Dhru Purohit Show - 3 Things You Can Do to Age in Reverse with Dr. Kara Fitzgerald

Episode Date: August 15, 2022

This episode is brought to you by InsideTracker and Paleovalley. It’s true: getting older is inevitable, and our chronological age can only move in one direction. But we also have a biological age, which scientists can measure by assessing how our genes are expressed through epigenetics. On today’s mini-episode, Dhru sits down with Dr. Kara Fitzgerald to talk about the exciting new research that shows our biological age can actually move in reverse and her groundbreaking clinical trial that proved it’s possible. Dr. Fitzgerald received her doctorate in naturopathic medicine from the National College of Natural Medicine in Portland, Oregon, and is in private practice in Sandy Hook, Connecticut. She is the host of the New Frontiers in Functional Medicine podcast, is on faculty at the Institute for Functional Medicine, and is an Institute for Functional Medicine certified practitioner. Her study Potential Reversal of Epigenetic Age Using a Diet and Lifestyle Intervention is the first of its kind to show biological age reversal in humans. In this episode we dive into: -The top three things you can do to age in reverse  -Why stress is one of the biggest drivers of aging  -How much of our genetic makeup is set in stone  -How epigenetics is involved in cellular aging  -DNA methylation and how it powerfully influences epigenetic expression  -Zombie cells and aging  -Dr. Fitzgerald’s study for aging in reverse and the protocol followed by the participants    Listen to the full episode here. For more on Dr. Fitzgerald, follow her on Instagram @drkarafitzgerald, Facebook @drkarafitzgerald, Twitter @kfitzgeraldnd, YouTube @karafitzgeraldnd, and through her website, drkarafitzgerald.com. Get her book, Younger You, here. Check out her podcast, New Frontiers in Functional Medicine, here. This episode is brought to you by InsideTracker and Paleovalley. InsideTracker provides detailed nutrition and lifestyle guidance based on your individual needs. Right now, they’re offering my podcast community 20% off. Just go to insidetracker.com/DHRU to get your discount and try it out for yourself. Paleovalley is offering my listeners 15% off their entire first order. Just go to paleovalley.com/dhru to check out all their clean Paleo products and take advantage of this deal. Hosted on Acast. See acast.com/privacy for more information. Learn more about your ad choices. Visit megaphone.fm/adchoices

Hi everyone, Drew Brode here. On today's mini episode, we're featuring a chunk from a popular episode that we did with Dr. Cara Fitzgerald, who published the first of its kind study focused on how individuals could reverse their biological age. They could literally age in reverse. So on today's episode, we're going through some of the top sections of my interview with Kara, including three things that you can do today, simple things that anyone can do that the participants in Dr. Fitzgerald, study did to begin the process of aging in reverse, why stress is one of the biggest drivers of aging. Kara also talks about how much of our genes are set in stone and how much are variable. And if you are a fan of this podcast, you know that a lot are variable. She also talks about how epigenics are involved in the process of cellular aging. And lastly, she talks about her study and walks you through what the protocol was that participants followed to begin to age in reverse in this eight-week period where they aged in reverse

by almost about three years on average. I think you're going to enjoy today's episode. Let me know your feedback and stay tuned. Dr. Kara Fitzgerald, welcome to the podcast. It's an honor and pleasure to have you here. I'm going to jump right in and I'm going to talk about a little bit or I'm going to ask you to talk about aging in reversed. You were involved. And we're going to talk all about this study, but just to give a little preview, you were involved in a landmark study first of its kind study where you actually showed that within eight weeks you could reverse people's biological age. So let's give some immediate value to the audience that's listening and watching on YouTube. What are a couple things, one, two or three things that you could think of right off the bat that anybody who's listening today could do to begin that process to age in reverse? Add some rosemary to whatever you're eating. It's delicious. So literally, I've got a rosemary grinder on my desk and I'm popping it on my salad. If I have a good tea, I'm adding it. And tea, have some green tea and brew it strongly. And then, you know, enjoy curry. Get your turmeric in. And then the final thing I'll say is don't forget to take some deep breaths and just bring it down a notch from time. time. Beautiful. I love it. Those were great. That was like super succinct. So rosemary, green tea, probably because of the catacans, we'll talk a little bit more about that and the beautiful polyphenols

and all these foods that are there. And then we talked about curry, which of course I love, that's my background and we made all sorts of different spices and things like that and turmeric. It was one of the reasons that often India was cited. Unfortunately, it's changing as having a protective layer against Alzheimer's was all these incredibly anti-inflammatory spices that were there. Again, unfortunately, that's changing as we've exported our diets. The standard American diet starts to be exported all around the world. And the last one, deep breaths. Deep breaths.

You know what? I wouldn't have thought as that being one of them. Everybody knows the importance of breathing. Why deep breaths? Tell us about why that's so key and so important for folks. Because stress is like gasoline on aging. It just pushes it forward aggressively. And you see that in the literature.

The clock that we used in our study, a full 25% of those methylation sites are influenced by glucocorticoids. They're driven by stress. So it's one of the biggest things that we can do to interrupt that pro-aging. And when you look in the literature at stress reduction, like if you look at meditators, if you look at Tai Chi, if you look at yoga, et cetera, the outcome is actually beautiful. So long-term meditators are biologically younger. But thank God, and thank God for those of us who aren't sitting up perched on a mountain high, even one meditation practice can favorably change epigenetic expression. So clearly we want to do it for the long haul,

and we do want to cultivate a practice that works for us in our lives. But anywhere you enter into the distress conversation is going to be beneficial in anti-aging. So let's lay the groundwork a little bit. And let's talk about some of these keywords that you've used. And let's talk about them in the concept of this was the first of a kind study, as we mentioned earlier, because there's a lot of studies on meditation. There's a lot of studies that have been done. I think I looked the other day. And on green tea catechins, I found over 10,000 different publications that were in PubMed that in some way referenced the polyphenols in sort of green tea. Then there's a lot of studies that are being done on sleep. But your study, you combine all of these studies together, all these items together. And let's talk a little bit about that. And what were you specifically looking for? You've used the word epigenetics. Tell us a little bit about what you were looking for when you were thinking about the design of this landmark study.

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That's D-H-R-U to get your discount code and try out InsideTracker for yourself. That's inside, I-N-S-I-D-E, tracker, T-R-A-C-K-E-R-D-R-R-U for 20% off. This episode is brought to you by Paleo Valley's turmeric complex. You know, growing up, my family used turmeric all the time. So now it's kind of freaking amazing for me to look out into the world and see that turmeric has become this worldwide health trend, which is radically changing people's lives for the better. But, you know, when I was a kid, I did not love taking tumor.

My parents would mix a spoonful of turmeric with hot water and I just had to guzzle the whole thing down, often squeezing my nose. But now I think it's pretty cool that you can take turmeric and get all its amazing benefits in the form of a supplement. Now, one thing to consider is that even though we've seen turmeric everywhere and it's growing in popularity, a lot of companies out there started making supplements that just contained curcumin instead of the whole plant, which means that you're missing out on a lot of the synergistic benefits that you can only get from ingesting the entire plan. That's why I love taking turmeric complex by Paleo Valley. It contains a whole food turmeric, coconut oil, and black pepper, which have been shown to increase its absorption by up to 2,000 percent. Plus, it includes anti-inflammatory super herbs like organic ginger,

rosemary, and cloves. If you're interested in tapping into the healing properties of turmeric today, right now, Paleo Valley is offering my listeners 15% off at PaleoValley.com slash Drew. That's Paleo, P-A-L-E-O-V-A-L-E-Y.com slash D-H-R-U for 15% off today. I'm starting to think, and we can circle back to this in a minute, but I want to throw it out there that, you know, those 10,000 studies you just pulled up on green tea, we know it's anti-cancer, it's anti-inflammatory, it helps cognition, you know, it helps, you know, bone health, skin health, you can kind of, you can go on and on with this group of catacons in green tea and how amazing they are. It's my thinking that as we move towards being able to measure gene expression

and look what's happening at the level of, you know, right on our DNA and the modifying factors, what they're doing to allow certain genes on and to inhibit certain genes, it's my belief that we're going to see that these beautiful polyphenols exercise, meditation, the things that we looked at in our study, that where they do, their heavy lifting, their most impactful lifting, is right there at genetic expression. And then we've been for a long time looking at this downstream effect, okay, it's anti-inflammatory, it preserves brain health, et cetera, et cetera. But fundamentally, I think as the science moves forward, we're going to see that it influences genetic expression.

And that's what we were really interested in studying. This diet and lifestyle intervention, our read on the literature, is that this is going to optimize DNA methylation pattern. So this is a biochemical process that happens on the genome and influences which genes are on and which genes are off. It becomes wonky. You know, there's my scientific word, as we age. it actually when we look at the chronic diseases of aging so aging is the biggest risk factor for all the chronic diseases and when we look at them together when we look at them epigenetically we see the chronic diseases share the same sort of damaged gene expression that aging itself does so if we get in

there and we optimize gene expression for aging we should by extension be reducing risk considerably for all of the associated diseases of aging. But I just want to stop because I've said a mouthful and I just want to see what you think and what you want to add. It's kind of super mind-blowing. And sometimes we hear something and we know it's mind-blowing, but we don't know all the reasons that it is mind-blowing like in detail. So that's exactly the beauty of long-format podcasts like this.

We can tease every single one of those things out. So let's start at the basics. You know, many people have gone to their doctor's office, especially as genetics have become more popular and companies like 23 and me and other stuff. And we've heard terms like, hey, you're at a genetic risk for something. You have a higher likelihood that's there. Sometimes we hear the other side that's still pervasive in the medical community, which is, you know, you're going to end up with this disease because it just runs in your genes. Your dad had it. You know, your grandfather had it. You're most likely going to have it.

And there's other people that are out there, practitioners and physicians like yourself, they're starting to introduce this other concept that actually that may not be the full story. So talk to us about our genes and how much is set in stone and how much is variable based on everything that you've learned. Right. That's a, you know, that's a really important question. I would say that what is happened, our environmental exposure, so that is how we're living our life, actually how we're living our lives, how we have been over the course of time,

our exposures to toxins, the stress that we've been raised with, you know, what we've eaten or haven't eaten, how we move our bodies or don't, like all of these, the interface of environment and gene is more influential, ultimately, on genetic expression than the genetic changes themselves. So it's that environmental interface or the epigenome, if you will, that will play a role in whether we get a disease or not with a far greater likelihood than what's happening or what's happened to our genetic material or what mutations we've inherited. But I do want to be clear, though, that there is a continuum. You know, so there are some genetic conditions that can show up at birth. You know, they can be fatal or they can, you know, they can, you know, they can

be associated with a very short life expectancy. I'm actually, but even there, you know, we get to get involved and we can influence it. One of the, I wrote about this in Younger You, just an incredibly important case in my lifetime. I was a new, I was into my new postdoc, a new graduate, and I was consulting with clinicians around the world, looking at laboratory, patient laboratory data, complex patient laboratory data and helping them interpret how they would treat based on these labs. And I worked for years with a physician who was treating a boy who had a rare collagen defect. And this collagen defect was excellent. So, you know, it's worse in males.

And it's fatal in single digits. I think, you know, maybe around life expectancy is around five years old or so. he was wheelchair bound he had a feed tube you know he had he had some pretty significant physical deformities but this physician this brilliant physician would run a battery of testing on him to identify all of his micronutrient needs his macronutrient needs he would look at what was going on in his stool microbiome and he would design that feed tube intervention based on V's laboratory data, exactly what this boy needed and in the amounts that he needed. So this is a fatal genetic condition, but he's getting in there with very individualized treatment.

And the last I had contact with this clinician, this young boy was the oldest individual with this particular genetic defect. He was actually graduating high school. So a condition that's considered to be absolutely fatal, you know, we can get in there and influence it. And the other example, nobody's going to argue, I mean, Angelina Jolie brought this to the fore that if you've got the BRCA mutation, your likelihood for cancer, a hormone-sensitive cancer like breast cancer ovarian uterine is very, very high. It's, you know, it's 80% plus. And for that reason, the appropriate course of action for many women is mastectomy, is hysterectomy, and so forth. However, when they looked retrospectively at blood, and identified women who had the mutation, you know, early on in the 40s and 50s, the incidence of cancer in that population was much, much lower, showing a clear environmental interface, even for that particular, you know, what's considered a deadly or a shoe-in for cancer gene. So environment still plays a big role, even in the most significant genetic mutations.

those are the exception. You know, the vast majority of cancers have nothing to do with the genetic mutation. The vast majority of cancers are something we need to be thinking about. I think it's like 90% of cancers are not directly related to and primarily influenced by the gene. They're going to be lifestyle-related, smoking, diet, all the other things that are there. And cancer is one of those ones that having had a mom who's had cancer, she's doing great, knock on wood. Cancer is one of those ones that people often.

think like, oh, you are just, oh, it was your genetics. You just got dealt a bad set of cards. And they forget that there's this term epigenetics. And a lot of people don't even know epigenetics. So let's even just break that down. I know I cut you off. But I want to add in here to just to tease, tease out a little bit, define epigenetics and tell everyone how it actually, you know, works inside of the body. Sure. And you can interrupt me at any time. And you can ask clarifying questions as needed. I know some of this gets complex and I want to make sure I get it out in a way that's understandable. And by the way, a few-way street, anytime you want to chime in, please cut me off because the thing is that when we get excited, we cut each other off. That's what

friends do when they're talking together. So I'll be mindful of that. You know, like hearing your your process on the journey. So it's fun. All right. So I'm going to just go back and say that, you know, we mapped the genome. We mapped the human genome out, discovered there were about 23,000 genes in the early 2000s. And I you know, it was pretty simple. I mean, our genome is infinitely more simple than most plants. Plants' genomes are wildly complex. So we mapped out the genome and it was a little anticlimactic. I mean, it was extraordinary. It opened the door to sort of a revolution in technology, but it was also like we thought we were going to find one gene associated with one disease, something very simple. Oh, you know, you've got gene mutation X, you're getting heart disease. So if we influence gene mutation X, you won't or you won't get cancer or you won't get diabetes. That was the expectation. And it was

disheartening that in fact it was not the truth. Everything was wildly complex and many genes seem to have to get involved. Like for instance, just I'm in the topic of, you know, I'm looking at longevity. And, you know, there's plenty of scientists who think if you're going to live a long time, you know, it's genetics and you can look at, you know, you can look at some evidence for that. But can they nail a gene down? No. They can't. Can they nail even a ham. full of genes down? Not really. You know, they're small contributors. So what next? You know, we think we find the answer. We cracked the biggest nut. And in fact, we were like, oh, shoot. So it turns out that the epigenome, epigenome, epi-above the genome gene, above the genome gene,

those things which sort of regulate which genes get turned down, the processes and they're involved and it's incredibly complex, you know, that regulates who's on and who's off, is far more pertinent in what's happening physiologically than the genes are themselves. And it's been, Moshe Saf, who is a mentor actually in an author and an advisor on our study, refers to the genes as being our hardware, and then the epigenome being our software. You know, so the hardware is kind of inert until there's, you know, really complex software interface to make it do what you want. And so there are many different epigenetic processes.

So, for instance, DNA is wrapped around proteins called histones. And right in those proteins, there's ways that the gene might unwrap and wrap and that will influence, you know, expression. There's all sorts of complex interfaces. RNA, for instance, will influence it. But my area of focus has been on DNA methylation. So this is another epigenetic process. And this is simply a carbon and three hydrogen.

So that's what a methyl group is. And these are placed through DNMT enzymes or DNA methyl transferase enzymes on certain regions of the gene, primarily, well, they're all over the place, but primarily the most influential are on the promoter regions of genes. When there are a lot of these methyl groups placed down, that gene is turned off when those methyl groups are removed or when they're inhibited from being laid down, that gene can then be on. DNA methylation is compelling for a number of reasons. It's the most studied by far of all of the epigenetic marks, as they're referred to. It has built-in heritability

components. So when a DNA strand, when a DNA divides, when a cell goes through a division, one of those, a daughter, the DNA, the methylation patterns of the original DNA strand are faithfully transferred onto the daughter strand. That's not the case, as far as we understand now, with the other epigenetic marks. And why this is incredibly important is this heritability and this continuous potential for that particular mark to exist, not just in our own body and in the many cell divisions that we go through, but heritability from our parents, our grandparents, our great-grandparents, et cetera. So I think DNA methylation plays an incredibly important role of all of the epigenetic marks,

although I do want to say clearly that as we move forward in this amazing field, we will see these other epigenetic processes be, you know, sort of better able to test and we'll look at them in conjunction with each other. I mean, this is a new field and it's blowing up. The other piece is that DNA methylation is relatively easy to test these days, and it's pretty reliable and reproducible. So there's a number of different reasons. It's kind of moved to the fore. And I want to say one other piece about DNA methylation. We can talk about some studies looking at it, like out of Sinclair's lab that really suggest its importance. When we're just, you know, when during embryogenesis, when a, when a pluripotent stem cell is

getting its fate, if it's going to become a brain cell or a heart cell or a skin cell, that's via DNA methylation. Those marks that are laid down are incredibly important. And, you know, X chromosomes, I have two X chromosomes. It's through DNA methylation that one of those chromosomes is inhibited in each cell in my body. and obviously that's going to be replicated, you know, throughout my lifespan that one of those X-cremasomes is shut down. So it just plays a lot of incredibly important roles.

I want you to break down this term that goes along with all this research that you're doing that a lot more people are becoming aware of, and that's these senescent cells, or as we've sort of nicknamed zombie cells. What are they and where do they fit into this picture of us trying to influence our biological age and potentially age in reverse. Right, right, right. Well, these are basically, you know, cells that have, that are existing in sort of a static, well, I wouldn't even call it that.

So they've moved through their useful life as fighting inflammation, as fighting infection and so forth, and now they've moved into this zombie state, which, you know, it would be one thing if they were inert. But they actually begin to produce quite a few pro-inflammatory compounds. And they accumulate really kind of exponentially or the potential is there for them to accumulate as we age. And so- They're literally zombies.

Like if anybody's watched The Walking Dead, they've watched anything else. They know the characteristics of a zombie. They're scary. They once were functional and they spread to other people causing damage and havoc all along the way. Yeah. Yeah. It's pretty extraordinary. So they do. They release, they move into this, what we call a pro-inflammatory phenotype where, you know, wherever they are, they're wreaking havoc, not just locally, but they can have a systemic effect. So, yeah, we want, zombie cells are something that we want to be, you know, directly addressing in some form in our diet and lifestyle program. So that would be a piece of the puzzle. I mean, again, over here, we're focused on DNA methylation. However, our program is designed.

So circling back to some of those amazing polyphenols, some of those help directly combat zombie cells. And one of the most classic compounds to do that is called quercetin. Resveratrol does, interestingly, but it's hard to get, and I know you're thinking, well, resperatrol is in wine, but it's hard to get actually a therapeutic amount of resperatrol from wine. But there are a host department. Yeah, you have to take a lot, which some people want to, but then you get the side effects of too much wine. We had some gentle intermittent fasting in our program, which is another way to address the so-called zombie cells as well. So before we break down your study and a little bit of what your inspiration was in designing it and how you did it and you're kind of walking us through the results of the participants.

Again, many people, part of it, aging in reverse, and we'll talk about what that means. Let's tease out a few more definitions of some words. We just did an entire newsletter to my audience about the groundbring. working work and research about the world of polyphenols, and you've been a huge advocate of this for such a long time. So let's just remind people, what are polyphenols and why are they so much more important to not just our human cells, but our bacterial cells, our bacteria in the body? So what are they? What do they do? And what are some of the items that you've mentioned along the way in this interview that have the highest concentrations of the ones that

we know that are beneficial for health? So polyphenols are, interestingly, you know, early science, we dismissed them. I mean, they're not minerals, they're not vitamins. I mean, we refer to them as nutrients, but technically, by the hardest definition, they don't, you know, they're not minerals or vitamins. But, you know, they're the, they're the, they just play such incredible roles in a plant's life. So again, recall that I mentioned plants have an infinitely more complex genome than us. I mean, they're right there.

They're stuck in the ground. You know, they're interacting with the soil, with the compounds in the soil, with the microbes in the soil. They need to produce compounds, you know, much like we have an immune system to sort of balance life with good and bad soil microbes. So they produce a host of these antimicrobial compounds, for example. And these fall into the polyphenol camp. They, you know, they're taking in sun to make their energy. So they are, by extension, generating loads of potential oxidative, oxidative compounds.

They need to protect themselves from that exposure as well as harness the sun to make their energy. The polyphenols are key players in that. So they're generating antioxidants and, you know, other mitochondrial supportive compounds. Just a really interesting and complex and sort of underappreciated array of compounds that act on plant survival. We call it, we call it's been referred to as the dark matter of nutrition. There's tens of thousands of these compounds that we haven't characterized yet. We're only starting to characterize them and characterize what their mechanisms are in plant life. And then when we look, I mean, we evolved, obviously, eating plants.

And so what we're starting to appreciate now is when we consume the complexity of whole food, the complexity of that entire plant nutrient status, those compounds were hardwired to interact with. We're hardwired to have them transform when they're exposed to our microbiome, as you alluded to. So our polyphenols are acted upon by our gut bugs, and that changes their behavior. That changes our ability to absorb them into circulation. And it also changes what they do once they're in circulation. So if you can imagine eating a salad, I just had a really big salad with probably 20 different veggies. So that's tens of thousands, maybe hundreds of thousands of information I've just fed my body. Hundreds of thousands of compounds, and they know how to interact

with each other, with my microbiome, they're absorbed into circulation, and then they, these compounds, and they're transformed and absorbed, and then they really kind of cascade over, you know, our cell membranes, the receptors, they enter into the cytosol of the cell and ultimately into the nucleus, or they influence what's happening in the nucleus and DNA expression. So it's an extraordinarily complex cascade of events that we were designed to experience, really, with every bite. I mean, This is how we evolved. And in real time, with every bite, with food being information and our gut bugs interacting with these, we have to understand that in real time, those metabolites and a whole bunch of

other things that are happening, they're turning certain genes on and turning certain genes off. So this is not just theoretical. This is not just happening over years or decades or centuries. This is happening on a regular basis. And that's the power of food. but also sleep and also love and community and exercise and all these beautiful things that you've highlighted in your book. That we have, and yes, you know, as we blast out into the stratosphere of technology where we can

look at gene expression with the kind of insight that we're able to now, the take home has been, you know, walking more closely from where we came. There's an appreciation from this whole foods, you know, minimally processed diet from moving, moving our bodies, sleeping enough, et cetera. I mean, it's really extraordinary. The more complex we get as a species in our understanding, the more validation there is for the simplicity from, you know, where we came. I'm thinking also that you can't digest food if you're in a sympathetic state, which you know, you have to be, you know, your parasympathetic system has to be on. You have to rest and digest. I mean, to allow that full cascade of digestive events that I just outlined,

I mean, it actually starts mentally with turning the volume down, going back to taking a few breaths. That, just that step alone can help us harness the nutrient potential from our food. We won't access the full nutrient potential if we're rushing between meetings or we're in a, you know, horrible New York City traffic jam or, you know, the suburbs of New York, which are basically where I live. I mean, you're not going to be, you may be eating a beautiful, well-prepared organic salad, but if your mind space isn't able to actually receive that nutrition, you're not going to harvest its potential.

I mean, it's really kind of extraordinary. So the build on top of everything that you've shared, just to make sure that it's super clear for everyone, walk us through the big picture of the study and the protocol that people were put on. Were you looking at starting it from the beginning when you were doing an intake in, what was the average biological age or how are you sort of measuring that for folks? The big picture, you know, and then we'll dive into some of the details on it, protocol that they were placed on, and then the end results and findings that came out of it. Yeah. So we wanted to look, we wanted to look at the aging phenotype. We know methylation, DNA methylation gets wonky.

So we didn't want to look at, you know, really young, healthy people. We looked at a population between the ages of 50 and 72. So we knew we would see some, we should see some changes there, some negative changes. It's just the journey of aging. But we wanted our participants to be healthy. We didn't want to look at, you know, diabetics or people with cardiovascular disease. So we, you know, we had to, it took us a year, interestingly, to recruit for an eight-week study because we had to sift through a lot of people who wanted to participate and weren't sufficiently healthy.

And it's a relatively rigorous eight-week program. I think it's highly doable, but, you know, they needed to be all in. So it took us a while to recruit. We limited, because we had a, it's a pilot study, we limited our population to a total of 40. In the end, we ended up having 18 in our study group and then 20 in our control group. We looked at men only. We did not include women in this first go, and certainly that's one of the biggest criticisms I've gotten, but the fact of the matter is women in the age range of 50 to 72 will be premenopausal, they'll be perimenopausal, and they'll be postmenopausal. And we would need much higher numbers for us to tease out the hormonal influence, because there's no question that hormones absolutely influence DNA methylation and biological age.

And we just couldn't, in that small population, tussle with that level of information. We are now recruiting for a larger study, and of course, women are involved, and it's really important to me. So we were looking at healthy men, middle-aged to healthy men. What else do I want to say about these guys? The study was, again, done at my alma mater at HealthGut Institute. We did a whole battery of testing on them at baseline, including. the Illumina Epic array or the DNA methylation. The study group...

And when you were doing their intake of where they started off with so that you could see how you could reverse the biological age, and if the protocol did end up reversing the biological age, is there... And again, it may not be helpful in the context of this interview, but just asking, because I didn't get a chance to go through this in the paper, was there an average median? biological age, you gave us the age range of the 40 participants that were there, but was there,

or was it just, you know, people were all over the map, and it's not really how you kind of think about it. You know what? I don't actually, I don't know, interestingly enough. I mean, it would be easy enough for us to figure out, but we, I mean, well then, well then, yeah, let's actually, since, since that part, you know, it may not be as useful, again, so that's why I prefaced it. Take us to the end of it. After going through this eight-week protocol, which is also many of the things that you put people on are outlined in the book and the things that you did. Again, we're talking about not just diet interventions, but also sleep recommendations that were brought into it. So diet, sleep, anything else, any other big categories that you have been doing? Yeah. So diet, we wanted them to get,

we wanted them to go for seven hours. I mean, you obviously can't make people sleep, but we supported them in good sleep hygiene practices and we checked in with them. I need to talk, about when I say that we checked in with them, our nutritionists here worked with our participants, and it's an important, important piece, I think, in our success. Our nutritionists met with our participants at least weekly. That was a requirement. And they could meet with them more. And they did that through like the first month of the study and then they were able to drop back if they had their sea legs around the intervention. They used a very dry institutional review board script to communicate with the study participants. Like, do you have any questions?

Are you meeting your vegetable targets? Have you gotten your cruciferous? Like boring questions. But that contact was, in my mind, a likely imperative piece of adherence. And we will at some point hopefully publish on our adherence data because it's really, really good. And nutritional interventions are notoriously just sloppy and poorly recorded. And outcome is it's difficult to tease out what's significant and what's not. And nutrition interventions are often challenged.

So I think having the nutrition team work with them, even in this dry capacity, was the difference between success and failure. If we had just given them a printout at the beginning of the study and said, you know, Godspeed to you. I just don't think we would have seen the changes at all. And on the topic of the polyphenols, was there an amount that you recommended that people had daily? Was there specific ones that you recommended for folks to include? Yeah. Yes. So, yes, absolutely.

Just as I mentioned in the beginning, we gave them a greens powder. So they had to go with at least seven cups of vegetables. We needed them to get some beets. And in the breakdown of those vegetables, they were getting cruciferous veggies. They were getting colorful veggies. The veggies that we wanted them to choose were lower glycemic. So we didn't want them to do a ton of carrots or sweet potatoes. They can, they can.

But we just wanted to be mindful around glycemic load. and, you know, just sugar cycling. For the polyphenols, so those vegetables are all going to include some of the epinutrient polyphenols, but we specifically wanted them to do consume green tea. We wanted them to have daily turmeric powder. We wanted them to have rosemary. We wanted them to consume pumpkin seeds and, you know, a host of other seeds, but primarily pumpkin seeds and sunflower seeds, although.

So they had some basic targets that they needed to achieve daily, which I just outlined. And then they had subcategories of things that we would encourage. So the daily targets wouldn't be calorically sufficient for them. So they'd need to incorporate some of these secondary components. And they could choose additional polyphenols and additional really nutrient-dense foods as well. We wanted them to have a little. Liver was one of those foods that you recommended them. That's right. So five eggs a week, five to ten eggs a week, I should say. So a minimum of five eggs. They don't have to have them every day, but we gave them a weekly target. We wanted them to try for three servings of liver per week. So not a daily thing, but three servings per week. And really most of our participants were able to do so. The nutritionists would guide them towards where they could get quality sources. Our study was, again, it was out in Portland, Oregon, where there's pretty readily accessible.

clean sources. So they were able to do that. We gave them a probiotic lactobacillus plantarium. We know all of the benefits of a healthy microbiome and certainly lots of research on the healthy microbiome influencing healthy epigenetic expression. But the lactobacillus plantarium specifically was with the potential that it could increase microbial production of folate, of a natural folate. And we did, with all of these interventions, increased circulating folate in our participants by 15%. So, you know, it was significant and quite appreciable. We can't target it back to the probiotic, but it could have been a piece of it. We also gave them a greens powder concentrate, so more of those really beautiful polyphenols, and they were to take that twice daily.

sleep tracking, a twice daily relaxation response breathing practice. So just twice daily, you know, 10 to 20 minutes at each time, you know, a meditation, a basic meditation practice. Exercise was prescribed at a minimum of five days per week, minimum of 30 minutes time, with a perceived exertion of 60 to 80 percent. So 60 is, you know, you. you might be breathing slightly heavy, 80 is you're breathing heavier, but you're still able to carry on a conversation. One could do whatever they were called to do for that. And what were the

most common ones? We're things that would be recommended because I know that a lot of people struggle with finding that movement, and we've done whole episodes on this. It's all about figuring out what works for you. That could be tennis. They could be going on a, you know, on a hike with friends or a long walk, a little bit of uphill action. What did you find that? that a lot of the study participants were doing that met that requirement of exercise that you were looking for at the exertion levels that you wanted to see. I'm going to say that probably the biggest activity was actually walking. I know one guy in the study I remember started walking back to and forth to his job,

which is, yeah, what a smart habit to develop. But again, these guys are healthy. And so they came to us with exercise practices by and large. What's interesting is that some of the. had to drop back on their exercise. One guy wanted to do it. He was going to go hike in the Rockies or something. And he wanted to do the intervention while he was on this.

And, you know, that was going to be outside of our exercise prescription. So he had to wait until he got back from it. I think, you know, there's a range of what's going, my healthy exercise is not going to be yours. I mean, there's a real individualization of exercise. And I think we're still working on teasing that out. And I think, you know, the more we're able to readily measure biological. age and what's influencing it favorably and not. And the more we're able to kind of to have these tools at our fingertips and wearables,

the more we'll be able to see, oh, this exercise is fabulous for me. Might not be for you. And even though you mentioned that all these folks are healthy, but the vast majority of them are doing walking, there's probably not many people here who are listening that cannot take advantage of that. That's a double negative, but almost everybody here. can walk at a level and then if they want to turn it up a little bit, then they can do that contextually for themselves.

That might, for some people who are more active, be going a little bit uphill and carefully downhill. For other people, it just might be you're picking up the pace a little bit. Instead of a very gentle walk, you're getting a little bit faster of a step in. So that piece, which was a crucial piece, a part of the study on top of the diet, the sleep, the other components of relaxation, anybody, anybody who's listening to things, Well, they were also doing exercise too, but you can do that same version for yourself, a little bit of walking and then just turn up the volume just slightly to get that 60% exertion that you're talking about.

Yeah, 60% is not a high bar. And, you know, okay, you have bad knees. Well, you know, you can do an exercise bike. You can do a rowing machine. You can dance if you like dancing. I mean, you can clean the house. Honestly, there's research on favorable epigenetic changes with house cleaning and house clean. People who have really long, long-term house cleaning habits are biologically younger.

So I'm sure some people out there are thinking about that one. Not me, but it's really anything that our participants felt like doing. And that's the same way that I'm approaching it in the book. It's the act of actually doing it. And I talk a lot about in the book, you know, how to do it. And I think you brought this up earlier. Community is a huge component, I think, for, establishing an exercise habit that's going to be sticky. You know, who can you, my, my best conversations,

I think, happen. I'm a cyclist and I like being outside on my bike because I love the feeling of the outside. But, you know, that's when I get to catch up with my sister. You know, that's when I kind of, I make sure I go on safe roads and I can chit chat and, you know, I'll get a hill climb in, so I'll be huffing away sometimes. But I also get to bond with people. And it's just such an important part of my exercise routine. And it keeps me going. The key term that you use there is sticky. You know, we want to set this up in a way so that we don't kill ourselves by trying to be perfect in any one of these categories, but we do it in a way that we can make it a regular part of our life. And when it becomes a regular part of our life, that's when the results end up taking

place because anybody can do this for a week using willpower, but really we want to set it up as a lifelong habit. And that's a big part of your recommendations inside of the book. So take us to the results, the results, and what you're going to do. And what you're going to do. And what you're you guys showed in the course of eight weeks. And again, all this is listed out in the book. And you can turn it into your own plan that's there for yourself where you can have the same results that you talked about in the book. So tell us what the results were and how you measured them. So we saw, as I mentioned earlier, that folate increased significantly in our participants. Their triglycerides dropped. And we did, you know, we wanted it to be slightly keto-leaning.

And so there was a, you know, lower glycemic load on, on what they were consuming. And we did a gentle intermittent fasting, 12 hours on, 12 hours off. And so their triglycerides dropped, their LDL and total cholesterol dropped a little bit. These were healthy guys, so they didn't need to be making any great changes here. This was like a refinement. And then, you know, the biggest, the most exciting finding was that their biological age as measured by sort of the flagship biological age clock, it's called DNAM age, put out by Steve Horvath at UCLA, as compared to our control group.

it dropped by 3.24 years. So in eight weeks' time, our study subjects got, you know, over three years younger as compared to our controls, which hasn't been shown before. It still, you know, it still hasn't. Yeah, it's a big freaking deal. And it just shows you that the right combinations of things, because these are all designed. Often in the world of pharmaceutical drugs and even in the world of a lot of supplement research, the way that scientific, studies are set up is you want to isolate. You want to isolate that one specific compound, that one thing, whether it's vitamin D or that one prescription drug metformin or nexium

or whatever it is that people are studying so that you can say, hey, just take this pill and this pill will have impact on this area. And those are needed. Those are studies that are needed. And a lot more of what we're looking at now is these multivariate studies that reflect more that the true power and the true results that come into anybody's life who's listening and watching really happens when we combine these things. So I think that I'm excited to see a study like this because that will hopefully encourage more people instead of just looking at isolated things, which are of course needed and is very much a part of the way that we develop drugs, a lot of life-saving drugs that are out there and the way that we research, a lot of supplement

protocols that might be there. But for the average person who's listening, what is the true potential of combining these protocols together, combining these individual areas into one protocol so that we can show that you can make a significant difference in your health. In this case, reversing three plus years in biological age by a simple program. Now that begs the question. And as you mentioned, this was just a pilot study. What happens when somebody's doing this over months or over years? What is the potential then, not just in terms of living law,

But of course, in terms of living healthier, not just in terms of the lifespan, which we may not be able to, you know, significantly have that big of a difference on. We're still sort of figuring that out. But definitely we can live into our 80s, 90s, 100s and 100s plus being a way healthier version of ourselves, not, you know, knock on wood in a nursing home where we don't have the capacity to take care of ourselves or look after ourselves or function at a level. that allows us to fully show up in life.