#819: Rhonda Patrick, Ph.D. — Protocols for Fasting, Lowering Dementia Risk, Reversing Heart Aging, Using Sauna for Longevity (Hotter is Not Better), and a Few Supplements That Might Actually Matter

Rhonda Patrick, Ph. D. (@foundmyfitness https://x.com/foundmyfitness) is a biomedical scientist and the founder of FoundMyFitness https://www.foundmyfitness.com/, a platform dedicated to delivering rigorous, evidence-based insights on improving healthspan and mitigating age-related diseases. Sponsors: Helix Sleep https://helixsleep.com/tim premium mattresses: https://HelixSleep.com/Tim https://helixsleep.com/tim (27% off all mattress orders) Momentous https://livemomentous.com/tim high-quality creatine and other supplements: https://livemomentous.com/tim (code TIM for up to 35% off) David Protein Bars https://davidprotein.com/pages/tim 28g of protein, 150 calories, and 0g of sugar: https://davidprotein.com/tim (Buy 4 cartons, get the 5th free.) Monarch Money https://www.monarchmoney.com/?s=tim&promoCode=tim&utm_source=arm&utm_medium=podcast&utm_campaign=tim&utm_campaign_id=201847 track, budget, plan, and do more with your money: MonarchMoney.com/Tim https://www.monarchmoney.com/?s=tim&promoCode=tim&utm_source=arm&utm_medium=podcast&utm_campaign=tim&utm_campaign_id=201847 (50% off your first year at monarchmoney.com with code TIM) Timestamps: [00:00:00] Start. [00:04:54] Dealing with aging parents and other topics on the table. [00:10:43] How a common multivitamin helps reverse cognitive and memory aging. [00:12:04] The importance of supplementation — especially as we age. [00:13:10] Effectively supplementing with omega-3 fish oil to counter APOE4 and Alzheimer's risks. [00:16:50] The CoQ10 and omega-3 protocol that has helped Rhonda's father manage Parkinson's symptoms for nearly a decade. [00:19:28] Sulforaphane: a potent NRF2 activator with an unexpected benefit for Rhonda's mother's tremors. [00:25:34] How Rhonda convinced her mom to start CrossFit and the power of community-based, senior-focused fitness. [00:26:52] The earlier the intervention, the better the outcomes. [00:32:25] Intermittent fasting vs. extended fasting and my own results. [00:44:31] Does fasting destroy muscle mass? Debunking the catabolism fear and understanding the crucial role of the re-feeding phase. [00:57:24] "Dirty" fasting: what really happens to autophagy and metabolic benefits when you add a splash of cream or MCT oil to your coffee? [01:00:44] VO2 max: the one metric that may predict lifespan more accurately than anything else, and how we work to improve it. [01:12:07] How a two-year exercise program reversed heart aging by 20 years in previously sedentary, middle-aged adults. [01:16:18] Lactate isn't the enemy: how vigorous exercise creates a superfuel that protects and grows the brain. [01:20:30] The optimal sauna protocol (temperature and frequency) for slashing dementia risk by 66%. [01:29:17] If you're human, you'll find a use for curcumin. [01:30:43] Creatine for cognition: moving beyond the gym with a powerful, science-backed tool for focus and combating sleep deprivation. [01:42:41] Still vitamin D deficient despite taking supplements? Here's the critical cofactor you're probably missing. [01:53:52] Shocking sources of microplastics in our daily lives, including chewing gum and teabags. [02:04:10] The uncomfortable truth about "moderate" alcohol consumption, cancer risk, and why the "sick quitter" hypothesis makes most older studies unreliable. [02:17:03] The ups and downs of ketamine and psilocybin on cognition and longevity. [02:24:19] Parting thoughts and where to find more from Rhonda. * Show notes for this episode: https://tim.blog/2025/07/24/dr-rhonda-patrick/ For show notes and past guests on The Tim Ferriss Show https://tim.blog/podcast, please visit tim.blog/podcast https://tim.blog/podcast/?utm_source=podcast&utm_medium=podcast&utm_campaign=podcast-description. For deals from sponsors of The Tim Ferriss Show https://tim.blog/podcast, please visit tim.blog/podcast-sponsors https://tim.blog/podcast-sponsors Sign up for Tim’s email newsletter (5-Bullet Friday) at tim.blog/friday https://go.tim.blog/5-bullet-friday-1/. For transcripts of episodes, go to tim.blog/transcripts https://tim.blog/transcripts. Discover Tim’s books: tim.blog/books https://tim.blog/books. Follow Tim: Twitter: twitter.com/tferriss https://twitter.com/tferriss Instagram: instagram.com/timferriss https://instagram.com/timferriss/ YouTube: youtube.com/timferriss https://www.youtube.com/timferriss Facebook: facebook.com/timferriss https://www.facebook.com/TimFerriss/ LinkedIn: linkedin.com/in/timferriss http://linkedin.com/in/timferriss See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Tim Ferriss?

  Hello, boys and girls, ladies and germs. This is Tim Ferriss, and welcome to another episode of the Tim Ferriss Show, where it is my job to interview and deconstruct world-class performers, but also sometimes to raid the learnings and toolkits and actionable takeaways from people like scientists who are also implementing what they learn on themselves. My guest today is one such person. I had her on very early in the podcast game, and I've had her on multiple times. Rhonda Patrick, PhD, here to share the latest and greatest. She is a biomedical scientist and the founder of Found My Fitness, a platform dedicated to delivering rigorous, evidence-based insights on improving health span and mitigating

• 0:43Tim Ferriss?

  age-related diseases. She and I text offline a lot about all of this and more through her podcast, website, and YouTube channel, reaching millions globally. She translates complex science into actionable strategies for metabolic health, brain aging, and overall improved health span. She is an associate scientist and board member at the Fatty Acid Research Institute, where her work focuses on the role of omega-3 fatty acids in metabolic health and brain aging. Her peer-reviewed publications have appeared in top-tier journals, including Nature Cell Biology, The Fast Sub Journal, and Experimental Gerontology. You can find all things Rhonda Patrick, PhD, at foundmyfitness.com, and you can find her

• 1:25Tim Ferriss?

  on X and other places at @foundmyfitness. So, just a few words from the folks who make this podcast possible, and then we'll get right into this very wide-ranging and actionable conversation with Rhonda Patrick. Creatine isn't just for muscle, it turns out. It's essential daily fuel for your brain, your body, and long-term performance. For me, I have Alzheimer's and dementia risk in my family. The cognitive benefits are the reason I take creatine every single day. And it also seems there's some evidence to support, if you don't get enough sleep, that you can use creatine to compensate, to recover from that. I also use it for that purpose. And today's episode sponsor, Momentous, is the gold standard in creatine. There's a

• 2:10Tim Ferriss?

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• 2:55Tim Ferriss?

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• 3:21Tim Ferriss?

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• 4:04Tim Ferriss?

  Monarch was named the Wall Street Journal's Best Budgeting App of 2025, and it's the top recommended personal finance app by users and experts with more than 30,000 five-star reviews. So get control of your overall finances, the whole shebang, with Monarch Money. Use code TIM at monarchmoney.com. Just type it into your browser for half off of your first year. That's 50% off of your first year at monarchmoney.com with code TIM.

• 4:31Tim Ferriss?

  At this altitude, I can run flat out for a half mile before my hands start shaking. Can I answer your personal question?

• 4:38Speaker 01

  No, we're just seeing an appropriate time.

• 4:41Speaker 02

  I'm a cybernetic organism, living tissue over metal endoskeleton.

• 4:54Tim Ferriss?

  Rhonda, it is very nice to see you again.

• 4:57Speaker 03

  Likewise.

• 4:57Tim Ferriss?

  Thanks for making the time.

• 4:58Speaker 03

  Yeah, I'm excited to be here.

• 5:00Tim Ferriss?

  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 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 "Our Saunas: The Next Big Performance Enhancing Drug." So, well done. That's become quite the topic.

• 5:35Speaker 03

  I know. I kind of like to take a little bit of that claim to making saunas popular.

• 5:43Tim Ferriss?

  The godmother, the fairy godmother of heat shock proteins, the context of saunas. And we are going to 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. 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 going to 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

• 6:26Tim Ferriss?

  it all, but if you'll bear with me, Rhonda, I'm just going to read some of these because 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 going to get a lot, because this is something... That is 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

• 7:11Tim Ferriss?

  cotton 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 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

• 7:51Tim Ferriss?

  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 or younger, no one's getting younger. So 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

• 8:35Tim Ferriss?

  have seemed to have an effect?

• 8:37Speaker 03

  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 sense that he played a team sport. 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. And neither is really a healthy diet. But 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

• 9:19Speaker 03

  pretty big outcome in terms of, 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. And this is where both of my parents are taking a multivitamin. And you might go, well, multivitamin, really, what's that going to 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

• 10:04Speaker 03

  cases, they can be harmful because they can allow cancer 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 this intervention, which in this case was a multivitamin, to a placebo. Because people taking anything are obviously going to want a positive effect. And many people do anticipate that. And they can actually change their biology. Placebo is a real thing. So three trials came out looking at the effect of multivitamins on cognition. And I'm talking

• 10:49Speaker 03

  the multivitamin that was used was the standard run of the mill, it was Centrum Silver. I mean, it was the thing that-

• 10:55Tim Ferriss?

  Centrum, I knew it was going to be Centrum, yeah.

• 10:56Speaker 03

  It was the vitamin that you would go, that's the one vitamin that's not going to have any effect. 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 luteins, ezanthin, these are actually really important for eye health, but also the brain. And these three randomized controlled 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 a battery of different tests

• 11:38Speaker 03

  that equated to like reducing global cognitive aging by about two years. 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 of reduced episodic memory brain aging. 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. You know, so these are older adults that were otherwise didn't have any sort of neurodegenerative disease. That's also important because

• 12:22Speaker 03

  once you get to a pathological state, you kind of have to do more things to help improve cognition than just a multivitamin. So 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 skin's ability to make vitamin D3 from the sun, from UV 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. So vitamin D supplement is a low hanging fruit.

• 13:07Speaker 03

  It's super easy to bring someone up to level.

• 13:09Tim Ferriss?

  Can I ask you a question about vitamin D? Because 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 Apo E4 and Omega 3 brain delivery. So my family, a lot of benefits to having my genetics, also a whole bunch of bugs in the code, including quite a bit of Apo E4. I'm Apo E34. And should that change how I consume vitamin D or consume fish oil or omega 3s? Having that type of status?

• 13:48Speaker 03

  I would say vitamin D, there hasn't really been any effect that I'm aware of in terms of having an ApoE4 allele, 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. When it comes to fish oil, particularly fish oil, there does seem to be, and this is, you know, 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 as when people without the alleles. And on top of that, in trials, people with

• 14:33Speaker 03

  mild cognitive decline, for example, if they supplemented with fish oil and they had ApoE4, they didn't have the cognitive benefits that the people that were not ApoE4 had. 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, and it's better if it's in phospholipid form. So fish, if you're eating fish, it's in phospholipid form, it's in triglyceride form as well.

• 15:11Tim Ferriss?

  Right. 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?

• 15:18Speaker 03

  You're getting more phospholipid form, exactly. Now, if you are taking your supplement oils, you can actually make phospholipid form, but you have to get to that like two gram dose range. That's when your, your body is also make converting into phospholipid form. And then the other way around that is actually consuming a phospholipid form of omega-3. 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 because 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. And you might go, why phospholipid form? Well, it turns out the way your brain, you actually get omega-3 into the brain. There's two ways.

• 16:02Speaker 03

  The first way doesn't require phospholipid form. It's just this omega-3 is 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. And that's why it seems as though people with ApoE4, their free fatty acid form isn't going into the brain as well because they have breakdown of the blood-brain barrier early, early on. ApoE4 tends to lead to early breakdown of the blood-brain barrier. And when your blood-brain barrier breaks down, it's hard for things to kind of just passively diffuse as well. I know that is counterintuitive, but without getting into all the crazy molecular and biochemistry involved, just take my word on that for the two different forms of omega-3.

• 16:48Speaker 03

  Or you can read that publication as well.

• 16:50Tim Ferriss?

  Okay. Let's step back for a second and just get 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 because like you said, it's sort of a low hanging fruit in a sense from a behavioral change perspective. What do you have them doing?

• 17:18Speaker 03

  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 several years ago. And I had mentioned that my dad was diagnosed with Parkinson's disease.

• 17:27Tim Ferriss?

  In that podcast, yep.

• 17:28Speaker 03

  Yeah. He was diagnosed with Parkinson's disease in 2017 and that's in important context to consider like what sort of supplements I'm giving my dad and also the fact that you have to think about compliance, like what were your parents? Do you have a parent that'll take a lot of vitamins?

• 17:43Tim Ferriss?

  Actually do.

• 17:44Speaker 03

  Or a few vitamins, right? 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, particularly as it relates to Parkinson's disease as well as Alzheimer's disease. 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. Now, coenzyme Q10 is actually something that we have inside

• 18:27Speaker 03

  of our cells and it's involved in mitochondrial health. So having a depleted CoQ10 can lead to mitochondrial toxicity. 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 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, almost 10 years, and he's really essentially had this Parkinson's disease limited to one tremor in his hand. So that's great. All I

• 19:10Speaker 03

  can say is, yeah, 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. 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.

• 19:28Tim Ferriss?

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

• 19:31Speaker 03

  I would also give him sulforaphane. Definitely tried. He doesn't want to take more pills. So sulforaphane is a compound that is formed when you eat cruciferous vegetables like broccoli, cauliflower, for example. 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. That's a technical thing. So I'm just going to talk about sulforaphane and call it sulforaphane as if it's part of, you know, the plant, but it's not, just so you know. So sulforaphane is, it's something that's formed in these cruciferous vegetables. Broccoli sprouts, the young, young sprout

• 20:15Speaker 03

  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.

• 20:26Tim Ferriss?

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

• 20:30Speaker 03

  I'm off the shelf now. I used to, I used to. It's work. It's not that much work, but it is work. But you also like, you have to be very fastidious about not having it contaminated. And that's where the real work comes in. But I like it because there are people that can't afford the supplement. And this gives them another way to basically get it. Yeah, for cheap. 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 N R F two, which is this major system. It's a transcription factor that activates a lot of different genes inside of our body. It activates genes that are involved in stress. Basically, it activates a lot of what are called stress response genes.

• 21:15Speaker 03

  And these are the kind of things that are activated when you're doing stress, stressful things like exercise. Or, you know, if you are fasting. So you really want this pathway to be active.

• 21:26Tim Ferriss?

  Because a little bit of stress, right? It's like chronic overdose of stress, bad. But little doses of stress has this, what would you call it, hormetic effect?

• 21:37Speaker 03

  Exactly.

• 21:38Tim Ferriss?

  Am I getting that right?

• 21:39Speaker 03

  You got, yeah, you nailed it. Yeah. So essentially, we're talking about what's sometimes called eustress or good stress. It's these small doses of stress where your body's responding to that stress by activating all these beneficial pathways that deal with stress. Whether we're talking about antioxidant pathways, anti-inflammatory pathways, pathways involved in clearing out damaged stuff from your cells, like autophagy, just all sorts of beneficial stuff, right? Those pathways are activated for a longer period of time than the acute stress that you're giving it. So in this case, the sulforaphane is a little bit of an acute stress, like polyphenols in general are. So you know, the amount of time that you're ingesting that polyphenol is very small and digesting in. And then the reality is, is that it's activating these stress response pathways that last, you know,

• 22:23Speaker 03

  on the orders of like 24 to 48 hours, sometimes longer. So you're having this beneficial effect that's overall beneficial from that little bit of stress. And so sulforaphane activates N R F two. And one of the main pathways that it's activating is Is increasing glutathione production. And it's been shown in a couple of different human studies that it increases glutathione in both plasma, but also in the brain. Glutathione was the major antioxidant that we have in our body and it's very important in the brain, super important for not only preventing brain aging, but also for dealing with dysfunction in the case of acute injury, like traumatic brain injury, or in the case of Alzheimer's disease or Parkinson's disease, which are other types of injury on the brain. Glutathione plays a big role there.

• 23:08Speaker 03

  And so I obviously would want my dad to be taking sulforaphane. And there's a supplement out there that I use that has been used in many, like 12 or so different studies. And so it's been shown to be beneficial across the board. And that is something that I do give my mom. The reason I gave it to my mom, well, I was kind of hoping, my mom, interestingly, has two other types of sort of brain dysfunction problems, but they're not neurodegenerative in the sense of Alzheimer's disease and Parkinson's disease are. It's kind of like a, something going wrong in the brain and it affects her motor control. So she has tremors. She has essential tremor and she has orthostatic tremor. And I have secretly wanted the increase in glutathione to affect those tremors.

• 23:49Speaker 03

  But when I gave the sulforaphane to my mom, because I knew the placebo effect, I did tell her that we were using it to detoxify, you know, these chemicals that are associated with plastic, like BPA, because that is also something that I'm using sulforaphane for because that NRF2 pathway does activate what are called phase two detoxification enzymes. And it's been shown to detoxify, even if you're living in like a city like New York or LA, where there's a lot of air pollution, it's been shown to detoxify benzene. Within 24 hours, people started excreting 60% more benzene from their body. Now benzene is something that is found in air pollution. It's also in cigarettes.

• 24:27Tim Ferriss?

  Don't drink your own urine if you're taking sulforaphane is what you're saying?

• 24:30Speaker 03

  Definitely don't do that. But also if you're living in a polluted place. I tell all my friends in LA, I'm like, you have to be taking sulforaphane. Like, it's just like, it's a non-negotiable, right? So I told her to take the sulforaphane because I wanted her to detoxify BPA because she does eat a lot of processed foods and stuff which are found in plastic. Anyway, so she started taking it and she came back to me and told me that it was helping her tremors and that she wanted more.

• 24:55Tim Ferriss?

  And I How long did that take?

• 24:58Speaker 03

  Not long. It was actually, I think, within a week or so, maybe two. It was very quick. It was very quick. And she is religious about it. I mean, she comes, I buy it for her. And I give her, you know, these bottles and she takes two a day and she takes a certain brand called Avmacall. I don't have any affiliation with them. They're a brand that, again, 12 different published studies using their supplement.

• 25:22Tim Ferriss?

  A V M A C O L.

• 25:25Speaker 03

  That's right. Yeah. And she takes two of their advanced formula. She's taking that. She's taking the multivitamin, the vitamin D, and she's also taking the omega three. She's doing great. What's funny is that I was able to then get her into CrossFit. And I don't know if it's because her tremors, I think 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

• 26:08Speaker 03

  know, pay for it and get her in it. It would be huge. And she's been doing it now for a couple of months, maybe like three or four months. 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. I mean, it's amazing.

• 26:33Tim Ferriss?

  Go, mom. That's amazing.

• 26:34Speaker 03

  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, it's really great.

• 26:52Tim Ferriss?

  Let me hop in for a second here, and I want to know if there's anything else to add to that, but we've talked about this, you and I have texted a hell of a lot about it, that I have Alzheimer's in my family. I now have multiple relatives who are moderate to advanced with respect to Alzheimer's. So my grandmother disintegrate terrifying to watch and terrifying to imagine yourself experiencing the same thing. And also, at least one of them is APOE 3.3, and I'm APOE 3.4. So I'm like, well, wait a second. If that is where they are right now, and I'm at hypothetically 2.5x greater risk of developing Alzheimer's disease, AD, I should really double down on paying attention to

• 27:37Tim Ferriss?

  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 the, on the omega-3 side of things, just like with sulforaphan, 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 I guess it's 1O.N.E. Pure Encapsulations. Is that what you have your, your parents taking? Or did you use a different brand?

• 28:17Speaker 03

  So with my dad, he is now taking the Zymogen brand, which is also very good. And the reason for that is because it's higher DHA, which is what I wanted. My mom is taking the one. 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.

• 28:38Tim Ferriss?

  Yep. So I've got my parents on those. I'm taking those. You mentioned lutein and zeaxanthin, which 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 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

• 29:13Tim Ferriss?

  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 some extended fasts. I don't think that's going to happen for a million different reasons, but perhaps exogenous ketones and have looked at that. This is kind of a work in progress I've been doing, and I know you have too, 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

• 29:55Tim Ferriss?

  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 $150 or something like that, maybe even more. So there's a sort of a cost question. But I'm just going to 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'll say they're going to do something to please me, and then they won't do it.

• 30:38Tim Ferriss?

  So getting the trainer to actually pick them up at their house is something that I decided to do because there are a lot of reasons. Exercise is amazing, one of which is the natural 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.

• 31:07Tim Ferriss?

  Just a quick thanks to one of our sponsors and we'll be right back to the show. I am always on the hunt for protein sources that don't require sacrifices in taste or nutrition. I don't want to eat sawdust. I also don't want a candy bar that's disguised as a protein bar. And that's why I love the protein bars from today's sponsor, David. They are my go-to protein source on the run. I throw them in my bag whenever I am in doubt that I might be able to get a good source of protein. David has 28 grams of protein, 150 calories, and zero grams of sugar. And on top of that, David tastes great. Their bars come in six delicious flavors. They are all we're trying. Adequate protein intake is critical for building and preserving muscle mass, especially as we age. And one of the biggest things that

• 31:52Tim Ferriss?

  you want to pay attention to is counteracting sarcopenia, age-related muscle loss. And for that, you need enough protein. When in doubt, up your protein. And now, you guys, listeners of the Tim Ferriss Show, who buy four boxes get a fifth box for free. You can check it out. You can also buy one box at a time. Try them for yourself at davidprotein.com/tim. Learn all about it. That's davidprotein.com/tim to get a free box with a four-box purchase or simply learn more. Check it out. davidprotein.com/tim.

• 32:25Tim Ferriss?

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

• 32:34Speaker 03

  There's commentary, but we can get into that if you want to go dive into the why the keto nesters are beneficial and why the exercise is beneficial. We can go into that because I'm, I love talking about it.

• 32:45Tim Ferriss?

  Yeah, so this is going to be a conversation, right? Just between you and me. That's how I treat all of these things. And I'm very self-interested because I think the personal's 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. 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 have noticed...

• 33:31Tim Ferriss?

  Is, for instance, doing 16-8 fasting, which was, I'm so sorry, the scientist you mentioned before, whose podcast interview I listened to on your podcast, what was his name again?

• 33:40Speaker 03

  Dr. Mark Mattson.

• 33:41Tim Ferriss?

  Yeah, Mark Mattson, amazing, amazing scientist, fantastic conversation, 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 till, 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

• 34:24Tim Ferriss?

  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 metabolic machinery was ready for the task. Very unpleasant, but I have some chronic inflammation, or at least chronic pain in

• 35:06Tim Ferriss?

  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 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

• 35:52Tim Ferriss?

  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. 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 akin to the fast mimicking diet, but they'll do that with people for 30, 60, 90 days. Or am I better off doing shorter water fasts?

• 36:37Tim Ferriss?

  Or maybe even a 14 day water fast? And a lot of the questions came down to, I know this is mouthful, but as you know, I've been thinking about this nonstop. I was up until 2 AM this morning, reading really, really old stuff out of the Soviet Union on psychiatric clinics fasting patients for schizophrenia. 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.

• 37:22Tim Ferriss?

  And that is a huge, huge mouthful. Thank you for coming to my TED Talk. But where is your current thinking when it relates to all of this stuff? And 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 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.

• 38:06Tim Ferriss?

  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?

• 38:18Speaker 03

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

• 38:23Tim Ferriss?

  Yeah, chew on one bit at a time.

• 38:25Speaker 03

  Right, let's chew on one bit at a time and zoom out for a minute and talk about this intermittent fasting concept and why do people want to do intermittent fasting? What are the benefits that they're looking for? Now, you mentioned some metabolic benefits that you had noticed after doing your intermittent fasting. So, there's lots of different types of intermittent fasting. You've talked about, you mentioned the 16/8. So essentially, you're talking about not eating food for a period of time. And that period of time, you know, can either be 16 hours, it can be 24 hours, it can be longer. In which case, it would not be an intermittent fast, it would be more prolonged fast, which you also talked about. But with respect to the intermittent fasting,

• 39:06Speaker 03

  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 want to actually lose weight. And the weight that they want to lose is not necessarily their lean body mass. They actually want to lose their fat mass, right? So they want to 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 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.

• 39:47Speaker 03

  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 eight 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 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. 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

• 40:32Speaker 03

  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, you know, fasting glucose, postprandial glucose, HbA1c, which is a long-term marker of glucose regulation. Their, you know, lipids are more favorable. And then they have improvements in blood pressure, for example. That's another big one that people get with a more of a longer type of intermittent fasting. So they're, they're fasting more like 18 hours and eating their food within like a six-hour window. That's another benefit. Now, you go even further, and I know this is something you're very interested in. So beyond, you know, metabolic benefits and people want to get them, they want to get into what's called ketosis. So they want to have, they want

• 41:14Speaker 03

  to be making ketones, these, you know, things that we're talking about earlier with respect to taking an exogenous ketone ester. Well, you make something naturally when you start to actually burn fat as energy, you start to make something called beta-hydroxybutyrate. But it takes about 12 hours or so. It depends on the person. It depends on how heavy of a carb diet they eat, or how physically active they are. It can be a range, right? So if someone's doing a more ketogenic type of diet, they can actually deplete their liver glycogen quicker than 12 hours. It might even cut it down to like eight. If they're physically active on top of that, you might go down to like even six or something like. So there's, there's a big range here, right? But for a standard person on like a normal diet, they're going to take around 12 hours before they start to deplete their

• 41:58Speaker 03

  liver glycogen and then start to immobilize fatty acids from their adipose tissue and use that as energy. And when you start to do that, then you start to get into ketosis. Your body starts to then make beta-hydroxybutyrate, the major circulating ketone. Why do people want that in their system? Because it's not just a very energetically favorable source of energy. What I mean by that is that it takes less energy to use beta-hydroxybutyrate to make energy than it does to use glucose, for example. It takes more energy to actually use glucose. So it's more energetically favorable.

• 42:29Tim Ferriss?

  It's a clean fuel. Yeah. Also, BHB, the beta-hydroxybutyrate, as I understand it, I mean, highly anti-inflammatory effects as well, right?

• 42:39Speaker 03

  Exactly. That was the next point I was going to make is that it's called a signaling molecule. So your body knows that it's in this stress mode. Okay, there's no food. It's food scarcity time, right? And this is something that it's evolutionarily tapped into our system, into our DNA, where times of food scarcity, when we're not eating, our body switches into ketosis, beta-hydroxybutyrate's produced, and it signals to these other Genes to basically make more of something beneficial. So it's been shown to reduce inflammation. It depresses something called the inflammasome, which causes inflammation. It's an HDAC inhibitor. So it's a histone deacetyls inhibitor.

• 43:19Speaker 03

  So it's globally affecting gene expression in such a way that it reduces genes that are involved in making oxidative stress. It actually activates brain derived neurotrophic factor. That's the beneficial neurotrophic compound that's made in the brain. That exercise also activates as well. So it's doing all these beneficial things, right? And the other thing that it's doing is it's getting into the brain. It's being used as a very great source of energy. And so you have this sort of, you know, bypass for glucose where the glucose can then be shunted to be used to make glutathione, that very important antioxidant I talked about earlier that sulforaphane activates. Well, it turns out when you give your body ketones or your body's making ketones, your brain actually consumes a lot of that.

• 44:04Speaker 03

  There've been, you know, tracer studies that have looked at that. And what happens is because neurons are now using the beta hydroxybutyrate as energy, glucose is no longer needed. And so that glucose that is there is then used to make NADPH, which is a precursor to make glutathione. And so it's called glucose sparing. You get this glucose sparing effect. And so that's another reason why people are interested in intermittent fasting. And then another main reason, and there's many others, I'm not going to like touch on everything, but the other main reason is it activates repair processes. 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.

• 44:48Speaker 03

  People get so freaked out by the word catabolism.

• 44:51Tim Ferriss?

  Oh, yeah. Last night when I was walking around New York City, we were talking about this, the catabolism.

• 44:58Speaker 03

  And I think even over the last few years, intermittent fasting has kind of gotten a bad rap because people now equate it with, oh, loss of muscle mass, I'm going to be catabolic. Well, in order to be in a repair mode, you actually do need to be in a catabolic sort of mode. 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 signuclein, 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

• 45:40Speaker 03

  role in cardiovascular disease. But it also cleans out even damaged little, what are called organelles. And so mitochondria are organelle. And our organelles get damaged. So you want to 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. Okay. So talking about those sort of outcomes that people are interested in, those different endpoints that people are interested in achieving, I think something that you're specifically interested in is

• 46:23Speaker 03

  the metabolic effects of intermittent fasting, as well as the repair processes, like the autophagy.

• 46:30Tim Ferriss?

  Yeah, for sure. And that's why I was asking, because I don't really, look, I'm as vain as the next person. I like looking less fat if I can. But it's not my main driver. It's mental acuity and hopefully staving off on some level, things like neurodegenerative disease, and even cancer, possibly, 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 nuts by doing that.

• 47:09Speaker 03

  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'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,

• 47:52Speaker 03

  what we don't have a lot of evidence on is like, what's the minimal effect of fasting dose to activate autophagy?

• 47:59Tim Ferriss?

  Yeah, I wish we had this.

• 48:01Speaker 03

  Right. 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. 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, you know, 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. And so it's not that I don't think a 16 hour fast doesn't activate. I believe it does in humans. I believe there's

• 48:44Speaker 03

  some autophagy going on. It's probably not that much. But if you go into that, you know, 48 hour fast, then you're really starting to get more robust activation of autophagy.

• 48:54Tim Ferriss?

  You mentioned sleep, and I've been looking, trying to look at Alzheimer's from every possible

• 49:01Tim Ferriss?

  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 because 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 deep wave sleep specifically, which does what? It helps the cleanup crew, right? To do its work and to actually take out the garbage

• 49:44Tim Ferriss?

  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, it might be Dora. I would also look at, and this is something obviously not suitable for most elderly people, but potentially lower dose psilocybin or psilocyn. And there are, there is some actually very interesting, I don't want to call them speculative, hypothetical applications of that to Alzheimer's disease, which you can find on PubMed and like them from a mechanistic perspective, they're, they're super, super interesting. So I just want to double click on the sleep because that is

• 50:27Tim Ferriss?

  such 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.

• 50:52Speaker 03

  Great. I mean, yeah, so true. The slow wave sleep does activate the glymphatic system, which is cleaning out the amyloid beta aggregates as well. And the last thing I kind of want to mention is that 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. There's a lot of things going on. So, 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.

• 51:34Speaker 03

  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, a little bit, not much, but they can gain it too. So I think the key here is that if you're doing an intermittent type of fast, like a 16/8, where you're fasting for 16 hours, that's really not a long, long fast. There's not a lot of concern with losing muscle mass if you're, you know, resistance training. Now, a more prolonged type of fast, you're talking about 14 days, that's a long fast. And definitely, you're going to be losing some muscle mass no matter what. Now, how much you lose depends on how, I guess, if you can resistance train lightly while you're fasting,

• 52:14Speaker 03

  that would be huge because you would be then activating muscle protein synthesis through another, you know, signal, which is not protein, it's mechanical force, right? So that, I think, would be really important for preventing the loss of a lot of muscle mass. But what is interesting is that you do lose lean body mass, a lot of it, when you are doing a prolonged fast like that. And looking at, you know, the old literature and some of the literature that's been done, a lot of water, up to 10 pounds of like water, it's just crazy. You lose that, and your organs shrink. And this is something that's been also shown in animal studies and also by Dr. Walter Longo many years ago. He's shown in animal studies prolonged type of fasting actually causes organs to shrink

• 52:59Speaker 03

  because a lot of the damaged cells, not only is autophagy getting activated and you're cleaning out damage within a cell, but cells that are so damaged that autophagy can't even fix them, they actually undergo death, cell death. And so you end up getting a lot of cells that die. And then what happens is during the refeeding phase, and this is key, the refeeding phase is the growth phase. And this is when you regrow organs. It's when your muscle mass comes back. You can, you know, go back, get your muscle mass gains back. And so having that refeeding phase is really important and getting the right nutrients like protein, for example, is key for that refeeding phase. But you also lose fat during

• 53:41Speaker 03

  that fast and you're losing visceral fat. And you had brought this up last night when we were talking and it was, I like did some reading on it because it was like, oh, it made perfect sense because your organs are shrinking, you're losing a lot of cells in your organs, you're also losing some of the visceral fat that surrounds the organs, right?

• 53:57Tim Ferriss?

  That can get misclassified.

• 53:59Speaker 03

  Exactly. It gets misclassified as lean body mass. And so you look at this lean body mass and all you think about is muscle. Well, it turns out muscle's a small part of that. There's a lot of other stuff that's going into that lean body mass. So yeah, it's a pretty big undertaking, a 14 day fast. But I'll say this, and this kind of like goes into what you mentioned about the fasting mimicking diet and perhaps even adding, you know, cream, we can talk about that as well. I do think, I mean, the fasting mimicking diet, you're not going to get the same amount of autophagy that you would get if you did a five day fast, water fast, because it's just impossible. You're getting some protein, you're getting some amino acids, that's activating mTOR, that shuts down autophagy.

• 54:42Speaker 03

  You're getting energy, ATP, there's a ratio called the ATP to AMP ratio, which you want it to be low to activate something called AMP kinase for autophagy to happen. And so when you're eating, when you're eating heavy cream or eating whatever, fill in the blank, any type of calories, you're changing that ratio and so that AMP kinase is not getting activated as robustly. Now, the amount of inactivation of those pathways, which then will inactivate autophagy, depends on how much you're feeding, right? How many calories that you're eating, how much of that is amino acids?

• 55:14Tim Ferriss?

  Specifically leucine, right? In the case of Longo, like really trying to minimize leucine as an activator of mTOR and so on.

• 55:24Speaker 03

  Yes, exactly. Yeah. So I think for the cream, if you're trying to do 16A, if someone is trying to do 16A on a daily basis, and it's a non-negotiable for having an earlier feeding window because social, just everything compliance-wise isn't going to work, and you have to do it later, which means you have to wake up and still be fasting in the morning, right? Then you either like have to love black coffee, learn to love it, or try maybe MCT powder, MCT oil, because then you're not getting the amino acids in there to activate the mTOR. But you can do like a small, maybe like a tablespoon of it, and so you'll maybe just get a little bit of depression of autophagy, but not much. That would be my recommendation.

• 56:11Tim Ferriss?

  Just a quick thanks to one of our sponsors, and we'll be right back to the show. As many of you know, for the last few years, I've been sleeping on a Midnight Luxe mattress from today's sponsor, Helix Sleep. I also have one in the guest bedroom downstairs, and feedback from friends has always been fantastic. It's something they comment on without any prompting from me whatsoever. I also recently had a chance to test the Helix Sunset Elite in a new guest bedroom, which I sometimes sleep in, and I picked it for its very soft but supportive feel to help with some lower back pain that I've had. The Sunset Elite delivers exceptional comfort while putting the right support in the right spots. It is made with five tailored foam layers, including a base layer with full perimeter zoned lumbar support right where I need it, and middle layers with premium

• 56:55Tim Ferriss?

  foam and micro coils that create a soft contouring feel. Helix offers a 100-night sleep trial, fast free shipping, and a 15-year warranty. So check it all out. And now you can get 27% off anything on their website, so site-wide. So just go to helixsleep.com/tim. One more time, helixsleep.com/tim. With Helix, better sleep starts now.

• 57:24Tim Ferriss?

  I also want to clarify for folks listening, just to really make it specific. When I have had, I just like saying dirty fasting. I didn't realize that was an expression. I just think it's some feels, it feels fun, like a dirty martini. So dirty fasting is kind of 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, 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.

• 58:05Tim Ferriss?

  It's just like liquid fat effectively, but the MCT powder is a good idea. I tell you what, let's, if you're open to it, let's shift gears a little bit. I will just say, I wish somebody, nobody's going to 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, 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 and I might just go to 30, but then the refeeding gets really tricky.

• 58:49Speaker 03

  Yeah, I think people are concerned with gallstones. So when you don't eat for a period of, a long period of time, then you're not stimulating the gallbladder and the gallstone risk increases, which is what I think is the, the big concern with a, with the long, long fasts. But I mean, if you're doing something like that once a year, I don't know if it's that big of a deal.

• 59:12Tim Ferriss?

  Yeah. 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 going to fall over and, uh, 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

• 59:55Tim Ferriss?

  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 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 pretty well teed up for a longer water only fast. Maybe you supplement with electrolytes.

• 1:00:40Tim Ferriss?

  This gets into all sorts of controversial 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 two 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 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

• 1:01:20Tim Ferriss?

  test. Intermittent fasting plus ketosis really helps my zone two. 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? Do you want to start with V2 max?

• 1:01:38Speaker 03

  We can start with VO2 max, maybe, because they're kind of leading to each other. And people might be going, what is VO2 max? It's essentially a cardiorespiratory fitness. It's calculated by VO2 max, which is essentially the maximum 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. So there have now been enough studies that have come out looking at cardiorespiratory fitness 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

• 1:02:22Speaker 03

  from low to low normal, it's associated with a two-year increased life expectancy. And people with a low cardiorespiratory fitness actually have 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 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. 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.

• 1:03:06Speaker 03

  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. And once you get to that cliff, everything becomes a maximal effort. Like 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 and you don't want to be there. So you want to like start from a higher up point so that when you're going down, that cliff is much further away. And that's where the training comes in because you want to sort of, you want to find... A training program that's going to improve that cardio respiratory fitness.

• 1:03:51Speaker 03

  And that's where you talked about zone two training. And that's the kind of what I would call moderate intensity exercise. 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. 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 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 want to 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

• 1:04:33Speaker 03

  of moderate intensity physical activity, people that do that for two months. Forty percent of those people still can't improve their VO2 max.

• 1:04:41Tim Ferriss?

  Yeah, yeah, yeah. Just different gears.

• 1:04:45Speaker 03

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

• 1:04:47Tim Ferriss?

  Yep.

• 1:04:48Speaker 03

  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, you're going harder. Your heart rate is about 80, 85%. You know, it's above 80% max heart rate. 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. You're doing sort of these intervals of going more vigorous intensity exercise. And then you have recovery periods where your heart rate goes down. So there's been a variety of different protocols out there that have been shown to improve the VO2 max. If you do them.

• 1:05:29Speaker 03

  Generally speaking, what's happening is you're putting a stronger stress on your cardiovascular system. So on your muscular system, even on your brain. So the adaptations are greater. One of those adaptations is increasing your stroke volume. So being able to like basically transport oxygen to tissues faster. And that's an adaptation that happens when you're going at a harder, when you're training at a harder intensity.

• 1:05:51Tim Ferriss?

  What do you do personally? What's your hit look like?

• 1:05:54Speaker 03

  I do a lot of, so my training is, three days a week, I do some sort of CrossFit training that involves high intensity interval training with it as well. And the high intensity interval training will either be on a rowing machine, or it'll be on a stationary bike, or a salt bike, or it'll be like a skier, like those skiers, or jumping rope. And I also do longer intervals, so I'll do the Norwegian four by four. So that's where I do, on a stationary bike, or do it on the rowing machine actually as well. I do four minutes of as hard as I can go and maintain for that entire four minutes. So this is obviously not an all out 30 second sprint. This is, I'm just working hard, as hard as I can, and maintain that for four minutes.

• 1:06:39Speaker 03

  And then you recover for three minutes, and then you do it four times. I'm thinking of a variation I do sometimes with my husband, I recover for four minutes because we're switching on the rower. So I sometimes do a little bit longer recovery. But that Norwegian four by four, where you're doing as hard as you can for four minutes and maintain that intensity for the four minutes, and then you recover for three minutes, you do that four times. That's been shown to be one of the best ways to improve VO2 max. But you can also do one minute on, one minute off, which I've also done. So, you know, you do that 10 times, it's more like a 20 minute workout. That's also been shown to improve VO2 max. But also even doing something like 20 seconds on, 10 seconds off, like a Tabata. Again, has been shown. I do all of these, by the way. And I do variations of them depending on the week.

• 1:07:23Speaker 03

  Most of my, my exercise is high intensity interval training, CrossFit training, which incorporates, you know, it's more dynamic, so it's including like strength training stuff, but it's like more high intensity. And then I do a couple of runs. I do like, you know, two 30 minute runs a week, sometimes three, and that's more of my zone two stuff.

• 1:07:42Tim Ferriss?

  That's a nice roster. I'll share, just for people who might be curious. Some of my goals and program at the moment. So I'm about to turn 48 and feel good overall, but have realized that I really hate endurance training, generally speaking. So I've neglected that and specifically have neglected the stuff that makes me think I want to puke into a bucket, i.e. VO2 max training. The zone two is like, listen to a podcast. Maybe I have like a slightly breathy conversation. Like, it's pretty chill. Watch something on Netflix. That's pretty straightforward. VO2 max, specifically chatting with Peter Tia, I'm doing the zone two, which I do either on a stationary bike or on a treadmill, typically with a rucksack at a

• 1:08:26Tim Ferriss?

  lower incline. I found that when I had the speed too high, incline too high, I ended up getting lower back pain, just from a like really long stride with my lordosis and stuff. And then for the VO2 max, doing the four by four that you described, and I think I'm getting this translation right, but the way it was described to me was like, all right, for each of those four minutes, you have these four minute work intervals, and then you have three or four minutes of rest, and then you repeat four times. It's like, first minute, you're like, wow, this is a lot of work. Second minute, you're like, wow, this really sucks. Third minute, you're like, I don't know if I'm gonna make it. I don't think I'm gonna make it. And then minute four is like, I feel

• 1:09:08Tim Ferriss?

  like I'm going to die and I'm being chased by wolves. And so it's like, when we say like maximal effort, at least as it's been, and those are not Peter's words, but another words that I like a lot. It's a lot of work. Like, it's pretty pukey, but I'm gonna be doing that, given the longevity associations that you mentioned. Now, I would love just to get your two cents, and this relates to vitamin D2, a little bit for me, where I'm like, in these studies, looking at VO2 max as a predictor or correlate of longevity.

• 1:09:40Tim Ferriss?

  Are there other possible confounding variables that might actually be the real McCoy? Because you could say, and I know you know all this, but just for the, for people listening, it's like, okay, well, I'll make this up. Like, women who do Pilates in Manhattan have, you know, four years of additional lifespan. Okay, great. So you could conclude then, we should all do Pilates to improve lifespan. It's like, well, wait a second. Pilates is expensive. And maybe they're also following a better diet and so on and so on and so on. So are there any confounders that might apply, possible confounders to these VO2 max studies? I'm assuming they're observational more than intervention based. So what are your thoughts there?

• 1:10:25Speaker 03

  Yeah, I mean, there's absolutely a possibility for some sort of confounding factors in any sort of observational study, including the ones I'm discussing. Because, you know, yes, they're going in and measuring their cardio respiratory fitness, which is better than a lot of observational studies that are, you're going off a questionnaire, right? That's already sort of one, at least a one up over other observational data. But, you know, at the end of the day, you may have someone that has undiagnosed cancer or some kind of undiagnosed disease, because diseases are, I mean, they're supposed to be disease free, or if they have a disease, it's like known, right? And so everything's corrected for. But there's always the possibility that, you know, some people have some disease and that's why they can't exercise very well, because they're diseased, right?

• 1:11:08Speaker 03

  And it's the disease that's causing them to have a higher mortality rate than the, the lower cardio respiratory fitness is. There are, you know, studies always try to account for diet and all that stuff, but at the end of the day, you can never really establish causation, right? So that is why we turn to randomized controlled trials. And I will say, this is where the heart aging comes in and also this type of training.

• 1:11:30Tim Ferriss?

  So when I've done VO2 max training, my legs grow. My legs grow like weeds, like they adapt and get big. And so along with the age-related decrease in VO2 max, there's also sarcopenia and age-related loss of muscle mass. And so I'm like, I wonder if there's, you know, these people who also have higher VO2 max tend to have a higher percentage of lean body mass or muscle tissue be more heavily muscled than the people without. I don't know. I mean, that's just, I'm just kind of poking at it out of curiosity. Okay. So the heart aging.

• 1:12:09Speaker 03

  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. He's, by the way, he's just a phenomenal cardiovascular exercise physiologist. I mean, he trained with like 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,

• 1:12:53Speaker 03

  right? So they're 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 cardio respiratory fitness and our ability to exercise. And, you know, I mentioned our cardio respiratory fitness goes down with age, but it affects our cardiovascular disease risk as well. The reason our hearts get stiffer, by the way, does come down to a lot of glucose. So the more glucose stimulation, more glucose is around in your vascular system, it through a chemical reaction forms

• 1:13:36Speaker 03

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

• 1:13:55Tim Ferriss?

  Doesn't sound good.

• 1:13:56Speaker 03

  So just like you don't want your blood vessels to be stiff. So what he wanted to do was see if he could change the structure and the trajectory of these aging hearts. And so he put them on a two-year training program, which involved The Norwegian four by four, by the way, and when you start someone out that's, you know, not physically active and you want them to do the Norwegian four by four, 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.

• 1:14:28Tim Ferriss?

  Yeah, you do have to last four minutes, right?

• 1:14:30Speaker 03

  You have to last four minutes. And so some people even start off, they're just briskly walking because that's hard for them.

• 1:14:38Tim Ferriss?

  Yeah, totally.

• 1:14:39Speaker 03

  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 Norwegian four by four, 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 four by fours a week, and then they went down to just doing one a week. But, you know, over the course of two years, they were getting a lot of exercise, about five hours a week. And essentially, at the end of those two years, the structure of their heart, so the stiffness

• 1:15:21Speaker 03

  of it and the, you know, shrinking of it, was reversed. 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 than 50 year olds, which is pretty incredible. 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. I mean, you can be in your 90s and get benefits, you know? So I think that's another really important 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 hours a week is about what I do, about five or six hours a week. It's a lot of work.

• 1:16:02Speaker 03

  I didn't always do that, but I've decided as I started to get into my mid 40s, I'm gonna spend less time podcasting and more time exercising because this is my health.

• 1:16:12Tim Ferriss?

  Foundational for everything else. That's the base of the pyramid. All right, so let's park.

• 1:16:21Tim Ferriss?

  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?

• 1:16:32Speaker 03

  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 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. 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.

• 1:17:16Speaker 03

  It's not like a black or white thing, right? It's there's sort of gray here. But the reality is, is that when you're not going intense, 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. 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, where when you start to do this vigorous intensity exercise, you get your lactate levels higher than baseline.

• 1:17:58Speaker 03

  Baseline, you're usually about 0.9 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, 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. 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.

• 1:18:41Speaker 03

  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 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 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. So the lactate is again a product of that vigorous intensity exercise.

• 1:19:26Speaker 03

  It's increasing norepinephrine in the brain, serotonin. It's a signaling molecule. It's basically your muscles' 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." Your brain is also working hard during exercise, and particularly vigorous intensity exercise. It's stressful in 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." That's essentially the adaptations that are happening. So that's why I like to also incorporate vigorous intensity exercise into my program because I am also prone to neurodegenerative disease.

• 1:20:11Speaker 03

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

• 1:20:29Tim Ferriss?

  So let me ask you about two other things related to brain health, since this is on the mind. Ha ha. But 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 want to be very careful with citing numbers. So I'm looking at a summary, I believe, of the findings of a large Finnish study published in JAM Internal Medicine 2015 that followed 2,000 middle aged men for 20 years. That's wild. And it looks like, please correct me if from memory you can correct any of this, but

• 1:21:11Tim Ferriss?

  all colors 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 this on a 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 than other ways of interpreting the data.

• 1:21:55Tim Ferriss?

  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?

• 1:22:09Speaker 03

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

• 1:22:55Speaker 03

  So that they become, basically the amyloid beta 42 aggregates informs these aggregates as these worms age and it happens very rapidly because their life expectancy is only 15 days. So within like a day or so, they start to become paralyzed where they can't move their lower half where their 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. And so I would do these experiments and then I would overact over, basically when you do a genetic manipulation and you can make them overexpress heat shock proteins, which are something that are robustly activated upon heat stress, as the name implies. And sauna has been shown to activate heat shock proteins.

• 1:23:39Speaker 03

  If you're in the 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 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 mouse and sort of give it Alzheimer's disease 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?

• 1:24:25Speaker 03

  So 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 you, 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. And that study looked at sauna use and dementia risk. There was very interesting results there.

• 1:25:10Speaker 03

  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 sauna has got. So in the Finnish studies and out of Finland, majority of the people are using the sauna at around equivalent of 174 degrees Fahrenheit. 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 for about 20 minutes. 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 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? And so people think that they need to go into 200 degrees sauna.

• 1:25:55Speaker 03

  And if they go into 200 degrees sauna, it's going to be better than going into 175 degree Fahrenheit sauna. Right? Apparently not the case. So in that study, again, you saw 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. People that started going into the 190 degrees to 200 degrees Fahrenheit range actually had an increased risk.

• 1:26:22Tim Ferriss?

  Oh, no.

• 1:26:23Speaker 03

  And so, so that was something that I don't know that anyone talks about. But I've done really, really hot saunas before. I personally don't like it. I get headaches, actually. 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, you know, for your head. Now, I don't want to say that with certainty because there could be all kinds of confounding factors, but it's something to keep in mind. And why do you have to go above 190? 190 is hot as hell. Like, that's good enough. You don't have to go above that.

• 1:26:56Tim Ferriss?

  Yeah, my default setting in my sauna is 194. So it's just kind of like, well, I guess I said it some time ago. So it's just been set at 194. So that's kind of my default. So maybe I want to dial it back.

• 1:27:07Speaker 03

  I think 190 is great. Yeah, 190 is great. And I, so you asked about me and how I use the sauna. Now, I should also mention that hot tubs are good as well. And in fact, the study just came out a few weeks ago showing that hot tubs have comparable effects on blood pressure regulation, all these parameters that are looked at with sauna use as well. And a lot of people ask that question, you know, oh, what about a hot tub or a hot bath? And I think not everyone has access to a sauna, not everyone has access to a hot tub, but a lot of people have access to a hot bath. And I think if you can get a sort of pool thermometer and keep the temperature of your bath 104 degrees Fahrenheit, which is what all the studies use, you have to keep adding hot water. That's fine.

• 1:27:48Tim Ferriss?

  It's pretty hot.

• 1:27:49Speaker 03

  But you want to stay in there.

• 1:27:50Tim Ferriss?

  Yeah, it's hot.

• 1:27:50Speaker 03

  Yeah, it's pretty hot. You stay in there for about 20 minutes and you're going to have comparable effects.

• 1:27:55Tim Ferriss?

  You'll be sweating like you're in a sauna. Don't worry about it. 104.

• 1:27:59Speaker 03

  Exactly. 104 is hot. And I actually do, I both, I do a hot tub and I do sauna. I like to do hot tub at night. It does seem to help with my sleep. But sometimes I'll do the sauna in the day and I'll do it after a workout and it sort of extends my workout. I particularly like doing them after a workout, like in the winter when it's cold and if I work out outside. So that's kind of how I use the sauna. I was doing hot tubs for a while, like every night. I don't do that in the summer because it's just hot. And so I don't like, I actually shift more to doing cold exposure more in the summer, which is kind of funny. Pretty much the only time I do it is in the summer. Such a wuss. I like doing the heat a lot in the winter.

• 1:28:36Tim Ferriss?

  I would be very curious to see if, you know, they measured like sperm motility and morphology for all the males who are doing this. And they're like, good news. You have this incredibly lowered risk of Alzheimer's. Bad news, you're effectively sterile from all the heat on your swimmers.

• 1:28:55Speaker 03

  Good point. You have to, yeah, there's been studies that have shown you do lower motility, for sure, the motility rate's lowered and that those changes are reversed after six weeks of abstaining. So it is reversible. Also, don't use it as a contraception method either, because I know some people that have tried that. It doesn't work. You can still get pregnant.

• 1:29:15Tim Ferriss?

  That's not so smart. Do you still use, if needed, curcumin or theracumin or any of these products? I think Mariva or Mariva 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?

• 1:29:35Speaker 03

  I actually just did it like a couple of days ago when I had a headache and I didn't know why. That's the thing that I go to still. I mean, there's some cases where it won't work, like where it's just like, I don't know, this is like a really bad headache. 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 Mariva, which is a phytosomal curcumin, which increases the bioavailability of the curcumin. I use the Thorn brand just because I think the brand is reliable, no affiliation with them, but it, it works for me. It really does. So it's, I think 500 milligrams of curcumin per capsule, I believe. And so I do four. So I'm getting two grams.

• 1:30:20Tim Ferriss?

  Yeah.

• 1:30:21Speaker 03

  But I do still use it.

• 1:30:22Tim Ferriss?

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

• 1:30:26Speaker 03

  I don't, it doesn't have the same effect.

• 1:30:27Tim Ferriss?

  Yeah. It doesn't have the same kind of COX2 inhibition as the other guys.

• 1:30:30Speaker 03

  It doesn't. Uh huh. And in fact, I think it helps with DOMS to late onset muscle soreness. And so sometimes actually I do use it actually after a really like hard squat workout.

• 1:30:41Tim Ferriss?

  All right. I'm glad I asked. So speaking of not getting enough sleep, let's hop to creatine because 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 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

• 1:31:26Tim Ferriss?

  benefits. But what, what else should we know about creatine? Because what you put in your newsletter not too long ago was forwarded to me and then you told me via text. I was like, okay, we should probably talk about this. So how should we think about creatine and best practices for different applications?

• 1:31:43Speaker 03

  Well, it's funny. As you mentioned, it's one of those supplements that have been, it was like in the Jim Breau world forever and still people associate it with that, but yet it's been.

• 1:31:53Speaker 03

  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 creatine exogenously, it's stored in our muscles as phosphocreatine and then used for energy. It's a way to make energy quicker, right? And so the more of it you have stored, 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 could do an extra set or whatever, whatever it is you're doing, right?

• 1:32:37Speaker 03

  And that leads to, obviously, if you're increasing your workload, you're going to 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 going to make your muscles grow. It's going to make you work harder. It's going to be easier for you to work harder. And so you end up increasing your exercise volume, which then has adaptations on your muscle, right? 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 the explosive power type of exercise, again, because you're getting that quick mobilization of producing energy.

• 1:33:19Speaker 03

  And I'm just glossing over decades of research and a lot of specifics here because I want to get to the brain. But it turns out creatine is something that our liver makes a little bit, I think like 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 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.

• 1:34:04Speaker 03

  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. I would argue that you might want to go above that to get the brain benefits. And here's why, because your muscle is a 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. That's probably why you take it. I took it because it was countless studies showing five grams a day was like 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.

• 1:34:47Speaker 03

  And you mentioned one that was 25 grams, I mean 20 to 25 grams, which is kind of a crazy study where they, you know, 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 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. 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.

• 1:35:31Speaker 03

  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 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 afternoon sleepiness kind of slump I get is completely gone if I take my 10 grams a day. 10 grams, I don't get afternoon sleepiness. I don't, 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. So I'm, I'm hooked on the 10 grams a day.

• 1:36:15Speaker 03

  If it's placebo, I don't care, it works, right? On top of that, what I've also been doing ever since 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 time and I'm, you know, giving a talk early in the morning, which is like 6:00 AM my time, I gotta 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 hard to explain.

• 1:36:52Tim Ferriss?

  Yeah, without the creepy crawly ants on your skin.

• 1:36:54Speaker 03

  Right. Without that like jittery thing.

• 1:36:57Tim Ferriss?

  Jittery caffeine overdose.

• 1:36:58Speaker 03

  And, and even that, sometimes the caffeine isn't enough. Like if you're really jet lagged, you know, it's just, especially if you're going across time zones.

• 1:37:06Tim Ferriss?

  Well, also for me, it's like I'm a caffeine fast metabolizer. If I have a cup of coffee, I'm on fire for 25 minutes and then I'm sleepy. I think some of that is actually a glucose response, but that's a whole separate thing. Like I, using glucometer when I was doing all my ketogenic experiments and so on, I'm like, wow. If I have too much coffee, there is a huge, which is not that surprising, spike in glucose and then a very predictable subsequent drop off. So it doesn't end up being net, net that helpful for me unless I'm doing a 20 minute sprint on something, which is probably never. So the creatine's super interesting to me. Let me ask some very specific, maybe mundane questions, but

• 1:37:45Tim Ferriss?

  I think they're practical, which is when these subjects were taking 20 or 25 grams, was that in one sitting? Was that in multiple divided doses? When you take it, is it in powder form? Is it little sachets that you can take with you on travel days? Is it encapsulated? What does it actually look like?

• 1:38:09Speaker 03

  With respect to all the studies, I don't remember if they were in one sitting. A lot of studies are, if they do like a 20 gram, it will be in one sitting. What I do is different. I do five gram doses. So creatine monohydrate is the form I take. It's the absolute tried and true. It's the gold standard. Yeah. There's a lot of other marketing out there that talks about other types of creatine, but that's really the gold standard. And I had Dr. Darren Kando on my podcast. He's a creatine researcher at the University of Regina in Canada. And like, you know, we talked all about this and he really convinced me creatine monohydrate is the way to go. I asked him about like every type of, you know, creatine under the sun. But the way I take it is in five gram doses. And so I do five grams first thing in the morning and then I'll do my workout.

• 1:38:54Speaker 03

  And then I do another five grams about 11 a.m. And that's my 10 grams that I get. When I'm traveling, I do have these sachets that, again Thorn makes, by the way, no affiliation. I mean, there's like probably a million other, you know, I like Thorn because their creatine is NSF certified and so it's, it's free of contaminants. I really like that. So again, find your own favorite brand, but I like this brand and I like they have sachets, which are five gram sachets. And so I will have my 10 grams for the day. Or again, if I'm traveling for work-related purposes, I will take 15 to 20 grams, depending on how much I need. In that case, I will do two 10 gram doses. For me, I can tolerate that. I don't have any GI problems with it.

• 1:39:34Tim Ferriss?

  Yeah, I was gonna bring that up.

• 1:39:36Speaker 03

  Yeah, some people do. I think doing the five gram doses is like pretty easy on the gut. Most people don't have a big problem with the five grams. It's when they go above that. Right?

• 1:39:47Tim Ferriss?

  So I'll say a few things. The NSF certified is a pretty simple cheat code, just to use as a filtering mechanism for a lot of supplements. And it is shocking how inconsistent supplement contents are. I mean, I've looked at lab reviews of like 20 off-the-shelf melatonin products and it ranges from zero melatonin up to like 20x the label amount. It's just bananas. So, you know, I use Momentous Creatine, but it's passing the same hurdle. And I will say like, good news, you can reduce the likelihood of cognitive deficit from sleep deprivation. Bad news is you could increase the likelihood of disaster pants

• 1:40:29Tim Ferriss?

  if you have 20 grams at one sitting. And I will say, You know, maybe from personal experience, maybe I'm just talking about somebody else. But if you really want to increase likelihood of disaster pants, then you can do like a bunch of caffeine, double espresso or black coffee with MCT powder and then have your creatine around the same time. That would be asking, you're going to want to pack some Pampers in your travel kit if you do that. So yeah, just be aware of the GI stuff. But I'm excited to up my intake because the science that you cited in the study or studies in your newsletter seemed really compelling. And it's also one of those supplements where it's like, okay, look, I assume this is on

• 1:41:14Tim Ferriss?

  the grass list, like the generally recognized as safe, seems very well tolerated over decades and decades of research, assuming you don't have some, who knows, right? Like really outstanding kidney dysfunction or something, maybe. So why not? And it's also relatively inexpensive compared to a lot of things. Let me ask you, just because this has been on my mind, with the sulforaphane, I mangled the pronunciation of it, sulforaphane, do you take that better on an empty stomach, better with food? This has become an issue when I'm doing the intermittent fasting sometimes, right? Especially if there's something like the ARIDS2, which I'm taking for the eye health, which is supposed to be twice a day. And I'm like, oh, it's part of the reason why I've been doing like the quote unquote

• 1:41:58Tim Ferriss?

  dirty fasting with a little bit of fat in the form of that heavy cream in coffee was to try to take supplements earlier in the day that are benefited from some type of fat in terms of absorption. So sulforaphane, does it matter?

• 1:42:17Speaker 03

  I think if you can take it fasted, that's great. Some people find it kind of is hard on their stomach and so they like to take it with food. And that's really the only reason to take it with food is because they get like upset stomach, like it's like, you know, GI problem. So that would be, again, the only really real reason that you'd have to really take it with food.

• 1:42:41Tim Ferriss?

  I want to loop back around just so people aren't like, Ferris, you forgot about vitamin D. I want to talk about vitamin D. So the vitamin D, I've taken vitamin D forever.

• 1:42:51Tim Ferriss?

  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 built 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. 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? Is it, in what set of circumstances is it

• 1:43:32Tim Ferriss?

  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?

• 1:43:42Speaker 03

  I can.

• 1:43:43Tim Ferriss?

  Yeah. 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? Please educate me.

• 1:43:54Speaker 03

  So the way vitamin D is measured, so vitamin D actually gets converted into a steroid hormone. And this steroid hormone, essentially it's going inside the nucleus of our cells where all of our DNA is and is activating 5% of the protein encoding human genome. Many of these genes, it activates clotho, by the way, you mentioned clotho. Vitamin D is important for activating clotho. Yeah. So very hugely important for dementia risk, which 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 hydroxy vitamin D, which is the precursor to the steroid hormone. So essentially vitamin D3, which is made in your skin, or if you supplement with it exogenously, gets into your bloodstream. And that vitamin

• 1:44:37Speaker 03

  D3 then goes to the liver and it's converted into 25 hydroxy vitamin D. That's the major circulating form of vitamin D. After it's, you know, 25 hydroxy vitamin 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 125 hydroxy vitamin 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. And there have been studies showing that with low magnesium, it doesn't happen readily at all. And so 50% of the US population has insufficient levels of magnesium. So you're talking about a coin toss here, right?

• 1:45:22Speaker 03

  One out of two, one out of two, right? You have a 50/50 chance a person's not going to be getting enough magnesium. That's been shown to actually play a role in circulating levels of vitamin D. So there have been N-Haden studies and stuff showing that people that are, that have low magnesium intake also have low circulating forms of 25 hydroxy vitamin D. So that's one thing. Another thing comes down to genetics. There's actually a lot of people that have SNPs, very common ones, that probably came from southern areas that don't make as much vitamin D3 from the sun exposure because probably they're getting so much sun, right? So essentially, there's the genetic component as well. And I've seen a lot of people's different SNP makeups, and I know quite a few people

• 1:46:04Speaker 03

  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. There have been studies on vitamin D supplements, and it's the same problem with melatonin. There are some vitamin D supplements with a fraction of what is stated in terms of concentration of vitamin D3 on the nutrition facts. And then some of them have like 10 times as much vitamin D. So there's just like this huge variation where you're like, it says it has 5,000 IUs, but it only has 500. There's a lot of different factors that could be contributing to that as well. And then there's also like, you know, in terms of like people getting sun exposure. You said you don't wear sunscreen. Some people do.

• 1:46:47Speaker 03

  People that have darker skin pigmentation have melanin, that's a natural sunscreen. There have been studies showing that like, for example, out of the University of Chicago, there was a study that was published a few years back showing African-Americans have to stay in the sun six to 10 times as long as a Caucasian to make the same amount of vitamin D3 from the same amount of sun exposure. Because they have a natural sunscreen, you know, melanin, which is that darker skin pigmentation, and it's a natural, you know, sunscreen. It's also why their skin always looks great as they're aging. You're like, oh, you're 75. Your skin looks like you're 30.

• 1:47:17Tim Ferriss?

  Yeah, I remember, I won't mention him by name, but meeting this African American fellow. And I thought he was like 25 and he was 53 and had like five bigs. And the way we got to that is I was like, oh, you, are you married? And he's like, yeah, five kids. And I was like, wait, what? You have five kids? You don't look Mormon like, wait, what's going on here? And, uh, and lo and behold, so let me, let me dig into some of this real quick. So recommended brands for vitamin D. And how much should someone like me potentially be taking as a starting point? Because I'm also wary of taking too much vitamin D. I don't want to overdose on vitamin D. It seems like there are some risks associated with that. I maybe I'm overstating them, but how do you think about that?

• 1:48:00Tim Ferriss?

  And then in terms of this rate limiting factor that you mentioned magnesium, what type of magnesium, how much? How should I think about both of these?

• 1:48:12Speaker 03

  Okay. So first of all, we need to talk about vitamin D levels and what the optimal levels are. And that's really important for someone to figure out how much they should supplement with. I tend to think anywhere between 40, 60 to 80, like 40 to 80 nanograms per mill. You're, you're in an optimal range. I like 40 to 60. I think that's my sweet spot and that's because there's lots of studies out there showing all cause mortality is lower within that range. So 50 nanograms per mill would be great. I mean, that's a great place to be if you're below, you know, 30, if you're about just 30, you might want to try to get up to 40. So depending on where you are.

• 1:48:47Tim Ferriss?

  Let's just say for argument's sake that I'm at 30. I think I'm probably closer to 40, but let's say, let's say it's 30.

• 1:48:54Speaker 03

  Okay. For someone that's at 30, nanograms per mill is supplementing with 5,000 IUs a day?

• 1:49:02Tim Ferriss?

  Yeah.

• 1:49:02Speaker 03

  Or 4,000?

• 1:49:04Tim Ferriss?

  I was thinking, yeah, five.

• 1:49:06Speaker 03

  5,000 IU's a day and getting an hour of sun in the summer without sunscreen, you probably should be closer to 50 nanograms per mill, I would say, if you're taking-

• 1:49:16Tim Ferriss?

  I'll check my last labs. I just had them pulled two weeks ago, so I'll double check.

• 1:49:21Speaker 03

  Right. So for someone in that case, you might go up to 7,000 IU's and check and see where you're at a month later. Then, or in the 40 to 50 range, then that's your optimal dose to take. And this is an important conversation to have, Tim, because it really is, there's an individual component here and people just want to, at the end of the day, they want to, "What, how much do I take? How much do I take?"

• 1:49:42Tim Ferriss?

  Yeah.

• 1:49:42Speaker 03

  Well, you have to get a vitamin D blood test. This is one of those-

• 1:49:44Tim Ferriss?

  For sure.

• 1:49:45Speaker 03

  This is one of those that you have to really measure because, as you mentioned, there's huge variation there in terms of absorption and then the magnesium issue, right? And that's something, again, so people, there's, there's the RDA for magnesium, right? So for men, it's about 400 milligrams a day. For women, it's about 300 milligrams a day of magnesium intake from diet or supplemental sources. If you're taking a supplement, and also if you're athletic and sweating a lot and using the sauna, those requirements can go up between 10 to 20%, depending on how physically active you are. If you're like the endurance athlete, you're on the 20% higher, you know, range. If you're more just like the average, like, "I'm a committed exerciser," then you might have to go up

• 1:50:27Speaker 03

  10% above that. So typically, the best forms of magnesium to take are the forms of magnesium that are the organic forms. So that would mean it's bound to like a salt, like magnesium citrate, or magnesium malate, or magnesium tarate. Those are more bioavailable than magnesium oxide, for example. There's also magnesium glycinate, which is also a very bioavailable form. It's the form that I take as well. And dose range, you know, you can take 300 milligrams a day and probably not have any GI distress. And so that gets you most of the way there, and then you get the rest from your diet, right? You're eating some leafy greens, you're eating maybe some almonds or something which are really high in, in magnesium.

• 1:51:13Speaker 03

  If you're not getting any greens at all, then you're going to have to go up a little bit more to the 400, 450 milligram range, especially if you're, if you're athletic. And but that if you're taking something like electrolytes, you're getting some magnesium there. So you can figure out how much magnesium is in your electrolyte and that's, that can be counted towards it as well. There's also magnesium threonate, which is the magnesium form that is allegedly able to cross the blood brain barrier better than other forms of magnesium that I mentioned. And I say allegedly because it's animal studies that have shown that. There have been a couple of human studies. Unfortunately, there's a conflict of interest. They were done by the makers of the magnesium 3 and 8 supplement.

• 1:51:58Speaker 03

  So that's always important to keep in mind. But they have shown that magnesium 3 and 8 could improve some cognitive scores if you kind of pulled all the cognitive scores together. And so I think that there's no reason why, if you're interested in cognition and stuff, trying the magnesium 3 and 8, a lot of people like it as well. So that's another form of magnesium. Although I do think you should probably take some magnesium glycinate along with that because you don't want all the magnesium going into your brain. You want some of it going into your liver and activating the, you know, enzymes that are converting vitamin D3 into 25 hydroxy vitamin D, right? So, so that is something to keep in mind. If that form of magnesium indeed is so, you know, is going into the brain more, you want to make sure you're getting some of the other forms to, to cover the other bases of other organs as well.

• 1:52:42Tim Ferriss?

  What brand of vitamin D supplementation and magnesium glycinate do you use? Is that also Thorne or are they other suppliers?

• 1:52:51Speaker 03

  I use Pure Encapsulations for the vitamin D. Some, I have some friends, mutual friends of ours that like the Vesysorb vitamin D3. So people that are not able to increase their vitamin D as well, Vesysorb really increases the bioavailability of a lot of things, including ubiquinol, the CoQ10 I mentioned. There's a, I should have mentioned that I buy my dad, that's the form I get for him because it increases the bioavailability. Also some fish oil, it's been shown to increase the bioavailability. So Vesysorb vitamin D3 can be found at Pure Encapsulations. I don't have an affiliation with them either. They also have a lot of clean, third-party tested products as well. And then I use their magnesium glycinate.

• 1:53:33Speaker 03

  For the magnesium 3 and 8, I use Zimogen. I like the Zimogen magnesium 3 and 8.

• 1:53:39Tim Ferriss?

  Great. All right. Thank you. I will get on the magnesium and I will also check my last labs. I mean, I am very bespoke about this stuff. And to your point, you gotta check your levels, guys. You can't just be shooting in the dark here. It's not a good idea.

• 1:53:52Speaker 03

  Right.

• 1:53:52Tim Ferriss?

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

• 1:54:02Speaker 03

  It's really a big mess and the microplastics are now, it's not just, okay, well, I'm not going to drink out of bottled water, plastic bottled water, or I, you know, if you can get any kind of water filter, any kind of water filter is great. Reverse osmosis is the best because it filters out the smallest, smallest nanoplastics, which are the kind that are actually crossing the blood brain barrier and getting into the brain. In the brain, they're associated with Alzheimer's disease and all 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. It's not the same, I'll tell you that. But it's in gum.

• 1:54:44Speaker 03

  It's tea bags, you know, tea bags, if you make tea with tea bags, all sorts of tea bags. They're releasing like just thousands of microplastic into your beverage. 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. And the reason for that, I know, I know. It's like, are you kidding me? Come on.

• 1:55:19Speaker 03

  Apparently the paint that's on the lid of the glass bottle is like shedding little particles into the beverage. And those are microplastics because the paint is like got plastic in it. And so essentially, my take home from this is if you're traveling 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. And that doesn't get absorbed in the gut very well at all, if any. You actually excrete it through feces. And so I think the next study that's going to 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.

• 1:56:04Speaker 03

  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. 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 one of those sensational headlines. The devil's in the details, right? There's always like nuance there.

• 1:56:26Tim Ferriss?

  Size matters. In this case, size matters.

• 1:56:29Speaker 03

  This size matters in this case, for sure. But, you know, when it comes to, you know, people want to know, well, is there anything I can do to sort of detox these microplastics? Right? Like, that's a big concern that people have. Well, if I can't reduce, 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 of this electroforesis sort of thing where you kind of filter your blood. But like, who's doing that? Like, maybe you'll do it, but like, you know, that's not something that the public's generally going to do. And I don't even know that I'm going to do it.

• 1:57:07Tim Ferriss?

  Yeah, it's also, even if they were going to do it or willing to do it, it's not readily accessible or cost effective for people to use.

• 1:57:18Speaker 03

  Exactly, yeah. So again, your best strategy here is minimizing your exposure to them. And the way to do that, for one, would be obviously a water filter, top of the list. Because the water that's coming through your tap, you know, through your sink, does have microplastics in it, and that's a major, major source of microplastic exposure for many, many people. So if you can get any type of water filter, again, you can even get countertop reverse osmosis water filters. Those are great for filtering out the majority of microplastics.

• 1:57:49Tim Ferriss?

  I wonder if the big Berkey countertop filtration system.

• 1:57:55Tim Ferriss?

  Is effective at filtering out microplastics? I don't know.

• 1:57:58Speaker 03

  It is. It's effective at filtering out microplastics. It's not clear about like the nano nano, like the super, super small sized ones. It might. It might not. I don't know. But it does definitely, the micro sized ones, it does filter out microplastics. So the, the thing with reverse osmosis is it's really filtering out all, like even the nanoplastics as well. Of course, you have to consider like re-adding like certain minerals and trace elements that are found in water back to your water. And some reverse osmosis companies do that. You can have them put on a filter that'll just add it back in after it filters out all the microplastics. But you can also just buy mineral drops and put those in your water, or you can take a mineral supplement that has some of these minerals that are taken out as well.

• 1:58:43Speaker 03

  The other thing I do want to mention is that the plastic associated chemicals are another concern, and that would be like the BPA, BPS. These chemicals are endocrine disruptors. They disrupt hormones. They're also associated with, you know, Alzheimer's disease, or associated with cancer, all sorts of things, right? And those can actually, I think, actually, this is a, a big speculation on my part, just based on animal studies. I think sulforaphane plays a role in detoxing BPA from our system. And that's because of the whole situation where it activates the very same enzymes that do excrete BPA through urine. It does that, and it's been, um, it's been shown in animal studies.

• 1:59:24Speaker 03

  Animal studies that are given sulforaphane and then given a high dose of BPA, it completely blunts the toxicity of the BPA, which is pretty interesting as well. So the other thing to keep in mind is heat. And this, I'll say this, all the to-go cups that you're out there buying when you go to a, your favorite coffee shop, fill in the blank, for the most part, with the exception of the blue bottle coffee, phenomenal. They're great. All these paper cups are lined with plastic. And when you add a hot beverage into the plastic lining, it, it releases like all these microplastics into your beverage, and it releases the chemicals like BPA into them like fifty fold. Blue Bottle Coffee, by the way, they apparently line their cups with sugarcane, polylactic acid, and

• 2:00:06Speaker 03

  And so they don't have any plastic. I remember the other day I went into a blue bottle coffee shop and I was like, I really wanted to get a hot tea. And I was like, you know, do you guys line your cups with plastic? And she's like, no, we line them with sugarcane. I was like, yes. So that's something to keep in mind. You see a lot of people drinking these to go cups everywhere. And you're pouring a hot beverage into it. It's a really, really major source of microplastic exposure because you're accelerating the breakdown of the plastic. Heat accelerates the breakdown of the plastic. And essentially, you're doing that in real time, like in an instant, right?

• 2:00:34Tim Ferriss?

  Right.

• 2:00:35Speaker 03

  Bring your own cup.

• 2:00:36Tim Ferriss?

  The tea bags, right?

• 2:00:37Speaker 03

  And the tea bags. So you have to do loose leaf tea, which is what now I'm like always, it's got to be loose leaf. I'll bring my own little, I'll sometimes open the tea bag out and I have, I bring my own little tea steeper thing with me.

• 2:00:49Tim Ferriss?

  The half globes that, that connect together?

• 2:00:52Speaker 03

  Exactly. Mine are the ones that like, you kind of like squeeze on it and opens up and then closes the clamps back together. But yeah, so I use that because the tea bags, again, you're getting the heat on top of the plastic, you know, polymers that are making up the tea bag and accelerating the breakdown of the plastic. So you're drinking, you know, plastic beverage, right? There's all these health consequences now associated with microplastics. You mentioned the brain. It's been found like 20 times to accumulate 20 times more in the brain than in other organs. And people with Alzheimer's disease have up to 20 times more microplastics in their brain than people that didn't have Alzheimer's disease. And then the same goes for like cardiovascular disease. There's been a study that was published in New England Journal of Medicine about a year ago, showing that people that had

• 2:01:35Speaker 03

  microplastics in their whatever aortic part that they were doing surgery on, those individuals like ended up dying of a heart attack like within the next three years versus ones that didn't have any microplastics. Anyways, all sorts of interesting stuff. We don't know enough about it. But I think enough said, we do know that they're not good and we want to try to avoid them as much as we can and that they are pervasive. They're everywhere, right? It's ubiquitous.

• 2:01:58Tim Ferriss?

  Yeah. And there's some simple things people can do. I mean, this is not necessarily in the same category, but it's, it's like, look, the effects at least seem to be. I don't know if they're well established. Maybe there are animal studies on this, but certainly there's a lot of seemingly compelling evidence pointing to the effects of, say, phthalates on, as endocrine disruptors on male fertility. And it's like, look, if you have shampoo or soap with a really strong fragrance, just stay away from it. I mean, they're like very simple guidelines for some of these things that I think can be very helpful. Yeah, the, the microplastic stuff is kind of terrifying. I did not realize the gum. I knew about the teabags, the water filtration, did not realize the gum. I don't

• 2:02:43Tim Ferriss?

  chew a lot of gum, but one of my relatives who has Alzheimer's has chewed like four packs of gum a day for 10 years. And I was like, oh shit. No wonder if that's a contributor.

• 2:02:56Speaker 03

  Wow, that's crazy. I started chewing gum when I learned about the research showing that xylitol could, you know, inhibit some of the S mutagens bacteria that are involved in cavity formation.

• 2:03:09Tim Ferriss?

  And then a few years later, you're like, god damn it.

• 2:03:11Speaker 03

  Well, I was able to reverse cavities multiple times. And my doctor was like, keep doing it. And I'm like, yes, xylitol. And then I, yeah, I found out like, it was like this year I found this out, Tim. This year, the study came out with the gum. And I was devastated. I mean, I've chewed so much gum, so much gum. And I've, I've let my child chew it. And it's like, all I could think about was how great it was for the teeth. And, and now it's like, oh my God, this has like been a source of microplastics that I had no idea. I did thankfully find an alternative xylitol source of gum that is microplastic free. But yeah.

• 2:03:47Tim Ferriss?

  It's like chewing on bark? Is this, is it like chewing on?

• 2:03:49Speaker 03

  Pretty, it's pretty much bark. It's actually made from bark. No, it's made from like trees, like some kind of sap or something from the bark.

• 2:03:58Tim Ferriss?

  Like resin or something. Yeah.

• 2:03:59Speaker 03

  Yeah.

• 2:03:59Tim Ferriss?

  Sounds delicious.

• 2:04:02Tim Ferriss?

  You can't just do xylitol mints. You have to chew it. I guess you have to get it up.

• 2:04:05Speaker 03

  You can do xylitol mints. Yeah, you can do xylitol mints. I have this as well.

• 2:04:10Tim Ferriss?

  Well, you know, just to on the same thread of, you know, you don't always get it right, completely right. I was looking at some of the research doc that I have in front of me. And there was, there's one section that's 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. And then one of your bullets was the effects of alcohol in the brain and cancer risk. And so I was reading this document over dinner. I sent this to you and my time zones are all screwed up because I just got back from Polynesia. And so I'm eating at like 10pm, first of all. And then I had a glass of wine.

• 2:04:55Tim Ferriss?

  So I put the glass of wine on top of my research document with all of this text visible and I sent it to you. And I was like, am I doing it right?

• 2:05:04Speaker 03

  Yeah.

• 2:05:05Tim Ferriss?

  You know, you're not going to always get it right. But let's, let's talk about, do you want to talk about the booze for a second?

• 2:05:10Speaker 03

  I mean, so alcohol, yeah, especially since we were talking about.

• 2:05:13Tim Ferriss?

  Just to depress people after the microplastics.

• 2:05:17Speaker 03

  I know. It's like, you can't have any enjoyment at all. If you want to live a long, healthy life. No, you need to, you need to find a good balance, obviously. So alcohol is, it's a toxin. It's also a lot of fun, right? I mean, it's fun to, to, to drink and have a glass of wine. Sometimes it helps kind of, it feels like you're lowering your stress, lowering some inhibitions. It's fun to do with a group of friends and stuff. It's not so great for the brain, though. 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 have, you know, if you're

• 2:06:01Speaker 03

  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 idea that alcohol, like a glass of wine a day is actually beneficial for you. So you should be drinking that.

• 2:06:14Tim Ferriss?

  It's actually these social interactions facilitated by alcohol versus the moderate alcohol itself. I wonder.

• 2:06:21Speaker 03

  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, that you would find that benefit, not in the APOE4 carriers. 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? In some cases, it can be, you know, seven drinks a day. In some cases-

• 2:06:55Tim Ferriss?

  Seven drinks a day?

• 2:06:56Speaker 03

  Sorry, a week. Oh, my gosh. No. In some cases, it's seven drinks a day, obviously, a week for a woman, but for a man, it's like 14 drinks a week.

• 2:07:05Tim Ferriss?

  Wonder who authored that study?

• 2:07:07Speaker 03

  Big, yeah, exactly. It's a big difference. But on average, like, moderate alcohol consumption is more like a seven drinks a week. Seven drinks a day would definitely be heavy alcohol consumption. That would be, you know, substance use or alcohol use disorder. Let's cut the substance abuse part out. Alcohol use.

• 2:07:24Tim Ferriss?

  Why can't you say abuse anymore? Why do these things have to keep changing? It's so ridiculous.

• 2:07:28Speaker 03

  And it's hard for me because I'm always tripping on my words.

• 2:07:30Tim Ferriss?

  Sounds better than abuse. I mean, do you know, what are the reasons, why, what are the reasons behind this? Do you know?

• 2:07:37Speaker 03

  I guess it's politically correct.

• 2:07:38Tim Ferriss?

  Because I'm finding all this psychedelic stuff, and it was like abuse for a long time, and then all of a sudden, nope, foreboding, can't say that. Who knows? Anyway.

• 2:07:48Speaker 03

  It's funny. I still, I've read so much of the literature that I still say abuse, because that's what I'm familiar reading. But anyways, back to this, what I was saying, which is seven weeks. Sorry. All right, we're gonna cut this out, Tim. Seven drinks a week.

• 2:08:02Tim Ferriss?

  How many drinks have you had before this podcast, Rhonda?

• 2:08:07Speaker 03

  Well, I did have some ketone ester, or there's a little bit of alcohol that like is involved with that.

• 2:08:11Tim Ferriss?

  Yeah, that's true. Yeah, watch out for the 1-3 butane dial, anyway.

• 2:08:17Speaker 03

  Right. There's something called the sick quitter.

• 2:08:22Speaker 03

  Hypothesis, which is essentially, a lot of these studies were comparing people that are drinking this moderate alcohol consumption with non-consumers, people that abstain from drinking. And it turns out that many, many, many, many studies did not account for this sick quitter aspect, which is essentially

• 2:08:40Tim Ferriss?

  Sick quitter, is that English?

• 2:08:41Speaker 03

  Someone gets sick.

• 2:08:42Tim Ferriss?

  Oh, sick quitter. I got it.

• 2:08:44Speaker 03

  Sick quitter. Quitter, yes. So essentially, what it means is, they get sick, and so they quit drinking alcohol. And then when they're filling out their questionnaire, you know, however many years later, whatever, they are asked, how many drinks do you have a week? And they say, zero, because they quit. The question wasn't asked, were you a former drinker?

• 2:09:07Tim Ferriss?

  Disclose the prior drinking habit.

• 2:09:08Speaker 03

  Yes. Very important. And now, more studies are, when they're doing the questionnaires, are asking that question. But many, many, many years and many, many studies did not ask that question. And so, it's very possible, when you're looking at these, you know, cohorts of people that are comparing moderate alcohol consumption to, you know, no alcohol consumption, they're saying, oh, look, there's a benefit. You have less cardiovascular disease risk, you have less dementia risk if you drink versus not drink. We don't really know if that's because these people were former drinkers and did so much damage already, that that's why they're getting dementia more.

• 2:09:48Tim Ferriss?

  In the non-drinker.

• 2:09:49Speaker 03

  In the supposed non-drinker.

• 2:09:51Tim Ferriss?

  Quote-unquote, non-drinker.

• 2:09:52Speaker 03

  Exactly. Right. Which could have been a former drinker. But I think at the end of the day, when you look at alcohol and cancer, it's just unambiguous, right? Alcohol is now classified as, I think it's a, is it a group one carcinogen? It's known to play a role in causing cancer. There's no gray area here. And there's many, many different cancers that it's associated with. So alcohol does get metabolized into acetaldehyde. That is something that can be a mutagen, it is a mutagen, can cause cancer, right? And so, there's a lot of different cancers that's associated with. Breast cancer, colon cancer, for example. Breast cancer is a big one, because women's lifetime risk of breast cancer is

• 2:10:37Speaker 03

  already high. I mean, a woman has a lifetime risk of One in eight of getting breast cancer. So if you have a room with eight people, one of those women, if you're at a dinner party, you know, and eight women are there, then one of those women will come down and be diagnosed with breast cancer in her lifetime. So when you add alcohol consumption on top of that, if you're talking about moderate alcohol consumption, that risk can go to one in six, which is very significant for a lifetime risk, right? So I do think that alcohol, I mean, obviously, like, some people enjoy it, and I don't know that there's any amount that's actually safe, but if you're really, like, looking for a number, it seems like one or two drinks a week

• 2:11:19Speaker 03

  seems to be the safe spot. I mean, the safest would be zero, zero drinks. But like, if you're really not wanting to have the damage, the light drinking, which is like the one to two drinks a week, that's where you're probably the best off. Talking about a weekend, right? You have a weekend and you're doing like a glass of wine, maybe Friday or Saturday night. That's the safest if you're looking for like some alcohol consumption. If you're going above that, just be aware. There is definitely a risk of increasing dementia, increasing cancer risk. However, there are other lifestyle factors that also play a role here, like being obese and exercise. In fact, there's some of the exercise, some of the alcohol and dementia studies that have shown an increase in dementia incidence with alcohol consumption

• 2:12:02Speaker 03

  were negated by people that were highly physically active. So I do think there's other things to consider. You can't just silo everything, right? I mean, you've got to look at the whole lifestyle.

• 2:12:11Tim Ferriss?

  So air squats before gelato and my tequila shots. Well, let me ask you, what is the purported mechanism, maybe it's known, by which alcohol increases the likelihood that you will experience some of these maladies like cancer, dementia, et cetera? Is it acting as a, acetylaldehyde acting as a mutagen and therefore just fucking up your, like smashing your DNA? So you have these mutations that then proliferate and turn into some type of...

• 2:12:44Tim Ferriss?

  Dangerous cancer, like is there more to the story of mechanism of action?

• 2:12:48Speaker 03

  Yeah, I mean, acetalaldehyde is one aspect of it. It's an important one, but the alcohol itself is causing inflammation. I mean, it's causing gut permeability essentially. It's very hard on the gut. And so what ends up happening is you release inflammatory factors into your bloodstream, like a polysaccharide gets released into the bloodstream. Inflammation gets, you know, activated inflammation is a major, major cause of cancer and also brain aging. So the brain aging aspect is definitely linked to the oxidative stress component and the inflammation component. Damage is happening to neurons. And I think, you know, one of the reasons why people with APOE IV are a little more sensitive to alcohol

• 2:13:29Speaker 03

  is because the repair processes in individuals with APOE IV isn't as robust.

• 2:13:34Tim Ferriss?

  It's compromised already.

• 2:13:36Speaker 03

  It's compromised already. Right? And so they're not able to repair that damage that's being generated from the alcohol, whereas people without the APOE IV somewhat can repair it a little bit better. And then you add the breakdown of the blood brain barrier on top of that. And then you're just getting more inflammation into the brain. And neuroinflammation is a major cause in Alzheimer's disease. I mean, it's really a known factor now. And you're disrupting mitochondria, you're disrupting, just everything you know about to be important for health is sort of affected by alcohol through a variety of mechanisms.

• 2:14:05Tim Ferriss?

  Do you ever drink?

• 2:14:07Speaker 03

  I don't drink very much. I used to drink more, you know, sometimes I go several months without having anything.

• 2:14:12Tim Ferriss?

  I do. So I'm not like, I'm not putting you on the stand here. I don't drink all the time, but I'm just, I'm just giving you a little leeway.

• 2:14:20Speaker 03

  Yeah, I used to drink like at least, you know, a couple of times a week, you know, where I would do like the weekend thing. But I don't drink much anymore. Once in a while, I'll have like a glass of prosecco for a celebration. I do enjoy it, but I definitely try to limit it to certainly once a week. But like I said, these days I have, I'll go like, you know, a couple of months without having anything. And then I'll have a social situation where I like to do it. And the great thing about that is I'm so sensitive to the alcohol that I'm such a lightweight. And it's great because I, I get like one glass of prosecco and I'm like, this is amazing.

• 2:14:57Speaker 03

  I forgot to mention with respect to the dementia risk and alcohol, you asked about mechanisms, the sleep aspect, right?

• 2:15:03Tim Ferriss?

  Oh, for sure. That's a huge one.

• 2:15:05Speaker 03

  Yes, it's a huge one because alcohol does disrupt sleep despite the fact that people-

• 2:15:10Tim Ferriss?

  That's massive.

• 2:15:11Speaker 03

  Massive. People use it because, I know people that use it because it helps them fall asleep easier. So it's definitely something that decreases that sleep latency. People can fall asleep easier, but it completely disrupts. So they have more awakenings in the middle in the night and it disrupts REM sleep. I mean, so there's every reason to definitely not drink and certainly don't drink close to bedtime. You want to kind of be able to get rid of the alcohol before you go to sleep. Going back to your picture, you were doing everything wrong, but-

• 2:15:42Tim Ferriss?

  Oh, that was, yeah, am I doing it right? Yeah, that was very much deliberate. Rhonda, one thing, and I'm so curious if maybe you've heard reports of this. I can ask my audience and figure it out. Wasn't placebo effect because I didn't expect it, but it seems like when in ketosis, like past 1.5 millimolars, even above like 1.2 for me, and I use a precision extra device to track that. I've tried a number of other devices that are remarkably erratic. In any case, I am much more sensitive to alcohol, much, much, much, much, much more sensitive to alcohol, which is great because then I'm a cheap date, right? I could have my one glass of mezcal or whatever and then I'm good. And I don't drink super often. I

• 2:16:25Tim Ferriss?

  might take like three or four weeks off, but then it'll be like this week I'm in New York City. This is a city of drinking. A lot of people have decided to do ketamine instead, which I think is a Faustian bargain shitty trade for a number of reasons. But, and then I'll stop, you know, party with my oldest friends this weekend. I'm sure there's going to be drinking and then I'll stop for two weeks and take a month off or two months off or something like that. It's kind of how I operate these days, but the ketosis seems to sensitize me, which is, I thought was pretty interesting. I hadn't noticed that before when I was in ketosis, probably because I wasn't drinking during those periods. But

• 2:17:03Tim Ferriss?

  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? Or, I mean, smoking is a whole different kettle of fish that we could unpack some other time.

• 2:17:45Tim Ferriss?

  Ketamine's pretty interesting, but lung cancer, less interesting. There is the as compared to what? When people find another coping mechanism? 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 feel a moral responsibility to mention it because it can be so, so incredibly addictive.

• 2:18:30Tim Ferriss?

  Fast acting, short duration, even though it is very successfully used to treat, say, treatment resistant depression when it's administered in a clinic at reasonably higher doses for, let's just say, six infusions over two weeks, something like that. John Cristel, he also has done a lot of great research and his teams and co-authors used recreationally actually increases your predisposition to depression.

• 2:18:56Speaker 03

  I think psilocybin is a better candidate when it comes to something like that, you know, because it's really not addicting. I don't know if you saw this, Tim, but this really, it's, of course, people may not be aware, but it's been shown to treat depression as well in more than one study.

• 2:19:10Tim Ferriss?

  Oh, yeah, yeah, yeah. Yeah, the two major applications are major depressive disorder and alcohol use disorder as it stands right now.

• 2:19:18Speaker 03

  This study just came out, like, gosh, this like last two weeks or something showing is the animal study that psilocybin. Increased life expectancy by almost 20% in mice.

• 2:19:31Tim Ferriss?

  Yeah, I saw that. And that was, I think that was at Emory. Am I making that up? I think it was at Emory.

• 2:19:36Speaker 03

  Yeah, I think it was.

• 2:19:37Tim Ferriss?

  And 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 going to 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 who are walking around at one, let's just call it whatever, 125 to 200 pounds, it's 25 to 30 milligrams. So on a like nigs per kicks basis, are those rats getting like the equivalent of 300 dried grams of mushrooms on a monthly basis? I was like, let me look at that. And let me look at that a little more closely.

• 2:20:21Tim Ferriss?

  And the metabolism is very different, but it's still non-trivial. Like I do think those, uh, those little furry friends are probably tripping balls. Because all of the, like, 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. But the, 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.

• 2:21:05Tim Ferriss?

  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 subperceptual quantities. You do not need any. Hallucination, any reality distortion to achieve the anti-inflammatory effects.

• 2:21:27Speaker 03

  So like a microdosing?

• 2:21:29Tim Ferriss?

  Yeah.

• 2:21:30Speaker 03

  A microdosing of it.

• 2:21:31Tim Ferriss?

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

• 2:22:14Tim Ferriss?

  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 antidepressant effects, the anxiolytic effects, this would be true for exogenous ketones as well, maybe largely, I don't think it's a trivial piece of the puzzle mediated by anti-inflammatory effects, addressing chronic inflammation, including neuroinflammation.

• 2:22:43Speaker 03

  Totally.

• 2:22:44Tim Ferriss?

  And so, as you said, right, if you're, if you're, if you're chronically suffering from neuroinflammation, does not bode well for later life with Alzheimer's and Parkinson's and things like this. So I'm trying to throw everything, the sort of the kitchen sink at this to see what the subjective and then measurable objective effects are. So it's like, okay, if I did intermittent fasting and I'm doing then cold exposure during, which by the way, past a certain point, does seem to shift from sympathetic to parasympathetic activation, particularly with certain breathing patterns. Like, okay, if I did that during the intermittent fast, I'm taking the sulforaphane, right, doing all that stuff. And then the

• 2:23:25Tim Ferriss?

  exercise we talked about. And once a quarter, doing a three to seven, let's call it probably every quarter, I used to do a three day fast. I don't think I'd do a seven day every quarter. That'd probably be once a year. But just looking at like, okay. And then like the curcumin, right? It's like, all right, can we throw? If we threw four or five at this problem and didn't get too crazy go Merica, like more is better, like we did the minimal effective dose, but recognized there might be a synergistic effect, what happens and what can we measure? So I'd like to do, and I'm in the position where I could spend a lot of money just to see like, okay, if we take out my white blood cells and then look at their ability to produce

• 2:24:09Tim Ferriss?

  cytokines after certain interventions, like, okay, cool, like, let's spend the money. Let's see what happens after you do this stuff for a couple of weeks. Very, very, very, very interested in all this. Listen to this Rhonda, where can people find you, find what you're up to, get into all things Rhonda Patrick?

• 2:24:26Speaker 03

  I have a podcast. You can find it on Spotify, Apple Podcasts, YouTube. It's called Found My Fitness. You can also just search Rhonda Patrick.

• 2:24:35Tim Ferriss?

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

• 2:24:37Speaker 03

  Doing it for a while, yeah. And I've got a website, foundmyfitness.com. You can find all my stuff there. You can follow me on Twitter, or sorry, X. And also, I still do it. I still do it. You can follow me on X or Instagram, foundmyfitness, all one word, or look, just search my name, Dr. Rhonda Patrick.

• 2:24:56Tim Ferriss?

  And you have a newsletter?

• 2:24:57Speaker 03

  I have a newsletter, yeah. I send out a weekly email that covers some fascinating 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 sent you the creatine one, 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.

• 2:25:27Tim Ferriss?

  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 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.

• 2:26:12Tim Ferriss?

  It is such a service to people who care about being scientifically 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 such a tremendous service. So I appreciate you, Rhonda. I really do.

• 2:26:41Speaker 03

  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. So you've, 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.

• 2:26:58Tim Ferriss?

  I know, I know. I just, 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. 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.

• 2:27:25Tim Ferriss?

  Hey guys, this is Tim again. Just one more thing before you take off and that is Five Bullet Friday. Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend? Between one and a half and two million people subscribe to my free newsletter, my super short newsletter called Five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every Friday to share the coolest things I've found or discovered or have started exploring over that week. It's kind of like my diary of cool things. It often includes articles I'm reading, books I'm reading, albums perhaps, gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends, including a lot of podcast guests.

• 2:28:08Tim Ferriss?

  And these strange esoteric things end up in my field and then I Test them and then I share them with you. So if that sounds fun, again, it's very short, a little tiny bite of goodness before you head off for the weekend, something to think about. If you'd like to try it out, just go to tim.blog/Friday, type that into your browser, tim.blog/Friday, drop in your email and you'll get the very next one. Thanks for listening. Traditional budgeting apps, they can be interesting. Yeah, they can be helpful. I've tried out a bunch, but they don't compare to the complete financial command center that you get with today's sponsor, Monarch Money. And a number of my friends have recommended them publicly, have recommended it to me.

• 2:28:49Tim Ferriss?

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• 2:29:33Tim Ferriss?

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• 2:29:44Tim Ferriss?

  Creatine isn't just for muscle, it turns out. It's essential daily fuel for your brain, your body, and long-term performance. For me, I have Alzheimer's and dementia risk in my family. The cognitive benefits are the reason I take creatine every single day. And it also seems there's some evidence to support if you don't get enough sleep, that you can use creatine to compensate, to recover from that. I also use it for that purpose. And today's episode sponsor, Momentus, is the gold standard in creatine. There's a lot of BS floating around, a lot of questionable creatine. But I choose them. Why? Because they source Creapure Creatine, the purest, most effective creatine monohydrate available, single sourced from Germany and not cut with fillers or junk, which is hard to avoid otherwise.

• 2:30:29Tim Ferriss?

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• 2:31:14Tim Ferriss?

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