036-Dr Kara Fitzgerald: Can lifestyle reverse epigenetic age?

Reversing DNA methylation can result in restoration of vision loss in old mice (Lu 2020).  Can human epigenetic methylation clocks be reversed using relatively straightforward lifestyle changes?  

Dr Kara Fitzgerald is the first-ever recipient of the 2018 Emerging Leadership Award from the Personalized Lifestyle Medicine Institute in recognition of her work on DNA methylation. She is on the faculty at the Institute for Functional Medicine (IFM) and is an IFM Certified Practitioner.

She received her doctorate in naturopathic medicine from the National College of Naturopathic Medicine in Portland, Oregon.

Dr. Fitzgerald runs a Functional Medicine Clinic Immersion program for professionals, hosts a very popular podcast New Frontiers in Functional Medicine, and maintains an active blog on her website.  Her new book ‘Younger You’ on how she was able to reverse aging with lifestyle is coming out in Jan 2022.  

Please join Dr Kara Fitzgerald for this masterclass in human epigenetic DNA methylation manipulation.

Take away points: 

-Increased DNA methylation age is associated with no significant net methylation change.

-~25% of methylation clock sites are related to glucocorticoid response elements underscoring the relationship of stress and aging.

—Supplemental methylation helpers (folate, b12, choline, etc) have a narrow effective range- with too little or too much having negative consequences.

-Lifestyle changes can reverse DNA methylation age in humans.

00:00 Kara’s vision for reversing global epidemic of chronic disease

03:10 Appeal of naturopathic medicine as a systems model similar to functional medicine 

06:04 Value of -omics; epigenomics, metabolomics, and microbiomics

07:39 DNA methylation process and epigenetic age

11:39 No net change in methylation with aging, just rearrangement of sites

12:25 Dose response of dietary methyl donors

15:18 Horvath methylation clock used in paper

19:23 Components of the lifestyle intervention 

25:32 Effect on triglycerides

28:34 Options for vegans instead of liver as a methyl donor

32:05 Ongoing program and forthcoming book

35:05 Personal lifestyle choices

37:02 10 cups of vegetables a day, 12 hour fast per day 

38:03 Exercise, relaxation, and sleep choices 

 https://www.drkarafitzgerald.com/ 

Lu, Yuancheng, Benedikt Brommer, Xiao Tian, Anitha Krishnan, Margarita Meer, Chen Wang, Daniel L. Vera, et al. “Reprogramming to Recover Youthful Epigenetic Information and Restore Vision.” Nature 588, no. 7836 (December 3, 2020): 124–29. https://doi.org/10.1038/s41586-020-2975-4.

 Fitzgerald, Kara N., Romilly Hodges, Douglas Hanes, Emily Stack, David Cheishvili, Moshe Szyf, Janine Henkel, et al. “Potential Reversal of Epigenetic Age Using a Diet and Lifestyle Intervention: A Pilot Randomized Clinical Trial.” Aging 13, no. 7 (April 15, 2021): 9419–32. https://doi.org/10.18632/aging.202913.

 

 

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#longevity  #wellness #antiaging #biologicalage #lifestylemedicine #younger #epigenetics #biohacking  #RobertLufkinMD #Karafitzgerald

 

 

Robert Lufkin 0:01
Have you ever wondered what secrets medical experts use themselves to maintain optimal health and longevity? Hi, everyone. My name is Dr. Robert Lufkin and welcome to the health longevity secrets show where we talk to the experts and find out their secrets for health and longevity, not only what they recommend, but what they actually do for themselves. Today’s expert is Dr. Kara Fitzgerald, the lead author of a groundbreaking scientific study which asks the important question, can lifestyle changes over eight weeks affect human epigenetic age as measured by a methylation clock? Hi, everybody. Welcome to health and longevity secrets what experts do themselves where we interview the best minds in health and longevity. I’m absolutely thrilled today to be here with Dr. Kara Fitzgerald. I share her vision of the widespread adoption of health the health care model that reverses the global epidemic of chronic disease and supports the development of vibrant longevity. Dr. Fitzgerald is the first ever recipient of the 2018 emerging leadership award from the personalized Lifestyle Medicine Institute. In recognition of her work on DNA methylation. She lectures globally on functional medicine. Dr. Fitzgerald is on the faculty at the Institute for Functional Medicine or IFM and is an IFM certified practitioner with a clinical practice in Newton, Connecticut, which we’ll hear more about today. She received her doctorate in naturopathic medicine from the natural College National College of naturopathic medicine in Portland, Oregon. truly passionate about educating clinicians and lay people like Dr. Fitzgerald runs a functional medicine clinic immersion program for professionals. She also hosts hosts of very popular podcast New Frontiers in functional medicine, which is one of my personal favorites that I listened to. And she maintains an active blog on her website. Her new book that we’ll also be hearing about is coming out in January 2022. She’s also an avid cyclist and a mother of a passionate for life toddler. Of particular attention to this audience. He’s also the lead author of a groundbreaking scientific article describing a randomized clinical trial, which asked if lifestyle changes over eight weeks can affect epigenetic age as measured by a methylation clock. Dr. Fitzgerald welcome again to health longevity secrets.

Kara Fitzgerald 2:42
Thank you. It’s great to be here. I appreciate and support your your vision to continue to change the medical paradigm. So thanks for jumping in.

Robert Lufkin 2:52
Yeah, I think I think we share we share that thought and it’s great to see some so many people taking an interest in this. Absolutely. What brought you here on your on your journey to work in this fascinating field?

Kara Fitzgerald 3:09
Well, I mean, we can go back, it depends on how far you want to go back. I can I can give you a little bit of a snapshot because I don’t want to just interrupt me if I go down any rabbit hole and anytime just interrupt me. No offense, and clarify if I say anything, that doesn’t make sense. I so just getting into naturopathic medicine, basically, you know, the decision for me around medical school came at a time that I was struggling with chronic fatigue. And of course, I went to doctor after doctor after doctor and didn’t get better until I saw a naturopathic physician and it was at that extraordinarily pivotal time of making my decisions for my training. And that’s and really that’s how it happened. I mean, he was one of the first Andy’s here and can can are one of the longest practicing Andy’s I think his license here is like number 23 or something. I mean, you know, we’re sort of it’s a small profession, but that directed me to naturopathic medicine. And the cool thing about naturopathic medicine is that it really is kind of a systems model. I mean, it’s very much in alignment with functional medicine. And I came upon Dr. Jeff bland, who’s a nutritional biochemist, when I was a student and I resonated so much with this sort of the the biochemistry and kind of the more orthomolecular piece and I was able to do a postdoc in laboratory science, you know, just it’s I just feel like it was great that I got to do that because it was so in alignment with my area of focus and I was working under Richard Lord who’s a really highly regarded nutritional biochemist in our space. And, and and you know, was able to from there leapfrog into functional medicine, which is again, it’s all of it is very deeply in alignment with things that are I’m passionate about and thinking about sort of reaction candidate getting into some of this, the biochemistry, some of the Arkana, around physiology and how we can tweak it using natural interventions really became a life focus. And, and it was a, you know, it’s a different story. But it was a natural progression for me to discover epigenetics and really begin to puzzle around how we’re influencing gene expression through epigenetics in functional medicine. So it was kind of a natural progression of my career.

Robert Lufkin 5:34
Oh, wow. That’s, yeah, that’s, that’s fantastic. And it’s so powerful, having mentors in our lives and just who we wind up with, can have such a dramatic effect. But but the area you’re working on now, it seems it’s it’s really transforming all of medicine, and, and even the mainstream, sort of the medical schools, where I’m coming from, they’re shifting this way. And this is truly the future I think,

Kara Fitzgerald 6:03
we are in a revolution in, in, in medicine, and in science, as significant as the Industrial Revolution was, you know, a few centuries ago. I mean, it’s, it’s we’re in extraordinary times here in science and in medicine.

Robert Lufkin 6:15
Yes, it’s such an exciting time. And and it’s great to get the message out to the people themselves, who who can benefit this directly, as well as other practitioners. Also,

Kara Fitzgerald 6:26
one of the I know, one of this, a huge aha for me, and this started to happen at the lab, but really it continues is that the more we’re able to sort of look at the omics, you know, the genetic expression, you know, epigenetic patterns, you know, metabolomics, all of the, you know, microbiome omics, and so forth, the more that we’re able to look with such sophistication at what’s happening to us physiologically, the more we realize that these simple truths, like you know, eat a whole foods diet, you know, get enough sleep, chew your food, exercise, move your body, we know, the more we see how impactful these things are. So it’s sort of this interesting paradox of these humble things from, you know, what we evolved, are, are as or more integral as we’re able to actually look at what they’re doing in the body with this omics insight we have now

Robert Lufkin 7:19
exactly and, and ultimately even more effective than doing than doing the giving drugs or, or this sort of thing. I mean, who would have thought that diet is so transformational in our lives? And who would have thought that brushing our teeth, for example, will prevent a heart attack and also prevent, you know, decrease our risk for dementia and things like that by decreasing inflammation? And, you know, simple lifestyle? It’s

Kara Fitzgerald 7:48
crazy. Yeah, simple lifestyle hacks at the end of the day, that’s where it’s at. It’s pretty crazy. But science is backing it up in spades.

Robert Lufkin 7:57
Exactly, exactly. Well, we have so many, so many exciting things to touch on today, when I’m really limited about a time but let’s first turn to your paper about the use of methylation clocks to validate possible effects of lifestyle changes. And maybe, maybe for our listeners, we can just take a moment and review methylation and methylation clocks, if you don’t mind.

Kara Fitzgerald 8:20
Yeah, absolutely. So people may be familiar with the methylation cycle. That is where we make s adenosine the finding. So if I, if maybe people have heard of homocysteine, it’s commonly thought of as a cardiovascular risk marker, that’s where it’s most famous, but it’s actually a major player in the full methylation cycle. So homocysteine gets recycled back to methionine, and then the finding is converted to ES adenosine refining, and that little compound that’s our universal methyl donor. And that goes around to to the hundreds of methyl transferase enzymes that that that are in our body engaged in methylation reactions, and is a cofactor in that reaction. So we do we’re doing methylation and every cell in the body really all of the time and you know methylation, a methylation reaction will help from detox, lead or or help with drug metabolism. It’ll help make dopamine one of our all important neurotransmitters, it also helps metabolize dopamine and adrenaline it helps metabolize estrogen. So methylation plays a massive role. It’s it’s just a carbon with three hydrogens. It’s an exquisitely simple molecule. And I think we just evolved, you know, having ready access to carbons and hydrogens, and so it just it’s got this huge multifaceted methylation has a huge multifaceted role in many, many parts of physiology. Our area of interest is specifically around DNA methylation, which is an epigenetic mark and there are a lot of there are different ways genes are gene expression. is regulated, but one of the key players is DNA methylation. And so these are this is when methylation when a methyl group is actually laid down on to a cytosine, which was one of the bases in DNA. And when there’s a collection of these methyl groups at a particular promoter region of a gene, it’ll actually have an inhibitory effect. Conversely, methyl groups can be removed or the body can prevent methyl groups from being laid down. And that and that promoter region will not be heavily methylated. And that gene will be on so methylation groups generally tend to turn a gene off. The lack of methylation groups tend to keep genes on. So that’s a little bit of background any.

Robert Lufkin 10:42
Yeah, yeah. I mean, one aha moment for me on methylation. That was a great explanation was that sort of the first approximation model for it was methylation was some sort of like Russ occurring on on the genes as they get older, or scratches on a CD, like, you know, David Sinclair talks about. But But actually, it seems it’s a bit nuanced than that. Correct. For example, in your paper, the net methylation didn’t change, but some areas went up and some areas went down, and it was the change in locations. And so as you say, there were methylation of promoter regions of tumor suppressor genes, which is a triple negative sort of,

Kara Fitzgerald 11:24
yes, that’s right. In the end, you don’t want that, that in the end, the take home is you don’t want that. But yeah, it is, it is kind of it is kind of complex. Yeah, yeah. So good guy genes, as we age, there’s a really pretty predictable pattern that good guy genes are turned off. And bad guy genes are turned on, like, it’s, it’s, it’s, it’s quite simple, our poor inflammatory genes tend to get turned on our ability to fight cancer tends to drop, you know, our it just on and on our ability to generate, you know, antioxidant compounds or antioxidant system tends to, you know, get muddied and, yeah, it’s, it’s, it’s, um, it’s kind of annoying. And it’s not a straight shot, it’s not, it’s not Oh, we just simply need to turn the methylation volume up, otherwise, we will, in functional medicine be, you know, incredibly, you know, healthy by just taking our B 12. and folate, but that’s not the case. It’s way more nuanced than that, that we don’t want hyper methylation, we don’t want too much methylation in certain regions. We don’t want too little methylation in other regions. And so it’s, you know, there’s really kind of a sweet spot.

Robert Lufkin 12:33
So yeah, so given that, I, as you say, if I understand you correctly, it’s not a simple matter of giving dietary methyl donors like folate, B, 12, and choline. Because it, it’s not increasing or decreasing overall methylation, but rather rearranging them in a in a non stochastic fashion, as you say, in your paper, that that will change the epigenetic clock to a lower age, then, yes. Great. So

Kara Fitzgerald 13:03
let me let me just say one thing for anyone out there saying, Oh, geez, do I throw my B vitamins out? You know, do I stop eating eggs? I want to say, I want to say you don’t I mean, we I we prescribe them in clinical practice all the time. And there are plenty of us who are deficient, who absolutely require them. And that’s a separate conversation. But we are arguing and, and we tend to become more deficient as we age. And so there’s, there’s a place for them. But we are arguing for this more nuanced approach and considering imbalance versus sort of the all or nothing thinking that is easy to fall into.

Robert Lufkin 13:40
But it’s it’s an it’s wonderful to have such a powerful biomarker for, for longevity as as these methylation clocks rather than, yeah, you know, individual lab values for blood lipids or waiting for a catastrophic event like a stroke or heart attack or some other factors along the line. This is your aged. Sudden Death. Yeah, yeah. Right. Well,

Kara Fitzgerald 14:06
there you go. Yeah. Yes, that’s right. We’re trying to avoid it. Yeah.

Robert Lufkin 14:09
So so maybe summarize what your paper found then and how that leads into your your current projects?

Kara Fitzgerald 14:18
Yeah. So one of the, you know, a massive aha for me is realizing that aging is the number one risk factor for all of these diseases that we’re talking about. You know, we always say that they’re the non communicable diseases, but COVID is right in there. I mean, it’s extraordinary to me eight aging makes us more vulnerable to to disease period. And I got into looking at diet and lifestyle in relation to DNA methylation because I was actually concerned about cancer. There’s a ton of research, arguably, most of the research is looking at cancer epigenetics, and so that was sort of my entry into thinking about a diet and lifestyle approach. To change if we could support cancer epigenetics, but then I zoomed, I began to unfold or really kind of unpack as I dove into the science further that, in fact, some of the derangements in cancer epigenetics look a lot, you know, look similar to aging in general and other chronic diseases. It’s, it’s so fascinating. I mean, as we age, we, you know, we start to hyper methylated, our tumor suppressor genes, just like a tumor, just like cancer itself does. I mean, it’s, it’s crazy. And so, if the idea became if we actually focus on it, you know, turning back the biological hands of aging journey, we’re addressing collectively, all of these diseases, including cancer, including COVID, I mean, it’s just phenomenal. And so we are using a methylation clock. In our study, we used the original Horvath 2013 clock, there are subsequent clocks, clocks are getting better and better. But when we started our study design back in 2017, that was the that was the main clock and it correlates very closely with chronological age. It’s it’s it’s really supplanted the other biological clocks as the gold standard. I mean, these DNA methylation clocks are just really extraordinary tools and it enables us to figure out what works you know, now versus you know, doing longevity trials, which obviously, we we we can’t real time longevity trials. So we are we we engaged in a diet and lifestyle program specifically geared at nuancing DNA methylation, so our diet was very high in methyl donor foods. So lots of green leaf ease, you know, Patane we wanted folks to have some eggs on a weekly basis. We wanted people to have some liver. Let’s see certain colorful fruits and veggies we included quite a bit of polyphenol compounds, players that you’re familiar with folks, curcumin, green tea, resveratrol, quercetin, food sourced polyphenol compounds, because there’s a pretty cool growing body of science that suggests that these polyphenol compounds are sort of like methylation. Adaptogens is kind of the common the colloquial term we’re using for them, they they sort of guide the methyl donor towards methylating the right gene. I mean, that’s what we think. I mean, and we wonder if that’s what our study suggests, because we didn’t increase net methylation, we actually rearranged it in a more favorable pattern. And these polyphenol compounds, sort of it can inhibit the methyl transferase is from laying methyl donors down on DNA. And it seems like they may support that in a specific sort of healthy pattern. Why? I mean, we know we look at curcumin or green, I mean, all of these guys have very good track records for being beneficial. So we had so our diet was very specifically rich in in, in a eating pattern designed to support DNA methylation. We also included a balanced exercise, we wanted folks to get enough sleep, so we paid attention to that. And we included a meditation protocol. All of those have science on them as being supportive of DNA methylation, and in some cases, actually, biologically age reversing as well. So really, we wanted to bring in a realistic lifestyle program where all ends pointed at improving biological age visa B DNA methylation, we included a supplement, a probiotic supplement lactobacillus plantarum, through metagenics. In fact, I want to say metagenics gave us an unrestricted grant. So they’re a supplement company, and they funded our study without taking any ownership or possession. They let us we were in the driver’s seat with every element of design, and I’m very eternally grateful for them for giving me this career changing opportunity. So lactobacillus plantarum has some suggestion in the literature that it may help our microbiome make more folate, so we wanted obviously, we wanted that methyl donor support. And we did end up showing that in that our participants increased circulating methyl folate by 15% Without any, you know, methyl, without any B vitamin supplements. And then we also gave them a greens powder concentrate again, a metagenics product called fight organics, the greens powder concentrate is another it was a twice daily dose of those important polyphenols. And so that was the nuts and bolts of our study. I can I can talk to you about results if you if you Sure

Robert Lufkin 19:35
yeah. And in particular, you made the decision not to do supplements other than the polyphenol i and the probiotic that yes, and that was just too. You didn’t feel it was necessary, really with the proper diet and we supplements and

Kara Fitzgerald 19:52
we wanted to highlight the power of a diet and lifestyle intervention for changing the methylome I mean, you know getting in not getting in there with a heavy hitting intervention like, like a B complex. We knew I mean, we know already that it’d be complex can manipulate the the methylome. I mean, we can a surrogate, a marker of those changes would be homocysteine, but you know, change lowering homocysteine, but we want it to be more nuanced than that. I can give you a little bit of a background, I don’t want to cause any kind of undue anxiety or panic, but there is suggestion in the literature. So when we look, we can think about our methyl donors and folate in particular as existing in a U curve. To little folate is always a problem, it’s always a problem, we can see everything from anemia to increased risk for cancer, when you have to insufficient folate, all sorts of problems ensue. Excess folate, similarly, there’s a growing body of literature to suggest that it might actually promote aberrant methylation, among other things, and you know, via turning off, you know, in suppressing tumor suppressor gene, so, excess methyl donors is something that we might be concerned with in certain populations. And some studies have, have demonstrated this again, you don’t necessarily want to throw out your B vitamins, you want to talk to your provider about it and see if you need to be thinking about it. But it just this you curb distribution of methyl donors suggests to us that they’re powerful, that they’re important. And we want to be at the bottom of the year, we want to be in the sweet spot. Nowhere in the literature, is there any evidence for food based methyl donor nutrients being problematic? So that was kind of our background rationale there.

Robert Lufkin 21:36
Yeah, yeah. Is the sweet spot for the methyl donors within the therapeutic range. And and the the deleterious effects way off the curve? Or are they dangerously close or determined yet?

Kara Fitzgerald 21:51
If that’s a great question, I think, I don’t I don’t know that it’s going to be a cut and dried answer. And, and I really want to be mindful that people don’t want to throw it out with the bath, you know, the baby out with the bathwater here, because, certainly, there’s all sorts of reasons for us to be using them. You know, what I would say, just so I don’t forget, when you’re using, if you’re taking B supplements, make sure you’re getting some of what we’re calling the methylation adaptogens. Make sure you’re eating a really polyphenol rich diet, make sure you’re getting curcumin, maybe some green tea, you know, resveratrol, Quizlet, whatever your favorites are, make sure those all important nutrients that may help direct traffic are in your diet along with a supplement. I think that’s an important piece of it. Right? Yeah, I will say that there was, you know, there have been some studies showing relatively low level supplementation. I mean, there was there was a study out looking actually at fracture risk in individuals in an aging population of individuals with higher homocysteine, and they gave them b 12, and folate, folic acid. And what they found is those oldest actually had in this population, when they did a secondary analysis, those oldest participants actually had had an increased risk of colorectal cancer. And these were modest amounts of B, 12. and folate. It may be that if a tumor is already present, that you just need to be thinking about it. I mean, we need we need to be teasing it out. And again, for the 5,000th time, I don’t want to be alarmist here, but it is it does suggest that we should lean on a food forward approach whenever we can. And you know, you can always lean on a food forward approach and then go and then lean on lower amounts of actual supplements. Yeah, yeah. So that, that kind of jumped us into this area investigation and listen, exercise. We don’t think about this in functional medicine, but exercise lowers homocysteine, I mean, exercise is favorable on methylation. It’s and let me tell you one more thing, and then I’m gonna stop, for those of us who are older exercise is actually can actually allow for the RE expression of tumor suppressor genes, actually, at any age exercise will help balance DNA methylation, but particularly in those who are older, you actually get more bang for your buck as far as balancing DNA methylation. Isn’t that

Robert Lufkin 24:21
interesting? I mean, it blew me away. My I’m a radiologist, what blew me away was seeing people with brain changes and hippocampal atrophy of the hippocampus part of the brain with memory. And it was shrunken and shriveled up and in, in three months on an exercise program, the brain would actually enlarge and the hippocampus would grow back and it was measurable on this scan. So it

Kara Fitzgerald 24:43
was just amazing coronary. Yeah. So imagine combining? Yes. Combine that with a healthy diet and some other things that you know, I mean, when you pull together a systems protocol, man, it’s it. The possibilities are really extraordinary. And that’s cool that you that you got to see that.

Robert Lufkin 25:01
Yeah, that’s great. So maybe let’s segue into the results of your of your study. I think everyone’s so excited now, what did you find out?

Kara Fitzgerald 25:10
So as compared to our control group, our study participants got 3.23 years younger, which is pretty astonishing, with a, you know, a very significant P value of point. 018. So, yeah, it was, yeah. And as compared to Yeah, I know. That’s right. It does suggest we say it’s its potential reversal biological age, because it’s a small trial. And we’re already recruiting for our next larger study. And hopefully, we’ll get to continue to, to study in and tweak our program. It’s a small trial, but we did see a real clear ping that suggests a true biological age reversal versus just slowing things down. And this was just this our study length was eight weeks, so three years in eight weeks. Compared to themselves, our study participants got almost two years younger, 1.96 years younger. Mm hmm. We also lowered Oh, yeah, go ahead. Go ahead. Sorry. Well, we lowered just we lower triglycerides by 25%. As I mentioned earlier, we increased circulating methyl folate we lowered our participants LDL and total cholesterol as well.

Robert Lufkin 26:22
Is there any evidence or what is the evidence pro or con showing that? How long this this effect would persist? In other words, is it? Is it it only works for eight weeks? And then it sort of tapers off? Or do you anticipate that continuing this program, people will just be able to dial back? dial back the epigenetic clock in some fashion? Continually over time?

Kara Fitzgerald 26:49
Well, I mean, I don’t know that I’m going to be reverting back to 15. To adolescence, nor do I know that I really want to know or

Unknown Speaker 26:58
do it right. Yeah, right.

Kara Fitzgerald 27:01
Um, we don’t know that answer yet. That’s a great question. I, you and we don’t we, we don’t have access to our study participants. Now we did originally want them on a Facebook group. And we and we linked to them there. But it was a lot. It’s a like, it’s a long time, we completed the study back in 20, at the beginning of 2019. And so we just haven’t hung on to them. I, I wished that we kept it going so that we could follow up with them and get another dietary and, you know, recall and and do another epigenetic age on them and so forth. But that would have that would require us to do an IRB amendment. So we don’t have those answers. Anecdotally, it looks like things can maintain and perhaps even yield greater benefit, we only looked at very healthy middle aged men, so our population was isolated to them, because it was a pilot study. We know, for example, if we if we worked with diabetics, the chances of age reversal might be greater because they are accelerated in their aging process, as are those others with with chronic illness. So, you know, illnesses an age accelerant. And so by extension, we may see greater reversal. But how long does it last? You know, we’ve got a follow up diet. So we’ve been using this program in clinical practice for years, and we’ve got a follow up that kind of a less stringent version that we transition folks to and will that maintain our changes all of these things we need to answer? And, you know, we hope to we’re building out a digital platform that will you know, as long as we can keep our IRB rolling, we’re going to be able to answer a lot of these can can vegans do it? I mean, our program requires, you know, some liver liver is an extraordinary metal donor superfood. But obviously, vegans aren’t going to eat it. So can we see the same kind of turnaround and benefits with vegans? And, you know, there’s a lot of questions remain to be answered. And how far back can we turn things if if people if participants continue, eight weeks is a pretty short time, although I will say I mean, it was kind of Cavalier for me to to do that. But adherence to this kind of a program with all of the, with all of the variables involved is, you know, it takes it takes a really committed participant. So yeah, definitely look at longer, longer segments as we continue.

Robert Lufkin 29:25
Now, I understand in your clinical practice, you you are using some of these tools, or many of these tools, and also, maybe you could share with the listeners about B access the younger you program. Can they enroll in it?

Kara Fitzgerald 29:43
love to have you? Yes, indeed. Yes. So you can go to just our website, which is my name Dr. Kara Fitzgerald, Dr. Kara fitzgerald.com. And it’s Kara K Ra. If you go there, you’ll see on our landing page, you know a link to joining younger you or it’s Join dot younger you.com I think and then you can sign up our first launch in August, there’s our beta 100. These, these are folks really kind of kicking the tires of our program, you may be able to get into our beta 100 If you’re in the US so you can Regardless though, even if you don’t get in the beta 100, because the waitlist is is pretty huge at this point. In January, we’ll have a full launch accompanying the book. And like I said, we’ll be continuing to study it, you can just do the program, you don’t have to be a research participant, you can opt out. That’ll be clearly delineated in the app itself. But I would suggest whatever you want to do if you want just the program, or if you want to participate in research, or you want to try to be a beta 100 participant, just get over to either the website or join dot younger you.com. And on sign up, just give us your email will keep you posted in the email.

Robert Lufkin 30:57
Great. And if they want to join your practice with some of your physicians, and they can do it through that same mechanism. Is that right? Yes,

Kara Fitzgerald 31:05
yeah, through our website, you can absolutely access our clinic everyone here we’ve got a large nutrition team here. In fact, our nutrition team. We’re the nutritionists for our study participants. And you’ll have access to nutritionists if you do it through the app. But you can absolutely we’re a clinical practice of MDS and MDs and nutritionists and we do work, we work internationally, people can work with us directly if they’d like to.

Robert Lufkin 31:36
Great, that’s so exciting, that there aren’t these barriers, and people from truly all over the world can participate in this. Yeah. Anything you can tell us about your upcoming book, I just pre ordered it from Amazon. January 2022.

Kara Fitzgerald 31:53
I appreciate that. It’s so the cool thing about the book is that you’ll get a few things you’ll get exactly what we did in the study. So you’ll learn exactly what our study participants did what they were prescribed the you know, the macros, we the kinds of nutrients we wanted them to eat just everything a blow by blow in really exquisite detail, you’ll get our everyday program so that that you’ll transition onto afterwards, you’ll get you’ll get our recommendations for pregnancy, you know, preconception and conception, I mean, embryo mutagenesis embryogenesis, talk about major methylation and demethylation important time, I talked about that in the book and and do a modified What am I calling it, I felt like the hybrid younger you for what you might consider in pregnancy. And we actually have some pretty cool statistics where they use our program and grow baby health. So they use our methylation, diet and lifestyle, in conjunction with their interventions at grow baby health and the out the birth outcomes that they have are just extraordinary, just absolutely extraordinary. So I think there’s a place for this nutrition program for a variety of, of indications, and we talk about that in the book. The other things that I’m talking about in the book, that are very interesting to me is just sort of understanding what DNA methylation is and what it’s doing in the body. There’s a particular cool bit where I talk about something called biological embedding. And that is where our life experience is translated to biochemical marks, DNA methylation, being a main one, and placed onto our genes to dictate expression. So our experience translated to biochemistry onto our genes. The most of the research here is looking at trauma, so we can see, you know, early life abuse, actually translating the way that our genes are expressed, we can see inherited trauma, Trent, you know, transferred on to our genes and altering genetic expression. I’m, I’m interested, I mean, it’s easy to look at trauma, but what about how we resolve it? And that’s something that I explored in the book, like how do we build resilience? How do we build a resilient genome so that, you know, we’re not likely to to fall to PTSD, and so on and so forth. So that so that they’re my broader interest in in epigenetics in general, I really get to express in the book. So I think I think it’s going to be a neat read. And I would love your feedback. It’s it’s been a real labor of love and kind of and a passion project for sure.

Robert Lufkin 34:37
Yeah, it’s great getting something out there like that, that people can purchase and then read or get it from their library and just sit down with it and digest it and really get up to speed with what you’re doing and find out about your program.

Kara Fitzgerald 34:49
One of the coolest things about the book I’ll say one more thing, and I’ll hash is that we have in it a nutrient appendix where we list food sources for Have all of these beautiful polyphenols that are epigenetically active, and it is a massive appendix. So if you want to go in there and create a diet for yourself, that is just epigenetically extraordinary. You can do that using our nutrient appendix. There’s nothing like it to my knowledge out there.

Robert Lufkin 35:18
Oh, wow, that that. That sounds great. Yeah, I can hardly wait. We just have a few minutes left, I wondered if you would be comfortable sharing with our listeners and viewers. What personal lifestyle choices you make in your your decision, you know? Oh, great.

Kara Fitzgerald 35:40
I’ll show you one of them. Well, actually, here’s Okay. So here’s my, here’s my lunch, which has my beats on it, it’s got my beats. This is actually I eat the young I use the younger you eating pattern in my in my daily life, I just find it great. I find it just works for me. And I’ve created a way that I can prep it easily. So that’s a massive amount of veggies, we want people to eat a minimum of about seven cups, actually is probably closer to 10. So it’s a it’s a very vegetable Forward program. Exercise.

Robert Lufkin 36:17
Before you move guy, just a couple other questions. When do we do do any sort of intermittent fasting?

Kara Fitzgerald 36:23
Question? Yeah, thanks for asking me that. Our program is keto leaning. And I think that our participants got into a little bit of a ketosis as evidenced by the drop in triglycerides. And we do we do have a modest mild intermittent fasting or time restricted eating so nothing after seven nothing before seven. So about a 12 and 12 eating. And I continue to practice that I actually monitor my blood sugar, I’m kind of a little bit of a me to monitor my sleep and my. Um, so I subscribe to the younger you program. It’s I’ve been doing it for a long time now. So it’s evolved for me a little bit my my exercise in our study, we prescribed at least 30 minutes, five days a week of a perceived exertion of 60 to 80%. So not an intensely rigorous the end. But that’s just, that’s a minimum, not an intensely rigorous time, I tend to go a little bit more towards high intensity interval training, at least a few days a week, I’m a cyclist, and I have a background as being a competitive athlete. So that’s something that is important and satisfying. For me. I pay very close attention to my sleep, I’ve got a toddler, as you mentioned. And, um, yeah, and if I don’t, if I’m not doing the best that I can, like intentionally making sure my room is really dark, that I go to bed in time to have a shot at a reasonable number of hours that I haven’t exercised so close to bedtime, or, you know, had any late caffeine, et cetera. I need to do that to be able to sleep. I mean, you you know, you’ve got kids running around, too. I mean, you just you have to, you have to put intention into getting adequate sleep. And it impacts the epigenome, you guys, I mean, honestly, this is not gratuitous. This this is in there. It absolutely impacts it, and it can impact it in a lasting way. And stress management. So that’s another huge piece of the puzzle. Meditate. So for me, it would it would be exercise meditation. Playing with my my kid is actually a big stress reliever because it really jacks up oxytocin. A extraordinary Aha, for me on the clock that we used is that 25% of the methylation sites on that Horvath 2013 clock are actually glucocorticoid response elements. Yes. Wow. glucocorticoid 12%. Isn’t that why? I mean, if that doesn’t underscore the stress, that stress is it is it is an pro aging experience. I mean, I don’t know what does.

Robert Lufkin 39:10
Yeah. For your meditation practice? Do you use any of the apps that are available? And which which type of practice would you recommend or that you use?

Kara Fitzgerald 39:19
So in our study, we use the very simple and again, this will be reproduced in the book and on the app, the very, very simple Herbert Benson relaxation response. It’s been used. He’s out he was out of Harvard. And it’s just been used many, many times and many, many research studies. So it’s just a well validated, simple breathing tool. That that we recommend, if, however, if you come from a practice, just continue with your practice. I mean, we didn’t study it. So I can’t technically say transcendental meditation or Zen meditation has benefit but the literature really strongly suggests that any, you know a verb Have these interventions are beneficial on on epigenetics, I, personally, I like actually, I don’t know if you’re an aura ring person, but the aura ring itself has a tool built in. That’s kind of nice. And it’ll check my heart rate variability, I’m a little bit of a data hound. So it’s just, it’s fine. It’ll check my skin temperature and my heart rate. And so that’s kind of cool. And I, and I like the, I just like the little background noises, they, they also will walk you through some guided meditation. So that’s a useful app. Calm is an awesome app. And, and these, you know, calm has premiums, that work. And so you can access those. And then what’s totally free, that I love is University of Wisconsin has a whole mindfulness meditation research institute there. Oh, we’ve got an app called Healthy Minds, and the whole thing is free. It’s extraordinary. So I’m using I’m really kind of experimenting with different apps right now. Healthy Minds is cool for me at the moment because they’ve got active meditation, so I can turn it on while I’m riding my bike. And I just, I need to, you know, if my if my if Isabella wakes up really early, I’m not going to be able to do meditation. I mean, that’s, you know, it’s it. But if I have a minute to hop on my bike, or I have a peloton at home, I can do I can actually do an active mindfulness exercise that won’t plant me into a tree. Oh, yeah. There’s some good tools out there.

Robert Lufkin 41:32
So yeah, good, good devices. I’m crossing my fingers for the Apple Watch, hopefully, glucose monitoring. Maybe in September, we’ll really

Kara Fitzgerald 41:40
is that right? If you’re gonna be able to hook up to like, the freestyle Libra? Or what is the

Robert Lufkin 41:45
both? No, actually, it would be it would be it’s not interstitial glucose, like the Libra there’s no needle, but it’ll it’ll it’s using new technology that Apple’s patent that Android also has access to. But it uses Raman spectroscopy to shine a light through the skin, and supposedly it will give us a type of continuous glucose monitoring. And can you imagine how that will change people’s behavior if they could change their glucose? Every time they eat something? And yeah, so it’s a game changer.

Kara Fitzgerald 42:14
It’s a game. I mean, it’s a game changer. It’s changed mine. I mean, I when I started wearing it, I thought that I, well, you know, you just see how you respond to food. I did have a good diet. I mean, I still do but yeah, it’s it’s definitely changed my behavior. And that, you know, another big aha for me, which may or may not have been for you is how high my glucose can spike sometimes when I’m doing like high intensity interval training. Yeah. And you know, how many people have been diagnosed as diabetic because they went to their doctor right after exactly, even a

Robert Lufkin 42:45
fasting glucose, I mean, even a fasting. I fast like 20 hours a day, and I can see my glucose going. I mean, it stays pretty low. But actually, one one experiment I did unintentionally on myself, I was I was, it was middle of the day like 10 in the morning, I did fasting since like six o’clock the night before. And I had a kidney stone. So exquisite pain, and my glucose just took off on the glucose monitor. I hadn’t eaten anything, just drank water. And it my glucose shot shot up through the roof and it didn’t come down until I got the IV morphine and UCLA emergency room. But it shows effects of pain in this case or stress on on glucose levels and how it spice it up. It was

Kara Fitzgerald 43:31
ordinary God we just this age of being able to see is just it’s just revolutionary and what it’s what it’s teaching us Yeah, yeah, we’re like seeing a little Dawn phenomena sometimes, you know, the exact like, and when it happens, like because I don’t always have it anyway, we could go down around

Robert Lufkin 43:47
like any other devices, acetone monitors, breath monitors, or blood or sound,

Kara Fitzgerald 43:54
I you know what I do do my blood sugar to track it with my interstitial glucose, and unfortunately, they don’t always correlate but you know, you just kind of get the gist of what’s happening over time. I do have I just got a lactic acid kit, which, yeah, so I haven’t I haven’t played around with it. But being a fan of Peter T. I love his podcasts. Yeah, he went through a phase of talking about him quite a bit. And I was like, you know, and I’m thinking about should I be training at a lower heart rate? You know, and I anyway, yeah, another conversation.

Robert Lufkin 44:27
Any, any labs or imaging that you that you use for lifestyle issues that you you find useful? Like medical imaging or any labs?

Kara Fitzgerald 44:38
Um, I would say that I mean, I’m, I’m definitely having done my postdoctoral training in a lab. I’m, I’m a big fan of getting, you know, a broad swath of labs as we’re able to and more and more of them are covered by insurance. So I like you know, some of the advanced lipid panels that we can get nowadays are access to FDA. So prostate, which is an awesome pro oxidant compound, what else we can get a broad swath of nutrients covered by insurance, you know from Quest, we can get good fatty acid panels looking at our omega sixes that are omega threes are saturates, or mono and saturates. I like the panel’s like, from Genova labs like the ion or the nutria vow, the ion has really all our condition are essential and conditionally essential nutrients, plus, it has toxic compounds. And in there, they’re actually the cool thing about the ion. And this is where I worked. It’s, they’re divided into quintile ranges. So it’s kind of like a CRP you can you can look at your patients trends over time, or you can look at where they fall within the population as a whole. So you’re you you’re more in control of how you’re going to work with the data versus a higher low that you just sort of accept, you can look at how are we you know, are they in the bottom 20th? Are they in the, you know, middle 60s Are they way, you know, outliers above the top population, we can look at organic acids and get a snapshot into mitochondrial health and function, there’s a lot of good oxidant stress markers. So and that’s only evolving, of course, we have stool testing, we can look at, you know, that’s just growing by by leaps and bounds. So we continue to be on the precipice of as a clinician, we continue to have, you know, more access to to better and deeper testing. And it’s coming forward. In fact, one of the things that I’m doing so in when in our digital platform, you will have access to epigenetic biological age. In fact, we’ll be looking at a way more clocks than we did in our study, just since we started our study in 2017. Till now, there’s a whole suite of second generation clocks that are arguably even, you know, more effective than the the Horvath original flagship clock, although that’s just it’s a great guy. I’m not gonna argue with it. But we were creating a, a custom test that will look at biological clocks, but it will also look at some of these genes that I’m hoping are nutrient responsive, like tumor suppressor gene, some of these things that we were talking about NF kappa B, you know, what’s the methylation status? Is it on? Is it off some of our antioxidant genes and just we’ll be looking at actually, you know, glucocorticoid genes, we’ll be looking at methylation patterns on oxytocin, the oxytocin receptor gene that can be hyper methylated. In trauma, I mean, we’re going to be looking at some really cool stuff. And all of that will be accessible in the app as it’s available. We want to look at things that are actionable for us through a diet or style lens.

Robert Lufkin 48:00
Sure, yeah. Do you recommend any any method any consumer facing methylation clocks that they’re for themselves? I mean, like true diagnostic, or there’s some out there

Kara Fitzgerald 48:12
to diagnostic actually marketing directly to consumers? I don’t think they are,

Robert Lufkin 48:15
they have to go through. Yeah, they have to go through, like two

Kara Fitzgerald 48:19
diagnostic, we didn’t use them. In our study, we went straight to a little to Illumina, who you know, Illumina works in the research in the research world, but true diagnostic is also using Illumina. We’re designing our customer ray with true diagnostics. So yeah, I think that they’re, I think that they’re really working hard. zymo has a direct to consumer biological clock that’s based on the original Horvath that I like, and I’ve used I think that they’re good solid lab. You know, you can’t argue with Illumina, you know, for diagnostic and zymo You know, they’re right in the thick of epigenetic research as well. They’re good. They’re not sort of startup Fly By Night labs, either of them Elysium has a proprietary biological age clock that I think that their their marketing direct to consumer, if I’m not mistaken. They are Morgan Levine, who’s just, you know, arguably one of the sort of best known APA geneticists sort of bio Informatica geneticists, I think is is part of Elysium. So I think they’re doing good work. It’s not it is proprietary so we don’t really know which clock they’re using. I, I guess as I as I move into science, I would like to know, but yeah, but I think that they’re doing good work there. So those are there’s some solid stuff out there that people people can access and you know, we hope to be able to offer something as well. Oh,

Robert Lufkin 49:48
that’s That’s great. It’s such such an exciting time and such a pleasure having you on the on the on the show today. I want to again, thank Dr. Fitzgerald for your for your amazing kind. attributions to the field and taking time to speak with us today’s please follow her podcasts or blog order her upcoming book, pre order it right now is on Amazon and elsewhere. And if you want to experience the possibilities of lifestyle and other functional metrics to get some tools to affect your biological age, first time, you get involved with a program and sign up, as well. And we’ll provide all the links to your information for our listeners. So they have that in the in the show notes. And once again, Kara, thank you so much for joining us today. We really, really appreciate it. Yeah, it’s

Kara Fitzgerald 50:36
an honor. Really, it’s a pleasure. I’m just thrilled to to get to know your great conversation really

Robert Lufkin 50:43
look forward to speaking to you again, and maybe we can reconnect after we get into the study and after the book comes out.

Kara Fitzgerald 50:50
Yes, I would like that. Yeah. And we’ll talk about imaging. I think there’s a place there’s absolutely a place for it. Yeah.

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