Eat These Foods + Spices for 8 Weeks To Get 3 Years Younger | Kara Fitzgerald : 1461

Summary

---

Podcast Summary

The Human Upgrade: Biohacking for Longevity & Performance

Episode: Eat These Foods + Spices for 8 Weeks To Get 3 Years Younger | Kara Fitzgerald : 1461
Host: Dave Asprey
Guest: Dr. Kara Fitzgerald
Date: May 5, 2026

---

Episode Overview

This episode delves into how specific dietary interventions, rich in select foods and spices, can significantly reverse biological age markers. Functional medicine clinician and researcher Dr. Kara Fitzgerald joins Dave Asprey to discuss the landmark study showing a reversal of biological age by over three years in just eight weeks, achieved through a protocol combining polyphenol-rich foods, methylation-supporting nutrients, meditation, and other healthy lifestyle practices. The conversation explores the science behind epigenetics, recent advances in measuring biological age, the potential risks and rewards of plant-based compounds, and the cutting edge of age-reversal therapies like Yamanaka factors.

---

Key Discussion Points & Insights

1. Study on Diet, Supplements & Biological Age

• Main finding: In an 8-week randomized controlled study, participants following a specific diet, supplement, and meditation protocol were biologically 3 years younger compared to controls.
  • Dr. Fitzgerald: “Compared to the control group, we had lowered biological age as measured by that first clock, by over three years in our study subjects, in eight weeks time.” [00:00]
• Diet Details:
  • Heavy in methyl donors: greens, eggs, liver, beets.
  • Dense in polyphenol-rich foods and spices: 7-11 cups of fruits, vegetables, herbs, and spices daily.
  • Focused on both methylation donors and what she formerly called “methylation adaptogens” (now “epi super nutrients”).
    • “These are largely polyphenol compounds that... help methylation happen where it should happen.” [05:20]
• Key Nutrients: EGCG (from green tea), urolithin A, various polyphenol compounds from herbs like rosemary, oregano, marjoram, thyme, and yarrow.

---

2. The Role of Polyphenols in Epigenetics

• Polyphenols: Critical for modulating gene expression and “dark matter of nutrition” whose mechanisms are not fully understood.
  • Dr. Fitzgerald: “A sophisticated collection of polyphenolic compounds are acting on gene expression in ways that we are only beginning to touch on.” [12:16]
  • Polyphenols can “turn back on” genes associated with youth and cellular repair.
• Supplements vs. Food:
  • Both food and supplements have a role; supplements provide controlled dosing but food provides a wider spectrum of bioactive compounds.
    • “You can’t bypass the information from a sophisticated dietary pattern... There is a place to layer on appropriate cocktails of higher concentration.” [13:12]
  • Concerns are raised around factors like oxalates in certain high-polyphenol plants (e.g., turmeric, buckwheat).
    • Dave Asprey: “The more I’ve played around with manipulating levels, the more I think oxalate is responsible for a lot of broad spectrum inflammation in people...” [16:26]

---

3. Oxalates: Risks and Sensitivity

• Oxalate discussion:
  • Some individuals are highly sensitive, experiencing inflammation, joint pain, and kidney stones.
  • Others (like Chelsea and Dr. Fitzgerald) seem not to be sensitive.
    • Dave Asprey: “If I eat a high oxalate meal, when I walk, it hurts and the crystals go there... calcium oxalate is directly toxic to mitochondria.” [18:44]
• Strategies:
  • Consider limiting high-oxalate foods if you are sensitive.
  • Use extracts or encapsulated forms of superfoods (e.g., curcumin instead of turmeric root).
    • Dr. Fitzgerald: "I'm a fan of getting this polyphenolic information encapsulated and isolated for sure." [21:03]

---

4. Yamanaka Factors & Yamanaka Mimetics: Cellular Rejuvenation

• Yamanaka factors: Four transcription factors that can revert adult cells to pluripotent stem cells, potentially erasing cellular age.
  • Dr. Fitzgerald: "They were able to take a somatic cell... and bring it all the way back, reduce its age, if you will, all the way back to pluripotent stem cells." [23:53]
• Risks: Direct use is not ready for humans; tightly controlled exposure needed. Risks of creating tumors or "grey goo."
• Yamanaka mimetics: Compounds or cocktails that simulate some of Yamanaka’s effects more gently—possible candidates include AKG, sodium butyrate, forskolin, polyphenols.
  • Dave Asprey: “So somehow in the longevity field, it feels like we know these things are working, but we don’t know the why. And you're figuring out it might be via Yamanaka... actions similar to what Yamanaka factors can do.” [33:41]

---

5. Advances in Measuring Biological Age

• Clocks:
  • First-generation (Horvath) clock measures epigenetic age via DNA methylation patterns.
  • Newer clocks (e.g., Polycomb Repressive Complex [PRC2] index) may more directly measure the “program phenomena” of aging.
    • Dr. Fitzgerald: “If we can get in there with more benign interventions and move the needle on what I think is touching on the program phenomenon... we have the potential to build, you know, we could, you know, be touching on something in more depth in the aging phenomena.” [37:55]
  • Polyphenols and caloric restriction are among the few interventions shown to move PRC2-based clocks.

---

6. AI in Health Assessment and Personalization

• Advanced Imaging:
  • AI analysis of MRIs can vastly increase early disease detection and track brain volumetrics.
    • Dr. Fitzgerald: “MRI is a Porsche, but we drive it like it's a Ford Fusion... If you can really take thousands of images and then run it through AI... you can get much more sophisticated data.” [31:29]
• Personalized Nutrition:
  • AI-driven epigenome-wide association studies and personalized supplement recommendations (e.g., Viome) are the future.
    • Dave Asprey: “We’re getting to the point where we can say for your biology, yeah, you should eat these 25 polyphenol things or take a pill with that, and it's going to have the most benefit.” [46:38]

---

7. Practical Applications and Takeaways

• “Eat the Rainbow” is out; personalization is in:
  • Frequency, dose, and source (food vs supplement) of polyphenols will likely be matched to one’s unique biology.
• Hormonal Health & Gender Differences:
  • Initial studies focused on men due to variability in women’s hormone cycles; later cohorts proved the effect in women, sometimes even more strongly.
    • Chelsea: “We did publish a collection of case reports in women, so we showed the same thing in women.” [53:56]
    • Dr. Fitzgerald: “Women are... the primary group who are interested in our dietary pattern... and they just absolutely responded to it profoundly.” [55:30]
  • Improved methylation diets may ease perimenopause symptoms.
    • Dr. Fitzgerald/Chelsea (on perimenopause): “Absolutely. 100%. Yes. Yes, yes, yes.” [56:33]
• Carnivore diets: Effective as short-term elimination diets for resolving inflammation but problematic long-term due to lack of polyphenols and potential gut lining issues.
  • Dr. Fitzgerald/Chelsea: “Carnivore diet, fabulous short-term for some individuals... A lot of long-term carnivore diet folks will probably crash and burn.” [49:00]

---

Notable Quotes & Memorable Moments

“Compared to the control group, we had lowered biological age as measured by that first clock, by over three years in our study subjects, in eight week’s time.” – Dr. Kara Fitzgerald [00:00]

“Polyphenols are acting on gene expression in ways that we are only beginning to touch on... It’s called the dark matter of nutrition.” – Dr. Kara Fitzgerald [12:16]

“My time as a raw vegan was not good for me because... I would get oxalate tartar on the back of my teeth. A dentist was flaking it off. Yeah, it was, it was weird.” – Dave Asprey [19:18]

“They can take a somatic cell... and bring it all the way back, reduce its age, if you will, all the way back to pluripotent stem cell status, which is the holy grail for stem cell cells.” – Dr. Kara Fitzgerald [23:50]

“Eat a rainbow, eat every color of food every day... historically we didn’t do that because plants don’t grow in winter... we’re getting to the point where we can say for your biology, yeah, you should eat these 25 polyphenol things or take a pill with that, and it’s going to have the most benefit.” – Dave Asprey [45:12 & 46:37]

---

Important Timestamps & Segments

| Timestamp | Topic/Quote | |-----------|-----------------------------------------------------------------------------------------------------------| | 00:00 | Landmark finding: 3-year reversal in biological age in 8 weeks | | 05:20 | Polyphenols as “epi super nutrients” and mechanism | | 10:54 | Do you get enough polyphenols from food vs supplements? | | 16:26 | Conversation on oxalates; Dave’s experience & clinical perspectives | | 22:52 | Yamanaka factors: the science & future risks | | 31:05 | AI and MRI—leveraging tech for better health tracking | | 37:31 | Next-gen biological clocks—PRC2 and programmatic vs exposomic aging | | 41:05 | Highest-polyphenol herbs and their role in anti-aging | | 49:00 | Carnivore diet: short-term solution, long-term concerns | | 53:56 | Case reports: Women get the same (or better) results | | 56:33 | Methylation-supporting protocols ease perimenopause | | 58:26 | Uterine fibroids and unmet research needs for women’s health |

---

Summary & Takeaways

• A targeted 8-week intervention with high-polyphenol, methylation-supporting foods and lifestyle practices can significantly lower measured biological age—by over three years—according to cutting-edge DNA methylation clocks.
• Polyphenols, from both food and supplements, are emerging as “epi nutrients” capable of influencing gene expression, promoting longevity, and possibly mimicking the profound effects of Yamanaka factors in cellular rejuvenation.
• Sensitivity to plant compounds like oxalates varies between individuals; clinical experimentation with food elimination and encapsulated extracts may help tailor optimal diets.
• AI-driven diagnostics and epigenetic study are making diet and supplement personalization possible, moving beyond one-size-fits-all recommendations like “eat the rainbow.”
• Both men and women benefit from these protocols, with emerging evidence that optimized nutrition may make transitions like perimenopause smoother.
• The field is quickly evolving; expect future therapies to combine smart supplementation, specific food choices, advanced measurement tools, and possibly novel delivery systems for beneficial compounds.

---

For further learning

• Check out Dr. Kara Fitzgerald’s work on dietary epigenetics, her podcast, and relevant publications.
• For practitioners, understanding methylation, polyphenols, and their individualized impacts is key to future functional medicine and biohacking protocols.

---

Transcript

[Dr. Kara Fitzgerald]

It was a very, very exciting moment for our biostatistician, Josh Middledorf, to, you know, to tell us that compared to the control group, we had lowered biological age as measured by that first clock, by over three years in our study subjects, in eight weeks time with some

[Dave Asprey]

food and supplements and meditation.

[Chelsea]

So our set of transcription factors, so these guys dictate gene expression, manipulate what proteins are being created from our DNA,

[Dr. Kara Fitzgerald]

and they were able to take a somatic cell and expose them to these transcript factors and bring it all the way back, reduce its age, if you will, all the way back to pluripotent stem cells. So they've looked at really old skin cells, taken samples from people in their 90s, and they can wind them back, you know, to their 20s. I mean, they can just shave decades off.

[Dave Asprey]

In the meantime, probably rosemary, marjoram and yarrow would be really good. There's some of the highest polyphenol foods, and I eat about 2 tablespoons of all those. And we're going to go really deep on things like polyphenols and what they really do in the body, reversing cells back to the way they were in the womb, even, and some more research like that. So this is a fascinating episode. You're listening to the Human Upgrade with Dave Asprey. As you age, one very important thing quietly declines. It's your stem cells. You're not going to feel them declining. And it's not just the number, but it's their ability to repair and recover and renew every part of your body. And that's why your recovery can stall, even if your habits are the right ones, like that hangover that hits harder

[Sponsor Voice (Stemregen)]

or the gy workout that leaves you

[Dave Asprey]

aching for days, or waking up tired even though you did get eight hours of sleep and you thought it was the best. Stem regen supports your body's natural renewal process because it triggers the release of about 10 million of your own stem cells every single time you take it.

[Sponsor Voice (Stemregen)]

It also supports circulation, so those cells

[Dave Asprey]

can actually get to where they need to be.

[Sponsor Voice (Screenfit)]

So stem regen helps your body do

[Dave Asprey]

what it already knows how to do, which is just to prioritize smarter strategies for healing instead of just working harder when your body can't heal.

[Sponsor Voice (Stemregen)]

So go to Stemregen co and get 30% off your next order of Stemm Regen.

[Dave Asprey]

This stuff works, and I use it all the time.

[Sponsor Voice (Liberty Mutual)]

And Doug, there's nowhere I wouldn't go to help someone customize and save on car insurance with Liberty Mutual, even if it means sitting front Row at a comedy show.

[Chelsea]

Hey everyone, check out this guy and his bird. What is this, your first date?

[Sponsor Voice (Liberty Mutual)]

Oh, no. We help people customize and save on car insurance with Liberty Mutual together. We're married. Me to a human, him to a bird.

[Chelsea]

Yeah, the bird looks out of your league.

[Sponsor Voice (Liberty Mutual)]

Anyways, get a'@libertymutual.com or with your local agent.

[Narrator/Disclaimer Voice]

Liberty, Liberty.

[Chelsea]

Liberty, Liberty.

[Dave Asprey]

So you did the first study that at least that I'm aware of, was looking at an eight week methylation supporting supplements for longevity specifically. What did you find?

[Dr. Kara Fitzgerald]

Yeah, that's right. Well, let me, I'll give you a little background on the study and again, I just want to extend the opportunity to interrupt me as needed. I think the background is interesting and it's illuminating. So it was around 2013, I think, when epigenetics as a field really started to catch me through a functional medicine lens. So I'm a functional medicine clinician by training and my first question is always, okay, here's a mechanism we're starting to see incredibly complex. This is how genes are regulated. How might we think about this in terms of interventions through a functional lens? How might we alter diet, lifestyle, et cetera, et cetera, to shift epigenetics? So that was our first, that was my first entry into it. And the big thinking then, because biological age clocks were, that's not only did we not have them, but the father of this whole area of measuring biological age did not think as they came to pass that we would be able to manipulate them. So Steve Horvath is on record many times just saying he didn't anticipate us being able to shift our biological age.

[Dave Asprey]

I like Steve.

[Dr. Kara Fitzgerald]

Yeah, yeah, it's pretty amazing. So the area of science that was heavy at this time was in cancer. Cancer super efficiently hijacks the epigenetic machinery from us. So the tumor microenvironment will take over gene expression from us to, you know, to grow for its own nefarious end. So it will turn off tumor suppressor genes, genes that protect us from cancer. Cancer very reliably turns them off to move cancer forward and it will turn on oncogenes. So genes that we have turned off it will turn on. And in that the tumor microenvironment, the cancer spreads and grows and it's so I just, it's such a huge area that the sophisticated testing that we have now, like grail and so forth, where we can do a sweep through many different cancers and identify them really early, are they're using DNA methylation Patterns. So there's just a lot of good science around and it's been going for a long time. And so me with my right hand woman in, you know, in this area of investigation. She's our lead nutritionist in my clinic, Romilly Hodges. She and I started to dialogue about how we might look at this through a functional medicine lens. And we developed a diet and lifestyle intervention that was very heavy in methyl donors.

[Dave Asprey]

Yay TMG and things like that.

[Dr. Kara Fitzgerald]

Yeah, yeah, totally. Like lots of greens, eggs, liver, et cetera, you know, beets and so on and so forth. And then there was this other piece that was largely unknown at the time. And this is what we called the methylation adaptogens. But we're now we're calling them epi. Epi super nutrients. I'm so sorry, I can't remember what we're calling them. But back in the day we called the methylation adaptogens. These are largely polyphenol compounds that aren't involved in the methylation cycle. They're not methyl donors help it. They help methylation happen where it should happen.

[Dave Asprey]

What are examples?

[Dr. Kara Fitzgerald]

A classic polyphenol compound would be EGCG and green tea or one of my favorites. Yeah, it's so important. I mean in my book Younger your, we have a nutrient appendix, an epinutrient appendix. And it's really like my favorite part of the book. You will see that there are hundreds and hundreds and hundreds of foods that contain these, both the methyl donors and these adaptogens. So we married these together. And the diet is very dense in there's about 7 to 11 cups of fruit and veg and spices and herbs that can move this needle. And so that was arm one and then it was protein, protein dense, good fats, et cetera. It's a clean, healthy dietary pattern focused on these methylation manipulating compounds. And my interest was basically, you know, can we move the needle on gene expression? Can we move epigenetics? And you know, we hired a clinical research center to run the study for us. It was a randomized controlled study, you know, first of its kind in the world. We included an exercise component, a meditation component. We talked about sleep, hygiene, all of the things in the literature where there were, and sometimes it was preclinical that showed that we could move the needle. We brought them together and put a group of healthy middle aged men. So we wanted to try to get.

[Dave Asprey]

Did you find a group of healthy.

[Dr. Kara Fitzgerald]

It took us a long time. There was a rolling enrollment. It took us about a year to run this eight week study. Yeah. So between 50 and 70 control group, intervention group. During that time, it was 2019, the TRIM study, Greg Fay study came out showing that indeed biological age could be manipulated. So we had the measurement, we had the epigenetic data to be able to check the clocks. But we became very excited to see whether we had moved the needle. So we wanted to see more broadly, did we change tumor suppressor genes, did we change, you know, all sorts. We had all sorts of questions we wanted to probe the data on. But the first question we decided to answer was whether we moved the needle. And at that time it was the Horvath multi tissue clock that was available to us. And it was a very, very exciting moment for our biostatistician, Josh Middledorf, to, you know, to tell us that compared to the control group, we had lowered biological age as measured by that first clock by over three years in our study subjects.

[Dave Asprey]

In eight weeks time with some food and supplements.

[Dr. Kara Fitzgerald]

Yeah, yeah.

[Dave Asprey]

And meditation and.

[Dr. Kara Fitzgerald]

Yeah, yeah.

[Dave Asprey]

So one of the things that I think is awesome, but there could also be a criticism is the same thing that Dean Ornish used was saying, oh, look at my weird malnutrition diet, the DASH diet. But he combined with meditation and exercise and got exactly the same effects as meditation, exercise without his weird diet. Right. So it was a confounding thing. But in the world of biohacking and functional medicine, we don't assume that it's just one thing. It's that you have to set up the whole environment as a system to support it. So you did all of that. Right. Did you compare the results you got from people who just do diet or just do exercise?

[Dr. Kara Fitzgerald]

You know what, in fact we did inadvertently because we had this healthy middle aged male population. So our control group exercised. It was a wash. Okay, so we just rule it out. Yeah.

[Dave Asprey]

Exercise was.

[Dr. Kara Fitzgerald]

Isn't that amazing? We didn't, we, we were not able to pull any compelling data. In fact, we just published this year a reanalysis of our original study and really identified the elements that seemed to move the needle. And they were, and they were the nutrients. And again, there were these methylation adaptogens, these polyphenol, the most dense polyphenol compounds were doing the heavy lift.

[Dave Asprey]

It's funny, Bruce Lipton years ago read a book called the Biology of Belief, and I was so excited to have him on the show because he opened my eyes to epigenetics sometime in the late 90s when I was running a longevity nonprofit group in Palo Alto. And so that formed most of the thinking behind my first book on fertility. It was called the Better Baby Book because I didn't want my kids to have autism the way I did, because that would be bad. So I focus on methylation, methyl donors. I even wrote take folinic acid instead of methylfolate because it's superior, just because it mechanistically looked like it would be. But I came up with all this I published in 2011, is like, Epigenetics gives you the ability to have healthier babies.

[Chelsea]

Yes.

[Dave Asprey]

And then the next big book, obviously Bulletproof Diet, where epigenetics was a part of it and polyphenols are at the very center.

[Dr. Kara Fitzgerald]

Yes.

[Dave Asprey]

Right. So here's a question for you about polyphenols. You can drink green tea and you get micro doses of EGCG and you get reasonable amounts of oxalate. So I take, I think 800 milligrams of EGCG on a daily basis. I would have to basically boil myself in tea to get that much.

[Chelsea]

Right.

[Dave Asprey]

Do we really get enough from food or is a supplement made from a food going to be more effective?

[Chelsea]

I think that study needs to happen.

[Dr. Kara Fitzgerald]

I mean, what I would say is, so after we published our, I mean, even during the time we were working on our research, there were other dietary pattern studies coming out, you know, Mediterranean dietary patterns. And they might, you know, like the direct trial, they bumped up the polyphenols or the new age study, like there's been there, There is a growing database of human, there's a growing body of evidence of human polyphenol dense dietary interventions, really showing that we're effectively moving the needle on epigenetics through a variety of measures, including the clocks. So I would suggest that, yeah, diet can definitely move the needle, but it's different. I mean, think about a very sophisticated forkful of, you know, a well designed salad and the amount of information, the amount of polyphenolic touch points that are happening, you know, and repeating that multiple times per. Per day. So it's going to have a different impact than a, you know, single dose intervention.

[Dave Asprey]

Right.

[Dr. Kara Fitzgerald]

Like a green tea, you know, a EGCG supplement or, you know, one of my favorites, urolithin A. We can talk about that. It's so badass.

[Dave Asprey]

The first urolithin A launched in the US Launched on the show. Yeah.

[Chelsea]

Oh, did it?

[Dr. Kara Fitzgerald]

Oh, that's really cool. So I would say that a sophisticated collection of polyphenolic compounds are acting on gene expression in ways that we are only beginning to touch on it's called the dark matter of nutrition, as you know, and the technology to be able to understand the interactions, the transformations, et cetera, et cetera, is just beginning to come forward. But when you look at something very well studied like urolithin A, you see how profoundly impactful it is at this therapeutic dose. So I guess what I would say to you is you can't bypass the information from a sophisticated dietary pattern like, you know, the one that we used. It's incredibly important, you know, for physiology, for gene expression. And there is a place to layer on, you know, appropriate cocktails of higher concentration, maybe appropriately designed for bioavailability or transformation in the microbiome, et cetera. Like there is a place for both of these pieces in, you know, really optimizing gene expression.

[Sponsor Voice (Caldera Lab)]

Your face is the first thing people see, and you can work out clean. But if you still look older than you feel, especially if you're a guy, you're not maximizing your potential. Your skin is a signal of how

[Dave Asprey]

well you're really taking care of yourself.

[Sponsor Voice (Caldera Lab)]

And if it looks inflamed or tired or just old, that's what people are going to notice. Even if you're doing your best to eat well. The good news is there's a company called Caldera Lab that's here to fix that for you. This isn't your girlfriend's 20 step routine. It's skincare designed specifically for men, which means it has to be simple and effective and backed by science, but not too much work. After using caldera lab products, 100% of men said their skin looks smoother and healthier. And 97% said they had improved hydration and texture. And 93% reported a more youthful appearance. Caldera Lab has spent years developing and testing each of their formulas with leading cosmetic chemists. So you can tell it actually works.

[Dave Asprey]

And if they don't love it, they

[Sponsor Voice (Caldera Lab)]

don't release it, which is the same

[Dave Asprey]

way I am with my own products.

[Sponsor Voice (Caldera Lab)]

Some of the products you might want to try are the good, which is a face serum that has 3.4 million antioxidant units per drop. There's the eye serum. These are peptides that make you look fully rested even when you stayed up all night doing something you wanted to do. And the base layer, which is a stem cell powered moisturizer that isn't going to give you pimples by clogging your pores. And all their products are cruelty free and plastic neutral. And for every product they sell, they pull the same amount of plastic from the environment, which is good because having little bits of plastic in your mitochondria actually sucks. So upgrade your routine with caldera lab and see the difference for yourself. Go to calderalab.com Dave use code Dave and they'll give you 20% off your first order. So if you're not taking care of your skin because it's just been too much work, now you have a solution.

[Sponsor Voice (Screenfit)]

Calderalab.com Dave staring at screens all day is wrecking your vision and your brain. You might just think it's aging, but it's not. It's a broken eye brain connection. And it gets worse every hour you spend looking at a screen. If you plan to live to 180 and beyond, you need to protect your dominant sense. Now here's the good news. You can train your visual system just like you train your body or your brain. Screen fit is a science backed method built by Dr. Bryce Applebaum that rebuilds how your brain and eyes work together. No eye drops, no appointments, no gimmicks, just 15 minutes a day to sharpen focus, reduce fatigue and protect your vision

[Dave Asprey]

for the long haul.

[Sponsor Voice (Screenfit)]

I saw real results in just a week. If you strive for peak performance or plan to live a very long time like I do, you want clear vision to match? Go to screenfit.com Dave or use code Dave to get $200 off and try it for yourself. You'll see what I mean. Literally

[Dave Asprey]

over time, I've moved more towards supplements for that. Yes, because something like turmeric. Yes, turmeric is exceptionally high in oxalate.

[Chelsea]

I know.

[Dr. Kara Fitzgerald]

You're an oxalate guy.

[Dave Asprey]

Yeah, I didn't used to be. I mean, I did put oxalate in the first chapter of the bulletproof diet. But the more I've played around with manipulating levels, the more I think oxalate is responsible for a lot of broad spectrum inflammation in people because we know how much people can excrete. So I look at something like turmeric, if I'm going to chop it up and cook, which I certainly did, then I'm getting more than my body can excrete that day. If I eat 4 inches of turmeric root, but if I take curcumin, the extract of it.

[Dr. Kara Fitzgerald]

You're bypassing that?

[Dave Asprey]

Yeah, I'm bypassing that and I'm still getting the stuff.

[Dr. Kara Fitzgerald]

Well, okay, so you're concerned about oxalate elimination, but what, you know, what kind of problems have you associated with excessive oxalate ingestion? Like moving beyond theoretical into like Actual phenotypic or.

[Dave Asprey]

Oh, well, we can excrete about 200 milligrams per day, give or take. If you're one of the rare humans that has bacteria in the gut, you might get to 300 a day. And so a lot of the traditional food preparation techniques that we don't use anymore, like fermenting vegetables, which is to reduce oxalate. So what you see is broad spectrum connective tissue issues, because you get these little microscopic crystals in your connective tissue. You see damaged line of the arteries. You see oxalate coming out. When people are doing plasmapheresis, it's actually in the filter bag. And you'll see 70% of kidney stones are caused by oxalate. And then the weird things are you get little styes in your eye as oxalates coming out, and you see it in the brain, especially high in autistic kids.

[Chelsea]

I mean, how do you measure it?

[Dave Asprey]

How can you calculate calcium? Oxalate shows up on a microscope, and it shows up. If you have higher amounts of it as calcium, how did you identify it

[Dr. Kara Fitzgerald]

in the brain of individuals? Diagnosis?

[Dave Asprey]

I don't know how they did that study. I didn't do it.

[Dr. Kara Fitzgerald]

I need to do a little bit. We'll need to do a little bit of a drill down. I'm definitely pushing. I think it's compelling and absolutely. Calcium oxalate stones.

[Chelsea]

Calcium.

[Dr. Kara Fitzgerald]

There is an oxalate arthritis for sure.

[Chelsea]

But I. Yeah, I mean, on the

[Dr. Kara Fitzgerald]

continuum, you're over here with pulling them out, and I don't.

[Dave Asprey]

I've been getting more and more that way just by experimenting. And when I quit eating chocolate for a while and I really monitored my levels and excreted what I had, I don't have pain in my body anywhere. And I've had pain in my body my entire life.

[Chelsea]

Okay.

[Dave Asprey]

And, like, I had the joint in my big toe rebuilt after a yoga injury. It doesn't hurt at all. But if I eat a high oxalate meal when I walk, it hurts and the crystals go there. And so, yeah, the amount of musculoskeletal tension. And the most compelling is multiple studies now exist showing that calcium oxalate is directly toxic to mitochondria because it's penetrating their membrane. It's just like little bits of ground glass in the body. So I'm not saying don't eat any oxalates. I'm just saying that keep it to a dull roar. And if I want to crank up my superfoods, I just go through the list and I say I'm going to eat the superfoods that don't have a lot of oxalate.

[Chelsea]

So we need two cohorts that we oxalate sensitive. Such as you. You clearly are, you've identified that you would, you would be a gout candidate. No doubt what you're describing for sure.

[Dr. Kara Fitzgerald]

And then there are plenty of people

[Chelsea]

such as myself who eat plenty of oxalate dense foods. And I don't have an experience of what I would describe as oxalate toxicity. I mean, yeah, you know, in the last, you know, kidney, I had a CT scan in the not so distant future past.

[Dr. Kara Fitzgerald]

I don't think I have any. There's no evidence of stones of it.

[Chelsea]

So I think I, I think there's

[Dr. Kara Fitzgerald]

a continuum of sensit.

[Dave Asprey]

There certainly is. And some of it's made metabolically and Candida makes it. And I would suggest just to get a good picture of the background for this. Toxic Superfoods by Sally Fallon. And she's a everything is oxalate person. And I don't think that's the case. I was surprised that when I did high amounts of citrate and lemon juice and I've got oxalate out of my body, my time as a raw vegan was not good for me because I was getting incredibly 100%. I would get oxalate tartar on the back of my teeth. A dentist was flaking it off. Yeah, it was, it was weird. But I, I don't want to overstate the case, but I think we're understating it and people have this weird inflammation. They can't figure it out.

[Dr. Kara Fitzgerald]

Yes.

[Dave Asprey]

Sometimes where it's.

[Dr. Kara Fitzgerald]

It can be worthy, it can absolutely be worthy to do an oxalate elimination. No doubt about it. And I have seen it clinically and

[Chelsea]

I think what you're describing. Yeah.

[Dave Asprey]

It's just the question is like, how do I remove plant toxins and still get the benefits of polyphenols?

[Dr. Kara Fitzgerald]

Right. That's right. That's an absolutely reasonable and fair question. And it can be. So for me, I do a lot of the. I get a lot of those polyphenols encapsulated.

[Chelsea]

In fact, I don't eat.

[Dr. Kara Fitzgerald]

I'm of liver and I take it encapsulated at the same point. Same thing.

[Dave Asprey]

Liver's gross.

[Chelsea]

It is pretty gross.

[Dr. Kara Fitzgerald]

So I'm a fan of getting this polyphenolic information, you know, encapsulated and isolated for sure. I do think it's going to be, you know, an endeavor that I, I'm more Excited to undertake is studying the element that we identified in our paper

[Chelsea]

and just, you know, putting together a protocol to see how we move the

[Dr. Kara Fitzgerald]

needle using a formulation. So, yeah, to your point, there's a place for that.

[Dave Asprey]

It's something that I think we're going to see more and more of because it's also hard to know how much polyphenol is in plants. And the most abundant polyphenol in our diet is from coffee. And Danger Coffee is my new coffee company. Not with bulletproof anymore for people who haven't heard. But even there, the amount of polyphenol varies widely based on how the coffee plant is, how stressed it is, whether there were bugs. And so we didn't forgetting. I like the idea. If we're going to live a long time, let's take enough polyphenols in the form of supplements to know that we're getting benefits and let's eat a broad spectrum of stuff so that we're getting all the other things we don't know matter. But I don't want to count on the food to deliver a therapeutic dose because it doesn't have enough in it.

[Chelsea]

I think that's fair. And we did move the needle on bioage using a dietary.

[Dave Asprey]

It's also fair.

[Chelsea]

And we are just doing our EWAs, our epigenome wide association study, and we significantly moved the needle on, you know, a host of different genes. We altered the methylation patterns on, you know, well beyond the content of the clock. So we know that diet. We know that diet moves the needle like you just can't discount it. And, you know, when we're thinking about, like, you know, going back to our conversation off air on Yamanaka mimedics, it's my belief that, yeah, we're gonna have to go into concentrations that, you know, exceed what we can get in a diet. Unless you want to just eat all day.

[Dave Asprey]

You said my happy wor. Yamanaka. Tell me about Yamanaka factors.

[Chelsea]

So Yamanaka factors are, you know, a set of transcription factors. So these guys, you know, dictate gene expression, you know, just manipulate, you know, what proteins are being created from our DNA. And Yamanaka discovered them, I guess.

[Dr. Kara Fitzgerald]

Well, and who was his colleague who, who received the Nobel?

[Dave Asprey]

I don't remember off the top of my head. No.

[Dr. Kara Fitzgerald]

We should.

[Dave Asprey]

I know, I wrote about it, Chelsea, and Google it.

[Chelsea]

I know, I know.

[Dr. Kara Fitzgerald]

I've read. I've written about it too. It's easy to remember that Yamanaka was one of the guys who got the Nobel. But I mean, the incredible thing was they put together this cocktail of four factors and they were able to take a somatic cell, so an established cell with an identity like a muscle cell or a heart cell or whatever, and expose them to these transcription factors and bring it all the way back, reduce its age, if you will, all the way back to a pluripotent stem cell

[Dave Asprey]

status, which is the holy grail for stem cell cells.

[Dr. Kara Fitzgerald]

It's extraordinary. Yeah, it's like the starting point, you know, it's like building a baby. You start with these undefined cells, and then, you know, you go on to manipulate, using epigenetics to. To define what that cell will become. So if you're building a baby, you're going to make a bunch of, you know, neurons and muscle cells and heart cells, et cetera, et cetera. So it was an extraordinary achievement. Of course, they both deserved the Nobel deeply. These are Yamanaka factors.

[Dave Asprey]

And you can't buy Yamanaka factors.

[Dr. Kara Fitzgerald]

Right. Maybe from a lab supply house, but I don't know that you want to be sucking down a cocktail of Yamanaka factors at this point. We could talk about risks around that. So now, as you know, they're experimenting with Yamanaka factors in cell models and animal models. There are two human trials that I'm aware of. One in skin.

[Chelsea]

I think one for Sinclair is doing

[Dr. Kara Fitzgerald]

one in optic neuropathy. I mean, really right now they're phase one in their safety trials, but so they started to experiment with using the Yamanaka factors, but controlling the amount of exposure. So you don't go all the way back to pluripotent stem cells that might

[Dave Asprey]

not be good in it at all.

[Dr. Kara Fitzgerald]

Right?

[Chelsea]

That's right.

[Dr. Kara Fitzgerald]

Do you remember when spontaneous human combustion was really big? That's my visual on if you took a cocktail, turn into grey goo, like, that's my visual. So, yeah, I don't think they're quite ready for prime time.

[Dave Asprey]

There must be a TV show. I know that TV writers listen to this. So someone has to make a Yamanaka factor, like assassination thing that turns people into balls of pus or something. This is gonna be a great show. Okay. Wouldn't that be funny?

[Dr. Kara Fitzgerald]

It's so funny.

[Dave Asprey]

Just mark my waist three years, you're gonna see this.

[Dr. Kara Fitzgerald]

That's so funny. So they're working on controlling it, and they're exposing all sorts of different cell types and just rewinding the cell to a younger timeframe. So they've looked at really old skin cel samples from, you Know, people in their 90s and they can wind them back, you know, to their 20s. I mean, they can just shave decades off. And they're getting better and more sophisticated at controlling them. So as you know, if you, there are dangers around taking something back to a pluripotent stem cell and then, and then recreating a somatic cell or beyond

[Dave Asprey]

that, you create a bone cell in the middle of your eye, that's probably a bad thing, right?

[Dr. Kara Fitzgerald]

Teranotomas, yeah, there's like all sorts of mischief, but they're, you know, they're hard at work. And certainly Sinclair has shown some extraordinary, extraordinary work out of his lab, reversing age associated optic neuropathies using Yamanaka factors. And then they go back in and they test the neurons, and the neurons are younger.

[Dave Asprey]

How do you get it in? Like, how do you get a Yamanaka factor into your eye?

[Dr. Kara Fitzgerald]

Oh, my God. That's a good question. How did they actually deliver it? Yeah, I don't, you know, that's a great question.

[Chelsea]

I don't know.

[Dr. Kara Fitzgerald]

I mean, it was a mouse model. It definitely wasn't a human model.

[Dave Asprey]

So, you know, I'll be the first guy to drip some in my eye and God knows what'll happen, but wouldn't be the first time I was a guinea pig.

[Dr. Kara Fitzgerald]

Victoria Sebastiano out of, out of, of Stanford. Their laboratory has done some really cool work in a variety of applications. They're looking at now. I think they're moving into ovarian rejuvenation that we can talk about and we talk about why. Yes, but they're working in a skin model now and jumping the FDA hoop. So they'll be able to test a topical application to reverse aging. And they're showing some really cool data

[Chelsea]

in terms of changing. I'll tell you what, the other what

[Dr. Kara Fitzgerald]

is walking hand in hand with that

[Chelsea]

is the use of, use of solid

[Dr. Kara Fitzgerald]

AI in fast tracking identification.

[Chelsea]

I mean, it is no joke what's happening.

[Dr. Kara Fitzgerald]

But I want to talk, I want to make a point like why I

[Chelsea]

wouldn't suck down a cocktail for many reasons.

[Dr. Kara Fitzgerald]

But Victoria Sebastiano, who was, by the

[Chelsea]

way, on my podcast, just really, really interesting, who's influenced my thinking quite a bit, thinking about ovarian rejuvenation. So it seems like probably the entry point into using Yamanaka in humans will be, you know, targeting, I mean, because.

[Dr. Kara Fitzgerald]

Targeting an organ or a cell type,

[Chelsea]

because all, you know, the duration of

[Dr. Kara Fitzgerald]

exposure to any cell type, any organ

[Chelsea]

system is going to vary. It's going to be different. It has to be so highly controlled ovaries.

[Dr. Kara Fitzgerald]

And so the next question is what

[Chelsea]

organ is going to yield the best leverage? Right. And in women, of course, it's going to be ovaries.

[Dr. Kara Fitzgerald]

So if we can keep hormones around

[Chelsea]

longer, you know, brain health is sustained cardiovascular health, you know, skin, GI bone

[Dr. Kara Fitzgerald]

health, on and on.

[Chelsea]

And obviously, woman wants to have a baby for they want to maintain reproductive

[Dr. Kara Fitzgerald]

health, there's that opportunity as well.

[Chelsea]

But in terms of a leverage point

[Dr. Kara Fitzgerald]

in women, it's really extraordinary to start

[Chelsea]

thinking about ovarian rejuvenation.

[Dave Asprey]

Have you seen the experiments? These are mice, but I think they might be doing it in people where they take from a young woman who's healthy, they take a small biopsy of ovarian tissue and then put it in a tissue bank. And then when perimenopause starts, they reimplant it and it rejuvenates the ovaries. They get another 20 years of no menopause.

[Chelsea]

Absolutely extraordinary.

[Dave Asprey]

So this is something that I hope some company is doing right now.

[Dr. Kara Fitzgerald]

Yes, yes, yes. Well, you know what, to that point, because probably you're dialed in on this. I was just talking to, you know, Darshan Shah.

[Chelsea]

You must.

[Dr. Kara Fitzgerald]

Yes, of course. He's a good friend and colleague of mine and, you know, banking stem cells in our kids or, you know, just taking a specimen to have or for me, you know, for all of us. But I was specifically, you know, just wondering about my daughter. She's seven now, just, Just, you know, bio banking, something that she'll have access to later. And now she's only seven. So, you know, she's just. It would be a perfect time. And that's out there somewhere. So it's something that I would like to find and if anybody can find it, I'm sure, I'm sure that you can.

[Dave Asprey]

It'll happen. And, you know, cord blood and all that.

[Dr. Kara Fitzgerald]

Yes.

[Dave Asprey]

Good. I think the most important time is when you're probably about 23 to get, you know, your stem cells. Banks.

[Chelsea]

Yeah.

[Dave Asprey]

Get your hormone levels. Because now you know the right range. At least if you're healthy. And there's such a wide range of healthy hormone levels, some guys are actually muscular and performant at 600 and other people need 1100. And if you never knew what your healthy levels were.

[Chelsea]

Right.

[Dave Asprey]

When you're 40 or 50 and you start hitting andropause or women on perimenopause.

[Chelsea]

Right.

[Dave Asprey]

Like you have to kind of guess around so you find a range that feels right. But if you just had the data and that's like a $300 test.

[Dr. Kara Fitzgerald]

Yes.

[Dave Asprey]

And then banking a little bit of fat that you can amplify to make stem cells.

[Chelsea]

Yes.

[Dave Asprey]

And we don't need to do bone marrow the way we used to. I've had mine tapped twice. But now you can actually take a drug that causes your marrow cells to be excreted into your blood, and you can just filter them out, and once those are banked, you have them for life.

[Chelsea]

Yeah. So I do think. I do think that this is important, and it's where we're headed. You know, the other really cool thing

[Dr. Kara Fitzgerald]

is, are you familiar with brain cancer?

[Chelsea]

You must be familiar.

[Narrator/Disclaimer Voice]

No.

[Dr. Kara Fitzgerald]

Brain key. So this is.

[Chelsea]

It was developed in Stanford. A Stanford science scientist, Owen Phillips, who was on my podcast, by the way. It was a really cool conversation. He's. He's quite a badass scientist. You should talk to him.

[Dave Asprey]

Okay, I'd love an input, but they've.

[Dr. Kara Fitzgerald]

So they just moved the knee. They're using MRI technology to its full

[Chelsea]

or fuller capabilities by really marrying it with AI that they developed, you know, painstakingly over many, many, many, many, many,

[Dr. Kara Fitzgerald]

many years, like doing his. During his postdoc and.

[Chelsea]

Or his doctorate and postdoc with his. With the group there. So they can take a highly sophisticated brain image now and glean far more information from, you know, your. Your mother's mri.

[Dave Asprey]

Oh, because of AI?

[Chelsea]

Yes. Well, because of AI, yes, because they can.

[Dr. Kara Fitzgerald]

As he describes it, you know, MRI is.

[Chelsea]

Is a.

[Dr. Kara Fitzgerald]

Is a Porsche, but we drive it like it's a Ford Fusion. Seriously. We don't use it. And that's because it's mostly humans who are looking at.

[Chelsea]

At.

[Dr. Kara Fitzgerald]

And you can only look at so many images. But if you can really take, you know, thousands of images and then run it through AI and there is, you know, there is some human involvement in there. You can get much more sophisticated data. So a baseline, just. My point is getting a baseline brain MRI is also a nice tool to have in your pocket for later.

[Dave Asprey]

In fact, I'm a huge fan of Prenuvo because they're the first company to do AI with this. And I went to their first location, it was the only one in Vancouver, and did mine years ago, and I just did it recently, and they were able to do brain volumetrics they couldn't do before, which is really interesting.

[Dr. Kara Fitzgerald]

So they're evolving it. Good.

[Dave Asprey]

They're evolving it so we get better data.

[Dr. Kara Fitzgerald]

Yeah.

[Dave Asprey]

And when they came on the show, I got a call from them, like, six months later, and they said, Dave, that episode saved 25 lives. I said, what do you mean? They said, well, of the people who came in when they saw the show, X number of them had aneurysms. Like, go to the hospital right now.

[Dr. Kara Fitzgerald]

Wow.

[Dave Asprey]

And another person had a 3 centimeter brain tumor with no. No symptoms and was able to get it removed with no problems. And she was actually an oncology nurse and didn't even know. But it's amazing what we can do with mri, right?

[Dr. Kara Fitzgerald]

I mean, we're just. It's an exciting time to be in

[Chelsea]

this space, both as a recipient of

[Dr. Kara Fitzgerald]

the evolution of these tools, but also to be able to talk about them.

[Chelsea]

It is.

[Dr. Kara Fitzgerald]

It's pretty extraordinary.

[Dave Asprey]

Let's talk about Yamanaka factor.

[Chelsea]

Okay, let's get back.

[Dave Asprey]

You teased me ahead of the show and you said, I know about Yamanaka memetics. That sounds like something I want a pound of. So what's a Yamanaka memetic and how do I use it?

[Chelsea]

Well, I guess there's a couple.

[Dr. Kara Fitzgerald]

There's two arms that one could think about it in.

[Chelsea]

I mean, there's the published work of, you know, again, Sinclair and the various chemical cocktails he's put together that can

[Dr. Kara Fitzgerald]

behave as Yamanaka factor.

[Chelsea]

So he calls it chemical, I think, cellular rejuvenation. You're familiar with that work.

[Dr. Kara Fitzgerald]

And there are compounds that we're using

[Chelsea]

now already, like alpha ketoglutarate, forskolin and what else? Sodium butyrate and then a whole bunch of.

[Dave Asprey]

It makes me happy to hear these, that I launched a forskolin supplement when I was at bulletproof and sodium butyrate. Done episodes on it. So somehow in the longevity field, it feels like we know these things are working, but we don't know the why. And you're figuring out it might be

[Chelsea]

via Yamanaka, via actions similar to what Yamanaka factors can do.

[Dr. Kara Fitzgerald]

So if you look at Yamanaka factors

[Chelsea]

as being able to, you know, rejuvenate cells all the way back to a pluripotent stem cell.

[Dr. Kara Fitzgerald]

So if you look at this as a continuum or a walk, if you

[Chelsea]

will, you know, some of these other interventions can take. Well, I mean, his cocktails, I think

[Dr. Kara Fitzgerald]

can pretty aggressively rejuvenate, but those aren't

[Chelsea]

ready for human ingestion. It's not just sodium butyrate and alpha ketoglutarate and forskolin. It's mixed with a whole bunch of chemicals that aren't ready for human consumption.

[Dave Asprey]

Got it. I would just do a shout out. You should be Taking AKG and sodium butyrate for sure, and probably Coleus Forskolin, although there might be questions about that for some people. But anything else on that list?

[Chelsea]

Yeah, I think AKG is pretty small. Yeah, and butyrate is as well. Vittorio Sebastiano's lab, where they're working with Yamanakas, they developed what they call an index.

[Dr. Kara Fitzgerald]

Looking at these proteins that regulate gene expression from development, you know, through age. They're called PRC, Polycomb Repressive Complex 2, specifically. And so they've created this. They've created an ability to track the changes wrought by Yamanaka factors. And they're able to see, you know, when we look at all the hallmarks of aging, that. That it's the epigenetic manipulation that can then manipulate downstream the other hallmarks of aging. And there's sort of more to it than that. But they have an ability, they have a tool now to be able to measure this epigenetically and identify what the Yamanakas are doing in this arena in the cell reversal. So using this tool, they're able to begin to check other compounds to see whether or not they can move the needle on these polycomb repressive complexes. And therefore, the suggestion would be that they're walking along with Yamanaka. Not again, as far as Yamanaka, but like a gentle manipulation along the path of what these might do.

[Dave Asprey]

So if we wanted to draw a parallel, you go back 10 years, we couldn't tell whether a longevity intervention worked. And we came out with these biological clocks to say, are you older or younger than your biological age? And now these Yamanaka clocks, if you want to call them, that, are able to say, well, is a compound turning your cells to be younger or older? So that now we can measure the efficacy of all these different ingredients or combinations, which is part of what we need to do to live way longer than we're supposed to.

[Sponsor Voice (Stemregen)]

Want to know which foods and supplements work best for your body? VIOME takes the guesswork out of it. Their full body intelligence test reads your rna, not your DNA. So you see what's happening in your body right now. While standard labs measure around 100 markers, Viome's AI analyzes over 10,000 active pathways across your gut, oral and cellular health. Then it translates that into personalized food and supplement recommendations built for your unique biology. They'll tell you what foods to eat and which ones to avoid. They even create custom supplements and oral care products based on your results. So what you're getting is what will work for your body. Not someone else's. Your results update as your lifestyle changes, so your plan evolves with you. Check it [e-mail] and use code 10Dave for 10% off. It's time to stop guessing and start knowing your body.

[Dr. Kara Fitzgerald]

I think the possibility of these PRC2 clocks is that, that they may be more intimately touching on what I think is a program phenomena of aging. So there's like expose aging, the wear and tear of existence, exposures to toxins, stress, et cetera, all of our exposomic variables.

[Dave Asprey]

Taxes.

[Dr. Kara Fitzgerald]

Yeah, taxes. I think that we're pretty good now in manipulating those clocks. Like we've got a lot of solid interventions that can extend quality of life, reduce our developing the chronic diseases of aging for sure. So this exomic arena functional medicine I think already kicks butt. And we're moving forward with like TPE and you know, all sorts of new compounds that will continue to kind of push against the ravages of the experience of life. But we all age. You know, we have this, we have a built in life expectancy. And so there's another phenomena I think that is occurring and that's a program phenomena. And, and I think Yamanaka is manipulating that in the way that we can. One of the ways that we may be able to test that is by looking at whether or not we're moving the needle on these polycomb repressive complexes, which you know, basically are key in building a baby. And you know, they're shut down over time, predictably with age and death. And so if we can get in there with more benign interventions and move the needle on what I think is touching on the program phenomenon, not the exposeomic phenomena, although there's crossover, then you know, we have the potential to build, you know, we could, you know, be touching on something in more depth in the aging phenomena, caloric restriction. So that, so they showed that caloric restriction moved the needle in these clocks. And that to my knowledge is the only two pieces, the only two interventions. Yamanaka and then pretty intense caloric restriction in an animal model has moved the needle on these polycombs. Repressive complex data I think. So one of the things that I'm kind of bullish on is that there is probably a collection of polyphenols because there are preclinical data out there that these guys may be able to do something similar with regard to this collection of protein. So yeah, we're terming them Yamanaka mimetics. And you know, it's an area that I'm eager to Kind of do a drill down in and explore and measure and play around and you know, just dance in. And I'll tell you one other really interesting thing. And I know just, I'm sorry that

[Chelsea]

I'm attempting to articulate this as clearly as possible.

[Dr. Kara Fitzgerald]

And it's a little bit convoluted.

[Dave Asprey]

You're synthesizing. It's great.

[Dr. Kara Fitzgerald]

Is it? Okay. So in the preclinical data, we can see that polyphenolic compounds can without question help to re express. So as we age, we predictably hypermethylate and shut these proteins down. Predictably, this is the aging phenomena. They're really on during development, they're on during, in utero development. And then just predictably over time they shut down. And so we do, you know, we can see Yamanaka turns them on. Effective anti aging interventions turn them on. And yes, preclinical polyphenols will turn these babies back on. And so probably there's a cocktail, probably it's pretty aggressive. It may have a different delivery system that may be able to play around with these guys.

[Dave Asprey]

So this is the future of it. And in the meantime, probably rosemary, oregano, marjoram, thyme and yarrow would be really

[Dr. Kara Fitzgerald]

good things that you would.

[Dave Asprey]

Yeah, there's some of the highest polyphenol foods and I eat about 2 tablespoons of all those, except for yarrow, which is more common in France, but has unique polyphenols for aging in it. I probably should. I just don't know how to get yarrow that tastes good.

[Dr. Kara Fitzgerald]

So let me tell you a couple

[Chelsea]

more things about these clocks.

[Dr. Kara Fitzgerald]

So the Horvath multi tissue clock, you, you probably know at this point has been kind of poo pooed as a first generation clock. And now we're on to second and third generations.

[Dave Asprey]

Let me explain that.

[Dr. Kara Fitzgerald]

Yeah.

[Dave Asprey]

Listeners, we've had a couple episodes on DNA methylation as a way to measure your aging clock. Like how old is your body versus how old does the calendar think it is? And they're looking at at least 600,000 different DNA methylation points to do this. But there's a lot of math involved to figure out what's the right way to look at all that data. And Steve Horvath proposed the first clock that we've all used. And since then there's probably 18 more clocks or something like that that are out there, there. And so there's the context for this.

[Dr. Kara Fitzgerald]

Yeah. And so his clock, his first clock

[Chelsea]

was thought to be, you know, something you might use in forensics. It can, you know, identify chronological age. It walks in step with chronological age. But now as we're moving towards understanding

[Dr. Kara Fitzgerald]

these polycomb, the polycomb collection of clocks,

[Chelsea]

or as Sebastiano calls it, an index. In his case, we can see that the Horvath clock, this original clock actually is dense with this polycomb data, you know, maybe touching on the aging phenomena

[Dr. Kara Fitzgerald]

more than some of the next generation

[Chelsea]

clocks that are trained against, you know,

[Dr. Kara Fitzgerald]

biomarkers that are associated with exposomic exposures. So anyway, this is super dense, but I think there's a full circle moment here in realizing this clock, which we thought was only useful for measuring chronological age, which basically makes it non useful, might be touching on something, you know, rather extraordinary, rather, you know, closer to programmatic aging. And we did move the needle on that clock and we did identify the polyphenol kind of heavy lift of that. So there's a preliminary piece of data from our research and then again the preclinical stuff. But I want to just tell you a little bit more about these clocks because they're so badass, they're so interesting. We can, these clocks are across mammals. So we all, all mammals have this, take this polycomb repressive complex journey, you

[Chelsea]

know, where they develop, you know, the

[Dr. Kara Fitzgerald]

baby, the, the fetus is developed, you know, manipulated by these guys and, and you know, turning genes on and off. And then they're slowly, over time, inhibited. So you can use these clocks to measure the biological age of any mammal. And we can actually, for example, now

[Chelsea]

see that polar bears age is accelerating

[Dr. Kara Fitzgerald]

because they're losing habitat or they can start to identify the age of, you know, mammals that they really, that we haven't had access to, to be able to track, you know, to really establish

[Chelsea]

their, their rate of aging or their age.

[Dr. Kara Fitzgerald]

And so we can use these clocks across the board.

[Chelsea]

And these clocks also can pick up

[Dr. Kara Fitzgerald]

maximum life expectancy across mammals as well. So I'm excited that we're on to something heavy duty. And my passion is, you know, and my commitment is to figure out, you know, again, using this functional med lens, how we might play into this. So we always, in clinical practice, we'll always use these exposomic clocks. We'll always be using our full toolkit of interventions to optimize biological age as we can to reduce our risk of developing diseases. But then the next step is to actually play around with the, you know, the, the underlying programmatic aging phenomena as well. And there may be some tools that we're already using that will, you know, that, that will do that, that will help us.

[Dave Asprey]

That's so impressive. The amount of data there is something that no human can do, but AI can do that really well. So our ability to discover new associations, it's truly a golden age for longevity because of that. And you can ask these complex questions, and then you can look at the real data and say, wow, no one ever knew that before.

[Chelsea]

And we can sort the hallmarks kind

[Dr. Kara Fitzgerald]

of according to, you know, is this

[Chelsea]

exposomic or could this be programmatic?

[Dr. Kara Fitzgerald]

I mean, we can begin to look

[Chelsea]

at, you know, a lot of information that we have through this lens. And, you know, Horvath, you know, quite a while ago published, like, the intrinsic

[Dr. Kara Fitzgerald]

and the extrinsic aging clocks. And so this has been floating around, but I don't know, I'm just excited to kind of, you know, play in

[Chelsea]

this sandbox, at least, you know, think about it and, you know, hopefully be able to engage in some real science

[Dr. Kara Fitzgerald]

around it as well.

[Dave Asprey]

When you look at some of the nutritional recommendations, the ones that always kind of drive me nuts, eat a rainbow, eat every color of food every day. And I think historically we didn't do that because plants don't grow in winter, right? So you generally eat whatever color is in front of you and it changes based on the time of year. So there's some sort of circadian seasonal matching here that we haven't really done that much work on. But we know seasonality eating can change. And then there's a lot of plants you can eat that provide calories, but they may not be that good for you in the long term. So the old school, just, you know, eat one of everything. Better than not eating one of everything. But we're getting to the point where we can say for your biology, yeah, you should eat these 25 polyphenol things or take a pill with that, and it's going to have the most benefit. Right? And that just is so much data. But we're getting there.

[Chelsea]

Yeah.

[Dave Asprey]

And we do have anecdotal data that some polyphenols are better than others. Like my friends from Vinia were just on talking about red grape polyphenols and how they've been able to get a hundred times more of them with cell culturing to do that. So we're even getting the ability to manufacture, like, superhuman levels of polyphenols that have, in that case, a direct effect on nitric oxide signaling in the body and blood flow and things. So all we need to do now is come up with the right recipe and it May be personalized.

[Chelsea]

Yeah, that's right. The right recipe as well as, you know, that I could see us perhaps manipulating delivery. You know, I mean, there's some pretty badass science out, you know, looking at sort of like, you know, nano polyphenolic structures, like shutting down cancer stem cell production. And I think, you know, the take home is that polyphenols are no joke.

[Dr. Kara Fitzgerald]

Yeah.

[Chelsea]

But to your end, there's thousands of them and, and they interact synergistically, they interact with our microbiome, they interact with digestive juices. Some of them are absorbed and used intact. Some of them are completely transformed. We need different quantities for different actions. Some of them. To your point, I think we want high dose concentrates like urolithin A. I mean, the data on urolithin A is just super impressive. But that is just one player in a sea of many, many, many compounds that we just really have yet to unpack. I'm a F of Himalayan Tardui buckwheat and the, you know, the work that Dr. Jeff Bland and Dr. Austin Pomerod are doing. And I think, you know, there's something about the collection of polyphenols in that compound and I appreciate their commitment to the science as well.

[Dave Asprey]

There's good evidence for that.

[Dr. Kara Fitzgerald]

Yeah.

[Dave Asprey]

I bought a bunch of it and started cooking with it. Buckwheat's one of the highest oxalate grains. After a week of it, I got all the joints and I was like, damn. So it's like I can have a sprinkling of it for the polyphenols.

[Chelsea]

Right.

[Dave Asprey]

Give me a Himalayan tartary buckwheat polyphenol extract and I'm all over it.

[Dr. Kara Fitzgerald]

That's right. Yeah, that's right. That makes sense.

[Chelsea]

So it is exciting. But, you know, I would say we, you know, let's consume these. You know, do the well designed fork full of salad. Get that information. It's interesting to me, you know, eating along with the seasons. Yeah. There's gonna be times when we're eating mostly like protein, you know, when plants aren't really aren't flourishing or maybe protein plus apples or something like that.

[Dave Asprey]

Is a carnivore diet bad for you?

[Chelsea]

You know, that's funny. That' that's funny. I think it's fabulously effective short term for some individuals. Fabulously effective. There are people who are, who are at it long term. I think a lot of long term carnivore diet folks will probably crash and burn.

[Dave Asprey]

Most of them do.

[Dr. Kara Fitzgerald]

Yeah.

[Chelsea]

But short term, if you really want to shut down a lot of damaging physiological processes. You can do that, you know, remarkably effectively.

[Dave Asprey]

It's like the world's best elimination diet. Just eliminate everything that might be a problem.

[Chelsea]

Right, right.

[Dave Asprey]

Okay, so we're aligned on that. And I tested out a long term carnivore diet before we called it that. I was stress testing the bulletproof diet before I published it. And I went on only meat and butter for months and I felt amazing. I got leaner than I'd ever been. This is magic.

[Dr. Kara Fitzgerald]

Yes.

[Dave Asprey]

But then I tracked my sleep and suddenly I started waking up 10, 12 times a night without knowing it and I needed more sleep and things just weren't right. And this oftentimes happens. Right. And I think I gave myself leaky gut. In fact, I got an egg allergy from doing that.

[Dr. Kara Fitzgerald]

Oh, you did.

[Dave Asprey]

Just, you know, if you have nothing to feed the lining of your gut, those Akkermansia will dig right through and give you leaky gut. And plus I have a history of autoimmunity, I'm probably high risk, etc, but I tell lots of people, go carnivore for two to four weeks and see how you feel. And they come back and go, go, my life has changed. It's like right now. Find out which of the foods you were eating was causing the problem. And I'm going to bet first on lectins and second on oxalate. But it could be many other things like histamine or mold or whatever. But I'm glad that you're sort of talking about that. So if you're on a long term carnivore, it's great. I just have pancakes on Saturday and keep doing it, you'll probably be much better off. Cyclical ketosis seems to work better if people.

[Chelsea]

What about the Inuit though? You know, they did pretty well back in the day on a pretty like whale blubber diet.

[Dave Asprey]

They did, but it wasn't just whale blubber. It was also very high omega 3. So they're getting EPA pha at incredible levels. Like Nick Norwitz, who's been on the show, just did a sardine diet.

[Dr. Kara Fitzgerald]

Yes, that's right.

[Dave Asprey]

You'll see some really interesting things that happen. So they also had a lot of

[Chelsea]

polyphenols in their diet, berries and so forth.

[Dave Asprey]

Yeah. And they dried them and they had a whole thing where they would mash the whale blubber up with basically herbs and so. So even some of the French paradox, maybe not the obvious French paradox, is why don't Americans just eat like French people with Lots of butter and then not get all the health problems. But anyway, the thing that the French do though is they use a lot more herbs than Americans do. And it's the polyphenols. I think that's a big part of the question. We're looking at macros when we should be looking at polyphenols.

[Dr. Kara Fitzgerald]

Yeah, I mean, I think we should be looking at the whole gamut. But indeed, yeah, indeed. This whole area, you know, this whole

[Chelsea]

sort of so called dark matter of nutrition. I mean there's just a ridiculous amount of information.

[Dave Asprey]

Are you into flavones as well as polyphenols?

[Dr. Kara Fitzgerald]

I mean, I, I think that they're important.

[Chelsea]

I have less command of what they're doing.

[Dr. Kara Fitzgerald]

Although I would imagine that, that it's shared. They all. And they track together.

[Dave Asprey]

Yeah, they're very similar. They, they hang out together and they have similar effects biologically.

[Dr. Kara Fitzgerald]

Yes.

[Dave Asprey]

And some of them are profound. My favorite one is not implants, it's synthetic, but it's dihydroxyflame. And this is so small, like a lot of polyphenols, it can cross the blood brain barrier and it directly attaches to the BDNF receptor, which causes neuroplasticity. And young brains can learn more easily. And so these flavones are having direct activation of receptors just the same way that biological human made compounds would or made inside our body compounds would. So there's this whole realm and we're talking about all these sexy peptides which I know you and I are fantasies of, but looking at these, you know, good old fashioned oregano, 100%.

[Chelsea]

I mean, I. And you know, the soy derived isoflavones and you know, you can get them elsewhere, they're badass. I mean when you look at the

[Dr. Kara Fitzgerald]

in vitro data around re expressing like

[Chelsea]

a hypermethylated BRCA gene, you know, they're potent players. So yeah, you know, isoflavones or flavones in that arena, you know, just important interventions. Again, who we're just touching on our ability to understand what they're doing. And this guy, this one sounds interesting. It's new to me. It's interesting.

[Dave Asprey]

Leave it to me to find the weird stuff. Yes, Kara, you also have a unique ability to find the weird stuff even, even on this, this path. And it's really fascinating and thanks for sharing what's going on in the world of polyphenols and methylation and for doing real longevity research on phenol food because you've proven beyond a shadow of a doubt that at least in middle aged, healthy men, you can get three years of improvement on your biological box just in eight weeks of eating the right foods.

[Dr. Kara Fitzgerald]

Yeah.

[Chelsea]

We did publish a collection of case reports in women, so we showed the same thing in women.

[Dave Asprey]

Great.

[Chelsea]

Yes.

[Dr. Kara Fitzgerald]

Yeah.

[Chelsea]

So, yeah. And onward. We want to refine it and keep going. Humans. Yeah.

[Dave Asprey]

Why did you choose to only study men in the first one? That seems kind of sexy.

[Chelsea]

Super sexist. Super sexist. Because middle aged women, we were concerned about the fact that there would be

[Dr. Kara Fitzgerald]

challenges with regard to where they are

[Chelsea]

in their hormonal journey.

[Dave Asprey]

You sound like a 1970s white doctor, Kara. I'm offended right now.

[Chelsea]

No, we, our cohort, our cohort was

[Dr. Kara Fitzgerald]

small enough so we would have.

[Chelsea]

Have premenopausal women, perimenopausal women, and postmenopausal women in a small group. And that would be a confounding variable.

[Dave Asprey]

Oh, 100%. And just to be really fair, there's huge amounts of research on men and women in all these different fields and much more so in the last 20 years than there was before. But some people say, you know, biohacking's just for men. 58% of biohackers are women and have been since I started the biohacking movement. Like women are great biohackers because of that change that your bodies go through. And it's actually very reasonable to say that I don't want to study for. If you'll give a broad effect. I don't want to study women in perimenopause unless I'm working on perimenopausal symptoms, because you can't get a cohort because every month things are different until they stabilize. But maybe hormone replacement therapy, if you have them all on properly managed hormones, you could do it.

[Dr. Kara Fitzgerald]

Yes, yes, yes.

[Chelsea]

Well, you know, we ended up studying, I mean, women are, are the primary group who are interested in our dietary pattern. And we, and we went on to do, you know, groups through the clinic, like nationally, internationally, and, you know, primarily they were women. And so we got to just track their data. Many of them came to us already using our dietary pattern for a long time and they started biologically just really young. You know, we use the pace of aging now as our measure. So just, you know, well, less than, than the Dunedin pace. Less than 1. Yeah, we use the Dunan pace and just responding fabulously. And in the publication, they actually sort of outperformed the men as far as their bio age reversal. But we used a different specimen and, you know, the testing parameters were slightly Different. Although we used the same clock. But, you know, they did. They're great. They did. They just absolutely responded to it and do respond to it profoundly.

[Dave Asprey]

Do you find that women who go know on these protocols around methylation and on nutrition when they enter perimenopause, that they have less symptoms?

[Dr. Kara Fitzgerald]

Absolutely.

[Sponsor Voice (Caldera Lab)]

Exactly.

[Chelsea]

100%. Yes.

[Dr. Kara Fitzgerald]

Yes, yes, yes. Yeah.

[Chelsea]

The symptoms of the transition period are as.

[Dr. Kara Fitzgerald]

Can be as much about, you know,

[Chelsea]

what's going on in the exposed zone.

[Dave Asprey]

Yeah. It's not supposed to hurt to go through perimenopause.

[Dr. Kara Fitzgerald]

That's right.

[Chelsea]

That's right.

[Dr. Kara Fitzgerald]

And there's plenty of sort of less

[Chelsea]

evolved areas of the world that don't experience the same. Same drama that we do.

[Dave Asprey]

And it's an area that needs. It has a lot of research right now, but it needs even more. And I feel like a doctor, like you, a functional medicine doctor who's educated on all these things, you can take a woman who's having a really strong perimenopausal reaction, and with the right labs and the right prescriptions, usually hormones and some other things, you can stabilize it and take away 90% of the suffering. It's just that most people don't know we can do that. So we have. Have this thing that's going on, and I'm incredibly stoked that they just made hormone replacement therapy the standard of care for women after 23 years of just punishing women because of a press release. So I'm hopeful that that becomes a population that we can study because we've got perimenopause stabilized and it's just a normal thing.

[Chelsea]

Yeah, we've got, you know, a ways to go as far as having, you know, really paying attention to women. But, yeah, it's huge. It's really, really, really huge. The other thing for, because I'm on your show, is looking at fibroids. Like, we still don't really get fibroids. Almost every woman has uterine fibroids, and we don't know why, nor do we really get how to address them adequately. Yeah, it's. It's a. It's a massive mess, in my opinion. Just a massive miss.

[Dave Asprey]

I've worked with a few friends who have them on biohacking them, and it is really tough, very challenging. And it's different than regular tissue fibrosis, which I think I know how to punch that in the face. You can stop fibrotic tissue unless it's caused by hormones. And that's a dark art right now. So we got to fix that.

[Dr. Kara Fitzgerald]

For sure.

[Chelsea]

And actually there was just a publication out attaching it to increase risk of cardiovascular disease, which completely makes sense because it's really inflammatory driven. But you know, the narrative around them is that they're benign and don't worry about them unless you're anemic, et cetera, et cetera. But you know, they're problem players and they shouldn't be there. Absolutely. And we should really, really drill down and understand what it's all about. And we just haven't done. We haven't done it.

[Dave Asprey]

We'll get there. I'm sure there's somebody working on it. We'll find out who they are and get them on the show.

[Dr. Kara Fitzgerald]

Cool.

[Dave Asprey]

Good. And thank you for coming and spending some time with me and going deep on this and your work is fascinating and you're doing real longevity in combination with the lifestyle stuff that's part of biohacking, part of functional health. So you're providing the science that makes it so it's impossible for big food companies to sell us garbage and tell us it's healthy, healthy virus. So thank you.

[Chelsea]

Thanks for having me on. It was a lot of fun.

[Dave Asprey]

Drcarafitchshell.com Yep. Dr.

[Dr. Kara Fitzgerald]

Right.

[Dave Asprey]

Okay, guys, check her out. And if you are a functional practitioner, I know that we have lots listening. You should listen to her show. It's pretty cool. It's very doctory, but it's cool.

[Sponsor Voice (Stemregen)]

See you next time on the Human Upgrade Podcast.

[Narrator/Disclaimer Voice]

A Human Upgrade, formerly Bulletproof Radio, was created and is hosted by Dave Asprey. The information contained in this podcast is provided for informational purposes only and is not intended for the purposes of diagnosing, treating, curing, or preventing any disease. Before using any products referenced on the podcast, consult with your healthcare provider carefully read all labels and heed all directions and cautions that accompany the products. Information found or received through the podcast should not be used in place place of a consultation or advice from a healthcare provider. If you suspect you have a medical problem or should you have any healthcare questions, please promptly call or see your healthcare provider. This podcast, including Dave Asprey and the producers, disclaim responsibility for any possible adverse effects from the use of information contained herein. Opinions of 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. This podcast may contain paid endorsements and advertisements for products on or services. Individuals on this podcast may have a direct or indirect financial interest in products or services referred to herein. This podcast is owned by Bulletproof Media.