 studies, in which the person is the control to themself. And I think [that], as this technology is developed, this new study protocol, we’re starting to really see the validity for personalization. Now, a person might ask, “Well, why weren’t we doing n-of-1 studies before?” Because they’re actually more complex statistically to analyze than a group aggregate study. Now we have these new computer systems, informatics systems, that can analyze datasets that are much more complex to design answers than we did before. So now we’re starting to see, “Oh, my word, these n-of-1 studies where the person has their own internal control actually produce valid outcomes that are statistically significant.” It begs for personalization, which begs for the Functional Medicine model, basically. Treating each individual as they need.

Chris Kresser:  Absolutely. And even some of the studies that have compared Functional Medicine against standard care can be a useful model, as well. Going back to supplements, I saw those same studies, and they made my blood boil, as they often do. Some of the questions going through my mind were, “What were the doses of the supplements taken? What forms were the nutrients in? For example, was it folic acid, or folate? Or, was it methylcobalamin versus cyanocobalamin for [vitamin] B12? What were the blood levels of vitamin D attained?” In other words, if we know that someone was taking 400 IU of vitamin D, which is a pretty standard dose in a multivitamin, we don’t know anything about whether that actually raised their serum 25-[hydroxyvitamin] D level to the range that most researchers, like Dr. Holick and others who spent a lifetime studying vitamin D, suggest it should be. Which is, by the way, much higher than the lower end of the conventional lab range of 30 nanograms per deciliter in the [United States].

We could go on. But there’s so many questions that have to be asked about a study that shows that supplements were not effective. And I want to tie this together and use it as a segue to talking about immunity, because I know this is a topic you’re passionate about and have written about lately. One of my big disappointments in the last two years was exactly what you referred to in terms of the lack of acknowledgement of the role that nutrition plays in overall health, generally, [and] in immunity, specifically. We know from pioneering research from so many different clinicians that the body needs 40 micronutrients to function properly. Dr. Bruce Ames at UC Berkeley has done incredible research on what he calls triage theory, which states that if we get even a suboptimal amount of one particular nutrient, that can cause a whole cascade of reactions in the body that lead to problems over time. During the pandemic, I saw very little discussion, at least in mainstream media sources, on the role that nutrients play in immune health. I know this is something you’ve spoken a lot about, that nutrition is critical for immunity and overall health. So maybe we could start there as a segue of immune function. What are the most important nutrients for immunity? And why are they so important to our immune function?

Immune Health and Immuno-Rejuvenation

Jeffrey Bland:  Well, Chris, you’ve just crossed the rubicon here. This, to me, is where I’ve been led in the last five years of my life, professionally. I started asking more and more, “What are the ways that our body communicates 24/7/365 with the outside world that changes our inside function?” Because our genes are there to pick up information and translate that information into function. So I started asking, “What are the ways our body does that communication process?” And there are three places that our body is in direct contact with the outside world that makes information available to every cell in our body, all the time, every day, all of our life. Those are the nervous system, which most people are very familiar with, both the peripheral and central nervous systems. Secondly, our mucosal surfaces, like the linings of our lungs and our digestive system and our skin, [are] picking up information all the time from the environment. The third is our immune system. And of those three, the one that can change the most rapidly, in terms of its cellular architecture, turns out to be the immune system. People don’t recognize this, but we turn over our immune systems to new cells replacing old cells about every two to three months. Every minute of our life, we’re producing hundreds of thousands of new white blood cells. Our immune cells are being produced every minute. The question is, are those immune cells that are being produced the same as the ones that they’re going to take the place of? Are they better functioning, or are they worse functioning?

The powerful lesson that we’ve learned from immunology [in] the last decade is that our bodies are responding to how our immune system is functioning based upon the information that our immune system is getting through the way those cells are being produced out of the bone marrow and through our thymus gland, and so forth. So there’s a lot of variability in the education that our immune system is getting, based upon the signals that we’re sending it in a 24/7/365 lesson plan. Therefore, there’s a lot of opportunity for our immune system [to] either collect bad experiences that become debris, some people call these zombie cells, or they become aged cells that have bad experiences locked into them, so they become inflammation-type cells, or the alternative of that is cells that can be regenerated into a younger state. We call that immuno-rejuvenation. That dynamic process between the aging of the immune system and the rejuvenation of the immune system is going on in all of us, all the time. The problem is, right now, as a consequence of what we’re exposed to, how we eat, how we live, stress patterns, sleep patterns, [and] all the toxins that we’re exposed to, for many people, the bad experiences our immune systems are experiencing are collecting faster than the rejuvenation experiences.

That means our immune system gets senescent. It gets aged, and as it gets aged, it is less resilient and is more at battle with the body. It’s producing [more] inflammation. That’s called “inflammaging.” Therefore, our [actual] age may be less than the age of our immune system. We can be 30 years [old] and have an immune system functioning like a 60-year-old because it’s collected all these bad experiences [and] it can’t rejuvenate. To me, this construct today of how diet and lifestyle and environment impact our immune system function and resiliency, particularly now that we’ve gone through SARS-CoV-2 and seen how different cultures have responded to that virus based upon their immune system capability, we recognize how important that system is that signals to all other systems. Like the gut to the brain, the gut–immune system to the joints in arthritis, to the thyroid gland with [auto]immune thyroiditis, to the muscles with regard to fibromyalgia. All of these things become part of this immune system’s capability to rejuvenate itself and get rid of the damaged memories it’s had, the so-called immune scars, from past experiences and exposures.

Chris Kresser:  I love this conversation because it does a couple of things that I think are really important. Number one, it expands the understanding of what the immune system is. I think when a lot of people hear “immunity” or “immune system,” they think of defending against pathogens, like a virus or a [bacterium] or something like that. They may not understand inflammation, as you mentioned, as a core characteristic of immune function. If we were going to talk about inflammation, we’re really talking about that umbrella of the immune system. That’s what it falls under. Then, of course, diseases like cancer are essentially dysfunction of the immune system. Cancer is one of the leading causes of death, and it’s something that we still haven’t been able to get a handle on with modern medicine. This idea of a one-pill cure for cancer, despite a lot of years and a lot of research, hasn’t come about. And I think you’d probably agree [it’s] because we’re barking up the wrong tree there. We’re not really understanding the systems approach that you mentioned.

The second thing is, I love the distinction you’re making between immunosenescence, which is the aging of the immune system over time, and immuno-rejuvenation, which is the flip side of that, where we actually have an opportunity to rejuvenate and regenerate our immune system. There’s an analogy I like to use, which you basically just explained, of a bank account, where if you make a lot more withdrawals from your bank account than you do deposits, I think we all know where that’s going to end up. Not very well. And things like stress, poor diet, not getting enough sleep, and not getting enough physical activity are all withdrawals from the bank account. Things like eating a nutrient-dense diet, managing your stress, getting enough exercise, spending time outside, [and] smart supplementation are all deposits in the bank account. As you’ve studied immunity over the years, what are the biggest drivers in that process of contributing to immuno-rejuvenation and slowing down the process of immunosenescence?

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Discovery of Himalayan Tartary Buckwheat

Jeffrey Bland:  Yeah, so this has been a revelation for me. I started hanging out with immune scientists about six or seven years ago because I really wanted to know what they were studying and what kind of discoveries they were making. And there was a revolution in breakthroughs in making discoveries about the immune system. It’s similar to what was happening back in the early ‘80s with HIV [and] AIDS. That was another great period of learning a lot about the immune system. I wanted to keep abreast of what was going on, and in so doing, what I started to recognize is that these mechanisms by which the immune system can rejuvenate itself were being discovered. In fact, a Nobel Prize in medicine and physiology was awarded in 2013 for the discovery of one of the fundamental processes by which this occurs, which is called autophagy. Then it started to really gain even more traction as people started to look at the epigenetic impact on the immune system of being exposed to stress or being exposed to toxins or to poor-quality diets. These things would mark our immune system of our genes, and within the genes of our immune system, create alternative responses that become these inflammatory responses you’re talking about.

So, all this new discovery was starting to come about. Then it was an “a-ha” [moment] for me, because [as] Pasteur used to say, “Chance favors the prepared mind.” I was in the mode of really thinking about this, and then all of a sudden, I started having these coincidences. I’m not sure they were really coincidences, but they seemed like it. The first coincidence was [that] I met an investigator at Vanderbilt University Medical School who was doing some extraordinary work on treating high blood pressure through modification to the immune system. I’d never thought about how the immune system [could] be connected to blood pressure. He had discovered a molecule that could influence the immune system in such a way that it improved the way the immune system spoke to the vascular endothelium, the lining of the blood vessels, and it relaxed the blood vessels and lowered blood pressure. That molecule was called 2-hydroxybenzylamine. When I looked into that and spoke to him in greater length, I found out that he had [discovered] that there was only one place in nature, in one food, where that specific molecule was found. It was in an interesting plant that I was not familiar with at all called Himalayan Tartary buckwheat. I [knew] common buckwheat, but I didn’t know anything about Himalayan Tartary buckwheat, [which is] a different genetic form of it. So that was number one.

Then number two, I went to my colleague of 25 years, Trish Eury, and I said, “Trish, do you know anything about this Himalayan Tartary buckwheat?” She said, “No, I don’t. But I could maybe do some sleuthing on the web and see if I can find out more about it and who is growing it and so forth in the United States.” She was able to locate one, and only one, grower, Sam and Lucia Beer in upstate New York. A former Cornell University [agriculture] professor, now retired, and his [retired] nurse wife [who] had a hobby farm and were growing a few acres of this unique cultivar that they had gotten the seeds [of] from the USDA, and were doing it for fun. Then I just happened, at that same time, to take a trip to China. I had an invitation to speak to the Chinese Health Check Center annual meeting in Harbin, China, and my guide host there was a very interesting Chinese doctor trained in the United States. As we were taking the bullet train from Harbin to Shanghai, I asked him, “Do you know anything about Himalayan Tartary buckwheat?” And it was like the train had stopped and time was frozen. He said, “You’ve got to be kidding me. I have been wondering, my colleagues and I, if we could find someone in the United States that was interested in this particular plant and its immune-activating principles because we are the largest research group studying Himalayan Tartary buckwheat.”

So those three things all happened within a period of just a few weeks of one another. I then connected those things together. We now own organic farms in upstate New York that are producing the first organically certified Himalayan Tartary buckwheat, maybe in the world, but certainly in the United States. We have this collegial partnership with Sam Beer, who is now retired, and we’re collaborating in research with the Vanderbilt group on the immune effects of these plant bioactives. Therefore, what I came to recognize, and this was a big “a-ha” for me, was that we had forgotten [about] a very important family of immune active nutrients. We knew about vitamin C, we knew about vitamin D, we knew about zinc, we knew about glutamine. We had a whole arsenal of nutrients that we were familiar with that were immune important, vitamin E being in that, [too]. But what I did not recognize until we got into this work about three, four years ago [was] the important role that these plant phytochemicals have within the polyphenyl family or the flavonoid family. Specific members of that range of plant nutrients, [which] are often completely neglected in the traditional teaching of nutrition in standard textbooks, become extraordinarily important in how they signal the genes to activate these immune principles.

We’ve actually been studying the mechanisms of how they influence epigenetic regulation of the immune system. We’ve been looking at clinical human trials. We’re just finishing one up. It’s a [clinicaltrials.gov] approved study that we’ll have the results [from] in October, [and it’s a] human intervention trial. [We’re] looking at the repatterning of the immune system through these polyphenols that are found in these rich, phytochemical-dense foods like Himalayan Tartary buckwheat. This has been, to me, a major revolution in thinking. And I’ll just close because I know you’re going to follow on in this question, that what we recognize is that part of the effect is the direct effect of these polyphenols on [the] immune system. But then we ask, “Where is that immune system located that those things we eat in the diet can influence?” And it is in the gastrointestinal immune system, which is an intimate connection to the microbiome. So now, we’re brought into understanding the system. Diet, microbiome, gut–immune system function, polyphenols, and signaling to all other organs, like the brain, to the liver, to the endocrine glands. All these things are interconnected with regard to this new model that’s emerging around what I call immuno-rejuvenation. It’s a really fascinating time of discovery for the field, [and] I feel like it’s the next step for us in the Functional Medicine community.

Chris Kresser:  Yeah, I think this is fascinating as a microcosm into this larger discussion of what we’ve learned about nutrition and how it contributes to health, particularly [over] the last 20 to 30 years. You alluded to this, and I want to touch on it and come back to it, and then I want to expand a little bit on the [Himalayan] Tartary buckwheat, because I think it’s a really fascinating superfood that most people are not aware of. In the conventional nutrition understanding, we have essential vitamins and minerals. And that has a very specific meaning. It’s not just very important; “essential” in a nutritional context means that our body doesn’t synthesize those compounds and we need to get them from food. These are compounds that everybody’s familiar with, [like] iron and zinc, vitamin B12, [and] essential fatty acids like alpha-linolenic acid. And there’s a whole discussion about whether [eicosapentaenoic acid] (EPA) and [docosahexaenoic acid] (DHA) should be considered essential because many people can’t convert alpha-linolenic acid, but that’s sort of it. If you look at nutrient density studies and studies on what’s important, you’re going to mostly see reference to those essential compounds. And of course, they are very important. They are essential.

But I would say, and I know you would agree, that over the past 20 to 30 years, we’ve also seen the importance of these phytonutrients that you’re talking about. But there’s no real framework for understanding how important they are in our system because they don’t fall under that category of essential. Meaning, yes, we can live without them. We’re not going to die, [and] we’re probably not going to get scurvy or rickets or beriberi. But will we thrive? Will we have optimal health and longevity? Will we have optimal immune function? Probably not. What do you think about that? Should we be creating a new category or some way of understanding the importance of these phytonutrients? Because it seems to me that we don’t really have a bucket or a framework for emphasizing their importance at this point.

Drivers of Immuno-Rejuvenation

Jeffrey Bland:  Oh, Chris, I think that is really insightful. I want to really give you a stroke. I think that the way you contextualized that and said it is really the enigma and the challenge [that] we have today. I want to come back to your point about the word essential because words can be very important, obviously. Essential, in the context as you were describing in nutrition, has always meant [that] if you take them out of the diet, you will see some untoward pathology result. Something that will be identified as an illness downstream. If you recontextualize the word essential to tie to function [rather than] to pathology, suddenly, a new context for the word essential starts to emerge. What have we learned about phytochemicals? Well, we’ve learned that their role in human physiology is that they modify how our genes are expressed, how our book of life is read. Therefore, they pattern over time how our genes will be constructed into how we look, act, and feel in ways that are different than essential meaning the absence of a disease. It is the presence of resilience, the presence of function, the presence of ability to accommodate change [and] stress in our lives. So there is, as you’re alluding to, a need for us to rethink through what the term essential really means and what the role that these phytochemicals play in ultimate, high-level wellness and living a century of high-level living.

Now, let me say something quickly about that because I think it’s very important to see how, in the science of these phytochemicals, its language has emerged. When I first started studying flavonoids, which would be about, I don’t know, nearly 40 years ago probably, their construct was that they were antioxidants. We actually developed in food science ways of studying indirectly the antioxidant capability using things like the ORAC test, the oxygen reducing absorbance. We would evaluate the antioxidant capabilities based upon this study. We’d say, “Oh, this food has a higher ORAC value than this food. So that means it has higher antioxidant capability.” The whole thing around phytochemicals throughout much of the history that I’m aware of was antioxidants. Now, I’m not saying antioxidants are not valuable; I’m not saying that term is passe. I’m saying that’s not what we now recognize as the central tip of the spear as to how these phytochemicals work. They really work as modulators of gene expression.

They modulate through a process that is much more specific than just their antioxidant properties. That’s why the antioxidant phytochemicals that come from cruciferous vegetables like broccoli, cauliflower, Brussels sprouts, and cabbage have a different effect on the body than the antioxidant phytochemicals that come from apples and berries and whole grains. They have different effects [in] the way that they speak to the genes to create [an] outcome, [which] in terms of the case we’re speaking to here, [is] immune function. We have moved from a generalized concept to a much more precision concept as to the role of these various families of phytochemicals. This is a major step forward, by the way, in the personalization and precision of Functional Medicine. Now we don’t just say, “Eat foods of the rainbow.” That’s good. Different colored foods in their natural state have different kinds of phytochemicals in them. That’s a good first step. But now we might say in nutritional therapy that we need to ask what phytochemicals are going to impact the value in that individual, based on their genetic need, that will give the best outcome in things like autoimmune disease, chronic inflammatory bowel disease, metabolic syndrome, the list can go on and on. That’s really [the] next step forward that we’re so excited about because we’re improving the precision as to how to personalize these programs for need.

Chris Kresser:  That makes perfect sense. I would say, I think context makes a big difference here. Maybe a hundred years ago, when the biggest problem we were facing was still malnutrition, even in lots of parts of the developed world, it made sense to focus on essential vitamins and minerals, which prevent those acute diseases of malnutrition, like rickets, scurvy, beriberi, etc. Of course, there are still many parts of the world where malnutrition is a significant threat, and that should remain the major focus. In the developed world, many people are meeting their basic nutrition needs, although I think [we understand that] some [of] those needs are out of date now. The amount of a nutrient that’s actually needed for optimal function is higher, I think, than the typical [Recommended Dietary Allowance] (RDA) reference range would suggest. But what you’re speaking to is that, yes, even for those of us who are meeting our basic needs and avoiding those acute diseases of malnutrition, that’s not really the main issue anymore. The main issue is how we’re dealing with these constant threats that we face living in the modern world, [like] exposure to a growing number of environmental toxins, lack of sleep, chronic, unrelenting stress, and things that disrupt the gut microbiome like antibiotics, poor diet, and other medications. Those are really the challenges that most of us face today, and all of those issues contribute to chronic diseases, which now comprise seven of the 10 top causes of death.

Most of us are not dying from pneumonia or tuberculosis anymore, as we were at the turn of the 20th century. We’re dying from heart disease, diabetes, cancer, Alzheimer’s [disease], [and] dementia. These are the diseases of civilization. And phytonutrients, because of their role in regulating epigenetics, seem to be at least as important, if not more so, to those of us living in the modern world than, well, maybe not more important than essential nutrients, but at the same level of importance for sure.

Jeffrey Bland:  I think you just gave a summary to what takes me hours to describe. You did a beautiful job of summarizing it in very quick bullet points. I think this distills down, for me and our group that’s been pretty heavily immersed in this through our Big Bold Health activities, into three pillars. Three therapeutic categories, in terms of nutrition, for this rejuvenation of the immune system. We’ve talked a lot about one, which [is] the flavonoid polyphenol family of phytochemicals. That’s things like quercetin, luteolin, hesperetin, [and] rutin. Members of that family have all been found to be extraordinarily valuable for activating this process of immuno-rejuvenation. By the way, those are coincidentally some of the highest phytochemicals in Himalayan Tartary buckwheat. In fact, Himalayan Tartary buckwheat has 50 to 100 times higher levels of that. That wasn’t percent; that was times. Fifty to a hundred timeshigher levels than any other plant food. So it’s a really remarkable immune-active plant food relative to that family of nutrients.

The second one you’ve also mentioned, which are the essential fatty acids, or the omega-3 fatty acid family. You have EPA, DHA, [docosapentaenoic acid] (DPA), and you also [now] have [these] emerging other members of that family, the so-called pro-resolving mediators, or PRMs, that are found in minimally processed oil products [and] have very active resolving capability for inflammation. The 14, 17, and 15 pro-resolving mediator compounds that are found in minimally processed oils deliver enhanced immune resolving capability.

So I’ve first talked about the flavonoids and the polyphenols, second about the omega-3s, and the third are the pre- and probiotics. These all work together to give resilience to where 78 percent of our immune system is clustered around the gut. Our microbiome’s integrity. A friendly microbiome becomes an extraordinarily important component of rejeuvenating our immune system. So pre- and probiotics [are] one pillar, omega-3 fatty acids [are] another pillar, and the polyphenols [are] the third pillar that comes together to be the amino rejuvenation program. That’s how we would actually approach that as a dietary intervention program.

Chris Kresser:  Just fantastic. I’m such a big believer in superfoods and the role that they can play in optimizing our health and well-being. In a perfect world, and maybe the world that our ancestors lived in many, many years ago, we could get everything we needed just from consuming our regular nutrient-dense diet. But I no longer believe that’s possible for the vast majority of us. Just through my clinical experience, literally testing every patient that has walked through my door in 15 years for nutrient deficiencies, I can remember maybe 10 people in that time who didn’t have nutrient deficiency. [With] all the challenges we’ve talked about that we face in the modern world today, I think we need these kinds of foods like the [Himalayan] Tartary buckwheat that Big Bold Health has introduced to really give us some insulation, if you will, against all the challenges that we face today. I’ve often said the modern world is in many ways antithetical to health, and I wish that were not the case. I wish that the world that we lived in was more conducive to our health and well-being. But speaking personally, I’m approaching 50, [and] I want the next 50 years of my life to be even better than the first [50 years]. I actually believe that’s possible, and I’m going to take every step that I can to ensure that outcome.

A lot of that involves maximizing my intake of not just essential nutrients, but phytonutrients, essential fatty acids, and pro- and prebiotics, as you mentioned. So I’m really fascinated by the [Himalayan] Tartary buckwheat. I’m super excited that you brought this to market and made it available for everyone. Like you said, it’s packed with these phytonutrients, with Hobamine, D-chiro-inositol, prebiotic fibers, lots of essential vitamins and minerals, and I can’t wait for people to try this. So where can people learn a little bit more about this, Dr. Bland, and then if they’re interested in following you and your work, where’s the best place to do that?

Jeffrey Bland:  Well, thank you. By the way, Hobamine is the trade name for the 2-hydroxybenzylamine that I talked about, that [I learned about from] the investigator [at] Vanderbilt [University Medical School]. So it’s all part of this system. And we have done, I think, a pretty good job. It’s obviously been accelerated through the SARS-CoV-2 explosion of information about immunity to get that material up on our website, which is BigBoldHealth.com. You can find a treasure trove of information about this whole thing I’ve been speaking to. The excitement for me is this organization that we put together 10 years ago called the Personalized Lifestyle Medicine Institute that is kind of the companion organization to the Institute for Functional Medicine.

On its website, it has all sorts of free available educational programs around this whole explosion of information. So that’s PLM Institute, PLMinstitute.org, you can find that. And then lastly, if you’re interested in tracking what Jeff Bland is doing, where his travels take him, and what he’s doing in terms of talking to people in the field, JeffreyBland.com. But I really encourage people to go to our Big Bold Health website. I think you’ll find a lot of very interesting news to use there as it relates to this explosion about immuno-rejuvenation. I just had my 76th birthday about a half a year ago, so, for me, it becomes ever more important, obviously, this whole immune rejuvenation and resilience program. I’m pretty committed to our program, staying on it myself. I’m my own n-of-1 experiment. All of this is part of us moving forward and learning how we can have a hundred years at least of good living. That’s the objective.

Chris Kresser:  Absolutely. Dr. Bland, it’s been an honor and a privilege to have you on the show. [I] want to thank you again for all the work you’ve done in this field. I really enjoyed this conversation and hope to have you back on the show again in the future.

Jeffrey Bland:  Well, I extend it right back to you, Chris. You’re doing a magnificent job of spreading really important information that can be health-changing for all the people [who] are following you. So keep up the great work. I’m very privileged to be part of the community that we’re all sharing.

Chris Kresser:  Thanks, everybody, for listening. Keep sending your questions to ChrisKresser.com/podcastquestion. Thank you.

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