#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

0:00 Hello, boys and girls, ladies and germs. This is Tim Ferris, and welcome to another episode of the Tim Ferris 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. Ronda 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

0:40 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 and Brain aging and overall improved.

1:01 HealthSpan. She is an associate scientist and board member at the Fatty Acid Research Institute, where her work focuses on the role of omega-3 fatty acids in metabolic health and brain aging. Her peer-reviewed publications have appeared in top tier journals, including Nature Cell Biology, the Fast Ep Journal, and Experimental Gerontology. You can find all things Rhonda Patrick VHD at foundmyfitness.com, and you can find her on X and other places at FoundMyFitness. So Just a few words from the folks who make this podcast possible, and then we'll get right into this very wide ranging and actionable conversation with. Ronda 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

1:53 Are the reason I take creatine. Every single day. And it also seems there's some evidence to support if you don't get enough sleep that you can use creatine to compensate to recover from that. I also use it for that purpose. And today's episode sponsor, Mementus, is the gold standard in creatine. There's a lot of BS floating around. A lot of questionable creatine. But I choose them why? Because they source creapeure creatine, the purest, most effective creatine monohydrate available, single sourced from Germany and not cut with fillers or junk, which is hard to avoid otherwise. Their new lemon travel packs make consistency easy to

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4:31 At this altitude, I can run flat out for a half mile before my hands start shaking. So another personal question. Now it is. Cybernetic organism, living tissue over metal endoskeleton. No Bronda, it is very nice to see you again.

4:56 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

5:12 What Podcast number twelve of the Tim Farrow show, which is it was in June of twenty fourteen. And then Preceding that. By a few months.

5:23 April twenty fourteen was when you had A guest post on my blog called Arsauna's the Next Big Performance Enhancing Drug. So well done. That's become quite the topic. I know. I I kind of like to Take a little bit of that.

5:39 claim to to making 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.

6:06 And have published. Is that there's always more stuff to talk about. Things change. There are new developments, there are new discoveries, there are revisions, which makes me very excited to hop into the conversation. And for people listening, we're going to cover a lot of things that are very, very actionable and practical. And I just wanted to give people an idea of some of what's coming. We may not cover it all, but if you'll bear with me, Ronda 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 twenty years brain aging in the same context, or reversing brain aging, the benefits of exercise snacks on glucose regulation and mitochondrial function, we're gonna get a lot.

6:50 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 three index is as bad as smoking and what to do about it. Benefits of creatine for brain and muscle health and best practices.

7:20 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

7:45 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

7:56 Creatine. As one example. Right. There are potential applications. Two

8:03 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

8:21 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.

8:37 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 he was a baseball player and he did it for many, many years, all the way into his early sixties. 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

9:09 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

9:33 Both of my parents are taking A multivitamin. And you might go, Well multivitamin really, what's that gonna do? And I'll tell you We've come full circle, you know.

9:44 Ten years ago. There's a huge splash that was made in the media. 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, you know, ten years ago. But over the course of those ten years, and as you mentioned in the intro here.

10:15 You know, science is always changing and revisions are made, we learn new things and In that 10 year frame, three different randomized controlled trials have come out. And randomized controlled trials are really key because you are comparing this intervention, which in this case was a multivitamin to a placebo because people taking anything are obviously gonna want a positive effect, and many people do anticipate that and they can actually change their biology. Placebo's 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.

10:51 Was the standard run of the mill. It was Centrum Silver. I mean it was the thing. Centrum, I knew it was gonna be Centrum, yeah. It was the vitamin that you would go That's the one vitamin that's not gonna have any effect. But actually it turns out It's got over forty essential nutrients in it, and it's also got some other non-vitamins, so things that are like polyphenols like lutein, cazanthin, these are actually really important for eye health, but also the brain. And these three randomized control trials were two years long.

11:19 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

11:45 They reduce their episodic aging by five years, almost five years. It was four point eight years. Episodic memory is the kind of memory that's involved in remembering events, things that That happened 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

12:13 Yes, but they weren't older adults with neurodegenerative disease. You know, so these are older adults that were otherwise didn't have any sort of neurodegenerative disease. That's also important because 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 seventy percent of the US population has insufficient levels of vitamin D. Older adults are even higher than that. So you know, almost the majority of all older adults are vitamin D deficient. I mean, most people aren't going outside. And even if they are going outside, they're either wearing sunscreen or Just the fact that they're older affects their skin's ability to make vitamin D three from the sun from UVB radiation from the sun. And so

12:59 There's much less efficient at it. In fact, a seventy year old makes about four times less vitamin D than their former twenty year old self. So vitamin D 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? 'Cause I know you love vitamin D. So here's my question about vitamin D and it actually relates to, I believe This is a publication you had in two thousand nineteen, so we'll see if things have changed or not, but Ape O E four and Omega three brain delivery. So

13:25 My family. Lot of benefits to having my genetics, also a whole bunch of bugs in the code, including quite a bit of ApoE4. I'm ApoE three four. And Should that change how I consume vitamin D? or consume fish oil.

13:44 Or Omega Threes. 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 Apo E four allele, as you mentioned, and for people listening or watching, you know, Apo E four allele.

14:01 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

14:15 And this is, you know, where my publication came from, but also there's a lot of evidence that has shown People with Apollo 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 APOE four, they didn't have the cognitive benefits that the people that were not APOE four had.

14:45 There was this big question in the field as to why that is. And it's still not entirely known, although I will say What my take on that is and in fact I've you know talked to some of the experts in the field as well.

14:58 Is that You have to have a higher dose of fish oil for one. And it's better if it's in phospholipid form. So fish, if you're eating fish, it's in phospholipid form, it's in triglyceride form. As well.

15:11 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

15:23 Oils. You can actually make phospholipid form, but you have to get to that like two gram dose range. that's when your your body is also make converting into phospholipid form. And then the other way around that is actually consuming a phospholipid form of omega three. And so that's something that can be done if you're supplementing with Either you know, krill oil. Which I'm not a huge fan of'cause it's not very concentrated, so you'd have to really take a lot of it.

15:48 Or you could eat something like salmon roe, which is a really high phospholipid concentration of omega three fatty acids. And you might go, why phospholipid form? Well it w turns out the way you your brain you actually get omega three into the brain. There's two way. doesn't require phospholipid form. It's just this omega three 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

16:19 People with APOE four. 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. Apoe four 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 kinda just Passively diffuse. as well. I know that is counterintuitive, but without getting into all the crazy molecular and biochemistry involved.

16:45 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

17:05 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?

17:18 I guess I'll kind of zoom out and talk about, you know, I think you listened to a podcast I did with Doctor Mark Matson meant 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 twenty seventeen and

17:33 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 will 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 three.

18:03 can help with dopaminergic transmission. can help with um a lot of brain function and particularly as it's relates to Parkinson's disease as well as Alzheimer's disease. So that was the second supplements that he's, you know, taking. And then the last one that I could really get him to take was Ubiquinol, which is a reduced form of coQ10. Now, coenzyme Q10 is actually something that we have inside of our cells and it's involved in Mitochondrial health. So

18:33 having a depleted CoQ ten can lead to mitochondrial toxicity. So taking CoQ ten, there's actually been some early studies with even Parkinson's disease patients showing that supplementing with CoQ ten can be beneficial. And he's actually Taken those supplements for many, many years now. And Very I would say surprisingly, but also

18:53 I'm thankful. That his Parkinson's disease has progressed very, very slowly. So it's been nine years. almost ten years and He's really essentially had this Parkinson's disease limited to one tremor in his hand.

19:08 Yeah. 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

19:16 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 sulfurophane.

19:35 Definitely tried. He doesn't want to take more pills. So sulfurfane 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 glucoraffinin. When you break the plant tissue when you bite it or you know, chop it up or whatever, it forms sulfurophane. Sulfurphane's not necessarily in the plant itself. It just gets formed when you break the plant tissue. That's a technical thing so I'm just gonna talk about sulfurophane. and call it sulfurphane as if it's part of, you know, the plant, but it's not, just so you know. So sulfurphane is

20:11 It's I mean that's formed in these cruciferous vegetables. Broccoli sprouts, the young young sprout of broccoli actually is the best source of it. It has a hundred times more. of that active precursor glucoraftin 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 afford the supplement and This gives them another way to basically get it. Yeah.

20:48 For cheap. The reason I really like sulfurfane 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 NRF two, which is this major system. It's a Transcription factor.

21:06 That activates a lot of different genes inside of our body. It activates genes that are involved in stress. Basically it's it activates a lot of what are call stress response genes. And these are the kind of things that are activated when you're Doing stress. Stressful things like exercise. Or, you know, if you are fasting. So you really want this

21:25 Pathway to be active. Because a little bit of stress, right? It's like chronic Overdose of stress bad. But Little doses of stress.

21:34 Has this What would you call it? Hermetic effect? Ex exactly. Am I getting that right? You got yeah, you you nailed it. Yeah. So essentially we're talking about what sometimes called U stress 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 in clearing out damage stuff from your cells like autophagy, just all sorts of beneficial stuff, right?

22:02 Those pathways are activated for a longer period of time. than the the acute stress that you're giving it. So in this case, the sulfuriphane is a little bit of an acute stress, like polyphenols in general are. So you you know, the amount of time that you're ingesting that polyphenol is very small and digesting it and and then the reality is is that it's activating these stress response pathways that last, you know, on the orders of like twenty four to forty eight hours, sometimes longer. So you're having this beneficial effect that's overall beneficial from that little bit of stress. And so sulfurphane activates NRF2, and one of the main pathways that it's activating is

22:36 Increasing glutathione production. And it's been shown in h a couple of different human studies that it increases glutathione In both plasma, but also in the brain. Glutathine 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.

22:58 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 sulfurifane and there's a supplement out there that I use that has been used in many different like twelve or so different

23:17 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.

23:31 problems, but they're not neurodegenerative in the sense of Alzheimer's disease and Parkinson's disease are. It's kind of like a something going wrong in the brain and it affects her motor control. So she has tremors. She has essential tremor and she has orthostatic tremor. And I have secretly wanted the increase in glutathione to affect those tremors. But when I gave the sulfur fing to my mom Because I knew the placebo effect, I did

23:55 teller that we were using it to detoxify You know, these chemicals that are associated with plastic. Like BPA because that is also something that I'm using sulfurphane for because Yeah, NRF two 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.

24:19 Within twenty four hours, people start excreting sixty percent 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 sulfurica 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 sulfur of frame. Like it's just like it's a non negotiable, right? So I told her to take the sulfurphane because I wanted her to detoxify BPA because she does

24:45 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. And I How long did that take? Not long. It was actually, I think, within a week or so, maybe two.

25:03 It was very quick. It was very quick. And she's religious about it. I mean she comes I buy it for her and I give her, you know, these bottles and She takes two a day and she takes a certain brand called Avmacol. I don't have any affiliation with them. They're a brand that

25:19 Again, twelve 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.

25:34 She's doing great. What's funny is that I I was able to then get her into CrossFit. And I don't know if it's because her tremors I think her tremors have lessened a bit. And so she's been more active and wanting to be more active. Like she's out dancing more. My mom likes to dance. And I mentioned how I really wanted to get her into a seniors CrossFit class. And she sees me do it. I have a coach come to my house and do we do CrossFit training um at my house and 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

26:10 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.

26:20 She loves it, she's made friends there. Sometimes the coaches take videos and she sends them to me, she sends them to her friends. She's so proud. You know, she's doing kettlebell swings, she's doing wall squats. I mean, it's amazing. Go, Mom. That's amazing. It's a very different type of

26:36 atmosphere than your usual CrossFit class would be, right? You're aware that these are seniors and so they're not doing You know, barbell like squatting like heavy weights and stuff. There's they start out with wall squats and then they're Yeah, squatting, which is like a really light bar and it's it's really great.

26:52 Let me hop in for a second here. Um, and I wanna know if there's anything else to add to that, but we've talked about this, you and I or texted a hell of a lot about it. That I have Alzheimer's in my family. I have now have multiple relatives who are moderate to advanced with respect to Alzheimer's so my grandmother disintegrate Terrifying.

27:12 And terrifying to imagine yourself experiencing the same thing. And also at least one of them is ApoE three three. And I I may believe three, four. So I'm like, well, wait a second. If that is the where they are right now, and I'm at Hypothetically a two point five X. greater risk of developing Alzheimer's disease A D. I should really double down on paying attention to as much as possible for myself, certainly for them.

27:40 as well, but The earlier the intervention. The better the outcomes generally. So I've been looking at all sorts of things and just to reiterate a few things you said. So the On the omega 3 side of things, just like with sulfuripan, not all brands are created equal, right? There's a lot of garbage floating around out there. Would you say

28:03 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 and dot e pure encapsulations. Is that where you have your Your parents taking or did you use a different brand? So Um with my dad

28:20 She is now taking the Zymogen brand, which is also very good. And the reason for that is'cause it's higher DHA. Which is what I wanted. My mom is taking the one. Both those brands, by the way, are great. They've both been third party tested and have very high quality fish oil, and I don't have affiliation with either of them. Yep, so I've got my parents on those. I'm taking those. You mentioned lutein and zeaxanthin, which is good for quite a few things. Now, for those people who may be interested, and this probably won't help me with my particular presbyopia, so age related.

28:54 visual decline, particularly with near work, reading a book, let's say. But A Reds two, people could check out studies that have been done on A Reds II. And two of the principal ingredients are lutein and CZanthin. So There's that.

29:09 Now also have been very, very curious about How to activate some of the pathways that you mentioned. So furophane 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.

29:39 This is kind of a work in progress I've been doing and I know you have too of lots of self experimentation, but there are some case studies in the literature. One of which you sent to me that are pretty interesting, looking at Administration. In other words, giving an older patient with Alzheimer's disease No eh.

29:58 exogenous ketones. They tend to taste like jet fuel. They're not tasty. But the effects of at least in these case studies are pretty remarkable. Now, granted, with the mono ester they use in some of these The off the shelf cost per day would be like

30:14 a hundred and fifty dollars 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

30:40 Pick them up. At their house. It is something that I decided to do. Because

30:49 There are a lot of reasons exercise is amazing, one of which is the natural release of clothho. 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. I Just a quick thanks to one of our sponsors and we'll be right back to the show.

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32:20 David Protein dot com slash Tim. Anything else that you would have to do? Add to that or any commentary you wanna Sprinkle in. Am I missing any criticals? Multivitamin.

32:32 Yeah. There's commentary, but we can get into that if you want to go dive into the why The keto nesters are beneficial and Why the exercise is beneficial. We can go into that'cause I'm I love talking about it. Yeah, so this is gonna be

32:48 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.

33:23 I've been doing and this ties into the conversation around the parents because What I've noticed is for instance doing sixteen eight fasting, which was uh 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 Matson. Yeah, Mark Matson. Amazing, amazing scientist, fantastic conversation.

33:47 lot of seminal work related to intermittent fasting. So sixteen eight, 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 two PM and ten PM. There are arguments that it should be shifted earlier, like noon to eight PM or something like that. But

34:08 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 nine 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, 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

34:33 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.

35:02 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

35:18 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 kinda dirty fasting. But if I did that What am I accepting as a compromise or a penalty, if anything? Because then I

35:34 Think of it. say long goes work. and others looking at fast mimicing diets where I'm like, Well, wait a second, these people are doing Let's just say five days of fast mimicking dieting. per month for three months straight, and they seem to have all these benefits.

35:48 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 ten percent or less, avoiding animal products. That's The basic

36:14 way that I've been thinking of it. So I was like, Well, should I do something like Will Helmina 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 thirty, sixty, ninety days. Yeah.

36:34 Or Am I better off doing shorter water fasts or maybe even a fourteen day water fast? And a lot of The questions came down to I know this is a mouthful, but as you know, I've been thinking about this nonstop. I was up until two AM This morning reading. really, really old stuff out of the Soviet Union on

36:52 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.

37:11 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.

37:27 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

37:40 We looked at some of my relatives and I got my docs to come in and do like a real proper full work up 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.

38:06 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,

38:19 There's a lot there's a lot to talk about here and I think we gotta kinda Yeah, chew 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 talked about you mentioned the sixteen eight. So essentially you're talking about not eating food for a period of time. And that period of time

38:52 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 wanna actually lose weight. And the weight that they wanna lose is not

39:18 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.

39:37 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 two hundred fewer calories.

39:53 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 fourteen hours. If they do that, they end up actually eating two hundred 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. Uh but the weight loss

40:25 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

40:40 glucose regulation improvements, I mean, you know, fasting glucose, postprandial glucose, HBA one C, which is a long term marker of glucose regulation, they're you know, lipids are more favorable. And then they have improvements in blood pressure, for example. That's another big one that people get with a more of a longer type of intermittent fasting. So they're they're fasting more like eighteen hours and eating their food within like a six hour window. That's another benefit. Now You go even further, and I know this is something you're very interested in. So beyond, you know, metabolic benefits and people want to get then they wanna get into what's called ketosis. So they wanna have They wanna be making ketones, these you know, things that we're talking about.

41:18 earlier with r 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 twelve 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

41:42 deplete their liver glycogen quicker than twelve hours. It might even cut it down to like eight. If they're physically active on top of that, you might go down to like even six or something. Like so there's there's a big range here, right? But for a standard person on like a normal diet they're gonna 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 circulating ketone.

42:11 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 hydroxy butyrate 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 BHP, the beta hydroxy butyrate As I understand it, I mean highly anti inflammatory.

42:37 Effects as well. Right. Exactly. That was the next point I was gonna 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 where we're not eating

42:57 Our body switches into ketosis, beta hydroxybutyrates produce, and it signals to these other Jeans. to basically make more of something beneficial. So it's been shown to reduce inflammation. It depresses something called the uh inflammosome, which causes inflammation. It's an H DAC inhibitor. So it's a histone diace inhibitor. So it's globally affecting gene expression in in such a way that It reduces

43:24 genes that are involved in making oxidative stress. It actually activates brain derived neurotropic factor. That's the beneficial neurotropic 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

43:51 To make it Glutathione. very important antioxidant I talked about earlier that sulfurifane 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's been, you know, s tracer studies that have looked at that.

44:07 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 glucosparing. You get this glucos sparing effect. And so That's another reason why people are interested in intermittent fasting.

44:31 And then another main reason, and there's many others, I'm not gonna like touch on everything, but the other main reason is it activates repair. Processes. 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.

44:57 And I think we've even over the last few years, intermittent fasting's kind of gotten a bad rap because people now equate it with, oh, loss of muscle mass. I'm gonna be catabolic. Well, in order to be in a repair mode, you actually do need to be in a catabolic sort of mode. These repair systems are so important for

45:17 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 sign nuclein, 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

45:43 cleans out even damaged little or what are called organelles and so mitochondria are organelle. And our organelles get damaged, so You wanna be be able to repair that damage. And this process of autophagy is the process that does that. And

45:59 You know, there's lots of different types of autopeggy. So if it's a mitochondria repairing damage to itself, it's mitopgy. But for all this stuff to be active, you have to be in that more catabolic state, which can be induced by not eating, can also be induced by like heavy endurance exercise as well. Okay, so talking about those sort of outcomes that people are interested in, those different endpoints that people are interested in 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'cause I don't really

46:34 Look, I'm as vain as the next person I like looking less fat if I can, but it's not my main driver. It's mental acuity and hopefully staving off on some level things like neurodegenerative disease

46:51 And Even cancer, possibly. Which has been part of the reason I've done a lot of these extended water fasts. Which is I realize there are a couple of hops here in terms of speculation, but Seems plausible that you might zap, you know, punch a couple of precancerous cells in the in the nuts by doing that.

47:09 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

47:24 Yes, there are some people that have amyloid beta plaques that don't get Alzheimer's disease. They may be the more resilient non-ApoE4 type of person, but we do know that many, many people do get Alzheimer's disease with amyloid plaques. And in fact, people that have Again, the SNPs in what are what's called the amyloid precursor protein APP that leads to amyloid beta plaque build up, they get early onset Alzheimer's disease. So Autophagy plays an important role in clearing away those plaques and I will say what we what we don't have a lot of evidence i on is like

47:55 What's the minimal effective fasting dose to act an autophagy. 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 twenty four, forty eight hours in humans. Now Does that mean that that is

48:16 The only amount of time it takes to activate a Topegy, no. So Most humans are probably doing, you know, anywhere between a twelve to sixteen hour nightly fast, right? There's a period of time when we're not eating and that is when we're sleeping a little bit before bed, right?

48:31 Atophagy still happens in people. We just aren't measuring it because we don't have sensitive tools yet. And so It's not that I don't think a 16 hour fast doesn't act. I 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, you know

48:49 Forty eight hour fast, then you're really starting to get more robust activation of autophagy. And I've been looking, trying to look at All sounders from every possible angle and found literature looking at disruption of sleep architecture.

49:07 in patients with Alzheimer's disease. And the possible application Of Zyrem, I believe it is, which is another it's a brand name. in a bifurcated schedule for G H B. 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 G HP overdose.

49:29 But It actually is a tremendously interesting compound for Increasing I think it's it's deep wave sleep specifically, which does what? It helps the cleanup crew. Right, to do its work and to actually take out the garbage cellularly. And so if I could wave a magic wand.

49:49 I would have my relatives on something like Zyram might actually be a different type of of sleep medication, like the Nora class. Um Nora might be Dora. I would also look at And this is something obviously. Not suitable for most elderly people, but potentially

50:07 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 them from a mechanistic perspective, they're they're super, super interesting. So I just want to double click on the sleep because that is such a a critical component, whether you're fasting or not. to try to ensure that your sleep architecture is not

50:34 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.

50:50 Sleep whenever possible. Great. I mean, yeah, so true. The slow wave sleep does. activate the gymphatic system, which is cleaning out the amyloid beta aggregates as well. And the last thing I kinda wanna mention is you were talking about the intermittent fasting and

51:05 more prolonged fasting and the muscle mass loss or lean body mass, which people equate with muscle mass, which it's not. Yeah, there's a lot of things going on. So So the thing is when people are doing intermittent fasting, I mentioned they eat fewer calories, which means they're eating less meals. They're eating fewer meals. They're not eating as many meals. And so what ends up happening is people lower their protein intake. And that's an important signal for, you know, maintaining muscle mass and certainly growing muscle mass as well.

51:31 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 an sixteen eight, where you're fasting for sixteen hours, that's really not a long, long fast. There's not a lot of concern with losing muscle mass if you're you know, resistance training. Now a more prolonged type of fast, you're talking about fourteen days. Yeah. That's a long fast and

52:04 Definitely. you're gonna 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

52:18 muscle protein synthesis through another you know, signal, which is not protein, it's mechanical force, right? So that I think would be really important for preventing the loss of a lot of muscle mass. But what is interesting is that you do lose lean body mass, a lot of it, when you are doing a prolonged fast like that. And looking at you know, the old literature and some of the literature that's been done. A lot of water up to ten pounds of like water weight. It's just crazy. You lose that.

52:47 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 in animal studies. prolonged type of fasting actually causes organs to shrink because a lot of the damage cells not only is autophagy getting activated and you're cleaning out damage within a cell

53:07 But cells that are so damaged that Atophagy can't even fix them. They actually undergo death, cell death. And so you end up getting a lot of cells that die. And then What happens is during the refeeding phase, and this is key, the refeeding phase.

53:23 is the growth phase and this is when you regrow organs. It's when your muscle mass comes back. You can, you know, go back Get your muscle mass gains back. And so having that refeeding phase is really important and getting the right nutrients like protein, for example, is a is key for that refeeding phase. But you also lose fat during that fast and you're losing visceral fat.

53:44 And you had brought this up. last night when we were talking and it was I like did some reading on it'cause 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? I can get misclassified. Exactly. It gets misclassified as lean body mass. And so

54:04 You look at this lean body mass and all you think about is muscle. Well, it turns out Muscle's a small part of that. There's a lot of other stuff that's going into that lean body mass. So yeah. It's a pretty big undertaking at fourteen day fast. But

54:19 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 gonna get the same amount of autophagy that you would get if you did a five day fast. Waterfast. Because

54:37 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 is You want it to be low to activate something called AMP kinase. for autophagy to happen. And so when you're eating when you're eating heavy cream or eating whatever Fill in the blank, any type of calories.

54:59 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 autopogy, depends on how much you're feeding, right? How many calories that you're eating, how much of that is amino acids. And specifically leucine, right? In the case of longo. Like really trying to minimize Lucy and as an activator of MTOR and so on. Yes, exactly. Yeah. So I think for the cream, if you're trying to do sixteen eight, if someone is trying to do sixteen eight on a daily basis and

55:34 It's a non negotiable for having an earlier feeding window because social just everything compliance wise isn't gonna 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, M C T oil, because then you're not getting the amino acids in there. To activate the M Tor.

55:58 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.

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57:24 I also want to clarify for folks listening just to really make it specific. When I have I had d I just like saying dirty fasting. I didn't realize that was an expression. I just think it's some feels it feels fun, like a dirty martini. So dirty fasting is kinda cheating in this way, but when I do that, which is not all the time, I usually have black coffee or tea or something like that.

57:46 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. It's just like liquid fat, effectively. But the MCT powder is a good idea.

58:11 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, etc., to approve long term human studies again in fasting. That would be great. Uh because you used to be allowed to do it. There are case studies of people who literally fast for three hundred 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 um

58:42 We'll see if I do fourteen days. Um If I can do fourteen days then I might just go to thirty, 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 t long period of time.

58:57 Then you're not stimulating the gallbladder and the gallstone. risk increases, which is what I think is the the big concern with the 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 where I'd stand up and I felt like I was gonna fall over

59:26 And uh my you know, vision started to get funny and I was like, you know what? Maybe this isn't for me. But I think it's because my machinery just wasn't developed. for that. having seen really stark differences in

59:43 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.

1:00:03 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.

1:00:21 And then what I've done is like, all right, do the IF, maybe if you have some grains or in my case, legumes and stuff, okay, fine. And then shift to a mostly ketogenic diet. for a period of time. Then I feel like you're pretty well teed up for a longer water only fast. Maybe you supplement with electrolytes. This gets into all sorts of controversial territory. But if you're okay with let's talk about training for a minute because And I'll I'll force a really awkward Segue maybe, which is

1:00:51 One thing I noticed is that my ability to do zone two training. Let's just for simplicity's sake say that for people that's You're on a stationary bike or a bike, stationary is just easier to keep consistent. And you're you're cycling for 60 minutes at a wattage and a speed that leads you to the point where you could have a conversation with someone on the phone. in short full sentences, but you don't really want to, right? That's like the talk test.

1:01:21 Intermittent fasting plus ketosis. really helps by 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 twenty years. Do you want to start there or do you want to start with VO two max? Um we can start with

1:01:40 VO2 Mac maybe because they kind of lead into each other. And people might be you know going, what is VO two max? It's essentially a cardiore respiratory fitness. It's calculated by VO two 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

1:02:04 There have now been enough studies that have come out looking at cardiorrespiratory fitness in the in the sense of VO two max and how people with a higher cardiorrespiratory fitness have a five year increase life expectancy compared to people with a low cardiore respiratory 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 increase life expectancy. And people with a low cardiorespiratory fitness

1:02:30 Actually have higher all cause mortality that's comparable or worse than people with gnome diseases like type two diabetes or cardiovascular disease or Smokers, for example. So in in other words Being sedentary is a disease, and we need to think about it as a disease. And we should be trying to train to improve our VO2 max. And that is something that should be

1:02:54 in our minds. And I say this because like just having this conversation that you and I are having right now, it takes about eleven milliliters of oxygen Per minute. per kilogram body weight, just to have this conversation. Now just sit still and just breathe. It takes about

1:03:10 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.

1:03:27 Everything becomes a maximal effort. Like talking you're out of breath, you know, carrying groceries. to your car from the store, you're just out of breath. Everything is a maximal effort and you don't want to be there. So you 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 wanna s sort of you wanna find A training program that's going to improve that. cardio respiratory fitness.

1:03:51 And that's where You talked about zone two 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

1:04:07 On average, generally people are they're not at like seventy five or eighty percent max heart rate. They're kinda 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.

1:04:35 Physical activity. People that do that for two months. Forty percent of those people still can't improve their VO2 mics. Yeah, yeah. Just different gears. Mm-hmm. Well, unless they actually add in high intensity interval training. Yep.

1:04:48 And that's where I kind of get into this. I think people should be doing vigorous intensity exercise. That's the type of exercise where you're unable to talk. Right. So you you can't have a conversation because you're going you're going harder. your heart rate is about eighty, eighty five percent, you know, it it's above eighty percent max heart rate. That type of exercise has been shown to improve VO two max, especially if you're doing sort of What's called high intensity interval training, as you know, you've you've talked about this a lot as well.

1:05:15 You're doing sort of these intervals of going more vigorous intensity exercise and then you have recovery periods where your heart rate goes down. So there's been a variety of different protocols out there that have been shown to improve the BO two 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.

1:05:40 One of those adaptations is increasing your stroke volume. So being able to like basically transport oxygen to tissues faster. And that's an adaptation that happens when you're going at a harder when you're training at a harder intensity. What do you do personally? What's your hit look like? I do a lot of h 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.

1:06:06 And the high intensity novel training will either be on a rowing machine or it'll be on a stationary bike or a salt bike. Or it'll be like a skier, like those skiers, or jumping rope. And I also do longer intervals, so I'll do the Norwegian four by four. So that's where I do on a stationary bike. Or uh do it on the rowing machine actually as well.

1:06:27 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 thirty second sprint. This is 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

1:07:06 You know, you do that ten times. It's more like a twenty minute workout. That's also been shown to improve BO two max, but also even doing something like twenty seconds on Ten seconds off, like a Tabata. Again, it's been shown. I do all of these, by the way. And I Do variations of them depending on the week.

1:07:22 Most of my my exercise is High intensity interval training, crossfit. training which incorporates you know, it's more dynamic, so it's including like strength training stuff, but it's like more high intensity. And then I do a couple of runs. I do like

1:07:37 You know, two thirty minute runs a week, sometimes three. And that's more of my zone two stuff. That's a nice roster. I'll share just for people who might be curious. Some of my goals and program at the moment. So I'm about to turn forty eight. And uh feel good.

1:07:53 overall, but have realized that I really hate endurance training, generally speaking. So I've neglected that and specifically have neglected the stuff that makes me think I want to puke into a bucket. I. e. VO2 max training. The zone two, it's 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, it's pretty straightforward. VO2 Max. Specifically chatting with Peter T.

1:08:21 I'm doing the zone two, which I do either on a stationary bike or on a treadmill. Typically uh 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 like really long stride with my lower doses and stuff. And then for the VO two 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.

1:08:51 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

1:09:00 Wow, this really sucks. Third minute, you're like I don't know if I I'm gonna make it. I don't think I'm gonna 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 ma like maximal effort. At least as it's been. And those are not Peter's words, but another person I like a lot.

1:09:20 It's a lot of work. Like it's pretty pukey, but I'm gonna be doing that given the longevity. associations that you mentioned. Now I would love just to Get your two cents. And this relates to vitamin D too. A little bit for me where I'm like In these studies looking at VO two max as a predictor or correlate of longevity,

1:09:40 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 the for people listening, it's like okay, well I'll make this up. Like women who do Pilates in Manhattan. Have You know, four years of additional lifespan.

1:09:57 Okay, great. So you could conclude then we should all do Pilates to improve life spends 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 Macs. Studies.

1:10:18 I'm assuming they're observational more than uh 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, you know, yes, they're going in and measuring their cardiovascular fitness, which is

1:10:37 better than a lot of observational studies that are 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

1:10:49 has undiagnosed cancer or some kind of undiagnosed disease because diseases are they 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 the lower cardior respiratory fitness is. There are, you know, studies always try to account for diet and all that stuff, but at the end of the day, you can never really establish causation, right? So that is why we turn to randomized controlled trials. And I will say This is where the heart aging comes in. And also this type of training. So when I've done VO2 Max training.

1:11:33 My legs grow. My legs grow like weeds. Like they adapt and get big. And so along with the age related decrease in VO two 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

1:11:52 Higher VO two max. tend to have a higher percentage. Uh Lean body mass or muscle tissue.

1:12:00 be more heavily muscled than the people without. I don't know. I mean that's just I mean just kinda poking at it out of curiosity. Okay, so the heart aging. This goes into why randomized control trials are important because you can establish more causation, right, from an intervention. And This study was done by Ben Levine out of U T South West and Dallas.

1:12:21 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 Fifty year olds that were sedentary.

1:12:40 The middle age. Fifty 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 two diabetes or hypertension, right? So they were otherwise healthy, just not active. And He wanted to see if he could put these guys on a

1:12:59 Pretty Long two year old. Training protocol. How would that affect the aging of their heart? So as we age, our hearts typically shrink in size.

1:13:11 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.

1:13:38 So this glycation Essentially stiffens the collagen that surrounds your myocardium and your pericardium and so you get like this stiffer heart that can't respond to stress well. So you want your heart to be very plastic and malleable and flexible, right? You don't want it to be stiff.

1:13:55 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 him on a two year training program, which involved Norwegian four by four, by the way. And when you start someone out that's, you know, not physically active and you want them to do the Norwegian four by four, when you have them doing their interval, their four minute interval. And this speaks to you as well or anyone. You don't have to necessarily go as hard as you can the whole four minutes. You just have to be working hard. Yeah, you do have to last four minutes, right? So you have to last four minutes. And so some people even start off, they're just briskly walking.

1:14:37 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, I just there's no way I could ever do that. Well, actually these people did do it and they started out doing Norwegian four by four. But they also did a variety of other exercises, including moderate intensity and some more vigorous intensity exercise, as well as some resistance training. And the control group was just this like yoga flexible training sort of stuff that people were doing. By the end of the two years, these people were working out about five hours a week.

1:15:07 And at some point they were doing two Norwegian four by fours a week and then they went down to just doing one a week. But you know, over the course of two years, they were getting a lot of exercise, about five hours a week. And essentially at the end of those two years, the structure of their heart, so the stiffness of it and the, you know, shrinking of it. was reversed. So their hearts grew and they became More flexible. And it was reversed in such a way that it was Twice. Less aging, so their hearts looked more like thirty year olds.

1:15:37 than fifty year olds, which is pretty incredible. It's amazing. And I think it's also like, well, you think fifty it's too late to start exercising. Well it's not too late. I mean, you can be in your nineties and get benefits, you know. So I think that's another really important take home with that story is that, you know, you can reverse your your aging of your heart by twenty years if you really put in the effort. Five hours a week. is about what I do. I bo I've five or six hours a week. It's a lot of work. I

1:16:03 Didn't always do that, but I've decided as I started to get into my mid forties I'm gonna spend less time podcasting and more time exercising because this is my health. Foundable for everything else. That's the base of the pyramid. Alright, 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 exercise? Is it a different type of exercise or do you get two birds with one stone?

1:16:33 You do get two births 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 to somewhat to anaerobic metabolism. So You're working so hard. That you can't get oxygen to your muscles fast enough to use mitochondria.

1:16:56 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 call 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 a a black or white thing, right? It's there's sort of gray here. But the reality is is that when you're not going intense you're not doing anaerobic exercise. And so what happens is when you're doing that sort of

1:17:27 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 U C 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 point

1:18:00 nine millimolar or so met lactate. You start to go above that and well beyond you're getting seven, ten millimolar, fifteen millimolar, right? Yeah. The lactate gets into your bloodstream And it's used by other tissues. So it goes back into the muscle. It's used for energy, gets into the brain, it gets into the heart, liver quickly. It happens within twenty minutes. You can do a hit workout, see your lactate go up to fifteen millimolar.

1:18:23 measure it twenty 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 a v energetically favorable source of energy, lactate. is used by neurons to make energy, just like beta hydroxybutyrate is very similar. It's energetically favorable. All that stuff is happening, same stuff. So you're using the lactate, glucose is being spared, you're making glutathione. Lactate's also a signaling molecule.

1:18:56 So in the brain it's activating brain drive 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

1:19:16 losing one to two percent of the hippocampus that usually happens as you get in older age. So the lactate is again a 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, you know, time. Let's respond to that stress. Your brain is also working hard during exercise and particularly vigorous intensity exercise. It's stressful in the brain. Anybody that's done it knows it. Resistance training also

1:19:46 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

1:20:05 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.

1:20:29 So let me Ask you about Two other things related to brain health since this is on. On the mind. Ha ha. For the first is related to saunas. And the second one is vitamin D.

1:20:40 So with saunas I was looking back. And I think this is probably Summarized by Some L M, 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 finish study published in Jam Internal Medicine twenty fifteen that followed two thousand middle aged men for twenty years.

1:21:03 That's wild. And it looks like Please correct me if if you're not going to be able to From memory you can correct any of this, but all callers of mortality, twenty four percent lower risk. With two to three times per week.

1:21:16 This is sauna use and four to seven times per week was associated with forty percent lower risk. And I'll just cut to the one that's of greatest interest to me right now. Says in a follow up paper, using the sauna four to seven times per week was associated with a sixty-six percent lower risk of dementia and sixty five percent lower risk of Alzheimer's. Now At face value If those numbers are roughly. Accurate.

1:21:38 Those numbers seem to be a little bit more. Incredible. Right. And I guess what I'm wondering Is how should we

1:21:44 Think about Those results. Because if out of a hundred people Two people were getting dementia and now it's one person. It's less interesting than other ways of interpreting the data. Um, how should we think about this? And

1:21:59 How do you personally Use if you do. sauna or Hot tub or Heat stress at this point.

1:22:09 So those numbers are accurate. By the way. There Spot on. And

1:22:16 There is a dose dependents there, which kind of strengthens the data, right? So people that are using this on a more frequently are having a more robust effect. You mentioned twenty four percent lower all cause mortality, then forty percent If they're doing two to three times. a week versus four to seven times a week they're they're having a forty percent 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 butting young biologist at the Salk Institute, where

1:22:43 I was working with these little nematode Celligan worms. And Injecting human amyloid beta forty two into these worms and essentially injecting it into their muscle so that they become basically the the the amyloid beta forty two aggregates and forms these aggregates as these worms age. And it happens very rapidly because their life expectancy is only fifteen days. So with an like day or so

1:23:09 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 um I would do these experiments and then I would overact. Over basically when you do a genetic manipulation and you can make them over express 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 One hundred and sixty three degree Fahrenheit sauna for around thirty minutes, you can activate your heat shock proteins by fifty percent more than baseline. So when I would add heat shock proteins that would be activated in these worms.

1:23:52 it would prevent this from happening. These protein aggregates don't happen. And that's because one of the things that he chalk proteins do is they help repair damaged proteins that are misfolded and prevent them from aggregating. And so you want to have more active heat shock proteins. if you're wanting to prevent Alzheimer's disease. Now there's a lot of animal studies that have shown this as well. For example, you can take a a mouse and sort of give it Alzheimer's disease in this 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 delay it, right?

1:24:25 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 chuck proteins are activated upon the sauna use that you would probably see a lower incidence of Alzheimer's disease and even dementia. There's other things as well. Cardiovascular health is really improved with the sauna, so sauna sort of mimics moderate intensity exercise. And so you if you're having improved cardiovascular health, that means more blood flow to the brain, lots of things are happening right. The one thing I do wanna mention, Tim, and this is this study was I think it came out in Twenty twenty ish.

1:24:58 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

1:25:12 looked at people that are using saunas, but they also sort of Categorise them based on the amount of heat, so how hot their zona's got. So in the Finnish studies in added phenoline Majority of the people are using the sauna at around equivalent of one hundred and seventy four degrees Fahrenheit. That's about what the average temperature of

1:25:30 pretty much any of those studies that you cited, that's about the average temperature that they're using'em and they're in there For about twenty minutes. Now this other study looked at a wide range of different temperatures. That temperature versus like the really, really high extreme end. So people that were doing like two hundred degrees Fahrenheit. Or more. And this is something that you can see nowadays, like there's this sort of

1:25:50 You know. Go all in, go hard or go home, right? And so people think that they need to go in a two hundred degree sauna. And if they go in a two hundred degree sauna, it's gonna be better than going in a one hundred and seventy five degree Fahrenheit sauna, right? Apparently not the case. So in that study Again, you saw a protective effect of people that use the sauna and I think it was also dose dependent, but I can't recall. There was a protective effect, but only if they used saunas that were less than a hundred and ninety degrees Fahrenheit.

1:26:17 People that started going into the hundred and ninety degrees to two hundred degrees Fahrenheit range. actually had an increased risk. Oh no. And so So that was something that um I don't know that anyone talks about. But I've done really, really hot saunas before. I personally don't like it. I get headaches actually. So, you know, your head is in there and you have to think about that. Your head is getting heated up.

1:26:38 And so I don't know that it's necessarily good to go in a two hundred and twelve degree Fahrenheit sauna. You know, for your head. Now I don't wanna say That was 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 one ninety? One ninety's hot as hell. Like that's good enough. You don't have to go above that. Yeah, my default setting of my song is one ninety four, so it's just kind of like Well, I guess I said it some time ago, so it's just been set at one ninety four. So that's kind of my defense. So maybe I want to dial it back.

1:27:07 I think one ninety's great. Yeah, one ninety's great. And I so you asked about me and w how I use the sauna. Now I should also mention that hot tub are are good as well. And in fact, the study just came out a few weeks ago showing That hot tubs. have you know comparable effects on blood pressure regulation, all these parameters that are

1:27:24 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 a hundred and four degrees Fahrenheit, which is what all the studies use. You have to keep adding hot water. That's fine. It's pretty hot. But you want to stay in there.

1:27:50 Yeah, it's pretty hot. You stay in there for about twenty minutes. And you're gonna have comparable effects. You'll be sweating like you're in a sauna. Don't worry about it. One oh four. Exactly. One oh four 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. I 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 work out. 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.

1:28:21 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 kinda funny. Pretty much the only time I do it is in the summer. Such a was. I like doing the heat.

1:28:35 A lot in the in the winter. I would be very curious. You know, they measured like sperm motility and morphology a lot for all the males who are doing this. And they're like, Good news. You have this incredibly lowered risk of Alzheimer's. Bad news you're effectively sterile from all the heat. On your swimmers.

1:28:55 Good point. You have to yeah, there's been studies that have shown You do lower motility. For sure the mortality rate's lowered and that Those changes are reversed after six weeks of abstaining. So it is reversible. Also don't use it as a

1:29:10 contraception method either because I know some people that have tried that it it doesn't work. You can still get pregnant. Do you still use If needed. curcumin or thericumin or any of these products. I think Mariva or Mariva. was one that you mentioned as a formulation in place of N said like ibuprofen or Naproxin.

1:29:33 Or is that something that you may have changed your mind on? I actually just did it like a couple days ago when I had a headache and I didn't know why. That's the thing that I go to. Still. I mean, there's some cases where it won't work.

1:29:44 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'll get a headache and I use it. I use four Mariva, which is a phytosomal curcumin which increases the bioavailability of the curcumin. I use the Thorn brand just because I I think the brand is reliable, um no affiliation with them. But it It works for me. It really does. So it's I think five hundred milligrams.

1:30:12 Uh curcumin per Capsule, I believe. And so I do four. So I'm getting two grams. Yeah. But I do still use it. Yeah, just don't take it right after your workout, right?

1:30:26 I don't it doesn't have the same effect. Yeah, it doesn't have the same kind of cocks to inhibition as the other guys. It doesn't. Uhhuh. And in fact I think it helps with DOMs to lay down some muscle soreness. And so sometimes actually I do use it actually after really like hard squat work out. All right. Glad I asked. So speaking of not getting enough sleep. Let's hop to creatine.

1:30:49 Because God, I don't know where I read this, but that higher doses of creatine, maybe like twenty five grams, twenty, twenty five grams could combat sleep loss or some of the effects of sleep loss. What should we know about creatine, right? Creatine's been around for a long time. There are Dozens of questionable sports performance, athletic performance products come out every year. Most of them are all marketing, no substance. Creatine. has been used by athletes for a very long time.

1:31:16 But for at least the last. Five years. I have been taking it. Typically five grams a day.

1:31:23 F more for the cognitive Or potential cognitive benefits. Uh, but what el what else should we know about uh 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 should we think about creatine and best practices for different applications?

1:31:43 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.

1:32:00 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 phosphreatine. When you take it creatine exogenously

1:32:14 It's stored in our muscles as phosphorcreotine 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 an extra set or whatever whatever it is you're doing, right? And that leads to obviously if you're Increasing your workload, you're gonna have increased muscle mass and muscle strength because you're increasing your workload. It doesn't work like protein in the sense that You can increase muscle mass because it's anabolic. You need to put the work in. So creatine by itself isn't gonna make your muscles grow. It's gonna make you work harder. It's gonna be easier for you to work harder.

1:32:56 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 that explosive power type of exercise, again, because you're getting that quick mobilization of Producing energy.

1:33:19 And I'm just glossing over decades of research and a lot of specifics here because I want to get to the brain. But It turns out Creatine is something that our liver makes A little bit. I think like maybe one to two grams a day. It's also something that's found in dietary sources, particularly animal products. So it's high in like meat, poultry. Fish dairy.

1:33:39 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

1:34:00 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.

1:34:20 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 twenty five grams. I mean twenty to twenty five grams, which is kind of a crazy study where they you know did about twenty one hours of sleep deprivation essentially. They were barely sleeping at all.

1:34:57 And Giving them the twenty five grams of creatine, twenty to twenty five grams depending on their weight, seemed to n not only negate the negative effects of sleep deprivation on their cognition, but it also improved their cognition beyond what their baseline normal cognition is when they were Sleeping. Um, and that's what was really intriguing to me. As well as some of the other studies where older adults were given, you know, twenty grams of creatine and it improved their cognition. We now have the first pilot study in Alzheimer's disease, where again twenty grams were given to a very small number of people with Alzheimer's disease. It also improved cognition.

1:35:31 It turns out that when you start to go above the five grams And you get into more the ten 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 ten grams a day What I have noticed

1:35:53 Is that The afternoon sleepiness kinda slump I get. is completely gone if I take my ten grams a day. Ten grams, I don't get afternoon sleepiness. I don't I miss it.

1:36:05 I get it. So it's not like a stored up kinda thing. It's like no if I miss it that day It's noticeable. If I travel and I don't have it, it's noticeable. So I'm I'm hooked on the 10 grams a day. If it's placebo, I don't care what works, right? On top of that, what I've also been doing ever since that study came out with the twenty one hours of sleep deprivation. I take about twenty grams of creatine.

1:36:27 when I'm traveling and I have to give a talk or I'm doing a podcast, particularly because oftentimes I'm traveling either to Central Time or to Eastern Time. And I'm, you know, giving a talk early in the morning, which is like six AM my time. I gotta be like on my game. So I take the twenty grains, and I kid you not. It's like You get this brain boost, but without like the caffeine.

1:36:51 It's hard to explain. Creepy, crawly ants on your skin. Right. Without the thing. And and even that, sometimes the caffeine isn't enough. Like if you're really jet lagged, you know, it's just especially if you're going across the. I think some of that is actually a glucose response. But that's a whole separate thing. Like I I using glucometer when I was doing all my ketogenic experiments and so on. I'm like, wow. If I have too much coffee, there is a huge which is not that surprising. spike in glucose and then a very predictable subsequent drop off. So it doesn't end up being net net that helpful for me. Unless I'm doing a twenty minute sprint on something, which is probably never. So the creatine's super interesting to me. Let me ask some very specific

1:37:44 maybe mundane questions, but I think they're When these subjects were taking twenty or twenty five 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?

1:38:07 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 twenty gram, it will be in one sitting. What I do is different. I do five gram doses. So creatine monohydrate is the form I take. It's the Absolute tried and true. It's it's the gold standard. Yeah.

1:38:27 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 Cando 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 s type of you know, creatine under the sun. But The way I take it is in five gram doses. And so I do five grams first thing in the morning and then I'll do my workout.

1:38:54 And then I do another five grams. Tchau. Eleven AM. And that's my ten grams that I get. When I'm traveling, I do have these sachets that Again, Thorn makes, by the way, no affiliation. I mean there's like probably a million other

1:39:06 Yeah, I like Thorn because their creatine is N S F certified and so it's It's free of contaminants. I I really like that. So again, find your own favorite brand, but I like this brand and I like they have sachets, which are five gram sachets. And so I will have my 10 grams for the day. Or again, if I'm traveling for work related purposes, I will take 15 to 20 grams, depending on how much I need. In that case, I will do two ten. gram doses for me I can tolerate that I don't have any GI problems with it. Some people do. Yeah, some people do. I think doing the five gram doses is like pretty easy on the gut. Most people don't have a big problem with the five grams. It's when they go above that.

1:39:46 Yeah. So I'll say a few things. The NSF certified is a pretty simple cheat code. Just to use as a filtering mechanism for a lot of supplements and It is shocking how inconsistent. Supplement contents are. I mean I've looked at lab reviews of like

1:40:02 twenty off the shelf melatonin products and it ranges from zero Melatonin up to like twenty X the Label amount. It's just bananas. So you know, I use momentous creatine, but it's passing the same hurdle.

1:40:17 And I will say the 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 twenty cramps at one sitting. And I will say You know, maybe from personal experience, maybe I'm just talking about somebody else. But

1:40:38 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 M C T powder. And then have your creatine around the same time. That would be asking. You're gonna wanna pack some pamper 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

1:41:02 The science that you cited in uh leave a study. 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 as safe.

1:41:16 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.

1:41:29 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 sulforophane I mangled the pronunciation of it. Sulfurfane. You

1:41:43 Take that. Better on an empty stomach, better with food. This has become an issue w 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

1:42:07 take s supplements earlier in the day that are benefited from some type of Fat. In terms of absorption. So I sulfurophan, uh, does it matter?

1:42:18 I think if you can take it faster, 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

1:42:32 They get like upset stomach. Like it's like Yeah, GI problem. So That would be, again, the only really real reason that you'd 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 wanted to talk about vitamin D. So the vitamin D. I've taken vitamin D forever.

1:42:49 Yeah. Tend to take five thousand I. U a day. I particularly in the summer, get I would say at least an hour in the sun.

1:42:59 Without Skin protection and I build up to that. I'm not an idiot about it. And yet I am barely in my labs, I'm always Barely squeaking by on vitamin D.

1:43:09 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

1:43:31 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't 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.

1:43:53 Please educate me. Yeah. 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 five percent of the protein encoding human genome. Many of these genes, it activates clothho, by the way. You mentioned clothho. Vitamin D is important for activating clothho. Yeah. So

1:44:16 Very hugely important for dementia risk, which we could we can talk about, but To sort of answer your question, so your your vitamin D levels are measured by a proxy and it's called twenty five hydroxy vitamin D, which is the the precursor to the steroid hormone. So essentially vitamin D three, which is made in your skin, or if you supplement with it. exogenously gets into your bloodstream. And that vitamin D three then goes to the liver and it's converted into 25 hydroxyvitamin D. That's the major circulating form of vitamin D. After it's

1:44:47 you know, twenty five hydroxy vitamin D is made in the liver, it then goes to the kidneys and it's made into the actual active steroid hormone, which is called one twenty five hydroxy vitamin D. Well, it turns out the enzymes that are doing the conversion of vitamin D three into that stable form that Everyone gets, you know, when they're getting a vitamin D blood test, that's what they're looking at. Requires magnesium to work. And there have been studies showing that in l with low magnesium It doesn't happen.

1:45:13 Readily at all. And so Fifty percent 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 fifty-fifty chance a person's not gonna be getting enough magnesium. That's been shown to actually play a role in

1:45:29 circulating levels of vitamin D. So there then there have been NHANE studies and stuff showing that people that are that have low magnesium intake also have low Circulating forms of twenty five hydroxy vitamin D. So that's one thing. Another thing comes down to genetics. There's actually a lot of people that have Snips, very common ones that

1:45:48 Probably came from southern areas that don't make as much vitamin D three from the sun exposure. Because probably they're getting so much sun, right? So um essentially There's the genetic component as well. And I've seen a lot of people's different SNP makeups, and I know quite a few people that actually have to take a super high level. a vitamin D three. to actually get

1:46:08 Enough vitamin D. Yeah. 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 D three on the nutrition facts. And then some of them have like ten times as much vitamin D. So there's just like this huge variation where you're like, it says it has five thousand IUs, but it only has five hundred. There's a lot of different factors that could be contributing to that as well.

1:46:40 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 skin 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 ten times as long as a Caucasian to make the same amount of vitamin D three from the same amount of sun exposure. Because they have a natural sunscreen.

1:47:07 You know melanin, which is that Darker. Skin pigmentation. It's a natural you know, sunscreen. It's also why their skin always looks great as they're aging. You're like, Oh, you're seventy five? Your skin looks like you're thirty. Yeah, I remember I won't mention him by name, but meeting this African American fellow. And I thought he was like twenty five and he was fifty three and had like five because and the way we got to that is I was like, Oh, you are you married? And he's like, I have five kids. And I was like, Wait, what? You have five kids? You don't look Mormon. Like, wait, what's going on here? And uh and lo and behold. So let me let me dig into some of this real quick. So

1:47:40 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.

1:47:53 I don't wanna overdose on vitamin D. It seems like there are some risks associated with that. I maybe I'm overstating them. But how would you think about that? And then In terms of this rate limiting factor That you mentioned magnesium. What type of magnesium

1:48:08 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 forty, sixty to eighty, like forty to eighty. nanograms per mil, you're you're in a optimal range. I like forty to sixty. I think that's my sweet spot, and and that's because there's lots of studies out there showing all cause mortality is lower

1:48:34 within that range. So fifty nanograms per mil would be great. I mean that's a great place to be if you're below you know, thirty, if you're about just thirty, you might want to try to get up to forty. So depending on where you are. Let's just say for argument's sake that I'm at thirty. I think I'm probably closer to forty, but let's say Let's say it's thirty.

1:48:54 Okay, for someone that's at thirty Danagrams for mill is supplementing with Five thousand I use a day. Yeah. Or four thousand. I was taken? Yeah, five.

1:49:05 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 laps. I just had'em pulled two weeks ago, so I'll double check. Right. So for someone in that case you might go up

1:49:23 to seven thousand I use. And check and see where you're at. A month later. than or the in the forty to fifty range, then that's your optimal dose to take. And this is a an important conversation to have, Tim, because it really is there's an individual component here and people just wanna at the end of the day, they wanna 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 this is one of those that you have to really measure because as you mentioned, there's huge variation there in terms of

1:49:51 absorption and then the magnesium issue, right? And that's something Again, so People Uh there's there's the R D A for magnesium, right? So for men it's about four hundred milligrams a day for women.

1:50:04 It's about three hundred 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 ten to twenty percent depending on how physic you are. If you're like the endurance athlete, you're on the twenty percent higher, you know, range. If you're more just like the average, like I'm a committed exerciser. Then you might have to go up Ten percent above that. So

1:50:30 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

1:50:57 Dose range. you know, you can take three hundred milligrams a day and probably not have any GI distress. And so that gets you most of the way there, and then you get the rest from your diet, right? You're eating some leafy greens, you're eating maybe some almonds or something, which are really high in in magnesium. If you're not getting any greens at all, then you're gonna have to go up a little bit more to the four hundred, four hundred and fifty milligram range, especially if you're if you're athletic. Yeah, but that if you're taking something like um electrolytes You're getting some magnesium there, so you can figure out how much magnesium's in your electrolyte and that's that can be counted towards it as well.

1:51:33 There's also magnesium three and eight, which is the Magnesium form that is Allegedly able to cross the blood brain barrier better. then

1:51:45 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 three and eight supplement. So that's always important to keep in mind. But they have shown that magnesium three and eight could improve some cognitive scores if you kinda pulled all the cognitive scores together. And so I think that there's no reason why if you're interested in

1:52:11 Cognition and stuff, trying the magnesium three and A. A lot of people like it. Yeah. As well. So that's another form of magnesium. Although I do think you should probably take some magnesium glycinate along with that because you don't want all the magnesium going into your brain. You want some of it going into your liver and activating the, you know, enzymes that are converting vitamin D three into twenty five hydroxy vitamin D, right? So So that is something to keep in mind if that form of magnesium indeed is so

1:52:35 you know, is going into the brain more, you wanna make sure you're getting some of the other forms to 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 Thorn or are they other suppliers? I use pure encapsulations for the vitamin D. Um some I have some friends, um mutual friends of ours that like The Vesi Sorb vitamin D three. So

1:53:03 People that are not able to increase their vitamin D as well. Bessie Sorb really increases the bioavailability of a lot of things, including ubiquinol, the coquet I mentioned. There's a I should have mentioned that I buy my dad. That's the form I I get for him because it increases the bioavailability. Also some fish oil that's been shown to increase the bioavailability. So Vestis Sorb vitamin D3 can be found up here 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 three and a I use Zymogen.

1:53:36 I like the Zymogen Magnesium three and eight. Great. All right. Thank you. I will get on the magnesium and I'll also check my last labs. I mean I am very Bespoke about this stuff and to your point, you gotta check your levels, guys. You can't just be shooting in the dark here. It's not a good idea. Right. All right. Where should we zig in zag to next? Do you want to talk about microplastics and Mitigation strategies?

1:54:02 It's really a big mess and The microplastics are now it's not just Okay, well I'm not gonna drink out of bottled water, plastic bottled water, 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'cause it filters 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

1:54:30 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.

1:54:40 It's not the same, I'll tell you that. But um 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 microplastics into your beverage. They're in essentially everything. And the problem is that it's very hard to avoid. The best things that you can do to avoid them is reduced exposure, which would be the water filter. Uh try to avoid drinking out of any type of, you know, water that's in a plastic bottle. But it turns out a new study just came out showing it's also been found in glass bottles. And the reason for that

1:55:13 I know, I know. It's like, are you kidding me? Come on. Um 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

1:55:32 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 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.

1:55:52 You actually excrete it through feces. And so I think the next study that's gonna be done will be show this. Essentially, I'm sort of speculating here, but because the size matters, the size of plastics and 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 and 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 a one of those sensational headlines. The devil's in the details, right? There's always like a nuance there. And in this case. In this case size matters. This 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 a

1:56:37 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 this Electrophoresis sort of thing where you kind of filter your blood.

1:56:58 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 gonna do. And I don't even know that I'm gonna do it. Yeah, it's it's also even if they were going to do it, it or willing to do it, it's not readily accessible or Cost effective for people. to use.

1:57:18 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 you know, through your sink does have microplastics in it and that's a major, major source of micropl microplastic exposure for many, many many people. So if you can get any type of water filter, again, you can even get

1:57:42 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.

1:58:01 It's not clear about like The nano nano like 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 the thing with reverse osmosis is it's really filtering out all like even the nanoplastics as well. Of course you have to consider like re-adding like certain minerals and trace elements that are found in water.

1:58:24 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 filter 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. Yeah.

1:58:43 Um, the other thing I do want to mention is that the plastic associated chemicals are another concern, and that would be like the BPA, BPS. These chemicals are endocrine disruptors. They disrupt hormones. They're also associated with, you know, Alzheimer's disease or associated with cancer, all sorts of things, right? And those can actually

1:59:03 I think actu uh this is the a a big speculation on my part just based on Animal studies, I think sulfurophane plays a role in detoxing BPA From our system. And that's because of the whole situation where it it activates the very same enzymes that do excrete BPA through urine. It does that and it's been um it's been shown in animal studies animal studies that are given sulfurphane and then given a high dose of BPA, it completely blunts the toxicity.

1:59:30 of the BPA, which is pretty interesting as well. So The other thing to keep in mind is heat, and this I'll say this. All the to go cups. that you're out there buying when you go to a c your favorite coffee shop, fill in the blank for the most part, with the exception of the blue bottle. Phenomenal.

1:59:46 They're great. All these paper cups are lined with plastic. And when you add a hot beverage into the plastic Lining it br it releases like all these microplastics into your beverage and it releases the chemicals like BPA into them like fifty fold. Blue bottle coffee, by the way. They apparently line their cups with sugar cane.

2:00:04 Polylactic acid. And And so they don't have any plastic. I remember the other day I went into a blue bottle coffee shop and I was like, I really wanted to get a hot tea and I was like, you know, do you guys line your cups with plastic? And she's like, No, we line them with sugarcane. I was like, Yes. So that's something to keep in mind. You see a lot of people drinking these to go cups everywhere. And it's 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. He accelerates the breakdown of the plastic and essentially You're doing that in real time, like in an instant, right? Right.

2:00:35 Bring your own cup. The tea bags, right. So And the tea bag. 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 have m I bring my own little tea

2:00:48 Steeper thing with me. Exactly. Mine are the ones that like you kinda 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 to break down the plastic. So you're drinking You know, plastic beverage, right? There's all these health consequences now associated with microplastics. You mentioned the brain. It's been found like twenty times to accumulate twenty times more in the brain than in other organs. And people with Alzheimer's disease have

2:01:22 up to twenty 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.

2:01:41 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 en enough said, we do know that they're not good and we want to try to avoid them as much as we can and that they are pervasive. They're everywhere, right? It's ubiquitous. Yeah, and there's some simple things people can do. I mean, this is not necessarily in the same category, but it's it's like look. The effects At least

2:02:06 Seem to be a little bit more than a little bit. 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. Yeah. And it's like look.

2:02:23 If you have shampoo or soap with a really strong fragrance, just stay away from it. I mean, they're like very simple guidelines. For Some of these things that I think can be very helpful. Yeah, the the microplastic stuff is kind of terrifying. I did not realize the gum. I knew about the tea bags. The water filtration. Did not realize the gum. I don't chew a lot of gum. But

2:02:45 One of my relatives who has Alzheimer's has chewed like four packs of gum a day. Four. Ten years. And I was like, Oh shit.

2:02:54 I wonder if that's a contributor. Wow, that's crazy. I started chewing gum when I learned about the research showing that xylitol could You know, inhibit some of the S mutagens bacteria that are involved in cavity formation. 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

2:03:20 It was like this year I found this out, Tim, this year the study came out with a gum. And I was devastated. I mean, I've chew so much gum, so much gum. And I've I've let my child chew it and it's like all I could think about was how great it was for the teeth and And now it's like oh my god, this has like been a source of microplastics that I had no idea. I did thankfully find an alternative xylitol source of gum that is microplastic free. But yeah, chewing on bark. It's pretty much spark. It's actually made from bark. No, it's made from like trees like some kind of sap or something from the bar. Yeah. Sounds delicious. You can't just do xylitol mints, you have to chew it. I guess you have to get it on the case. You can do xylitol mints. Yeah, you can do other telemets. I have those as well. Well, you know

2:04:12 Just to on the same thread of you know, you don't always get it right, completely right. I was looking at the some of the research doc that I have in front of me. And uh there's there's one section that's I highlighted, which was each three hour increase in nighttime fasting was linked to twenty percent lower odds of elevated hemoglobin A1 C, right? This long term 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 said 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

2:05:03 It's like you know, you're not gonna always get it right. But let's let's talk about do you wanna talk about the booze? For a second? So alcohol, yeah, and especially since we were talking to you. I know it's like any enjoyment at all if you want to live a long, healthy life. No, you need to you need to find a good balance, obviously. So Alcohol is

2:05:29 It's a toxin. It's also a lot of fun. Right. I mean it's fun to to To drink and Have a glass of wine. Sometimes it helps kind of it feels like you're lowering your stress, lowering some inhibitions. Um it's fun to do with a group of friends and stuff. It's not so great for the brain, though. And and certainly

2:05:48 If you're concerned about Alzheimer's disease and dementia risk in 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 you know, this idea that alcohol, like a glass of wine a day is actually beneficial for you. So you can 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.

2:06:24 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-Apo E4 carriers, like you would find that benefit, not in the Apewe four carriers. And then on top of that,

2:06:40 There's been all this research that you know, over the years has looked at moderate alcohol consumption and depending on the study, that number changes, which is such a big bummer. It's like well, what does that even mean? In some cases it can be s you know, seven Drinks a day. In some cases. Seven drinks a day. Sorry. A week. Oh my gosh. No. Some in some cases it's seven drinks a day a week for a woman.

2:07:03 But for a man it's like fourteen drinks a week. Wonder who authored that study. Big yeah, exactly. It's a big difference. Um but on average, like moderate alcohol consumption is more like a seven drinks a week. Seven drinks a day would definitely be heavy alcohol consumption. That would be You know, it's a good thing. 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 the other thing.

2:07:32 Do you know what are the reas what why what are the reasons behind this? Do you know? I guess it's I'm part of all this psychedelic stuff. And it was like abuse for a long time and then all of a sudden Nope. Forboten.

2:07:45 Can't say that. Who knows? It's anyway. It's funny. I I still like read so much of the literature that I still say abuse because that's what I'm familiar reading. But anyways, back to this what I was saying, which is seven weeks. Sorry. All right, we're gonna cut this out, Jim. Seven drinks a week. How many drinks have you had before this podcast, Randa?

2:08:05 Well I did have some ketone ester, or there's a little bit of alcohol that like is involved with that. Yeah. Yeah, watch out for the the one one three butan dial anyway. Right. There's something called the sick quitter. hypothesis which is

2:08:24 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. Which is essentially. Someone gets sick. Oh six quitter. I got it. Sick quitter.

2:08:45 Quitter, yes. So essentially what it means is They get sick. And so they quit drinking alcohol. And then when they're filling out their questionnaire You know, however many years later

2:08:58 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. Prior drinking habit.

2:09:08 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

2:09:20 It's very possible when you're looking at these, you know, cohorts of people that are comparing moderate alcohol consumption to you know, no alcohol consumption, they're saying, Oh, look at 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

2:09:47 In the non dr in the non-drinker. In the supposed non drinker. 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?

2:10:02 Alcohol is now classified as a I think it's a is it a group one carcinogen? It's known to play a role in causing cancer. Um there's no gray area here. And there's many, many different cancers that it's associated with. So alcohol does get metabolized into acetylaldehyde. That is something that. Can be a mutagen. It is a mutagen.

2:10:25 Can cause cancer, right? Um and so There's a lot of different cancers is 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.

2:10:52 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, right? Um, so I do think that alcohol, I mean, obviously like Some people

2:11:08 Enjoy it and I don't know that there's any amount that's actually safe. But If you're really like looking for a number, it seems like one or two drinks a week seems to be the safe spot. I mean the safest would be zero.

2:11:23 zero drinks. But like if you're really not wanting to have the damage, um the light drinking, which is like the one to two drinks a week, that's where you're probably the best off Talking about a weekend, right? You have a weekend and you're doing like a glass of wine maybe Friday or Saturday night. That's the safest if you're looking for like some alcohol consumption. If you're going above that, just be aware there is definitely a risk of Increasing dementia, increasing cancer risk. However There are other lifestyle factors that also play a role here, like being obese and exercise. In fact, there's some of the exercise some of the alcohol

2:11:57 And dementia. studies that have shown an increase in dementia incidents 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 thing. Well, let me ask you, what is the Purported mechanism. Maybe it's known.

2:12:19 By which Alcohol increases The Likelihood. that you will experience some of these maladies like cancer.

2:12:29 Dementia. Et cetera. Is it acting as a acetyl aldehyde 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

2:12:57 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 you know, activate inflammation is a major major cause of cancer and also brain aging. So The brain aging aspect is definitely linked to the oxidative stress component and the inflammation component. Damage is happening to neurons and I think You know, one of the reasons why people with ApoE4 are a little more sensitive to alcohol is because

2:13:30 Yeah. the repair processes in individuals with APOE four 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 eight point four somewhat can repair it a little bit better. And then you add the breakdown of the blood brain barrier on top of that and then you're just getting more inflammation into the brain. And Neuroinflammation is a major cause in Alzheimer's disease. I mean, it's really a known factor now. And you're disrupting mitochondria, you're disrupting other just everything you know about to be important for health.

2:14:02 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 you know, sometimes I go several months without having to I do, so I'm not like I'm not putting you on the stand here. Um drink all the time, but I'm just I'm just giving you a little leeway. Yeah, I used to drink like at least, you know, a couple times a week.

2:14:23 You know where I would do like the weekend thing? But um I don't drink Much. Anymore. Once in a while I'll have like a glass of proseco for a celebration. I do enjoy it. But I definitely try to limit it to

2:14:36 Certainly once a week, but like I said These days I I'll go like You know, a couple of months without having anything and then I'll have a social situation where I like to do it, and the great thing about that is I'm so sensitive to the alcohol. that I'm such a lightweight and it's great because I I get like one glass of prosecco and I'm like, this is amazing.

2:14:57 I forgot to mention with respect to the dementia risk and 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. Massa. 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.

2:15:22 But it completely disrupts. So they have more waken 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 wanna kinda be able to Get rid of the alcohol before you go to sleep.

2:15:39 Going back to your picture, you were doing everything wrong, but Oh, that was yeah, am I doing it right? Yeah, that was very much deliberate. Rhonda, one thing, and I'm so curious if maybe You've heard reports of this. I can ask my audience and figure it out. Wasn't placebo effect because I didn't expect it, but it seems like

2:15:59 when in ketosis like past one point five millimolars, even above like one point two for me, and I use a precision extra device to Track that. I've tried a number of other devices that are Remarkably. Erratic. I am much more sensitive to alcohol.

2:16:16 Much, much, much, much, much more sensitive to alcohol, which is great. 'Cause 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

2:16:39 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 kinda how I operate. These days, but the Ketosis seems to sensitize me.

2:16:54 Which is I thought was pretty interesting. Um I hadn't noticed that before. when I was in ketosis probably because I wasn't drinking during those periods. But on the Cetamine. Substitute, right? Oh this is What I'm using now.

2:17:09 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

2:17:24 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.

2:17:40 Or I mean smoking's a whole different kettle of fish that we could unpack some other time. Lung cancer less interesting. There is the

2:17:51 As compared to what When people find another coping mechanism. So I just wanted to throw that out there as just another question that I think is is worth people asking. If they're going to abandon something, that's great. If you can just delete it without replacing it with something, but if there is a substitute. If there is an alternative or something that you may end up

2:18:13 adding to your behavior or your consumption just to be aware. Of that. Because you have to measure A versus B, not just A. versus lack of A. Just wanted to throw that out there. I've seen so many people unravel from ketamine that it's I I feel a moral responsibility to mention it because it it can be so, so incredibly addictive. Fast acting.

2:18:32 Short duration. even though it is very successfully used to treat, say, treatment resistant depression when it's administered in a clinic at r reasonably higher doses. For Let's just say six infusions over two weeks, something like that. John Crystal Yell's done a lot of great research and his teams and co-authors. used recreationally actually increases.

2:18:53 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 in in more than one study. Oh yeah.

2:19:10 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, this l like last two weeks or something showing is the animal study that psilocybin

2:19:26 Increased life expectancy by almost twenty percent in mice. Yeah, I saw that. And that was I think that was out of Emery. Am I making that up? I think it was out of Emery. 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

2:19:45 milligrams of psilocybin to these rats or mice. And I'm gonna mess up the numbers a little bit, but I was like, wait a second,'cause I've funded a lot of the science and for humans. Or walking around it. one let's just call it whatever, one twenty five to two hundred pounds. It's twenty five to thirty milligrams. So

2:20:07 on a like Migs for kicks basis. Are those rats getting like the equivalent of three hundred dried grams of mushrooms? Uh 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. Um, but it's still non-trivial. Like I I do think those uh those little furry friends are probably tripping balls. Because all of the the I do think the life extension stuff is interesting. And I would say just anecdotally looking at people who have consumed.

2:20:39 in South America, ayahuasca for decades. Like they are Can't prove cause and effect, but almost always sharper than the rest of the people in their age cohort. Almost always. Which is interesting. I mean there raises more questions than it provides answers. But the the life extension stuff is interesting and I've been funding some science that Chuck Nichols is doing.

2:21:00 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.

2:21:20 You do not need any Hallucination, any sort of reality distortion to achieve the anti inflammatory effects. So like a microdosing. Yeah, I mean but even even less than what someone would consider a microdose, like a a nanodose. It's remarkable. And part of my reason for looking at like the fasting, the ketogenic diet. Also looking at Cold exposure.

2:21:45 And most recently, this is a whole separate topic, obviously for another time. I'll be having a a scientist on this podcast soon. Super credible, very, very well cited to talk about vagus nerve stimulation. But when you look at how fasting, right? We I was talking about this old Soviet work looking at schizophrenia. Okay, interesting. ketosis for

2:22:08 Epilepsy and also all sorts of Psychiatric. conditions but also things like potentially rheumatoid arthritis. Or

2:22:18 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

2:22:34 Largely I don't think it's a trivial piece of the puzzle mediated by anti inflammatory effects. Address synchronic. Inflammation, including neuroinflammation.

2:22:43 Totally. And so Las you said, right, if you're If you're if you're chronically suffering from neuroinflammation, does not bode well for later life with Alzheimer's and Parkinson's and things like this. So I'm trying to throw everything the Sort of the kitchen sink. at this to see what these subjective and then measurable objective

2:23:03 effects are. So it's like okay, if I did intermittent fasting and I'm doing then cold exposure. During the by the way, past a certain point does seem to Shift from sympathetic to parasympathetic activation. particularly with certain breathing patterns. It's like okay, if I did that during

2:23:19 The intermittent fast. I'm taking the sulfurphane. 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.

2:23:34 I don't think I'd do a seven day every quarter that probably once a year, but just looking at like okay. And then like the Kircuman, right? All right. Can we throw If we threw or five.

2:23:45 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?

2:23:59 So I'd like to do and for 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, R where can people find you?

2:24:22 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, it's called Found My Fitness. You can also just search Rhonda Patrick.

2:24:35 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, found my fitness dot com. You can find all my stuff there. You can follow me on Twitter or sorry, X. And also and I still do it. I still do it. You can follow me on X or Instagram, found my fitness. All one word or look, just search my name, Dr. Ronda Patrick. And you have a newsletter. I have a newsletter. Yeah. I send out a weekly email that covers

2:25:03 Some fascinating new either science, health, fitness, nutrition related study and usually it's applicable. Sometimes it's something that's misunderstood in the in the in the media. And uh break it down every week. I I sent you the creatine one. You know, we covered a vitamin D, dementia one as well. I mean, a lot of different fascinating studies. So you can again find that on my website, foundmyfitness.com. You can sign up for the newsletter there.

2:25:28 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 timeline has just been wild to look back and I'm like wow, April twenty fourteen. talking about the stuff that now all the fitness influencers are Ranting and raving about.

2:25:54 Today in twenty twenty five. It's like yeah, you called. You've called a lot of things early. And I appreciate your ability to Simplify without Mangling.

2:26:07 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.

2:26:24 And translate it. Without mistransing it. into something that they can test. With limited downside and plausible or supported upside. I just think it's it's such a tremendous service. So

2:26:38 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 you've got great, insightful, thoughtful questions and I've read your books. So I appreciate all you do. So the feelings mutual and I'm glad we get to still have conversations over ten years later. I know, I know. I just I love it. Yeah.

2:27:01 The long game. It's fun to play the long game. So nice to see you, Rhonda. Everyone, we will put links to everything, Rhonda Patrick, in the show notes. Check her out. You will not be disappointed. And as always. Until next time. Be just a bit kinder than is necessary to others, but also to yourself. And Thank you for tuning in.

2:27:25 Hey guys, this is Tim again, just one more thing before you take off, and that is Five Bullet Friday. Would you enjoy getting a short email from me every Friday that provides a little fun before the weekend? Between one and a half and two million people subscribe to my free newsletter, my super short newsletter called Five Bullet Friday. Easy to sign up, easy to cancel. It is basically a half page that I send out every Friday to share the coolest things I've found or discovered or have started exploring over that week. It's kinda 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. 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 slash Friday. Type that into your browser. Tim.blog slash.

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