Rhonda Patrick, Ph.D. — Protocols for Fasting, Lowering Dementia Risk, Reversing Heart Aging, & More

1. 0:00 – 5:55

   Aging parents and other topics on the table.

   1. TFTim Ferriss0:00

      Rhonda, it is very nice to see you again.

   2. RPRhonda Patrick0:02

      Likewise.

   3. TFTim Ferriss0:03

      Thanks for making the time.

   4. RPRhonda Patrick0:04

      Yeah, I'm excited to be here.

   5. TFTim Ferriss0:05

      [laughs] Yeah. And I was going back through the archives doing my homework as I always do, looking at our past conversations, and it was such a trip down memory lane because our first podcast together was podcast number 12 of The Tim Ferriss Show, which is... was in June of 2014. And then preceding that by a few months, April 2014, was when you had a guest post on my blog called Are Saunas the Next Big Performance-Enhancing Drug? So well done. That's become quite the topic. [laughs]

   6. RPRhonda Patrick0:41

      I know. I kind of like to take a little bit of that, you know, claim to, to making saunas popular. [laughs]

   7. TFTim Ferriss0:49

      Yeah. The fairy godmother of heat shock proteins-

   8. RPRhonda Patrick0:52

      Yeah

   9. TFTim Ferriss0:52

      ... [laughs] within the context of saunas. And we are gonna run out of time before we run out of topics or questions as always, and what's so fun about having a conversation with someone like you, who is not only very scientifically credible and literate, but who's actively involved with the science, tracking the science, and have published, is that there's always more stuff to talk about. [laughs] Things change. There are new developments, there are new discoveries, there are revisions, which makes me very excited to hop into the conversation. And for people listening, we're gonna cover a lot of things that are very, very actionable and practical, and I just wanted to give people an idea of some of what's coming. We may not cover it all, but [laughs] if you'll bear with me, Rhonda, I'm just gonna read some of these because it's, it's great. How to increase VO2 max and why you should. Looking at VO2 max as a predictor of longevity with high intensity interval training. What type of exercise reduces heart aging by 20 years? Brain aging in the same context, or reversing brain aging. The benefits of exercise, snacks on glucose regulation and mitochondrial function. We're gonna get a lot because this is something that is a, a perennial topic for me, but I've been really doing a deep dive on all things fasting related, intermittent fasting, metabolic benefits, IF versus extended fasting versus ketogenic diet, et cetera, et cetera. Daily protein requirements and optimal timing for protein intake. The role of vitamin D in brain health and protection against cognitive decline. How a low omega-3 index is as bad as smoking and what to do about it. Benefits of creatine for brain and muscle health and best practices. Microplastic exposure, the biggest offenders, and so on. It, it just goes on and on. We could cover so much ground. And the way this conversation came to be, to give people a peek behind the curtain, is we were texting about all sorts of things, including aging parents and what we're trying and what we're thinking about, what has worked, what hasn't worked seemingly. And I thought we would just start there if you're open to sharing, because I really gained from our exchanges, enjoyed our exchanges and, for instance, talking about creatine as one example, right? There are potential applications to preserving or at least halting the decline or slowing the decline of cognitive deterioration, right? And why don't we just begin with the personal? Because I think that's the most universal, and all of my friends of my vintage, um, or younger... No one's getting younger, so [laughs] they're all contending with aging parents and what to do with them, how to help them. Can you speak to just some of the circumstances with your parents and what you have used as interventions that have seemed to have an effect?

   10. RPRhonda Patrick3:46

       I'm one of those people that, you know, my parents, neither of them are really physically active. My dad for many years was physically active in the ter- in the sense that he played a team sport. He, he was a baseball player, and he did it for many, many years, all the way into his early 60s, and then he kind of just couldn't do it anymore. So my mother never really got into any sports, and she wasn't the kind of person that would go out to the gym or go for runs or anything like that. And so physical activity really wasn't part of the equation.

   11. TFTim Ferriss4:14

       Mm-hmm.

   12. RPRhonda Patrick4:15

       And neither is really a healthy diet. As I started to do a lot of research into these sort of what I think are interventions that are low-hanging fruits, things that are easy for people to do that can have a pretty big outcome-

   13. TFTim Ferriss4:28

       Mm-hmm

   14. RPRhonda Patrick4:28

       ... in terms of the effect, you know, the size effect is greater than what you have to put in. So examples of that would obviously be something like a supplement that you could take, right? That's the easiest thing you can do is kind of swallow a pill and hope that it has a great effect.

   15. TFTim Ferriss4:41

       Mm-hmm.

   16. RPRhonda Patrick4:41

       And this is where both of my parents are taking a multivitamin, and you might go, "Well, multivitamin, really? What's that gonna do?" And I'll tell you, we've come full circle. You know, 10 years ago there was a huge splash that was made in the media. A big article came out, and it was called Enough is Enough: Multivitamins are Not Only Useless, They May Be Harmful. And it was a study that had looked at a variety of different studies, it's called a meta-analysis, that basically said, well, you know, all these vitamins that you're taking are useless, and in some cases they can be c- harmful because they can allow cancer to, to grow faster. And I sort of debunked that, you know, 10 years ago. But over the course of those 10 years, and as you mentioned in the intro here, you know, science is always changing and revisions are made. We learn new things. And in that 10-year frame, three different randomized controlled trials have come out, and randomized controlled trials are really key because you are comparing, you know, this intervention, which in this case was a multivitamin, to a placebo. Because people taking anything are obviously gonna want a positive effect, and many people do anticipate that, and they can actually change their biology. Placebo's a real thing.

   17. TFTim Ferriss5:54

       Mm-hmm.

2. 5:55 – 7:18

   How a common multivitamin helps reverse cognitive and memory aging.

   1. RPRhonda Patrick5:55

      So three trials came out looking at the effect of multivitamins on cognition And I'm talking the multivitamin that was used was the standard run-of-the-mill. It was Centrum Silver

   2. TFTim Ferriss6:06

      Centrum. I knew it was gonna be Centrum, yeah. [laughs]

   3. RPRhonda Patrick6:09

      It was the vitamin that you would go, "That's the one vitamin that's not gonna have any effect." It's like the... You know. But actually, it turns out it's got over 40 essential nutrients in it, and it's also got some other non-vitamins, so things that are like polyphenols, like lutein, zeaxanthin. These are actually really important for eye health, but also the brain.

   4. TFTim Ferriss6:27

      Yeah.

   5. RPRhonda Patrick6:27

      And these three randomized control trials were two years long, and what they showed was that taking a multivitamin for two years had pretty enormous effects on cognitive aging. These were in older adults. These were adults who were 65 years of age or older. That's where my parents are. And after two years of taking the multivitamin, they had improved cognition on, on a battery of different tests that equated to, like, reducing global cognitive aging by about two years.

   6. TFTim Ferriss6:56

      Hm.

   7. RPRhonda Patrick6:57

      And on top of that, they reduced their episodic aging by five years. Almost five years. It was 4.8 years. Episodic memory is the kind of memory that's involved in remembering events, things that, that happen in your life, and so that's a big effect. Five years-

   8. TFTim Ferriss7:13

      Mm-hmm

   9. RPRhonda Patrick7:13

      ... of reduced episodic brain aging. Episodic memory brain aging.

3. 7:18 – 8:28

   The importance of supplementation.

   1. TFTim Ferriss7:18

      Mm-hmm.

   2. RPRhonda Patrick7:18

      And so I think that anyone that's concerned about their parents, one of the easiest things that you can do in terms of improving cognition... Now, I should mention these were older adults, yes, but they weren't older adults with neurodegenerative disease.

   3. TFTim Ferriss7:33

      Mm.

   4. RPRhonda Patrick7:33

      So these, these were older adults that were... otherwise didn't have any sort of neurodegenerative disease. That's also important, because once you get to a pathological state, you, you kind of have to do more things to help improve cognition than just a multivitamin.

   5. TFTim Ferriss7:45

      Mm-hmm.

   6. RPRhonda Patrick7:46

      That's what I have my mom and my dad on, a multivitamin. That's the easiest thing. Vitamin D is also another no-brainer. I mean, 70% of the US population has insufficient levels of vitamin D. Older adults are even higher than that, so you know, almost the majority of all older adults are vitamin D deficient. I mean, most people aren't going outside, and even if they are going outside, they're either wearing sunscreen or just the fact that they're older affects their, their skin's ability to make vitamin D3 from the sun, from UVB radiation from the sun. And so there's much less efficient at it. In fact, a 70-year-old makes about four times less vitamin D than their former 20-year-old self.

   7. TFTim Ferriss8:23

      Hm.

   8. RPRhonda Patrick8:24

      So a vitamin D supplement is a low-hanging fruit. It's super easy to bring someone up to level.

4. 8:28 – 12:18

   Effectively supplementing with omega-3 fish oil

   1. TFTim Ferriss8:28

      Can I ask you a question about vitamin D? 'Cause I know you love vitamin D. So here's my question about vitamin D, and it actually relates to, I believe, this is a publication you had in 2019, so we'll see if things have changed or not, but ApoE4 and omega-3 brain delivery. So my family, lot of benefits to having my genetics. Also a whole bunch of bugs in the code, including [laughs] quite a bit of ApoE4. I'm ApoE 3/4, and should that change how I consume vitamin D or consume fish oil or omega-3s, having that type of status?

   2. RPRhonda Patrick9:09

      Right. I would say vitamin D, there hasn't really been any effect that I'm aware of in terms of-

   3. TFTim Ferriss9:15

      Mm

   4. RPRhonda Patrick9:15

      ... having an ApoE4 allele-

   5. TFTim Ferriss9:17

      Mm-hmm

   6. RPRhonda Patrick9:17

      ... as you mentioned. And for people listening or watching, you know, ApoE4 allele, if you have one of those, it can double your risk of Alzheimer's disease. If you have two of them, you can go up to a tenfold increased risk for Alzheimer's disease.

   7. TFTim Ferriss9:29

      Yep.

   8. RPRhonda Patrick9:30

      When it comes to fish oil, particularly fish oil, there does seem to be... And this is where my publication came from, but also there's a lot of evidence that has shown people with ApoE4 alleles, they don't tend to have as much DHA getting into their brains, brains as, when people without the-

   9. TFTim Ferriss9:52

      Mm

   10. RPRhonda Patrick9:52

       ... alleles. And on top of that, in, in trials, people with mild cognitive decline, for example, if they supplemented with fish oil and they had ApoE4, they didn't have the cognitive benefits-

   11. TFTim Ferriss10:04

       Mm

   12. RPRhonda Patrick10:04

       ... that the people that were not ApoE4 had.

   13. TFTim Ferriss10:07

       Mm-hmm.

   14. RPRhonda Patrick10:07

       And so there was this big question in the field as to why that is, and it's still not entirely known. Although, I will say what my take on that is, and in fact, I've, you know, talked to some of the experts in the field as well, is that you have to have a higher dose of fish oil, for one.

   15. TFTim Ferriss10:25

       Mm-hmm.

   16. RPRhonda Patrick10:25

       And it's better if it's in phospholipid form. So fish, if you're eating fish, it is... it's in phospholipid form. It's in triglyceride form as well.

   17. TFTim Ferriss10:34

       So just for clarity, if you're taking capsules, it may not be the case. But if I'm eating my can of sardines in the morning, then phospholipid form?

   18. RPRhonda Patrick10:43

       You're getting more phospholipid form, exactly.

   19. TFTim Ferriss10:45

       Yeah.

   20. RPRhonda Patrick10:45

       Now, if you are taking your supplement oils, you can actually make phospholipid form, but you have to really... You have to get to that, like, two gram dose range.

   21. TFTim Ferriss10:55

       Mm-hmm.

   22. RPRhonda Patrick10:55

       That's when your body is also converting into phospholipid form. And then the other way around that is actually consuming a phospholipid form of omega-3.

   23. TFTim Ferriss11:03

       Mm-hmm.

   24. RPRhonda Patrick11:03

       And so that's something that can be done if you're supplementing with either, you know, krill oil, which I'm not a huge fan of 'cause it's super... It's not very concentrated, so you'd have to really take a lot of it, or you could eat something like salmon roe, which is a really high phospholipid concentration of omega-3 fatty acids.

   25. TFTim Ferriss11:21

       Hm.

   26. RPRhonda Patrick11:22

       And you might go, "Why phospholipid form?" Well, it turns out the way your brain... You actually get omega-3 into the brain.

   27. TFTim Ferriss11:28

       Mm-hmm.

   28. RPRhonda Patrick11:28

       There's two ways. The first way doesn't require phospholipid form. It's just this omega-3 sort of in a free fatty acid form, and it diffuses across the membrane and gets into the brain that way. The second way actually is through a transport mechanism, and that is phospholipid form.

   29. TFTim Ferriss11:42

       Mm-hmm.

   30. RPRhonda Patrick11:42

       And that's why it seems as though people with ApoE4, their free fatty acid form isn't, isn't going into the brain as well because they have breakdown of the blood-brain barrier early, early on.
5. 12:18 – 14:54

   The CoQ10 and omega-3 protocol that has helped Rhonda's father manage Parkinson's symptoms for nearly a decade.

   1. TFTim Ferriss12:18

      Okay, let's step back for a second and just get, uh, into the parental specifics, and then we can zoom out and talk about mechanisms and all sorts of stuff. But if you just had to give a couple of bullets on the things that you feel confident in having your mom and dad continue doing or taking, let's start with the supplements 'cause like you said, it's sort of a low-hanging fruit in a sense from a behavioral change perspective.

   2. RPRhonda Patrick12:45

      Right.

   3. TFTim Ferriss12:46

      What do you have them doing?

   4. RPRhonda Patrick12:48

      I guess I'll kind of zoom out and talk about, you know, I think you listened to a podcast I did with Dr. Mark Mattson may- several years ago, and I had mentioned that my dad was diagnosed with Parkinson's disease.

   5. TFTim Ferriss12:57

      Yep.

   6. RPRhonda Patrick12:57

      In 2017. And that's an important context to consider, like, what sort of supplements I'm giving my dad, and also the fact that you have to th- think about compliance. Like, what will your parents... Or do you have a parent that'll take a lot of vitamins?

   7. TFTim Ferriss13:09

      Actually do. [laughs]

   8. RPRhonda Patrick13:10

      Or a few vitamins, right?

   9. TFTim Ferriss13:11

      Yeah.

   10. RPRhonda Patrick13:11

       So with my dad, knowing his disease was Parkinson's disease, multivitamin was in there because that's already, like, so important just to cover a lot of bases. You're getting a lot of different, you know, vitamins and minerals. And then it was omega-3, and in fact, it was a high DHA, and he's getting about two grams a day. And there's a lot of evidence that omega-3 can help with dopaminergic transmission, can help with a lot of brain function, and particularly as it relates to Parkinson's disease as well as Alzheimer's disease.

   11. TFTim Ferriss13:40

       Mm-hmm.

   12. RPRhonda Patrick13:40

       So that was the second supplements that he's, you know, taking. And then the last one that I could really get him to take was ubiquinol, which is a reduced form of CoQ10.

   13. TFTim Ferriss13:50

       Mm-hmm.

   14. RPRhonda Patrick13:51

       Now coenzyme Q10 is actually something that we have inside of our cells, and it's involved in mitochondrial health.

   15. TFTim Ferriss13:58

       Mm-hmm.

   16. RPRhonda Patrick13:59

       So having a depleted CoQ10 can lead to mitochondrial toxicity. And so taking CoQ10, there's actually been some early studies with even Parkinson's disease patients showing that supplementing with CoQ10 can be beneficial. And he's actually taken those supplements for, for many, many years now, and very, I would say, surprisingly, but also I'm thankful, that his Parkinson's disease has progressed very, very slowly. So it's been nine years, you know, almost 10 years, and he's really essentially had this Parkinson's disease limited to one tremor in his hand.

   17. TFTim Ferriss14:35

       Hmm.

   18. RPRhonda Patrick14:36

       So that's great, and that's... All I can say is-

   19. TFTim Ferriss14:40

       Yeah, that's great news

   20. RPRhonda Patrick14:41

       ... it's great news. And you never really know at the end of the day what is the reason for that, but he's convinced, I'm convinced, his doctor's convinced that he should keep doing what he's doing, and that it seems to be beneficial.

   21. TFTim Ferriss14:53

       Mm-hmm.

6. 14:54 – 21:12

   Sulforaphane: a potent NRF2 activator with an unexpected benefit for Rhonda's mother's tremors.

   1. RPRhonda Patrick14:54

      My dad is one of those guys that doesn't like to take a lot of pills. If he would take more, I would give him more.

   2. TFTim Ferriss14:58

      If he were willing to take more, what would you give him?

   3. RPRhonda Patrick15:01

      I would also give him sulforaphane.

   4. TFTim Ferriss15:04

      Mm-hmm.

   5. RPRhonda Patrick15:05

      Definitely tried, but he doesn't want to take more pills.

   6. TFTim Ferriss15:07

      [laughs]

   7. RPRhonda Patrick15:08

      So sulforaphane is... It's a compound that is formed when you eat cruciferous vegetables like broccoli, cauliflower, for example.

   8. TFTim Ferriss15:16

      Mm-hmm.

   9. RPRhonda Patrick15:17

      And it's formed from something inside of it called glucoraphanin. When you break the plant tissue, when you bite it or, you know, chop it up or whatever, it forms sulforaphane. Sulforaphane's not necessarily in the plant itself. It just gets formed when you break the plant tissue.

   10. TFTim Ferriss15:30

       Mm-hmm.

   11. RPRhonda Patrick15:31

       That's a technical thing, so I'm just gonna talk about sulforaphane and call it sulforaphane as if it's part of, you know, the plant, but it's not.

   12. TFTim Ferriss15:37

       [laughs]

   13. RPRhonda Patrick15:37

       Just so you know.

   14. TFTim Ferriss15:38

       Yeah.

   15. RPRhonda Patrick15:39

       Sulforaphane, like I said, it's something that's formed in these cruciferous vegetables. Broccoli sprouts, the young, young sprout of broccoli, actually is the best source of it. It has 100 times more of that active precursor, glucoraphanin, than mature broccoli. So that's the best dietary source of it.

   16. TFTim Ferriss15:56

       Are you growing your own broccoli sprouts, or are you doing off the shelf now?

   17. RPRhonda Patrick15:59

       [laughs] I'm off the shelf now. I used to.

   18. TFTim Ferriss16:01

       [laughs]

   19. RPRhonda Patrick16:01

       I used to. It's work. It's not that much work-

   20. TFTim Ferriss16:04

       Yeah

   21. RPRhonda Patrick16:04

       ... but it is work. But you also, like, you have to be very fastidious about n- not having it contaminated.

   22. TFTim Ferriss16:08

       Mm-hmm.

   23. RPRhonda Patrick16:08

       And that's where the real work comes in.

   24. TFTim Ferriss16:10

       Mm-hmm.

   25. RPRhonda Patrick16:10

       But I like it because there are people that can't afford the supplement, and this gives them another, another way to-

   26. TFTim Ferriss16:17

       Option

   27. RPRhonda Patrick16:17

       ... to basically get it. Yeah.

   28. TFTim Ferriss16:19

       Mm-hmm.

   29. RPRhonda Patrick16:19

       For cheap. So the reason I really like sulforaphane and why I want both my parents on it, and my mom has been taking it, we can talk about that in a minute, is because it is the most potent dietary activator of this system that we have called NRF2, which is this major system... It's a basically a transcription factor that activates a lot of different genes inside of our body, and it activates genes that are involved in stress. It activates a lot of what are called stress response genes. And these are the kind of things that are activated when you're doing stressful things like exercise.

   30. TFTim Ferriss16:52

       Mm-hmm.
7. 21:12 – 22:30

   How Rhonda convinced her mom to start CrossFit

   1. RPRhonda Patrick21:12

      She's doing great. What's funny is that I, I was able to then get her into CrossFit, and I don't know if it's because her, her tremors... I think her, her tremors have lessened a bit, and so she's been more active and wanting to be more active. Like, she's out dancing more. My mom likes to dance. And I mentioned how I really wanted to get her into a seniors CrossFit class, and she sees me do it. I have a coach come to my house and do... We do CrossFit training at my house. My mom has seen me doing it, and she's been interested in it. And I told her that there's a great seniors class and I would be willing to, you know, pay for it and get her in it. It would be huge. And she's been doing it now for a, a couple of months, maybe like three or four months.

   2. TFTim Ferriss21:55

      Mm-hmm.

   3. RPRhonda Patrick21:56

      And she goes three times a week, and she loves it. She loves it. She's made friends there. Sometimes the coaches take videos and she sends them to me. She sends them to her friends. She's so proud. You know, she's doing kettlebell swings. She's doing wall squats.

   4. TFTim Ferriss22:11

      [laughs]

   5. RPRhonda Patrick22:11

      I mean, it's amazing.

   6. TFTim Ferriss22:13

      Go, Mom. That's amazing.

   7. RPRhonda Patrick22:14

      It's a very different type of atmosphere than your usual CrossFit class would be, right? You're aware that these are seniors, and so they're not doing, you know, barbell, like squatting like heavy weights and stuff. There's... They start out with wall squats and then they're, you know, squatting with just like a really light bar and it's,

8. 22:30 – 27:00

   The earlier the intervention, the better the outcomes.

   1. RPRhonda Patrick22:30

      it's really great.

   2. TFTim Ferriss22:31

      Let me hop in for a second here, and I wanna know if there's anything else to add to that. But we've talked about this, you and I, or texted a hell of a lot about it, that I have Alzheimer's in my family. I have, now have multiple relatives who are moderate to advanced with respect to Alzheimer's. Uh, saw my grandmother disintegrate. Terrifying to watch and terrifying to imagine yourself experiencing the same thing. And also, at least one of them is APOE33, and, uh, I'm APOE34, so I'm like, well, wait a second. If that is the [laughs] where they are right now and I'm at hypothetically 2.5x greater [laughs] risk of developing Alzheimer's disease, AD, I should really double down on paying attention to as much as possible for myself. Certainly for them as well, but the earlier the intervention, the better the outcomes generally. So I've been looking at all sorts of things, and just to reiterate a few things you said. So on the omega-3 side of things, just like with sulforaphane, not all brands are created equal, right? There's a lot of garbage floating around out there. Would you say... Neither of us have any affiliation with this company, but I know our mutual friend Kevin Rose had this particular brand tested that, uh, I guess it's One O.N.E. Pure Encapsulations. Is that what you have your, your parents taking, or did you use a different brand?

   3. RPRhonda Patrick24:00

      So with my dad, he is now taking the Xymogen brand, which is also very good, and the reason for that is 'cause it's higher DHA-

   4. TFTim Ferriss24:09

      I see

   5. RPRhonda Patrick24:09

      ... which is what I wanted.

   6. TFTim Ferriss24:10

      Mm-hmm.

   7. RPRhonda Patrick24:11

      My mom is taking The One.

   8. TFTim Ferriss24:12

      Got it. Cool.

   9. RPRhonda Patrick24:13

      Both those brands, by the way, are great. They've both been third-party tested and have very high quality fish oil, and I don't have affiliation with either of them.

   10. TFTim Ferriss24:20

       Yep. I've got my parents on those. I'm taking those. You mentioned lutein and zeaxanthin, which [laughs] is, is good for quite a few things Now, for those people who may be interested, and this probably won't help me with my particular pres- presbyopia, so age-related visual decline, particularly with near work, reading a book, let's say. But AREDS2, people could check out studies that have been done on AREDS2, and two of the principal ingredients are lutein and zeaxanthin. So there's that. Now, also have been very, very curious about how to activate some of the pathways that you mentioned. Sulforaphane would be a good option for that. Also looking at, and we don't have to spend a ton of time on this, but exogenous ketones, right? Because ideally, sure, I would have my parents maybe do intermittent fasting or [laughs] some extended fasts. I don't think that's gonna happen for a million different reasons, but perhaps exogenous ketones and have looked at that. This is kind of a work in progress I'm, I've been doing, and I know you have, too, of lots of self-experimentation. But there are some case studies in the literature, one of which you sent to me, that are pretty interesting looking at administration. In other words, giving an older patient with Alzheimer's disease oral exogenous ketones. They tend to taste like jet fuel. They're not tasty. But the effects of, at least in these case studies, are pretty remarkable. Now, granted, with the monoester they use in some of these, the off-the-shelf cost per day would be like [laughs] $150 or something like that, maybe even more, so there's a sort of a cost question. But I'm just gonna throw a couple of more things out there that are on my mind. So you mentioned the exercise piece. This has been so important for me, so I've hired a trainer. And I realize my parents are kind of sneaky and sometimes a little... I don't want to say passive-aggressive, but they, they'll say they're gonna do something to please me, and then they won't do it. So getting the trainer to actually pick them up at their house [laughs] is, is, is something that I decided to do because there, there are a lot of reasons exercise is amazing, one of which is the natural re- release of klotho. And people can look this up. I'm hoping that you'll be able to inject this in the next handful of years. We'll see in humans. But K-L-O-T-H-O, also worth checking out.

9. 27:00 – 39:28

   Intermittent fasting vs. extended fasting and my own results.

   1. TFTim Ferriss27:00

      Anything else that you would add to that or any commentary you want to sprinkle in? Am I missing any critical... Multivitamin, yeah.

   2. RPRhonda Patrick27:08

      There's definitely commentary. There's commentary, but we can get into that if you want to go dive into the why the ketone esters are beneficial and-

   3. TFTim Ferriss27:16

      Yeah

   4. RPRhonda Patrick27:16

      ... why the exercise is beneficial. We can go into that because I'm, I love talking about it. [laughs]

   5. TFTim Ferriss27:21

      Yeah. This is gonna be a conversation, right? Just between you and me. That's how I treat all these things, and I'm, I'm very self-interested because I think [laughs] the personal is the most universal. Maybe that's just an excuse to make this all about what I want. But we have been texting also because I told you I've been thinking about doing a 14-day fast, and actually I ratcheted that back from doing a 30-day fast. [laughs] And I've done 10 days before water only. I've done lots of seven days. And part of the reason is I think I would be better equipped now to do longer fasts because of the intermittent fasting I've been doing. And this ties into the conversation around the parents because what I've noticed is, for instance, doing 16/8 fasting, which was... There's... And I'm so sorry. The scientist you mentioned before whose podcast interview I listened to on your podcast, what was his name again?

   6. RPRhonda Patrick28:18

      Dr. Mark Mattson.

   7. TFTim Ferriss28:20

      Yeah, Mark Mattson. Amazing, amazing scientist. Fantastic conversation. A lot of seminal work related to intermittent fasting. So 16/8, what does that actually mean? I did this today. I've done this most days now, which is basically eating between... For me, it's like 2:00 PM and 10:00 PM. There are arguments that it should be shifted earlier, like noon to 8:00 PM or something like that. But socially, just practically, again, coming back to compliance, like the good system you do being better than the perfect system you don't, generally it's like 2:00 to, let's say, 9:00 PM is when I eat, and then I fast the rest of the time. And for the first, like, five to seven days, pretty grumpy. Kind of pissy. I'm not gonna lie. You know, sent some emails that I probably shouldn't have. But then once I adapted, I did a recent set of labs, and they're my best set of labs that I've seen. I can't solely attribute it to the intermittent fasting, but the best set of labs I've had in ages on things that were very hard to move prior. Also did an oral glucose tolerance test, and my sort of insulin sensitivity and glucose management, the best it's been in ages. So I was like, "Okay, that's really interesting." The last time I did a seven-day fast, it was kind of brutal. I hadn't done one in a few years, and I don't think my meta- metabolic machinery was [laughs] ready for the task. Very unpleasant. But I have some chronic inflammation or at least chronic pain in my low back, and after doing that seven-day fast, I had four weeks of zero symptoms, and that's the first time in three years that that's been the case. So I was like, "Okay, that's pretty interesting." And so I've ended up harassing you with all sorts of questions, such as, "Well, what if I had a little bit of heavy cream in my coffee in the morning?" So it's kind of dirty fasting. But if I did that, what am I, what am I accepting as a compromise or a penalty, if anything? Because then I think of, say, Longo's work and others looking at fast-mimicking diets where I'm like, "Well, wait a second. These people are doing, let's just say, five days of fast-mimicking dieting per month for three months straight, and they seem to have all these benefits that may be of lower magnitude but mirror water fasting on some level." But they're consuming a few hundred calories, let's just say for simplicity, per day of those five days of, quote unquote, "fasting." If you look at the actual meal composition, it ends up being very low calorie keto basically. Very low calorie keto with very low protein, like 10% or less, avoiding animal products. That's the basic way that I've been thinking of it. And so I was like, well, should I do something like Wilhelmina in Germany who have, again, quote unquote, "fasted" thousands of people, but they do give them bone broth, a little bit of juice. It's, it's akin to the fast mimicking diet. But they, they'll do that with people for 30, 60, 90 days. Or am I better off doing shorter water fasts or maybe even a 14-day water fast? And a lot of the questions came down to... I know this is a mouthful, but as you know, I've been thinking about this nonstop. I was up until 2:00 a.m. [laughs] this morning reading really, really old stuff out of the Soviet Union on, [laughs] on psychiatric clinics fasting patients for schizophrenia. [laughs] And so that tells you metabolic psychiatry also goes back a long, long, long time, not to mention ketogenic diet for epilepsy, right? So there are a lot of similarities. But if I want the benefits, as many benefits as possible with the least pain possible, which includes not losing a ton of muscle tissue, which is not always the same thing as lean body mass, what should I do? Right? That's kind of the open question. And that is a huge, huge mouthful. Thank you for coming to my TED Talk.

   8. RPRhonda Patrick32:14

      [laughs]

   9. TFTim Ferriss32:14

      But where is your current thinking when it relates to all of this stuff? And I, I said earlier at the very beginning that it ties into my parents. Why is that? Because when we looked at some of my relatives and I got my docs to come in and do like a real proper full workup looking at all sorts of things that normally wouldn't be tested, absolutely some metabolic syndrome, right? In the sense that they're h- highly, highly insulin insensitive, like insulin off the charts. And it's like, okay, well this has been going on for years to get to this point, and Alzheimer's is sometimes called type 3 diabetes. And it's like, okay, well, if I can't help them, at least I want to try to help myself and other people who might be listening at an early enough stage. So how do you think about all this stuff? [laughs]

   10. RPRhonda Patrick33:05

       Well, [laughs] there's a lot to talk about here, and I think we gotta kind of-

   11. TFTim Ferriss33:09

       Yeah. Yeah, chew on one bit at a time. [laughs]

   12. RPRhonda Patrick33:11

       Right. Let's chew one bit at a time and zoom out for a minute-

   13. TFTim Ferriss33:13

       Yep

   14. RPRhonda Patrick33:14

       ... and talk about this intermittent fasting concept and why do people wanna do intermittent fasting.

   15. TFTim Ferriss33:19

       Yep.

   16. RPRhonda Patrick33:20

       What are the benefits that they're looking for?

   17. TFTim Ferriss33:22

       Yep.

   18. RPRhonda Patrick33:22

       Now, you mentioned some metabolic benefits that you had noticed after, after doing your intermittent fasting.

   19. TFTim Ferriss33:28

       Mm-hmm.

   20. RPRhonda Patrick33:29

       There's lots of different types of intermittent fasting. You mentioned the 16:8. So essentially you're talking about not eating food for a period of time.

   21. TFTim Ferriss33:35

       Mm-hmm.

   22. RPRhonda Patrick33:36

       And that period of time can either be 16 hours, it can be 24 hours.

   23. TFTim Ferriss33:41

       Mm-hmm.

   24. RPRhonda Patrick33:41

       It can be longer.

   25. TFTim Ferriss33:42

       Yep

   26. RPRhonda Patrick33:42

       In which case, it would not be an intermittent fast, it would be a more prolonged fast, which you also talked about. But with the... with respect to the intermittent fasting, there are a few things that happen, and there are a few reasons why people like to do intermittent fasting. First and foremost, I think most people like doing intermittent fasting is because they wanna actually lose weight, and the weight that they wanna lose is not necessarily their lean body mass, they actually wanna lose their fat mass, right?

   27. TFTim Ferriss34:06

       Yep.

   28. RPRhonda Patrick34:06

       So they wanna lose fat, and that's a big reason why people do intermittent fasting. Well, it turns out that intermittent fasting is more of a tool for weight loss. And what I mean by that is that there have been multiple studies now that have looked at different types of intermittent fasting in sort of a, a community dwelling aspect where people are just kind of free to eat the way they're going to eat, but they're supposed to be practicing intermittent fasting. And what it's been discovered is that naturally people end up eating about 200 fewer calories per day when they're doing some form of intermittent fasting. So if they're eating all their food within an 8 or 10-hour period, for example, usually they'll eat their food within a 10-hour period, and then they'll fast for 14 hours. If they do that, they end up actually eating 200 f- fewer calories. And so they end up performing what's called caloric restriction, which we know can lead to weight loss. And so a lot of the weight loss actually comes from reducing calorie intake.

   29. TFTim Ferriss35:02

       Mm-hmm.

   30. RPRhonda Patrick35:02

       But that doesn't necessarily mean that everything that's beneficial from intermittent fasting comes down to calories, because it doesn't. But the weight loss definitely seems to come down to the calories, because if you keep calories the same and then have people do intermittent fasting or not intermittent fasting, they won't lose the weight, but they will have a whole host of metabolic benefits. You mentioned glucose regulation improvements. I mean-
10. 39:28 – 51:17

    Does fasting destroy muscle mass? Debunking the catabolism fear.

    1. RPRhonda Patrick39:28

       And then another main reason, and there's many others, I'm not gonna, like, touch on everything, but the other main reason is it activates repair processes.

    2. TFTim Ferriss39:37

       Mm.

    3. RPRhonda Patrick39:37

       And what I mean by repair processes is to be in repair mode, you have to be in more of a catabolic state, and we were talking about this earlier. People get so freaked out by the word catabolism.

    4. TFTim Ferriss39:49

       Oh, yeah. Last night when I was walking around New York City, we were talking about this [laughs]

    5. RPRhonda Patrick39:53

       Right, right

    6. TFTim Ferriss39:54

       ... and catabolism. [laughs]

    7. RPRhonda Patrick39:56

       And I think even over the last few years, you know, intermittent fasting's kind of gotten a bad rap because people now equate it with, oh, loss of muscle mass. I'm gonna be catabolic. Well, in order to be in a repair mode, you actually do need to be in a catabolic sort of mode, and these repair systems are so important for cleaning up all the garbage that's inside of our cells, and that can be things like protein aggregates. These are things that lead to aggregation, you know, like alpha-synuclein, which is involved in Parkinson's, amyloid beta aggregates, which is involved in Alzheimer's disease. It's not the cause. It's like the cause and the symptom. It's like both. It's involved in Alzheimer's disease. And then aggregates in our cardiovascular system that play a role in cardiovascular disease. But it also cleans out even damaged little or- what are called organelles, and so mitochondria are an organelle, and our organelles get damaged, so you wanna be able to repair that damage, and this process of autophagy is the process that does that. And, you know, there's lots of different types of autophagy. So if it's a mitochondria repairing damage to itself, it's mitophagy. But for all this stuff to be active, you have to be in that more catabolic state, which can be induced by not eating, can also be induced by, like, heavy endurance exercise as well. So talking about those sort of outcomes that people are interested in, those different endpoints that people are interested in, in achieving, I think something that you're specifically interested in is the metabolic effects of intermittent fasting as well as the repair processes like the autophagy.

    8. TFTim Ferriss41:29

       Yeah, for sure, and that's why I was asking 'cause I don't really... I... Look, I'm as vain as the next person. I like [laughs] looking less fat if I, if I can, but it's not my main driver, right? It's mental acuity and hopefully staving off on some level things like neurodegenerative disease and even cancer possibly, right? Which has been part of the reason I've done a lot of these extended water fasts, which is, I realize there are a couple of hops here in terms of speculation, but seems plausible that you might zap, you know, punch a couple of precancerous cells in the, in the nuts by doing that.

    9. RPRhonda Patrick42:12

       Definitely. Not only does autophagy play a role in preventing Parkinson's disease but also Alzheimer's disease as well. Again, this has been shown in many animal studies. We know that autophagy plays a role in clearing away the amyloid beta plaques that are involved in Alzheimer's disease, and yes, there are some people that have amyloid beta plaques that don't get Alzheimer's disease. They may be the more resilient non-ApoE4 type of person. But we do know that many, many people do get Alzheimer's disease with amyloid plaques, and in fact, people that have, again, the SNPs in what are... what's called the amyloid precursor protein, APP, that leads to amyloid beta plaque buildup, they get early onset Alzheimer's disease. So autophagy plays an important role in clearing away those plaques, and I will say what we don't have a lot of evidence on is what's the minimal effective-

    10. TFTim Ferriss42:59

        Yeah

    11. RPRhonda Patrick42:59

        ... fasting dose to activate autophagy.

    12. TFTim Ferriss43:02

        I know.

    13. RPRhonda Patrick43:02

        Right?

    14. TFTim Ferriss43:02

        God, I wish we had this. [laughs]

    15. RPRhonda Patrick43:05

        I think what we do know in humans from, like, some of these old studies is that you do see some signal of autophagy activation after 24, 48 hours in humans.

    16. TFTim Ferriss43:14

        Yeah.

    17. RPRhonda Patrick43:15

        Now, does that mean that that is the only amount of time that it takes to activate autophagy? No. So most humans are probably doing anywhere between a 12 to 16-hour nightly fast, right? There's a period of time when we're not eating, and that is when we're sleeping, a little bit before bed, right? Autophagy still happens in people. We just aren't measuring it because we don't have sensitive tools yet.

    18. TFTim Ferriss43:39

        Yeah.

    19. RPRhonda Patrick43:40

        And so it's not that I don't think a 16-hour fast doesn't acti-... I, I believe it does in hu-... I believe there's ac- some autophagy going on. It's probably not that much.

    20. TFTim Ferriss43:48

        Mm-hmm.

    21. RPRhonda Patrick43:48

        But if you're... if you go into that, you know, 48-hour fast, then you're really starting to get more robust activation-

    22. TFTim Ferriss43:55

        Yeah

    23. RPRhonda Patrick43:56

        ... of autophagy.

    24. TFTim Ferriss43:56

        Can I s- throw something else in here, just for fun?

    25. RPRhonda Patrick43:59

        Yes.

    26. TFTim Ferriss44:00

        So you mentioned sleep, and I've been looking... trying to look at Alzheimer's from every possible angle, and found literature looking at disruption of sleep architecture in patients with Alzheimer's disease and the possible application of Xyrem, I believe it is, which is another... it's a brand name in a bifurcated schedule for GHB, gamma-hydroxybutyrate, which you have to be very careful with. It's a party drug. People die of it 'cause it suppresses respiration. The person who bought my apartment in San Francisco died of a GHB overdose. But it actually is a tremendously interesting compound for increasing... I think it's, it's deep-wave sleep specifically, which does what? It helps the cleanup crew, right, to do its work and to actually take out the garbage cellularly. And so if I could wave a magic wand, I would have my relatives on something like Xyrem. Might actually be a different type of, of sleep medication, like the NORA class. NORA, might be DORA. I would also look at, and this is something obviously [laughs] not suitable for most elderly people, but potentially lower dose psilocybin or psilocyn. And there is some actually very interesting, I don't wanna call them speculative, hypothetical applications of that to Alzheimer's disease, which you can find on PubMed. And from a mechanistic perspective, they're, they're super, super interesting. So I just wanted to double-click on the sleep because that is such a, a critical component, whether you're fasting or not, to try to ensure that your sleep architecture is not hyper-disrupted, which can be the case with lots of different types of sleep medications that you might take. And if you have really bad insomnia, it's like, okay, you can do all of these other things, but boy, oh boy, it would make a lot of sense to try to fix sleep whenever possible.

    27. RPRhonda Patrick46:01

        Great. So true. The slow wave sleep does activate the lymphatic system, which is cleaning out the amyloid beta aggregates as well.

    28. TFTim Ferriss46:07

        Yep.

    29. RPRhonda Patrick46:08

        And the last thing I kinda wanna mention is, 'cause you were talking about the intermittent fasting and more prolonged fasting and the muscle mass loss or lean body mass, which people equate with muscle mass, which it's not. You know, there's a lot of things going on. So the thing is, when people are doing intermittent fasting, I mentioned they eat fewer calories, which means they're eating less meals. They're eating fewer meals. They're not eating as many meals, and so what ends up happening is people lower their protein intake, and that's an important signal for, you know, maintaining muscle mass and certainly growing muscle mass as well. So it increases muscle protein synthesis, which is important. If people are engaged in resistance training and doing intermittent fasting, they're not losing muscle mass, and in fact, they can even gain muscle mass.

    30. TFTim Ferriss46:50

        Mm-hmm.
11. 51:17 – 54:37

    "Dirty" fasting: what really happens to autophagy and metabolic benefits when you add a splash of cream or MCT oil to your coffee?

    1. TFTim Ferriss51:18

       And I also wanna clarify for folks listening, just to really make it specific. When I have had [laughs] I just like saying dirty fasting. I didn't realize that was an expression. I just think it feels fun, like a dirty martini. Dirty fasting is kinda cheating in this way. But when I do that, which is not all the time, I usually have black coffee or tea or something like that, but it is heavy cream.

    2. RPRhonda Patrick51:42

       Mm.

    3. TFTim Ferriss51:43

       Which is almost entirely fat. It is not creamer that you would just pull off the shelf. It is not half and half. It is heavy cream, which just from a macronutrient perspective is very, very, very different. And you can really overdo it on the calories also [laughs] 'cause it's just, like, liquid fat, effectively. But the MCT powder is a good idea. I tell you what, if you're open to it, let's shift gears a little bit. I will just say I wish somebody... Nobody's gonna do this, but would somehow get the ethics board, IRB, et cetera, to approve long-term human studies again in fasting. That would be great because you used to be allowed to do it. There are case studies of people who literally fasted for 300-plus days. I mean, uh, like, fat, what is it, 9,000 calories per pound? Like, there's... Like, you can do a lot with that fat. So we'll see if I do 14 days. If I can do 14 days, then I might just go to 30, but then the refeeding gets really tricky.

    4. RPRhonda Patrick52:41

       I think people are concerned with gallstones.

    5. TFTim Ferriss52:44

       Mm-hmm.

    6. RPRhonda Patrick52:44

       So when you don't eat for a period of t- long period of time, then you're not stimulating the gallbladder-

    7. TFTim Ferriss52:50

       Mm

    8. RPRhonda Patrick52:51

       ... and the gallstone risk increases, which is what I think is the big concern with, with the long, long fasts.

    9. TFTim Ferriss52:57

       Mm-hmm.

    10. RPRhonda Patrick52:58

        But, I mean, you know, if you're doing something like that once a year-

    11. TFTim Ferriss53:02

        Yeah

    12. RPRhonda Patrick53:03

        ... I don't know if it's that big of a deal.

    13. TFTim Ferriss53:04

        I mean, that's why I was doing a seven-day fast once a year for a long time, and then I took a break for a few years, and I did a seven-day water fast, and it was so incredibly unpleasant. And I had orthostatic hypotension where I'd stand up and I felt like I was gonna fall over, and my, you know, vision started to get funny, and I was like, "You know what? Maybe this isn't for me." But I think it's because my machinery just wasn't developed for that. Having seen really stark differences in my mental acuity and sustained focus with the intermittent fasting, I'm like, okay, I feel like doing intermittent fasting, which part of my reason behaviorally for my interest in that also is that getting people to change their diet is fucking hard, meaning their diet composition, the food they eat. So if you can just say, "Hey, look, keep eating whatever you want, same thing, but you have to fit it within this window," it's an interesting option B that might be, might work for people who otherwise aren't going to follow a paleo diet or whatever. But if you do the IF, and then what I've done is like, all right, do the IF. Maybe if you have some grains or, in my case, legumes and stuff, okay, fine. And then shift to a mostly ketogenic diet for a period of time. Then I feel like you're, you're pretty well teed up for a longer water-only fast. Maybe you supplement with electrolytes. This gets into all sorts of controversial

12. 54:37 – 1:06:24

    VO2 max: the one metric that may predict lifespan more accurately than anything else, and how we work to improve it.

    1. TFTim Ferriss54:37

       territory. But if you're okay with it, let's talk about training for a minute because, and I'll Force a really awkward segue maybe, which is one thing I noticed is that my ability to do zone 2 training, let's just for simplicity's sake say that for people, that's you're on a stationary bike or a bike. Stationary is just easier to keep consistent, and you're, you're cycling for 60 minutes at a, a wattage and a speed that leads you to the point where you could have a conversation with someone on the phone in short, full sentences, but you don't really want to, right? That's like the talk test. Intermittent fasting plus ketosis really helps my zone 2, and then this leads into the question of just training in general. So I have to click on this. What type of exercise reduces heart aging by 20 years? Do you want to start there, or do you want to start with VO2 max?

    2. RPRhonda Patrick55:30

       We can start with VO2 max maybe because they kind of bleed into each other.

    3. TFTim Ferriss55:34

       Great. Let's do it.

    4. RPRhonda Patrick55:35

       So people might be, you know, going, "What is VO2 max?" It's essentially a cardiorespiratory fitness. It's measured or calculated by VO2 max.

    5. TFTim Ferriss55:42

       Mm-hmm.

    6. RPRhonda Patrick55:42

       Which is essentially the maximal amount of oxygen you can take up during maximal exercise, and what's so fascinating about that is it's a really important predictor of longevity.

    7. TFTim Ferriss55:54

       Mm.

    8. RPRhonda Patrick55:54

       So there have now been enough studies that have come out looking at the cardiorespiratory fitness in the, in the sense of VO2 max and how people with a higher cardiorespiratory fitness have a five-year increased life expectancy compared to people with a low cardiorespiratory fitness. In fact, if you have a low cardiorespiratory fitness and you go anywhere above that, like from low to low normal, it's associated with a two-year increased life expectancy. And people with a low cardiorespiratory fitness actually have a higher all-cause mortality that's comparable or worse than people with known diseases like type 2 diabetes or cardiovascular disease or smokers, for example. So in, in other words, being sedentary is a disease, and we need to think about it as a disease, and we should be trying to train to improve our VO2 max.

    9. TFTim Ferriss56:42

       Mm-hmm.

    10. RPRhonda Patrick56:42

        And that is something that should be in our minds. And I say this because, like, just having this conversation that you and I are having right now, it takes about 11 milliliters of oxygen per minute per kilogram body weight just to have this conversation.

    11. TFTim Ferriss56:57

        Mm-hmm.

    12. RPRhonda Patrick56:57

        Now just sit still and just breathe, it takes about three milliliters of oxygen per minute per kilogram body weight, and that's important because as we're aging, we're sort of heading towards this cliff of VO2 max. Our VO2 max goes down as we age just naturally. Even if you're training and doing everything, it goes down.

    13. TFTim Ferriss57:15

        Yeah.

    14. RPRhonda Patrick57:16

        And once you get to that cliff, everything becomes a maximal effort. Like you talking, you're out of breath. You know, carrying groceries to your car from the store, you're just out of breath. Everything is a maximal effort.

    15. TFTim Ferriss57:27

        Mm-hmm.

    16. RPRhonda Patrick57:27

        And you don't wanna be there. So you wanna like start from a higher up point so that when you're going down, that cliff is much further away, and, and that's where, you know, the training comes in because you wanna sort of... You wanna find a training program that's going to improve that, that cardiorespiratory fitness.

    17. TFTim Ferriss57:45

        Mm-hmm.

    18. RPRhonda Patrick57:45

        Right? And that's where you talked about zone 2 training, and that's the kind of what I would call moderate intensity exercise.

    19. TFTim Ferriss57:53

        Yep.

    20. RPRhonda Patrick57:53

        So you're able to sort of the talk test. I like the talk test because heart rate is so dependent on the person's fitness level.

    21. TFTim Ferriss58:01

        Yeah.

    22. RPRhonda Patrick58:01

        But let's just say on average, generally people are... They're not at like 75 or 80% max heart rate. They're kind of below that.

    23. TFTim Ferriss58:08

        Mm-hmm.

    24. RPRhonda Patrick58:08

        On average. Now, some people may actually be above that, but the talk test is great because you can have a conversation. You're breathy. You don't wanna have a conversation, but you can or so. We know that people that are doing that moderate intensity type of training, if they do the standard guidelines of physical activity, which are about two and a half hours a week of moderate intensity physical activity, people that do that for two months, 40% of those people still can't improve their VO2 max.

    25. TFTim Ferriss58:36

        Yeah. Just different gears. [laughs]

    26. RPRhonda Patrick58:39

        Well, unless they actually add in high intensity interval training.

    27. TFTim Ferriss58:42

        Yep.

    28. RPRhonda Patrick58:43

        And that's where I kind of get into this. I think people should be doing vigorous intensity exercise. That's the type of exercise where you're unable to talk, right? So you, you can't have a conversation because you're going harder. Your heart rate is about 80, 85%. You know, it's above 80% max heart rate.

    29. TFTim Ferriss58:59

        Mm-hmm.

    30. RPRhonda Patrick58:59

        That type of exercise has been shown to improve VO2 max, especially if you're doing sort of what's called high intensity interval training. As you know, you've, you've talked about this a lot as well.
13. 1:06:24 – 1:10:40

    How a two-year exercise program reversed heart aging by 20 years in previously sedentary, middle-aged adults.

    1. TFTim Ferriss1:06:24

       Okay, so the heart aging.

    2. RPRhonda Patrick1:06:25

       Right.

    3. TFTim Ferriss1:06:26

       Yeah. [laughs]

    4. RPRhonda Patrick1:06:27

       Well, so... And, you know, this goes into why randomized controlled trials are important, because you can establish more causation, right, from an intervention. And this study was done by Ben Levine out of UT Southwest in Dallas, and it's a really... To me, it's just... It's seminal, groundbreaking study that isn't talked about enough. By the way, he's just a phenomenal cardiovascular exercise physiologist. I mean, he trained with- The biggest giants out there. And what he did was he took... him and his lab took 50-year-olds that were sedentary, so they're middle-aged, 50 years old, sedentary, but otherwise healthy. So you didn't have any other diseases besides being sedentary, which I think is a disease, but they didn't have any other diseases like cardiovascular disease or type 2 diabetes or hypertension, right? So they were otherwise healthy, just not active. And he wanted to see, if he could put these guys on a pretty long two-year training protocol, how would that affect the aging of their heart? So as we age, our hearts typically shrink in size, and they get stiffer, and that affects not only our cardiorespiratory fitness and our ability to exercise, and, you know, I've mentioned our cardiorespiratory fitness goes down with age, but it affects our cardiovascular disease risk as well. And so the reason our hearts get stiffer, by the way, does come down to a lot of glucose.

    5. TFTim Ferriss1:07:49

       Mm.

    6. RPRhonda Patrick1:07:49

       So the more glucose stimulation, more glucose is around in your vascular system, it, through a chemical reaction, forms advanced glycation end products. So this glycation essentially stiffens the collagen that surrounds your myocardium and your pericardium, and so you get, like, this stiffer heart that can't respond to stress well.

    7. TFTim Ferriss1:08:10

       Mm-hmm.

    8. RPRhonda Patrick1:08:10

       You know, so you want your heart to be very plastic and malleable and flexible, right? You don't want it to be stiff.

    9. TFTim Ferriss1:08:17

       Doesn't sound good.

    10. RPRhonda Patrick1:08:18

        Just like you don't want your blood vessels to be stiff. What he wanted to do was see if he could change the structure and the trajectory of these, these aging hearts. And so he put them on a two-year training program, which involved the Norwegian 4x4, by the way, and when you start someone out that's, you know, not physically active and you want them to do the Norwegian 4x4, when you have them doing their interval, their four-minute interval, and this speaks to you as well, or anyone, you don't have to necessarily go as hard as you can the whole four minutes. You just have to be working hard that interval.

    11. TFTim Ferriss1:08:49

        Yeah, you do have to last four minutes, right? So [laughs]

    12. RPRhonda Patrick1:08:52

        You have to last four minutes.

    13. TFTim Ferriss1:08:53

        [laughs]

    14. RPRhonda Patrick1:08:53

        And so some people even start off, they're just briskly walking-

    15. TFTim Ferriss1:08:57

        Mm

    16. RPRhonda Patrick1:08:57

        ... because that's hard for them.

    17. TFTim Ferriss1:08:59

        Yeah.

    18. RPRhonda Patrick1:08:59

        Right?

    19. TFTim Ferriss1:08:59

        Yeah, totally.

    20. RPRhonda Patrick1:09:00

        So it's all tailored to the individual, and so some people get really intimidated where they're like, "Oh, I just... There's no way I could ever do that." Well, actually, these people did do it, and they started out doing the Norwegian 4x4, but they also did a variety of other exercises, including moderate intensity and some more vigorous intensity exercise, as well as some resistance training. And the control group was just this, like, yoga, flexible training sort of stuff that people were doing. By the end of the two years, these people were working out about five hours a week, and at some point, they were doing two Norwegian 4x4s a week, and then they went down to just doing one a week. But, you know, over the course of two years, they did... They were getting a lot of exercise, about five hours a week.

    21. TFTim Ferriss1:09:39

        Mm-hmm.

    22. RPRhonda Patrick1:09:39

        And essentially, at the end of those two years, the structure of their heart, so the stiffness of it and the, you know, shrinking of it, was reversed.

    23. TFTim Ferriss1:09:47

        Right.

    24. RPRhonda Patrick1:09:48

        So their hearts grew, and they became more flexible, and it was reversed in such a way that it was 20 years less aging, so their hearts looked more like 30-year-olds-

    25. TFTim Ferriss1:09:59

        Hmm

    26. RPRhonda Patrick1:09:59

        ... than 50-year-olds, which is pretty incredible.

    27. TFTim Ferriss1:10:02

        Yeah, that is amazing.

    28. RPRhonda Patrick1:10:03

        Yeah, it's amazing, and I think it's also like, well, you think 50, it's too late to start exercising. Well, it's not too late.

    29. TFTim Ferriss1:10:08

        Mm-hmm.

    30. RPRhonda Patrick1:10:08

        You can be in your 90s and get benefits. I think that's another really important sort of take-home with that story is that, you know, you can reverse your, your aging of your heart by 20 years if you really put in the effort. Five, five hours a week is about what I do. About five or six hours a week. It's a lot of work.
14. 1:10:40 – 1:14:57

    Lactate isn't the enemy: how vigorous exercise creates a superfuel that protects and grows the brain.

    1. TFTim Ferriss1:10:40

       [laughs] All right. Let's park that particular piece of training for a moment. Do you want to piggyback on that and talk about reversing brain aging with exercise? Is it a different type of exercise, or do you get two birds with one stone?

    2. RPRhonda Patrick1:10:55

       You do get two birds with one stone, and that's why I do like the vigorous intensity exercise because when you're kind of shifting into working out harder, when you're getting that vigorous intensity exercise, you are shifting somewhat to anaerobic metabolism. So you're working so hard that you can't get oxygen to your muscles fast enough to use mitochondria, for, for the mitochondria to then make energy. And so your body goes, "I need energy quick, right now. There's not enough oxygen here," and so you start to use glucose outside of the mitochondria as energy, and that's called glycolysis.

    3. TFTim Ferriss1:11:31

       Mm.

    4. RPRhonda Patrick1:11:32

       And you're not just only doing glycolysis, by the way. I mean, even if you're doing an all-out sprint, you're still somewhat using your mitochondria. It's not like a black or white thing, right? There's sort of gray here. But the reality is, is that when you're not going intense, you are not... mostly you're not doing anaerobic exercise. And so what happens is when you're doing that sort of getting in that anaerobic state, what I mean is, like, you're not using oxygen to make energy, you're just using glucose, you actually make something called lactate as a byproduct, and lactate is what's essential for the brain health.

    5. TFTim Ferriss1:12:02

       Hmm.

    6. RPRhonda Patrick1:12:03

       So there have now been a variety of studies. This was pioneered by Dr. George Brooks at UC Berkeley decades ago. So many studies have now shown this now. It's no longer a hypothesis, but it used to be called the lactate shuttle hypothesis.

    7. TFTim Ferriss1:12:16

       Yeah.

    8. RPRhonda Patrick1:12:16

       Where when you start to do this vigorous intensity exercise, you get your lactate levels higher than baseline. Baseline, you're usually about .9 millimolar or so lactate. You start to go above that and well beyond. You're getting 7, 10 millimolar, 15 millimolar, right? The lactate gets into your bloodstream, and it's used by other tissues. So it goes back into the muscle. It's used for energy. It gets into the brain. It gets into the heart, liver quickly. It happens within 20 minutes. You can do a HIIT workout, see your lactate go up to 15 millimolar, measure it 20 minutes later, and it's back to baseline.

    9. TFTim Ferriss1:12:48

       Mm.

    10. RPRhonda Patrick1:12:48

        I mean, it's quick. It gets consumed. One of the major organs that consumes it is the brain. This has been shown in human studies. Not only is lactate very much like beta-hydroxybutyrate, our favorite ketone that we've been talking about, because it's an energetically favorable source of energy. Lactate is used by neurons to make energy, just like beta-hydroxybutyrate is very similar. It's energetically favorable. All that stuff is happening, same stuff. So you're, you know, using the lactate, glucose is being spared, you're making glutathione. Lactate's also a signaling molecule. So in the brain, it's activating brain-derived neurotrophic factor, which is important for your, you know, growing new neurons in the brain, which has been shown in human studies. So there have been human studies that have done exercise for even just one year and shown that you can increase the growth of the hippocampus by, like, 1% to 2% after that year of training versus losing 1% to 2% of the hippocampus. That usually happens as you get in older age. The lactate is, again, a product of that vigorous intensity exercise. It's increasing norepinephrine in the brain, serotonin. It's a signaling molecule. It's basically your body's... your muscle's way of communicating with the brain, "Hey, I'm really working hard. This is a stressful, you know, time. Let's respond to that stress," right? And so your brain is also working hard during exercise and particularly vigorous intensity exercise. It's stressful on the brain. Anybody that's done it knows that resistance training also increases lactate, and resistance training is very stressful on the brain. And so it's like this response to that stress. Your brain is now being communicated from the muscles by lactate, which is the communicator, and saying, "Hey, make all this good stuff so that we can, like, not die," right?

    11. TFTim Ferriss1:14:28

        [laughs]

    12. RPRhonda Patrick1:14:28

        That's essentially the adaptations that are happening.

    13. TFTim Ferriss1:14:31

        Hmm.

    14. RPRhonda Patrick1:14:31

        That's why I like to also incorporate vigorous intensity exercise into my program because I'm also prone to neurodegenerative disease. I have Parkinson's disease on my dad's side. I have Alzheimer's disease on my mom's side. So I'm very, very tuned in to neurodegenerative disease and wanting to prevent it and do what I can, and I do think that vigorous intensity exercise is part of that equation-

    15. TFTim Ferriss1:14:52

        Mm-hmm

    16. RPRhonda Patrick1:14:53

        ... because I want to get that lactate, which is so beneficial

15. 1:14:57 – 1:23:46

    The optimal sauna protocol (temperature and frequency) for slashing dementia risk by 66%.

    1. RPRhonda Patrick1:14:57

       for brain health.

    2. TFTim Ferriss1:14:58

       So let me ask you about two other things related to brain health since this is on, on the mind. [laughs] Uh, the first is related to saunas, and the second one is vitamin D. So with saunas, I was looking back, and I think this is probably summarized by some LLM, so I, [laughs] I want to be very careful with citing numbers. But I'm looking at a summary, I believe, of the findings of a large Finnish study published in JAMA Internal Medicine 2015 that followed 2,000 middle-aged men for 20 years. That's wild. And it looks like... Please correct me if, if from memory you can correct any of this, but all-cause mortality, 24% lower risk with two to three times per week, this is sauna use, and four to seven times per week was associated with 40% lower risk. And I'll just cut to the one that's of greatest interest to me right now. It says, in a follow-up paper, using the sauna four to seven times per week was associated with a 66% lower risk of dementia and 65% lower risk of Alzheimer's. Now, at face value, if those numbers are roughly accurate, those numbers seem incredible, right? And I guess what I'm wondering is how should we think about those results? Because if out of 100 people, two people were getting dementia and now it's one person, it's less interesting [laughs] than other ways of interpreting the data. How should we think about this, and how do you personally use, if you do, sauna or hot tub or heat stress at this point?

    3. RPRhonda Patrick1:16:38

       Those numbers are accurate, by the way. They're spot on.

    4. TFTim Ferriss1:16:42

       Mm-hmm.

    5. RPRhonda Patrick1:16:43

       And there is a dose dependence there, which kind of strengthens the data, right? So people that are using the sauna more frequently are having a more robust effect. You mentioned 24% lower all-cause mortality and then 40%... If they're doing two to three times a week versus four to seven times a week, they're, they're having a 40% lower all-cause mortality. And the dementia risk is also extremely interesting to me, and this goes back, Tim, to, like, some of the earliest experiments that I did as a sort of budding young biologist at the Salk Institute, where I was working with these little nematode C. elegans worms and injecting human amyloid beta 42 into these worms and essentially injecting it into their muscle so that they become... Basically, the amyloid beta 42 aggregates and forms these aggregates as these worms age, and it happens very rapidly 'cause their life expectancy is only 15 days. [laughs] Within, like, a day or so, they start to become paralyzed, where they can't move their lower half of their muscles, where mus- muscular cells are, and they can only move their nose to feed in this little Petri dish with E. coli bacteria, which is what they eat. I would do these experiments, and then I would overact... Basically, when you do a genetic mu- manipulation, and you can make them overexpress heat shock proteins, which are something that are robustly activated upon heat stress, as the name implies.

    6. TFTim Ferriss1:18:02

       Mm-hmm.

    7. RPRhonda Patrick1:18:02

       And sauna has been shown to activate heat shock proteins. If you're in this 163-degree Fahrenheit sauna for around 30 minutes, you can activate your heat shock proteins by 50% more than baseline. So when I would add, you know, heat shock proteins that would be activated in these worms, it would prevent this from happening. These protein aggregates don't happen, and that's because one of the things that heat shock proteins do is they help repair damaged proteins that are misfolded and prevent them from aggregating. And so you want to have more active heat shock proteins if you're wanting to prevent Alzheimer's disease. Now, there's a lot of animal studies that have shown this as well. For example, you can take a, a mouse and sort of give it Alzheimer's disease in a s- in a similar way, and if they have a lot of active heat shock protein genes, then they're not getting the Alzheimer's disease. It delays it, right? I remember reading this study, and it was like one of the things I was thinking about was, of course, you know, the heat shock proteins are activated upon the sauna use, that you would probably see a lower incidence of Alzheimer's disease and even dementia. There's other things as well. Cardiovascular health is really improved with the sauna, so sauna sort of mimics moderate intensity exercise. And so if you're having improved cardiovascular health, that means more blood flow to the brain, lots of things are happening, right? The one thing I do want to mention, Tim, and this is... This study was... I think it came out in 2020-ish. I don't remember the exact year, but it was not out of Finland. I believe it was a Polish study.

    8. TFTim Ferriss1:19:29

       Mm-hmm.

    9. RPRhonda Patrick1:19:30

       And that study looked at sauna use and dementia risk, and there was very interesting results there. So they sort of looked at people that are using saunas, but they also sort of categorized them based on the amount of heat, so how hot their saunas got.

    10. TFTim Ferriss1:19:46

        Mm-hmm.

    11. RPRhonda Patrick1:19:47

        So in the Finnish studies and out of Finland, majority of the people are using the sauna at around equivalent of 174 degrees Fahrenheit.

    12. TFTim Ferriss1:19:55

        Mm-hmm.

    13. RPRhonda Patrick1:19:55

        That's about what the average temperature of pretty much any of those studies that you cited. That's about the average temperature that they're using them, and they're in there m- for about 20 minutes.

    14. TFTim Ferriss1:20:04

        Mm-hmm.

    15. RPRhonda Patrick1:20:04

        Now, this other study looked at a wide range of different temperatures. That temperature versus, like, the really, really high extreme end, so people that were doing, like, 200 degrees Fahrenheit-

    16. TFTim Ferriss1:20:13

        Mm-hmm

    17. RPRhonda Patrick1:20:13

        ... or more. And this is something that you can see nowadays. Like, there's this sort of, you know, go all in, go hard or go home, right?

    18. TFTim Ferriss1:20:21

        Yeah.

    19. RPRhonda Patrick1:20:21

        And so people think that they need to go in a 200-degree sauna, and if they go in a 200-degree sauna, it's gonna be better than going in a 175-degree Fahrenheit sauna, right?

    20. TFTim Ferriss1:20:29

        Mm-hmm.

    21. RPRhonda Patrick1:20:29

        Apparently not the case. In that study, again, you saw a protective effect of people that use the sauna, and I think it was also dose-dependent, but I can't recall. There was a protective effect, but only if they used saunas that were less than 190 degrees Fahrenheit.

    22. TFTim Ferriss1:20:44

        Huh.

    23. RPRhonda Patrick1:20:44

        People that started going into the 190 degrees to 200 degrees Fahrenheit range actually had an increased risk.

    24. TFTim Ferriss1:20:50

        Oh, no. [laughs]

    25. RPRhonda Patrick1:20:51

        So that was something that I don't know that anyone talks about.

    26. TFTim Ferriss1:20:54

        Yeah.

    27. RPRhonda Patrick1:20:55

        But, you know, I've done really, really hot saunas before. I personally don't like it. I get headaches, actually.

    28. TFTim Ferriss1:21:01

        Yeah.

    29. RPRhonda Patrick1:21:01

        So, you know, your head is in there, and you have to think about that. Your head is getting heated up. And so I don't know that it's necessarily good to go in a 212-degree Fahrenheit sauna-

    30. TFTim Ferriss1:21:10

        Mm-hmm
16. 1:23:46 – 1:25:13

    If you're human, you'll find a use for curcumin.

    1. TFTim Ferriss1:23:46

       Do you still use, if needed, curcumin or Theracurmin or any of these products? I think Meriva or Meriva-

    2. RPRhonda Patrick1:23:57

       Mm-hmm

    3. TFTim Ferriss1:23:57

       ... was one that you mentioned as a formulation in place of NSAIDs like ibuprofen or naproxen. Or is that something that you may have changed your mind on?

    4. RPRhonda Patrick1:24:06

       I actually just did it like a couple days ago when I had a headache, and I didn't know why. That's the thing that I go to still. And I mean, there's some cases where it won't work.

    5. TFTim Ferriss1:24:15

       Mm-hmm.

    6. RPRhonda Patrick1:24:15

       Where it's just like, I don't know, this is like a really bad headache.

    7. TFTim Ferriss1:24:18

       Yeah.

    8. RPRhonda Patrick1:24:19

       I don't usually get headaches, but if I don't sleep well or something, something going on or my cycle, I will get a headache. And I use it. I use four of the Meriva, which is a phytosomal curcumin, which increases the bioavailability of the curcumin.

    9. TFTim Ferriss1:24:32

       Mm-hmm.

    10. RPRhonda Patrick1:24:33

        I use the Thorne brand just because I think the brand is reliable. No affiliation with them. But it works for me.

    11. TFTim Ferriss1:24:39

        Mm-hmm.

    12. RPRhonda Patrick1:24:39

        It really does. So it's, I think, 500 milligrams of curcumin per capsule, I believe. And so I do four.

    13. TFTim Ferriss1:24:49

        Yeah.

    14. RPRhonda Patrick1:24:50

        So I'm getting two grams.

    15. TFTim Ferriss1:24:51

        Cool.

    16. RPRhonda Patrick1:24:52

        But I do still use it.

    17. TFTim Ferriss1:24:53

        Yeah. Just don't take it right after your workout, right? [laughs]

    18. RPRhonda Patrick1:24:56

        Yeah. It doesn't have the same effect.

    19. TFTim Ferriss1:24:58

        Yeah, it doesn't have the same kind of COX-2 inhibition as the other guys, right?

    20. RPRhonda Patrick1:25:02

        It doesn't. And in fact, I think it helps with DOMS, delayed onset mus- muscle soreness.

    21. TFTim Ferriss1:25:06

        Oh, I'm sure. Yeah.

    22. RPRhonda Patrick1:25:07

        And so sometimes actually I do use it actually after a really, like-

    23. TFTim Ferriss1:25:10

        [laughs]

    24. RPRhonda Patrick1:25:11

        ... hard squat workout.

    25. TFTim Ferriss1:25:12

        All right.

17. 1:25:13 – 1:37:31

    Creatine for cognition: moving beyond the gym with a powerful, science-backed tool for focus and combating sleep deprivation.

    1. TFTim Ferriss1:25:13

       I'm glad I asked. Speaking of not getting enough sleep, let's hop to creatine. Because I... God, I don't know where I read this, but that higher doses of creatine, maybe like 25 grams, 20, 25 grams could combat sleep loss or some of the effects of sleep loss. What should we know about creatine, right? Creatine's been around for a long time. There are dozens of questionable sports performance, athletic performance products that come out every year. Most of them are all marketing, no substance. Creatine has been used by athletes for a very long time. But for at least the last five years, I have been taking it, typically five grams a day, more for the cognitive or potential cognitive benefits, right? But what el- what else should we know about creatine? Because you, what you put in your newsletter not too long ago was forwarded to me, and [laughs] then you told me via text, and I was like, "Okay, we should probably talk about this."

    2. RPRhonda Patrick1:26:07

       Yes.

    3. TFTim Ferriss1:26:07

       So h- how should we think about creatine and best practices for different applications?

    4. RPRhonda Patrick1:26:12

       Well, it's funny. As you mentioned, it's one of those supplements that have been... It was, like, in the gym bro world forever, and still people associate it with that. But yet it's been one of the supplements that's actually stuck, right? It's worked, and there's been countless studies showing its effectiveness, particularly with respect to increasing exercise volume. So in other words, what creatine is, is it's essentially... It's stored in our muscles as something called phosphocreatine. When you take a creatine exogenously, it's stored in our muscles as phosphocreatine and then used for energy.

    5. TFTim Ferriss1:26:45

       Mm-hmm.

    6. RPRhonda Patrick1:26:45

       And so it's a way to make energy quicker. And so the more of it you have stored, the, the quicker you can sort of make that energy. And so what it's been shown to do is really help with increasing exercise volume. In other words, you can do one to two more reps per set or sets. You know, you can do an extra set or whatever, whatever it is you're doing, right? And that leads to, obviously, if you're increasing your workload, you're gonna have increased muscle mass and muscle strength because you're increasing your workload. It doesn't work like protein in the sense that you can increase muscle mass because it's anabolic. You need to put the work in. So creatine by itself isn't gonna make your muscles grow, but it is gonna make you work harder. It's gonna be easier for you to work harder. And so you end up increasing your exercise volume, which then has adaptations on your muscle, right?

    7. TFTim Ferriss1:27:30

       Mm-hmm.

    8. RPRhonda Patrick1:27:30

       And that's why a lot of people like it because, for one, they want their muscles to grow bigger and stronger, and two, some people like to use it during competitions or something because they want to be able to increase that exercise volume as well. It's also really good for that explosive power type of exercise, again, because you're getting that quick mobilization of producing energy.

    9. TFTim Ferriss1:27:49

       Mm-hmm.

    10. RPRhonda Patrick1:27:49

        And I'm just glossing over decades of research-

    11. TFTim Ferriss1:27:52

        [laughs]

    12. RPRhonda Patrick1:27:52

        ... and a lot of specifics here because I want to get to the brain.

    13. TFTim Ferriss1:27:55

        Yeah.

    14. RPRhonda Patrick1:27:55

        But it turns out creatine is something that our liver makes a little bit, I think like one, maybe one to two grams a day. It's also something that's found in dietary sources, particularly animal products. So it's high in, like, meat, poultry, fish, dairy, not so much in vegetables. So vegans and vegetarians actually end up... They can have lower creatine if they're not supplementing with it because they're not eating animal products, right? Well, it turns out that it seems as though if you're, if you're supplementing and eating a high meat diet, you're getting a good amount of creatine. Five grams seems to be about the point at which your muscles get saturated, at least over the course of, like, a month or so.

    15. TFTim Ferriss1:28:35

        Mm-hmm.

    16. RPRhonda Patrick1:28:35

        So if you've been using creatine for a month or two, your muscle stores are saturated, and five grams a day is kind of what's consumed by the muscle on a daily basis to kind of maintain that. So I would argue that you might want to go above that to get the brain benefits, and here's why. Because your muscles are very, very greedy when it comes to creatine. So that five grams that you're taking, I used to take five grams a day until about last April or March or something like that. So the five grams a day is what's been shown in countless studies, and that's probably why you take it. I took it-

    17. TFTim Ferriss1:29:08

        Right

    18. RPRhonda Patrick1:29:08

        ... because it was countless studies showing five grams a day was, like, the, the dose. That was the dose that you needed to get the muscle benefits. All these brain benefits now coming out seem to be at higher doses, and you mentioned one that was 25 grams, I mean 20 to 25 grams, which is kind of a crazy study where they did about 21 hours of sleep deprivation, essentially. They were barely sleeping at all. And giving them the 25 grams of creatine, 20 to 25 grams, depending on their weight, seemed to n- not only negate the negative effects of sleep deprivation on their cognition, but it also improved their cognition beyond what their baseline normal cognition is when they were sleeping.

    19. TFTim Ferriss1:29:47

        Yeah.

    20. RPRhonda Patrick1:29:48

        And that's what was really intriguing to me, as well as some of the other studies where older adults are given, you know, 20 grams of creatine and it improved their cognition. We now have the first pilot study in Alzheimer's disease where, again, 20 grams were given to a very small number of people with Alzheimer's disease. It also improved cognition. It turns out that when you start to go above the five grams and you get into more the 10 grams range, then some of that creatine is getting into the brain-

    21. TFTim Ferriss1:30:14

        Right

    22. RPRhonda Patrick1:30:14

        ... versus being all consumed by the muscle, right? I personally use creatine now. I do 10 grams a day every day. And what I have noticed, and this could be totally placebo, but I'll tell you, when I don't do my 10 grams a day, what I have noticed is that the, the afternoon sleepiness kind of slump I get is completely gone if I take my 10 grams a day.

    23. TFTim Ferriss1:30:37

        Hmm.

    24. RPRhonda Patrick1:30:38

        10 grams, I don't get afternoon sleepiness. I miss it, I get it. So it's not like a stored up kind of thing. It's like, no, if I miss it that day, it's noticeable. If I travel and I don't have it, it's noticeable.

    25. TFTim Ferriss1:30:49

        Hmm.

    26. RPRhonda Patrick1:30:49

        I'm hooked on the 10 grams a day. If it's placebo, I don't care. It works, right?

    27. TFTim Ferriss1:30:52

        [laughs]

    28. RPRhonda Patrick1:30:53

        On top of that, what I've also been doing ever since, you know, I... that study came out with the 21 hours of sleep deprivation, I take about 20 grams of creatine when I'm traveling and I have to give a talk or I'm doing a podcast, particularly because oftentimes I'm traveling either to Central Time or to Eastern's time and I'm, you know, giving a talk early in the morning, which is, like, 6:00 AM my time.

    29. TFTim Ferriss1:31:15

        Yeah.

    30. RPRhonda Patrick1:31:15

        I got to be, like, on my game. So I take the 20 grams and, I kid you not, it's like You get this brain boost, but without, like, the caffeine. It's, it's hard to explain
18. 1:37:31 – 1:48:51

    Still vitamin D deficient despite taking supplements? Here's the critical cofactor you're probably missing.

    1. TFTim Ferriss1:37:31

       I want to loop back around just so people aren't like, "Ferriss, you forgot about vitamin D." I wanted to talk about vitamin D. So the vitamin D, I've taken vitamin D forever. Tend to take 5,000 IU a day. I, particularly in the summer, get I would say at least an hour in the sun without skin protection, and I build up to that. I'm not an idiot about it. And yet I am barely... In my labs, I'm always barely squeaking by on vitamin D. And for almost all of my adult friends who get labs, and this is also race agnostic, right? Everybody is deficient or just on the border of being deficient, even if they seem to be taking a lot of supplemental vitamin D and getting a lot of sunshine. And I have to ask myself, what the hell is going on here? In what set of circumstances is it possible that everyone would be so deficient if they seem to be getting a bunch of sunlight, they're taking a bunch of supplemental vitamin D? Can you shed any light on this?

    2. RPRhonda Patrick1:38:38

       I can.

    3. TFTim Ferriss1:38:38

       Or is there a problem with this measurement in the first place, which is why I was talking about like proxies and confounders and stuff earlier with respect to some of the other studies. Yeah, so please, please educate me. [laughs]

    4. RPRhonda Patrick1:38:52

       The way vitamin D is measured... So vitamin D actually gets converted into a steroid hormone.

    5. TFTim Ferriss1:38:56

       Mm-hmm.

    6. RPRhonda Patrick1:38:56

       And this steroid hormone, essentially it's going inside the nucleus of our cells where all of our DNA is and it's activating 5% of the protein encoding human genome. Many of these genes... It activates klotho, by the way. You mentioned klotho.

    7. TFTim Ferriss1:39:09

       Yeah.

    8. RPRhonda Patrick1:39:09

       Vitamin D is important for activating klotho.

    9. TFTim Ferriss1:39:11

       Nice.

    10. RPRhonda Patrick1:39:11

        Yeah, so very hugely important for dementia risk, which we can, we can talk about. But to sort of answer your question, so your vitamin D levels are measured by a proxy, and it's called 25 hydroxyvitamin D, which is the precursor to the steroid hormone.

    11. TFTim Ferriss1:39:26

        Mm-hmm.

    12. RPRhonda Patrick1:39:26

        So essentially vitamin D3, which is made in your skin, or if you supplement with it exogenously, gets into your bloodstream. And that vitamin D3 then goes to the liver and it's converted into 25 hydroxyvitamin D. That's the major circulating form of vitamin D.

    13. TFTim Ferriss1:39:43

        Mm-hmm.

    14. RPRhonda Patrick1:39:44

        After it's, you know, 25 hydroxyvitamin D is made in the liver, it then goes to the kidneys and it's made into the actual active steroid hormone, which is called 1,25-hydroxyvitamin D. Well, it turns out the enzymes that are doing the conversion of vitamin D3 into that stable form that everyone gets, you know, when they're getting a vitamin D blood test, that's what they're looking at, requires magnesium to work.

    15. TFTim Ferriss1:40:06

        Mm.

    16. RPRhonda Patrick1:40:06

        And there have been studies showing that in, with low magnesium it doesn't happen readily at all.

    17. TFTim Ferriss1:40:12

        Interesting.

    18. RPRhonda Patrick1:40:13

        50% of the US population has insufficient levels of magnesium, so you're talking about a coin to- toss here, right? One out of two. One out of two, right?

    19. TFTim Ferriss1:40:21

        Mm-hmm.

    20. RPRhonda Patrick1:40:22

        50/50 chance the person's not gonna be getting enough magnesium. That's been shown to actually play a role in circulating levels of vitamin D.

    21. TFTim Ferriss1:40:29

        Mm.

    22. RPRhonda Patrick1:40:29

        So there have been enhanced studies and stuff showing that people that are, that have low magnesium intake also have low circulating forms of 25 hydroxyvitamin D. So that's one thing.

    23. TFTim Ferriss1:40:40

        Mm-hmm.

    24. RPRhonda Patrick1:40:40

        Another thing comes down to genetics. There's actually a lot of people that have SNPs, very common ones, that probably came from more southern latitude areas that don't make as much vitamin D3 from the sun exposure.

    25. TFTim Ferriss1:40:53

        Mm-hmm.

    26. RPRhonda Patrick1:40:54

        Because probably they're getting so much sun, right?

    27. TFTim Ferriss1:40:55

        Yeah.

    28. RPRhonda Patrick1:40:56

        So essentially there's the genetic component as well, and I've seen a lot of people's, you know, different SNP makeups, and I know quite a few people that actually have to take a super high level of vitamin D3 to actually get enough vitamin D. And then the other thing is that you mentioned earlier the variation between supplements. S- there have been studies on vitamin D supplements, and it's the same problem with melatonin. There's some vitamin D supplements with a fraction of what is stated in terms of concentration of vitamin D3 on the nutrition facts.

    29. TFTim Ferriss1:41:28

        Mm-hmm.

    30. RPRhonda Patrick1:41:28

        And then some of them have like 10 times as much vitamin D.
19. 1:48:51 – 1:59:10

    Shocking sources of microplastics in our daily lives, including chewing gum and teabags.

    1. RPRhonda Patrick1:48:51

       Right.

    2. TFTim Ferriss1:48:51

       Where should we zig and zag to next? Do you want to talk about microplastics and mitigation strategies?

    3. RPRhonda Patrick1:49:00

       It's really a big mess, and the microplastics are now... It's not just, okay, well, I'm not gonna drink out of bottled water, plastic bottled water. If you can get any kind of water filter, any kind of water filter is great. Reverse osmosis is the best 'cause it filters out the smallest, smallest nanoplastics, which are the kind that are actually crossing the blood-brain barrier and getting into the brain.

    4. TFTim Ferriss1:49:23

       Mm.

    5. RPRhonda Patrick1:49:23

       In the brain, they're associated with Alzheimer's disease and all ki- kinds of things. But we now know they're in chewing gum. So anything with the word gum base is made of a plastic polymer. So if you chew gum, it has to be plastic-free gum, and it's not the same, I'll tell you that. Like [laughs]

    6. TFTim Ferriss1:49:40

       [laughs]

    7. RPRhonda Patrick1:49:40

       But it's in gum. It's teabags. Teabags, if you make tea with teabags, all sorts of teabags, they are releasing just thousands of microplastic into your beverage.

    8. TFTim Ferriss1:49:50

       Mm.

    9. RPRhonda Patrick1:49:50

       They're in essentially everything, and the problem is, is that it's very hard to avoid. The best things that you can do to avoid them is reduce exposure, which would be the water filter. Try to avoid drinking out of any type of, you know, water that's in a plastic bottle. But it turns out a new study just came out showing it's also been found in glass bottles.

    10. TFTim Ferriss1:50:09

        [laughs]

    11. RPRhonda Patrick1:50:10

        I know. It's like are you kidding me? Come on.

    12. TFTim Ferriss1:50:13

        Yeah.

    13. RPRhonda Patrick1:50:13

        Apparently the paint that's on the lid of the glass bottle is like shedding little particles-

    14. TFTim Ferriss1:50:20

        [laughs]

    15. RPRhonda Patrick1:50:20

        ... into the beverage, and those are microplastics 'cause the paint has got plastic in it. Essentially my take home from this is if you're traveling and you h- and you have to choose between a plastic water bottle with water in it and a glass one to buy, I would still buy the glass one because the particle size is higher, it's larger in the glass bottles.

    16. TFTim Ferriss1:50:42

        Yeah.

    17. RPRhonda Patrick1:50:42

        And that doesn't get absorbed in the gut very well at all, if any.

    18. TFTim Ferriss1:50:45

        Mm-hmm.

    19. RPRhonda Patrick1:50:45

        You actually excrete it through feces. And so I think the next study that's gonna be done will be- show this essentially. I'm sort of speculating here. But because the size matters, the size of plastics in the plastic bottles are super small, and that's really absorbed well by the gut epithelia and taken up into the bloodstream and gets to the other organs. Also, the plastic chemicals like BPA are in plastic, they're not in the glass. So I still think that opting for glass is the best option even though that study came out, oh, glass has more plastic than plastic bottles. It's like a, one of those sensational headlines.

    20. TFTim Ferriss1:51:17

        Yeah.

    21. RPRhonda Patrick1:51:17

        The devil's in the details, right? There's always like nuance there. And in this case-

    22. TFTim Ferriss1:51:22

        In this case, size matters. [laughs]

    23. RPRhonda Patrick1:51:23

        Th- size matters in this case, for sure.

    24. TFTim Ferriss1:51:25

        [laughs]

    25. RPRhonda Patrick1:51:26

        When it comes to, you know, people wanna know, well, is there anything I can do to sort of detox these microplastics, right? That's the big concern that people have. If it's impossible to reduce my exposure because they're just absolutely everywhere, then can I sort of get rid of them? And unfortunately there's not a lot of evidence right now out there that you can. Perhaps some, this electrophoresis sort of thing where you kind of filter your blood.

    26. TFTim Ferriss1:51:49

        Yeah.

    27. RPRhonda Patrick1:51:50

        But like who's doing that? Maybe you'll do it.

    28. TFTim Ferriss1:51:53

        [laughs]

    29. RPRhonda Patrick1:51:53

        That's not something that the public's generally gonna do.

    30. TFTim Ferriss1:51:56

        Yeah.
20. 1:59:10 – 2:12:14

    The uncomfortable truth about "moderate" alcohol consumption, cancer risk, and why the "sick quitter" hypothesis makes most older studies unreliable.

    1. TFTim Ferriss1:59:10

       just to, on the same thread of, you know, you don't always, don't always get it right, [laughs] completely right, I was looking at some of the research doc that I have in front of me, and there's one section that's [laughs] I highlighted, which was each three-hour increase in nighttime fasting was linked to 20% lower odds of elevated hemoglobin A1c. Right? This long-term marker of blood glucose. [laughs] And then one of your bullets was the effects of alcohol on the brain and cancer risk, and so [laughs] I was reading this document over dinner. I sent this to you. And my time zones are all screwed up 'cause I just got back from Polynesia, and so I'm eating at, like, 10:00 PM, first of all, and then I had a glass of wine. So I put the glass of wine on top of my research document with all of this text visible, [laughs] and I sent it to you and I was like, "Am I doing it right?" [laughs]

    2. RPRhonda Patrick1:59:59

       Yeah.

    3. TFTim Ferriss1:59:59

       Because it's like, you know, you're not gonna always get it right. But let's, let's talk... Do you wanna talk about the booze for a second?

    4. RPRhonda Patrick2:00:07

       Alcohol, yeah, and especially since we were talking about APOE4.

    5. TFTim Ferriss2:00:10

       Just to depress people after the microplastics. [laughs]

    6. RPRhonda Patrick2:00:13

       I know. It's like [laughs] you can't have any enjoyment at all if you want to live a long, healthy life.

    7. TFTim Ferriss2:00:19

       [laughs]

    8. RPRhonda Patrick2:00:19

       No, you need to find a good balance, obviously. Alcohol is... it's a toxin. [laughs]

    9. TFTim Ferriss2:00:25

       Yeah.

    10. RPRhonda Patrick2:00:25

        It's also a lot of fun.

    11. TFTim Ferriss2:00:26

        Yeah, yeah.

    12. RPRhonda Patrick2:00:27

        Right? I mean, it's fun to drink and have a glass of wine. Sometimes it helps kind of... it feels like you're lowering your stress, lowering some inhibitions.

    13. TFTim Ferriss2:00:35

        Mm-hmm.

    14. RPRhonda Patrick2:00:36

        It's fun to do with a group of friends and stuff. It's not so great for the brain, though.

    15. TFTim Ferriss2:00:40

        Yeah.

    16. RPRhonda Patrick2:00:40

        And, and certainly if you're concerned about Alzheimer's disease and dementia risk. And I will say that there's been a lot of mixed research out there looking at alcohol consumption and dementia and Alzheimer's disease where some of it says, well, if you're doing moderate alcohol consumption, you can actually have a protective effect against dementia and Alzheimer's disease, right? Where it's like, you know, this, this idea that alcohol, like a glass of wine a day, is actually beneficial for you, so you should be drinking that.

    17. TFTim Ferriss2:01:08

        I wonder if it's actually the social interactions facilitated by alcohol versus the moderate alcohol itself. I wonder.

    18. RPRhonda Patrick2:01:15

        Well, there's a lot of things going on here. Certainly social interactions, that's a confounding factor. Also, when people were then looked for their APOE genotype, it was found that it was actually in the non-APOE4 carriers-

    19. TFTim Ferriss2:01:28

        [laughs] Right

    20. RPRhonda Patrick2:01:28

        ... that you would find that benefit.

    21. TFTim Ferriss2:01:30

        Yeah.

    22. RPRhonda Patrick2:01:30

        Not in the APOE4 carriers.

    23. TFTim Ferriss2:01:31

        [laughs]

    24. RPRhonda Patrick2:01:32

        And then on top of that, there's been all this research that, you know, over the years has looked at moderate alcohol consumption, and depending on the study, that number changes, which is such a big bummer. It's like, well, what does that even mean?

    25. TFTim Ferriss2:01:44

        Mm.

    26. RPRhonda Patrick2:01:44

        In some cases it can be s- you know, seven drinks a day.

    27. TFTim Ferriss2:01:48

        Seven drinks a day?

    28. RPRhonda Patrick2:01:49

        Sorry.

    29. TFTim Ferriss2:01:50

        [laughs]

    30. RPRhonda Patrick2:01:50

        A week.
21. 2:12:14 – 2:19:24

    The ups and downs of ketamine and psilocybin on cognition and longevity.

    1. TFTim Ferriss2:12:14

       But on the ketamine substitute, right? Oh, this is what I'm using now as a healthier alternative. I think the is this risky question is often is this risky or is this bad for me can be answered in absolute terms, but it can also be answered in relative terms. So zero alcohol might be better than two drinks. Seems pretty unequivocally that's the case. But if you then ask in relative terms, as compared to what? If you're swapping in another behavior or smoking after your dinner... I mean, smoking's a whole different kettle of fish that we could unpack some other time. Nicotine's pretty interesting, but lung cancer, less interesting. There is the as compared to what when people find another coping mechanism, right? So I just wanted to throw that out there as just another question that I think is, is worth people asking. If they're going to abandon something, that's great if you can just delete it without replacing it with something. But if there is a substitute, if there is an alternative or something that you may end up adding to your behavior or your consumption, just to be aware of that, because you have to measure A versus B, not just A versus lack of A. Just wanted to throw that out there. I've seen so many people unravel from ketamine that it's... I, I feel a moral responsibility to mention it because it, it can be so, so incredibly addictive. Fast acting, short duration, and even though it is very successfully used to treat, say, treatment-resistant depression, when it's administered in a clinic at r- reasonably higher doses for, let's just say six infusions over two weeks, something like that. John Krystal at Yale's done a lot of great research, and his, his teams and coauthors. Used recreationally, it actually increases your predisposition to depression.

    2. RPRhonda Patrick2:14:10

       I think psilocybin is a better candidate when you, when it comes to something like that, you know?

    3. TFTim Ferriss2:14:14

       Yeah.

    4. RPRhonda Patrick2:14:14

       Because it's really not addicting.

    5. TFTim Ferriss2:14:16

       No.

    6. RPRhonda Patrick2:14:16

       And I don't know if you saw this, Tim, but this really... Of course, people may not be aware, but it's been shown to treat depression as well.

    7. TFTim Ferriss2:14:22

       Oh, for sure.

    8. RPRhonda Patrick2:14:23

       In more than one study.

    9. TFTim Ferriss2:14:24

       Oh, yeah. The two major applications are major depressive disorder and alcohol use disorder. As it stands right now.

    10. RPRhonda Patrick2:14:30

        Right.

    11. TFTim Ferriss2:14:30

        Yeah.

    12. RPRhonda Patrick2:14:31

        This study just came out like, gosh, this l- like last two weeks or something showing, it was an animal study, that psilocybin increased life expectancy by almost 20% in mice.

    13. TFTim Ferriss2:14:43

        Yeah, yeah, I saw that. I think that was out of A- Emory. Am I making that up? I think it was out of Emory.

    14. RPRhonda Patrick2:14:48

        Yeah, I think it was.

    15. TFTim Ferriss2:14:49

        I remember looking at it because I was like, "Wait a fucking second." I think they were giving something like five milligrams of psilocybin to these rats or mice, and I'm gonna mess up the numbers a little bit, but I was like, "Wait a second," 'cause I've funded a lot of the science, and for humans [laughs] who are walking around at 1, let's just call it, whatever, 125 to 200 pounds [laughs] , it's 25 to 30 milligrams. So on a, like mgs per kgs basis, are those rats getting [laughs] like the equivalent of 300 dried grams of mushrooms-

    16. RPRhonda Patrick2:15:28

        [laughs] No

    17. TFTim Ferriss2:15:29

        ... on a monthly basis? I was like, let me look at that a little more closely. And the metabolism is very different.

    18. RPRhonda Patrick2:15:34

        Yeah.

    19. TFTim Ferriss2:15:35

        It's still non-trivial. I do think those little furry friends are probably tripping balls. [laughs]

    20. RPRhonda Patrick2:15:40

        [laughs]

    21. TFTim Ferriss2:15:40

        I do think the life extension stuff is interesting, and I would say just anecdotally, looking at people who have consumed in South America ayahuasca for decades, like they are, can't prove cause and effect, but almost always sharper than the rest of the people in their age cohort. Almost always. Which is interesting. I mean, there raises more questions than it provides answers.

    22. RPRhonda Patrick2:16:01

        Right.

    23. TFTim Ferriss2:16:01

        But the life extension stuff is interesting, and I've been funding some science that Chuck Nichols is doing looking at the anti-inflammatory applications of different psychedelic compounds, and they are profound. Really profound. And what makes it most interesting is that it can be achieved, depending on the compound, and he's tested dozens of them, with very, very trace quantities, in sub-perceptual quantities. You do not need any hallucination, any sort of reality distortion to achieve the anti-inflammatory effects.

    24. RPRhonda Patrick2:16:36

        So like a microdosing.

    25. TFTim Ferriss2:16:38

        Yeah.

    26. RPRhonda Patrick2:16:38

        A microdosing of it.

    27. TFTim Ferriss2:16:40

        Even less than what someone would consider a microdose, like a, a nano dose.

    28. RPRhonda Patrick2:16:45

        Wow.

    29. TFTim Ferriss2:16:45

        It's remarkable. And part of my reason for looking at like the fasting, the ketogenic diet, also looking at cold exposure, and most recently, this is a whole separate topic obviously for another time, I'll be having a, a scientist on this podcast soon, super credible, very, very well-cited, to talk about vagus nerve stimulation. But when you look at how fasting, right, I was talking about this old Soviet work looking at schizophrenia, okay, interesting. Ketosis for epilepsy and also all sorts of psychiatric conditions, but also things like potentially rheumatoid arthritis or any number of Crohn's disease, let's say in the case of like vagus nerve stimulation. My theory also with psychedelics is that in a lot of cases the anti-depressive effects, antidepressant effects, the anxiolytic effects, this would be true for exogenous ketones as well, may be largely, I don't think it's a trivial piece of the puzzle mediated by anti-inflammatory effects addressing chronic inflammation, including neuroinflammation.

    30. RPRhonda Patrick2:17:54

        Totally.
22. 2:19:24 – 2:22:31

    Parting thoughts and where to find more from Rhonda.

    1. TFTim Ferriss2:19:24

       Rhonda. Where can people find you, find what you're up to, get into all things Rhonda Patrick?

    2. RPRhonda Patrick2:19:31

       I have a podcast.

    3. TFTim Ferriss2:19:32

       Mm-hmm.

    4. RPRhonda Patrick2:19:32

       You can find it on Spotify, Apple Podcast, YouTube. It's called Found My Fitness. You can also just search-

    5. TFTim Ferriss2:19:38

       Yeah

    6. RPRhonda Patrick2:19:38

       ... Rhonda Patrick.

    7. TFTim Ferriss2:19:39

       One of the OGs. You've been doing, you've been doing it for a while now.

    8. RPRhonda Patrick2:19:41

       Doing it for a while, yeah.

    9. TFTim Ferriss2:19:42

       Yeah, yeah I am.

    10. RPRhonda Patrick2:19:43

        And I've got a website, foundmyfitness.com. You can find all my stuff there. You can follow me on Twitter or, sorry, X.

    11. TFTim Ferriss2:19:51

        [laughs] I still say Twitter.

    12. RPRhonda Patrick2:19:53

        I still do it.

    13. TFTim Ferriss2:19:54

        [laughs]

    14. RPRhonda Patrick2:19:54

        I still do it. You can follow me on X or Instagram, FoundMyFitness.

    15. TFTim Ferriss2:19:57

        Mm-hmm.

    16. RPRhonda Patrick2:19:58

        All one word, or look, just search my name, Dr. Rhonda Patrick.

    17. TFTim Ferriss2:20:01

        And you have a newsletter.

    18. RPRhonda Patrick2:20:02

        I have a newsletter, yeah. I send out a weekly email that covers some fascinating, you know, new either science, health, fitness, nutrition related study, and usually it's applicable. Sometimes it's something that's misunderstood in the, in the media and I break it down every week. I, I sent you the creatine one.

    19. TFTim Ferriss2:20:22

        Yeah.

    20. RPRhonda Patrick2:20:22

        You know, we covered a vitamin D dementia one as well. I mean, a lot of different fascinating studies. So you can again find that on my website, foundmyfitness.com. You can sign up for the newsletter there.

    21. TFTim Ferriss2:20:33

        Awesome. Yeah, I took so many notes. As always, I always take a lot of notes when we have our conversations, not necessarily on the podcast, but also in our text exchanges. Very actionable. I so appreciate what you do in the world. You've called a lot of things early. Looking at our timelines, it's just been wild to look back and I'm like, "Wow, April 2014," talking about the stuff that now all the fitness influencers are ranting and raving about [chuckles] today in 2025. It's like, yeah, you called, you've called a lot of things early, and I appreciate your ability to simplify without mangling, simplify without disfiguring the science. I really respect that. It's not easy to do. It is such a service to people who care about being scientific lite- literate, but they also care about and benefit from someone who can take what could be impenetrable and translate it without mistranslating it into something that they can test with limited downside and plausible or supported upside. I just think it's, it's such a tremendous service. So I appreciate you, Rhonda. I really do.

    22. RPRhonda Patrick2:21:50

        I appreciate you too, Tim. Thank you for all you do, and your podcasts have been great. I've listened to them over the years. You're one of the few podcasts that I've listened to. You've got great, insightful, thoughtful questions, and I've read your books, so I appreciate all you do, so the feeling's mutual, and I'm glad we get to still have conversations over 10 years later.

    23. TFTim Ferriss2:22:06

        I know. I love it. Yeah. The long game. It's fun to play the long game. So nice to see you, Rhonda. Everyone, we will put links to everything Rhonda Patrick in the show notes. Uh, check her out. You will not be disappointed. And as always, until next time, be just a bit kinder than is necessary to others, but also to yourself. And thank you for tuning in

Episode duration: 2:22:41