How you age and how you can age well

How you age and how you can age well, with Dr. Kara Fitzgerald

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Meet Dr. Kara Fitzgerald. With her pioneering work around biological clocks and the concept of a Methylation Diet, Dr. Fitzgerald works on the cutting-edge of longevity. This is a conversation for anyone who cares about aging well.

This podcast is for educational purposes only. It is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services.

Transcript

Dr. Jeff Bland:
Well, welcome to this extraordinary conversation with the Big Bold Immunity Podcast. And in each of these episodes, I have the chance for exploration with individuals that are life changing for me. It’s a little bit of a very maybe selfish thing that I have the fortune of bringing people that I really consider to be extraordinary guides, and thought leaders, and that have changed my thinking. And hopefully, I can share those with you and they can be powerful ways for you to rethink certain things. And so this podcast with Dr. Kara Fitzgerald is one of those epic moments. It’s an epic moment because of her leadership in the field. It’s an epic moment because of the years that I’ve had the pleasure of knowing her as she traveled in her journey, as we are all on our separate journeys.

Her journey starting really through health sciences into her naturopathic degree at Western States in Portland, Oregon, and ultimately into a postdoctoral work with Genova Labs, and Metametrix, and Dr. Richard Lord, arguably one of the top people in metabolic medicine in our field. And then on into authorship, and research and development in clinical practice, and ultimately, then, her path took her into wanting to advance into the research clinical area, in an area that she alone was really starting to pioneer. And that is you’re going to hear more about it, but I’ll just summarize it by saying, how do we really understand, at a molecular reproducible level, how people age? And how does that relate to biological function of those individuals, so that there’s a difference between the age they have in birthdays and the age of their biological system, which we call biological age? And how would we quantify the difference? Most of us would like to think that our age in birthdays would be greater than the age of our biology. We like to be younger than that of which our birthdays would tell us.

And Dr. Fitzgerald has been on that quest and that understanding through the principles of lifestyle medicine, functional medicine, integrated medicine, natural medicine, all these concepts that we’ve heard about, but maybe they appear a little squishy. We don’t have the quantification and the precision to really understand exactly how they all fit together, but she undertook this process and this thought process in a way that I would call expansive, courageous, probably against other people’s recommendation because they would say, “Oh, that’s not going to work. It’s way too problematic,” but always look to the people who can do the impossible to see how you’re going to carve out new ground. And that’s what we see with Dr. Fitzgerald. So Kara, welcome to the Big Immunity Podcast, and thank you so much for both who you are, what you’re doing, and for being present. So maybe we should just start with me giving you the opportunity to say a little bit about how your journey, now through your eyes and experience, has resulted in what now we’re going to talk about.

Dr. Kara Fitzgerald:
What an honor. And just thank you for that introduction. And God, it’s so nuanced and you getting it right down to some of the forces against us doing this study, or challenging us in our study design, and so forth. And I if it wasn’t for you, your constant reassuring, calming voice of reason and unwavering face in what we were doing, who knows if we would’ve buckled at some point? And because as benign as it seems at a glance that we’re researching a very safe diet and lifestyle intervention, I can see, in hindsight, how radical it was. And I always want to give credit where credit is due and thank the foresight of Brent Eck, the CEO at Metagenics, for being willing to grant us the unrestricted funding to answer this question, to embark this journey. And I have deep, deep, deep gratitude. So I think there’s an alchemy of a handful of events going back to choosing to become a naturopathic physician and being exposed to nutrition, nutritional biochemistry, just a different lens, a systems lens in looking at physiology and how we address it.

And concurrent to that, of course, becoming aware of your work and seeing you speak because you’re right there in the Pacific Northwest, so I had access to steep in what you were thinking about then. And of course, it’s always rooted in nutritional biochemistry. And I was enthralled with that, in thinking mechanistically about what it was we were doing and influencing physiology, and pathways, and so on, and so forth. And so that catapulted me into being able to do this amazing postdoc in a lab and continue to further that thinking. Of course, we were moving into the omics revolution where we were looking at the genome was mapped, and we were looking at organic acids, and proteins, and fatty acids, and so forth. So we were really dancing in a broad investigation of higher throughput technology, getting to look at a lot of stuff. And you’ve always been at that interface of translating science and for clinical application. And we’ve been sitting at having access to some of these bigger technologies, like the epigenetics investigation that I just undertook.

So I think… And you’ve been mentoring me all along, so I think it’s just this gift that I was in a position to ask the questions. My training led me to think about, what are we doing to the epigenome? So what are our interventions doing? And it was clear to me that… And so we’ve been talking about it for a long time. This is nutrigenomic medicine. Of course, we’re influencing genetic expression. I think we’ve been pretty confident, but there comes a time when you actually have to say, “Are you? Are we actually doing it?” And we needed to wait for that technology to be available. My entry into seeing it as very important was probably, in epigenetics, was probably 2013 when I finally… I want to be honest and say I had some resistance to reading the epigenetic literature because it’s complicated. You know that cartoon, just say it’s too complicated, say it’s epigenetics. It is like a whole new science. It is an entirely new paradigm. And I was tucked into my own model, and into my own thinking, and into my clinical practice, and so on, and so forth.

And to ingest this new, really revolutionary way of thinking about medicine, it felt a little bit overwhelming. And yet, I knew. I knew it was important, and so I made myself hunker down with papers back then. And a lot of them, the best science was really coming out, looking at cancer. And we know that cancer, the tumor microenvironment, very efficiently hijacks the epigenetic machinery and directs gene expression towards its own nefarious end. And we can see… So the area that I was interested in specifically was DNA methylation for a variety of reasons. It’s certainly one of the best studied of all of the epigenetic works, and these are the biochemical processes that direct genetic expressions. So we’ve got 23,000 genes. We’ve got a simple genome as humans. Very simple. And then you look at genetic regulation and that’s really where the rubber meets the road and it’s as complex as our genome is simple, but of the myriad ways in which we express our genes, probably the best researched, and really, arguably one of the strongest, I think, because we see that it’s heritable, is DNA methylation.

And very simply, it’s methyl groups placed on certain regions of the DNA. And when there are quite a few methyl groups on a promoter region, that gene is generally inhibited. When those methyl groups are removed, as they can be, or they’re inhibited from being placed, that gene can be on. So simply, lots of methyl groups, gene is off. Less methyl groups, gene can be turned on. And so the earlier science was in cancer and we could see that cancer could turn off all important tumor suppressor genes and turn on, which would protect us from getting cancer, so they would turn the genes off and then they turn on oncogenes. So they remove the methyl groups from these genes that promote cancer, and to this, in this way, they drive cancer forward. And we know from research henceforth that epigenetics are incredibly important and an area of not only diagnosing cancer, as with the GRAIL assay, but how we address cancer. So we know this hyper/hypomethylation pattern happening in the DNA is extremely important.

So as I was reading this, Jeff, you can imagine, I was stopped in my tracks. We talked about this back then. What are our interventions doing? How are we influencing this aberrant, this imbalanced, methylation pattern? And so that was the first piece that stopped me. Do we always want to supplement with extra B vitamins, and folate, and B12? And would that be contraindicated in any case? And so we started to have questions here in my clinic. And fortunately, I’ve just got an extraordinarily bright team here of physicians, MDs, NDs, as well as a nutritionist. And my partner, Romilly Hodges and I, she’s the director emeritus, but she was the director of our nutrition programs back then, decided that we would create a food forward plan, actually a food plus diet and lifestyle, to attempt to balance DNA methylation, as radical as that was. And we ended up publishing, put an e-book out as to our rationale behind it and how we set about doing it.

We incorporated it into clinical practice right away and we saw great results. People would feel better. It’s a smart dietary pattern. We’ll talk a little bit about some of the ways that it’s different than other dietary prescriptions, but we saw people get better. We saw homocysteine drop without B vitamins and so forth. And people felt good. But of course, the lingering question is, are we actually influencing genetic expression? Are we doing what we want to be able to do? And as we scratched our heads on being able to research it, we could do a subjective symptom questionnaire, we could measure homocysteine, et cetera, everything was lacking. We needed to look at genetic expression if we were going to demonstrate whether or not our hypotheses had any validity. And that’s when Brent Eck came in and agreed to sponsor the investigation. Now, I want to say, where does biological aging come into this? Can I make that comment? Or should I keep going? Or do you want to make any comments?

Dr. Jeff Bland:
Yeah. Let me take a break just for a second then, so you can oxygenate those frontal lobes because we’re going to have another run at it here. But I want the people that are fortunate to experience what you just said to take a pause and ask the question, what is it that is within the human spirit that creates our ability to do something great? Because that potential resides in all of us. How does that actually happen? And how does a person go from a state of inquiry to a state of becoming an expert? What are the driving forces that create that? And if, in fact, our genes are to be capable of expressing the full potential that we inherited through those 23 pairs of chromosomes, how do we squeeze out the maximum value? And you just gave a classic example of how that occurs in a person’s life. This isn’t abstract. It’s not some hairy fairy blue sky thing. This is real person living a real life who has then created an impetus in their need to know that, finds solutions to problems that maybe at first level, would’ve seemed maybe impossible, or overwhelming, or gee, I don’t even think I want to try this because there are too many barriers in box in the road and I’d like to take a different path.

It’s easier. I don’t believe that, probably, ever in this process that you just described and the oratory eloquence in which you described your own learning in ways that is deep and wide, that you ever really felt that there are insurmountable barriers to you learning this information and gaining some ability to ultimately help people. That was a driving force. And I think that that power, that energy resides in all of us at some level. It doesn’t always have to be on epigenetics. It can be anything. Anything a person then sees in their life as a need to know that is so powerful that it goes to sleep with them, they awake with them. As Salinger said in Franny and Zooey, with every beat of their heart, it becomes part of their being. And that is the Dr. Fitzgerald I’ve known and had the pleasure of knowing as I’ve watched you mature and develop your career in that you’ve been a model. Not just a model as a woman, but as a model as a person in our field that is establishing a tone of excellence in your pursuit because there’s always the chance along the road that you’ll end up in blind alleys, and then you have to find a way out of those blind alleys.

It’s a natural process through discovery that you’re going to end up in places that you got to back out of and find a new place. And you’ve just described, it sounds like, a smooth process. It was not a smooth process of your own education, or the pursuit of your research, or the ultimate oversight of how that was conducted, and the final assembly of the data, and being the person to be a principal author on the first study ever published showing how nutrition and diet in lifestyle influences the epigenetic aging of cells. That, to me, is a success story that models across all sorts of other applications, not just this one, singular endeavor. So I just want to take a moment to acknowledge that because often in our life, we all need champions upon which we can model ourselves. And you are one of those, and your colleagues. I know you would say you didn’t do this all by yourself, but someone has to lead the band and you certainly have. So I just want to take a breath, oxygenate our neurons, and acknowledge that.

Now, for those individuals who maybe got lost in a lot of the very, very eloquent and complicated discussion you just shared with us, there was out of density of materials, it reminded me of Jeff Bland on steroids, the way you were describing that, that this concept of epigenetics, just to remind people, was resisted for years as a feature of importance in anything other than developing embryos, and because it sounded a little bit like what we were saying is that a person could adapt to their environment. And adaptation to an environment was stricken from all medical health sciences curriculum. It was all around natural selection, Darwinian natural selection. There was no such thing as adaptation. Now, suddenly, we have reintroduced the concept that there are these different tuning knobs. There’s a course tuning knob that’s genetic selection, and there’s a fine tuning knob that’s epigenetic modeling.

And this has come to life, and now it’s being seen as a major driver for how every person changes their architecture in the way their genes are expressed as they age, depending upon the experiences that they’ve had in their life, including things like post-traumatic stress syndrome, or exposure to chemical pollutants, or all these variables that imprint our genes. So I just want to acknowledge that what you’ve just described is a paradigm shift of epic proportions that, quite honestly, changed the whole of healthcare in the 21st century. And I authored an article on this not too long ago, saying that, if we were to categorize all the discoveries that have been made over the last 100 years, this concept of epigenomic patterning through intervention by exposure to the environment is a major agent of change that will ultimately change all the way we see healthcare. So that’s a pretty big deal, and you were right at the forefront of that. Now, I’ll turn it back over to you to talk about the study and this extraordinary work.

Dr. Kara Fitzgerald:
Thank you. God, that’s very, very, very meaningful to me. I’m glad that my camera’s a little blurry because I’m tearing up with what you’ve said. I just want to… I don’t want to talk about it too much because then I won’t be able to continue to dialogue, I’ll be so teared up. But I’ve just had very important humans, including you, walking with me saying, “Yes.” Just saying yes to me. That thought is a good thought. That’s a reasonable thought. Continue on that trajectory. I had such a good relationship with Richard Lord, my mentor and postdoc advisor. He would ask me… Well, he always needed to get me out of his office. I’ll say that because we were in there dialoguing and he couldn’t get anything done, and so he would send me off with almost like a biochemistry assignment. It would be a challenging question like, what is the amino acid that sits in the aconitase, at the center of the aconitase, the catalytic center of the aconitase enzyme? And why is that amino acid there? And then he would shut his door. And that would take me a long time to actually figure that out. And of course, it was cysteine, it was a sulfur amino acid, and that’s because it could complex with the iron, and blah, blah, blah. And I got it wrong. I actually said histidine. And I think that that’s why it’s with me now as strongly as it is because I got it wrong. But to have people in my universe who are bright, big thinkers encouraging me consistently to continue to think. And the other thing that Richard told us often was to embrace the uncertainty. And so there’s some value in… That’s one of the most sage pieces of advice I’ve gotten. If you can sit with the uncertainty, there’s so much possibility in that.

And perhaps, that really informed my ability to move forward with this question. And the other thing he said to me that was extremely important, and I continue to share that with the folks that I mentor, is that if you train your eyes, you’ll see the way before you, but there’s a lot of opportunity, but there’s a lot of low hanging fruit. We have access in our field still. Our field’s not so big that you don’t get to speak directly with or connect with big thinkers in our field. And there is much opportunity and much to do. And I believe that my foundation, both intellectually, with the intellectual rigor that I was exposed to, and the support and the belief, really put forth this possibility. And there’s just no question that you’ve been a big piece of that for me throughout my career. Okay.

Dr. Jeff Bland:
Okay. So let me then just quickly respond by saying, what you’ve done is then to share this wisdom that you’ve accrued through all these efforts and these associations, you’re forming a younger universe of collaborative thinkers. This is how we spread ideas. Ideas grow geometrically. They’re like a virus in the nervous systems. And they ultimately serve the test of time when people feel that they’re of value enough that they tell them to somebody else. And that’s what great ideas do. No one owns ideas. Ideas are free to change the universe by testing the great cauldron of human society. And that’s what you’re doing. You’re collecting together like minds to move forward this concept.

And I want to say this concept is extraordinarily powerful because if you believe that societies change on belief systems of the aggregated, then what we can say about this is that if people believe that how they think, act, and behave marks their genes with messages that create their outcome as human beings, how they see their lives. Is it a happy life? Is it a fulfilled life? Is it a life of peace? Is it a life of grace? Or is it a life in terror, in fear, in harm, in hostility, in war? Those are all available accessed emotions within the human nervous system that get partitioned based upon the experiences that we have that start with our inquiry of how we as human beings live in the world about us. And so this epigenetic principle is not just a younger you. It is a resilient you. It is a resilient related to your connection to others. It is a communication of, I can be better because my genes will serve me better if I treat them right. That is a powerful concept. And you’re-

Dr. Kara Fitzgerald:
It’s very powerful.

Dr. Jeff Bland:
You’re building that concept through the studies that you’re doing at basic science.

Dr. Kara Fitzgerald:
Thank you. Thank you. I have to say, I’m curious about, I would love to have Siddhartha Mukherjee come back to a PLMI and talk to him about this because I know he has to embrace it as a big thinker, but he’s also challenged the power of epigenetics as well. So just note to you, Dr. Bland, maybe Dr. Mukherjee could come back.

Dr. Jeff Bland:
Yes.

Dr. Kara Fitzgerald:
I think it would be great to talk to him. So to move to biological aging, so I want to say a couple things. So my entry into really thinking strongly about epigenetics, and translating it into this diet and lifestyle program, and starting to think about it in clinical practice was through the lens of cancer, but one of the things that we know about biological aging is that it is the number one risk factor, or we can just say aging, more broadly, for all the chronic diseases, including cancer, and heart disease, and diabetes, and autoimmune disease, and even infectious disease like COVID. So aging itself is… Well, it’s been posited that maybe aging itself is a disease, but it’s certainly the number one risk factor for all of these. So we started over here thinking about cancer, but what we ended up uncovering, a huge a-ha for me, that I actually talk about in the book that’s coming out in January, where I outline this trajectory, is that changes to epigenetics, in particular, DNA methylation is where I put my focus, are really shared across these chronic diseases.

So if you look at the changes that drive aging forward on the epigenome, they’re the same that move cancer forward. They’re the same that move cardiovascular disease forward, or immune system degeneration, deterioration, stem cell changes. The stem cell microenvironment of an older individual doesn’t look that dissimilar from cancer. It’s crazy. It’s really extraordinary. And so we realized that we may be changing the aging journey itself with this intervention, so that was the huge a-ha for us and the first question we really set out to answer. So we saw that our participants did well on the study. It’s an eight-week intervention, again, diet, exercise, a meditation prescription, sleep, hygiene, encouragement to get at least seven hours, we did a greens powder, and we had a probiotic (Lactobacillus planetarium), but the first thing we looked at when we unpacked our DNA methylation data was whether or not we influenced biological age because that underpins really everything else. And I was confident, Jeff, that we shifted epigenetics.

My read on the literature was things can change quickly, even though I was challenged. People certainly challenged our duration of our study and thought we should have done it for six months, but try to do a new nutrition and lifestyle intervention on any human for six months. We would lose them. So these are scientists talking, people without clinic experience. And they’re coming from a different vantage point. As a clinician, I knew eight weeks was really the far end of time we were going to get people to adhere and we wanted them to adhere. We actually had nutritionists tracking with them, supporting them in their adherence journey because it was very important. But the first question we unpacked was, did we influence biological aging? Because if we did, then these other questions, the suggested answer is that we’re reducing their risk of all chronic diseases. So it was hugely exciting when we saw that we changed it profoundly at that time, when we crunched our data in 2019. So as compared to our control group, our subjects got 3.24 years younger as compared our control group.

I remember talking to Brent about it, and it was at night, and I was pacing back and forth, and it was a mic drop. It was a phone drop moment. It was very, very powerful. And telling you and just being up at McGill University with Moshe Szyf, who is, again, a huge supporter of our work, and has walked with us closely on this journey. And I met him through you. I met him at PLMI and he’s one of our authors. And anyway, it was just a spine tingling, extraordinary moment to see that we had done that with the then main biological age clock, the Horvath 2013 clock. So it was one of the first biological age clocks in our pattern clearly suggested that these folks got over three years younger in just eight weeks. Well, even to this day, we’re only in 2021, but that study hasn’t been repeated, nor have we really seen… Our study had a control group, which is unique. This is a new field, and so we were first for a lot of things, but including having a randomized control trial. I just want to stop and see if you’ve got any comments before I continue.

Dr. Jeff Bland:
Well, my only comment of course is yahoo. And I think that it’s very important for those individuals who may not be so steeped in some of this science jargon to know that your book, Younger You: Reversing Your Bio Age really demythologizes a lot of this and makes it consumer friendly. And that comes out in January, so I think that’s going to be a great tool for people who maybe a little bit geeky, but not maybe as steeped in some of the deep science that we’re discussing right now. So I think the book is going to make a significant contribution to spreading this message and giving news to use that people can apply. The other thing that I think is really important is when you look at your diet construction, you might want to just comment on how you were designing the diet relative to certain foods that had certain principles that were at least implicated as having epigenetic influences.

Dr. Kara Fitzgerald:
Yes. So we really hedged our bets that if we work, if we design a diet to optimize DNA methylation expression that we were getting to root cause, in 2017 that wasn’t quite as conclusive as it is now, but we knew that, in general, it was a healthy eating pattern, but we wanted to load it up with nutrients that help with DNA methylation, so they’re methyl donor nutrients. These are nutrients like leafy greens, seeds, pumpkin seeds, sunflower seeds, sesame seeds, some nuts, betaine from beets, so beets are important. Choline helps in methylation and that comes from eggs, so that’s one of the reasons eggs are so good for us. And liver. The often maligned is a beautiful multivitamin in a food matrix. Our read on the literature is that is delivering things in a food matrix, delivering these nutrients in a whole food matrix, yields more bang for our buck for a variety of reasons, not just because it’s so of safe to do this, but the synergistic interaction among nutrients just helped transform their behavior in the body and their ability to influence genetic expression. And I know you’ll have thoughts on that.

So our diet was packed with these methyl donors to move methylation forward. But if you recall, from my comment on cancer, we don’t want to push methylation too far forward. There is hypermethylation that can be negative, and so we needed to be mindful about that. We wanted balanced methylation, and so preliminary research, again, at the time, a lot of it was in vitro. So in cell studies or animal studies suggested that polyphenols, so the colors, the nutrients we find in fruits and vegetables, good examples include curcumin, and turmeric, or EGCG in green tea, or quercetin, and rutin, and the beautiful packed polyphenols of Himalayan Tartary in buckwheat. I just am so excited to see what Himalayan Tartary buckwheat actually does to the epigenome because it’s an extraordinary nutrient, really, almost on par with what I just described liver to be. It’s just so packed with so many important nutrients, but the research on these guys suggest that they maybe direct how methylation happens. That it’s happening on the right gene. And I’m extrapolating somewhat. Research in vitro research has shown that these beautiful polyphenols help turn on genes we want on. And in some cases, there’s less research here, but help turn off genes we don’t want on, but to keep expression going of those all important tumor suppressor genes to protect us against cancer and so forth. We see polyphenols are very important here. And we know from their time immemorial use, curcumin and green tea, for example, that they are all important anti-cancer molecules, and it probably has to do, I would say, in significant part, with their ability to help regulate genetic expression. So we wanted our diet absolutely drenched, as much as possible, in these all important polyphenol compounds. And to that end, our participants had at least seven cups of fruits and veggies a day, with extra for bonus points if they wanted them. And then additionally… Yeah. Right. And additionally, we gave them the greens powder. So I just… And oh, let me make one comment. So in our data, it does suggest that we found that because our participants got biologically younger, as measured by DNA methylation, it looks like there was a rearrangement of how methylation was happening towards a more favorable pattern. So we didn’t push net methylation higher on the genome, we rearranged it. And I would argue that that suggests exactly what we speculated.

Dr. Jeff Bland:
Well, I think that you said so many things there that are just like, wow, we could go on a riff here playing in B flat for many, many bars because there is a tremendous amount of density in what you said. But one that I want to stop for a moment, because I think that… And this is a shame on me. So I’m acknowledging a mea culpa here that 10 or so years ago, when we first started really talking about methylation as a process that regulated gene expression, I was a pretty strong believer that this process was regulated principally through the folate methyltransferase pathway, and that we really, the regulation points, the pinch points could be related to factors that influence, directly, the metabolism through the folate cycle into the principal methylating downstream component of that network. And I do believe that’s still important, so I don’t want to discount that and throw the baby out the bath water.

But I think what you’ve said is really the frontier of what we have learned over those last 10 years, and that is upstream to that are the regulators that maybe these specific polyphenols have, based on their structure, function relationships with certain cell signaling processes that regulate the gene expression or the activity of enzymes that are involved with the architecture of where methyl groups are to be put. And so it’s really who organizes how methylation is going to occur? And then do we have the available methyls to go where you need them to go? So it’s a combination of those two factors. And then we add to that, of course, the discoveries that are now with the microbiome, where we say, but when we eat stuff, that stuff doesn’t go directly into our bloodstream.

It has an effect by its metabolic influence by gut microbes that then influence our gut immune system, that then influence factors related to… And so it’s a much more complex orchestrated web. And that’s why what you said about food based delivery systems, versus one nutrient at a time, because it’s an orchestral process. It’s not like the best first violinist playing by themselves. So there’s so many any takeaways from your study. And I know you’ve read that… Because I’ve had the privilege of reading a preprint version of your book, you’ve really discussed this beautifully in the new book coming out on the first of the year. So all of this is made user friendly in a way that we start accessing this extraordinary new science that you’re discovering.

Dr. Kara Fitzgerald:
Thank you. It’s so exciting. And I want to say, so you and I have dialogued about, say, the NU-AGE trial. There are studies looking at nutrition and they’re very, very important, looking at how nutrition influences the epigenome and it is favorable. The volume is not quite as turned up as we saw with our study, so using a Mediterranean eating pattern is favorable on epigenetic expression. I do not… It seems pretty unequivocal at this point, and I’m sure we’ll have more and more research as time moves on, but I’m excited to see that our design, which has Mediterranean components, but really thinks about what the methyl donors are the all important polyphenol epinutrients, which we call methyl donor adaptogens, how they are influencing. And we turn those volumes up, perhaps beyond a typical Mediterranean diet pattern. I also want to throw one other thing out there because I’m with you in being very educated on the methylation cycle and the folate vitame cycle. And thinking there, I think it’s been a little bit myopic and we are blowing out.

So we had lifestyle components, meditation twice daily, sleep, and exercise. Exercise behaves, folks, this is going to sound crazy, like a polyphenol. There’s a fabulous study that I wrote about in the book where it talks about exercise influencing tumor suppressor genes, allowing them to get turned back on, like we see some of these beautiful polyphenols doing as well. And actually there’s a heritability component. We can hand the benefits of our hard work, of our getting on that Peloton every day, or you going out in Bainbridge, your beautiful neck of the woods, but those hard efforts, if we’re preconception, we can hand some of those patterns down. It’s amazing. So exercise, correct exercise, not get up off the couch and start CrossFit-ing tomorrow, but balanced exercise is remarkably epigenetically potent. And it addresses DNA methylation. And it is not in the DNA… It’s not in the methylation cycle. Likewise with stress. What blew my mind, Jeff, is how 25…

So the clock that we looked at, a full 25% of those methylation sites that are measured are influenced by the glucocorticoids. They’re influenced by stress. They’re called glucocorticoid response elements. If that doesn’t cause us to want to tune out and meditate or really think about the stress influence on our life as being pro aging, I don’t know what does. That was very profound. And there’s more literature where that comes from. And likewise, we see people, meditators, experienced meditators have a younger biological age, but heartening for those of us who aren’t living in an ashram or a monastery, one single meditation episode can have favorable epigenetic marks. Obviously, they accumulate and you get more benefit if you really engage in this activity over time. And the same with sleep. We see insomnia as being very pro-aging, and likewise, better sleep as being balancing. So we brought in all of these because we wanted to hedge our bets. We knew they were important for a variety of reasons, but our read on the literature, in terms of epigenetic expression, was clear that they’re very important.

Dr. Jeff Bland:
So obviously, you have left us with a trail of extraordinary ideas for which we could now spend hours, at least hours, probably days to really fully describe and explicate, but I think we want to titillate our viewers and give them the opportunity to go to your book, Younger You: Reversing Your Bio Age. And I think that there’s an acknowledgement I want to make, which I have not acknowledged until this moment, but I think it’s appropriate time. The whole reason that I came out of… What do I want to say? A period where I was more serving in mentorship, and from an educational model, and listening to what you were doing, and how you were doing it. And then hopping on this Himalayan Tartary buckwheat story, it was because of you and your work that I said, “I need to really get involved with Himalayan, Tartary buckwheat regenerative agriculture. I need to bring this crop back in America.” It was really the motivation of your work that stimulated me to now become a gentleman farmer. And our farm’s in upstate New York, and all this whole process that we’re now resurrecting this crop that has been lost since colonial America, that has probably the highest level of these immune active epigenetic modulators of any single fruit seed that’s available. So I just want to thank you because it set me on a whole other journey to interface in this latter phase of my career, what we might be able to give back to the system.

Dr. Kara Fitzgerald:
It’s very exciting.

Dr. Jeff Bland:
That’s how we build our community, so thank you. And to all of the listeners of this, you’ve just been graced with one of the most extraordinary forces of nature, Dr. Kara Fitzgerald. And if this is a model for all of us, how to pursue our dreams, and to stay at task, and to collect the right people around us to make our dreams become reality, then you miss the intention and the outcome of this extraordinary podcast. So thank you, Dr. Fitzgerald, for all that you’ve done.

Dr. Kara Fitzgerald:
Thank you.

Dr. Jeff Bland:
Be well.

Also available on：

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Date Effective: March 2019

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