{"id":11250,"date":"2025-07-27T17:59:53","date_gmt":"2025-07-27T21:59:53","guid":{"rendered":"http:\/\/parmaks.com\/Resources\/the-tim-ferriss-show-transcripts-rhonda-patrick-ph-d-protocols-for-fasting-lowering-dementia-risk-reversing-heart-aging-using-sauna-for-longevity-hotter-is-not-better-and-a-few-supp\/"},"modified":"2025-07-27T17:59:53","modified_gmt":"2025-07-27T21:59:53","slug":"the-tim-ferriss-show-transcripts-rhonda-patrick-ph-d-protocols-for-fasting-lowering-dementia-risk-reversing-heart-aging-using-sauna-for-longevity-hotter-is-not-better-and-a-few-supp","status":"publish","type":"post","link":"https:\/\/parmaks.com\/Resources\/the-tim-ferriss-show-transcripts-rhonda-patrick-ph-d-protocols-for-fasting-lowering-dementia-risk-reversing-heart-aging-using-sauna-for-longevity-hotter-is-not-better-and-a-few-supp\/","title":{"rendered":"The Tim Ferriss Show Transcripts: Rhonda Patrick, Ph.D. \u2014 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 (#819)"},"content":{"rendered":"<p> <a href=\"https:\/\/hop.clickbank.net\/?affiliate=infohatch&amp;vendor=J1R2C\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-10614 aligncenter\" src=\"http:\/\/parmaks.com\/Resources\/wp-content\/uploads\/2025\/05\/profit-gen400px.png\" alt=\"Profit Gen\" width=\"400\" height=\"217\" srcset=\"https:\/\/parmaks.com\/Resources\/wp-content\/uploads\/2025\/05\/profit-gen400px.png 400w, https:\/\/parmaks.com\/Resources\/wp-content\/uploads\/2025\/05\/profit-gen400px-300x163.png 300w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/a><br \/>\n<\/p>\n<div>\n<p>Please enjoy this transcript of <a href=\"https:\/\/tim.blog\/2025\/07\/24\/dr-rhonda-patrick\/\">my interview with Rhonda Patrick, Ph.D.<\/a> (<a target=\"_blank\" href=\"https:\/\/x.com\/foundmyfitness\">@foundmyfitness<\/a>), a biomedical scientist and the founder of <a target=\"_blank\" href=\"https:\/\/www.foundmyfitness.com\/\"><strong>FoundMyFitness<\/strong><\/a>, a platform dedicated to delivering rigorous, evidence-based insights on improving healthspan and mitigating age-related diseases. Through her podcast, website, and YouTube channel, reaching millions globally, she translates complex science into actionable strategies for metabolic health, brain aging, and overall improved healthspan.<\/p>\n<p>Dr. Patrick\u2019s research explores genetic determinants of nutritional response, metabolic health, micronutrient deficiencies, sleep biology, and hormetic stressors, such as exercise, heat, cold exposure, fasting, and phytochemicals. 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 <em>Nature Cell Biology<\/em>, <em>The FASEB Journal<\/em>, and <em>Experimental Gerontology<\/em>.<\/p>\n<p>By uniting scientific integrity with protocol-driven precision, Dr. Patrick equips individuals and organizations alike with practical, scientifically sound strategies for optimizing health and longevity.<\/p>\n<p>Transcripts may contain a few typos. With many episodes lasting 2+ hours, it can be difficult to catch minor errors. Enjoy!<\/p>\n<p><strong>Listen to the episode on\u00a0<a target=\"_blank\" href=\"https:\/\/podcasts.apple.com\/us\/podcast\/819-rhonda-patrick-ph-d-protocols-for-fasting-lowering\/id863897795?i=1000718736625\">Apple Podcasts<\/a>,\u00a0<a target=\"_blank\" href=\"https:\/\/open.spotify.com\/episode\/6NiKaEotfTKlZIGj4GR7M8?si=d4SzAvm9Rk2MmH9bJrr6tQ\">Spotify<\/a>,\u00a0<a href=\"https:\/\/overcast.fm\/+AAKebvPI7t8\" target=\"_blank\" rel=\"noreferrer noopener\">Overcast<\/a>,\u00a0<a href=\"https:\/\/podcastaddict.com\/podcast\/2031148#\" target=\"_blank\" rel=\"noreferrer noopener\">Podcast Addict<\/a>,\u00a0<a href=\"https:\/\/pca.st\/timferriss\" target=\"_blank\" rel=\"noreferrer noopener\">Pocket Casts<\/a>,\u00a0<a href=\"https:\/\/castbox.fm\/channel\/id1059468?country=us\" target=\"_blank\" rel=\"noreferrer noopener\">Castbox<\/a>,\u00a0<a target=\"_blank\" href=\"https:\/\/music.youtube.com\/playlist?list=PLuu6fDad2eJyWPm9dQfuorm2uuYHBZDCB\">YouTube Music<\/a>,\u00a0<a href=\"https:\/\/music.amazon.com\/podcasts\/9814f3cc-1dc5-4003-b816-44a8eb6bf666\/the-tim-ferriss-show\" target=\"_blank\" rel=\"noreferrer noopener\">Amazon Music<\/a>,\u00a0<a href=\"https:\/\/www.audible.com\/podcast\/The-Tim-Ferriss-Show\/B08K58QX5W\" target=\"_blank\" rel=\"noreferrer noopener\">Audible<\/a>, or on your favorite podcast platform. You can <a target=\"_blank\" href=\"https:\/\/youtu.be\/T2FV1Ir344A\">watch my interview with Rhonda on YouTube<\/a>. <\/strong><\/p>\n<div class=\"wp-block-tim-podcast-link-main podcast-block wp-embed-aspect-16-9 wp-has-aspect-ratio\"><a class=\"podcast-block__link\" target=\"_blank\" rel=\"noopener noreferrer\" href=\"https:\/\/podcasts.apple.com\/us\/podcast\/819-rhonda-patrick-ph-d-protocols-for-fasting-lowering\/id863897795?i=1000718736625\"><img data-recalc-dims=\"1\" decoding=\"async\" class=\"podcast-block__link-icon\" src=\"https:\/\/i0.wp.com\/tim.blog\/wp-content\/themes\/timferriss\/inc\/blocks\/podcast-link\/images\/apple-podcast.png?ssl=1\"\/><noscript><img data-recalc-dims=\"1\" decoding=\"async\" src=\"https:\/\/i0.wp.com\/tim.blog\/wp-content\/themes\/timferriss\/inc\/blocks\/podcast-link\/images\/apple-podcast.png?ssl=1\" class=\"podcast-block__link-icon\"\/><\/noscript><span class=\"podcast-block__link-text-top\">Listen on<\/span><span class=\"podcast-block__link-text\">Apple Podcasts<\/span><\/a><\/div>\n<div class=\"wp-block-tim-podcast-link-main podcast-block wp-embed-aspect-16-9 wp-has-aspect-ratio\"><a class=\"podcast-block__link\" target=\"_blank\" rel=\"noopener noreferrer\" href=\"https:\/\/open.spotify.com\/episode\/6NiKaEotfTKlZIGj4GR7M8?si=d4SzAvm9Rk2MmH9bJrr6tQ\"><img loading=\"lazy\" width=\"35\" height=\"35\" decoding=\"async\" class=\"podcast-block__link-icon\" src=\"https:\/\/tim.blog\/wp-content\/themes\/timferriss\/inc\/blocks\/podcast-link\/images\/spotify.svg\"\/><noscript><img loading=\"lazy\" width=\"35\" height=\"35\" decoding=\"async\" src=\"https:\/\/tim.blog\/wp-content\/themes\/timferriss\/inc\/blocks\/podcast-link\/images\/spotify.svg\" class=\"podcast-block__link-icon\"\/><\/noscript><span class=\"podcast-block__link-text-top\">Listen on<\/span><span class=\"podcast-block__link-text\">Spotify<\/span><\/a><\/div>\n<div class=\"wp-block-tim-podcast-link-main podcast-block wp-embed-aspect-16-9 wp-has-aspect-ratio\"><a class=\"podcast-block__link\" target=\"_blank\" rel=\"noopener noreferrer\" href=\"https:\/\/overcast.fm\/+AAKebvPI7t8\"><img loading=\"lazy\" width=\"1000\" height=\"1000\" decoding=\"async\" class=\"podcast-block__link-icon\" src=\"https:\/\/tim.blog\/wp-content\/themes\/timferriss\/inc\/blocks\/podcast-link\/images\/overcast.svg\"\/><noscript><img loading=\"lazy\" width=\"1000\" height=\"1000\" decoding=\"async\" src=\"https:\/\/tim.blog\/wp-content\/themes\/timferriss\/inc\/blocks\/podcast-link\/images\/overcast.svg\" class=\"podcast-block__link-icon\"\/><\/noscript><span class=\"podcast-block__link-text-top\">Listen on<\/span><span class=\"podcast-block__link-text\">Overcast<\/span><\/a><\/div>\n<div class=\"podcast-player\">\n<div class=\"podcast-player-inner-wrap\">\n<p>Rhonda Patrick, Ph.D. \u2014 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<\/p>\n<p><noscript><iframe src=\"https:\/\/www.art19.com\/shows\/58dacbdc-646e-4585-9914-19c3de11d1ba\/episodes\/66e28d66-ac6a-49ea-a972-f370f388a90d\/embed?type=micro\" style=\"width: 100%; height: 30px; border: 0 none;\" scrolling=\"no\"><\/iframe><\/noscript><\/div>\n<\/div>\n<blockquote class=\"wp-block-quote is-layout-flow wp-block-quote-is-layout-flow\">\n<p><em>DUE TO SOME HEADACHES IN THE PAST, PLEASE NOTE LEGAL CONDITIONS: <\/em><\/p>\n<p><em>Tim Ferriss owns the copyright in and to all content in and transcripts of The Tim Ferriss Show podcast, with all rights reserved, as well as his right of publicity. <\/em><\/p>\n<p><em>WHAT YOU\u2019RE WELCOME TO DO:<\/em> <em>You are welcome to share the below transcript (up to 500 words but not more) in media articles (e.g., <\/em>The New York Times<em>, <\/em>LA Times<em>, <\/em>The Guardian<em>), on your personal website, in a non-commercial article or blog post (e.g., Medium), and\/or on a personal social media account for non-commercial purposes, provided that you include attribution to \u201cThe Tim Ferriss Show\u201d and link back to the tim.blog\/podcast URL. For the sake of clarity, media outlets with advertising models are permitted to use excerpts from the transcript per the above.<\/em> <\/p>\n<p><em>WHAT IS NOT ALLOWED:<\/em> <em>No one is authorized to copy any portion of the podcast content or use Tim Ferriss\u2019 name, image or likeness for any commercial purpose or use, including without limitation inclusion in any books, e-books, book summaries or synopses, or on a commercial website or social media site (e.g., Facebook, Twitter, Instagram, etc.) that offers or promotes your or another\u2019s products or services. For the sake of clarity, media outlets are permitted to use photos of Tim Ferriss from <\/em><a href=\"https:\/\/tim.blog\/media\/\" target=\"_blank\" rel=\"noreferrer noopener\"><em>the media room on tim.blog<\/em><\/a><em> or (obviously) license photos of Tim Ferriss from Getty Images, etc.<\/em><\/p>\n<\/blockquote>\n<hr class=\"wp-block-separator has-alpha-channel-opacity\"\/>\n<p><strong>Tim Ferriss: <\/strong>Rhonda, it is very nice to see you again. Thanks for \u2014\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Likewise.<\/p>\n<p><strong>Tim Ferriss: <\/strong>\u2014 making the time.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, I\u2019m excited to be here.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. I was going back through the archives, doing my homework as I always do, looking at our past conversations. And it was such a trip down memory lane because our first podcast together was podcast number 12 of <em>The Tim Ferriss Show<\/em>, which was in June of 2014. And then preceding that by a few months, April 2014 was when you had a guest post on my blog called \u201cAre Saunas the Next Big Performance Enhancing Drug?\u201d So well done. That\u2019s become quite the topic.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I know. I like to take a little bit of that claim to making saunas popular.<\/p>\n<p><strong>Tim Ferriss: <\/strong>The godmother, the fairy godmother of heat shock proteins, the context of saunas. And we are going to run out of time before we run out of topics or questions, as always. And what\u2019s so fun about having a conversation with someone like you who is not only very scientifically credible and literate, but who\u2019s actively involved with the science, tracking the science, and have published, is that there\u2019s 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\u2019re 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\u2019s coming. We may not cover it all, but if you\u2019ll bear with me, Rhonda, I\u2019m just going to read some of these because it\u2019s great. How to increase VO2 max and why you should. Looking at VO2 max as a predictor of longevity with high intensity interval training. What type of exercise reduces heart aging by 20 years? Brain aging in the same context or reversing brain aging. The benefits of exercise snacks on glucose regulation and mitochondrial function. We\u2019re going to get a lot because this is something that is a perennial topic for me, but I\u2019ve 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.<\/p>\n<p>Daily protein requirements and optimal timing for protein intake. The role of vitamin D and brain health and protection against klotho decline. How a low Omega-3 index is as bad as smoking and what to do about it. Benefits of creatine for brain and muscle health and best practices. Microplastic exposure: the biggest offenders, and so on. It just goes on and on. We could cover so much ground. And the way this conversation came to be, to give people a peek behind the curtain, is we were texting about all sorts of things, including aging parents and what we\u2019re trying and what we\u2019re thinking about what has worked, what hasn\u2019t worked seemingly.<\/p>\n<p>I thought we would just start there if you\u2019re open to sharing because I really gained from our exchanges, enjoyed our exchanges. And for instance, talking about creatine as one example. There are potential applications to preserving or at least halting the decline or slowing the decline of cognitive deterioration. And why don\u2019t we just begin with the personal, because I think that\u2019s the most universal. All of my friends of my vintage or younger \u2014 no one is getting younger, so they\u2019re 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?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I\u2019m one of those people that my parents, neither of them are really physically active. My dad for many years was physically active in the sense that he played a team sport. He was a baseball player and he did it for many, many years all the way into his early 60s and then he just couldn\u2019t do it anymore. So my mother never really got into any sports and she wasn\u2019t 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\u2019t part of the equation and neither is really a healthy diet.<\/p>\n<p>But as I started to do a lot of research into these sort of what I think are interventions that are low-hanging fruits, things that are easy for people to do that can have a pretty big outcome in terms of the effect, the size effect is greater than what you have to put in.<\/p>\n<p>So examples of that would obviously be something like a supplement that you could take. That\u2019s the easiest thing you can do is kind of swallow a pill and hope that it has a great effect. And this is where both of my parents are taking a multivitamin. And you might go, \u201cWell, multivitamin? Really what\u2019s that going to do?\u201d And I\u2019ll tell you, we\u2019ve come full circle. 10 years ago, there was a huge splash that was made in the media. A big article came out and it was called enough is enough. Multivitamins are not only useless, they may be harmful.<\/p>\n<p>It was a study that had looked at a variety of different studies. It\u2019s called a meta-analysis that basically said, \u201cWell, all these vitamins that you\u2019re taking are useless.\u201d And in some cases they can be harmful because they can allow cancer to grow faster. I debunked that 10 years ago. But over the course of those 10 years, and as you mentioned in the intro here, science is always changing and revisions are made. We learn new things. And in that 10-year frame, three different randomized controlled trials have come out. And randomized controlled trials are really key because you are comparing this intervention, which in this case was a multivitamin to a placebo because people taking anything are obviously going to want a positive effect. And many people do anticipate that and they can actually change their biology. Placebo is a real thing.\u00a0<\/p>\n<p>So three trials came out looking at the effect of multivitamins on cognition. And I\u2019m talking the multivitamin that was used was the standard, run-of-the-mill. It was Centrum Silver. I mean it was the same \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Centrum. I knew it was going to be Centrum, yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It was the vitamin that you would go, \u201cThat\u2019s the one vitamin that\u2019s not going to have any effect.\u201d It\u2019s like that, but actually it turns out it\u2019s got over 40 essential nutrients in it and it\u2019s also got some other non-vitamins. So things that are like polyphenols, like lutein and zeaxanthin. These are actually really important for eye health, but also the brain. And these three randomized controlled trials were two years long. 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\u2019s where my parents are.<\/p>\n<p>And after two years of taking the multivitamin, they had improved cognition on a battery of different tests that equated to reducing global cognitive aging by about two years. And on top of that, they reduced their episodic aging by five years. Almost five years. It was 4.8 years. Episodic memory is the kind of memory that\u2019s involved in remembering events, things that happen in your life. And so that\u2019s a big effect. Five years of reduced episodic brain aging, episodic memory, brain aging.<\/p>\n<p>And so I think that anyone that\u2019s concerned about their parents, one of the easiest things that you can do in terms of improving cognition \u2014 now I should mention these were older adults, yes, but they weren\u2019t older adults with neurodegenerative disease. So these were older adults that were \u2014 otherwise, didn\u2019t have any sort of neurodegenerative disease. That\u2019s also important because once you get to a pathological state, you have to do more things to help improve cognition than just a multivitamin.<\/p>\n<p>I have my mom and my dad on a multivitamin. That\u2019s the easiest thing. Vitamin D is also another no-brainer. I mean 70 percent of the US population has insufficient levels of vitamin D. Older adults are even higher than that. So almost the majority of all older adults are vitamin D deficient. I mean, most people aren\u2019t going outside and even if they are going outside, they\u2019re either wearing sunscreen or just the fact that they\u2019re older affects their skin\u2019s ability to make vitamin D3 from the sun, from UVB radiation from the sun. And so they\u2019re much less efficient at it.<\/p>\n<p>In fact, a 70-year-old makes about four times less vitamin D than their former 20-year-old self. So vitamin D supplement is a low-hanging fruit. It is super easy to bring some up to that level.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Can I ask you a question about vitamin D, because I know you love vitamin D? So here\u2019s my question about vitamin D, and it actually relates to, I believe this is a publication you had in 2019, so we\u2019ll see if things have changed or not, but APOE4 for an Omega-3 brain delivery. So my family, a lot of benefits to having my genetics. Also, a whole bunch of bugs in the code, including quite a bit of APOE4, I\u2019m APOE34. And should that change how I consume vitamin D or consume fish oil or Omega-3s to having that type of status?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I would say vitamin D, there hasn\u2019t really been any effect that I\u2019m aware of in terms of having an APOE4 allele as you mentioned. And for people listening or watching, APOE4 allele, if you have one of those, it can double your risk of Alzheimer\u2019s disease. If you have two of them, you can go up to a tenfold increased risk for Alzheimer\u2019s disease. When it comes to fish oil, particularly fish oil, there does seem to be \u2014 and this is where my publication came from, but also there\u2019s a lot of evidence that has shown people with APOE4 alleles, they don\u2019t tend to have as much DHA getting into their brains as people without the alleles.<\/p>\n<p>And on top of that, in trials, people with mild cognitive decline, for example, if they supplemented with fish oil and they had APOE4, they didn\u2019t have the cognitive benefits that the people that were not APOE4 had. And so there was this big question in the field as to why that is. And it\u2019s still not entirely known. Although I will say what my take on that is, and in fact I\u2019ve talked to some of the experts in the field as well, is that you have to have a higher dose of fish oil, for one, and it\u2019s better if it\u2019s in phospholipid form. If you\u2019re eating fish, it is in phospholipid form, it\u2019s in triglyceride form as well.\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>So just for clarity, if you\u2019re taking capsules, it may not be the case, but if I\u2019m eating my can of sardines in the morning, then phospholipid form?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>You\u2019re getting more phospholipid form, exactly. Now, if you are taking your supplement oils, you can actually make phospholipid form, but you have to get to that two gram dose range. That\u2019s when your body is also converting into phospholipid form. And then the other way around that is actually consuming a phospholipid form of Omega-3.<\/p>\n<p>And so that\u2019s something that can be done if you\u2019re supplementing with either krill oil, which I\u2019m not a huge fan of because it\u2019s super \u2014 it\u2019s not very concentrated, so you\u2019d have to really take a lot of it. Or you could eat something like salmon roe, which is a really high phospholipid concentration of Omega-3 fatty acids. You might go, \u201cWhy phospholipid form?\u201d Well, it turns out the way your brain, you actually get Omega-3 into the brain, there\u2019s two ways. The first way doesn\u2019t require phospholipid form. It\u2019s just this Omega-3 is in a free fatty acid form and it diffuses across the membrane and gets into the brain that way.<\/p>\n<p>The second way actually is through a transport mechanism, and that is phospholipid form. And that\u2019s why it seems as though people with APOE4, their free fatty acid form isn\u2019t going into the brain as well because they have breakdown of the blood-brain barrier early, early on. APOE4 tends to lead to early breakdown of the blood-brain barrier. And when your blood-brain barrier breaks down, it\u2019s hard for things to kind of just passively diffuse as well.<\/p>\n<p>I know that is counterintuitive, but without getting into all the crazy molecular and biochemistry involved, just take my word on that for the two different forms of Omega-3, or you can read that publication as well.<\/p>\n<p><strong>Tim Ferriss: <\/strong>So let\u2019s step back for a second and just get into the parental specifics and then we can zoom out and talk about mechanisms and all sorts of stuff. But if you just had to give a couple of bullets on the things that you feel confident in having your mom and dad continue doing or taking, let\u2019s start with the supplements because like you said, it\u2019s sort of a low-hanging fruit in a sense from a behavioral change perspective. What do you have them doing?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I think you listened to a podcast I did with Dr. Mark Mattson several years ago. I had mentioned that my dad was diagnosed with Parkinson\u2019s disease in 2017. And that\u2019s an important context to consider what sort of supplements I\u2019m giving my dad. And also the fact that you have to think about compliance. What were your parents? Do you have a parent that\u2019ll take a lot \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>I actually do.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>\u2014 of vitamins or a few vitamins? Right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So with my dad knowing his disease was Parkinson\u2019s disease, multivitamin was in there because that\u2019s already so important just to cover a lot of bases. You\u2019re getting a lot of different vitamins and minerals. And then it was Omega-3, and in fact it was a high DHA and he\u2019s getting about two grams a day. And there\u2019s a lot of evidence that Omega-3 can help with dopaminergic transmission, can help with a lot of brain function, and particularly as it relates to Parkinson\u2019s disease as well as Alzheimer\u2019s disease.<\/p>\n<p>So that was the second supplement that he\u2019s 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\u2019s involved in mitochondrial health. So having a depleted CoQ10 can lead to mitochondrial toxicity. And so taking CoQ10, there\u2019s actually been some early studies with even Parkinson\u2019s disease patients showing that supplementing with CoQ10 can be beneficial. And he\u2019s actually taken those supplements for many, many years now and very, I would say surprisingly, but also I\u2019m thankful that his Parkinson\u2019s disease has progressed very, very slowly.<\/p>\n<p>So it\u2019s been nine years, almost 10 years, and he\u2019s really essentially had this Parkinson\u2019s disease limited to one tremor in his hand. So that\u2019s great. And that\u2019s all I can say is \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>That\u2019s great news.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, it\u2019s great news. And you never really know at the end of the day what is the reason for that. But he\u2019s convinced, I\u2019m convinced, his doctor is convinced that he should keep doing what he\u2019s doing and that it seems to be beneficial. My dad is one of those guys that doesn\u2019t like to take a lot of pills. If he would take more, I would give him more.\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>If he were willing to take more, what would you give him?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I would also give him sulforaphane. Definitely tried, but he doesn\u2019t want to take more pills. So sulforaphane is, it\u2019s a compound that is formed when you eat cruciferous vegetables like broccoli, cauliflower, for example. And it\u2019s formed from something inside of it called glucoraphanin. When you break the plant tissue, when you bite it or chop it up or whatever, it forms sulforaphane.<\/p>\n<p>Sulforaphane is not necessarily in the plant itself, it just gets formed when you break the plant tissue. That\u2019s a technical thing. So I\u2019m just going to talk about sulforaphane and call it sulforaphane as if it\u2019s part of the plant, but it\u2019s not, just so you know. Sulforaphane is, like I said, it\u2019s something that\u2019s 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 glucoraphanin than mature broccoli. So that\u2019s the best dietary source of it.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Are you growing your own broccoli sprouts or are you doing off the shelf now?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I\u2019m off the shelf now. I used to. It\u2019s work. It\u2019s not that much work, but it is work. But you also, you have to be very fastidious about not having it contaminated, and that\u2019s where the real work comes in. But I like it because there are people that can\u2019t afford the supplement, and this gives them another way to basically get it for cheap. So the reason I really like sulforaphane and why I want both my parents on it and my mom, it has been taking it, we can talk about that in a minute, is because it is the most potent dietary activator of this system that we have called NRF2, which is this major system. It\u2019s basically a transcription factor that activates a lot of different genes inside of our body, and it activates genes that are involved in stress.<\/p>\n<p>Basically, it activates a lot of what are called stress response genes. And these are the things that are activated when you\u2019re doing stress, stressful things like exercise or if you are fasting. So you really want this pathway to be active.\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>It gives a little bit of stress, right? It\u2019s like chronic overdose of stress, bad, but little doses of stress has this, I guess, what would you call it, hormetic effect. Right?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Exactly.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Am I getting that right?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>You got it. Yeah, you nailed it. Yeah. So essentially we\u2019re talking about what\u2019s sometimes called eustress or good stress. It\u2019s these small doses of stress where your body is responding to that stress by activating all these beneficial pathways that deal with stress, whether we\u2019re talking about antioxidant pathways, anti-inflammatory pathways, pathways involved in clearing out damaged stuff from your cells like autophagy. Just all sorts of beneficial stuff.<\/p>\n<p>And those pathways are activated for a longer period of time than the acute stress that you\u2019re giving it. So in this case, the sulforaphane is a little bit of an acute stress like polyphenols in general are. So the amount of time that you\u2019re ingesting that polyphenol is very small and digesting it. And then the reality is that it\u2019s activating these stress response pathways that last on the orders of 24 to 48 hours, sometimes longer. So you\u2019re having this beneficial effect that\u2019s overall beneficial from that little bit of stress.<\/p>\n<p>And so sulforaphane activates NRF2, and one of the main pathways that it\u2019s activating is increasing glutathione production. And it\u2019s been shown in a couple of different human studies that it increases glutathione in both plasma but also in the brain. Glutathione is the major antioxidant that we have in our body, and it\u2019s very important in the brain. Super important for not only preventing brain aging, but also for dealing with dysfunction in the case of acute injury like traumatic brain injury or in the case of Alzheimer\u2019s disease or Parkinson\u2019s disease, which are other types of injury on the brain.<\/p>\n<p>Glutathione plays a big role there. And so I obviously would want my dad to be taking sulforaphane, and there\u2019s a supplement out there that I use that has been used in many 12 or so different studies. And so it\u2019s been shown to be beneficial across the board. And that is something that I do give my mom. Now, the reason I gave it to my mom, well, I was kind of hoping my mom interestingly has two other types of brain dysfunction problems, but they\u2019re not neurodegenerative in the sense of Alzheimer\u2019s disease and Parkinson\u2019s disease are there. It\u2019s kind of like something going wrong in the brain and it affects her motor control. So she has tremors. She has essential tremor, and she has orthostatic tremor.<\/p>\n<p>I have secretly wanted the increase in glutathione to affect those tremors. But when I gave the sulforaphane to my mom, because I knew the placebo effect, I did tell her that we were using it to detoxify these chemicals that are associated with plastic like BPA because that is also something that I\u2019m using sulforaphane for because that NRF2 pathway does activate what are called phase two detoxification enzymes, and it\u2019s been shown to detoxify. Even if you\u2019re living in a city like New York or L.A. where there\u2019s a lot of air pollution, it\u2019s been shown to detoxify benzene. Within 24 hours, people start excreting 60 percent more benzene from their body. Now, benzene needs something that is found in air pollution. It\u2019s also in cigarettes.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yes. So don\u2019t drink your own urine if you\u2019re taking sulforaphane is what you\u2019re saying.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Definitely don\u2019t do that. But also if you\u2019re living in a polluted place \u2014 I tell all my friends in L.A., I am like, you have to be taking sulforaphane. It\u2019s just like a non-negotiable, right? So I told her to take the sulforaphane because I wanted her to detoxify BPA because she does eat a lot of processed foods and stuff, which are found in plastic. Anyway, so she started taking it and she came back to me and told me that it was helping her tremors and that she wanted more.\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>How long did that take?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Not long. It was actually, I think within a week or so, maybe two.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Wow.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It was very quick.<\/p>\n<p><strong>Tim Ferriss: <\/strong>That\u2019s wild.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It was very quick. And she is religious about it. I mean she comes \u2014 I buy it for her and I give her these bottles and she takes two a day. She takes a certain brand called Avmacol. I don\u2019t have any affiliation with them. They\u2019re a brand that, again, 12 different published studies using their supplement.<\/p>\n<p><strong>Tim Ferriss: <\/strong>A-V-M-A-C-O-L.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>That\u2019s right.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Avmacol.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>She takes two of their advanced formula. So she\u2019s taking that. She\u2019s taking the multivitamin, the vitamin D, and she\u2019s also taking the Omega-3. She\u2019s doing great. What\u2019s funny is that I was able to then get her into CrossFit. And I don\u2019t know if it\u2019s because her tremors, I think her tremors have lessened a bit, and so she\u2019s been more active and wanting to be more active. She\u2019s out dancing more. My mom likes to dance. I mentioned how I really wanted to get her into a seniors CrossFit class, and she sees me do it.<\/p>\n<p>I have a coach come to my house and we do CrossFit training at my house. My mom has seen me doing it and she\u2019s been interested in it. I told her that there\u2019s a great seniors class and I would be willing to pay for it and get her in it. It would be huge. She\u2019s been doing it now for a couple of months, maybe like three or four months. She goes three times a week and she loves it. She loves it. She\u2019s made friends there.<\/p>\n<p>Sometimes the coaches take videos and she sends them to me. She sends them to her friends. She\u2019s so proud. She\u2019s doing kettlebell swings. She\u2019s doing wall squats. I mean, it\u2019s amazing.\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Go, Mom. That\u2019s amazing.<\/p>\n<p><strong>Dr. Rhonda Patrick:<\/strong> It\u2019s a very different type of atmosphere than your usual CrossFit class would be, right? You\u2019re aware that these are seniors, and so they\u2019re not doing barbell, squatting like heavy weights and stuff. They start out with wall squats and then they\u2019re squatting with just a really light bar and it\u2019s really great.<\/p>\n<p><strong>Tim Ferriss: <\/strong>So let me hop in for a second here and I want to know if there\u2019s anything else to add to that. But we\u2019ve talked about this, you and I. Or texted a hell of a lot about it that I have Alzheimer\u2019s in my family. I now have multiple relatives who are moderate to advanced with respect to Alzheimer\u2019s. Saw my grandmother disintegrate. Terrifying to watch and terrifying to imagine yourself experiencing the same thing.<\/p>\n<p>And also at least one of them is APOE33. And I\u2019m APOE34, so I\u2019m like, \u201cWell, wait a second. If that is where they are right now, and I\u2019m at hypothetically 2.5x greater risk of developing Alzheimer\u2019s disease, AD, I should really double down on paying attention to as much as possible for myself, certainly for them as well.\u201d But the earlier the intervention, the better the outcomes generally. So I\u2019ve been looking at all sorts of things. And just to reiterate a few things you said. So on the Omega-3 side of things, just like with sulforaphane, not all brands are created equal, right? There\u2019s a lot of garbage floating around out there.<\/p>\n<p>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\u2019s O.N.E. Pure Encapsulations. Is that what you have your parents are taking or did you use a different brand?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So with my dad, he is now taking the Zymogen brand, which is also very good. And the reason for that is because it\u2019s higher DHA, which is what I wanted.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Fascinating.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>My mom is taking the O.N.E.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, got it.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Cool.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, both those brands, by the way, are great. They\u2019ve both been third-party tested and have very high quality fish oil, and I don\u2019t have affiliation with either of them.<\/p>\n<p><strong>Tim Ferriss: <\/strong>So I\u2019ve got my parents on those. I\u2019m 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\u2019t help me with my particular presbyopia. So age-related visual decline, particularly with near work, reading a book, let\u2019s say, but AREDS2, people could check out studies that have been done on AREDS2. And two of the principle ingredients are lutein and zeaxanthin. So there\u2019s that.<\/p>\n<p>Now, also have been very, very curious about how to activate some of the pathways that you mentioned. Sulforaphane would be a good option for that. Also, looking at, and we don\u2019t have to spend a ton of time on this, but exogenous ketones because ideally, sure, I would have my parents maybe do intermittent fasting or some extended fasts. I don\u2019t think that\u2019s going to happen for a million different reasons, but perhaps exogenous ketones and have looked at that.<\/p>\n<p>This is a work in progress I\u2019ve been doing, and I know you have too. Lots of self-experimentation, but there are some case studies in the literature, one of which you sent to me that are pretty interesting, looking at administration. In other words, giving an older patient with Alzheimer\u2019s disease, oral exogenous ketones. They tend to taste like jet fuel. They\u2019re not tasty. But the effects of, at least in these case studies are pretty remarkable.<\/p>\n<p>Now, granted with the monoester they use in some of these, the off-the-shelf cost per day would be like $150 or something like that. Maybe even more. So there\u2019s sort of a cost question. But I\u2019m just going to throw a couple of more things out there that are on my mind. So you mentioned the exercise piece. This has been so important for me. So I\u2019ve hired a trainer and I realize my parents are kind of sneaky and sometimes a little, I don\u2019t want to say passive-aggressive, but they\u2019ll say they\u2019re going to do something to please me and then they won\u2019t do it.<\/p>\n<p>So getting the trainer to actually pick them up at their house is something that I decided to do because there are a lot of reasons. Exercise is amazing, one of which is the natural release of klotho and people can look this up. I\u2019m hoping that you\u2019ll be able to inject this in the next handful of years. We\u2019ll see in humans. But K-L-O-T-H-O. Also worth checking out.\u00a0<\/p>\n<p><strong>Tim Ferriss:<\/strong> Anything else that you would add to that or any commentary you want to sprinkle in? Am I missing any criticals?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>There\u2019s definitely commentary.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Multivitamin, yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>There\u2019s commentary, but we can get into that if you want to go dive into the why the ketone esters are beneficial and why the exercise is beneficial. We can go into that because I love talking about it.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. This is going to be a conversation just between you and me. That\u2019s how I treat all of these things. And I\u2019m very self-interested because I think the personal is the most universal. Maybe that\u2019s just an excuse to make this all about what I want. But we have been texting also because I told you I\u2019ve been thinking about doing a 14-day fast, and actually I ratcheted that back from doing a 30-day fast.<\/p>\n<p>I\u2019ve done 10 days before, water only. I\u2019ve done lots of seven days. And part of the reason is I think I would be better equipped now to do longer fasts because of the intermittent fasting I\u2019ve been doing. And this ties into the conversation around the parents because what I have noticed is, for instance, doing 16:8 fasting, which was, and I\u2019m so sorry, the scientist you mentioned before, whose podcast interview I listened to on your podcast, what was his name again?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Dr. Mark Mattson.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, Mark Mattson. Amazing, amazing scientist. Fantastic conversation. A lot of seminal work related to intermittent fasting. So 16:8, what does that actually mean? I did this today, I\u2019ve done this most days now, which is basically eating between, for me it\u2019s like 2 p.m. and 10 p.m. There are arguments that it should be shifted earlier, like noon to 8 p.m. or something like that. But socially, just practically, again, coming back to compliance, like the good system you do being better than the perfect system you don\u2019t, generally it\u2019s like two till, let\u2019s say 9 p.m. is when I eat and then I fast the rest of the time. And for the first five to seven days, pretty grumpy, kind of pissy, I\u2019m not going to lie. Sent some emails that I probably shouldn\u2019t have. But then once I adapted, I did a recent set of labs and they\u2019re my best set of labs that I\u2019ve seen.<\/p>\n<p>I can\u2019t solely attribute it to the intermittent fasting, but the best set of labs I\u2019ve 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\u2019s been in ages. So I was like, okay, that\u2019s really interesting. The last time I did a seven-day fast, it was kind of brutal. I hadn\u2019t done one in a few years and I don\u2019t think my metabolic machinery was ready for the task, very unpleasant. But I have some chronic inflammation or at least chronic pain in my low back. And after doing that seven day fast, I had four weeks of zero symptoms and that\u2019s the first time in three years that that\u2019s been the case. So I was like, okay, that\u2019s pretty interesting.<\/p>\n<p>So I\u2019ve 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\u2019s kind of dirty fasting, but if I did that, what am I accepting as a compromise or a penalty if anything? Because then I think of, say, Longo\u2019s work and others looking at fast-mimicking diets where I\u2019m like, well, wait a second, these people are doing, let\u2019s just say five days of fast-mimicking dieting per month for three months straight. And they seem to have all these benefits that maybe of lower magnitude, but mirror water fasting on some level, but they\u2019re consuming a few hundred calories, let\u2019s just say for simplicity per day of those five days of \u201cfasting.\u201d If you look at the actual meal composition, it ends up being very low calorie keto, basically very low calorie keto with very low protein, like 10 percent or less avoiding animal products.<\/p>\n<p>That\u2019s the basic way that I\u2019ve been thinking of it. And so I was like, well, should I do something like Wilhelmi in Germany who have, again, \u201cfasted thousands of people,\u201d but they do give them bone broth, a little bit of juice, it\u2019s akin to the fast-mimicking diet, but they will do that with people for 30, 60, 90 days or am I better off doing shorter water fasts or maybe even a 14-day water fast? And a lot of the questions came down to, I know this is mouthful, but as you know, I\u2019ve been thinking about this nonstop. I was up until 2 a.m. this morning reading really, really old stuff out of the Soviet Union on psychiatric clinics fasting patients for schizophrenia.<\/p>\n<p>And so that tells you metabolic psychiatry also goes back a long, long, long time, not to mention ketogenic diet for epilepsy. So there are a lot of similarities, but if I want the benefits, as many benefits as possible with the least pain possible, which includes not losing a ton of muscle tissue, which is not always the same thing as lean body mass, what should I do? Right? That\u2019s kind of the open question. And that is a huge, huge mouthful. Thank you for coming to my TED talk.<\/p>\n<p>But where is your current thinking when it relates to all of this stuff? And I said earlier at the very beginning that it ties into my parents. Why is that? Because when we looked at some of my relatives and I got my docs to come in and do a real proper full workup, looking at all sorts of things that normally wouldn\u2019t be tested, absolutely some metabolic syndrome in the sense that they\u2019re highly, highly insulin insensitive, like insulin off the charts. And it\u2019s like, okay, well this has been going on for years to get to this point and Alzheimer\u2019s is sometimes called type 3 diabetes. And it\u2019s like, okay, well if I can\u2019t 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?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, there\u2019s a lot to talk about here, and I think we\u2019ve got to kind of \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Let\u2019s \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Let\u2019s chew on one bit at a time.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right. Let\u2019s chew 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\u2019re looking for? Now, you mentioned some metabolic benefits that you had noticed after doing your intermittent fasting.<\/p>\n<p>So there\u2019s lots of different types of intermittent fasting. You\u2019ve mentioned the 16:8. So essentially you\u2019re talking about not eating food for a period of time, and that period of time can either be 16 hours, it can be 24 hours, it can be longer, in which case it would not be an intermittent fast. It would be more prolonged fast, which you also talked about. But with respect to the intermittent fasting, there are a few things that happen and there are a few reasons why people like to do intermittent fasting. First and foremost, I think most people like doing intermittent fasting is because they want to actually lose weight and the weight that they want to lose is not necessarily their lean body mass. They actually want to lose their fat mass, so they want to lose fat, and that\u2019s a big reason why people do intermittent fasting.<\/p>\n<p>Well, it turns out that intermittent fasting is more of a tool for weight loss. And what I mean by that is that there have been multiple studies now that have looked at different types of intermittent fasting in sort of a community dwelling aspect where people are just kind of free to eat the way they\u2019re going to eat, but they\u2019re supposed to be practicing intermittent fasting. And what it\u2019s been discovered is that naturally, people end up eating about 200 fewer calories per day when they\u2019re doing some form of intermittent fasting. So if they\u2019re eating all their food within an eight or 10 hour period, for example, usually they\u2019ll eat their food within a 10-hour period and then they\u2019ll fast for 14 hours. If they do that, they end up actually eating 200 fewer calories. And so they end up performing what\u2019s called caloric restriction, which we know can lead to weight loss.<\/p>\n<p>And so a lot of the weight loss actually comes from reducing calorie intake, but that doesn\u2019t necessarily mean that everything that\u2019s beneficial from intermittent fasting comes down to calories because it doesn\u2019t. But the weight loss definitely seems to come down to the calories because if you keep calories the same and then have people do intermittent fasting or not intermittent fasting, they won\u2019t lose the weight, but they will have a whole host of metabolic benefits. You mentioned glucose regulation improvements. I mean fasting glucose, postprandial glucose, HbA1c, which is a long-term marker of glucose regulation, their lipids are more favorable, and then they have improvements in blood pressure, for example, that\u2019s another big one that people get with more of a longer type of intermittent fasting. So they\u2019re fasting more like 18 hours and eating their food within a six-hour window. Now that\u2019s another benefit.<\/p>\n<p>Now you go even further, and I know this is something you are very interested in, so beyond metabolic benefits and people want to get then, they want to get into what\u2019s called ketosis. So they want to be making ketones, these things that we\u2019re talking about earlier with respect to taking an exogenous ketone ester, well, you make something naturally when you start to actually burn fat as energy, you start to make something called beta hydroxybutyrate, but it takes about 12 hours or so. It depends on the person. It depends on how heavy of a carb diet they eat or how physically active they are. It can be a range. So if someone\u2019s doing a more ketogenic type of diet, they can actually deplete their liver glycogen quicker than 12 hours. It might even cut it down to like eight if they\u2019re physically active on top of that, you might go down to even six or something.<\/p>\n<p>So there\u2019s a big range here, but for a standard person on a normal diet, they\u2019re going to take around 12 hours before they start to deplete their liver glycogen and then start to immobilize fatty acids from their adipose tissue and use that as energy. And when you start to do that, then you start to get into ketosis, your body starts to then make beta-hydroxybutyrate the major circling ketone. Why do people want that in their system? Because it\u2019s not just a very energetically favorable source of energy. What I mean by that is it takes less energy to use beta-hydroxybutyrate to make energy than it does to use glucose, for example. It takes more energy to actually use glucose, so it\u2019s more energetically favorable, right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s a clean fuel. Yeah. Also, BHB, the beta-hydroxybutyrate, as I understand it, I mean highly anti-inflammatory effects as well, right?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Exactly. That was the next point I was going to make is that it\u2019s called a signaling molecule. So it\u2019s actually a way so your body knows that it\u2019s in this stress mode, okay, there\u2019s no food. It\u2019s food scarcity time. And this is something that it\u2019s evolutionarily tapped into our system, into our DNA where times of food scarcity, when we\u2019re not eating, our body switches into ketosis, beta-hydroxybutyrates produce, and it signals to these other genes to basically make more of something beneficial. So it\u2019s been shown to reduce inflammation. It depresses something called the inflammasome, which causes inflammation. It\u2019s an HDAC inhibitor, so it\u2019s a histone deacetylase inhibitor. So it\u2019s globally affecting gene expression and in such a way that it reduces genes that are involved in making oxidative stress, it actually activates brain-derived neurotrophic factor. That\u2019s the beneficial neurotrophic compound that\u2019s made in the brain that exercise also activates as well.<\/p>\n<p>So it\u2019s doing all these beneficial things. And the other thing that it\u2019s doing is it\u2019s getting into the brain. It\u2019s being used as a very great source of energy. And so you have this sort of bypass where the glucose can then be shunted to be used to make glutathione, that very important antioxidant I talked about earlier that sulforaphane activates.<\/p>\n<p>Well, it turns out when you give your body ketones or your body\u2019s making ketones, your brain actually consumes a lot of that. There\u2019ve been tracer studies that have looked at that. And what happens is because neurons are now using the beta-hydroxybutyrate as energy, glucose is no longer needed. And so that glucose that is there is then used to make NADPH, which is a precursor to make glutathione, and so it\u2019s called glucose sparing. You get this glucose sparing effect. And so that\u2019s another reason why people are interested in intermittent fasting.\u00a0<\/p>\n<p>And then another main reason, and there\u2019s many others, I\u2019m not going to touch on everything, but the other main reason is it activates repair processes. And what I mean by repair processes is to be in repair mode, you have to be in more of a catabolic state. And we were talking about this earlier, people get so freaked out by the word catabolism.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Last night when I was walking around New York City, we were talking about this catabolism \u2014<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>And I think even over the last few years, intermittent fasting has kind of gotten a bad rap because people now equate it with, \u201cOh, loss of muscle mass. I\u2019m going to be catabolic.\u201d Well, in order to be in a repair mode, you actually do need to be in a catabolic mode. And these repair systems are so important for cleaning up all the garbage that\u2019s inside of our cells. And that can be things like protein aggregates. These are things that lead to aggregation like alpha-synuclein, which is involved in Parkinson\u2019s, amyloid beta aggregates, which is involved in Alzheimer\u2019s disease. It\u2019s not the cause. It\u2019s like the cause and the symptom. It\u2019s like both. It\u2019s involved in Alzheimer\u2019s disease and then aggregates in our cardiovascular system that play a role in cardiovascular disease, but it also cleans out even damaged little what are called organelles.<\/p>\n<p>And so mitochondria or an organelle, and these, our organelles get damaged. So you want to be able to repair that damage. And this process of autophagy is the process that does that. And there\u2019s lots of different types of autophagy. So if it\u2019s a mitochondria repairing damage to itself, it\u2019s mitophagy but for all this stuff to be active, you have to be in that more catabolic state, which can be induced by not eating, can also be induced by heavy endurance exercise as well.<\/p>\n<p>Okay. So talking about those sort of outcomes that people are interested in, those different endpoints that people are interested in achieving, I think something that you are specifically interested in is the metabolic effects of intermittent fasting as well as the repair processes like the autophagy.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, for sure. And that\u2019s why I was asking because I don\u2019t really, look, I\u2019m as vain as the next person. I like looking less fat if I can, but it\u2019s not my main driver, right? It\u2019s mental acuity and hopefully staving off on some level things like neurodegenerative disease and even cancer possibly, which has been part of the reason I\u2019ve done a lot of these extended water fasts, which is I realize there are a couple of hops here in terms of speculation, but it seems plausible that you might zap punch a couple of pre-cancerous cells in the nuts by doing that.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Definitely. Not only does autophagy play a role in preventing Parkinson\u2019s disease, but also Alzheimer\u2019s 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\u2019s disease. And yes, there are some people that have amyloid beta plaques that don\u2019t get Alzheimer\u2019s disease. They may be the more resilient non-APOE4 type of person, but we do know that many, many people do get Alzheimer\u2019s disease with amyloid plaques. And in fact, people that have, again, the SNPs in what\u2019s called the amyloid precursor protein APP, that leads to amyloid beta plaque buildup, they get early onset Alzheimer\u2019s disease. So autophagy plays an important role in clearing away those plaques. And I will say what we don\u2019t have a lot of evidence on is what\u2019s the minimal effect of fasting dose to activate autophagy?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, I know. God, I wish we had this<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right. We don\u2019t. I think what we do know in humans from some of these old studies is that you do see some signal of autophagy activation after 24, 48 hours in humans. Now, does that mean that that is the only amount of time that it takes to activate autophagy? No. So most humans are probably doing anywhere between a 12 to 16 hour nightly fast. There\u2019s a period of time when we\u2019re not eating, and that is when we\u2019re sleeping a little bit before bed autophagy still happens in people, we just aren\u2019t measuring it because we don\u2019t have sensitive tools yet. And so it\u2019s not that I don\u2019t think a 16-hour fast doesn\u2019t activate. I believe it does in human. I believe there\u2019s some autophagy going on. It\u2019s probably not that much. But if you go into that 48 hour fast, then you\u2019re really starting to get more robust activation of autophagy.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Can I throw something else in here just for fun?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yes.<\/p>\n<p><strong>Tim Ferriss: <\/strong>So you mentioned sleep, and I\u2019ve been looking, trying to look at Alzheimer\u2019s from every possible angle and found literature looking at disruption of sleep architecture in patients with Alzheimer\u2019s disease and the possible application of Xyrem, I believe it is, which is another, it\u2019s a brand name in a bifurcated schedule for GHB gamma hydroxybutyrate, which you have to be very careful with. It\u2019s a party drug. People die of it because it suppresses respiration. The person who bought my apartment in San Francisco died of a GHB overdose, but it actually is a tremendously interesting compound for increasing, I think it\u2019s deep wave sleep specifically, which does what? It helps the cleanup crew to do its work and to actually take out the garbage cellularly. And so if I could wave a magic wand, I would have my relatives on something like Xyrem, might actually be a different type of sleep medication like the NORA class. NORA, might be DORA.<\/p>\n<p>I would also look at, and this is something obviously not suitable for most elderly people, but potentially lower dose psilocybin or psilocin. And there is some actually very interesting, I don\u2019t want to call them speculative, hypothetical applications of that to Alzheimer\u2019s disease, which you can find on PubMed. And from a mechanistic perspective, they\u2019re super, super interesting. So I just want to double click on the sleep because that is such a critical component, whether you\u2019re fasting or not, to try to ensure that your sleep architecture is not hyperdisrupted, 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\u2019s like, okay, you can do all of these other things, but boy, oh boy, it would make a lot of sense to try to fix sleep whenever possible.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Great. Yeah, so true. The low-wave sleep does activate the glymphatic system, which is cleaning out the amyloid beta aggregates as well. And the last thing I kind of want to mention is you were talking about the intermittent fasting and more prolonged fasting and the muscle mass loss or lean body mass, which people equate with muscle mass, which it\u2019s not, there\u2019s a lot of things going on. So the thing is, when people are doing intermittent fasting, I mentioned they eat fewer calories, which means they\u2019re eating less meals, they\u2019re eating fewer meals, they\u2019re not eating as many meals. And so what ends up happening is people lower their protein intake, and that\u2019s an important signal for maintaining muscle mass and certainly growing muscle mass as well. So it increases muscle protein synthesis, which is important. If people are engaged in resistance training and doing intermittent fasting, they\u2019re not losing muscle mass.<\/p>\n<p>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\u2019re doing an intermittent type of fast, like 16:8 where you\u2019re fasting for 16 hours, that\u2019s really not a long, long fast. There\u2019s not a lot of concern with losing muscle mass if you\u2019re resistance training. Now a more prolonged type of fast, you\u2019re talking about 14 days, that\u2019s a long fast. And definitely, you\u2019re going to be losing some muscle mass no matter what. Now, how much you lose depends on how, I guess if you can resistance train lightly while you\u2019re fasting, that would be huge because you would be then activating muscle protein synthesis through another signal, which is not protein, it\u2019s mechanical force.<\/p>\n<p>So that, I think, would be really important for preventing the loss of a lot of muscle mass. But what is interesting is that you do lose lean body mass, a lot of it, when you are doing a prolonged fast like that and looking at the old literature and some of the literature that\u2019s been done, a lot of water up to 10 pounds of water rate, which is crazy, you lose that and your organs shrink. And this is something that\u2019s been also shown in animal studies and also by Dr. Valter Longo many years ago, and he\u2019s shown in animal studies, prolonged type of fasting actually causes organs to shrink because a lot of the damaged cells, not only is autophagy getting activated and you\u2019re cleaning out damage within a cell, but cells that are so damaged that autophagy can\u2019t even fix them, they actually undergo death, cell death.<\/p>\n<p>And so you end up getting a lot of cells that die. And then what happens is during the re-feeding phase, and this is key, the re-feeding phase is the growth phase, and this is when you regrow organs, it\u2019s when your muscle mass comes back, you can go back, get your muscle mass gains back. And so having that refeeding phase is really important. And getting the right nutrients, like protein for example, is key for that refeeding phase. But you also lose fat during that fast and you\u2019re losing visceral fat. And you had brought this up last night when we were talking and I did some reading on it because it was like, oh, I made perfect sense because your organs are shrinking, you\u2019re losing a lot of cells in your organs. You\u2019re also losing some of the visceral fat that surrounds the organs, right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>And that can get misclassified. Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Exactly. It gets misclassified as lean body mass. And so you look at this lean body mass and all you think about is muscle. Well, it turns out, muscle\u2019s a small part of that. There\u2019s a lot of other stuff that\u2019s going into that lean body mass. It\u2019s a pretty big undertaking, a 14-day fast. But I\u2019ll say this, and this kind of goes into what you mentioned about the fasting mimicking diet and perhaps even adding cream. We can talk about that as well. I do think, I mean the fasting mimicking diet, you\u2019re not going to get the same amount of autophagy that you would get if you did a five-day fast, water fast, because it\u2019s just impossible.<\/p>\n<p>You\u2019re getting some protein, you\u2019re getting some amino acids that\u2019s activating mTOR, that shuts down autophagy. You\u2019re getting energy, ATP, there\u2019s a ratio called the ATP to AMP ratio, which you want it to be low to activate something called AMP kinase for autophagy to happen. And so when you\u2019re eating heavy cream or eating whatever, fill in the blank, any type of calories, you are changing that ratio. And so that AMP kinase is not getting activated as robustly. Now, the amount of inactivation of those pathways, which then will inactivate autophagy, depends on how much you\u2019re feeding, how many calories that you\u2019re eating, how much of that is amino acids.<\/p>\n<p><strong>Tim Ferriss: <\/strong>And specifically leucine, right? In the case of Longo, really trying to minimize leucine as in an activator of mTOR and so on.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yes, exactly. Yeah. So I think for the cream, if you\u2019re trying to do 16:8, if someone is trying to do 16:8 on a daily basis, and it\u2019s a non-negotiable for having an earlier feeding window because social, just everything compliance wise isn\u2019t going to work and you have to do it later, which means you have to wake up and still be fasting in the morning, then you either have to love black coffee, learn to love it, or try maybe MCT powder, MCT oil, because then you\u2019re not getting the amino acids in there to activate the mTOR, but you can do a small, maybe a tablespoon of it, and so you\u2019ll maybe just get a little bit of depression of autophagy, but not much. That would be my recommendation.<\/p>\n<p><strong>Tim Ferriss: <\/strong>And I also want to clarify for folks listening just to really make it specific. When I have had, I just like saying dirty fasting, I didn\u2019t realize it was an expression, I just think it feels fun like a dirty martini. So dirty fasting is kind of cheating in this way. But when I do that, which is not all the time, I usually have black coffee or tea or something like that, but it is heavy cream, which is almost entirely fat. It is not creamer that you would just pull off the shelf. It is not half-and-half. It is heavy cream, which just from a macronutrient perspective is very, very, very different. And you can really overdo it on the calories also, it\u2019s just liquid fat effectively. But the MCT powder is a good idea.<\/p>\n<p>I tell you what, if you\u2019re open to it, let\u2019s shift gears a little bit. I will just say, I wish somebody, nobody\u2019s going to do this, but would somehow get the ethics board, IRB, etc, to approve long-term human studies, again, in fasting, that would be great because you used to be allowed to do it. There are case studies of people who literally fast for 300 plus days, I mean fat, what is it? 9,000 calories per pound. You can do a lot with that fat. So we\u2019ll see if I do 14 days. If I can do 14 days, then I might just go to 30. But then the refeeding gets really tricky.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I think people are concerned with gallstones. So when you don\u2019t eat for a long period of time, then you\u2019re not stimulating the gallbladder and the gallstone risk increases, which is what I think is the big concern with the long, long fasts. But I mean, if you\u2019re doing something like that once a year, I don\u2019t know if it\u2019s that big of a deal.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, I mean that\u2019s 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 stand up and I felt like I was going to fall over and vision started to get funny and I was like, you know what? Maybe this isn\u2019t for me, but I think it\u2019s because my machinery just wasn\u2019t developed for that. Having seen really stark differences in my mental acuity and sustained focus with the intermittent fasting, I\u2019m like, okay, I feel like doing intermittent fasting, which part of my reason behaviorally for my interest in that also is that getting people to change their diet is fucking hard, meaning their diet composition, the food they eat. So if you can just say, Hey, look, keep eating whatever you want, same thing, but you have to fit it within this window.<\/p>\n<p>It\u2019s an interesting option B that might work for people who otherwise aren\u2019t going to follow a paleo diet or whatever. But if you do the IF, and then what I\u2019ve 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\u2019re pretty well teed up for a longer water only fast. Maybe you supplement with electrolytes. This gets into all sorts of controversial territory.<\/p>\n<p>But if you\u2019re okay with it, let\u2019s talk about training for a minute because, and I\u2019ll force a really awkward segue maybe, which is one thing I noticed is that my ability to do Zone 2 training, let\u2019s just for simplicity\u2019s sake, say that for people that you\u2019re on a bike, stationary, is just easier to keep consistent and you\u2019re 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\u2019t really want to, right? That\u2019s like the talk test. Intermittent fasting plus ketosis really helps my Zone 2. And then this leads into the question of just training in general. So I have to click on this, what type of exercise reduces heart aging by 20 years? Do you want to start there or do you want to start with VO2 max?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>We can start with VO2 max maybe because \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Okay, let\u2019s do it.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>\u2014 they kind of lead in to each other.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Great.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>And so people might be going, what is VO2 max? It\u2019s essentially a cardio respiratory fitness. It\u2019s measured by VO, it\u2019s measured or calculated by VO2 max, which is essentially the maximum amount of oxygen you can take up during maximal exercise. And what\u2019s so fascinating about that is it\u2019s a really important predictor of longevity. So there have now been enough studies that have come out looking at cardiorespiratory fitness in the sense of VO2 max and how people with a higher cardiorespiratory fitness have a five-year increased life expectancy compared to people with a low cardiorespiratory fitness. In fact, if you have a low cardiorespiratory fitness and you go anywhere above that from low to low normal, it\u2019s associated with a two-year increased life expectancy. And people with a low cardiorespiratory fitness actually have a higher all cause mortality that\u2019s comparable or worse than people with known diseases like type 2 diabetes or cardiovascular disease or smokers, for example.<\/p>\n<p>So in other words, being sedentary is a disease and we need to think about it as a disease and we should be trying to train to improve our VO2 max. And that is something that should be in our minds. And I say this because just having this conversation that you and I are having right now, it takes about 11 milliliters of oxygen per minute, per kilogram body weight just to have this conversation. Now, just sit still and just breathe. It takes about three milliliters of oxygen per minute, per kilogram body weight. And that\u2019s important because as we\u2019re aging, we\u2019re sort of heading towards this cliff of VO2 max. Our VO2 max goes down as we age just naturally. Even if you\u2019re training and doing everything, it goes down.<\/p>\n<p>And once you get to that cliff, everything becomes a maximal effort like talking, you\u2019re out of breath. Carrying groceries to your car from the store, you\u2019re just out of breath. Everything is a maximal effort, and you don\u2019t want to be there.<\/p>\n<p>So you want to start from a higher-up point so that when you\u2019re going down, that cliff is much further away. And that\u2019s where the training comes in because you want to find a training program that\u2019s going to improve that cardiorespiratory fitness, right?<\/p>\n<p>And that\u2019s where you talked about Zone 2 training and that\u2019s the kind of what I would call moderate intensity exercise. So you\u2019re able to sort of the talk test, I like the talk test because heart rate is so dependent on a person\u2019s fitness level. But let\u2019s just say on average, generally people, they\u2019re not at like 75 or 80 percent max heart rate. They\u2019re kind of below that on average.<\/p>\n<p>Now some people may actually be above that, but the talk test is great because you can have a conversation, you\u2019re breathy. You don\u2019t want to have a conversation, but you can or so.<\/p>\n<p>We know that people that are doing that moderate intensity type of training, if they do the standard guidelines of physical activity, which are about two and a half hours a week of moderate intensity physical activity, people that do that for two months, 40 percent of those people still can\u2019t improve their VO2 max.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Just different gears.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, unless they actually add in high intensity interval training.<\/p>\n<p>And that\u2019s where I kind of get into this. I think people should be doing vigorous intensity exercise. That\u2019s the type of exercise where you\u2019re unable to talk, so you can\u2019t have a conversation because you\u2019re going harder. Your heart rate is about 80, 85 percent. It\u2019s above 80 percent max heart rate.<\/p>\n<p>That type of exercise has been shown to improve VO2 max, especially if you\u2019re doing sort of what\u2019s called high intensity interval training, as you know, you\u2019ve talked about this a lot as well. But you\u2019re 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\u2019s been a variety of different protocols out there that have been shown to improve the VO2 max if you do them.<\/p>\n<p>Generally speaking, what\u2019s happening is you\u2019re putting a stronger stress on your cardiovascular system, so on your muscular system, even on your brain. So the adaptations are greater, and one of those adaptations is increasing your stroke volume, so being able to like basically transport oxygen to tissues faster. And that\u2019s an adaptation that happens when you\u2019re going at a harder, when you\u2019re training at a harder intensity.<\/p>\n<p><strong>Tim Ferriss: <\/strong>What do you do personally? What\u2019s your HIIT look like?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So my training is three days week I do some sort of CrossFit training that involves high intensity interval training with it as well. And the high intensity interval training will either be on a rowing machine, or it\u2019ll be on a stationary bike or AssaultBike, or it\u2019ll be like a skier, like those skiers or jumping rope.<\/p>\n<p>And I also do longer intervals, so I\u2019ll do the Norwegian 4\u00d74. So that\u2019s where I do, on a stationary bike, or I do it on a rowing machine actually as well. I do four minutes of as hard as I can go and maintain for that entire four minutes. So this is obviously not an all-out 30-second sprint. I\u2019m just working hard, as hard as I can, and maintain that for four minutes.<\/p>\n<p>And then you recover for three minutes, and then you do it four times. I\u2019m thinking of a variation I do sometimes with my husband. I recover for four minutes because we\u2019re switching on the rower. So I sometimes do a little bit longer recovery.<\/p>\n<p>But that Norwegian 4\u00d74 where you\u2019re 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\u2019s been shown to be one of the best ways to improve VO2 max.<\/p>\n<p>But you can also do one minute on, one minute off, which I\u2019ve also done. So you do that 10 times. It\u2019s more like a 20-minute workout. That\u2019s also been shown to improve VO2 max.<\/p>\n<p>But also even doing something like 20 seconds on, 10 seconds off like a Tabata, again has been shown.<\/p>\n<p>And I do all of these, by the way, and I do variations of them depending on the week. Most of my exercise is high intensity interval training, CrossFit training, which incorporates, it\u2019s more dynamic. So it\u2019s including like strength training stuff, but it\u2019s like more high intensity.<\/p>\n<p>And then I do a couple of runs. I do like two 30-minute runs a week, sometimes three. And that\u2019s more of my Zone 2 stuff.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, it\u2019s a nice roster.<\/p>\n<p>So I\u2019ll share, just for people who might be curious, some of my goals and program at the moment, right?<\/p>\n<p>So I\u2019m about to turn 48 and feel good overall, but have realized that I really hate endurance training, generally speaking. So I\u2019ve 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 2 is like listen to a podcast, maybe I have like a slightly breathy conversation. Like it\u2019s pretty chill. Watch something on Netflix. It\u2019s pretty straightforward.<\/p>\n<p>VO2 max, specifically chatting with Peter Attia, I\u2019m doing the Zone 2, which I do either on a stationary bike or on the treadmill, typically 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 lordosis and stuff.<\/p>\n<p>And then for the VO2 max, doing the 4\u00d74 that you described. And I think I\u2019m getting this translation right, but the way it was described to me was like, all right, for each of those four minutes you have these four-minute work intervals, and then you have three or four minutes of rest, and then you repeat four times.<\/p>\n<p>It\u2019s like first minute you\u2019re like, \u201cWow, this is a lot of work.\u201d Second minute you\u2019re like, \u201cWow, this really sucks.\u201d Third minute you\u2019re like, \u201cI don\u2019t know if I\u2019m going to make it. I don\u2019t think I\u2019m going to make it.\u201d And then minute four is like, \u201cI feel like I\u2019m going to die and I\u2019m being chased by wolves.\u201d So it\u2019s like when we say like maximal effort, at least as it\u2019s been, and those are not Peter\u2019s words, but another person that I like a lot.<\/p>\n<p>It\u2019s a lot of work. Like it\u2019s pretty pukey, but I\u2019m going to be doing that, given the longevity associations that you mentioned.<\/p>\n<p>Now, I would love just to get your two cents, and this relates to vitamin D2 a little bit for me where I\u2019m like in these studies looking at VO2 max as a predictor or correlate of longevity, are there other possible confounders, confounding variables that might actually be the real McCoy?<\/p>\n<p>In other words, because you could say, and I know you know all this, but just for people listening, it\u2019s like, okay, well, I\u2019ll make this up. Like women who do Pilates in Manhattan have four years of additional lifespan. Okay, great. So you could conclude then we should all do Pilates to improve lifespan. It\u2019s like, well, wait a second, Pilates is expensive, and maybe they\u2019re also following a better diet and so on and so on and so on.<\/p>\n<p>So are there any confounders that might apply, possible confounders to these VO2 max studies? I\u2019m assuming they\u2019re observational, more than experimental, or sort of intervention-based. So what are your thoughts there?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, I mean there\u2019s absolutely a possibility for some sort of confounding factors in any sort of observational study, including the ones I\u2019m discussing. Because, yes, they\u2019re going in and measuring their cardio respiratory fitness, which is better than a lot of observational studies that you\u2019re going off a questionnaire, right? So that\u2019s already sort of one, at least a one up over other observational data.<\/p>\n<p>But at the end of the day, you may have someone that has undiagnosed cancer or some kind of undiagnosed disease because diseases are, I mean, they\u2019re not, they\u2019re supposed to be disease free or if they have a disease, it\u2019s known and so everything\u2019s corrected for. But there\u2019s always the possibility that some people have some disease and that\u2019s why they can\u2019t exercise very well because they\u2019re diseased, and it\u2019s the disease that\u2019s causing them to have a higher mortality rate than the lower cardiorespiratory fitness is.<\/p>\n<p>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.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Can I do one more thing real quick? Before we get to the heart aging, real quick.<\/p>\n<p>So when I\u2019ve done VO2 max training, my legs grow, my legs grow like weeds, like they adapt and get big. So along with the age-related decrease in VO2 max, there\u2019s also sarcopenia and age-related loss of muscle mass.<\/p>\n<p>So I\u2019m like, I wonder if these people who also have higher VO2 max tend to have a higher percentage of lean body mass or muscle tissue be more heavily muscled than the people without, I don\u2019t know. I mean, that\u2019s just \u2014 I\u2019m just kind of poking at it out of curiosity.\u00a0<\/p>\n<p>Okay, so the heart aging.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>This goes into why randomized controlled trials are important because you can establish more causation from an intervention. And this study was done by Ben Levine out of UT Southwest and Dallas. And really, to me, it\u2019s a seminal, groundbreaking study that isn\u2019t talked about enough.<\/p>\n<p>By the way, he\u2019s just a phenomenal cardiovascular exercise physiologist. I mean, he trained with, like, the biggest giants out there.<\/p>\n<p>And what he did was he took, him and his lab took 50-year-olds that were sedentary. So they\u2019re middle-aged, 50 years old, sedentary, but otherwise healthy. So you didn\u2019t have any other diseases besides being sedentary, which I think is a disease, but they didn\u2019t have any other diseases like cardiovascular disease or type 2 diabetes or hypertension, right? So they were otherwise healthy, just not active. And he wanted to see if he could put these guys on a pretty long two-year training protocol, how would that affect the aging of their heart?<\/p>\n<p>So as we age, our hearts typically shrink in size, and they get stiffer. And that affects not only our cardiorespiratory fitness and our ability to exercise, and I mentioned our cardiorespiratory fitness goes down with age, but it affects our cardiovascular disease risk as well.<\/p>\n<p>So the reason our hearts get stiffer, by the way, does come down to a lot of glucose. So the more glucose stimulation, more glucose is around in your vascular system, it through a chemical reaction forms advanced glycation end products. So this glycation essentially stiffens the collagen that surrounds your myocardium and your pericardium, and so you get like this stiffer heart that can\u2019t respond to stress well.<\/p>\n<p>So you want your heart to be very plastic and malleable and flexible, right? You don\u2019t want it to be stiff.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Doesn\u2019t sound good, yep.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So just like you don\u2019t want your blood vessels to be stiff, right.<\/p>\n<p>So what he wanted to do was see if he could change the structure and the trajectory of these aging hearts. So he put them on a two-year training program, which involved the Norwegian 4\u00d74, by the way. And when you start someone out that\u2019s not physically active and you want them to do the Norwegian 4\u00d74 when you have them doing their interval, their four-minute interval, and this speaks to you as well, or anyone, you don\u2019t have to necessarily go as hard as you can the whole four minutes. But you just have to be working hard that interval.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, you do have to last four minutes, right? So \u2014\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>You have to last four minutes. So some people even start off, they\u2019re just briskly walking because that\u2019s hard for them, right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. Yeah, totally.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So it\u2019s all tailored to the individual. So some people get really intimidated where they\u2019re like, \u201cOh, there\u2019s no way I could ever do that.\u201d<\/p>\n<p>Well, actually these people did do it, and they started out doing the Norwegian 4\u00d74, 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.<\/p>\n<p>By the end of the two years, these people were working out about five hours a week, and at some point they were doing two Norwegian 4x4s a week, and then they went down to just doing one a week. But over the course of two years, they were getting a lot of exercise, about five hours a week.<\/p>\n<p>And essentially at the end of those two years, the structure of their heart, so the stiffness of it and the shrinking of it was reversed. So their hearts grew and they became more flexible. And it was reversed in such a way that it was 20 years less aging. So their hearts looked more like 30-year-olds than 50-year-olds, which is pretty incredible.<\/p>\n<p><strong>Tim Ferriss: <\/strong>That is amazing. And I think it\u2019s also like, well, you think 50, it\u2019s too late to start exercising.<\/p>\n<p>Well, it\u2019s not too late. I mean you can be in your 90s and get benefits. So I think that\u2019s another really important sort of take-home with that story is that you can reverse your aging of your heart by 20 years if you really put in the effort.<\/p>\n<p>Five hours a week is about what I do, five or six hours a week. It\u2019s a lot of work. I didn\u2019t always do that, but I\u2019ve decided as I started to get into my mid-40s, I\u2019m going to spend less time podcasting and more time exercising because this is my health.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, foundational for everything else, that\u2019s the base of the pyramid.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right.<\/p>\n<p><strong>Tim Ferriss: <\/strong>All right. So let\u2019s 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?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>You do get two birds with one stone. And that\u2019s why I do like the vigorous intensity exercise because when you\u2019re kind of shifting into working out harder, when you\u2019re getting that vigorous intensity exercise, you are shifting somewhat to anaerobic metabolism.<\/p>\n<p>So you\u2019re working so hard that you can\u2019t get oxygen to your muscles fast enough to use mitochondria for the mitochondria to then make energy. So your body goes, I need energy quick right now, there\u2019s not enough oxygen here, and so you start to use glucose outside of the mitochondria as energy, and that\u2019s called glycolysis.<\/p>\n<p>And you\u2019re not just only doing glycolysis, by the way. I mean even if you\u2019re doing an all-out sprint, you\u2019re still somewhat using your mitochondria. It\u2019s not like a black-or-white thing, right? There\u2019s sort of gray here. But the reality is, is that when you\u2019re not going intense, you are not, mostly you\u2019re not doing anaerobic exercise.<\/p>\n<p>So what happens is when you\u2019re doing that, sort of getting in that anaerobic state, what I mean is like you\u2019re not using oxygen to make energy. You\u2019re just using glucose. You actually make something called lactate as a byproduct, and lactate is what\u2019s essential for the brain health.<\/p>\n<p>So there have now been a variety of studies. This was pioneered by Dr. George Brooks at UC Berkeley decades ago. So many studies have now shown this now. It\u2019s no longer a hypothesis, but it used to be called the lactate shuttle hypothesis where, when you start to do this vigorous intensity exercise and you get your lactate levels higher than baseline, baseline, you\u2019re usually about 0.9 millimolar or so lactate.<\/p>\n<p>You start to go above that and well beyond, you\u2019re getting 7, 10 millimolar or 15 millimolar, right? The lactate gets into your bloodstream and it\u2019s used by other tissue. So it goes back into the muscle. It\u2019s used for energy, gets into the brain, it gets into the heart, liver quickly. It happens within 20 minutes. You can do a HIIT workout, see your lactate go up to 15 millimolar, measure it 20 minutes later, and it\u2019s back to baseline. I mean, it\u2019s quick. It gets consumed.<\/p>\n<p>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\u2019ve been talking about, because it\u2019s an energetically favorable source of energy. Lactate is used by neurons to make energy, just like beta hydroxybutyrate is very similar. It\u2019s energetically favorable. All that stuff is happening, same stuff. So you\u2019re using the lactate, glucose is being spared, you\u2019re making glutathione.<\/p>\n<p>Lactate is also a signaling molecule. So in the brain, it\u2019s activating brain-derived neurotrophic factor, which is important for growing new neurons in the brain, which has been shown in human studies. So there\u2019ve been human studies that have done exercise for even just one year and shown that you can increase the growth of the hippocampus by like one to two percent after that year of training versus losing one to two percent of the hippocampus. That usually happens as you get in older age.<\/p>\n<p>So the lactate is again a product of that vigorous intensity exercise. It\u2019s increasing norepinephrine in the brain, serotonin. It\u2019s a signaling molecule. It\u2019s basically your body\u2019s, your muscle\u2019s way of communicating with the brain, \u201cHey, I\u2019m really working hard. This is a stressful time. Let\u2019s respond to that stress,\u201d right? So your brain is also working hard during exercise and particularly vigorous intensity exercise. It\u2019s stressful in the brain. Anybody that\u2019s done it knows it.<\/p>\n<p>Resistance training also increases lactate and resistance training is very stressful on the brain. And so it\u2019s like this response to that stress. Your brain is now being communicated from the muscles by lactate, which is the communicator and saying, \u201cHey, make all this good stuff so that we can not die,\u201d right? That\u2019s essentially the adaptations that are happening.<\/p>\n<p>So that\u2019s why I like to also incorporate vigorous intensity exercise into my program because I am also prone to neurodegenerative disease. I have Parkinson\u2019s disease on my dad\u2019s side, I have Alzheimer\u2019s disease on my mom\u2019s side, so I\u2019m 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.<\/p>\n<p><strong>Tim Ferriss: <\/strong>So let me ask you about two other things related to brain health since this is on the mind, ha-ha. For the first is related to saunas and the second one is vitamin D.<\/p>\n<p>So with saunas, I was looking back, and I think this is probably summarized by some LLM, so I want to be very careful with citing numbers. But I\u2019m looking at a summary, I believe, of the findings of a large Finnish study published in JAMA Internal Medicine 2015 that followed 2,000 middle-aged men for 20 years. That\u2019s wild. And it looks like, please correct me from memory, you can correct any of this, but all-cause mortality, 24 percent lower risk with two to three times per week. This is sauna use and four to seven times per week was associated with 40 percent lower risk.<\/p>\n<p>And I\u2019ll just cut to the one that\u2019s of greatest interest to me right now. It says in a follow-up paper, using the sauna four to seven times per week was associated with a 66 percent lower risk of dementia and 65 percent lower risk of Alzheimer\u2019s. Now at face value, if those numbers are roughly accurate, those numbers seem incredible, right?<\/p>\n<p>And I guess what I\u2019m wondering is how should we think about those results? Because if out of 100 people, two people were getting dementia and now it\u2019s one person, it\u2019s less interesting than other ways of interpreting the data. How should we think about this, and how do you personally use if you do sauna or hot tub or heat stress at this point?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. So those numbers are accurate, By the way. They\u2019re spot on, and there is a dose-dependence there, which kind of strengthens the data. So people that are using the sauna more frequently are having a more robust effect. You mentioned 24 percent lower all-cause mortality, and then 40 percent if they\u2019re doing two to three times a week versus four to seven times a week, they\u2019re having a 40 percent lower all-cause mortality. And the dementia risk is also extremely interesting to me.<\/p>\n<p>And this goes back, Tim, to some of the earliest experiments that I did as a sort of budding young biologist at the Salk Institute where I was working with these little nematode C. elegans worms and injecting human amyloid beta-42 into these worms, and essentially injecting it into their muscle so that they become basically the amyloid beta-42 aggregates and forms these aggregates as these worms age.<\/p>\n<p>And it happens very rapidly because their life expectancy is only 15 days. So within a day or so, they start to become paralyzed where they can\u2019t move their lower half of their muscles, 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.<\/p>\n<p>So I would do these experiments and then I would overact, basically when you do a genetic manipulation and you can make them overexpress heat shock proteins, which are something that are robustly activated upon heat stress as the name implies. And sauna has been shown to activate heat shock proteins. If you\u2019re in the 163 degree Fahrenheit sauna for around 30 minutes, you can activate your heat shock proteins by 50 percent more than baseline.<\/p>\n<p>So when I would add heat shock proteins that would be activated in these worms, it would prevent this from happening. These protein aggregates don\u2019t happen. And that\u2019s because one of the things that heat shock proteins do is they help repair damaged proteins that are misfolded and prevent them from aggregating. So you want to have more active heat shock proteins if you\u2019re wanting to prevent Alzheimer\u2019s disease.<\/p>\n<p>Now, there\u2019s a lot of animal studies that have shown this as well. For example, you can take a mouse and sort of give it Alzheimer\u2019s disease in this similar way. And if they have a lot of active heat shock protein genes, then they\u2019re not getting the Alzheimer\u2019s disease. It delays it, right?<\/p>\n<p>So when I remember reading this study, and it was like one of the things I was thinking about was, of course, the heat shock proteins are activated upon the sauna use that you would probably see a lower incidence of Alzheimer\u2019s disease and even dementia.<\/p>\n<p>There\u2019s other things as well. Cardiovascular health is really improved with the sauna. So sauna sort of mimics moderate intensity exercise. So if you\u2019re having improved cardiovascular health, that means more blood flow to the brain. Lots of things are happening, right?<\/p>\n<p>The one thing I do want to mention, Tim, and this study was, I think it came out in 2020-ish, I don\u2019t 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, and there was very interesting results there.<\/p>\n<p>So they sort of looked at people that are using saunas, but they also sort of categorized them based on the amount of heat, so how hot their saunas got.<\/p>\n<p>So in the Finnish studies and out of Finland, majority of the people are using the sauna at around equivalent of 174 degrees Fahrenheit. That\u2019s about what the average temperature of pretty much any of those studies that you cited. That\u2019s about the average temperature that they\u2019re using in, and they\u2019re in there for about 20 minutes.<\/p>\n<p>Now, this other study looked at a wide range of different temperatures, that temperature versus like the really, really high extreme end so people that were doing like 200 degrees Fahrenheit or more.<\/p>\n<p>And this is something that you can see nowadays, like there\u2019s this sort of go all in, go hard or go home, right? So people think that they need to go in a 200 degree sauna. And if they go in a 200 degree sauna, it\u2019s going to be better than going in a 175 degree Fahrenheit sauna, right? Apparently, not the case.<\/p>\n<p>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\u2019t recall, there was a protective effect, but only if they used saunas that were less than 190 degrees Fahrenheit. People that started going into the 190 degrees to 200 degrees Fahrenheit range actually had an increased risk.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Oh, no.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So that was something that I don\u2019t know that anyone talks about, but I\u2019ve done really, really hot saunas before. I personally don\u2019t like it. I get headaches, actually. So your head is in there and you have to think about that. Your head is getting heated up. So I don\u2019t know that it\u2019s necessarily good to go in a 212 degree Fahrenheit sauna for your head.<\/p>\n<p>Now I don\u2019t want to say that with certainty because there could be all kinds of confounding factors, but it\u2019s something to keep in mind.<\/p>\n<p>And why do you have to go above 190? Well, 190 is hot as hell. That\u2019s good enough. Like you don\u2019t have to go above that.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, my default setting, my sauna is 194, so it\u2019s just kind of like \u2014 well, I guess I set it some time ago, so it\u2019s just been set at 194, so that\u2019s kind of my default. So maybe I want to dial it back. Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I think 190 is great. Yeah, 190 is great.<\/p>\n<p>So you asked about me and how I use the sauna. Now I should also mention that hot tubs are good as well. And in fact, the study just came out a few weeks ago showing that hot tubs have comparable effects on blood pressure regulation, all these parameters that are looked at with sauna use as well.<\/p>\n<p>And a lot of people ask that question. \u201cOh, what about a hot tub or a hot bath?\u201d 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.<\/p>\n<p>And I think if you can get a sort of pool thermometer and keep the temperature of your bath 104 degrees Fahrenheit, which is what all the studies use, you have to keep adding hot water. That\u2019s fine.<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s pretty hot.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>But you want to stay in there.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, it\u2019s hot.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, it\u2019s pretty hot. You stay in there for about 20 minutes and you\u2019re going to have comparable effects.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, you\u2019ll be sweating like you\u2019re in a sauna. Don\u2019t worry about it. Yeah, 104.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Exactly. 104 is hot. And I actually do both. I do a hot tub and I do sauna.<\/p>\n<p>I like to do hot tub at night. It does seem to help with my sleep. But sometimes I\u2019ll do the sauna in the day and I\u2019ll do it after a workout, and it sort of extends my workout. I particularly like doing them after a workout like in the winter when it\u2019s cold and if I work out outside. So that\u2019s kind of how I use the sauna.<\/p>\n<p>I used to do hot, I was doing hot tubs for a while like every night. I don\u2019t do that in the summer because it\u2019s just hot and so I don\u2019t like \u2014 I actually shift more to doing cold exposure more in the summer, which is kind of funny. Pretty much the only time I do it is in the summer. Such a wuss. I like doing the heat a lot in the winter.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I would be very curious to see if they measured sperm like motility and morphology for all the males who are doing this. And they\u2019re like, \u201cGood news. You have this incredibly lowered risk of Alzheimer\u2019s. Bad news. You\u2019re effectively sterile from all the heat on your swimmers.\u201d<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Good point. Yeah, there\u2019s been studies that have shown you do lower motility, for sure. The motility rate\u2019s lowered and that those changes are reversed after six weeks of abstaining. So it is reversible.<\/p>\n<p>But also don\u2019t use it as a contraception method, either, because I know some people that have tried that. It doesn\u2019t work. You can still get pregnant.<\/p>\n<p><strong>Tim Ferriss: <\/strong>That\u2019s not so smart. Do you still use, if needed, curcumin or Theracurmin or any of these products? I think Meriva or Meriva was one that you mentioned as a formulation in place of NSAIDs, like ibuprofen or naproxen? Or is that something that you may have changed your mind on?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I actually just did it like a couple days ago when I had a headache, and I didn\u2019t know why. That\u2019s the thing that I go to still, and I mean, there\u2019s some cases where it won\u2019t work, where it\u2019s just like, I don\u2019t know, this is like a really bad headache. I don\u2019t usually get headaches, but if I don\u2019t sleep well or something, something going on or my cycle, I will get a headache and I use it.<\/p>\n<p>I use four of the Meriva, which is a phytosomal curcumin, which increases the bioavailability of the curcumin. I use the Thorne brand just because I like the, I think the brand is reliable, no affiliation with them, but it works for me. It really does. So it\u2019s, I think, 500 milligrams of curcumin per capsule, I believe. And so I do four, so I\u2019m getting two grams.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, cool.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>But I do still use it.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, just don\u2019t take it right after your workout, right?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, It doesn\u2019t have the same effect.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, it doesn\u2019t have the same kind of COX-2 inhibition as the other does, right?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It doesn\u2019t. Uh-huh. And in fact, I think it helps with DOMs, delayed onset muscle soreness.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Oh, I\u2019m sure, yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>And so sometimes, I do use it actually after a really, like, hard squat workout.<\/p>\n<p><strong>Tim Ferriss: <\/strong>All right. I\u2019m glad I asked.<\/p>\n<p>So speaking of not getting enough sleep, let\u2019s hop to creatine because, God, I don\u2019t know where I read this, but that higher doses of creatine, maybe like 25 grams, 20, 25 grams could combat sleep loss or some of the effects of sleep loss.<\/p>\n<p>What should we know about creatine? Creatine has been around for a long time. There are dozens of questionable sports performance, athletic performance products come out every year. Most of them are all marketing, no substance.<\/p>\n<p>Creatine has been used by athletes for a very long time, but for at least the last five years, I have been taking it typically five grams a day, more for the cognitive or potential cognitive benefits.<\/p>\n<p>But what else should we know about creatine? Because what you put in your newsletter not too long ago was forwarded to me, and then you told me via text. I was like, okay, we should probably talk about this. So how should we think about creatine and best practices for different applications?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, it\u2019s funny. As you mentioned, it\u2019s 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\u2019s been one of the supplements that\u2019s actually stuck, right? It\u2019s worked. And there\u2019s been countless studies showing its effectiveness, particularly with respect to increasing exercise volume.<\/p>\n<p>So in other words, what creatine is, is it\u2019s essentially, it\u2019s stored in our muscles as something called phosphocreatine. When you take creatine exogenously, it\u2019s stored in our muscles as phosphocreatine and then used for energy. So it\u2019s a way to make energy quicker, right? So the more of it you have stored, the quicker you can sort of make that energy.<\/p>\n<p>So what it\u2019s 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. I mean, you could do an extra set, or whatever it is you\u2019re doing. And that leads to obviously if you\u2019re increasing your workload, you\u2019re going to have increased muscle mass and muscle strength because you\u2019re increasing your workload. It doesn\u2019t work like protein in the sense that you can increase muscle mass because it\u2019s anabolic. You need to put the work in.<\/p>\n<p>So creatine by itself isn\u2019t going to make your muscles grow, but it is going to make you work harder. It\u2019s going to be easier for you to work harder, and so you end up increasing your exercise volume, which then has adaptations on your muscle. And that\u2019s 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\u2019s also really good for that explosive-power type of exercise, again, because getting that quick mobilization of producing energy.<\/p>\n<p>And I\u2019m 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 maybe one to two grams a day. It\u2019s also something that\u2019s found in dietary sources, particularly animal products. So it\u2019s high in meat, poultry, fish, dairy, not so much in vegetables. So vegans and vegetarians actually end up \u2014 they can have lower creatine if they\u2019re not supplementing with it because they\u2019re not eating animal products. Well, it turns out that it seems as though if you\u2019re supplementing and eating a high meat diet, you\u2019re getting a good amount of creatine. Five grams seems to be about the point at which your muscles get saturated at least over the course of a month or so. So if you\u2019ve been using creatine for a month or two, your muscle stores are saturated, and five grams a day is kind of what\u2019s consumed by the muscle on a daily basis to kind of maintain that.<\/p>\n<p>So I would argue that you might want to go above that to get the brain benefits, and here\u2019s why. Because your muscle is very, very greedy when it comes to creatine. So that five grams that you\u2019re taking \u2014 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\u2019s been shown in countless studies, and that\u2019s probably why you take it. I took it because it was countless studies showing five grams a day was the dose. That was the dose that you needed to get the muscle benefits.<\/p>\n<p>All these brain benefits now coming out seem to be at higher doses, and you mentioned one that was 25 grams, I mean 20 to 25 grams, which is kind of a crazy study where they did about 21 hours of sleep deprivation, essentially. They were barely sleeping at all. And giving them the 25 grams of creatine, 20 to 25 grams, depending on their weight, seemed to not only negate the negative effects of sleep deprivation on their cognition, but it also improved their cognition beyond what their baseline normal cognition is when they were sleeping.<\/p>\n<p>And that\u2019s what was really intriguing to me as well as some of the other studies where older adults are given 20 grams of creatine and it improved their cognition. We now have the first pilot study in Alzheimer\u2019s disease where, again, 20 grams were given to a very small number of people with Alzheimer\u2019s disease. It also improved cognition. It turns out that when you start to go above the five grams and you get into more the 10 grams range, then some of that creatine is getting into the brain versus being all consumed by the muscle. 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\u2019ll tell you when I don\u2019t do my 10 grams a day, what I have noticed is that the afternoon sleepiness kind of slump I get is completely gone if I take my 10 grams a day. 10 grams. I don\u2019t get afternoon sleepiness. I miss it. I get it.<\/p>\n<p>So it\u2019s not like a stored-up kind of thing. It\u2019s like, no, if I miss it that day, it\u2019s noticeable. If I travel and I don\u2019t have it, it\u2019s noticeable. So I\u2019m hooked on the 10 grams a day. If it\u2019s placebo, I don\u2019t care. It works. On top of that, what I\u2019ve also been doing ever since that study came out with 21 hours of sleep deprivation, I take about 20 grams of creatine when I\u2019m traveling and I have to give a talk or I\u2019m doing a podcast, particularly because oftentimes I\u2019m traveling either to Central Time or to Eastern Time. And I\u2019m giving a talk early in the morning, which is 6:00 a.m. my time. I got to be on my game. So I take the 20 grams and I kid you not, it\u2019s like you get this brain boost, but without the caffeine. It\u2019s hard to explain.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Without creepy crawly ants on your skin, jittery caffeine overdose.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right. Without that jittery thing. And even that, sometimes the caffeine isn\u2019t enough if you\u2019re really jet-lagged, especially if you\u2019re going across time zones.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Well, also for me, it\u2019s like I\u2019m a caffeine fast metabolizer. If I have a cup of coffee, I\u2019m on fire for 25 minutes and then I\u2019m sleepy. I think some of that is actually a glucose response, but that\u2019s a whole separate thing. I\u2019ve been using glucometer when I was doing all my ketogenic experiments and so on. I\u2019m 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\u2019t end up being net net that helpful for me unless I\u2019m doing a 20-minute sprint on something, which is probably never.<\/p>\n<p>So the creatine is super interesting to me. Let me ask some very specific, maybe mundane questions, but I think they\u2019re practical, which is, when these subjects were taking 20 or 25 grams, was that in one sitting? Was that in multiple divided doses? When you take it, is it in powder form? Is it little sachets that you can take with you on travel days? Is it encapsulated? What does it actually look like?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. With respect to all the studies, I don\u2019t remember if they were in one sitting. A lot of studies are. If they do like a 20 gram, it will be in one sitting. What I do is different. I do five-gram doses. So creatine monohydrate is the form I take. It\u2019s the absolute tried and true \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>The gold standard. Yeah, it\u2019s been around \u2014\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s the gold standard.<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s been around forever.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. There\u2019s a lot of other marketing out there that talks about other types of creatine, but that\u2019s really the gold standard. And I had Dr. Darren Candow on my podcast. He\u2019s a creatine researcher at the University of Regina in Canada, and we talked all about this and he really convinced me, creatine monohydrate is the way to go. I asked him about every type of creatine under the sun. But the way I take it is in five-gram doses. And so I do five grams first thing in the morning, and then I\u2019ll do my workout and then I do another five grams about 11:00 a.m. And that\u2019s my 10 grams that I get.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Got it.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>When I\u2019m traveling, I do have these sachets that, again, Thorne makes. By the way, no affiliation. I mean, there\u2019s probably a million other \u2014 I like Thorne because their creatine is NSF-certified, and so it\u2019s free of contaminants. I really like that. So again, find your own favorite brand, but I like this brand. And they have sachets, which are five-gram sachets. And so I will have my 10 grams for the day, or again, if I\u2019m traveling for work-related purposes, I will take 15 to 20 grams depending on how much I need. In that case, I will do two 10-gram doses. For me, I can tolerate that. I don\u2019t have any GI problems with it. Some people do.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. I was going to bring that up.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. Some people do. I think doing the five-gram doses is pretty easy on the gut. Most people don\u2019t have a big problem with the five grams.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, five is fine.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s when they go above that.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. So I\u2019ll say a few things. So 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\u2019ve looked at lab reviews of 20 off-the-shelf melatonin products, and it ranges from zero melatonin up to 20x the label amount. It\u2019s just bananas. So I use Momentous creatine, but it\u2019s passing the same hurdle.<\/p>\n<p>And I\u2019ll say good news, you can reduce the likelihood of cognitive deficit from sleep deprivation. Bad news is you could increase the likelihood of disaster pants if you have 20 grams at one sitting. And I will say, maybe from personal experience, maybe I\u2019m just talking about somebody else, but if you really want to increase the likelihood of disaster pants, then you can do a bunch of caffeine, like a double espresso or black coffee with MCT powder, and then have your creatine around the same time. That would be asking, you\u2019re going to want to pack some Pampers in your travel kit if you do that. So yeah, just be aware of the GI stuff.<\/p>\n<p>But I\u2019m excited to up my intake, because the science that you cited in the study or studies in your newsletter seemed really compelling. And it\u2019s also one of those supplements where it\u2019s like, okay, look, I assume this is on the grass list. They generally recognized it\u2019s safe, seems very well-tolerated, over decades and decades of research, assuming you don\u2019t have some who knows, right? Really outstanding kidney dysfunction or something, maybe. So why not, in a sense? It\u2019s also relatively inexpensive compared to a lot of things.<\/p>\n<p>Let me ask you, just because this has been on my mind. With the sulforaphane \u2014 I mangled the pronunciation a bit. Sulforaphane. Do you take that better on an empty stomach? Better with food? This has become an issue when I\u2019m doing the intermittent fasting sometimes, especially if there\u2019s something like the AREDS 2, which I\u2019m taking for the eye health, which is supposed to be twice a day. And I\u2019m like, oh, it\u2019s part of the reason why I\u2019ve been doing the, quote, unquote, \u201cdirty fasting,\u201d with a little bit of fat in the form of that heavy cream in coffee, was to try to take supplements earlier in the day that are benefited from some type of fat in terms of absorption. Sulforaphane. Does it matter?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I think if you can take it fasted, that\u2019s great. Some people find it kind of as hard on their stomach and so they like to take it with food, and that\u2019s really the only reason to take it with food is because they get upset stomach. It\u2019s like GI problem. So that would be, again, the only really real reason that you would have to really take it with food.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I wanted to loop back around just so people aren\u2019t like, \u201cFerriss, you forgot about vitamin D.\u201d I wanted to talk about vitamin D. So the vitamin D, I\u2019ve taken vitamin D forever, tend to take 5,000 IU a day. I particularly in the summer get I would say at least an hour in the sun without skin protection. And I built up to that. I\u2019m not an idiot about it. And yet, I am barely \u2014 in my labs, I\u2019m always barely squeaking by on vitamin D.<\/p>\n<p>And for almost all of my adult friends who get labs \u2014 and this is also race agnostic, right? Everybody is deficient or just on the border of being deficient, even if they seem to be taking a lot of supplemental vitamin D and getting a lot of sunshine. And I have to ask myself, what the hell is going on here? In what set of circumstances is it possible that everyone would be so deficient if they seem to be getting a bunch of sunlight, they\u2019re taking a bunch of supplemental vitamin D? Can you shed any light on this?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I can.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Or is there a problem with this measurement in the first place? Which is why I was talking about proxies and confounders and stuff earlier with respect to some of the other studies. Yeah, so please and please educate me.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yes. Okay. So the way vitamin D is measured, so vitamin D actually gets converted into a steroid hormone, and this steroid hormone, essentially, it\u2019s going inside the nucleus of our cells where all of our DNA is and it\u2019s activating 5 percent of the protein encoding human genome. Many of these genes, it activates Klotho. By the way, you mentioned Klotho. Vitamin D is important for activating Klotho.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. Nice.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. So very hugely important for dementia risk, which we can talk about. But to answer your question, so your vitamin D levels are measured by a proxy and it\u2019s called 25-hydroxy vitamin D, which is the precursor to the steroid hormone. So essentially, vitamin D3, which is made in your skin, or if you supplement with it, exogenously gets into your bloodstream. And that vitamin D3 then goes to the liver and it\u2019s converted into 25-hydroxy vitamin D. That\u2019s the major circulating form of vitamin D.<\/p>\n<p>After 25-hydroxy vitamin D is made in the liver, it then goes to the kidneys and it\u2019s made into the actual act of steroid hormone, which is called 1,25-hydroxy vitamin. Well, it turns out the enzymes that are doing the conversion of vitamin D3 into that stable form that everyone gets when they\u2019re getting a vitamin D blood test, that\u2019s what they\u2019re looking at, requires magnesium to work. And there have been studies showing that with low magnesium, it doesn\u2019t happen readily at all.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Interesting. Interesting.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>And so 50 percent of the US population has insufficient levels of magnesium. So you\u2019re talking about a coin toss here, right? One out of two. One out of two. You have 50\/50 chance a person\u2019s not going to be getting enough magnesium. That\u2019s been shown to actually play a role in circulating levels of vitamin D. There have been NHANES studies and stuff showing that people that have low magnesium intake also have low circulating forms of 25-hydroxy vitamin D. So that\u2019s one thing.<\/p>\n<p>Another thing comes down to genetics. There\u2019s actually a lot of people that have SNPs, very common ones that probably came from more southern areas, that don\u2019t make as much vitamin D3 from the sun exposure because probably they\u2019re getting so much sun, right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So essentially, there\u2019s the genetic component as well. And I\u2019ve seen a lot of people\u2019s different SNP makeups, and I know quite a few people that actually have to take a super high level of vitamin D3 to actually get enough vitamin D. And then the other thing is that you mentioned earlier the variation between supplements. There have been studies on vitamin D supplements, and it\u2019s the same problem with melatonin. There\u2019s some vitamin D supplements with a fraction of what is stated in terms of concentration of vitamin D3 on the nutrition facts, and then some of them have 10 times as much vitamin D.<\/p>\n<p>So there\u2019s just this huge variation where you\u2019re like, it says it has 5,000 IUs but it only has 500. So there\u2019s a lot of different factors that could be contributing to that as well. And then there\u2019s also in terms of people getting sun exposure, you said you don\u2019t wear sunscreen, some people do. People that have darker skin pigmentation have melanin. That\u2019s a natural sunscreen. There have been studies showing that, for example, out of the University of Chicago, there was a study that was published a few years back showing African-Americans have to stay in the sun six to 10 times as long as a Caucasian to make the same amount of vitamin D3 from the same amount of sun exposure. Because they have a natural sunscreen, melanin, which is that darker skin pigmentation. It\u2019s a natural sunscreen. It\u2019s also why their skin always looks great as they\u2019re aging. You\u2019re like, \u201cOh, you\u2019re 75? Your skin looks like you\u2019re 30.\u201d<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. I remember, I won\u2019t mention him by name, but meeting this African-American fellow. And I thought he was 25, and he was 53 and had five big \u2014 and the way we got to that is I was like, \u201cOh, are you married?\u201d And he\u2019s like, \u201cYeah, I have five kids.\u201d And I was like, \u201cWait, what? You have five kids? You don\u2019t look Mormon.\u201d Like, \u201cWait, what\u2019s going on here?\u201d And lo and behold.<\/p>\n<p>So let me dig into some of this real quick. So recommended brands for vitamin D and how much should someone like me potentially be taking as a starting point, because I\u2019m also wary of taking too much vitamin D. I don\u2019t want to overdose on vitamin D. It seems like there are some risks associated with that. Maybe I\u2019m overstating them, but how do you think about that? And then in terms of this rate limiting factor that you mentioned, magnesium, what type of magnesium? How much? How should I think about both of these?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Okay. So first of all, we need to talk about vitamin D levels and what the optimal levels are, and that\u2019s really important for someone to figure out how much they should supplement with. I tend to think anywhere between 40, 60 to 80, 40 to 80 nanograms per mil, you\u2019re in an optimal range. I like 40 to 60. I think that\u2019s my sweet spot, and that\u2019s because there\u2019s lots of studies out there showing all-cause mortalities lower within that range. Fifty nanograms per mil would be great. I mean, that\u2019s a great place to be. If you\u2019re below 30, if you\u2019re about just 30, you might want to try to get up to 40.\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Let\u2019s just say for argument\u2019s sake that I\u2019m at 30. I think I\u2019m probably closer to 40, but let\u2019s say it\u2019s 30.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Okay. For someone that\u2019s at 30 nanograms per mil is supplementing with 5,000 IUs a day and getting an hour of sun in the summer without sunscreen, that you probably should be closer to 50 nanograms per mil, I would say, if you\u2019re taking that \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. I\u2019ll check my last labs. I just had them pulled two weeks ago, so I\u2019ll double check.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right. So for someone in that case, you might go up to 7,000 IUs and check and see where you\u2019re at a month later. And if you then are in the 40 to 50 range, then that\u2019s your optimal dose to take. And this is an important conversation to have, Tim, because it really is, there\u2019s an individual component here and people just want to, at the end of the day, they want to \u2014 how much do I take? How much do I take?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, you have to get a vitamin D blood test. This is one of those \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>For sure.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>This is one of those that you have to really measure because, as you mentioned, there\u2019s huge variation there in terms of absorption. And then the magnesium issue, there\u2019s the RDA for magnesium. So for men, it\u2019s about 400 milligrams a day. For women, it\u2019s about 300 milligrams a day of magnesium intake from diet or supplemental sources. If you\u2019re taking a supplement, and also if you\u2019re athletic and sweating a lot and using the sauna, those requirements can go up between 10 percent to 20 percent, depending on how physically active you are. If you\u2019re like the endurance athlete, you\u2019re on the 20 percent higher range. If you\u2019re more just like the average, like I\u2019m a committed exerciser, then you might have to go up 10 percent above that.<\/p>\n<p>So typically, the best forms of magnesium to take are the forms of magnesium that are the organic forms. So that would mean it\u2019s bound to salt, like magnesium citrate or magnesium malate or magnesium taurate. Those are more bioavailable than magnesium oxide, for example. There\u2019s also magnesium glycinate, which is also a very bioavailable form. It\u2019s the form that I take as well. And dose range, you can take 300 milligrams a day and probably not have any GI distress. And so that gets you most of the way there. And then you get the rest from your diet. You\u2019re eating some leafy greens. You\u2019re eating maybe some almonds or something, which are really high in magnesium. If you\u2019re not getting any greens at all, then you\u2019re going to have to go up a little bit more to the 400-450 milligram range, especially if you\u2019re athletic. But that if you\u2019re taking something like electrolytes, you\u2019re getting some magnesium there so you can figure out how much magnesium is in your electrolyte and that can be counted towards it as well.<\/p>\n<p>There\u2019s also magnesium threonate, which is the magnesium form that is allegedly able to cross the blood-brain barrier better than other forms of magnesium that I mentioned. And I say allegedly because it\u2019s animal studies that have shown that. There have been a couple of human studies that were, unfortunately, there\u2019s a conflict of interest. They were done by the makers of the magnesium threonate supplement. So that\u2019s always important to keep in mind. But they have shown that magnesium threonate could improve some cognitive scores if you kind of pulled all the cognitive scores together. And so I think that there\u2019s no reason why if you\u2019re interested in cognition and stuff, trying the magnesium threonate.<\/p>\n<p>A lot of people like it as well. So that\u2019s another form of magnesium, although I do think you should probably take some magnesium glycinate along with that because you don\u2019t want all the magnesium going into your brain. You want some of it going into your liver and activating the enzymes that are converting vitamin D3 into 25-hydroxy vitamin D. So that is something to keep in mind if that form of magnesium indeed is going into the brain more, you want to make sure you\u2019re getting some of the other forms to cover the other bases of other organs as well.<\/p>\n<p><strong>Tim Ferriss: <\/strong>What brand of vitamin D supplementation and magnesium glycinate do you use? Is that also Thorne, or are they other suppliers?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I use Pure Encapsulations for the vitamin D. I have some friends, mutual friends of ours, that like the VESIsorb Vitamin D3. So people that are not able to increase their vitamin D as well, VESIsorb really increases the bioavailability of a lot of things, including ubiquinol, the CoQ10 I mentioned. I should have mentioned that I buy my dad. That\u2019s the form I get for him because it increases the bioavailability. Also, some fish oil, it\u2019s been shown to increase the bioavailability. So VESIsorb Vitamin D3 can be found at Pure Encapsulations. I don\u2019t 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 threonate, I use Xymogen. I like the Xymogen magnesium threonate.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Great. All right, thank you. I\u2019ll get on the magnesium, and I\u2019ll also check my last labs. I mean, I am very bespoke about this stuff, and to your point, you got to check your levels, guys. You can\u2019t just be shooting in the dark here. It\u2019s not a good idea.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right.<\/p>\n<p><strong>Tim Ferriss: <\/strong>All right. Where should we zig and zag to next? Do you want to talk about microplastics and mitigation strategies?\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s really a big mess. And the microplastics are now, it\u2019s not just, okay, well, I\u2019m not going to drink out of bottled water, plastic bottled water. If you can get any kind of water filter, any kind of water filter is great. Reverse osmosis is the best because it filters out the smallest, smallest nanoplastics, which are the kind that are actually crossing the blood brain barrier and getting into the brain. In the brain, they\u2019re associated with Alzheimer\u2019s disease and all kinds of things, but we now know they\u2019re in chewing gum. So anything with the word \u201cgum base\u201d is made of a plastic polymer. So if you chew gum, it has to be plastic-free gum. And it\u2019s not the same. I\u2019ll tell you that. But it\u2019s in gum. It\u2019s tea bags. Tea bags. If you make tea with tea bags, all sorts of tea bags, they\u2019re releasing just thousands of microplastic into your beverage.<\/p>\n<p>They\u2019re in essentially everything. And the problem is that it\u2019s very hard to avoid. The best things that you can do to avoid them is reduce exposure, which would be the water filter, try to avoid drinking out of any type of water that\u2019s in a plastic bottle. But it turns out a new study just came out showing it\u2019s also been found in glass bottles. I know. It\u2019s like, are you kidding me? Come on.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Apparently, the paint that\u2019s on the lid of the glass bottle is shedding little particles into the beverage, and those are microplastics because the paint has got plastic in it. And so essentially my take home from this is still, you want to probably use \u2014 if you\u2019re traveling and you have to choose between a plastic water bottle with water in it and a glass one to buy, I would still buy the glass one because the particle size is higher. It\u2019s larger in the glass bottles, and that doesn\u2019t get absorbed in the gut very well at all. If any, you actually excrete it through feces.<\/p>\n<p>And so I think the next study that\u2019s going to be done will be to show this essentially. I\u2019m sort of speculating here, but because the size matters, the size of plastics and the plastic bottles are super small, and that\u2019s really absorbed well by the gut epithelia and taken up into the bloodstream and gets to the other organs. Also, the plastic chemicals like BPA are in plastic. They\u2019re not in the glass. So I still think that opting for glass is the best option. Even though that study came out, \u201cOh, glass has more plastic than plastic bottles.\u201d It\u2019s like one of those sensational headlines. The devil\u2019s in the details, right? There\u2019s always a nuance there. And in this case, the size does \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>The size matters. In this case, size matters.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Size matters in this case, for sure. But when it comes to people want to know, is there anything I can do to sort of detox these microplastics? That\u2019s the big concern that people have. Well, if I can\u2019t reduce, if it\u2019s impossible to reduce my exposure because they\u2019re just absolutely everywhere, then can I sort of get rid of them? And unfortunately, there\u2019s not a lot of evidence right now out there that you can perhaps some of this electrophoresis sort of thing where you kind of filter your blood. But who\u2019s doing that? Maybe you\u2019ll do it, but that\u2019s not something that the public\u2019s generally going to do. And I don\u2019t even know that I\u2019m going to do it.<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s also, even if they were going to do it or willing to do it, it\u2019s not readily accessible or cost-effective for people to use.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Exactly. 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\u2019s coming through your tap, through your sink, does have microplastics in it, and that\u2019s a major, major source of microplastic exposure for many, many people. So if you can get any type of water filter again. You can even get countertop reverse osmosis water filters. Those are great for filtering out the majority of microplastics. Big, big, big \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>I wonder if the Big Berkey countertop filtration system is effective at filtering out microplastics? I don\u2019t know.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It is. It\u2019s effective at filtering out microplastics. It\u2019s not clear about the nano-nano, like the super, super small size ones. It might. It might not. I don\u2019t know, but it does, definitely the micro size ones, it does filter out microplastics. So the thing with reverse osmosis is it\u2019s really filtering out all, even the nanoplastics as well. Of course, you have to consider re-adding certain minerals and trace elements that are found in water back to your water. And some reverse osmosis companies do that. You can have them put on a filter that\u2019ll just add it back in after it filters out all the microplastics. But you can also just buy mineral drops and put those in your water, or you can take a mineral supplement that has some of these minerals that are taken out as well.<\/p>\n<p>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\u2019re also associated with Alzheimer\u2019s disease or associated with cancer, all sorts of things. And those can actually \u2014 I think, actually. This is a big speculation on my part, just based on animal studies. I think sulforaphane plays a role in detoxing BPA from our system, and that\u2019s because of the whole situation where it activates the very same enzymes that do excrete BPA through urine. It does that, and it\u2019s been shown in animal studies, animal studies that are given sulforaphane, and then given a high dose of BPA, it completely blunts the toxicity of the BPA, which is pretty interesting as well.<\/p>\n<p>So the other thing to keep in mind is heat, and I\u2019ll say this. All the to-go cups that you\u2019re out there buying when you go to your favorite coffee shop, fill in the blank for the most part, with the exception of the Blue Bottle Coffee, phenomenal, they\u2019re great, all these paper cups are lined with plastic. And when you add a hot beverage into the plastic lining, it releases all these microplastics into your beverage, and it releases the chemicals like BPA into them, like 50-fold. Blue Bottle Coffee, by the way, they apparently line their cups with sugarcane, polylactic acid, and so they don\u2019t have any plastic.<\/p>\n<p>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, \u201cDo you guys line your cups with plastic?\u201d And she\u2019s like, \u201cNo, we line them with sugarcane.\u201d I was like, \u201cYes.\u201d So that\u2019s something to keep in mind. You see a lot of people drinking these to-go cups everywhere, and you\u2019re pouring a hot beverage into it. It\u2019s a really, really major source of microplastic exposure because you\u2019re accelerating the breakdown of the plastic. Heat accelerates the breakdown of the plastic, and essentially, you\u2019re doing that in real time, like in an instant, right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>And ditto for the \u2014\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Bring your own cup. Yeah.<\/p>\n<p><strong>Tim Ferriss: <\/strong>\u2014 teabags, right? So.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>And the teabags, so you have to do loose leaf tea, which is what \u2014 now I\u2019m always, it\u2019s got to be loose leaf. I\u2019ll bring my own little \u2014 I\u2019ll sometimes open the teabag out and I bring my own little tea steeper thing with me that you can \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Like the little half globes that connect together.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, exactly. Mine are the ones that you kind of squeeze on it and opens up and then closes the clamps back together. But yeah, so I use that because the teabags, again, you\u2019re getting the heat on top of the plastic, polymers that are making up the teabag and accelerating the breakdown of plastic. So you\u2019re drinking plastic beverage.<\/p>\n<p>And there\u2019s all these health consequences now associated with microplastics. You mentioned the brain. It\u2019s been found 20 times \u2014 to accumulate 20 times more in the brain than in other organs. And people with Alzheimer\u2019s disease have up to 20 times more microplastics in their brain than people that didn\u2019t have Alzheimer\u2019s disease. And then the same goes for cardiovascular disease. There\u2019s been a study that was published in the New England Journal of Medicine about a year ago, showing that people that had microplastics in their whatever aortic part that they were doing surgery on, those individuals ended up dying of a heart attack within the next three years versus ones that didn\u2019t have any microplastics.<\/p>\n<p>Anyways, all sorts of interesting stuff. We don\u2019t know enough about it. But I think enough said, we do know that they\u2019re not good and we want to try to avoid them as much as we can, and that they are pervasive. They\u2019re everywhere. It\u2019s ubiquitous.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah. Yeah. And there\u2019s some simple things people can do. I mean, this is not necessarily in the same category, but it\u2019s like, look, the effects at least seem to be, I don\u2019t know if they\u2019re well established, maybe there are animal studies on this, but certainly there\u2019s a lot of seemingly compelling evidence pointing to the effects of, say, phthalates as endocrine disruptors on male fertility. And it\u2019s like, look, if you have shampoo or soap with a really strong fragrance, just stay away from it. I mean, they\u2019re very simple guidelines for some of these things that I think can be very helpful.<\/p>\n<p>Yeah, the microplastic stuff is kind of terrifying. I did not realize the gum. I knew about the teabags, the water filtration. Did not realize the gum. I don\u2019t chew a lot of gum, but one of my relatives who has Alzheimer\u2019s has chewed four packs of gum a day for 10 years. And I was like, \u201cOh, shit. I wonder if that\u2019s a contributor.\u201d<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Wow, that\u2019s crazy. I started chewing gum when I learned about the research showing that xylitol could inhibit some of the S-mutagens bacteria that are involved in cavity formation.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Then a few years later, you\u2019re like, \u201cGoddamn it.\u201d<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, I was able to reverse cavities multiple times, and my doctor was like, \u201cKeep doing it.\u201d I\u2019m like, \u201cYes, the xylitol.\u201d And then I found out, it was like this year, I found this out, Tim. This year the study came out with the gum, and I was devastated. I mean, I\u2019ve chewed so much gum, so much gum, and I\u2019ve let my child chew it, and it\u2019s like, all I could think about was how great it was for the teeth, and now it\u2019s like, oh my God, this has 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 \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s like chewing on bark? Is it like chewing on \u2014<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s pretty much bark.<\/p>\n<p><strong>Tim Ferriss: <\/strong>\u2014 tasteless bark?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s actually made from bark.<\/p>\n<p><strong>Tim Ferriss: <\/strong>That\u2019s awesome.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>No, it\u2019s made from trees, like some kind of sap or something from the bark.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Resin or something, yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Sounds delicious. You can\u2019t just do xylitol mints? You have to chew it? I guess you have to get it up \u2014<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>You can do xylitol mints. Yeah.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Okay.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>You can do xylitol mints. I have those as well.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Well, just to, on the same thread of you don\u2019t always get it completely right, I was looking at some of the research docs that I have in front of me, and there\u2019s one section that I highlighted, which was each three-hour increase in nighttime fasting was linked to 20 percent lower odds of elevated hemoglobin A1C, this long-term marker of blood glucose. And then one of your bullets was the effects of alcohol in the brain and cancer risk, and so I was reading this document over dinner. I sent this to you, and my time zones are all screwed up, because I just got back from Polynesia, and so I\u2019m eating at 10:00 p.m., 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? You\u2019re not going to always get it right. But let\u2019s talk about \u2014 do you want to talk about the booze for a second?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I mean, so alcohol, yeah, and especially since we were talking about APOE4.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Just to depress people after the microplastics?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I know. It\u2019s like, \u201cYou can\u2019t have any enjoyment at all if you want to live a long, healthy life.\u201d No, you need to find a good balance, obviously. So alcohol is \u2014 it\u2019s a toxin. It\u2019s also a lot of fun. I mean, it\u2019s fun to drink and have a glass of wine. Sometimes it helps \u2014 it feels like you\u2019re lowering your stress, lowering some inhibitions. It\u2019s fun to do with a group of friends and stuff.<\/p>\n<p>It\u2019s not so great for the brain though, and certainly, if you\u2019re concerned about Alzheimer\u2019s disease and dementia risk, and I will say that there\u2019s been a lot of mixed research out there looking at alcohol consumption and dementia and Alzheimer\u2019s disease, where some of it says, well, if you\u2019re doing moderate alcohol consumption, you can actually have a protective effect against dementia and Alzheimer\u2019s disease, where it\u2019s like this idea that alcohol, like a glass of wine a day is actually beneficial for you. So you should be doing that.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I wonder if it\u2019s actually the social interactions facilitated by alcohol versus the moderate alcohol itself, I wonder.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, there\u2019s a lot of things going on here. Certainly social interactions, that\u2019s a confounding factor. Also, when people then looked for their APOE genotype, it was found that it was actually in the non-APOE4 carriers that you would find that benefit, not in the APOE4 carriers. And then on top of that, there\u2019s been all this research that, over the years, has looked at moderate alcohol consumption, and depending on the study, that number changes, which is such a big bummer. It\u2019s like, well, what does that even mean? In some cases, it can be seven drinks a day in some cases.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Seven drinks a day?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Sorry, a week.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Okay.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Oh, my gosh. No. In some cases it\u2019s seven drinks a week for a woman, but for a man, it\u2019s like 14 drinks a week.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I wonder who authored that study.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, exactly. It\u2019s a big difference. But on average, moderate alcohol consumption is more like seven drinks a week. Seven drinks a day would definitely be heavy alcohol consumption. That would be more like substance abuse, substance use or use disorder. Let\u2019s cut the substance abuse part out. Alcohol use \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Why can\u2019t you say abuse anymore? Why do these things have to keep changing? It\u2019s so ridiculous.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>And it\u2019s hard for me because I\u2019m always tripping on my words.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Use disorder sounds better than abuse? I mean, what are the reasons behind this? Do you know?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I guess it\u2019s politically correct.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Because I\u2019m finding all this psychedelic stuff, and it was abuse for a long time, and then all of a sudden, nope. Verboten. Can\u2019t say that. Who knows? Anyway.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s funny. I still have read so much of the literature that I still say abuse, because that\u2019s what I\u2019m familiar reading. But anyways, back to this, what I was saying, which is seven weeks \u2014 sorry. All right, we\u2019re going to cut this out, Tim. Seven drinks a week.<\/p>\n<p><strong>Tim Ferriss: <\/strong>How many drinks have you had before this podcast, Rhonda?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Well, I did have some ketone ester, where there\u2019s a little bit of alcohol that is involved with that.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, that\u2019s true. Yeah. Watch out for the \u2014\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>There\u2019s been \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>\u2014 1,3-Butanediol. Anyway.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right. There\u2019s something called the sick quitter hypothesis, which is essentially a lot of these studies we\u2019re 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 the sick-quitter aspect, which is essentially \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>What is sick quitter? Is that English?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>\u2014 someone gets sick. Yes.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Oh, sick quitter. I got it. Okay.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Sick quitter.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Okay.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Quitter, yes. So essentially, what it means is they get sick, and so they quit drinking alcohol. And then when they\u2019re filling out their questionnaire, however many years later, whatever, they are asked, \u201cHow many drinks do you have a week?\u201d And they say \u201cZero\u201d because they quit, but they don\u2019t \u2014 the question wasn\u2019t asked, \u201cWere you a former drinker?\u201d<\/p>\n<p><strong>Tim Ferriss: <\/strong>The prior drinking habit.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yes, very important. And now, more studies are, when they\u2019re doing the questionnaires, are asking that question. But many, many, many years and many, many studies did not ask that question. And so it\u2019s very possible when you\u2019re looking at these cohorts of people that are comparing moderate alcohol consumption to no alcohol consumption, they\u2019re saying, \u201cOh, look, there\u2019s a benefit. You have less cardiovascular disease risk. You have less dementia risk if you drink versus not drink. We don\u2019t really know if that\u2019s because these people were former drinkers and did so much damage already that that\u2019s why they\u2019re getting dementia more.<\/p>\n<p><strong>Tim Ferriss: <\/strong>In the non-drinker group.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>In the supposed non-drinker group.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Quote-unquote non drinker group.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Exactly.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>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\u2019s just unambiguous. Alcohol is now classified as \u2014 I think it\u2019s a \u2014 is it a group-1 carcinogen? Where it\u2019s known to play a role in causing cancer. There\u2019s no gray area here, and there\u2019s many, many different cancers that it\u2019s associated with. So alcohol does get metabolized into acetaldehyde \u2014 that is something that can be a mutagen. It is a mutagen. It can cause cancer.<\/p>\n<p>And so there\u2019s a lot of different cancers that\u2019s associated with breast cancer, colon cancer, for example. Breast cancer is a big one because women\u2019s 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\u2019re at a dinner party, and eight women are there, then one of those women will come down and be diagnosed with breast cancer in her lifetime.<\/p>\n<p>So when you add alcohol consumption on top of that, if you\u2019re talking about moderate alcohol consumption, that risk can go to one in six, which is very significant for lifetime risk. So I do think that alcohol, I mean obviously some people enjoy it, and I don\u2019t know that there\u2019s any amount that\u2019s actually safe, but if you\u2019re really looking for a number, it seems like one or two drinks a week seems to be the safe spot.<\/p>\n<p>I mean, the safest would be zero, right? Zero drinks. But if you\u2019re really not wanting to have the damage, the light drinking, which is the one to two drinks a week, that\u2019s where you\u2019re probably the best off. Talking about a weekend, you have a weekend and you\u2019re doing a glass of wine, maybe Friday or Saturday night. I think that\u2019s the safest if you\u2019re looking for some alcohol consumption. If you\u2019re going above that, just be aware there is definitely a risk of increasing dementia, increasing cancer risk.<\/p>\n<p>However, there are other lifestyle factors that also play a role here, like being obese and exercise. In fact, some of the alcohol and dementia studies that have shown an increase in dementia incidence with alcohol consumption were negated by people that were highly physically active. So I do think there\u2019s other things to consider. You can\u2019t just silo everything, right? I mean, you\u2019ve got to look at the whole lifestyle.<\/p>\n<p><strong>Tim Ferriss: <\/strong>So air squats before gelato and my tequila shots?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Well, let me ask you, what is the purported mechanism, maybe it\u2019s known, by which alcohol increases the likelihood that you\u2019ll experience some of these maladies like cancer, dementia, et cetera? Is acetaldehyde acting as a mutagen and therefore just smashing your DNA, so you have these mutations that then proliferate and turn into some type of dangerous cancer? Is there more to the story of mechanism of action?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. I mean, acetaldehyde is one aspect of it. It\u2019s an important one. But the alcohol itself is causing inflammation. I mean, it\u2019s causing gut permeability, essentially. It\u2019s very hard on the gut. And so what ends up happening is you release inflammatory factors into your bloodstream, like the polysaccharide gets released into the bloodstream. Inflammation gets activated. Inflammation is a major cause of cancer and also brain aging. So the brain aging aspect is definitely linked to the oxidative stress component and the inflammation component. Damage is happening to neurons, and I think one of the reasons why people with APOE4 are a little more sensitive to alcohol is because the repair processes in individuals with APOE4 isn\u2019t as robust.<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s compromised already.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>It\u2019s compromised already, right. And so they\u2019re not able to repair that damage that\u2019s being generated from the alcohol, whereas people without the APOE4 somewhat can repair it a little bit better. And then you add the breakdown of the blood-brain barrier on top of that, and then you\u2019re just getting more inflammation into the brain. And neuroinflammation is a major cause in Alzheimer\u2019s disease. I mean, it\u2019s really a known factor now. And you\u2019re disrupting mitochondria, you\u2019re disrupting \u2014 just everything you know about to be important for health is sort of affected by alcohol, through a variety of mechanisms.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Do you ever drink?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I don\u2019t drink very much. I used to drink more. Sometimes I go several months without having anything.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I do. So I\u2019m not putting you on the stand here.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, no.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I don\u2019t drink all the time, but I\u2019m just giving you a little leeway.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah. I used to drink at least a couple times a week where I would do the weekend thing, but I don\u2019t drink much anymore. Once in a while I\u2019ll have a glass of Prosecco for a celebration. I do enjoy it, but I definitely try to limit it to certainly once a week. But like I said, these days I\u2019ll go a couple of months without having anything, and then I\u2019ll have a social situation where I like to do it. And the great thing about that is I\u2019m so sensitive to the alcohol that I\u2019m such a lightweight, and it\u2019s great because I get one glass of Prosecco and I\u2019m like, \u201cThis is amazing.\u201d<\/p>\n<p><strong>Tim Ferriss: <\/strong>So I\u2019ll say, what fringe benefit, and this could be \u2014\u00a0<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Oh.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Go ahead.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Can I mention one other thing, Tim?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Jump in. Yeah, yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So I forgot to mention with respect to the dementia risk and alcohol, you asked about mechanisms, the sleep aspect, right?<\/p>\n<p><strong>Tim Ferriss: <\/strong>Oh, for sure. That\u2019s a huge one.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yes, it\u2019s a huge one because alcohol does disrupt sleep.<\/p>\n<p><strong>Tim Ferriss: <\/strong>That\u2019s massive, yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Massive. I know people that use it because it helps them fall asleep easier, so it\u2019s definitely something that decreases that sleep latency. People can fall asleep easier, but it completely disrupts. So they have more awakenings in the middle in the night, and it disrupts REM sleep. So there\u2019s every reason to definitely not drink and certainly don\u2019t drink close to bedtime. You want to kind of be able to get rid of the alcohol before you go to sleep. Going back to your picture, you were doing everything wrong, but \u2014\u00a0<\/p>\n<p><strong>Tim Ferriss: <\/strong>Oh, that was, yeah. Am I doing it right? Yeah, that was very much deliberate.\u00a0<\/p>\n<p>Rhonda, one thing, and I\u2019m so curious if maybe you\u2019ve heard reports of this, I could ask my audience and figure it out. Wasn\u2019t placebo effect because I didn\u2019t expect it, but it seems like when in ketosis past 1.5 millimolars, even above 1.2 for me, and I use a precision extra device to track that. I\u2019ve tried a number of other devices that are remarkably erratic. In any case, I am much more sensitive to alcohol, much, much, much more sensitive to alcohol, which is great, because then I\u2019m a cheap date. I could have my one glass of mezcal or whatever, and I\u2019m good. And I don\u2019t drink super often. I might take three or four weeks off, but then it\u2019ll be like this week I\u2019m 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.<\/p>\n<p>And then I\u2019ll stop. I\u2019ve a party with my oldest friends this weekend. I\u2019m sure there\u2019s going to be drinking, and then I\u2019ll stop for two weeks, and take a month off or two months off or something like that. It\u2019s kind of how I operate these days. But the ketosis seems to sensitize me, which I thought was pretty interesting. I hadn\u2019t noticed that before when I was in ketosis, probably because I wasn\u2019t drinking during those periods.<\/p>\n<p>But on the ketamine substitute, right? \u201cOh, this is what I\u2019m using now as a healthier alternative.\u201d I think the \u201cIs this risky?\u201d question is often, \u201cIs this risky or is this bad for me?\u201d can be answered in absolute terms, but it can also be answered in relative terms. So zero alcohol might be better than two drinks. Seems pretty unequivocally that\u2019s the case. But if you then ask in relative terms as compared to what, if you\u2019re swapping in another behavior or smoking after your dinner, or \u2014 I mean, smoking\u2019s a whole different kettle of fish that we could unpack some other time. Nicotine\u2019s pretty interesting, but lung cancer less interesting. There is the, as compared to what, when people fight another coping mechanism.<\/p>\n<p>So I just wanted to throw that out there as just another question that I think is worth people asking. If they\u2019re going to abandon something, that\u2019s great if you can just delete it without replacing it with something. But if there is a substitute, if there is an alternative or something that you may end up adding to your behavior or your consumption, just to be aware of that, because you have to measure A versus B, not just a versus lack of A. So just wanted to throw that out there. I\u2019ve seen so many people unravel from ketamine and that I feel a moral responsibility to mention it because it can be so, so incredibly addictive. Fast-acting, short duration, and even though it is very successfully used to treat, say, treatment-resistant depression when it\u2019s administered in a clinic at reasonably higher doses for, let\u2019s just say, six infusions over two weeks, something like that. John Krystal at Yale\u2019s done a lot of great research, and his teams and co-authors \u2014 used recreationally, it actually increases your predisposition to depression.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I think psilocybin is a better candidate when it comes to something like that, because it\u2019s really not addicting. And I don\u2019t know if you saw this, Tim, but this really \u2014 it\u2019s, of course, people may not be aware, but it\u2019s been shown to treat depression as well, and in more than one study.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Oh, for sure. Oh yeah, yeah. Yeah. The two major applications are major depressive disorder and alcohol use disorder, as it stands right now.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Right. This study just came out, like, gosh, this last two weeks or something showing \u2014 is the animal study that psilocybin increased life expectancy by almost 20 percent in mice.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah, I saw that. And I think that was out of Emory? Am I making that up?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Yeah, I think it was.<\/p>\n<p><strong>Tim Ferriss: <\/strong>And I remember looking at it because I was like, wait a fucking second. I think they were giving something like five milligrams of psilocybin to these rats or mice. And I\u2019m going to mess up the numbers a little bit, but I was like, wait a second, because I\u2019ve funded a lot of the science, and for humans who are walking around at one, let\u2019s just call it whatever, 125 to 200 pounds, it\u2019s 25 to 30 milligrams. So on a mix-per-kicks basis, are those rats getting the equivalent of 300 dried grams of mushrooms on a monthly basis?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>No.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I was like, let me look at that. Let me look at that a little more closely. And the metabolism is very different, but it\u2019s still non-trivial. I do think those little furry friends are probably tripping balls, even though I \u2014 I do think the life-extension stuff is interesting, and I would say just anecdotally, looking at people who have consumed in South America, ayahuasca for decades, they are \u2014 can\u2019t 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 it raises more questions than it provides answers.<\/p>\n<p>But the life extension stuff is interesting. And I\u2019ve been funding some science that Chuck Nichols is doing, looking at the anti-inflammatory applications of different psychedelic compounds, and they are profound, really profound. And what makes it most interesting is that it can be achieved depending on the compound, and he\u2019s tested dozens of them with very, very trace quantities, in sub-perceptual quantities. You do not need any hallucination, any sort of reality distortion to achieve the anti-inflammatory effects.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>So like a microdosing.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Yeah.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>A microdosing of it.<\/p>\n<p><strong>Tim Ferriss: <\/strong>Even less than what someone would consider a microdose, like a nanodose.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Wow.<\/p>\n<p><strong>Tim Ferriss: <\/strong>It\u2019s remarkable. And part of my reason for looking at the fasting, the ketogenic diet, also looking at cold exposure, and most recently, this is a whole separate topic, obviously for another time. I\u2019ll be having a scientist on this podcast soon, super credible, very, very well-cited, to talk about vagus nerve stimulation. But when you look at how fasting, I was talking about this old Soviet work looking at schizophrenia, okay, interesting, ketosis for epilepsy and also all sorts of psychiatric conditions, but also things like potentially rheumatoid arthritis or any number of Crohn\u2019s disease, let\u2019s say in the case of vagus nerve stimulation.<\/p>\n<p>My theory also with psychedelics is that in a lot of cases, the anti-depressive effects, anti-depressant effects, the anxiolytic effects, this would be true for exogenous ketones as well, maybe largely, I don\u2019t think it\u2019s a trivial piece of the puzzle, mediated by anti-inflammatory effects addressing chronic inflammation, including neuroinflammation.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Totally.<\/p>\n<p><strong>Tim Ferriss: <\/strong>And so as you said, if you\u2019re chronically suffering from neuroinflammation does not bode well for later life with Alzheimer\u2019s and Parkinson\u2019s and things like this, so I\u2019m trying to throw everything sort of the kitchen sink at this to see what these subjective and then measurable objective effects are. So it\u2019s like, okay, if I did intermittent fasting and I\u2019m doing then cold exposure during \u2014 which, by the way, past a certain point seems to shift from sympathetic to parasympathetic activation, particularly with certain breathing patterns. Like, okay, if I did that during the intermittent fast, I\u2019m taking the sulforaphane, doing all that stuff, and then the exercise we talked about and once a quarter doing a three to seven \u2014 let\u2019s call it probably every quarter. I used to do a three-day fast. I don\u2019t think I\u2019d do a seven-day every quarter. That\u2019s probably once a year.<\/p>\n<p>But just looking at like, okay, and then the curcumin. It\u2019s like, all right. If we threw four or five at this problem and didn\u2019t get too crazy, go \u201cMurica!\u201d Like more is better, we did the minimal effective dose, but recognized there might be a synergistic effect, like what happens, and what can we measure? So I\u2019d like to do, and I\u2019m in the position where I could spend a lot of money just to see, okay, if we take out my white blood cells and then look at their ability to produce cytokines after certain interventions, like, oh, okay, cool, let\u2019s spend the money. Let\u2019s see what happens after you do this stuff for a couple of weeks. Very, very, very, very interested in all of this.\u00a0<\/p>\n<p>Let\u2019s do this, Rhonda. Where can people find you, find what you\u2019re up to, get into all things Rhonda Patrick?<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I have a podcast. You can find it on Spotify, Apple Podcasts, YouTube. It\u2019s called FoundMyFitness. You can also just search Rhonda Patrick.<\/p>\n<p><strong>Tim Ferriss: <\/strong>One of the OGs. You\u2019ve been doing it for a while now.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Doing it for a while, yeah. And I\u2019ve got a website, foundmyfitness.com. You can find all my stuff there. You can follow me on Twitter, or sorry, X.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I still say Twitter.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I still do it. I still do it. You can call me on X or Instagram, FoundMyFitness, all one word, or look, just search my name, Dr. Rhonda Patrick.<\/p>\n<p><strong>Tim Ferriss: <\/strong>And you have a newsletter.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I have a newsletter. I have a newsletter, yeah. I send out a weekly email that covers some fascinating new either science, health, fitness, nutrition-related study, and usually it\u2019s applicable. Sometimes it\u2019s something that\u2019s misunderstood in the media, and I break it down every week. I sent you the creatine one. 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.<\/p>\n<p><strong>Tim Ferriss: <\/strong>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\u2019ve called a lot of things early. Looking at our timelines has been wild, to look back and I\u2019m like, \u201cWow, April, 2014, talking about the stuff that now all the fitness influencers are ranting and raving about today in 2025.\u201d It\u2019s like, yeah, you\u2019ve called a lot of things early, and I appreciate your ability to simplify without mangling. Simplify without disfiguring the science. I really respect that. It\u2019s not easy to do. It is such a service to people who care about being scientifically literate, but they also care about and benefit from someone who can take what could be impenetrable and translate it without mistranslating it into something that they can test with limited downside and plausible or supported upside. I just think it\u2019s such a tremendous service. So I appreciate you, Rhonda. I really do.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>I appreciate you too, Tim. Thank you for all you do, and your podcasts have been great. I\u2019ve listened to them over the years. You\u2019re one of the few podcasts that I\u2019ve listened to, so you\u2019ve got great, insightful, thoughtful questions and I\u2019ve read your books, so I appreciate all you do. So the feeling\u2019s mutual, and I\u2019m glad we get to still have conversations over 10 years later.<\/p>\n<p><strong>Tim Ferriss: <\/strong>I know, I know. I love it. Yeah. The long game. It\u2019s 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\u2019ll 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.<\/p>\n<p>All right, so that\u2019s a wrap. Thank you, Rhonda. Really appreciate it.<\/p>\n<p><strong>Dr. Rhonda Patrick: <\/strong>Same. Thank you.<\/p>\n<\/div>\n<p><a href=\"https:\/\/hop.clickbank.net\/?affiliate=infohatch&amp;vendor=J1R2C\"><img loading=\"lazy\" decoding=\"async\" class=\"size-full wp-image-10614 aligncenter\" src=\"http:\/\/parmaks.com\/Resources\/wp-content\/uploads\/2025\/05\/profit-gen400px.png\" alt=\"Profit Gen\" width=\"400\" height=\"217\" srcset=\"https:\/\/parmaks.com\/Resources\/wp-content\/uploads\/2025\/05\/profit-gen400px.png 400w, https:\/\/parmaks.com\/Resources\/wp-content\/uploads\/2025\/05\/profit-gen400px-300x163.png 300w\" sizes=\"auto, (max-width: 400px) 100vw, 400px\" \/><\/a><br \/><\/p>\n","protected":false},"excerpt":{"rendered":"<p>Please enjoy this transcript of my interview with Rhonda Patrick, Ph.D. (@foundmyfitness), a biomedical scientist and the founder of FoundMyFitness, a platform dedicated to delivering [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":11226,"comment_status":"","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[13],"tags":[],"class_list":["post-11250","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-growth"],"_links":{"self":[{"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/posts\/11250","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/comments?post=11250"}],"version-history":[{"count":0,"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/posts\/11250\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/media\/11226"}],"wp:attachment":[{"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/media?parent=11250"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/categories?post=11250"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/parmaks.com\/Resources\/wp-json\/wp\/v2\/tags?post=11250"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}