Reversing Biological Age with Dr. Kara Fitzgerald | Longevity Optimization Podcast

Today I'm speaking with Dr. Kara Fitzgerald on the Longevity Optimization Podcast. In this conversation, we explore her journey into functional medicine and longevity, emphasizing the importance of dietary and lifestyle interventions in reversing biological age. Dr. Fitzgerald highlights the role of diagnostic tests in understanding health status, the impact of technology on health monitoring, and the significance of epigenetics in influencing gene expression.

Throughout our discussion, we cover various dietary patterns and protein requirements essential for optimal health. Dr. Kara also addresses the accessibility of health interventions for individuals from diverse backgrounds, advocating for inclusive approaches to wellness that empower everyone to take charge of their health journey.

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Timestamps

00:00 Introduction to Functional Medicine and Longevity

05:07 Exploring Diagnostic Tests in Functional Medicine

10:03 The Role of Technology in Health Monitoring

13:01 Reversing Biological Age: A Groundbreaking Study

19:56 Dietary Interventions for Longevity

30:00 Protein Requirements and Nutritional Strategies

34:26 Nutritional Foundations for Health

35:00 The Role of Exercise in Longevity

37:48 Sleep and Its Impact on Health

39:47 Stress Management and Mindfulness

44:46 Nutrition as the Key Lever for Health

47:14 Bio Age Reversal: Study Insights

50:20 Gut Microbiome and Dietary Impact

52:18 Supplementation Strategies for Longevity

53:43 Exploring Senolytics and Their Benefits

58:11 Individualized Approaches to Longevity

Transcript

[00:00:00.00] - KAYLA BARNES-LENTZ

Dr. Kara, it's such a pleasure to have you here with me today. I'm so excited about this podcast. You've just done really incredible work, not only in the functional medicine space, but in the longevity space. I've mentioned my female group, we're reading your book together. So welcome to the podcast.

[00:00:18.13] - DR. KARA FITZGERALD

Thank you. It's really fun to be here. And yeah, it's pretty cool to really discover the work that you're up to. So bravo you for bringing this important information to women.

[00:00:29.00] - KAYLA BARNES-LENTZ

Well, thank you so I'm going to watch and write back at you. Before we dive into so many fun questions on longevity and biological age reversal, some of your work, I would love to just hear, how did you get interested in functional medicine? Walk us through how you are where you are today.

[00:00:45.05] - DR. KARA FITZGERALD

Sure. I would say it goes back to my upbringing, just having a savvy mom and a savvy grandma. So maybe a generational thing, growing our own food. I mean, it was more common. It was common for grandparents to have a garden. But my mom was aware of... Back then, the things that were really big were like brewer's yeast and vitamin C and whole grains. All of those things were nonexistent. Yogur, making our own, doing her own fermentation, grinding nuts, making her own nut butters and stuff like that. She was savvy to that. She fed us certain means. I remember opening, clearing a lunch table when I was in sixth grade with a sardine sandwich on whole wheat bread. That's a trauma. I definitely went through a rebellion. I went through a rebellion around that for sure. But we were raised with a foundational knowledge that there's just no doubt that it made a difference in my career choices. Flash forward, when I was looking at graduate programs and really debating what to do, medical school, I was thinking about psychology, and I started to work in a health food store, so this full circle experience.

[00:02:08.07] - DR. KARA FITZGERALD

But what I became very excited about there was Uder Erasmus published this amazing book, called Fats that heal, Fats that kill. And this was a drill down, especially for a lay audience, into the biochemistry around omega-3 and omega-6 fatty acids and compounds that they made. And that, I think, just take my background interests, even prior to that, just gave me an immediate and continuing love of biochemistry and nutritional biochemistry and the power of food as medicine and all of that, and ultimately dictated my choice to become a naturopathic physician. Although when I did become an ND, it was with this awareness that I would go on to do... I wanted to be in a laboratory setting, and I considered going on for a PhD in nutritional biochemistry. But I ended up at a clinical lab doing these really sophisticated tests, really developing these sophisticated tests, like the first clinically available DNA stool test we developed. I was just telling you about a toxins panel that we developed using some technology from the CDC that I thought was amazing. But we were just doing some of these really early cutting edge things. And that established my career, I think.

[00:03:39.10] - DR. KARA FITZGERALD

And then just bringing that into functional medicine, it was the functional medicine audience that was really interested in our testing. So I immediately started educating other professionals in the functional medicine world. People like Mark Hyman was on the phone talking. We We were talking through labs years ago, and so he's been a friend for many years. But people who you guys know who are influencers, we all were in the trenches really learning functional medicine. I finished there in 2008, so it's a few years ago. But I shaped my interest. So this naturopathic training, this background from my mom, and then this real strong interest in the science of it and the power of nutrients and lifestyle medicine to really influence health.

[00:04:37.13] - KAYLA BARNES-LENTZ

Well, I love that. And also, you may have not liked the sardines back then, but I mean, I love that your mom does that.

[00:04:44.12] - DR. KARA FITZGERALD

Can you imagine?

[00:04:46.03] - KAYLA BARNES-LENTZ

Yeah, quite scary to a child. I had the opposite. I grew up in a standard American diet, so I had to go back and fix all of these things. I was eating pop tarts and things things of that nature, which I don't even classify as food. So I love that your mom did that, and really incredible story. Just to stick on the test, obviously, I've done quite a few. What are some of your favorite tests just in general?

[00:05:15.17] - DR. KARA FITZGERALD

Some of my favorite tests. Well, honestly, I was just telling you off recording, I was looking at some of the labs that you report using, and I think you've got a good panel going there. I What am I a big fan of these days? I think there's a lot of labs that we can access through standard laboratories like West and LabCore that are essential and really useful. So all of our standard chemistries, we can get a good look at thyroid function. We can look at nutrients. We can get a good iron panel, antibodies, autoantibodies that I'm sure that you've talked about. We can diagnose or at least identify somebody who's moving towards an autoimmune process long before it's actually there. So we can get a lot covered in that arena. And then beyond that, toxins are an essential investigation, at least annually and probably semi-annually for a lot of us. I mean, it depends on what shows up in our original panel. I'll just say over the years, being in this space for a long time, I did not see high blood mercury levels to the extent that I do now. I'm working with people who are sophisticated in how they choose fish, and some of them are the quote, unquote biohackers.

[00:06:46.15] - DR. KARA FITZGERALD

So something has changed our food supply, and it's pretty depressing, but we can look at it. It's easy to get a blood mercury. If you have health insurance, it's covered, and we can change what we're eating, and we should see, we should clear it really pretty quickly. But yeah, I mean, toxins across the board, we need to keep an eye on these days more so than we did, although we always have needed to. But things are, I think things are deteriorating somewhat. What else? I think we can look at omega-3 and omega-6 beta-s. Super important information. We can really get a good sense of what's going on, what's in our red blood cell membrane. There are just amazing science there supporting certain ratios. There's something called organic acids, which is basically the body in action, metabolomic information that can provide good actionable data. We can look at amino acids and certain proteins. And of course, we can look at genetics. I think doing that investigation once, we only have to do it once, is useful. And of course, epigenetics, where you ended up finding me, where I've been focused on, and it's where I've been conducting my research.

[00:08:06.11] - DR. KARA FITZGERALD

So we can cast a pretty cool wide net. And there's all these new labs coming down the pike that I'm keeping my eye on, looking at the so-called liquid biopsy or DNA methylation patterns associated with cancer and cell-free DNA. I think that's awesome. That's game-changing technology that we can use these days. There's a lab that's tasks that will be clinically available, giving an idea of whether we need to go hard or soft with sentalytics. And so that is going to really allow us to individualize that intervention, which I think is important, and maybe we'll talk about later. Those are some of the labs that I like to look at in the majority of my patients who are coming to me wanting a broad and deep exploration.

[00:08:58.16] - KAYLA BARNES-LENTZ

Interesting. Yeah. I I love all of what you mentioned. I'm doing a once yearly. I'm doing the Grail test, the gallery test. I don't know your thoughts on that one.

[00:09:08.15] - DR. KARA FITZGERALD

No, that's the one that I'm using.

[00:09:11.11] - KAYLA BARNES-LENTZ

Okay. So yeah, I've been doing that once a year. I feel like Hopefully, the price will decrease a bit because it's quite a costly test. But I think it's exciting that you can just have a little bit of peace of mind. And then I pair it with one of these full-body MRIs just to have a high-level overview of potential because it's really concerning. Cancer is just becoming more and more prevalent, but also seemingly starting in younger and younger people.

[00:09:35.21] - DR. KARA FITZGERALD

Yeah, for sure. I'm in agreement with Peter Atia that we should be getting colonoscopes probably earlier and more frequently. I'm also pretty bullish on some of the AI technology coming down the pike. The Clearly Scan, I think, is a worthy investment for most of us, especially those of us over Over 40 and over 50. Brainkey is another company just doing extraordinary work, really using an AI interface to look at brain MRI data with infinitely more sophisticated education than a standard MRI these days. That's just really cool technology. I actually have a podcast as well. If people want to hear our own Phillips, who's the Chief Science Officer, actually founder, they developed this at Stanford. There's a podcast with me talking about him or talking with him, excuse me. It's been helpful and interesting in delivering good quality patient care, really identifying changes super early. We're at this very game-changing and exciting moment, Kyla, with technologies evolving and becoming available. The Clearly scan just got Medicare coverage. If you're symptomatic, you can get coverage for it if you're in Medicare. It will become standard. It'll be picked up by insurances eventually. I mean, these things will eventually become more and more affordable.

[00:11:17.12] - DR. KARA FITZGERALD

But yeah, you're right. It's a huge financial commitment right now.

[00:11:23.13] - KAYLA BARNES-LENTZ

Yeah. I wonder what the regulations around getting that covered will be. I've had it clearly. I'm about to do a second one. But I wonder if they're going to put a minimum age or something on it.

[00:11:35.13] - DR. KARA FITZGERALD

Yeah. So it would be in the '60s, obviously, when one qualifies for Medicare coverage, and the You have to be symptomatic. But it's gotten through. And so that's the first step. And they've been really diligent in pushing it, in jumping the necessary hoops to get coverage. I love it. I know. I think I just think we're going to see changes. I noticed that you are from Cleveland, or at least you lived there. I'm a Cleveland girl as well. Yeah, originally. That's where I landed on the planet. Cleveland Clinic. They have done an amazing job at just bringing functional medicine forward in publishing. We're getting more and more literature into the scientific databases. It The more we all move forward in this conversation and use these investigations, and I use them in my patients, and you're using them in your clinic setting and really educating a lot of people, the more they're going to be covered by insurance, the price point is going to come down, it's going to become standard care.

[00:12:50.03] - KAYLA BARNES-LENTZ

Yeah, that's super exciting. I mean, the Cleveland Clinic is incredible, and they've published... I mean, it's so clear, obviously, that functional medics and outcomes are far better than standard outcomes.

[00:13:00.12] - DR. KARA FITZGERALD

Let's make sure, though. Let me just throw out there the idea that we can talk about to what we can do now if you can't afford a lab, because there's just plenty, plenty, plenty, plenty of low hanging fruit that we can talk about, so we can circle back to that.

[00:13:21.07] - KAYLA BARNES-LENTZ

Yeah, absolutely. Let's jump into that. You published some incredible data on being able to reverse the biological age in, I believe eight weeks, right? Yeah. With lifestyle and nutritional interventions. So I would love for you to just... And I'm so excited to talk about this because I don't want... I think the, let's call biohacking or longevity industry is really painted to be like, you have to be very wealthy to join it. But what you're demonstrating is that the basics, mastering those, can get you massive results. So I would love to talk about that. Yeah.

[00:13:56.07] - DR. KARA FITZGERALD

I really toggle in two ponds where I I have an eye towards things coming down the pike, and I really want to explore them. I think it's incredibly important, and I'm curious and excited about them. And then I grew up with just not being able to afford a lot. Just in my universe as a kid, I have appreciation for being able to do things simply, just like going back to my mom and how she was able to raise us so healthily with a shoestring. She We had no money. How do you do that? That definitely informed our thinking around our diet and lifestyle program. We measured biological age using an epigenetic clock. So I know there's debate around what bioage is, can you reverse this, et cetera, et cetera. So just for any scientists listening, I just want to acknowledge that the change we saw was specifically in the first-generation multi-tissue horobath epigenetic clock. We measured that using saliva. We did our study. It's interesting, Kyla. We became pretty excited about the idea of epigenetics and how functional medicine could influence epigenetics before there was any notion that biological age could be changed. In fact, Steve Horbath, the developer of the first clock, the clock that we used, really the father of the field, didn't think that we could change it.

[00:15:39.12] - DR. KARA FITZGERALD

And that was not a long time ago. This field is just really just blown up. I mean, so much science, and so many of us are paying attention to it now, but it was like 2019 when the first bioage reversal paper was published, and that was the TRIM study That was a year long intervention using growth hormone and some other interventions. That was just nine men without a control group. I'm going to tell you, time stood still when that study came out, and Horvath was an author on it. He himself did all the validation of the clocks. The fact that the clocks consistently were able to change using that year long intervention, I don't know. It was just one of the most breathtaking findings. Our study was already underway. Our We were doing a randomized control study in Oregon at the HealthCat Institute, and we were underway, and we had the tools to measure biological age. But when we first developed it, we were thinking more broadly that our intervention would change epigenetics, change gene expression towards something more favorable. We were pretty bullish on that as our hypothesis. But this little corner of the globe where you can measure biologic age using epigenetics and actually change that, we weren't holding our breath because it quite simply hadn't been done.

[00:17:09.16] - DR. KARA FITZGERALD

So that was mid-study when that was published, and we were just gaga and excited. It made us more excited to look at the clock. We had been anticipating looking at the clock because we had the epigenetic data, too, but it just hadn't happened yet. When we did, so when we looked at the the Horvath clock and saw that in eight weeks time, a diet and lifestyle intervention was able to slow that clock down by over three years in our study group as compared to our control The BOLD group, it was really big news. It's changed the trajectory of my career. Then, of course, we wanted to publish what the protocol was, and it's been very exciting. To see that a simple diet and lifestyle intervention can be that powerful. Let me say that we weren't looking in unhealthy individuals. It took us a long time to run this eight-week study because we only wanted to recruit healthy individuals. In our study, because it was a pilot, we looked at middle-aged men because we wanted to capture when the aging phenomenon is happening in motion. If we had had women in our study, we would be working through premenopause, perimenopause, and postmenopause, and we were concerned that our numbers wouldn't be high enough for that as a variable.

[00:18:40.00] - DR. KARA FITZGERALD

That's why we chose men. But just as a side note, we subsequently published a case series looking at women using the same intervention, and they actually outperformed the guys a little bit. There's some differences, but they did really well. This is a dietary pattern we can talk about. We wanted people to pay attention to getting sufficient amounts of sleep. We wanted them to do a little bit for stress. We wanted to make sure that they were exercising. We didn't require them to use organic, to buy organic food. We wanted it to be broadly accessible. There's cool data out there showing that the compounds in food will help us detox out some of those toxins we're going to be exposed to or we are exposed to, especially if we're not eating an organic diet. So we felt confident that despite allowing any source of vegetable or any source of organic or not organic food, that we would see some decent outcome. So, yeah, it was needless to say, it was exciting.

[00:19:56.00] - KAYLA BARNES-LENTZ

That is incredible. Well, I'll definitely link your book, but can we walk through some of those interventions? So what did diet broadly look like, exercise, and so forth?

[00:20:06.17] - DR. KARA FITZGERALD

Yeah, sure. And I can tell you now, we just had accepted a study analyzing, just going back and looking at what did the heavy lifting in our intervention. So I can give you that now. We have the benefit of hindsight, and that paper will be coming out pretty soon. So the diet is a What we call epineutrient dense. We wanted every single forkfall to be packed with as many epinutrients or all epinutrients. These are foods that are going to influence gene expression. They've been identified to be able to influence gene expression vis-a-vis epigenetics. Particularly one way that one biochemical mark under the epigenetic umbrella is something called DNA methylation. We were really, really looking to sweet talk DNA methylation as much as possible with this dietary pattern. There are two ways that one does that, two broad categories with some nuanced on the side. We need to be able to make the methyl groups that can engage in DNA methylation. The foods have to be rich in those that support the methylation cycle. What we call methyl donor foods to support methylation, to produce these methyl donors that can then go and influence DNA methylation and gene expression.

[00:21:40.03] - DR. KARA FITZGERALD

People are familiar with those nutrients required in the methylation cycle. We know folate is important. We might not know why, but this is fundamentally why. We know B12 is important. Then additionally, Zinc is in there. The other B vitamins are in there. Betaine from beets. We might know beets are healthy or choline and eggs. We know that the eggs are really important, but why? Certainly one of the reasons it's going to be right in there helping the nutrient choline with methylation. Magnesium, potassium, even indirectly DHA, the long-chain omega-3 fatty acid is there. We wanted to pack, pack, pack the diet with that. We were actually successful. We increased circulating methylfolia in our study participants, and significantly as compared to the control group, and we didn't give them supplements. Then there's the category of a second epineutrient category. We called them loosely Methylation adaptogens. These have nothing to do with making the Methyl donors. These have to do with where that methylation is happening on the epigenome. You could You could turn genes on that you don't want on, turn genes off that you don't want off, that's protective. You want your protective genes on, your anti-inflammatory genes on, your longevity genes, your health, all of that.

[00:23:13.00] - DR. KARA FITZGERALD

You want your good genes on and your pro-inflammatory disease promoting, cancer promoting, et cetera, et cetera. You want those genes inhibited. As we age, the opposite occurs. There's this global change in how methylation is happening in the body. It's what they call it aberrant. It's in balance. There's genes turned off that we don't want to be off, and then pro-inflammatory genes are on. This is the aging phenomenon. It's crazy. Now, layer in exposure to environment and blah, blah, blah, blah, blah, blah. You can just have all of us experience this double whammy. These methylation adaptogen seem to sweet talk how methylation is happening. These, again, are familiar to us and have really time-honoured use histories. Things like green tea and curcumin, mushrooms, rosemary or rosmarinic acid in mushrooms. What else? Phycedin, risveratrol, really on and on. Quercitin, luteolin, just those beautiful polyphenol compounds that are in our colorful and green veg, in our cruciferous, in our fruits berries, anthocyanidins. What else? Urolithin A or the precursor, gallic acid, and just on and on. There are many, many, many, many different nutrients in a good Whole Foods diet that have the ability to shape how methylation is happening.

[00:24:53.17] - KAYLA BARNES-LENTZ

I mean, it sounds delicious and very similar. I think, how I'm eating, too. I'm always trying to. One question, because this is such a controversy in longevity, protein requirements. So what were the protein requirements? There's some people saying we were meant to have low protein for longevity. Then there's also people saying, of course, we need a lot of protein. So what did you land on?

[00:25:17.06] - DR. KARA FITZGERALD

Right. That's so interesting. I would say that overall, the pattern is a lower protein leaning, although in the study group, however, one can increase it. And I cover this more carefully in the book. Obviously, if you're pregnant or if you're preconception and planning, you want to be doing more. If you're older, you want more. If you're engaged in building muscle, you want more. So there are times when our body requires more protein. But I would say overall, our dietary pattern is not in keeping with the really strongly pro-protein conversation that's happening right now. As a lifter myself, I shifted somewhat from the original lower protein, and I guess just analyzing the data. I've had Valtrer. Valtrer long ago has been the big advocate of a lower protein dietary pattern. I mean, it's not that low, but a lower protein, and then bumping it up as we age. I think his research bears that out. There's an argument there for it. We can also look at blue zones, and they're not consuming a ton of protein. But I know it's something that we tease out and it's sticky. But the pro-cancer idea that he and others posited with higher protein intake, I think that's been adequately demonstrated to not be the case when the overall dietary pattern is healthy.

[00:26:49.23] - DR. KARA FITZGERALD

Higher protein in the context of an overall healthy dietary pattern, in my mind, is not a problem, and especially with regards to those times when we want to build muscle or we're growing a baby or post-surgery, et cetera, et cetera, or when we're older and we want to maintain the muscle and hopefully increase it. I've shifted somewhat to being really comfortable with the idea of higher protein as appropriate. To the extent that I blogged about, and people can access this, how one would do the younger eudontary pattern with high protein, a high protein overlay. The challenge with doing the high protein as it's being recommended in certain places right now is that it will supplant all of these epi-nutrients because you'll just literally be eating all day long. A high protein dietary pattern is incredibly filling. There's not a lot of room for the basically nine cups of veg and fruit that we're recommending or some of the eggs, liver and so forth. I I landed on toggling, doing these high protein days on a lifting day and then going back to the full younger EU dietary pattern where it's really dense in the veg, the epinutrient veg, and Then when you average it out over the week, it's a decent amount.

[00:28:20.16] - DR. KARA FITZGERALD

One can achieve a decent amount of protein. My position today is there's a place for high protein. I'm not dogmatic about it. I think we can be individualized about it, but I do think we don't want to lose this extraordinary epineutrient information as we're trying to ingest more protein. We really need to look and design a decent dietary pattern.

[00:28:51.02] - KAYLA BARNES-LENTZ

For you, what does it look like to be... Well, what did the younger you, like how many grams of protein per pound or kilogram bodyweight? Then what do you think is okay to trend up to on maybe heavier lifting days?

[00:29:05.23] - DR. KARA FITZGERALD

I think we could go as high as maybe a gram per pound body weight or 2 grams per kilogram on heavy lifting days, and then down to maybe 1-1. 2 grams per kilogram on younger U-focused days, on epineutrient-focused days. That's what I wrote about. I think sky's the limit on a lifting day. You can go ahead and ingest it and turn the volume down on some of the other epineutrients, and then just jump into catching up on those epiutreants on off days. There's wiggle room in the literature between 1. 4 up to 2, and then the lower protein days, maybe as low as 1 to maybe 1. 2 grams per kilogram.

[00:30:00.22] - KAYLA BARNES-LENTZ

Well, thank you for giving us an answer on that. I feel like it's a big question going around because there's just two very different camps.

[00:30:07.15] - DR. KARA FITZGERALD

Huge question. It's a huge question. And I'm not giving a simple answer. I'm not just saying, Okay, everybody, do this. I'm saying that you really want to think it through. I think the blog lays out how I approach it. But if I am going to simplify my answer, it would be, some days are your high protein days, some days. But you're going to be losing... If you think about... I think about food as information. If you are going to go solid high protein all day long, you are going to lose a body of information that is wildly essential that we're only beginning to tap into. All of these epinutrients are just extraordinarily important.

[00:30:46.13] - KAYLA BARNES-LENTZ

Hi, guys. I'm going to interrupt this episode for a brief announcement. As you may or may not know, I started a community for females, by females, and it's a female longevity optimization community. This is a place that you can connect with like-minded women. We are all here to support each other, and there's a variety of different benefits to being a member. You get a monthly Ask Me Anything, so submit your questions and I'll answer them directly. We also have an entire library of courses on all of the important components of longevity, such as labs, nutrition, exercise, sleep optimization, longevity optimization protocols that I'm doing, along with real-time updates to my personal protocols. There are so many benefits of being a member of the community. We'll also be doing in-person live events here in California and virtual events for anyone that can't attend. But if you're interested in joining the community, I would absolutely love to see you there, and I will include a link in the show notes. How do you feel about seasonal eating then? So if we think about what we used to do, do you think that's most compatible?

[00:31:56.05] - DR. KARA FITZGERALD

Yeah, I think so. If it's doable, I don't have a No real dogmatic feeling around that at all. I have a little kid at home. I mean, actually, everything is here in Mexico all the time. Winter is basically summer, where I'm from originally. The growing season is all year long, basically. Maybe there's a little break in the highest heat summer. But I think seasonal eating is probably a real fabulous thing to do for some people. It might If it's too stressful for other people. If it works for you, do it. If it enables you to get a good complement of epineutrients, do it. If it doesn't work for you, if it feels stressful and you're super busy in other arenas, just don't sweat it. Do get all of that epinutrient information, but do it in a way that works for you.

[00:32:52.17] - KAYLA BARNES-LENTZ

Yeah. Love that. Well, any other points on nutrition?

[00:32:59.12] - DR. KARA FITZGERALD

We did a little... So we had a gentle intermittent fasting structure or time-restricted eating structure. We just wanted people to eat for 12 hours and then ask for 12 hours, which, as a friend of mine pointed out, was how we always ate. Until that era of fast ultra-processed food, and we're just eating all the time now. So it was gentle, and we wanted people to do that. We wanted it to be broadly adaptable. I mean, that's the fundamental goal of this. When we developed this program, we were using it in our clinic practice originally, and we just wanted to hold the branch down and really make sure everybody was going to tolerate the dietary pattern, be able to do the dietary pattern. So a gentle intermittent fasting structure. I think, again, depending on who you are, you can turn the volume up on that for sure. And depending on where you are in your life. If you're a premenopausal woman, you're going to have different needs when you're menstruating versus when you're not. And if you're older, you might have different needs versus being middle-aged or younger, et cetera. So within the window of what's reasonable for you, the individual, I think the 12 on, 12 off is broadly adoptable by all of us.

[00:34:13.18] - DR. KARA FITZGERALD

And then for some of us, and at different times in our lives, we can certainly turn the volume up on that. I'm not a huge fan of the one meal a day just because nutrient deficiencies are a likely shoe unless it's extraordinarily well-designed and well-planned out. I don't know that metabolically all of us are designed for that, but there's always exceptions. But yeah, I think those are the biggest pieces of the dietary pattern. And like I said, I can make this information available to folks later. Thank you.

[00:34:53.07] - KAYLA BARNES-LENTZ

Yeah, we'll definitely include links in the show notes. So then moving on to exercise. What did that look like?

[00:35:00.03] - DR. KARA FITZGERALD

Well, let me say right now that it didn't make a difference in the final outcome.

[00:35:06.12] - KAYLA BARNES-LENTZ

You're late, right?

[00:35:08.08] - DR. KARA FITZGERALD

Yeah. So stop exercising people. Sleep late. Whatever. No, I'm kidding. I'm kidding. I I'm a very committed exerciser. It's my sanity. The reason is because we were looking at healthy individuals, and so our control group was exercising also. So it was a wash when we we did our final analysis. That's why. In what we prescribed in the program and what you would read about in the book or in the papers is, again, something we wanted to be broadly adoptable, which is a minimum of five days a week, 30 minutes a day. So that's the minimum of whatever you want to do, hitting your own perceived exertion of 60 to 80% of your max. So 60%, you might be starting to perspire a little bit. Maybe you're breathing a little bit harder. And then 80, obviously, you can still carry a conversation on, but it's going to be a little bit harder. You're going to be sweating. So whatever works for you, you could do and do it for a minimum of 30 minutes, five days a week. For my mom, this is gardening and walking through her neighborhood. For me, I'm a cyclist, a super committed cyclist.

[00:36:29.12] - DR. KARA FITZGERALD

I'm on my most days, or I go to the gym and I'll do some lifting routine that will elevate my heart rate. It could be dancing. I mean, it even could... There's research on cleaning the house, which It's funny. I would never participate in that study. I don't know about you. I would never participated. But it actually changed gene expression. It had good outcomes cleaning the house. So whatever works for you. There's cool research on community-centric exercise as being more effective because you get that connection on top of the physical activity. My daughter here in Mexico loves football, as they call it, soccer. She just loves her teammates, and a lot of them are in her school. It's just really nice and juicy for her. I think that's beneficial for us at any age. If we can do that, if we have a sport that's community-centric, that's all the better. We just weren't able to tease it out of our data because both cohorts were exercising. Sleep is hugely important. You can't make people sleep, but we had... I think the reason our study ultimately showed what it showed, not only did we lower the biological age as measured through Horvath's clock, we lowered triglycerin pterides, suggesting they were in a little bit of ketosis.

[00:38:02.07] - DR. KARA FITZGERALD

We increased circulating metholfolate. We lowered LDL. People lost weight. Basically, they weren't overweight, really, to begin with, because we were recruiting a healthy cohort. So they were just tightening up a little bit metabolically, which is really pretty cool. And I think the reason we were successful is that we had nutritionists acting as as nutrition coaches, and they were required to connect with the nutritionists at least weekly for the first month, and then most of them just kept connecting with them. The nutritionists would help them with regard to sleep. They'd answer any of their questions, help them brainstorm on sources, on recipes, blah, blah, blah, whatever they needed to do the program. But with regard to sleep, we would give them sleep hygiene tips. Go to bed at the same time in a cool room, make it's dark, adjusting schedule and phone and on and on. But the usual sleep hygiene tips we used with these guys. We also had people engage in a meditation, so we wanted people to do... And this is just a basic relaxation response. Incidentally, every element of this program is built with our best read on the science of epigenetics.

[00:39:34.07] - DR. KARA FITZGERALD

So brick by brick, every single component had data as beneficially changing DNA methylation. So Sleep is a huge player. Exercise is massive. In fact, sometimes I refer to exercise as being like a vegetable. It can change gene expression. It's like kale. It can change gene expression, not dissimilar to what kale does or a huge well-designed salad. It's really pretty extraordinary. Stress. Stress is, I think, gasoline on the fire of aging. Stress may prove to be one of the most potent toxins with regard to accelerated aging. We knew we needed to work with our community with this study on grounding, on really getting centered and engaging in some a mindful practice. So we kept it super simple, and it was the relaxation response as created by Benson out of Harvard many years ago. He was one of the first guys to research the benefits of meditation. We I think that that was an important component.

[00:40:48.10] - KAYLA BARNES-LENTZ

Yeah. I think that could be one of the most difficult ones to really manage because we can take supplements, we can eat the right foods, know that we're going to the gym. But the stress piece, I find it be one of the more difficult ones. What I've observed, and it seems to support this in the literature that women tend to perceive stress at a little higher levels. It's funny because I'll look at my husband's aura ring, my aura ring stress levels, and we're both very busy running businesses, and he somehow is in restored all day on the aura ring where I- Interesting. It's super interesting. And then I'm fluctuating between engaged, sometimes stressed. I found something interesting And with Hbot, though. As soon as the pressure... I have a hardshell chamber at my house, and as soon as the chamber gets pressurized, I immediately drop into restored, and I stay there the entire session.

[00:41:41.16] - DR. KARA FITZGERALD

Wow. Isn't that cool? God, that's great. Jeez. I think I noticed that my stress response, oh my God, when we moved to Mexico, that's a huge reason why we're here, just addressing the quality way of life and turning the volume down, it's just massive. So I noticed a similarly powerful change for me being here. And I think just for your listeners, exploring what really dials them in as far as being able to tune out and tune down the stress experience. But to your point, the meditation practice that we prescribed was the least adhered to of all the elements. And we had these nutritionists sticking to the participants like glue. We were given an unrestricted grant to do this study, and it's a six-figure study. It's conducting human research, especially in a randomized control trial and using a clinical research center like we did. It's so expensive. I thought, It's just not every day I'm going to get that a grant. I really wanted the participants to adhere to the intervention. They stuck with them. They stuck to them like glue. Still, of all of the components, it was the least adhered to. But when we went back and analyzed the diet, they did it.

[00:43:14.12] - DR. KARA FITZGERALD

They did it. They hung in there. We wanted them eating liver. That was the least adhered to of the foods, but they did. But plenty of them actually stuck their toes into consuming liver. Now, I just do liver caps. There's plenty of I wish I had known that at the time, maybe given everybody liver cata.

[00:43:34.20] - KAYLA BARNES-LENTZ

How much did they have to eat? Because it tastes really bad.

[00:43:38.03] - DR. KARA FITZGERALD

I know. And just preparing it. But you know what? They have this fabulous nutrition team who could really help them create liver that tastes good and how you do it and how you source it.

[00:43:50.10] - KAYLA BARNES-LENTZ

Oh, wow. I need that tip, too, because my liver, I just freeze it into these little things now.

[00:43:56.18] - DR. KARA FITZGERALD

That's what you do. That's awesome. I take caps. Yeah. Kind of the same difference. It's a little freeze, dry, non-dif added liver. What was your question? How they prepared it? How did they do? We wanted them to just do... I think our recommendations is twice a week, a minimum of twice a week. I mean, it's not horrible, but still. It's the element of our program I've been... I'll admit, I've not been... Well, now I'm perfectly successful because it's encapsulated. But back then, yeah, I wasn't doing a great job. Well, I don't blame you.

[00:44:34.06] - KAYLA BARNES-LENTZ

It's hard. It's hard. It's hard. It's hard for a very hard game changer. Okay, so anything else? We talked about the exercise, we talked about... So the nutrition was the biggest lever here Is that correct?

[00:44:46.02] - DR. KARA FITZGERALD

Yeah. For our post-study re-analysis of our data, the nutrition was doing the heavy lifting. And of the nutritional components, it appears like what we're calling the methylation adaptogen. Those beautiful polyphenols did the heavy lift. I would say, and it remains to be seen, and hopefully we will continue to research it. I would not go to a McDonald's dietary pattern and throw some strawberries and curcumin and green tea in there. I don't think you're going to get the outcome. I think it's the entire dietary pattern. But it's cool to see validation with this group of nutrients. That's actually pretty extraordinary. What's extra neat is that since we did our study, and our study was the first randomized control diet and lifestyle intervention in humans, looking at biological age, it was the first one ever done, which is amazing to me still. But since then, there have been other studies. We have more and more human data. I'm sure you're aware that the Mediterranean diet continues to prove its worth with regard to changing DNA methylation, which is so cool. We can see that some of the Mediterranean diet studies show that they're able to slow bioage as measured by using epigenetic clocks.

[00:46:20.12] - DR. KARA FITZGERALD

It's awesome. It's validating to us because our dietary pattern is similar in many ways. It's not completely There's some real key differences, but it's similar to a Mediterranean dietary pattern. Our polyphenol content is higher than almost any other, certainly any other dietary pattern and includes including Mediterranean dietary patterns, including Mediterranean dietary patterns with a strong polyphenol content. Ours is even higher. So we're getting validated for this nutrient category for sure, like how extraordinarily important it is and how it did the heavy lifting in ours and how we're seeing other corroborating studies.

[00:47:14.12] - KAYLA BARNES-LENTZ

I love Yeah. And what was the final average of bioage reversal?

[00:47:20.05] - DR. KARA FITZGERALD

The average was 3. 23, I think. Maybe 3. 24. And that's as compared, 3. 23 three years as compared to our control group. And then there was also a significant within-group change of a little over two years. So that's the people compared to themselves at baseline, the follow-up. A big change within the two groups, or as compared to the two groups, and then a significant change within the study group from baseline and follow-up.

[00:47:58.20] - KAYLA BARNES-LENTZ

Then you were Such a short period of time.

[00:48:01.22] - DR. KARA FITZGERALD

Yeah, eight weeks. I know. That's extraordinary. And arguably, I mean, maybe we'll look at doing this a little bit longer. We might see better outcome. I think it's a pretty rigorous dietary pattern. Just using it in clinical practice, just having the advantage of having tested it for years before we studied it in the clinical setting and making Taking massive dietary changes, as we do as physicians in the clinical setting, eight weeks is a reasonable amount of time where many people can be successful in a huge change like that. And so that felt realistic to us. But some of the other studies that I'm mentioning, looking at Mediterranean dietary patterns, which are easier, are much longer. And so there's probably a sweet spot. What I would say is, and what we recommend frequently is that people do this eight-week, maybe a couple... You could actually do it full-time. You could eat this full-time. It's nutritionally replete. You could do it all of the time and not worry about any micro or macronutrient deficiency. But you could also just do what we call the intensive, this eight-week dietary pattern, maybe a couple of times a year or a few times a year, and then ease up a little bit.

[00:49:25.17] - DR. KARA FITZGERALD

If your body tolerates dairy, you can bring some dairy in. If your body handles some whole grains and so forth, you can bring those in. Lagooms, we actually take lagooms out of the eight weeks, and I think those are incredibly important for many of us, so you can bring those in. It may be that you're ultimately... The best dietary pattern for you is a combination program. The way that one will know that, just as we do this in clinic practice, is by getting some laboratory assessments. You can your biological age assessment. We like the pace of aging clock. That's our current favorite. Get those at baseline and then see where you are at the end. If you augment your pattern after that, maybe test in another 2-4 months after that just to see if you're dialed in. Then, of course, see how you feel, importantly.

[00:50:21.19] - KAYLA BARNES-LENTZ

I'm so grateful for this study. It would have been really fun to see because I'm just personally curious how much the gut microbiome could shift given a diet like that in that same time period. Yeah. I'm sure it changed massively, but it would be so fun to see that data.

[00:50:39.17] - DR. KARA FITZGERALD

And we did give them a probiotic. We used a basic probiotic formula that has some data behind it as being able to support the microbiome and produce in folate. A healthy microbiome can basically produce a multivitamin. A good healthy gut microbiome is going to be giving us those all-important macronutrients as well as our diet. We wanted to lean into that, and we did give them a probiotic. We can't really tease out whether that made the difference. In fact, I don't know. Intuitively, I would just argue that the amount of folate that they were consuming is what increased or circulating folate because the dietary pattern was very folate dense. But yeah, there's no doubt we radically changed the microbiome. There's no doubt. It's When you get a ton of data like that, you're going to be spending a ton of time analyzing it. It's a huge job. We're still actually will be publishing a paper in the not so distant future doing what's called an epigenome-wide association study. Going back to our original question that we were curious about, we can see now that we moved the needle not just on clocks, but hundreds of genes Hundreds of methylation sites on different genes changed methylation patterns.

[00:52:05.18] - DR. KARA FITZGERALD

We can see that they're related to inflammation, related to cancer, related to metabolism, to fatty acid metabolism, and on and on. So that's something that we want to publish as well.

[00:52:18.20] - KAYLA BARNES-LENTZ

Yeah, that's so exciting. So they did one probiotic. Was there any other supplementation involved?

[00:52:24.16] - DR. KARA FITZGERALD

We gave them a greens powder. So just being bullish on those on the polyphenol compounds I'm talking about, we gave them a greens powder, which it just was a combination of basically fruit and veg in a powder, and we had them do that.

[00:52:43.11] - KAYLA BARNES-LENTZ

Any specific brand that you want to mention?

[00:52:46.00] - DR. KARA FITZGERALD

Yeah, both of them are metagenics. Both of these are metagenics. In fact, it was metagenics that funded our whole study. So I'm happy to just give them some love because it was pretty extraordinary. And they gave us complete control I love study design, 100 %. They did not influence what we did in this study. In fact, we own all of the data. There's nothing proprietary that those guys own. They were very hands-off. Yeah.

[00:53:13.23] - KAYLA BARNES-LENTZ

I mean, I love Metagenics, too. It's one of my favorite brands. Well, that is all amazing. I know that we're coming up on time here, but I would love to... I mean, we could probably talk for three days about this stuff. So I would love to go back a comment you made earlier about this analytics because I'm personally interested. So yes, I feel like this is a huge question. How often do you dose them? Can you stay on them for extended periods of time? Would love to hear anything you're thoughts on that.

[00:53:46.21] - DR. KARA FITZGERALD

I think so I'll just say that P16, there's a lab, Sapier Biosciences, that will have or has a P16 test available available now that gives us a window into who is appropriate for a senalytic. I mean, actually, let me step back.

[00:54:09.14] - KAYLA BARNES-LENTZ

Food as senaletics.

[00:54:11.08] - DR. KARA FITZGERALD

So what are the big ones? Like, phyceton. I think querceton might have some senalytic properties. Who else am I missing? What are the really obvious ones that are coming to mind right now? There's a whole handful of botanical compounds or polyphenol compounds that have these phenolite properties. I think EGCG does. I think curcumin has a little bit. We want these in our diet all the time. We want to be eating that senalytic information. Of course, it did. I think I mentioned that, is important. There's no need to limit that. When we move into more aggressive Actually, urolithin A, I would argue, probably has some centylated properties as well. So pomegranate, natto, that you had mentioned. Important. So I think food as medicine, we can always do it. We can always do it. We can lean on it. We can take it daily. But we want to evaluate who's the best candidate for using some of the more aggressive interventions. I mean, this would help us design the quasi using rapamycin. Rapamycin is a quasi acetylindic agent. This would help us tease out who's an appropriate candidate and maybe give us some ideas around dosing and stuff like that.

[00:55:43.06] - DR. KARA FITZGERALD

Then we can do follow up and make sure everybody's doing well. You can do a confirmation that if you're deciding to do rapamycin, that your dose is dialed in. I think that's just going to be a really useful tool. Probably the majority of us would benefit from regular intentional senaletic agents in our lives, be them whole food dietary pattern, including be them some carefully selected senaletic supplement protocols or adding in rapamycin, probably most of us will. I think there's an important role for most of us taking senalytic agents. I think we can do a food forward approach and make sure we have some of them in our diet all of the time. If we're eating a good whole food dietary pattern with lots of fruits and veg, we can be confident we're getting some senalytic phytochemicals in our diet. We can turn the volume up and do a specific phenolithic supplement with a combination, a higher concentrate than we would get in food, and I think that that's appropriate. Then we can turn the volume up and go for some of the medications, the most famous being rapamycin. I think if we opt to do a more aggressive approach, it's useful for us to look at a newly available test called P16.

[00:57:16.03] - DR. KARA FITZGERALD

That test will give us insight into maybe perhaps how aggressive we should go or how gently we should go with using senalytic agents. But I do think a food forward approach is always going to be safe, really for the majority of us.

[00:57:32.16] - KAYLA BARNES-LENTZ

I love that. I'm excited to see, because now it felt really confident on the rapamycin being able to slow bioage. But then some new literature has come out that almost is the opposite, if you've seen that. Then there's also the consideration because I was taking rapamycin. I was really taking it, though, for the potential ovarian longevity impact because there's a new... It hasn't been peer reviewed yet, but there's information showing that it could potentially delay ovarian aging by five years. So where are you falling right now, given a little bit of conflicting info, but what's your take?

[00:58:10.03] - DR. KARA FITZGERALD

I think that, well, for some of us, rapamycin is probably a really awesome choice. And mechanistically, it may be doing something that's outside of the purview of some of the clocks that we're using now. The clocks, by and large, I don't know that we're actually measuring what aging is. It's a whole separate conversation, but I think there's surrogate markers of the aging phenomena, so they're suggesting the age is accelerated or decelerated. All of the interventions that we're considering now are not necessarily going to move the data needle on some of the clocks. I think we have to sit tight. I'm still a fan of Rabba Myson. I would, again, probably lean towards looking at senescence activity using an assay like P16. I think if we're dosing it in the very modest way that a lot... Well, there are some biohackers that are going extremely aggressive, and I think you can run into some trouble there. But if you're dosing it in the relatively modest way that many folks are doing, I think it's a reasonable intervention to consider, even as not all of the clocks are perhaps, responding as we were all hoping. I think it's just...

[00:59:48.10] - DR. KARA FITZGERALD

And that may speak more to the limitations of the clock. We just have to keep our eyes open and be careful and be modest in our dosing and make sure we're a good for that intervention. It is ultimately individualized medicine at the end of the day. We have to be... As a functional medicine provider, we look at functional medicine as being longevity medicine, and it's really through a very individualized lens. So what's right for you in your protocol isn't right for, really, everybody else. So Some of it is, some of it's going to be important and inspiring, but it's going to be their own spin.

[01:00:36.10] - KAYLA BARNES-LENTZ

Yeah, absolutely. Okay, last quick question is, favorite longevity supplements or what does your stack look like?

[01:00:45.04] - DR. KARA FITZGERALD

Yeah. I am a huge fan of your olipine A, like yourself. I'm a huge Mitopure fan. I love their investment in science. They're just knocking it out of the park with all of their preclinical clinical and clinical data. They have a ton of human data. I'm a big fan of Pendulum probiotics. Again, I think they've got awesome, exciting, pretty sexy science. I am a fan of MitoQ, which is a CoQ10-like molecule. It's not CoQ10, it's a little bit different. Again, it's just because they've got really bad ass science on it that's suggesting it really does some extraordinary beneficial mitochondrial supportive things different mechanistically than what urolithin A does. There's some cool compounds out there. I'm also a fan of liver and what else? Vitamin D every day, fish oil. I don't get enough fatty fish in my diet, and I'm concerned about the quality of the fish that we can readily I definitely take fish oil supplements. If I didn't say magnesium, of course, magnesium is in there as well. But those are some of my favorites.

[01:02:10.19] - KAYLA BARNES-LENTZ

I love that. I agree on all those. The only one I haven't tried, did you say it's called MitoQ?

[01:02:16.23] - DR. KARA FITZGERALD

Mito, like mitochondrial, MitoQ. Okay, amazing.

[01:02:21.09] - KAYLA BARNES-LENTZ

Yeah, check it out. I'll put that one. Well, it has been such a pleasure to have you here. Really, really fun. I just Thank you on behalf of everyone for doing this type of research and studies and putting it out there. I think it should exci... I remember the first time I saw it, I was so excited. I was like, makes so much sense. But to have this in papers and the data there, it's just absolutely incredible. So thank you for that. I would love to have you on another time, too. We can just continue to dive into all things longevity. But thank you for being here. This podcast is for informational purposes only, and The use expressed on this podcast are not medical advice. This podcast, including Kayla Barnes, does not accept responsibility for any possible adverse effects from the use of the information contained herein. Opinions of their guests are their own, and this podcast does not endorse or accept responsibility for statements made by guests. This podcast does not make any representations or warranties about guest qualifications or credibility. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein.

[01:03:31.07] - KAYLA BARNES-LENTZ

If you think you have a medical issue, consult a licensed physician.