The Tim Ferriss Show - #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

Episode Date: July 23, 2025

Rhonda Patrick, Ph.D. (@foundmyfitness) is a biomedical scientist and the founder of FoundMyFitness, a platform dedicated to delivering rigorous, evidence-based insights on improving healthspan and mitigating age-related diseases.Sponsors:Momentous high-quality creatine and other supplements: https://livemomentous.com/tim (code TIM for up to 35% off)David Protein Bars 28g of protein, 150 calories, and 0g of sugar: https://davidprotein.com/tim (Buy 4 cartons, get the 5th free.)Monarch Money track, budget, plan, and do more with your money: MonarchMoney.com/Tim (50% off your first year at monarchmoney.com with code TIM)Helix Sleep premium mattresses: https://HelixSleep.com/Tim (27% off all mattress orders)Timestamps (more detailed timestamps will be added): 00:00 Intro08:10 Aging Parents 32:59 Fasting 41:05 Ketosis 01:01:29 VO2 Max 01:20:29 Sauna01:30:43 Creatine01:42:41 Vitamin D01:53:55 Microplastics02:05:10 Alcohol 02:18:22 Psychedelics *For show notes and past guests on The Tim Ferriss Show, please visit tim.blog/podcast.For deals from sponsors of The Tim Ferriss Show, please visit tim.blog/podcast-sponsorsSign up for Tim’s email newsletter (5-Bullet Friday) at tim.blog/friday.For transcripts of episodes, go to tim.blog/transcripts.Discover Tim’s books: tim.blog/books.Follow Tim:Twitter: twitter.com/tferriss Instagram: instagram.com/timferrissYouTube: youtube.com/timferrissFacebook: facebook.com/timferriss LinkedIn: linkedin.com/in/timferrissPast guests on The Tim Ferriss Show include Jerry Seinfeld, Hugh Jackman, Dr. Jane Goodall, LeBron James, Kevin Hart, Doris Kearns Goodwin, Jamie Foxx, Matthew McConaughey, Esther Perel, Elizabeth Gilbert, Terry Crews, Sia, Yuval Noah Harari, Malcolm Gladwell, Madeleine Albright, Cheryl Strayed, Jim Collins, Mary Karr, Maria Popova, Sam Harris, Michael Phelps, Bob Iger, Edward Norton, Arnold Schwarzenegger, Neil Strauss, Ken Burns, Maria Sharapova, Marc Andreessen, Neil Gaiman, Neil de Grasse Tyson, Jocko Willink, Daniel Ek, Kelly Slater, Dr. Peter Attia, Seth Godin, Howard Marks, Dr. Brené Brown, Eric Schmidt, Michael Lewis, Joe Gebbia, Michael Pollan, Dr. Jordan Peterson, Vince Vaughn, Brian Koppelman, Ramit Sethi, Dax Shepard, Tony Robbins, Jim Dethmer, Dan Harris, Ray Dalio, Naval Ravikant, Vitalik Buterin, Elizabeth Lesser, Amanda Palmer, Katie Haun, Sir Richard Branson, Chuck Palahniuk, Arianna Huffington, Reid Hoffman, Bill Burr, Whitney Cummings, Rick Rubin, Dr. Vivek Murthy, Darren Aronofsky, Margaret Atwood, Mark Zuckerberg, Peter Thiel, Dr. Gabor Maté, Anne Lamott, Sarah Silverman, Dr. Andrew Huberman, and many more.See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.

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 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 FASEP Journal, and Experimental Gerontology. You can find all things Rhonda Patrick-PhD at foundmyfitness fitness.com and you can find her on X and other places at found my fitness 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

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Can I answer your personal question? Now is the appropriate time. I'm a cybernetic organism living this year over metal and skeleton. Rhonda, it is very nice to see you again. Thanks for making the time. Yeah, I'm excited to be here. 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 proceeding that by a few months, April 2014 was when you had a guest post on my blog called Are Saunas the Next Big Performance Enhancing Drug? So well done. That's become quite the topic. I know, I kind of like to take a little bit of that claim to making saunas popular.

The godmother, the fairy godmother of heat shock proteins, the context of saunas popular. The godmother, the fairy godmother of heat shock proteins, the context of saunas. And we are gonna run out of time before we run out of topics or questions as always. And what's so fun about having a conversation with someone like you, who is not only very scientifically credible and literate, but who's actively involved with the science,

tracking the science and have published is that there's always more stuff to talk about. Things change, there are new developments, there are new discoveries, there are revisions, which makes me very excited to hop into the conversation. And for people listening, we're gonna cover a lot of things that are very, very actionable and practical. And I just wanted to give people an idea

of some of what's coming. We may not cover it all, but if you'll bear with me, Rhonda, I'm just gonna 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 cognitive decline,

how a low omega-3 index is as bad as smoking and what to do about it, benefits of creatine for brain and muscle health and best practices, microplastic exposure, the biggest offenders and so on. It just goes on and on. We could cover so much ground. And the way this conversation came to be,

to give people a peek behind the curtain, is we were texting about all sorts of things, including aging parents and what we're trying and what we're thinking about, what has worked, what hasn't worked seemingly. And I thought we would just start there if you're open to sharing, because I really gained from our exchanges, enjoyed our exchanges. And for instance, talking about creatine as one example, right? There are

potential applications to preserving or at least halting the decline or slowing the decline of cognitive deterioration, right? And why don't we just begin with the personal? Because I think that's the most universal. And all of my friends of my vintage 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 have seemed to have an effect? 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 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 looked at a variety of different studies, it's called a meta-analysis, that basically said, well, you know, all these vitamins that you're taking are useless and in some cases, they can be harmful because they can allow cancer to grow faster. And I sort of debunked that 10 years ago. But over the course of those 10 years, and as you mentioned in the intro here, 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. Placebos are a real thing. So three trials came out looking at the effect of multivitamins on cognition. And I'm talking the multivitamin that was used was

the standard run-of-the-mill. It was centrum silver. I mean, it was the same thing. CB It was centrum. I knew it was going to be centrum, yeah. BT 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 lutein, zeaxanthin, 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 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 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. So these are older adults that were otherwise didn't have any sort of neurodegenerative disease. That's also important because once you get to a pathological state, you 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 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 UVB radiation from the sun. And so there's

much less efficient at it. In fact, a 70-year-old makes about four times less vitamin D than their former 20-year-old self. So vitamin D supplement is supplement is a low hanging fruit. It's super easy to bring someone up to level. 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 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 E3 for, and should that change how I consume vitamin D or consume fish oil or

Omega 3s having that type of status. 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 people without the alleles. And on top of that, in trials, people with mild cognitive decline, for example, if they supplemented with fish oil and they had APOE4, they didn't have the cognitive benefits 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 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. 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. You're getting more phospholipid form. Exactly. Now, if you are taking your supplement oils, you can actually make 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 body is also 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 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. 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 APOE-4, 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. without getting into all the crazy molecular and biochemistry involved. Um,

just take my word on that for the two different forms of omega three, or you can read that publication as well. 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. Cause 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? 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 mentioned that my dad was diagnosed with Parkinson's disease. In that podcast, yep. Yeah. He was diagnosed with Parkinson's disease in 2017. And that's an important context to consider like what sort of supplements I'm giving my dad and also the fact that you have to think about compliance.

Like what were your parents? Do you have a parent that'll take a lot of vitamins or a few vitamins, right? So with my dad, knowing his disease, with 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 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 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 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. If he were willing to take more, what would you give him? I would also give him sulforaphane. Definitely tried, he doesn't wanna 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 chop it up or whatever, it forms sulforaphane. Sulforaphane is 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 the plant, but it's not, just so you know. So sulforaphane is something that's formed in these cruciferous vegetables. Broccoli sprouts, the young, young sprout of broccoli actually is the best source of it. It has 100 times more of that active precursor glucoraphanin than mature broccoli. So that's the best dietary source of it. Are you growing your own broccoli sprouts or are you doing off the shelf now?

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 NRF2, 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.

And these are the kind of things that are activated when you're doing stress, stressful things like exercise, or if you are fasting. So you really want this pathway to be active. 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? Exactly. Am I getting that right?

You got it. Yeah, you nailed it. Yeah. So essentially we're talking about what is 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 the amount of time that you're ingesting that polyphenol is very small and digesting in and then the reality is that it's activating these stress response pathways that last 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 Nrf2 and one of the main pathways that it's activating is increasing glutathione production. And it's been shown in a couple 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. 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 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. 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 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 screening 60% more benzene from their body. Now benzene is something that is found in air pollution. It's also in cigarettes. Don't drink your own urine if you're taking sulforaphane is what you're saying. 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. How long did that take? 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 these bottles and she takes two a day and she takes a certain brand called Avamacol. I don't have any affiliation with them. They're a brand that, again, 12 different published studies using their supplement. A V M A C O L. 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 we do crossfit training at my house. My mom has seen me doing it and she's been interested in it.

And I told her that there's a great seniors class and I would be willing to, you know, pay for it and get her in it. It would be huge. And she's been doing it now for a 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. She's doing kettlebell swings. She's doing wall squats. I mean, it's amazing. Go mom. That's amazing. It's a very different type of atmosphere than your usual CrossFit class would be. You're aware that these are seniors and so they're not doing barbell squatting heavy weights and stuff. They start out with wall squats and then they're squatting with just a really light bar and it's really great. 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, or 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 advance

with respect to Alzheimer's. Saw 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, AED, I should really double down on paying attention to as much as possible for myself, certainly for them as well, but the earlier the intervention, the better the outcomes generally. So I've been looking at all sorts of things and just to reiterate a few things you said.

So on the omega-3 side of things, just like with sulforaphane, not all brands are created equal, right? There's a lot of garbage floating around out there. Would you say neither of us have any affiliation with this company, but I know our mutual friend Kevin Rose had this particular brand tested that I guess it's one O dot N dot E pure encapsulations. Is that what you have your your parents taking or did you use a different brand?

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 both been third party tested and have very high quality fish oil and I don't have affiliation with either of them.

Yep, so I've got my parents on those. I'm taking those. You mentioned Lutein and Ziazanthin, 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 areds too, people could check out studies that have been done on areds too. And two of the principal ingredients

are lutein and zeaxanthin. So there's that. Now also have been very, very curious about how to activate some of the pathways that you mentioned. Sulfurifane 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 gonna happen for a million different reasons, but perhaps exogenous ketones and have looked at that. This is kind of a work in progress I've been doing and I know you have too, lots self-experimentation but there are some case studies in the literature one of which you sent to me that are pretty interesting looking

at administration in other words giving an older patient with Alzheimer's disease oral exogenous ketones they tend to taste like jet fuel they're tasty. But the effects of at least in these case studies are pretty remarkable. Now granted with the mono ester 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 gonna throw a couple of more things out there

that are on my mind. So you mentioned the exercise piece. This has been so important for me. So I've hired a trainer and I realized 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. 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

clotho 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. 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 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're 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.

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Check it out. davidprotein.com slash tim. Anything else you would add to that or any commentary you want to sprinkle in? Am I missing any criticals? Multivitamin. Yeah. There's commentary, but we can get into that if you want to go dive into the why the ketone esters are beneficial and why the exercise is beneficial. We can go into that because I'm I love talking about it. Yeah, so this is gonna be a conversation, right?

Just between you and me. That's how I treat all these things. And I'm very self-interested because I think the personal is the most universal. Maybe that's just an excuse to make this all about what I want. But we have been texting also because I told you, I've been thinking about doing a 14 day fast.

And actually I ratcheted that back from doing a 30 day fast. And I've done 10 days before water only. I've done lots of seven days. And part of the reason is I think I would be better equipped now to do longer fasts because of the intermittent fasting I've been doing. And this ties into the conversation around the parents because what I've noticed is, for instance, doing 16 eight 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? Dr. Mark Mattson. 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 PM and 10 PM. There are arguments that it should be shifted earlier, like noon to 8 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 two to let's say 9 PM is when I eat, and then I fast the rest of the time. And for the first like five to seven days, pretty grumpy, kind of pissy, I'm not gonna lie. You know, sent some emails that I probably shouldn't have.

But then once I adapted, I did a recent set of labs and they're my best set of labs that I've seen. I can't solely attribute it to the intermittent fasting, but the best set of labs I've had in ages on things that were very hard to move prior. Also did an oral glucose tolerance test and my sort of insulin sensitivity and glucose management, the best it's been in ages.

So I was like, okay, that's really interesting. The last time I did a seven day fast, it was kind of brutal. I hadn't done one in a few years and I don't think my metabolic machinery was ready for the task. Very unpleasant. But I have some chronic inflammation

or at least chronic pain in my low back. And after doing that seven day fast, I had four weeks of zero symptoms. And that's the first time in three years that that's been the case. So I was like, okay, that's pretty interesting. And so I've ended up harassing you with all sorts of questions such as,

well, what if I had a little bit of heavy cream in my coffee in the morning? So it's kind of dirty fasting. But if I did that, what am I 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 or three months straight. And they have all these benefits that may be of lower magnitude, but mirror water fasting on some level, but they're consuming a few hundred calories, let's just say for simplicity per day of those five days of quote unquote fasting. If you look at the actual meal composition, it ends up being very low calorie keto, basically. Very low calorie keto with very low protein, like 10% or less avoiding animal products. That's the basic way that I've been thinking of it. 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, 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 a.m. 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. 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 three diabetes. And

it's like, okay, well, if I can't help them, at least I want to try to help myself and other people who might be listening at an early enough stage. So how do you think about all this stuff? Well, there's a lot there's a lot to talk about here. And I think we got to kind of let's let's you on one bit at a time. 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 mentioned the 16-8. 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, 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. 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 ten hour period, for example, usually they'll eat their food within a ten 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 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 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 fasting more like 18 hours and eating their food within like a six-hour window. That 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 then they want to get into what's called ketosis. So they want to have they want 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 8. If they're physically active on top of that, you might go down to like even 6 or something. So 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 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 circling 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 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. It's a clean fuel. Yeah. Also BHB, the beta hydroxybutyrate, as I understand it,

I mean, highly anti-inflammatory effects as well. Right? 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 hydroxybutyrates produce 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 deacetylase inhibitor. So it's globally affecting gene expression in such a way that it reduces genes that are involved in making oxidative stress. 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. 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 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. People get so freaked out by the word catabolism. Oh yeah.

Last night when I was walking around New York City, we were talking about this, the catabolism. 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 role in cardiovascular disease. But it also cleans out even damaged little what are called organelles. 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 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 end points that people are interested in achieving, I think something that you're specifically

interested in is the metabolic effects of intermittent fasting as well as the repair processes like the autophagy. Yeah, for sure. And that's why I was asking because I don't really look 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 pre-cancerous cells in the nuts by doing that. 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 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 what we don't have a lot of evidence on is like, what's the minimal effect of fasting dose to activate autophagy? Right. God, I wish we had this. 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 it takes to activate autophagy? No. So, most humans are probably doing anywhere between a 12 to 16 hour nightly fast, right? There's a period of time when we're not eating and that is when we're sleeping a little bit for bad right. I talk to you 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 it's sixteen hour fast doesn't act i believe it does in human. I believe there's some autophagy going on. It's probably not that much, but if you go into that 48 hour fast, then you're really starting to get more robust activation of autophagy.

So you mentioned sleep, and I've been trying to look at Alzheimer's from every possible angle and found literature looking at disruption of sleep architecture in patients with Alzheimer's disease and the possible application of Zyram, 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 to do its work and to actually take out the garbage cellularly. And so if I could wave a magic wand, I would have my relatives on something like Zyrem, might actually be a different type of sleep medication like the Nora class. Nora 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 psilocin. 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 the, from a mechanistic perspective, they're, they're super, super interesting. So I just want to double click on the sleep because that is 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 these other things. But boy, oh boy, it would make a lot of sense to try to fix sleep whenever possible. Dr. Patrick Saarbrueck Great. I mean, yeah, so true. This low wave sleep does activate the glimthatic 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, 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 maintaining muscle mass and certainly growing muscle mass as well. So it increases muscle protein synthesis, which is important. If people are engaged in resistance training and doing intermittent fasting, they're not losing muscle mass.

And in fact, they can even gain muscle mass 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 or 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 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, that would be huge because you would be then activating muscle protein synthesis through another 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 the old literature and some of the literature that's been done, a lot of water, up to 10 pounds of water rate, 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. Valter Longo many years ago. He's shown in animal studies, prolonged type of fasting actually causes organs to shrink

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 re-feeding phase, and this is key, the re-feeding phase is the growth phase. And this is when you regrow organs. It's when your muscle mass comes back.

You can 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 that fast and you're losing visceral fat. And you had brought this up last night when we were talking and I 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?

That can get misclassified. 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 is 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. 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 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 autopsy depends on how much you're feeding, right? How many calories that you're eating, how much of that is amino acids. Specifically leucine, right? In the case of Longo, like really trying to minimize leucine as an activator of mTOR and so on. Yes, exactly. Yeah. So I think for the cream, if you're trying to do 16 eight, if someone is trying to do 16 eight 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. 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 lux 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,

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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 I was an expression. I just think 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. So 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 gonna do this, but would somehow get the ethics board, IRB, et cetera, to approve long-term human studies again in fasting, that would be great. Because you used to be allowed to do it. There are case studies of people who literally fasted for 300 plus days. I mean, 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. Yeah, I think people are concerned with gallstones. So when you don't

eat for a period of long period of time, then you're not stimulating the gallbladder and the gallstone risk increases, which is what I think is the big concern 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. 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, or I'd stand up and I felt like I was gonna fall over. And my vision started to get funny. And I was like, you know what?

Maybe this isn't for me. But I think it's because my machinery just wasn't developed for that. Having seen really stark differences in my mental acuity and sustained focus with the intermittent fasting. I'm like, okay, I feel like doing intermittent fasting, which part of my reason behaviorally, for my interest in that also is that getting people to change their diet is fucking hard, meaning their diet composition, the food they eat. so if you can just say hey look

Keep eating whatever you want same thing, but you have to fit it within this window. It's an interesting Option B that might 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 alright 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. 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 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 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 test.

Intermittent fasting plus ketosis really helps my zone too. And then this leads into the question of just training in general. So I have to click on this. What type of exercise reduces heart aging by 20 years? Do you want to start there or do you want to start with VO2 max? We can start with VO2 max, maybe because they kind'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 the 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 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. 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. Carrying groceries to your car from the store, you're just out of breath. Everything is a maximal effort, and you don't wanna be there. So you wanna like start from a higher up point,

so that when you're going down, that cliff is much further away. And 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 cardiorespiratory fitness and that's where you talked about zone 2 training 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 of moderate intensity physical activity, people that do that for two months, 40% of those people still can't improve their VO2 max. Yeah, yeah, yeah. Just different gears. Well, unless they actually add in high intensity interval training. 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 can't have a conversation because you're going harder. Your heart rate is about 80, 85%. It's above 80% max heart rate. That type of exercise has been shown to improve VO2 max, especially if you're doing what's called high intensity interval training. As you know, you've talked about this a lot as well. You're doing 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. 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 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. What do you do personally? What's your hit look like? I do a lot of hits. 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 4x4 so that's where I do on a stationary bike or I'll 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. I'm just working hard, as hard as I can and maintain that for four minutes.

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 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. Most of my exercise is high intensity interval training, CrossFit training, which incorporates, it's more dynamic, so it's including

strength training stuff, but it's more high intensity. And then I do a couple of runs. I do two 30 minute runs a week, sometimes three. And that's more of my zone two stuff. Yeah, it'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

IE vo2 max training the zone 2 is like listen to a podcast. Maybe I have like a slightly breathy conversation Like it's pretty chill watch something on the on Netflix. You know, that's pretty straightforward view to max Specifically chatting with Peter Tia. I'm doing the zone 2 which I do either on a stationary bike or on a treadmill Typically out with a rucksack at a 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 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 going to make it. I don't think I'm going to make it. And then minute four is like, I feel 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 person I like a lot. It's a lot of work. Like it's pretty pukey, but I'm going to 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 D too, a little bit for me where I'm like in these studies looking at VO2 max as a predictor or correlate of longevity, are there other possible confounding variables that might actually be their real McCoy?

Because you could say, and I know you know all this, but just for people listening, it's like, okay, well, I'll make this up. Like women who do Pilates in Manhattan have 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? 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 yes, they're going in and measuring their cardiorespiratory fitness, which is better than a lot of observational studies that you're going off a questionnaire, right? That's already sort of one, at least 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? And it's the disease that's causing them to have a higher mortality rate than the lower cardiorespiratory fitness is.

There are 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. 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 muscle than the people without. I don't know. I mean, that's just, I mean, just kind of poking out of curiosity. Okay, so the heart aging. 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, 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 cardiorespiratory fitness and our ability to exercise and, you know, I mentioned our cardiorespiratory 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 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. It doesn't sound good. 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 in the trajectory of these aging hearts. And so he put them on a two yearyear training program, which involved the Norwegian four by four, by the way. And when you start someone out that's 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. Yeah, you do have to last four minutes, right? You have to last four minutes. And so some people even start off, they're just briskly

walking because that's hard for them, right? Yeah, totally. So it's all tailored to the individual. And so some people get really intimidated where they're like, oh, there's no way I could ever do that. Well, actually, these people did do it and they started out doing Norwegian 4x4, but they also did a variety of other exercises including moderate intensity and some more vigorous intensity exercise as well as some resistance training. The control group was just this 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 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 of it and the 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 aging of your heart by 20 years if you really put in the effort. Five hours a week is about what I do. I have five or six hours a week.

It's a lot of work. I didn't always do that, but I've decided as I started to get into my mid forties, I'm going to spend less time podcasting and more time exercising because this is my health. Foundational for everything else. That's the base of the pyramid. All right. So let's park that particular piece of training for a moment. Do you want to piggyback on that and talk about reversing brain aging with 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? 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.

It's not like a black or white thing, right? They're sort of gray here. But the reality 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. 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. It gets into the brain. It gets into the heart, liver quickly. It happens within 20 minutes. You can do a HIIT workout, see your lactate go up to 15 millimolar, measure it 20 minutes later and it's back to baseline.

I mean, it's quick. It gets consumed. One of the major organs that consumes it is the brain. This has been shown in human studies. Not only is lactate very much like beta-hydroxybutyrate, our favorite ketone that we've been talking about because it's an energetically favorable source of energy. Lactate is used by neurons to make energy, just like beta-hydroxybutyrate is very similar. It's energetically favorable. All that stuff is happening in the same stuff. So you're using the lactate, glucose is being spared,

you're making glutathione. Lactate is 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 one to two percent after that year of training versus losing one to two percent of the hippocampus. That usually happens as you get an older age. So the lactate is again a product of that vigorous intensity exercise. It's increasing norepinephrine in the brain, serotonin.

It's a signaling molecule. It's basically your muscles way of communicating with the brain, hey, I'm really working hard. This is a stressful 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'm also prone to neurodegenerative disease. I have Parkinson's disease on my dad's side. I have Alzheimer's disease on my mom's side. So I'm very, very tuned in to neurodegenerative disease and wanting to prevent it and do what

I can. And I do think that vigorous intensity exercise is part of that equation because I want to get that lactate which is so beneficial for brain health. So let me ask you about two other things related to brain health since this is on the mind. 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 JAMA Internal Medicine 2015 that followed 2000 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 all cause mortality, 24% lower risk with two to three times per week. This is sauna use and four to seven times per week was associated with 40% lower risk. And I'll just cut to the one that's of greatest interest to me right now. It says in a follow-up paper, using 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 are getting dementia and now it's one person, it's less interesting than other ways of interpreting the data. How should we think about this? And how do you personally use if you do sauna or hot tub or heat stress at this point. 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 having a 40% lower all-cause mortality. And the dementia risk is also extremely interesting to me. And this goes back, Tim, to like some of the earliest experiments that I did as a sort

of budding young biologist at the Salk Institute where I was working with these little nematode C. elegans worms and injecting human amyloid beta 42 into these worms and essentially injecting it into their muscle. So that they become basically the amyloid beta 42 aggregates and forms these aggregates as these worms age and it happens very rapidly because their life expectancy is only 15 days. So with an like 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. 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? So I remember reading this study and it was like one of the things I was of active heat shock protein genes, then they're not getting the Alzheimer's disease. It delays it, right? 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 if you're having improved cardiovascular health, that means more blood flow to the sauna. So sauna sort of mimics moderate intensity exercise. And

so if you're having improved cardiovascular health, that means more blood flow to the brain, lots of things are happening, right? The one thing I do want to mention, Tim, and this 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. So they sort of looked at people that are using saunas, but they also sort of categorized them based on the amount of heat, so how hot their saunas got. 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 ends.

So people that were doing like 200 degrees Fahrenheit or more, and this is something that you can the really, really high extreme ends. So people that were doing 200 degrees Fahrenheit or more. And this is something that you can see nowadays. There's this sort of go all in, go hard or go home. And so people think that they need to go in a 200 degrees sauna. And if they go in a 200 degrees sauna, it's going to be better than going in a 175 degree Fahrenheit sauna. Apparently not the case. So in that study, again, you saw a protective

effect of people that use this 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. Oh, no. 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 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 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. That's good enough. You don't have to go above that. Yeah, my default setting of my song 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 part of my default. So maybe I want to dial it back. I think 190 is great. Yeah, 190 is great. And 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. But you wanna stay in there.

Yeah, it's pretty hot. You stay in there for about 20 minutes and you're gonna have comparable effects. You'll be sweating like you're in a sauna. Don't worry about it. 104. 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 was, I like doing the heat a lot in the winter.

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. Good point. You have to, yeah, there's been studies that have shown you do lower motility, for sure. The motility rates 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.

That's not so smart. Do you still use if needed curcumin or theracumin or any of these products, I think, Meriva or Meriva 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? 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 4-Mareva, which is a phytosomal curcumin, which increases the bioavailability of the curcumin. I use the Thorne brand just because I think the brand is reliable, no affiliation with them, but 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. But I do still use it. Yeah. Just don't take it right after your workout, right? It doesn't have the same effect.

Yeah, it doesn't have the same kind of cox-2 inhibition as the other guys, right? It doesn't, and in fact, I think it helps with DOMS, delayed onset muscle soreness, and so sometimes actually I do use it actually after a really hard squat workout. 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 has 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 benefits. I put what else should we know about creatine because you 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 do you think about creatine and best practices for different applications? Well it's funny as you mentioned it's one of those supplements that have been, it was like in the gym bro world forever

and still people associate it with that. But yet it's been one of the supplements that's actually stuck, right? It's worked and there's been countless studies showing its effectiveness, particularly with respect to increasing exercise volume. So in other words, what creatine is, is it's essentially, it's stored in our muscles

as something called phosphocreatine. When you take a creatine exogenously, it's stored in our muscles as phosphocreatine and then used for energy. 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 can do an extra set or whatever it is you're doing, right? 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. 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 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. 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. And you mentioned one that was 25 grams, I mean 20 to 25 grams, which is kind of a crazy

study where they did about 21 hours of sleep deprivation essentially. They were barely sleeping at all. And giving them the 25 grams of creatine, 20 to 25 grams depending on their weight, seemed to 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 20 grams of creatine and it improved their cognition.

We now have the first pilot study in Alzheimer's disease where again 20 grams are given to a very small number of people with Alzheimer's disease. It also improved cognition. It turns out that when you start to go above the five grams and you get into more the 10 grams range, then some of that creatine is getting into the brain 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 miss it, I get it. So it's not like a stored up kind of thing. It't get afternoon sleepiness. I miss it, I get it. So it's not like a stored up kind of thing. It's like, no, if I miss it that day, it's

noticeable. If I travel and I don't have it, it's noticeable. So I'm hooked on the 10 grams a day. If it's a 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 giving a talk early in the morning, which is like 6 a.m. my time, I got to be like on my game.

So I take the 20 grams and I kid you not, it's like you get this brain boost, but without like the caffeine. It's hard to explain. Yeah, without the creepy crawly ants on your skin. Right, without that like. Jittery caffeine over your skin. Jittery thing.

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. Well, also for me, it's like I'm a caffeine fast metabolizer. If you're really jet lagged, especially if you're going across time zones. 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. 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 super interesting to me. Let me ask some very specific, maybe mundane questions, but I think they're practical, which is when the 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? 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 try 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 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. 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, Thorne makes, by the way, no affiliation. I mean, there's

like probably a million other. I like Thorn because their creatinine is NSF certified, and so it's free of contaminants. I really like that. So again, find your own favorite brand, but I like this brand, and 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. 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. 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 20 X the label amount. It's just bananas. So you know, I use Momentus Creatium, it's passing the same hurdle. And I will say that good news, you can reduce the likelihood of cognitive deficit from sleep deprivation.

Bad news is you could increase the likelihood of disaster pants. If you have 20 cramps 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 the 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. It's also one of those supplements where it's like, okay, look, I assume this is on the grass list, like the generally recognized is safe. It 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? In a sense, 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 A-REDs too, 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 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 I, sulfurophane, does it matter? 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 would have to really take it with food. 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 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 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? I can. 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. 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 it's 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, it gets into your bloodstream. And that vitamin 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-hydroxyvitamin D. That's the major circulating form of vitamin D. After 25-hydroxyvitamin D is made in the liver, it then goes to the kidneys and it's made into the actual active steroid hormone, which is called 125-hydroxyvitamin D. Well, it turns out the enzymes that are doing the conversion of vitamin D3 into that stable form that everyone gets 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? 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 NHANES studies and stuff showing that people that have low magnesium intake also have low circulating forms of 25-hydroxyvitamin 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 make-ups, and I know quite a few people that actually have to take a super high level of vitamin D3 to actually get enough vitamin D. And then the other thing is that you mentioned earlier the variation between supplements. There have been studies on vitamin D supplements, and it's the same problem with melatonin. There's some vitamin D supplements with a fraction of what is stated in terms of concentration of vitamin D3 on the nutrition facts.

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. 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. It's a natural 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. 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, and the way we got to that is I was like, oh, 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 lo and behold. So 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. Maybe I'm overstating them, but how do you think about that? 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 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 mil, 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 mortalities lower within that range. So 50 nanograms per mil would be great. I mean, that's a great place to be if you're below 30. If you're about just 30, you might want to try to get up to 40. So depending on where you are. 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 it's 30. Okay.

For someone that's at 30 dg per ml is supplementing with 5,000 IUs a day or 4,000. Yeah, 5 four thousand. I was like thousand. Yeah five Five-thousand I use a day and getting an hour of sun in the summer without sunscreen You probably should be closer to fifty nanograms per mil. I would say if you're taking I'll check my last labs I just had them pulled two weeks ago. So I'll double check Right. So for someone in that case, you might go up to 7,000 IUs and check and see where you're at a month later than 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? Well, you have to get a vitamin D blood test. 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 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 percent depending on how physically active you are. If you're like the endurance athlete, you're on the 20 percent higher range. If you're more just like the average, like I'm a committed exerciser, then you might have to go up 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 magnesium. 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 athletic. 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 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. So that's always important to keep in mind. But they have shown that magnesium 3 andNA 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 3NA, 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 enzymes that are converting vitamin D3 into 25-hydroxy vitamin D, right? So that is something to keep in mind. If that form of magnesium indeed is going into the brain more, you want to make sure you're getting some of the other forms to cover the other bases of other organs as well.

What brand of vitamin D supplementation and magnesium glycinate do you use? Is that also a Thorne or are they other suppliers? I use Pure Encapsulations for the vitamin D. I have some friends, mutual friends of ours, that like the Vessisorb vitamin D3. So people that are not able to increase their vitamin D as well. Vessi Sorb really increases the bioavailability of a lot of things, including

ubiquinol, the CoQ10 I mentioned, I should have mentioned that by my dad, that's the form I get for him because it increases the bioavailability. Also, some fish oil has been shown to increase the bioavailability. So Vessi Sorb 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. For the magnesium 3-anate, I use Zymogen. I like the Zymogen magnesium 3-anate. 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 got to check your levels guys. You can't just be shooting in the dark here. It's not a good idea. Right. All right. Where should we zig and zag to next?

Do you want to talk about microplastics and mitigation strategies? 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, 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 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.

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 show this, essentially I'm sort of speculating here, but because the

size matters, the size of plastics in the plastic bottles are super small and that's really absorbed well by the gut epithelia and taken up into the bloodstream and gets to the other organs. Also, the plastic chemicals like BPA are in plastic, they're not in the glass. 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. The size matters. In this case, size matters. The 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 the 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 electrophoresis 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.

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. 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, 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. I wonder if the big Berkey countertop filtration system is effective at filtering out microplastics. I don't know. It is. It's effective at filtering out microplastics. It's not clear about like the nanonano, the super, super small

size ones. It might. It might not. I don't know. But it does definitely, the micro size ones, it does filter out microplastics. So the thing with reverse osmosis is it's really filtering out all, even the nanoplastics as well. Of course, you have to consider re-adding 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. 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 Alzheimer's disease. They're associated with cancer, all sorts of things. And those can actually, I think actually, this is 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 shown in animal studies. 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 I'll say this, all the to-go cups that you're out there buying when you go to 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 releases all these microplastics into your beverage, and it releases the chemicals like BPA into them, like 50-fold. Blue Bottle Coffee, by the way,

they apparently line their cups with sugar cane, polylactic acid. 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, 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? Right. Bring your own cup. The tea bags, right? And the tea bags, so you have to do loose leaf tea, which is what now I'm like always, it's gotta be loose leaf, I'll bring my own little, I'll sometimes open the tea bag out, and I bring my own little tea steeper thing with me.

Like the half globes that connect together. 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 plastics. So you're drinking 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 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 the New England Journal of Medicine about a year ago showing that people that had 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? That's ubiquitous. Yeah. And there's some simple things people can do. I mean, this is not necessarily in the same category, but 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 microplastic stuff is kind of terrifying. I did not realize the gum.

I knew about the tea bags, the water filtration, did not realize the gum. I don't 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. Wow, that's crazy. I started chewing gum when I learned about the research

showing that xylitol could inhibit some of the S mutagens, bacteria that are involved in cavity formation. And then a few years later, you're like, God damn it. Well, I was able to reverse cavities multiple times and my doctor was like, keep doing it. I'm like, yes, the 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 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, chewing on bark is this is it like chewing on pretty it's pretty much spark bark. It's actually made from bark. No, it's made from like trees like some kind of sap or something like resin or something. Yeah. Sounds delicious. You can't just do

xylitol mints. You have to chew it. I guess you have to get it up. You can do xylitol mints. Yeah, you can do xylitol mints. I have this as well. 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 this, some of the research doc that I have in front of me. And there's one section that I highlighted which was each three hour increase in nighttime fasting was linked to 20% lower odds of elevated hemoglobin A1C, right? This longterm marker of blood glucose.

And then one of your bullets was the effects of alcohol on 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 10 PM, first of all. And then I had a glass of wine. So I put the glass of wine on top of my research document

with all of this text visible and I sent it to you and I was like, am I doing it right? Because it's like, you know, I could always get it right, but let's talk about, do you want to talk about the booze for a second? I mean, so alcohol, yeah, and especially since we were talking about 8.4. Just to depress people after the microplastics.

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 find a good balance obviously. So alcohol is a toxin. It's also a lot of fun, right? I mean, it's fun to drink and have a glass of wine. Sometimes it helps kind of, it feels like you're lowering your stress, lowering some inhibitions. It's fun to do with a group of friends and stuff. It's not so great for the brain though. 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 doing moderate alcohol consumption, you can actually have a protective effect against dementia and Alzheimer's disease, right? Where it's like this idea that alcohol, like a glass of wine a day is actually beneficial for you. So you should be drinking that. I wonder if it's actually these social interactions facilitated by alcohol versus the moderate alcohol itself, I wonder. 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 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 seven drinks a day. In some cases-

Seven drinks a day? 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. Wonder who authored that study. Yeah, exactly. It's a big difference.

But on average, moderate alcohol consumption is more like a seven drinks a week. Seven drinks a day would definitely be heavy alcohol consumption. That would be substance use or alcohol use disorder. Let's cut the substance abuse part out, alcohol use. Why can't you say abuse anymore? Why do these things have to keep changing? It's so ridiculous. And it's hard for me because I'm always tripping

on my words. Use disorder sounds better than abuse. I mean, do you know what are the reasons behind this? Do you know? I guess it's politically correct. Because I'm finding all this psychedelic stuff and it was like abuse for a long time and then all of a sudden, Nope, verboten. Can't say that. Who knows? Anyway, 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 going to cut this out. Seven drinks a week. How many drinks have you had before this podcast, Rhonda? Well, I did have some ketone ester or there's a little bit of alcohol that like is involved with that. Yeah, but yeah, watch out for the one, one, three butan dial anyway. Right. There's something called the sick quitter 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 someone gets sick. Oh, sick quitter. I got it. Sick quitter. Is that English? Someone gets sick. Oh, sick quitter. Yes. I got it. 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, 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? 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 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.

In the non-drinker. In the supposed non-drinker group. Quote unquote non-drinker group. 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 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 associated with breast cancer, colon cancer, for example.

Breast cancer is a big one because women's lifetime risk of breast cancer is 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 lifetime risk. So I do think that alcohol, I mean, obviously some people enjoy it and I don't know that

there's any amount that's actually safe, but if you're really looking for a number, it seems like one or two drinks a week seems to be the safest spot. I mean, the safest would be zero, zero drinks. But if you're really not wanting to have the damage, the light drinking, which is the one to two drinks a week, that's where you're probably the best off. Talking about a weekend, you have a weekend and you're doing a glass of wine, maybe Friday or Saturday night, that's the safest if you're looking for 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 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 gotta look at the whole- 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, if acetaldehyde acting as a mutagen and therefore just fucking up your D like smashing your DNA. So you have these mutations that then proliferate and turn into some type of dangerous cancer. Like is there more to the story of mechanism of action? Yeah, I mean, acetylaldehyde 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, lipopolysaccharide gets released into the bloodstream.

Inflammation gets activated. Inflammation is a 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 one of the reasons why people with APOE4 are a little more sensitive to alcohol is because the repair processes in individuals with APOE4 isn't as robust. It's compromised already. 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 APOE4 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's a major cause in Alzheimer's disease. I mean, it's really a known factor now.

And you're disrupting mitochondria, you're disrupting, there's just everything you know about to be important for health is sort of affected by alcohol through a variety of mechanisms. Do you ever drink? I don't drink very much. I used to drink more. Sometimes I go several months without having anything.

I do. So I'm not putting you on the stand here. I don't drink all the time, but I'm just giving you a little leeway. Yeah. I used to drink at least a couple of times a week where I 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'll go like, you know, a couple 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 get like one glass of Prosecco and I'm like, this is amazing. I forgot to mention with respect to the dementia risk in alcohol, you asked about mechanisms, the sleep aspect, right? Oh, for sure. That's a huge, yes. It's a huge one because alcohol does disrupt sleep. Despite the fact that people that's massive, 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 awaken, 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. Oh, that was, yeah. Am I doing it right? Yeah. Oh, 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 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 gonna 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 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. They contain is 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 worth people asking. If they're gonna 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. 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 Crystal, he has done a lot of great research and his teams and co-authors used recreational actually increases your predisposition to depression. 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.

And more than one study. Oh, yeah. Yeah. Yeah. Yeah. The two major applications are major depressive disorder and alcohol use disorder as it stands right now. This study just came out like, gosh, just like last two weeks or something showing is the animal study that psilocybin increased life expectancy by almost 20% in mice. I mean- Yeah, I saw that. And I think that was at Emory. Am I making that up?

I think it was at Emory. I think it was. 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, because 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. Let me look at that a little more closely. And the metabolism is very different, but it's still non-trivial. Like I do think those little furry friends

are probably tripping balls. Because all of the, 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 life extension stuff is interesting. And I've been funding some science that Chuck Nichols is doing, looking at the anti-inflammatory applications of different psychedelic compounds. And they are profound, really profound. looking at the anti-inflammatory applications of different psychedelic compounds, and they are profound, really profound. And what makes it most interesting

is that it can be achieved, depending on the compound, and he's tested dozens of them, with very, very trace quantities, in sub-perceptual quantities. You do not need any hallucination, any sort of reality distortion to achieve the anti-inflammatory effects. So like a micro-dosing.

Yeah. A micro-dosing of it. Even less than what someone would consider a micro-dose, like a nano-dose. Wow. 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 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. Totally. And so as you said, right, 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, sort of the kitchen sink at this to see what these 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 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 Murica, like more is better. Like we did the minimal effective dose, but recognize 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 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. Let's do this Rhonda, where can people find you, find what you're up to, get into all things Rhonda, where can people find you, find what you're up to, get into all things Rhonda Patrick?

I have a podcast. You can find it on Spotify, Apple Podcast, YouTube is called Found My Fitness. You can also just search Rhonda Patrick. One of the OGs, you've been doing it for a while now. 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. And you have a newsletter. 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 media and I break it down every week. I sent to 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 and sign up for the newsletter there. 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've called a lot of things early.

And I appreciate your ability to simplify without mangling, simplify without disfiguring the science. I really respect that. It's not easy to do. It is such a service to people who care about being scientific 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. 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 got great, insightful, thoughtful questions and I've read your books. So I appreciate all you do. So the feeling is mutual and I'm glad we get to still have conversations over 10 years later. I know. I know. I just 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. yourself and thank you for tuning in. 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 podcasts, gadgets, gizmos, all sorts of tech tricks and so on that get sent to me by my friends including a lot of podcast guests 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.

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