Micronutrients for Health & Longevity | Dr. Rhonda Patrick

My guest is Rhonda Patrick, Ph. D. She earned her doctoral degree in biomedical science from St. Jude Children’s Research Hospital at the University of Tennessee Health Science Center and has become one of the leading public health educators on the brain and general health, aging, cancer, and nutrition. We discuss the four major categories of micronutrients that regulate cellular and organ stress and antioxidants, inflammation, hormone regulation, immune system, and longevity. Dr. Patrick provides actionable protocols for obtaining key micronutrients from food and/or supplement-based sources. Additionally, Dr. Patrick outlines protocols for deliberate cold and deliberate heat exposure to benefit metabolism, cardiorespiratory fitness, mental health, and lifespan. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1: https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/hubermanlab Waking Up: https://wakingup.com/huberman Momentous: https://livemomentous.com/huberman Timestamps (00:00:00) Dr. Rhonda Patrick – Micronutrients, Cold & Heat Exposure (00:03:12) Sponsors: AG1, LMNT (00:09:42) Stress Response Pathways, Hormesis (00:16:38) Plants, Polyphenols, Sulforaphane (00:21:12) Tools 1: Sulforaphane - Broccoli Sprouts, Broccoli, Mustard Seed (00:23:50) Tool 2: Moringa & Nrf2 Antioxidant Response (00:25:25) Sulforaphane: Antioxidants (Glutathione) & Air Pollution (Benzene Elimination) (00:27:10) Plants & Stress Response Pathways, Intermittent Challenges (00:29:35) Traumatic Brain Injury, Sulforaphane, Nrf2 (00:35:08) Tools 3: Omega-3 Fatty Acids (ALA, EPA & DHA), Fish Oil, Oxidation (00:48:40) EPA Omega-3s & Depression (00:52:02) Krill Oil vs. Fish Oil Supplements? (00:54:23) Benefits of Omega-3 Fatty Acids, Omega-3 Index & Life Expectancy (00:59:24) Tool 4: Food Sources of EPA Omega-3s (01:06:07) Omega-3 Supplementation, Omega-3 Index Testing (01:10:22) Benefits of Omega-3s (01:14:40) Tool 5: Food Sources of DHA Omega-3s (01:17:07) Vitamin D & Sun Skin Exposure (01:22:18) Role of Vitamin D, Gene Regulation (01:25:30) Tool 6: Vitamin D Testing & Vitamin D3 Supplementation (01:33:15) Tool 7: Skin Surface Area & Sun Exposure, Vitamin D (01:34:23) Vitamin D & Longevity (01:36:46) Sun Exposure & Sunscreen (01:40:30) Role of Magnesium, Magnesium Sources, Dark Leafy Green Vegetables (01:44:50) Tool 8: Magnesium Supplements: Citrate, Threonate, Malate, Bisglycinate (01:50:57) Tool 9: Deliberate Cold Exposure Protocol & Mood/Anxiety (01:59:22) Tool 10: Cold Exposure, Mitochondria UCP1 & Heat Generation (02:02:30) Tool 11: Cold & Fat ‘Browning’, PGC-1alpha, Metabolism (02:05:08) Cold Exposure & High-Intensity Interval Training (HIIT), PGC-1alpha, Muscle (02:08:04) Tools 12: Exercise, HIIT, Tabata & Sauna (02:13:30) Tool 13: Sauna, Endorphins/Dynorphins, Mood (02:17:45) Tool 14: Mild Stress, Adrenaline & Memory (02:19:53) Sauna, Vasodilation & Alzheimer’s and Dementia Risk (02:25:30) Sauna Benefits, Cardiorespiratory Fitness, Heat Shock Proteins (HSPs) (02:31:29) Insulin signaling, FOXO3 & Longevity (02:33:22) Tools 16: Sauna Protocols, Hot Baths & Fertility (02:37:41) Tool 17: Exercise & Longevity, Osteocalcin (02:41:37) Tools 18: Red Light Sauna? Infrared Sauna? Sauna & Sweating of Heavy Metals (02:47:20) FoundMyFitness Podcast, Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous Supplements, Huberman Lab on Instagram & Twitter Disclaimer Learn more about your ad choices. Visit megaphone.fm/adchoices

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

• 0:00Andrew D. Huberman?

  Welcome to the Huberman Lab Podcast where we discuss science and science-based tools for everyday life.

• 0:09Andrew D. Huberman?

  I'm Andrew Huberman and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. Rhonda Patrick. Dr. Patrick is known to some of you as a podcaster and one of the premier educators in the landscape of mitochondria, metabolism, stress, and other aspects of brain and body health. Her podcast, Found My Fitness, is one of the premier podcasts in the world for disseminating knowledge about how the brain and body work and how we can use behavioral tools, micronutrients, supplements, and other protocols in order to maximize our immediate and long-term health. Dr. Patrick did her formal training in cell biology, exploring the links between mitochondrial

• 0:51Andrew D. Huberman?

  metabolism, apoptosis, which is naturally occurring cell death, which is a healthy form of cell death that occurs in our brain and body throughout the lifespan, and cancer biology. She then went on to do postdoctoral training with Dr. Bruce Ames, investigating the effects of micronutrients, meaning vitamins and minerals, and how they affect metabolism, inflammation, DNA damage, and the aging process. She has published landmark review articles and primary research, meaning original research articles, in some of the premier journals in the world, including Science, Nature Cell Biology, Trends in Cell Biology, and FASEB. Indeed, Dr. Patrick is an expert in an extraordinarily broad range of topics that impact our health.

• 1:34Andrew D. Huberman?

  For today's episode, we focus primarily on the major categories of micronutrients that are essential for brain and body health. I have to confess that before the discussion with Dr. Patrick, I was aware of only one of the categories of micronutrients that we discuss, and so you'll notice that I am rapt with attention throughout the discussion, and I think that you'll want to have a pen and paper handy because she offers not only a very clear understanding of the biological mechanisms by which other micronutrients operate, but some very clear and actionable tools and items that we can all embark on if we are to optimize our brain and body health. We also discuss behavioral protocols. Dr. Patrick is well-known for her understanding of the scientific literature on sauna and

• 2:19Andrew D. Huberman?

  the use of heat and cold for optimizing things like metabolism, longevity, cardiovascular health. And I'm delighted to say that we discussed that as well and how behavioral protocols can interface with supplement-based and nutritional protocols. I'm confident that you'll learn a tremendous amount of information from Dr. Patrick, much of which is immediately actionable. And if you're not already following and listening to her excellent podcast, you'll absolutely want to do that. It's foundmyfitness.com is the website where you can get access to that podcast. It's also on Apple and Spotify and YouTube as Found My Fitness. Dr. Patrick also has a terrific newsletter that I recommend signing up for. It's foundmyfitness.com/newsletter is where you'll find it.

• 3:03Andrew D. Huberman?

  And it includes research on fasting, micronutrients, sleep, depression, fitness, longevity, and far more, along of course with actionable protocols. I'm pleased to announce that the Huberman Lab Podcast is now partnered with Momentous Supplements. Our motivation for partnering with Momentous is to provide people one location where they can go to access the highest quality supplements in the specific dosages that are best supported by the scientific research and that are discussed during various episodes of the Huberman Lab Podcast. If you go to livemomentous.com/huberman, you will see those formulations. I should mention that we are going to add more formulations in the months to come. And you will see specific suggestions about how best to take those supplements, meaning

• 3:47Andrew D. Huberman?

  what dosages and times of day, and in fact, how to combine those supplements with specific behavioral protocols that have been discussed on the podcast and are science-supported in order to derive the maximum benefit from those supplements. And many of you will probably also be pleased to learn that Momentous ships not just within the United States, but also internationally. So once again, if you go to livemomentous.com/huberman, you will find what we firmly believe to be the best quality supplements in the precise dosages and

• 4:20Andrew D. Huberman?

  The best protocols for taking those supplements, along with the ideal behavioral protocols to combine with those supplement formulations. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast.

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• 6:24Andrew D. Huberman?

  And now for my discussion with Dr. Rhonda Patrick. Rhonda, welcome. It's been a long time coming, even longer than you know, because even before we discussed you coming on this podcast as a guest, I've been watching your content for a very long time. So I want to start off by saying thank you. You were the spearhead to break through from academic science to public education. So I consider you first in, and the rest of us are just in your wake. So thank you for that. It's been...

• 6:54Dr. Rhonda Patrick?

  Oh, that is so kind. Thank you. Thank you so much.

• 6:56Andrew D. Huberman?

  Well, it's absolutely true.

• 6:57Dr. Rhonda Patrick?

  I am so excited to be here having a conversation with you.

• 7:00Andrew D. Huberman?

  Thank you. It's absolutely true. If anyone does their research, they will realize that the statement I just made is absolutely true. And there isn't even a close second, you know, any other public facing educators that have formal science training and do regular posting of content came in several years after you initiated it. So we're all grateful. I have so many questions, but I want to start off with a kind of a new but old theme that you're very familiar with. So, temperature is a powerful stimulus, as we know, for biology. And you've covered a lot of material related to the utility of cold, but also the utility

• 7:42Andrew D. Huberman?

  of heat. And as I learn more and more from your content and from the various papers, it seems that there's a bit of a conundrum in that cold can stimulate a number of things like increases in metabolism, brown fat, et cetera, et cetera. Hopefully you'll tell us more about those. But heat seems to be able to do a lot of the same things. And I wonder whether or not the discomfort of cold, deliberate cold exposure, and the discomfort of heat might be anchoring to the same pathway. So would you mind sharing with us a little bit about what happens when we get into a cold environment on purpose, and what happens when we get into a hot environment on purpose? And I'm hoping that this might eventually

• 8:25Andrew D. Huberman?

  lead us to some point of convergent understanding. So if you would.

• 8:29Dr. Rhonda Patrick?

  I would love to. Let's take a step back. And I think you brought up a really important point here. And I think that point has to do with... The intermittent challenging of yourself and whether that is through, you know, temperature changes like cold or heat, or through other types of stressors like physical activity, or perhaps even dietary compounds that are found in plants. These are things like polyphenols or flavonols. Humans were, you know, we evolved to intermittently challenge ourselves. And before we had Instacart, where you could basically just get your food delivered to you, before the industrial revolution, you know, occurred, we were out hunting.

• 9:13Dr. Rhonda Patrick?

  And I say we, not us, but humans. We were out, you know, gathering, we were moving. And we had to be physically fit. You couldn't, you know, catch your prey if you were a sedentary slob, right? You were moving and you had to like, you know, pick your berries. You had to move. And so, physical activity was a part of everyday life. And caloric restriction or intermittent fasting was also a part of it. This is another type of of of challenge. You know, we, we didn't always, you know, have a prey that we caught, or maybe temperatures were such that, you know, there was nothing for us to gather, right? So, food scarcity was something common as well as eating plants. So, getting these compounds that I mentioned. So, this is, these, these are all types of stress,

• 9:56Dr. Rhonda Patrick?

  intermittent challenges that activate genetic pathways in our bodies. These are often referred to in science as stress response pathways because they respond to a little bit of stress. You know, physical activity is strenuous. Fasting is a little bit stressful. Heat, cold, these things are all types of little intermittent challenges. And there is a lot of crosstalk between these stressors and the genetic pathways that they activate. And these genetic pathways that are activated help you deal with stress. And, and, and they do it in a way that is not only beneficial to help you deal with that little stressor, exercise or heat. It stays active and it helps you deal with the stress of

• 10:40Dr. Rhonda Patrick?

  normal metabolism, normal immune function happening, just life aging, right? So this concept is referred to as hormesis, right? This is a little bit of stressful challenge that activates these stress response pathways in a beneficial way that is a net positive that actually, you know, it has a very profound antioxidant, anti-inflammatory response, or, you know, or whatever the response is. It could be the production of more stem cells. These are cells that help regenerate different cells within tissues or something like autophagy, which is a process that can clear away all the gunk inside of our cells, pieces of DNA, protein aggregates. So you'll find that these stress response pathways are activated like by a variety of stressors.

• 11:23Dr. Rhonda Patrick?

  So for example, one pathway is called heat shock proteins. And as their name would apply, one would go, oh, they're activated by heat. Well, correct, they are activated very robustly by heat and we can talk about that. But, you know, you can eat a plant like broccoli sprouts, which is high in something called sulforaphane. This is a compound that is sort of like a hormetic compound. Or as David Sinclair likes to say, it's a xenohormetic compound. I love that. I love that term. And it activates heat shock proteins, among other things. It also activates a very powerful detoxification pathway called N R F two, which helps you detoxify things like carcinogens that you're exposed to. Well, guess what? Heat activates that. So what I'm getting at is there is overlap. Like cold also activates heat shock proteins.

• 12:08Dr. Rhonda Patrick?

  You're like, really? Cold? Yes, it activates. These are stress response pathways and they are activated by various types of stressors. Now, you know, you're going to more robustly activate heat shock proteins from heat versus cold, but there is some overlap. So I think that sort of forms a foundation there.

• 12:28Andrew D. Huberman?

  Yeah, that's very helpful. And, you know, it brings to mind, in the context of the nervous system, I always tell people, you know, you only have a small kit of neurochemicals to work with. There isn't dopamine for Netflix and then dopamine for relationship and dopamine for work, et cetera. There, dopamine is a generic pathway by which motivation, craving and pursuit emerge.

• 12:50Andrew D. Huberman?

  Et cetera, just like adrenaline is a generic theme of many different behaviors. And I, it seems that it is the job of biological systems to be able to take a diverse range of inputs, even unknown inputs, like, we don't know what technology will look like in three years, but you can bet that some of those novel technologies will tap into the very systems that I'm talking about now. And there certainly will be other stressors to come about that will tap into these pathways. I have two questions related to what you just said, before we talk a little bit more about cold and heat. You mentioned plants as a route to creating intermittent challenge. There's a lot of debate, mostly online, about whether or not plants are our friends, or

• 13:32Andrew D. Huberman?

  plants are trying to kill us. The extreme version from the carnivore types, pure carnivore diet types, is that plants are trying to kill us. From the plant-based diet folks, it seems like it's more about what's healthy for the planet, animals, and maybe for us. But if we set aside that argument, and we just raise the hypothesis that plants have compounds that are bad for us, but maybe by consuming them in small amounts, they're creating this hormesis-type scenario. So then I think we conceivably solve the problem. We could say, yes, plants are bad for us, but in small amounts, they provide this hormetic response, and they're good for us. Right? So in the same way that heat is, too much

• 14:16Andrew D. Huberman?

  heat is bad for us, too much cold is bad for us, can kill us, can kill neurons, but appropriately dosed, in an intermittent challenge-type of scenarios, can be good for us. Is that how I should think about plants and these compounds? Do you think of them as good for us, or as bad for us? They're a very sharp blade, and we want to use them potently?

• 14:33Dr. Rhonda Patrick?

  I actually, I think that it's almost impossible. I mean, you'd have to eat nothing but the same plant all day, every day. I mean, the bioavailability of these, these compounds in the plants, they're attached to a food matrix, you know, it's, it's not like taking it in a supplement form as well. It's, it's such that, like, it's, it's very difficult to make it Toxic. Now, there are some cases, for example, if you eat cabbage, and I think there's some group in Africa somewhere that like, that's all they eat is cabbage. And there is a goitrogen in cabbage. It's not sulforaphane, it's another compound. But that's all they eat every day. Nothing but that. They get goy to the thick neck.

• 15:16Dr. Rhonda Patrick?

  Yeah, and they're like iodine deficient on top of that. So, um, you know, I do think there's there, you can, of course, make, I mean, there are types of plants that are toxic in small quantities, right? I mean, that- Hemlock. Hemlock, exactly. So- Will kill you.

• 15:30Andrew D. Huberman?

  Folks, don't, don't play this game with hemlock.

• 15:32Dr. Rhonda Patrick?

  But you're not going to get poison from eating, you know, your, your, your serving of broccoli at dinner, right? So, I mean, it, it depends on the plant. It's, it's, I don't, these generalizations are kind of, they're just not useful. And I think that a lot of people online, um, in the blogosphere, it, it, it, they gravitate towards them because it's just easier and it's a lot more sensational.

• 15:55Andrew D. Huberman?

  I eat plants, meat and starches. I'm one of those rare omnivores out there now.

• 16:00Dr. Rhonda Patrick?

  I do too.

• 16:00Andrew D. Huberman?

  I feel like I'm rare, or it's rare to be an omnivore. But I think, once you step out of the social media, as you said, the blogosphere, that most people, I would say 99% of people on the planet are probably omnivores.

• 16:13Dr. Rhonda Patrick?

  Right.

• 16:13Andrew D. Huberman?

  And someone will probably correct me, but I doubt the number falls below 90, 98.

• 16:18Dr. Rhonda Patrick?

  I think if you look at data, you know, um, and, and when we have carnivore data, I like, I can't wait to see it, but like, right now, it's a lot of, okay, well, this is a lot of anecdotal evidence and there's, you know, there's a good, there's a lot of, uh, good starts with anecdotes, but like, people change a thousand things at once. And they don't realize that, but they do. And so anecdotal data is only so good, right? It's, it's, it's a starting point. Um, and so we don't really know long-term what carnivore diets are going to do, you know? They may be beneficial short-term. Um, they may, you know, be beneficial for reasons of elimination of other things, like, who knows, right? Lots of possibilities. But I do think with respect to plants, um-

• 17:00Dr. Rhonda Patrick?

  You know, there's so much evidence, like for example, sulforaphane is one that I really like because there's just evidence that sulforaphane is a very powerful activator of the N R F two pathway. And this is a pathway that regulates a lot of genes and a lot of genes that are related to like glutathione production, genes that are involved in detoxifying compounds that we're exposed to from our food, like heterocyclic amines. In fact, there have been GWAS studies. So these are genetically, these are studies that are genome-wide associated studies for people listening that aren't familiar. People have a variety of versions of genes and we have a gene that's able to make heterocyclic amines to basically

• 17:45Dr. Rhonda Patrick?

  detoxify it. So it's not as harmful. And people that don't have a certain version of that that's doing it well are very prone to like colon cancer and increased cancer risk. But if they eat a lot of broccoli and cruciferous vegetables, it negates that risk because they're getting sulforaphane, which activates a lot of the glutathione transfer transphases and synthase genes. So glutathione is a major antioxidant in our brain and in our vascular system and our body, basically. So, you know, there's evidence that eating things like, you know, compounds that are like sulforaphane or broccoli or broccoli

• 18:26Dr. Rhonda Patrick?

  sprouts, which have like 100 up to 100 times more sulforaphane than broccoli are activating glutathione in the brain. There's human evidence of that. I mean, that's amazing.

• 18:34Andrew D. Huberman?

  That is amazing.

• 18:35Dr. Rhonda Patrick?

  In plasma. Yeah.

• 18:36Andrew D. Huberman?

  Sorry, I didn't trouble. I just want to make sure when, so broccoli sprouts are different than broccoli. And you just told us that they have much, they're much richer in these, these compounds. So note to self, I should have broccoli sprouts, not just broccoli. Can we cook the broccoli and still get these nutrients? Or do we have to eat raw? I confess, eating raw broccoli is really aversive to me.

• 18:58Dr. Rhonda Patrick?

  So the sulforaphane is formed from a compound called glucoraphanin, which is in the broccoli. And the enzyme that converts it into sulforaphane is myrosinase, and it's heat sensitive. So you do somewhat lower the sulforaphane levels when you when you cook the broccoli. However, there was a study a few years back that showed adding one gram of mustard seed powder, ground mustard seed powder, which also contains the myrosinase enzyme, to your cooked broccoli increases the sulforaphane by fourfold.

• 19:32Andrew D. Huberman?

  So this is great, because I confess, I like broccoli if it's cooked to the appropriate density, not too mushy, but definitely not raw. The idea of eating raw broccoli, to me, just sounds horrible, but I like the way mustard seed sounds. So just a little bit of mustard seed powder added to the cooked broccoli can recover some of these compounds.

• 19:52Dr. Rhonda Patrick?

  Yes. So what I do is I will, you know, lightly steam my broccoli, and then I add a little bit of my Kerrygold butter, and then I add some mustard seed powder on the top of that. And it's got a little little kick, like, it's just a little spice, you know, and if you don't taste that, it's expired, like, it should have a little kick.

• 20:11Andrew D. Huberman?

  And because I know people will want to know how often and how much, you know, are you eating this every day, or most days of the week?

• 20:18Dr. Rhonda Patrick?

  Well, I had shifted to supplementation with sulforaphane. I've I've admitted, I'm admitting right now that I've been terrible about it the past, like, I don't know, six months or so.

• 20:30Andrew D. Huberman?

  The supplementation or the broccoli?

• 20:32Dr. Rhonda Patrick?

  Yes, the supplementation. And, and so there's another way to get, there's another compound, and it's actually called moringa. And Dr. Jed Fahey, who's really the expert on sulforaphane, he's a good friend of mine, he's been on the podcast a couple of times, he, he, he basically thinks, and, you know, has done a lot of research on moringa as well, that it's like a cousin, and it activates the N R F two pathway similarly to sulforaphane. And so I've been buying this Cooley Cooley moringa powder. I don't have any affiliation with them.

• 21:06Andrew D. Huberman?

  Cooley Cooley is a brand?

• 21:07Dr. Rhonda Patrick?

  Cooley Cooley is the brand.

• 21:08Andrew D. Huberman?

  That you have no affiliation to?

• 21:09Dr. Rhonda Patrick?

  I have no affiliation, but Jed Fahey, like, has researched it, like, like, that specific brand. And so it's like legitimate, it's legit, you know, it's like science back, in terms of actually containing moringa and activating N R F two. And I add it to my smoothies. So that's what I've been doing.

• 21:26Andrew D. Huberman?

  What are some dose ranges? And of course, we give the usual recommendations that people should talk to their physician, et cetera, et cetera. But if people are going to, what do you take? That's always the, uh, let's take the David Sinclairian approach. What do you, where he'll talk about what he does as a way to deal with this. And of course, everybody's different and should, in all seriousness, should, anytime you add or delete something from your consumption, should consult some trusted healthcare professional, trusted by you. What, do you recall the dosages?

• 21:59Dr. Rhonda Patrick?

  I do a big heaping tablespoon.

• 22:02Andrew D. Huberman?

  So moringa, cooly, cooly, moringa. It sounds like a song.

• 22:05Dr. Rhonda Patrick?

  It's with a K, I know.

• 22:09Dr. Rhonda Patrick?

  But, you know, for people also listening, it's like, well, why would I do that? You know, I mentioned the glutathione in the brain. I mentioned it in plasma. It's been shown a lower DNA damage in people and white blood cells. It's also been shown, there's been several different studies in China. You know, in China, there's a lot of air pollution. And I mentioned that, you know, it's a very powerful activator, N R F two. And I know you're familiar with N R F two, but N R F two is like, it's your transcription factor. That is, it is, it is binding to a little specific sequence in a variety of different genes. And it's like turning them on, or in some cases, turning them off. It's regulating what's being activated or what's not being activated, being turned off. And some of the genes are basically these, these detoxifying pathways.

• 22:51Dr. Rhonda Patrick?

  We talked a little bit about the glutathione, but there's also ones that are involved in airborne carcinogens like benzene. So benzene is found in air pollution, I mean, cigarette smoke. If you're smoking cigarettes still, like, please try to quit.

• 23:05Andrew D. Huberman?

  Yeah, you're mutating your DNA.

• 23:06Dr. Rhonda Patrick?

  Yeah.

• 23:07Andrew D. Huberman?

  Just saying nothing of the lung cancer, you're mutating your DNA.

• 23:09Dr. Rhonda Patrick?

  And heart disease risk, heart disease risk. But anyways, people, and this has been repeated in more than one study, that literally after 24 hours of taking, I can't remember off the top of my head, what the dose of sulforaphane from broccoli extract, broccoli seed extract was, or broccoli sprouts extract, not the seed, it was the sprouts. Anyways, they started excreting like 60% benzene and acrylene. I mean, that's something that we get in cooked food.

• 23:37Andrew D. Huberman?

  It's coming out in their urine.

• 23:38Dr. Rhonda Patrick?

  Coming out in their urine. Yeah.

• 23:40Andrew D. Huberman?

  Well, I'm not a smoker and I have to be honest, it's rare that I hear of a supplement for the first time because I've been, you know, deep diving on supplements since I was in my teens. Uh, this is fascinating and it brings me back to this question that we had before and I, I appreciate that you answered it very clearly. Plants have compounds that are good for us. They're not just stressing us, they're activating pathways that are reparative. That's what, that's what I'm taking away from everything you're telling me.

• 24:06Dr. Rhonda Patrick?

  Right. And, and, and that, our bodies, we're supposed to be getting that stress to have those pathways activated. Like it is like, you know, right? I mean, this is conserved among different animals. Like this is, this is, this is something that is, is supposed to happen. And in our modern day world, we don't have to eat plants. We don't have to move anywhere or exercise. We don't have to go through periods of not eating food because we can have it at our fingertips at any second, right? So, I mean, we've got this conundrum of we're never activating these stress response pathways that we're supposed, that we're supposed to activate. We're supposed to.

• 24:47Andrew D. Huberman?

  I find that fascinating. And again, uh, drawing a parallel to the nervous system. Um, so what I'm hearing you say is that historically, we would have to go through some stress, some confront cold or confront heat or confront effort or, or hunger in, have to exercise essentially in order to obtain these compounds. And then those compounds are reparative. Yeah. I, I feel that resembles, uh, the dopamine pathway. I always say, you know, there's nothing wrong with dopamine. People think about dopamine hits as bad or dopamine is bad. There's absolutely nothing wrong with dopamine. The problem is dopamine, especially high levels of dopamine, released without the need for effort to access that dopamine is problematic. So a line of cocaine gives you a ton of dopamine with no effort except

• 25:31Andrew D. Huberman?

  to ingest the drug. Whereas, um, working for four years or more to get your degree will release a lot of dopamine and a lot of cortisol along the way, as we know. And it's considered a healthy accomplishment in most cases. A tremendous amount of, we're approaching the spring and there'll be a lot of graduations. Weddings are coming up now that the pandemic is kind of hopefully slowing. And there'll be a lot of dopamine. High levels of dopamine are great, but only after the effort of having done something in order to access it. And so that's what I'm taking away from what you're saying is that we need to go through this intermittent.

• 26:06Andrew D. Huberman?

  Different types of intermittent challenge and we can, we are rewarded with particular compounds that are reparative, both for the challenge, but then make us stronger. It is, hormesis really is, it seems, a case of what doesn't kill us makes us stronger. What, so you mentioned-

• 26:21Dr. Rhonda Patrick?

  Can I add to that one thing you just said?

• 26:23Andrew D. Huberman?

  Please.

• 26:23Dr. Rhonda Patrick?

  Because this has been shown with, for example, sulforaphane in animal studies. You precondition, give the animal sulforaphane and then you expose them to like, you know, hypoxia or some sign of ischemic stroke condition, whatever they do to induce that. And the sulforaphane, it basically protects that, like, they're preconditioned and their stress response pathways are primed. And so when they're then exposed to the ischemic stroke, they, their outcomes are so much better, so much better than the animals that didn't get the sulforaphane 48 hours before, or whatever it was. You know, and, and this is like, this has been shown in multiple animal studies with sulforaphane specifically, in the brain. I know Mark Mattson, Dr. Mark Mattson, he's often thought of as the intermittent fasting king, but you know,

• 27:07Dr. Rhonda Patrick?

  he's a neuroscientist and he, he did publish some work and talks about sulforaphane as well.

• 27:13Andrew D. Huberman?

  I'm really glad you brought that up, that example up because many of the questions I get on social media and elsewhere are about traumatic brain injury and TBI in, you know, is just one example. And people always think, oh, sports, it's football. Whenever you say TBI, people always think football. And I just want to just take a moment to editorialize. 90% or more of traumatic brain injury is construction work, at-home accidents. Football players are, hockey players are, martial artists are a tiny fraction of the people who have TBI and concussion of various kinds. It just so happens that within those communities, many of them, 75% or more, experience those. So it's salient within those communities, but concussion is prominent.

• 27:57Andrew D. Huberman?

  People are always asking, what can I do? In order to offset brain injury. I had a concussion two years ago. What can I do? And it's been, it's been a tough question because we really don't have anything for them. I mean, you tell them, sleep well, eat well, exercise. But it sounds like some of these reparative pathways either should be explored in the context of brain injury, or I'm guessing are being explored in the context of brain injury.

• 28:21Dr. Rhonda Patrick?

  Yeah, so a couple of things there. One is that, I mean, traumatic brain injury, I mean, it's terrible, but it's also, it's so interesting because it's also like literal, real time brain aging. Like, you know, like it's, you're able to like accelerate it and understand. So I, I often think of, when I think of traumatic brain injury, I think of so much overlap between Alzheimer's disease and dementia and these neurodegenerative diseases because there is, there are, there are a lot of similarities that there, you know? And so sulforaphane, I personally think, and I do think there's been some animal research with TBI, I mean, and sulforaphane, mostly preconditioning rather than treatment.

• 29:03Dr. Rhonda Patrick?

  So again, it's like, well, I mean, if you're gonna, if you want a healthy lifestyle thing and you're a construction worker or you're fill in the blank, that's, you know, gonna, I mean, anyone that drives a car, I mean, you're at risk to some degree, right?

• 29:13Andrew D. Huberman?

  Or bicycle.

• 29:14Dr. Rhonda Patrick?

  Bicycle, yeah.

• 29:15Andrew D. Huberman?

  Around Stanford, we have, you know, I would say, people demonize motorcycles, people demonize a lot of things, but moving fast through space on a small object next to a 3,000 pound vehicle, I mean, we've lost, we have a number of friends that have died. We have a number of people with traumatic brain injury. I'm not against cycling or cyclists, but it is, it's a risky sport by any stretch. So in taking things like meringue or eating my broccoli sprouts, maybe cooking them a little less than I'm currently cooking them, putting on the mustard seed, is there evidence that, well, first of all, N R F two is expressed in neurons, right? So those, those cells should be protected.

• 29:56Andrew D. Huberman?

  Are there other cells of the body that could possibly gain protection from these pathways?

• 30:01Dr. Rhonda Patrick?

  Well, lungs for one, but you know, just even in plasma cells. I, I mean, I think it's pretty, N R F two is pretty ubiquitously expressed, liver. So there's, I mean, there's, there's so many animal studies that have looked at all those things. I try to kind of gravitate towards human ones because it's a little, a lot more relevant. But, but I think, you know, overall, like I mentioned, you know, DNA damage lower. It's like 24, 24 or 34% lower in human blood cells after broccoli, broccoli sprout powder supplementation.

• 30:34Andrew D. Huberman?

  Wow.

• 30:35Dr. Rhonda Patrick?

  And I made a video on this like years ago, 2016 maybe, and I think I have like the references on there to the exact amounts, I can't remember.

• 30:42Andrew D. Huberman?

  We can link to the video here.

• 30:43Dr. Rhonda Patrick?

  But it was, it's kind of an old video, it's 2016. But I also had Jed on the podcast and he did talk about this. But you know, it's also been shown in randomized controlled trials to help treat autism and autistic symptoms. And yet again, it's doing interesting things in the brain. And I think, I think it does have something to do with the oxidative stress and the glutathione, which would be relevant for TBI treatment. It hasn't been shown empirically that that helps with treatment, but I do think someone could do that study. I think that it should be done, honestly, because it's a low hanging fruit. I mean, if there's any impact, and there is at least one preliminary study that glutathione is increased in the brain after humans are, you know, basically taking sulforaphane. So.

• 31:28Andrew D. Huberman?

  Which is really, for people listening, that's so important because a number of compounds that people take in supplement form don't cross the blood brain barrier, or they get metabolized in ways that what's listed on the bottle almost becomes irrelevant for what your cells actually experience. So that's very reassuring. We will get back to heat and cold in this theme that I tried to surface, but I just find this too interesting to, to diverge at this point from, from these themes. So what other compounds or micronutrients do you place in the top tier of useful, interesting? There are animal studies, maybe there are hopefully also some human studies. We've talked about a few. I know you've talked a lot about omega-3 fatty acids. So if you had to do your kind of top three.

• 32:13Dr. Rhonda Patrick?

  Yeah.

• 32:14Andrew D. Huberman?

  Your, your superstars of nutrients for the brain and body, it sounds like we've got one, one set. What would you put in alongside them?

• 32:22Dr. Rhonda Patrick?

  Omega 3, the marine omega 3 fatty acids. So these are found in marine types of, you know, animals, fish, cold water fish, fatty fish. So there's, there's three fatty acids. There's one from a plant and, and that's often referred to as ALA. People call it short aflenylate acid. And then there's Ico-icosapentenoic acid or EPA and doca hexanoic acid, which is DHA.

• 32:47Andrew D. Huberman?

  Yeah. I'm amazed you can pronounce two of the most difficult words to pronounce right next to and spell, right next to ophthalmology, which if you can spell it, I know people who have appointments in ophthalmology departments that don't know how to spell ophthalmology. A little secret, there's, there's an extra P in there. So the ALA, the, I'm not going to attempt to pronounce it because your pronunciation was perfect of both of these two compounds. And you said are marine sources. So fish, so sardines, cod, this sort of thing. But what about krill? I've seen krill oil and there was a few years back, people were saying krill is a better source for omega 3s than is fish oil. I took some krill oil capsules, made me itch all over. So I stopped.

• 33:32Dr. Rhonda Patrick?

  Do you have a shellfish allergy?

• 33:33Andrew D. Huberman?

  No, I don't think so. I don't think so. I'm not a big fan of shellfish, but I like, you know, I'll have oysters every now and again, or shrimp or something and feel fine. So.

• 33:41Dr. Rhonda Patrick?

  Yeah, we can talk about sources. So krill is a, a source mostly of a type of DHA and EPA that's in phospholipid form. So it's a phosphatidylcholine omega 3 fatty acid. And that's different than most, most of the, well, if we're talking about fish oil supplements, that's a different story. But if you're talking about comparing fish to krill, eating krill, like we're talking about the foods.

• 34:08Andrew D. Huberman?

  I would never eat krill.

• 34:09Dr. Rhonda Patrick?

  Okay. Are we talking about the supplements?

• 34:10Andrew D. Huberman?

  Yes, I apologize. Yeah. Krill supplement versus fish oil supplement. And if you, if it fits in the conversation, talking about great sources of, of omega 3s in their whole form, I have a, I have a bad feeling you're going to tell me sardines.

• 34:27Dr. Rhonda Patrick?

  Sardines are, are, yeah, they're, they're awesome. Anyways.

• 34:29Andrew D. Huberman?

  Except for, except for the taste.

• 34:30Dr. Rhonda Patrick?

  And, and for the potential contaminants, mercury, I think was one, no, show is, yeah, it was mercury and.

• 34:40Dr. Rhonda Patrick?

  Joe was telling me about like he used to eat sardines every, Joe Rogan was telling me that he used to eat sardines every day. And, um, and then he had like really high mercury levels and I was really shocked because sardines are like, you know, low in the fish, you know, group. So they're, the, the higher up you get like swordfish and sharks, like really high mercury because they're eating all the other fish, right? But I think some brands, and if you look at like Consumer Lab, um, Consumer Lab, there's, it's like a third party site that I'm affiliated with, but I'll use them because they, they do a lot of analysis of different foods and supplements. And so you can look at like some of their sardines and they've like, they have a list of like ones that are pretty decent.

• 35:21Dr. Rhonda Patrick?

  But anyways, um, back to your question about fish oil supplements versus krill oil supplements. Uh, so the, one of the major differences is the, that fish oil supplements, if you get a high quality one, it's in a triglyceride form. Um, so you're, you've got like a glycerol backbone with three fatty acids and, and that's attached and those are either DHA or the EPA. And, um, or if you have a lower quality fish oil supplement, then you have what's called ethyl ester form. And typically, um, the reason for that is, it's when fish oil is purified, it's run through this column with alcohol or something, they cleave it off the glycerol backbone and then it's just kind of easier to leave it like that than like re-sterifying it, which costs more money.

• 36:06Dr. Rhonda Patrick?

  So you can get it in ethyl ester form, which, um, isn't as bioavailable. And in fact, if you don't take it with food, you're going to be in trouble. You're not going to absorb mu- much of it at all.

• 36:17Andrew D. Huberman?

  Would you see this on the packaging? Is it going to say it's in this ethyl, ethyl form?

• 36:21Dr. Rhonda Patrick?

  Some fish oil brands will put it on their website, perhaps on their packaging, but you, most of the time, um, you'll have to dig for it on the website and or call them. But I think for the most part, ones that are like higher end will will market it like triglyceride form. And it's not that ethyl esters bad, it just means take it with food. So so so the one of the major prescription omega threes out there is both of them, actually, Levazza, which is a mixture of DHA and EPA, as well as Vascepa, which is a highly purified EPA. These are both prescribed by physicians to patients with hyper triglyceridemia, so high triglycerides, among other things, I think, maybe dysregulation of lipids as well.

• 37:04Andrew D. Huberman?

  This is amazing. For people. So these are prescription drugs that are essentially very high potency purified omega threes, but they're given to people for lipid issues. So this is the treatment of issues with fat metabolism by giving people fat.

• 37:18Dr. Rhonda Patrick?

  Yes.

• 37:18Andrew D. Huberman?

  Just to really, I just want to push home, again, I'm not carnivore keto or anything, I'm an omnivore, but but to just push home that we one thing that's so wonderful that you've done over the years that you continue to do is to move away from these very broad sweeping statements about, you know, fat is bad. I mean, here's a case where we're saying fat is not only good, it can be used to combat issues with fat metabolism. And then there, you know, fats are not just one thing, there are many things. So anyway, I just didn't want to put a little highlighter and a point of appreciation there and make sure that people are are sensitized to the fact that if you hear that fat is bad, you have to ask what kind of fat, right? And here we're talking about these omega threes.

• 38:00Andrew D. Huberman?

  Okay, so the triglyceride form can be taken with or without food. And there's the prescription forms. What I can't get, I don't know if I can get a hold of the prescription form unless um,

• 38:13Dr. Rhonda Patrick?

  You have high triglycerides.

• 38:14Andrew D. Huberman?

  Or I have a friend with high triglycerides. No, it's illegal, folks. Don't don't share prescription drugs.

• 38:18Dr. Rhonda Patrick?

  Or you talk to your doctor and you say, I'm already taking this from, I mean, I don't know how it works. Anyways.

• 38:23Andrew D. Huberman?

  What's the dosage that you recommend people get?

• 38:26Dr. Rhonda Patrick?

  So.

• 38:27Andrew D. Huberman?

  One way or another?

• 38:28Dr. Rhonda Patrick?

  All right. Okay, so the dosage that physicians prescribe for high triglycerides, for example, is four grams a day.

• 38:35Andrew D. Huberman?

  Four grams of EPA?

• 38:36Dr. Rhonda Patrick?

  Of, yes, of the Vascepa. I think Levazza is also prescribed at four grams a day. And

• 38:45Dr. Rhonda Patrick?

  You can you can get either those from your physician. My father in law just got one of them prescribed because he was we were buying our own omega three for years and years. It's like, hey, you can actually get this and health insurance can cover it. And it's a really purified form, but you have to take it with food. That was the bottom line. I've totally gone on tangents, but like you're asking more interesting questions anyway. So

• 39:02Andrew D. Huberman?

  Well, normally I ask about mechanism and then I talk about protocols, but in the

• 39:06Dr. Rhonda Patrick?

  Or the why?

• 39:07Andrew D. Huberman?

  Or the why.

• 39:08Dr. Rhonda Patrick?

  I mean, we'd even gotten there yet.

• 39:09Andrew D. Huberman?

  But I think that and we definitely will get there. But I think a number of people nowadays are just really excited about what they can do for their health. And so here we're we're just raising the importance of omega threes. And then we'll definitely get to the why and the underlying mechanism.

• 39:22Dr. Rhonda Patrick?

  Yeah, I think four grams is, I mean, and in fact, like, you know, Bill Harris, Dr. Bill Harris is he's just one of the pioneers on omega three fatty acid research. He was on our podcast not, you know, last August. And he was saying that reason FDA chose that was literally just because how much they could get people to take at like, like, it wasn't like an upper end, like, oh, this is not anything above that is unsafe. That wasn't the case. I mean, it was, it was, it was just purely like, cost and like, like, you know, compliance, you know, so like what they can get into a pill, the amount they can get and how many pills they can get people to take.

• 40:01Andrew D. Huberman?

  I'm smiling because our good friend Sachin Panda at the Salk Institute, who's done a lot of important work on intermittent fasting and other incredible work on circadian rhythms, etc. When I was talking to him in preparation for an episode on intermittent fasting, he I said, why the eight hour feeding window? And he said, well, the graduate student who ran those studies had a partner, I think it was a girlfriend, as I recall, I hope I didn't get that backward. And the partner said, listen, you can be in lab 10 hours a day, but you can't be in lab 14 hours a day if you want this relationship to work. And so it was eight hours of feeding window, plus some measurements, I mean, and time to walk into the lab, park the car, etc. And so the eight hour feeding window that everyone

• 40:42Andrew D. Huberman?

  holds so holy was actually just born out of this relationship between these two graduate students, you know, had they been single, I was single all through graduate school, or most of it anyway, and I lived in the lab. So if it'd been me, we'd all be intermittent fasting would mean eating 14 hours a day. That was a joke, not a good one, but I just want to make clear I'm joking. But the point that you're making is a really good one that the four four gram.

• 41:06Andrew D. Huberman?

  Amount is not a threshold based on anything except the threshold of people's willingness to actually take the stuff. So, and I think that's important for people to hear because so often we hear the eight hour feeding window, you know, four grams of EPA, um, you know, 115 minutes of cardio. And it's really a question of what you can reasonably do in a study.

• 41:26Dr. Rhonda Patrick?

  So I take four grams a day. I take two in the morning, two grams in the morning, and I take two grams in the evening. I take my EPA in the morning and I take my DHA in the evening.

• 41:35Andrew D. Huberman?

  You split them.

• 41:36Dr. Rhonda Patrick?

  I do. Um, I don't know if, I don't think it's necessary, not necessarily. I'm, I just happen to buy, I happen to get a certain fish oil supplement that's like, separates them. Um, and so, you know, like LaVazza, LaVazza's a great one and it's all like in one and it's easier.

• 41:51Andrew D. Huberman?

  What if someone doesn't have a prescription? So I take over the counter fish oil. I know I feel better because I've done the experiment of going on and off. I take the mainly for, I don't have depression, but um, my mood is better. My joints feel better. I just feel better. Um, and I like to think that my platelets are slipperier and, and they're, they're, you know, cruising through any little uh, uh, obstructions in my, my veins or arteries. That's the image I have in my head, but I don't have any data to support that part.

• 42:17Dr. Rhonda Patrick?

  Yeah. I mean, so if you, if you're asking for like, where do people get these?

• 42:22Andrew D. Huberman?

  Well, let's say I look at the bottle and it says, um, two grams per serving, but then I look and it's, um, 750 milligrams of EPA, right? Um, or a thousand milligrams of EPA. Let's say half of it is EPA. Then do I want to hit a threshold of EPA or a threshold of, of what's listed on the bottle, right? On the, on the front of the bottle. And because my understanding is that we need to hit a threshold level of EPA in order to derive these important benefits.

• 42:53Dr. Rhonda Patrick?

  I think two grams is, um, is a good threshold. Now, um, the International Fish Oil Standards, IFSO, they have a website where they do third-party testing of.

• 43:07Dr. Rhonda Patrick?

  A ton of different fish oil supplements from around the world. And they measure the concentration of the omega-3 fatty acids in the actual supplement, because nothing is ever what it says on the bottle. And then they also measure contaminants, so mercury, PCBs, dioxins, things that you'd find potentially in fish that are harmful to humans. And they also measure mercury and then oxidized fatty acids. So these omega-3 fatty acids are polyunsaturated fatty acids, which are extremely prone to oxidation. So please keep your fish oil in the refrigerator, because it's colder. Yeah, they're extremely prone.

• 43:45Andrew D. Huberman?

  Mine's in the cupboard, so now I know.

• 43:46Dr. Rhonda Patrick?

  The shelf life's, you know, increased, is lower oxidation.

• 43:50Andrew D. Huberman?

  Makes perfect sense.

• 43:51Dr. Rhonda Patrick?

  Right. So anyways, they measure that. And I typically like to look for, they give you a total oxidation number. It's called toto, no, T-O-T-O-X, totox is what we call it for short. And I like it to be at the least under 10, ideally under 6. It's really hard to find all the right mixtures of things. But people can go to this website and they can browse through the products. I have put together an Excel sheet, which I have a YouTube little screencast that I'm yet to publish, press the publish button on. But it basically, you have to go back and check and update, because these are from different lot numbers, you know, of the products. They do have up to like 20, 27 or something.

• 44:34Dr. Rhonda Patrick?

  And so I've gone through and found my top picks of high EPA brands and high DHA brands, if I were to buy some, the ones that I would choose because of the low total oxidation and the high concentration of either EPA or DHA. Now, people can go and do this themselves. It just takes some work.

• 44:51Andrew D. Huberman?

  No, I'm glad that you did the work. I'm going to put up a tweet every week.

• 44:56Dr. Rhonda Patrick?

  Oh, no.

• 44:57Andrew D. Huberman?

  With you tagged until this list is published online. Sorry, Rhonda, but I'm gonna do it. I know, it's very sadistic of me, but in service to the community and myself.

• 45:06Dr. Rhonda Patrick?

  And I chose five brands from each, and I tried to choose, I tried to find one in like Europe and one in Canada, so there's like a great selection.

• 45:12Andrew D. Huberman?

  Thank you for doing that work. I don't want to do that work, and I trust you. So, yeah, I try and get two grams per day of EPA.

• 45:20Dr. Rhonda Patrick?

  Yeah.

• 45:21Andrew D. Huberman?

  From supplementation. I'll now put it in the refrigerator. Mood is better. I made that decision mainly based on the data that I'm aware of, looking at comparison of people doing that, anywhere from two to four grams of EPA per day compared to SSRIs, selective serotonin reuptake inhibitors and treatment of depression. And I don't want to take an SSRI if I don't have to. And fortunately, I don't have to. But the data, by my read, are remarkable. People that take these things in sufficient doses, meaning the EPAs are able to get by with much lower dosages of SSRIs for depression relief, or in some cases, to come off their SSRIs completely, or avoid going on antidepressant medication.

• 46:03Andrew D. Huberman?

  Now, of course, this is not something people should cowboy, you know, mental health issues are serious. But what other reasons? I'd love your thoughts on that, on the mental health part. And so maybe you could tell us, what are some things that getting two to four grams of EPA per day is going to help with in our brain and the rest of our body?

• 46:21Dr. Rhonda Patrick?

  So do you, do you know? So I actually published a paper back in 2015 about the role of omega-3 and vitamin D in depression, bipolar disorder, schizophrenia, and impulsive behavior. But so like, within that paper, like the, doing background research, and this was a review article, by the way, I was just connecting dots because I

• 46:43Andrew D. Huberman?

  No, I'm gonna, I'm gonna grab that. I confess, I don't know the paper, but I love quality reviews because the references they're in are so useful.

• 46:51Dr. Rhonda Patrick?

  Well, there's a huge role for inflammation, the cause of inflammation and depression. And, you know, I think we did a short animated video on this as well, like years ago, back when I was, you know, publishing that, that work, where, you know, people are injected with lipopolysaccharide. I mean, this is something that we're, we're generating from our, from our gut, mostly from, you know, our gut permeability, which happens a lot. Endotoxin, it's also called, it's like, it's endotoxin lipopolysaccharide. It's basically the outer membrane of bacterial cells when bacteria die. So like, when the immune cells in our gut come into contact with the bacteria because we drank alcohol five days in a row, or whatever.

• 47:32Dr. Rhonda Patrick?

  We release endotoxin or something stressed us out. We release endotoxin into our body. And that causes inflammation. And so you can inject people with lipopolysaccharide and cause depressive symptoms. However, if you take those same cohort of people, give them EPA, and I think it was somewhere around two grams, and then inject them with lipopolysaccharide. We're establishing causation here, right? It totally, the depressive symptoms versus the placebo. So the placebo was saline control. So there was, this was a placebo controlled because obviously it's hugely important for depression. It ameliorated the depressive symptoms that was caused by lipopolysaccharide.

• 48:07Andrew D. Huberman?

  Amazing. And LPS, lipopolysaccharide, is no joke. Years ago, when I was working on thermal regulation,

• 48:15Andrew D. Huberman?

  we would inject animals with LPS to induce fever. There's a, the vagus nerve registers the presence of LPS signals to these particular hypothalamic areas and cranks up body temperature because basically it's a signal that the body is infected, right?

• 48:32Andrew D. Huberman?

  Amazing. So I will continue with my two grams per day. Maybe I'll ramp it up to four. I'm not doing the DHA separately. There is DHA in the same supplement. Is that okay?

• 48:44Dr. Rhonda Patrick?

  Yes. Yeah. Yeah. And, and you know, to kind of, boy, we have, we got a lot of things to hit back on because your, one of your original questions was krill oil versus fish oil.

• 48:53Andrew D. Huberman?

  Yes.

• 48:53Dr. Rhonda Patrick?

  And DHA, DHA specifically is, it's, you know, in phospholipid form, it, it's more bioavailable. So our bodies, you know, if you're comparing exact quantity or concentration, you know, in triglyceride form versus phospholipid form, you will get more in your plasma cells, in your plasma, plasma cell, in your, in your plasma with krill oil. However, krill oil supplements are so low dose, like, I mean, good luck getting two grams of omega three from krill oil. And also krill oil supplements are notoriously rancid. I don't know for whatever reason.

• 49:35Andrew D. Huberman?

  Maybe that's what made me itchy all over.

• 49:37Dr. Rhonda Patrick?

  I, I think they're just, I, I like, I, I haven't found a good krill oil supplement. I, I pretty, pretty much stay away from it. I mean, if you smell it too, I mean, it's just like, like, it just smells rancid. So, but the thing is, and I also published a paper on this back in 20... Nineteen or yeah, something like that. Um, about DHA and phospholipid form getting into the brain. Um, in a, through a different mechanism than DHA in triglyceride form. And so it's going through a transporter called the MFS D2A transporter. And I think it's very relevant for people with an APOE four allele. So I kind of

• 50:16Andrew D. Huberman?

  With an Alzheimer susceptibility.

• 50:17Dr. Rhonda Patrick?

  Right. So, so like 25% of the population has an allele and a gene called APOE. Uh, four and um, basically it, it's APOE, but the four is, is referred to as the, the, the bad kind of version of it. Um, this is something in our, our bodies. It's also in our brain and if people have one of these versions, if they got one from their mom or their dad, they have a twofold increased risk for Alzheimer's disease if they get two, which is much, it's much more, um, it's less, it's less common. I think it's like 2% of the population or something has two alleles, but they have like a 10 or 11 fold increased risk of Alzheimer's disease. So, um, there is a role for phospholipid form, um, DHA in the brain, but you also make phospholipid DHA inside your body and you can do that by taking in more triglyceride form.

• 51:02Dr. Rhonda Patrick?

  So two grams, like the magic, more, two grams or more is the magic number, I think. So, so kind of back to like the, the why for fish oil and, and I, I personally think it is one of the most powerful anti-inflammatory, um, things, dietary lifestyle, things that we can, we can get easily, relatively easily, that, um, is, it's going to powerfully modulate the way you think, the way you feel and the way you age and a variety of different

• 51:37Dr. Rhonda Patrick?

  types of studies kind of led me to that conclusion. A, a variety of, you know, observational studies. So there's been lots of work by Dr. Bill Harris and his collaborators, looking at what it's called the omega three index. So this is actually the omega three level in red blood cells. So red blood cells turn over about every 120 days. So it's a, it's a long-term marker of omega three status. This is very different from 99.9% of any study you see or any, um, lab that you go to, to get your omega three levels tested. You're getting your plasma phospholipid levels tested, which is kind of like, you can think of it as, what did I eat a couple of days before? Oh, I had fish. My omega-3 levels are great, but did you eat fish like that every week?

• 52:21Dr. Rhonda Patrick?

  Or was it like, you know, was like you went out to dinner? So it's not a great biomarker for long-term omega-3 status. It's kind of like the, you know, fasting blood glucose levels versus the HbA1c, which is like a long-term marker, right, of your, of your blood glucose level. So the omega-3 index, he's done a variety of studies, observational studies. So for people listening, these are studies that are obviously flawed because they're not establishing causality. They're, you know, you're looking at people's lifestyles. But in the, in the case of Bill Harris's work, he's measuring something. So he's measuring the omega-3 index and he's measuring the omega-3 index in people and then looking at their mortality risk, for example, or their cardiovascular disease risk.

• 53:06Dr. Rhonda Patrick?

  And what he has found is that most, first of all, standard American diet has omega-3 index of 5%. Japan, by contrast, has an omega-3 index of around 10 to 11%. Big, big difference there. And they also have about a five-year increased life expectancy compared to people in the US.

• 53:28Andrew D. Huberman?

  And do you think that's mainly due to their fish intake, seafood intake?

• 53:30Dr. Rhonda Patrick?

  So what he showed was, I, I think it's a, a big part of it. I mean, you can't always say it's the only thing, but what he showed in his data was that in, and I think it was Framingham study where he, he looked at the omega-3 index and people that had a omega-3 index of 4% or lower, so close to what the standard American is, but a little bit lower. They had a five-year decreased life expectancy compared to people that had an 8% omega-3 index. And so, big difference there, right? Five, five years life expectancy. But here's the really interesting thing, Andrew. He also looked at smokers and smokers and their omega-3 levels. And so he stratified it, right?

• 54:11Dr. Rhonda Patrick?

  And he found smokers that had no omega-3 were like the worst of all. I mean, it was like, it was just like worse, right? We, we all know smoking is bad for us and will take, take years off our life expectancy. But smokers that had the high level, like smokers that were taking their fish oil or eating fish or whatever it was they were doing to get them up to 8%, they had the same life expectancy as non-smokers with the low omega-3 index.

• 54:36Andrew D. Huberman?

  Wow.

• 54:36Dr. Rhonda Patrick?

  Right?

• 54:37Andrew D. Huberman?

  Wow. And that's, that's amazing. And it's also amazing to me that people still smoke cigarettes. But I see a lot of people vaping. And I, and I'm, and I know a lot of people consume cannabis, right? People, has there been any studies of specifically of vaping or people smoking marijuana? And all cause mortality?

• 54:59Dr. Rhonda Patrick?

  I haven't seen those. I haven't seen those.

• 55:01Andrew D. Huberman?

  They're not motivated enough to come in as research subjects. That was, that was again, a poor joke. It is hard to study people marijuana use unless I'm told by my colleagues that study this stuff, unless you offer people marijuana, in which case they'll do it. But again, they're actually not very good research subjects in all seriousness, because they are not very motivated or consistent and they forget their appointments. So that's incredible. And you mentioned that the data on pollution related to the plant compounds earlier. So it's almost like these things are, again, are acting in a reparative way.

• 55:38Dr. Rhonda Patrick?

  The omega threes are, I mean, they're, they are resolving inflammation. They're like blunting inflammation. They're, they're doing so many different, like, they affect so many different parts of the inflammatory pathway, which is, I think, it plays a huge role in, in the way we age, the way our brain ages, the way we feel, our mood, just our joints, all that. And so it's, it's amazing, but it's not, you know.

• 56:02Andrew D. Huberman?

  I, I love fish oil. I feel better when I take it. I try to eat some fatty fish a couple of times a week. I do want to just touch on food sources for a moment. First of all, are there plants that are rich in omega threes? And second, I have some friends who are really into meat. And I like meat a lot. My dad's Argentine, but I don't eat very much of it. I try and eat high quality meats in relatively limited amounts, but I do eat pretty often. But I've been told by these sources of questionable authority that if an animal grazes on really good grasses, for instance, that the meat can contain a lot of omega threes,

• 56:44Andrew D. Huberman?

  which in principle makes sense based on this omega three index, because you're telling me that a lot of this omega three is sequestered into the red blood cells. So if I'm eating high quality grass fed meat and the grasses had omega threes, do my steaks have omega threes or no?

• 56:59Dr. Rhonda Patrick?

  So there was a study published that compared conventional meat, so meat that is, you know, that animals are fed, you know, corn or soy or whatever it is.

• 57:10Andrew D. Huberman?

  Which is terrible.

• 57:11Dr. Rhonda Patrick?

  Yeah.

• 57:12Andrew D. Huberman?

  For animals and people, as far as I can tell, I'm sure I'll get, I'll get some attacks, but that's okay. I won't read those comments. The, um, the, again, a joke, I read all the comments, but, um, the, it seems to me that these animals would have to get, either be taking fish oil or eat plants that are very rich in omega threes in order for the, the meat to actually contain sufficient omega threes.

• 57:35Dr. Rhonda Patrick?

  I, so, so the meat, comparing the conventional meat to like the grass fed or, you know, pasture raised cows or cattle, uh, there were higher levels of alpha linoleic acid and ALA is, it can be converted into EPA and DHA. Um, but the conversion is very inefficient and very dependent on a variety of factors, including genetics. Genetics, a huge, you know, regulator, like some people can do it much better. Others, like you're getting like 5% of conversion to EPA. Uh, estrogen is a major regulator of making that more

• 58:17Dr. Rhonda Patrick?

  efficient and, and makes sense because pregnancy, when your estrogen just goes through the roof. I mean, these omega three fatty acids play a very important role in brain development. So you're, you know, women are supposed to be converting any ALA they can into the longer chain omega three fatty acids, right? So, so estrogen does affect that, but I would say plant sources. So if you're looking for the ALA, plant sources would be, you know, walnuts, flax seeds, those are probably the highest. But if you're, if a person is a vegan or a vegetarian, their best bet is to actually get microalgae oil and you can supplement with microalgae oil because microalgae do, it's, they do make the, the DHA. And so,

• 59:02Dr. Rhonda Patrick?

  um, that would be a better source for, for people that are, that are vegetarian and vegan rather than doing the, the flaxseed oil because that conversion inefficiency, you know, the enzymes that convert ALA into EPA and DHA. Again, there's, it's inefficient.

• 59:19Andrew D. Huberman?

  And then for people that eat fish, um, sardines, you said?

• 59:23Dr. Rhonda Patrick?

  Salmon.

• 59:24Andrew D. Huberman?

  Salmon, and you have to eat the skin, as I understand.

• 59:27Dr. Rhonda Patrick?

  You don't have to, but it's good.

• 59:29Andrew D. Huberman?

  It's rich with.

• 59:30Dr. Rhonda Patrick?

  The oil, yeah, and, and, and the reason I say like, like I, I, I think the best would be wild Alaskan salmon versus the farm raised because the farm raised, again, they're feeding them, they're feeding them corn, they're feeding them like grain and stuff.

• 59:44Andrew D. Huberman?

  Really?

• 59:44Dr. Rhonda Patrick?

  And then they give them astaxanthin. So astaxanthin is a carotinoid. It's the carotinoid that's in things like chryl crustaceans that make their red pigment.

• 59:52Andrew D. Huberman?

  Yeah, it's also being used now as a supplement and there's a prescription form to try and rescue some age-related vision loss because of the, the role of the vitamin A pathway and photoreceptors.

• 1:00:05Dr. Rhonda Patrick?

  Yeah. Well, you know, actually the carotinoids themselves, so like lutonins, azanthin, they're really good at sequestering singlet oxygen, which is some damaging, right?

• 1:00:14Andrew D. Huberman?

  Yeah, as we age, they, um, because the retinal cells, the, uh, cells of the eye are so metabolically active, they accumulate a lot of reactive oxygen species and, uh, mitochondrial repair and limiting reactive oxygen species is, is a major, uh, theme of trying to rescue vision.

• 1:00:32Dr. Rhonda Patrick?

  Yeah.

• 1:00:32Andrew D. Huberman?

  That is, that's a whole other podcast and story. There's some really interesting data now on the use of red light to try and trigger these pathways.

• 1:00:38Dr. Rhonda Patrick?

  I've seen some.

• 1:00:39Andrew D. Huberman?

  Glenn, that's my, uh, good friend of many years and amazing scientist Glenn Jeffries lab at a university college London. I'm still, we should talk about that at some point, if not today.

• 1:00:48Dr. Rhonda Patrick?

  That study, like 2020, was it?

• 1:00:49Andrew D. Huberman?

  Now they have a second study.

• 1:00:50Dr. Rhonda Patrick?

  Oh, do they?

• 1:00:51Andrew D. Huberman?

  Yeah, it's looking real. I mean, you know, they're, they're cautious. They're, they're appropriately British and cautious about it. Uh, you know, I've, I always joke, if those studies have been done over here, everyone would already know about it. Glenn is a very conservative guy, but they've done this stuff now in, in pigs and rodent models, and now also two studies in humans. It's looking pretty, pretty interesting. So sardines, but also anchovies. I mean, all I, by the way, I hate all the food items that I'm describing. I can barely tolerate salmon. I don't like fish at all. Actually, I like live fish. I had fish tanks when I was a kid. I just don't, no, I find fish, unless it's in sushi form, I find it absolutely, um, repulsive. And I don't know why. I probably have some mutation.

• 1:01:31Dr. Rhonda Patrick?

  So raw fish is actually higher in mercury than cooked?

• 1:01:34Andrew D. Huberman?

  Okay. Well, that's good. Now I don't really like sushi that much anyway. You're giving me great reasons to not eat fish, but except I should eat these other fish sources or supplement more heavily. That's the message I'm getting.

• 1:01:45Dr. Rhonda Patrick?

  I eat sardine, my, my, like every day, my like first meal almost is like a can of sardines and an avocado with like.

• 1:01:51Andrew D. Huberman?

  Avocado is good.

• 1:01:52Dr. Rhonda Patrick?

  Yeah, with a little bit of lemon and then some little hot sauce like, you know.

• 1:01:56Andrew D. Huberman?

  Does avocado have omega threes?

• 1:01:58Dr. Rhonda Patrick?

  Avocado is very good in monoinsaturated fat. Um, it's not really high in polyinsaturated fat. Omega three really, I mean, it's, it's, it's either the, the DHA and EPA that's in the, the marine sources, fish, or it's the plant ALA source, which is like the flaxseed or the walnuts. Um, so.

• 1:02:15Andrew D. Huberman?

  It's rough. I mean, all these, um, companies now are, are making these, um, plant-based products that taste like meat. My wish is that they would just make a fish that tastes like a steak.

• 1:02:26Dr. Rhonda Patrick?

  You know, the fish come out albino, the ones that they farm raise because they don't eat any of the.

• 1:02:31Andrew D. Huberman?

  I'm joking. I don't want a genetically modified fish that tastes like a steak. All that, you know, I, I love the taste of steak. The point here is that if you don't, if you, if one doesn't see themselves regularly consuming these fish, uh, these, uh, fish sources of omega threes, it seems to me that the only way to really get them is from supplementation.

• 1:02:53Dr. Rhonda Patrick?

  And supplementation is a good way to get a, a high dose and, and to get back to your dose point. Uh, there was a, a couple of studies that, that basically, you know, I think there was, there was some way they showed that people that are in the four percent omega three index range, in order to get to the eight percent, right? The five-year increased life expectancy, if we're comparing the two groups, was to supplement with at least two grams. It was about two grams a day. Uh, and that, and I think it was a little bit less if it was triglyceride form, but I think two grams is a good, safe number. So, most Americans that are not eating a lot of fish and they're not supplementing are probably around a four to five percent omega three index.

• 1:03:33Dr. Rhonda Patrick?

  And to get to the eight percent, and I, and I think that's a good empirical way of thinking about it, right? Okay. Well, I want to get to that eight percent. By the way, I'm almost 16% omega three index.

• 1:03:43Andrew D. Huberman?

  Yeah, I was gonna ask about, um, about testing.

• 1:03:45Dr. Rhonda Patrick?

  Yes.

• 1:03:46Andrew D. Huberman?

  So, so where can somebody measure, where and how can somebody measure their omega three index? Which again, just to remind people is the, uh, essentially the percentage of omega threes that you have in your blood with the caveat that. The omega-3 index will be heavily biased by what you ate in the previous days.

• 1:04:04Dr. Rhonda Patrick?

  Not the omega-3 index. Okay.

• 1:04:06Andrew D. Huberman?

  Sorry, I misunderstood. I thought you said in red blood cells. If I ate salmon two days ago, my omega-3 index is gonna go up.

• 1:04:11Dr. Rhonda Patrick?

  No, that was plasma.

• 1:04:12Andrew D. Huberman?

  I misunderstood.

• 1:04:13Dr. Rhonda Patrick?

  So, most people are measuring, like, if you look at a lot of studies, and honestly, Andrew, I think a lot of the reason for conflicting data is because people are measuring plasma omega-3 levels.

• 1:04:25Andrew D. Huberman?

  Okay.

• 1:04:25Dr. Rhonda Patrick?

  The phospholipids, it's in a phospholipid, right? So, your phospholipids are carrying things, these are lipoproteins, they're carrying things like omega-3 and triglycerides and stuff and shuttling them around. So, the omega-3 index is actually in the red blood cells, and red blood cells take 120 days to turn over. So, if you're gonna do a baseline test, if you wanna know before supplementing what your level is, you have to wait 120 days before doing the second test after supplementing to know how much you went up, because that's how long it takes for your red blood cell to turn over. So, the omega-3 index, Bill Harris has a company that he co-founded, it's called Omega Quant, and they measure the omega-3 index. They have

• 1:05:09Dr. Rhonda Patrick?

  a variety of different index tests. You can do like a basic one, or a little more advanced.

• 1:05:13Andrew D. Huberman?

  This is from a blood draw?

• 1:05:14Dr. Rhonda Patrick?

  It is. It's a little blood spot thing, yeah. And, you know, like, he uses money to like funnel back into doing lipid research. Like, he's like out there doing all sorts of interesting studies on omega-3s. It's great. But, the omega-3 index is great. I think that, honestly, more people, more researchers should be using it, because the conflicting data, it always comes down to what we're measuring, the sensitivity of it, you know, are we even measuring anything? So, you know, you're giving someone 500mg of DHA, and you don't see any effect. Well, did you measure what their levels were, and did you measure the omega-3 index? You know, there's all sorts of problems with... Randomized controlled trials, and I think that it just, we need to like, as scientists,

• 1:05:58Dr. Rhonda Patrick?

  we need to come together and like, make some progress. I mean, you know, let's all talk to each other. Let's, let's, let's figure things out. Like, this, this test is out there. It should be used. It should be used not just by Bill's group, but like, everyone.

• 1:06:11Andrew D. Huberman?

  Yeah. Well, and I'm learning so much for me, and I agree, we need more collaboration. I've always enjoyed really fruitful collaborations in my lab at Stanford, and collaborating is just so much more fun. Online, there seems to be a bias more towards creating silos as opposed to bridges. But I appreciate that you bring up the need for more collaboration, and knowing which measures are best. And in this case, now I'll thank you for the clarification. I understand this omega-3 index is going to be best. You mentioned you, so basically when now I and I look at you, I think you are 16% omega-3.

• 1:06:44Dr. Rhonda Patrick?

  And dolphins are 19%. I'm almost.

• 1:06:47Andrew D. Huberman?

  Is that your goal? You're trying to get there?

• 1:06:48Dr. Rhonda Patrick?

  It is.

• 1:06:50Andrew D. Huberman?

  To, to, interesting. Actually, they should probably do something where you're trying to achieve the omega-3 ratio of the, your favorite species. Now that we've covered a bit of how to get these things into one's system, depending on what one eats, et cetera, and some of the better measurements, how is omega-3 and some of these other related lipids, how are they having these positive effects? In my mind, and this is incredibly elementary, but my understanding is that at some level, they're making platelets more slippery. Is that true or not? I hope, I'm happy to be wrong. How is it possibly impacting my mood? Is it through the synthesis of membrane on neurons that allows neurons to release

• 1:07:32Andrew D. Huberman?

  more transmitter like serotonin and dopamine? I mean, what are some of the purported, reported, and known mechanisms?

• 1:07:41Dr. Rhonda Patrick?

  I think some of the, the most well-known mechanisms do have to do with the, the omega-3 fatty acids being very powerful regulators of.

• 1:07:51Dr. Rhonda Patrick?

  The inflammatory process in some way, shape or form, whether that has to do with resolvins that are produced. So these from the metabolites of like DHA, for example, resolvins play a role in resolving inflammation. Like you want your inflammatory response to be activated when it's supposed to be, but you want to resolve that inflammation and inflammatory response in a timely manner, right? And resolvins help do that. And so resolvins are one. And then there's these specialized promediating molecules, the SPMs, that also help resolve the inflammation. There's, like you mentioned, the leukotrienes and prostaglandins, and these things are being affected by EPA, and they do affect platelets and platelet aggregation. And they, you know, they do affect that whole pathway as well.

• 1:08:36Dr. Rhonda Patrick?

  And so there's just, and there's, you know, I think there's just so many different ways and inputs. And so when we talk about inflammation, honestly, it's a big general term. But you're talking about, when you're talking about serotonin release, you know, at the level of neurons, you know, we know that these inflammatory molecules cross the blood-brain barrier. And I just mentioned ago about injecting people with lipoprotein saccharide and causing depressive symptoms. You know, it's known that, that omega-3, actually specifically EPA is able to help serotonin. Inflammation inhibits the release of serotonin. And so EPA is actually able to blunt inflammatory responses, along with DHA as well. DHA does that through B-solvents and stuff.

• 1:09:20Dr. Rhonda Patrick?

  And this then helps more serotonin be released because you're not having so much inflammation getting into the brain and affecting serotonin release, right? That's one mechanism. And then another would be, well, DHA itself has been shown, it's, it's a very important fatty acid that makes up cell membranes, many cell membranes, including in our neurons. And as you very well know, Andrew, the structure and function of receptors, of transporters, these membrane-bound proteins on the surface of our cells, including neurons. Are affected by the membrane fluidity, you know, like how rigid and how fluid the cell membrane is and DHA plays a role in that. And so, for example, in animal studies, if you make an animal deficient in DHA, their serotonin receptors, dopamine receptors,

• 1:10:05Dr. Rhonda Patrick?

  they're affected because the structure of them is affected through the fluidity of the membrane. And so I think that's another mechanism. And I'm talking sort of general because I'm not a neuroscientist.

• 1:10:18Andrew D. Huberman?

  No, but it makes perfect sense. I mean, we know, for instance, neuroplasticity and the almost always involves the recruitment of more receptors or an improvement in some feature of receptors to neurotransmitters. And they literally move laterally in the membrane. They kind of float around like little rafts. Sometimes they are in fact in lipid rafts. And so it makes perfect sense that these molecules like DHA, which are part of the structural fat of the neuron, because of course, the outsides of neurons are basically fat, not just the myelin that people have heard of, but the actual membranes, that if getting that right, you wouldn't want it as rigid as concrete, but you wouldn't want it as soft as, need to come up with something here. What's that gooey stuff that

• 1:11:00Andrew D. Huberman?

  kids play with? It's like that goo. Anyway, there's a, yeah, it's disgusting and it's too soft to be a membrane for a neuron. That's what we know.

• 1:11:08Dr. Rhonda Patrick?

  You get it in those machines, like claw machines.

• 1:11:09Andrew D. Huberman?

  Someone put it in the comments and tell me what that disgusting gooey stuff is. You don't want your neurons to be that gooey, and yet you don't want them to be like concrete either.

• 1:11:17Dr. Rhonda Patrick?

  It's a balance.

• 1:11:18Andrew D. Huberman?

  It's a balance. And in mentioning DHA, I'm just gonna, I realize I'm backtracking, but I want to make sure that we close all the hatches for people. We talked a lot about EPA, but are food sources of DHA that you find particularly attractive, either by taste or by potency for DHA, what are just a few that we could throw out? Because I am aware that there are supplements where you can get a nice ratio of EPA to DHA, or you take them separately as you do. But if I want to make sure that I'm getting enough DHA, what do I need to be sure I'm eating on a regular basis?

• 1:11:52Dr. Rhonda Patrick?

  Well, the fish is packaging the DHA and EPA in the ratio. And, but I also do eat salmon roe. Which is very salty and it's a really high source of the phosphatidylcholine DHA.

• 1:12:07Andrew D. Huberman?

  This is fish eggs.

• 1:12:09Dr. Rhonda Patrick?

  It is.

• 1:12:09Andrew D. Huberman?

  Yeah.

• 1:12:09Dr. Rhonda Patrick?

  Yeah, and actually.

• 1:12:10Andrew D. Huberman?

  That I like for some reason.

• 1:12:12Dr. Rhonda Patrick?

  Oh, do you?

• 1:12:12Andrew D. Huberman?

  Yeah, I'll eat. So I'm discovering something about myself. This was not meant to be nutritional psychotherapy, but you're doing that for me anyway. I'm discovering that, yeah, I like eating embryonic fish. I just don't like eating the actual fish.

• 1:12:25Dr. Rhonda Patrick?

  Okay, well.

• 1:12:26Andrew D. Huberman?

  Okay, so fish eggs are okay. So caviar, basically.

• 1:12:29Dr. Rhonda Patrick?

  Caviar, yes. And that's a good source of the phospholipid form. And I was consuming that a lot because I wanted to get the phospholipid form.

• 1:12:36Andrew D. Huberman?

  Yeah.

• 1:12:36Dr. Rhonda Patrick?

  So it's actually really good. There's been some animal studies and piglets and rodents as well, showing that consuming phospholipid DHA during fetal brain development, like gets like 10 times more DHA in the brain. Again, it's.

• 1:12:52Andrew D. Huberman?

  Makes sense based on fetal development. So do I need to buy Beluga caviar? Stuff can get pretty expensive at $200.

• 1:13:00Dr. Rhonda Patrick?

  I don't think you need to now. I think it's a matter of preference and if you're supplementing with your your two to four grams of fish oil, I mean, that you're gonna get phospholipid form anyway because your body's gonna make it.

• 1:13:15Andrew D. Huberman?

  Okay, I've seen some containers of what I assume to be quality fish eggs that are not at the caviar level you can find in the better grocery stores that aren't super expensive.

• 1:13:25Dr. Rhonda Patrick?

  Right.

• 1:13:25Andrew D. Huberman?

  I wouldn't dip as low as to go eat, for instance, like fishing bait. Like when we were kids, we used to go fishing. You put the fish egg on the thing. That's probably not good, although it's good enough for the fish apparently. Okay, only half joking here, folks. I'm just trying to protect you from yourselves. Don't get any crazy ideas about eating fishing bait. Okay, so that's great to know. So we have these plant-based compounds. We have the omega-3s, so EPA. And then you mentioned there's a third category. What would you place in your third category of foods or supplement-based nutrients that?

• 1:14:01Andrew D. Huberman?

  Our health, brain and or body health can really benefit from.

• 1:14:04Dr. Rhonda Patrick?

  I mean, I think the most obvious would be vitamin D, which is actually, as you know, a steroid hormone that we produce when we're in the sun. Depending on the time of year, we can make it in our skin and depending on how much melanin we have in our skin or whether or not we're wearing sunscreen or how old we are, it's a very, there's a sliding scale on how efficient that process is.

• 1:14:26Andrew D. Huberman?

  And it's sort of, as I understand, there's an inverse relationship where the darker, the more darker, the darker your skin is naturally, the more vitamin D you need to consume. Is that right?

• 1:14:36Dr. Rhonda Patrick?

  Well, the darker your skin is, the harder it is. So there was a study out of the University of Chicago. This was several years ago where they looked at African Americans and compared African Americans to Caucasians with light skin, fair skin, and how, how well they could make vitamin D from sun exposure. And, and how long they had to be in the sun to make X amount, right? And it turns out that African Americans with darker, darker pigmentation, which protects them from the burning rays of the sun. It's a natural sunscreen, had to stay in the sun like six times as long as someone with none, none of that natural sunscreen. So I think the, the, the take home there is, you know, a lot of people with a darker skin

• 1:15:18Dr. Rhonda Patrick?

  living in Sub-Saharan Africa or people living in India with darker skin or in the Philippines, you know, these equatorial regions where there's, you tend to see darker skin because it's protection from the burning rays of the sun.

• 1:15:30Andrew D. Huberman?

  An adaptation.

• 1:15:30Dr. Rhonda Patrick?

  They are in the sun war.

• 1:15:32Andrew D. Huberman?

  Right, yeah.

• 1:15:32Dr. Rhonda Patrick?

  And they're getting more vitamin D, but people that maybe moved to the United States, to like Minnesota or in a place where, you know, UVB radiation isn't, you know, getting to the atmosphere 12 months out of the year. It's only getting there four months, for example. Or even living in our modern day society where people just don't go outside anymore. I mean, we're inside, we're at our laptops in school, we're at work, we're in our cubicle, whatever. So. Supplementation does play a major role, not only for people with, you know, darker skin that aren't outside all the time, but for everyone. Seventy percent of the US population has inadequate vitamin D levels. Seventy of the whole

• 1:16:08Andrew D. Huberman?

  Amazing.

• 1:16:09Dr. Rhonda Patrick?

  US. So this is everyone. And, and so I think that insufficient levels defined as less than thirty nanograms per milliliter. And, and that's sort of defined by the, the Endocrine Society, looking, looking, looking at a lot of different aggregate studies and all-cause mortality, for example. There's been a lot of different meta-analyses of all-cause mortality studies where vitamin D levels are, are really seem to be ideal between forty to sixty nanograms per milliliter. And so, um, in order to get to that level, if you are not outside all the time, live in Southern California where you're always outside without sunscreen on, I always wear sunscreen because I'm trying to protect my

• 1:16:52Dr. Rhonda Patrick?

  skin from so many wrinkles and stuff, right? But also, skin cancer is, you know, somewhat of an issue as well. So, um, so, so basically, the point is that vitamin D is a steroid hormone, meaning it actually binds to a receptor, and another receptor dimerizes with it, vitamin, the, the retinoid receptor. And that complex goes into the nucleus of a cell, where your DNA is, and it recognizes little sequences of DNA called vitamin D response elements, they're called VDREs. They're specific sequences of DNA that this complex, vitamin D bound to the vitamin D receptor, goes inside and recognizes, and turns on a whole host of genes, turns off a whole host of genes. I mean, this is, this is important stuff. Like, imagine

• 1:17:37Dr. Rhonda Patrick?

  seventy percent of the population having insufficient testosterone, right? It's a steroid hormone.

• 1:17:42Andrew D. Huberman?

  Which might, we might be headed there. But probably not. No, I think that it's, names are very important, and I think that one of the issues is that vitamin D is called vitamin D. It's not called, um, DHEA, or, you know, variant blah, blah, blah. It doesn't sound like a hormone. I also, I'm glad that you're mentioning, um, skin as the major kind of interface between the Environment and vitamin D synthesis because a lot of people think of skin as just a protective sheath around us or something to adorn ourselves with earrings or tattoos or whatever. But skin obviously serves those roles, but the skin is an endocrine organ. It has the capacity to make things that impact hormones and to make hormones.

• 1:18:25Andrew D. Huberman?

  There's this beautiful study out this last year where this took place in over in Israel where they had people get outside for 20 or 30 minutes a day, three times a week, exposing a culturally acceptable, yet you know, substantial amount of their their skin during that time and saw big increases in testosterone and estrogen. And this is through a caratinocyte linked pathway involving P53. They did a bunch. This was done in humans, but they did some knockout studies in parallel. And what this study told me or reminded me is that skin is an endocrine organ. So the idea that sun could trigger the activation of of a production of a hormone is really interesting and makes total sense. So when vitamin D gets into cells and it's binding to these V D R

• 1:19:08Dr. Rhonda Patrick?

  E's.

• 1:19:08Andrew D. Huberman?

  E's. What what sorts of things are they triggering? So like for testosterone, we know it's going to trigger protein synthesis, muscle growth, tendon strength, et cetera. With estrogen, it's going to be keep your neurons going, your joints feeling good. I always remind people that, by the way, because guys are always seem to want to increase their testosterone and reduce their estrogen, just remind people if you reduce your estrogen, guys, your libido will plummet to near zero. Don't crush your estrogen. It'll also make you stupid. If you're not already stupid, it will make you stupid. So estrogen is vitally important for males and females. When vitamin D gets into cells, what sorts of things is it stimulating?

• 1:19:49Dr. Rhonda Patrick?

  Okay, so first of all, it's it's regulating more than 5% of the protein encoded human genome. More than and this was, you know, I say more than because when I was Looking at this data really in depth back in, starting in, you know, 2012 to 2014, it was that, and then it's now grown. But one of the important things that you'll find interesting that I published on back in 2014 was that I'd gone through this, this big published database where someone had, you know, published all these genes they found V D R E's in. And basically, I found that tryptophan hydroxylase 1 and tryptophan hydroxylase 2 was on there. And so then I started looking at the sequence and I was doing some in silico

• 1:20:32Dr. Rhonda Patrick?

  work. And it turns out that the V D R E's and tryptophan hydroxylase 2, so for people listening, tryptophan hydroxylase is an enzyme that converts tryptophan into serotonin. So tryptophan is what we, an amino acid that we get from our food. You convert serotonin, you convert tryptophan into serotonin into the gut, in the gut, but you also do it in the brain. However, serotonin does not cross the blood brain barrier. So tryptophan has to get into your brain, and then you have to convert it to serotonin in your brain. Well, the enzyme that does that in your brain is called tryptophan hydroxylase 2, and it's activated by vitamin D. The one in the gut is actually tryptophan hydroxylase 1. Some

• 1:21:16Dr. Rhonda Patrick?

  of my, my published work hypothesized that it might actually be repressed by vitamin D, because it has a sequence, the sequence itself, this 12 nucleotide sequence, it can determine, to some degree, whether it's going to be activated or turned off. And so like, I was able to kind of look at that and think, oh, maybe this and that. And so, since then, there have been some groups that have confirmed more with in vivo and or in vitro studies, because mine was all in silico and all that stuff. But anyways, so serotonin, a really important one. But most people, I mean, this is regulating our immune, our immune cell, immune system, it's regulating our blood pressure, you know, all that, that's water

• 1:21:56Dr. Rhonda Patrick?

  retention, you know, I mean, bone, of course, homeostasis, 5%, more than 5%, I mean, I can't tell you, like, so much.

• 1:22:04Andrew D. Huberman?

  I mean, and with 7, 0% of the US population deficient, I'm beginning to think that this could be the linchpin at a number of really important issues. So supplementing vitamin D3 is what I normally hear as the I do, I take, I think I end up taking 5,000 IU, sometimes 10 IU of vitamin D3 per day. Just done that for a long time and I've had my levels tested and they're in range. But I have a family member, I'll just mention this, I have a family member who was not feeling well, just kind of feeling off, a little low, had some digestive issues, this went on a long period of time, was taking on my recommendation 15,000 IU of D3 and was still deficient in D3.

• 1:22:49Andrew D. Huberman?

  Now takes, and I'm not suggesting anyone do this, this is a special case perhaps, but no chronic illness that we're aware of, needs to take 30,000 IU per day in order to bring their D3 range just into normal. Which is, to me, is striking because they eat quite well, they're a healthy weight, etc. But, and it's made a tremendous difference in terms of their mood. Now, of course, this is correlative, now they feel better, they're doing it, who knows, they're probably also getting outside more. But, I mean, I think people need to get tested, they need to get their D3 levels tested. But where, where and what is a good starting range for people to think about D3 supplementation? And again, foods that can increase D3.

• 1:23:31Dr. Rhonda Patrick?

  So, vitamin D3 is a good way to supplement with it. Their, vitamin D2 would be a plant source, you often find it fortified in like foods like milk, usually D2. There's been a few-

• 1:23:41Andrew D. Huberman?

  Does anyone still drink milk, besides kids?

• 1:23:45Andrew D. Huberman?

  Out here, it's like you can't find cow's milk-

• 1:23:47Dr. Rhonda Patrick?

  I mean, all the lattes that you're getting-

• 1:23:50Andrew D. Huberman?

  Soy milk, what's the other one?

• 1:23:51Dr. Rhonda Patrick?

  They're fortified in those as well.

• 1:23:53Andrew D. Huberman?

  Oh, they are?

• 1:23:54Dr. Rhonda Patrick?

  They are, yeah, they're fortified in-

• 1:23:55Andrew D. Huberman?

  I have a hard time finding-

• 1:23:56Dr. Rhonda Patrick?

  Almond milk and oat milk and all that stuff, yeah, they're in all that stuff. Vitamin D is naturally, to some degree, in fatty fish, like, you know, like you think about cod liver oil, right? It's like, it has vitamin D, but it's not, you're not gonna correct a deficiency with eating, with eating fish for your vitamin D. Like, you're either gonna correct it with sun exposure, being in the right area, having the right amount of sun, and being the right age, because as you get old, you become very inefficient at doing that, converting vitamin D, making vitamin D3 in your skin.

• 1:24:29Andrew D. Huberman?

  Well, that's probably what was going on here, because this person is getting up in their age.

• 1:24:32Dr. Rhonda Patrick?

  There's a lot of single nucleotide polymorphisms, we talked about APOE4 previously, but there's a variety of- Uh, genes that people have, very common, actually. In fact, I've had many people that have had to do, done that exact same thing. So, um, measuring your vitamin D levels before and after supplementation is the only way you're going to figure that out, right? Um, very important. If you don't measure it, like, you don't know. Like, you know, you can't know what you don't measure. So, um, so there's a variety of SNPs that basically make that conversion inefficient. And in fact, there've been a lot of these Mendelian randomization studies. So these are studies where people,

• 1:25:11Dr. Rhonda Patrick?

  scientists will look at common SNPs, people that have these common variations of a gene that's a little more than 1% of the population. So it's not a random mutation. It's actually found in a, in a sizable percent of the population. And then they've looked at various outcomes. And, um, a lot of times they'll look at genes that are also involved in some kind of lifestyle factors. So vitamin D, uh, and SNPs that basically make the conversion of vitamin, either vitamin D precursor into D3, or in D3 into 25 hydroxy vitamin D, or into the active steroid hormone, which is 125 hydroxy vitamin D. And there's a variety of different SNPs that show people, and so you're not looking at vitamin D levels at all.

• 1:25:53Dr. Rhonda Patrick?

  You're looking at just the SNPs, and you know if they have it, they have low vitamin D. Okay? So it's really a way of doing a beautifully randomized controlled trial with an observational study, because you're, you're not biased. You know, vitamin D levels are also associated with health. People that are, have higher vitamin D are either outside more, they're more physically active, or they're aware of their health and they're supplementing, right? So you always have to worry about that when you're, when you're, you're doing an observational study. But Mendelian randomization is beautiful for that reason, where you now just randomly, people randomly have these genes, and it's not like, there's no health status. Like, if you have the SNP, like your friend, like your family member was healthy and all that, you know, they were healthy and yet they couldn't get their D levels up, right? So, um, these, these

• 1:26:37Dr. Rhonda Patrick?

  Mendelian randomization studies have found that people that can't convert, um, into the, the precursor, the 25 hydroxy vitamin D, which is usually what's measured. It's the most stable form of vitamin D in the body. Um, they have a higher all-cause mortality if they can't do it. So people with, you know, that don't have it have a lower all-cause mortality. They have a higher respiratory-related mortality. They have a higher cancer-related mortality. So, um,

• 1:27:02Dr. Rhonda Patrick?

  To me, now, why did I get on this rant? Oh, because you're a family member. So, basically, they also are more likely to get multiple sclerosis. This has all been done with Mendelian randomization. And so it really does hammer home the importance of measuring your vitamin D levels and being very proactive about that. I mean, you can get it done anyway. Your doctor will do it. You ask him to do it, you know? So supplementation-wise, typically, if you don't have one of those SNPs, for the most part, taking 1,000 iUs of vitamin D will raise blood levels by around 5 nanograms per milliliter. So, let's say you're deficient, you're 20 nanograms per milliliter, and you want to get to 40. You're going to need at least 4,000 iUs if you're normal,

• 1:27:46Dr. Rhonda Patrick?

  don't have any of these SNPs that change your metabolism of vitamin D, right?

• 1:27:50Andrew D. Huberman?

  Does it matter when you take it relative to sun exposure? Time of day, with or without food?

• 1:27:56Dr. Rhonda Patrick?

  I've seen some not-so-great preliminary evidence suggesting maybe time of day is important. I don't think it real... Like, I can't seem to, you know, to find anything that really suggests, because like, for it to actually be converted into the hormone, I mean, it's stored.

• 1:28:14Andrew D. Huberman?

  It's slow-acting. These steroid hormones are slow-acting.

• 1:28:16Dr. Rhonda Patrick?

  Yeah, it's not like an immediate thing, right? So, like, you know, maybe we'll get some new data that's like otherwise, but I just don't...

• 1:28:23Andrew D. Huberman?

  Yeah. It simplifies the problem, anyway. So, for people who are going to be stubborn and not get their D3 levels tested, or their D levels tested, and simply say, "Oh, I'll just take some D3." That was me, by the way. Until I got tested, I threw 5,000 iUs into the mix and figured, "Well, it's not going to kill me. It'll bring my vitamin D levels up." I didn't realize that's a bit of a coarse way to approach it, but, you know, "I feel fine, and I'm still breathing in ambulatory." So, is that reasonable? 1,000 to 5,000 iUs for most people will be reasonably safe? Again, we're not making... Just assuming that people are going to just jump to it without the blood test?

• 1:29:03Dr. Rhonda Patrick?

  Of course, I think that if we if we if we look at the the the literature, the scientific literature, it is extremely hard to get like hypercalcemia, which would be the major concern with really high levels of vitamin D three supplementation. I mean, we're talking like hundreds of thousands of IU a day for a long time. So

• 1:29:23Andrew D. Huberman?

  Hundreds of thousands.

• 1:29:24Dr. Rhonda Patrick?

  Yes, yes. Now, the the the upper tolerable intake was set by the the the Medicine Institute to be 4,000. I just it was just like the safe. It was kind of like one of those things where it's safe. I I personally take 5,000 IU a day as well. And, you know, my levels really hover around 50 nanograms per mill. And I do out, you know, I don't I don't put sunscreen on like all the time. Like, I do put it on my face and I wear a hat, but like some of my skin is being exposed. So I do make it, you know, from the sun as well. But

• 1:29:56Andrew D. Huberman?

  I'm glad you brought up the fact that you keep arms exposed if you because in these studies that I mentioned before, looking at sun exposure on skin and increases in other hormones, testosterone, estrogen mainly, it was it became clear from looking at those data that the amount of skin that you expose is important, which makes perfect sense once you hear that. But I think most people are thinking, oh, I'm out in the sun. But are you wearing shorts and a T shirt? Or are you wearing a sweatshirt and it's a hoodie? Or, you know, are you are you all covered up out in the sun? Well, that might be great for setting your circadian rhythm by way of light through the eyes because that's the primary mechanism for that. But seems to me that the the more of your body surface

• 1:30:36Andrew D. Huberman?

  that you can safely and appropriately, please, folks, appropriately exposed to the sun, the more vitamin D you're going to create, right? So laying out and on your back deck in shorts and a T shirt with arms exposed and legs exposed is a very different stimulus than walking around in jeans and a sweatshirt.

• 1:30:55Dr. Rhonda Patrick?

  Absolutely.

• 1:30:56Andrew D. Huberman?

  Right? Okay.

• 1:30:56Dr. Rhonda Patrick?

  Yeah.

• 1:30:57Andrew D. Huberman?

  Okay. Especially if you have sunscreen on your face. I know it almost seems like trivially simple, but I I'm not sure that people are used to thinking about their skin as a interface to create these hormones.

• 1:31:07Dr. Rhonda Patrick?

  Yeah.

• 1:31:08Andrew D. Huberman?

  So surface area matters.

• 1:31:09Dr. Rhonda Patrick?

  And by the way, You know, there have been studies looking at people that are deficient in vitamin D. In this case, it was African Americans that were given a 4,000 IU a day vitamin D supplement to bring them back to sufficient levels. And this was a smaller, smaller study than I would like, but it reversed their epigenetic aging by like three years. Because, again, it's a hormone. It's regulating more than 5% of your protein encoding human genome. There was, there's been studies looking at vitamin D receptor knockout mice. And I use this a lot in my presentations when I'm talking about vitamin D and longevity. But if you look at these animals, the vitamin D receptor, as I mentioned earlier, vitamin

• 1:31:54Dr. Rhonda Patrick?

  D binds to the receptor and then it complexes with the retinoid receptor and they go into the nucleus of the complex and you turn on and turn off genes. Well, if you get rid of that receptor, which is what you can do in animal studies, you can just, you can sort of determine like what effects there'll be with no vitamin D, right? Like what, how do you study no, no vitamin D? And so what was found was that these animals, and in fact, I don't think it was a complete knockout or, you know, because I think it might be embryonic lethal, but.

• 1:32:21Andrew D. Huberman?

  Some hypo, some hypo.

• 1:32:22Dr. Rhonda Patrick?

  Yes.

• 1:32:23Andrew D. Huberman?

  Which is basically geek speak for a gene is very, is vastly reduced in its function, number and function, number, people know what I mean, but, but isn't eliminated completely.

• 1:32:33Dr. Rhonda Patrick?

  Yeah. Right. Well, these animals, if you look at them after the age of four months, I mean, the mice look like, I mean, they're accelerated aging, they're wrinkled, they have no hair. I mean, they just, I mean, their lifespan, lifespan's shorter. I mean, they just, they, you could look at this animal and not know anything about mice or work with them and be like, that animal looks like it's, you know, of course, mice lifespan's only like two, two and a half years, but like 500 years old.

• 1:33:00Andrew D. Huberman?

  Right. Looks like it, it went to graduate school twice.

• 1:33:02Dr. Rhonda Patrick?

  Yeah.

• 1:33:03Andrew D. Huberman?

  Actually, graduate school's a lot of fun. I like to think I aged backwards in graduate school, which is not true. I look at the photos, I definitely aged forward. You, on the other hand, look exactly the same way you did 10 years ago. I'm not saying that to flatter you, but it's absolutely true. I mean, the data are the data. It's remarkable. So I, I think it's, I'm definitely going to try and get my omega three percentage up there. I'm not going to, you know, hinge it all on that, but clearly you're doing a lot of things right. So if I'm taking vitamin D3.

• 1:33:31Andrew D. Huberman?

  I still need to get out into the sun.

• 1:33:33Dr. Rhonda Patrick?

  Absolutely.

• 1:33:34Andrew D. Huberman?

  Okay, I think a lot of people don't know that, or at least I have family members that have been a little bit resistant, like I take my vitamin D, so I don't need to get outside as much. I think people are really afraid of getting out into the sun because they're worried about melanomas. And, um, and I'm as, to be honest, I'm as scared of sunscreen as I am of melanoma. Like that, some of the things in sunscreen are really spooky. Mainly the compa-, and here I'm not one of these conspir-, I drink tap water. Listen folks, I like, people cringe with it. I, I drink tap water. I have the occasional croissant or donut. I'm, I'm not, you know, I'm, I'm 90%, 80% of the time I'm doing the right things the right way, I think, although I'm now going to improve on them with this new knowledge, but, um, but I don't like what I see in most sunscreens because if you look at these compounds, they cross the blood-brain

• 1:34:19Andrew D. Huberman?

  barrier. I don't want compounds crossing the blood-brain barrier.

• 1:34:23Dr. Rhonda Patrick?

  Titanium dioxide?

• 1:34:24Andrew D. Huberman?

  Dioxide, some of the triclosans that are also in these cleansers. I mean, it's, once you know a little bit about neurons, folks, you realize that ner-, the neurons you got are basically the ones you got for your entire life. You know, there's a reason why there's a blood-brain barrier, a blood-ovary and a blood-testes barriers, because the genetic material resides in the testes, the ovaries, and the brain, those neurons don't turn over. There are a few new neurons, but not that many unless you're a mouse, frankly. So protecting those is very key, and a lot of the things in sunscreen, um, are downright dangerous. So I think there are sunscreens that are safe, but it's very hard to figure out which sunscreens are free of these compounds. I'm amazed that they're still on the market, frankly.

• 1:35:05Dr. Rhonda Patrick?

  I've always geared towards the ones with the, the minerals that are like reflecting it. Um, it is, it is somewhat difficult to penetrate things all the way through the skin into the, get into the bloodstream. I don't, but I don't know, maybe some of these compounds get in there easily. I have seen the evidence with some of those things.

• 1:35:23Andrew D. Huberman?

  Yeah, they go, there is some evidence, they go transdermal and they.

• 1:35:27Dr. Rhonda Patrick?

  And they get in, okay, well, I know that there, some of them react with the sun, and while they do protect from the UVA and/or B, they like form massive reactive oxygen species and carcinogen. I mean, it's like the very thing you're trying to protect yourself from. Might actually cause.

• 1:35:43Andrew D. Huberman?

  Right.

• 1:35:44Dr. Rhonda Patrick?

  We don't know. I mean, like, it's completely speculation, but um, there is like, I think some more and more evidence coming out with some of those compounds. And I can't remember all of them off the top of my head, but um, a lot of high-end ones also have, have, you know, it's the chemical sunscreen ones.

• 1:35:59Andrew D. Huberman?

  Right.

• 1:35:59Dr. Rhonda Patrick?

  The chemical ones.

• 1:36:00Andrew D. Huberman?

  Right. We should do, I'm proposing that we do a journal club. A journal club, folks, is where academics get together and read papers. Well, they read papers and they get together and they pick apart the papers. Uh, there's a strong correlation between being an early graduate student and being the most critical. Cause once you've actually published some papers, you realize that, you know, most studies, people are doing their best within the context of what they can do. But it'd be great to do a journal club at some point about sunscreens, cause I'd love to really figure out what's in these compounds. I mean, people are using them like crazy and I'm not one of these people who's like, oh, I won't use commercial toothpaste or anything like that. I, I, like I said, I drink tap water. I use commercial toothpaste, whatever. But when it comes to sunscreen, it freaks me out because some of these compounds do go transdermal.

• 1:36:41Andrew D. Huberman?

  And some of them cross the blood-brain barrier and I'd like to keep my neurons free of that stuff. Anyway, we're speculating now.

• 1:36:47Dr. Rhonda Patrick?

  Wear a hat.

• 1:36:48Andrew D. Huberman?

  Wear a hat. Um, but get out in the sun and get your D3 levels up. Okay. So we've, we talked about these plant-based compounds, the omega-3s and D3. Unless there's something else that you just absolutely must throw into the mix, I probably will return us to the conversation I opened up with, which is about cold and heat, which admittedly I pulled us off that, that path. So I want to take full responsibility for that. But before I do that, I just want to offer you the opportunity, is there, are there, is there anything that um, fit to supplement-based or food-based compounds? That you, you know, you think are especially useful for brain and our body health?

• 1:37:29Dr. Rhonda Patrick?

  I do think magnesium is important in there as well. I mean, I think, you know, again, about 40% of the US population doesn't get enough magnesium. It's an essential mineral we're supposed to be getting from our diet and.

• 1:37:41Andrew D. Huberman?

  Involved in everything.

• 1:37:43Dr. Rhonda Patrick?

  It is. It's also involved in vitamin D metabolism. And in fact, um, being deficient in magnesium may make it more difficult for you to actually make vitamin D hormone. So that 125 hydroxy vitamin D. So one of those other factors, again, talking, we talked about genetics, but there's also magnesium status as well. Considering 40%, that's a big number. Um, now, you know, magnesium's also involved in.

• 1:38:10Dr. Rhonda Patrick?

  Making ATP, the energetic currency of our cells, they're, you know, basically all of our cells need ATP to do anything. And they're also, it's also involved in utilizing ATP as well as DNA repair enzymes. These are enzymes that are involved in repairing damage to our DNA. I personally think that magnesium insufficiency is a insidious type, causes an insidious type of damage daily that you can't look in the mirror and see, like when you're deficient in vitamin C, you're like, my gums are falling apart, I have scurvy, right? But like, you can't see DNA damage. You can't see it, but it's happening. It's happening right now in my body, and it's happening in your body. It's happening, normal metabolism is happening, you know, every day. But we repair that damage. We have repair

• 1:38:53Dr. Rhonda Patrick?

  enzymes in our body called DNA repair enzymes. They require magnesium. Magnesium is a cofactor for them. What that means is, you know, a cofactor means enzymes need it to function properly. And so without that cofactor, they're not doing it properly. And I like, the way I like to think about magnesium, it's easy, because people go, what food should I eat? Right? Naturally, that's the next question. Well, magnesium is at the center of a chlorophyll molecule. Chlorophyll is what gives plants their green color. So dark leafy greens are high in magnesium. It's one of the, and people, basically, what is the 40% insufficiency in the US tell us? People aren't eating their greens. They're not eating their greens. They're eating their packaged food, they're eating their processed food, and standard

• 1:39:36Dr. Rhonda Patrick?

  American diet isn't really high in dark leafy greens. So, so dark leafy greens are how I like to get my magnesium. I think it comes along with all these other important, I mean, you get calcium in them, you get vitamin K1, you're getting a lot of other micronutrients, and you're getting other compounds that we don't know about, and ones that we know about, like sulforaphane, right?

• 1:39:57Andrew D. Huberman?

  As with broccoli, do I need to eat the dark leafy greens raw? And in this case, I'm a little more open to it, because I actually like the taste of, dare I say, kale. And kale's a dark leafy green, right?

• 1:40:11Dr. Rhonda Patrick?

  And it's high in lutein and zeaxanthine as well.

• 1:40:13Andrew D. Huberman?

  Yeah, I'm a trichromat, meaning I'm not, I'm not colorblind, but I, but I just want to make sure it falls under the strict category.

• 1:40:18Dr. Rhonda Patrick?

  Yes.

• 1:40:18Andrew D. Huberman?

  Because every once in a while, I'm like, oh, I eat my vegetables. I like avocados. And people were like, my avocados are not vegetable. I love vegetables also. But, so kale, what are some other examples?

• 1:40:27Dr. Rhonda Patrick?

  Kale, spinach, chard, like Swiss chard, rainbow chard, romaine lettuce.

• 1:40:32Andrew D. Huberman?

  Is the bitterness an important component to this?

• 1:40:34Dr. Rhonda Patrick?

  For magnesium, no, but for, for sulforaphane. Sulfuraphane for cruciferous vegetables, that would be the brassica family. But your question about cooking them, so magnesium is, it is bound to the food matrix. And it can be somewhat less bioavailable. But, you know, so cooking it can somewhat release the magnesium, but it goes into the water too. So like you have to like either steam it or kind of, you know, like get your water in.

• 1:41:10Andrew D. Huberman?

  You could drink it.

• 1:41:11Dr. Rhonda Patrick?

  Like, yeah, you know, I personally don't worry about it.

• 1:41:14Andrew D. Huberman?

  Okay.

• 1:41:14Dr. Rhonda Patrick?

  Just don't worry.

• 1:41:15Andrew D. Huberman?

  Great. If you don't worry, I'm not gonna worry.

• 1:41:17Dr. Rhonda Patrick?

  But I also like, I do supplement with magnesium, I do take around, so supplementation with magnesium. I mean, we could go on and on, let's keep this short and sweet because we're gonna get back to the other stuff. But, you know, it can cause GI distress at like high doses. I personally like to take around 130 or 135 milligrams. That way it's not like a huge bolus to my gut.

• 1:41:39Andrew D. Huberman?

  I think it depends on the form of magnesium too.

• 1:41:41Dr. Rhonda Patrick?

  Yes, yeah, I mean, you can take like magnesium 3 and 8 for example, and it, you know, isn't as affect, you know, it doesn't affect the gut as much.

• 1:41:50Andrew D. Huberman?

  Magnesium citrate?

• 1:41:51Dr. Rhonda Patrick?

  Citrate is what I take.

• 1:41:52Andrew D. Huberman?

  Yeah, it's a pretty, pretty potent gut stimulus. I mean, I feel like it's a little bit harder to digest.

• 1:41:59Dr. Rhonda Patrick?

  Well, I take 135 milligrams should be pretty good. And citrate actually, oh boy, do we want to go here?

• 1:42:05Andrew D. Huberman?

  Sure. I mean, it's up to you and we can, we don't have to. I personally, I've been supplementing with magnesium for a long time.

• 1:42:12Dr. Rhonda Patrick?

  Yeah.

• 1:42:12Andrew D. Huberman?

  I've, I use 3 and 8 and bisglycinate and malate for different reasons. So I, yes, I would love to go there if you're, if you're willing.

• 1:42:23Dr. Rhonda Patrick?

  I would say malate would be the best and that, that has to do with the short chain fatty acids being good for the gut. And a lot of work done by a former colleague of mine and good friend Mark Shigenaga, showing that the short chain fatty acids, citrate, malate, lactate. But, but specifically malate really and lactate are the, are the major ones that get into the, to the gut epithelial cells and are an energy source for the mitochondria and the goblet cells. So anyways, whole other.

• 1:42:49Andrew D. Huberman?

  That's okay. Yeah, I take Malle because I was told that it would be helpful. First of all, it doesn't make me sleepy like some of the other forms of magnesium, which act as a mild sedative for me. They do tap into the gabbergic pathway, neurotransmitter folks that in general, broad sweeping generalization here can have somewhat of a sedative quality, which is why I take magnesium threonate and/or bisglycinate before sleep, 30 to 60 minutes before sleep. Definitely enhances my transition time to sleep and the depth of sleep. No question in my experience. There's some data that threonate can be neuroprotective, although those are still, those studies are still ongoing.

• 1:43:32Andrew D. Huberman?

  I'm getting the sense that maybe you're a little more skeptical of that than I am.

• 1:43:36Dr. Rhonda Patrick?

  Yeah, I know. I've seen the studies with the threonate. I think like looking at the actual data from the one clinical study, there wasn't statistical significance until all three of the pieces of data were pulled together. But that really could just be because their sample size was too small.

• 1:43:52Andrew D. Huberman?

  Right.

• 1:43:53Dr. Rhonda Patrick?

  Right?

• 1:43:53Andrew D. Huberman?

  Yeah, I'm thinking that paired with the, there's some work. Yeah, the Guo Song-lu's work on, so in the, this is getting kind of into inside ball of neuroscience. You know, the quality of the labs matters, folks. And that's something that's not accessible to people outside of fields. And you know, Guo Song-lu and some of the other folks at that time at MIT, I think very highly of their work. And so the animal studies are indeed just animal studies. But I was pretty impressed by what they did in those studies. Very pioneering when you think about this being done 10, 12, 15 years ago. And then, yes, we need more human clinical data. But I, for me, I figure that the, given the safety profile of mag-3,8, given that it helps me sleep better and sleeping better is just better for everything, frankly.

• 1:44:38Andrew D. Huberman?

  That's why I take it and bisglycinate and 3,8 seem to be somewhat interchangeable. But there's, I don't know of any reports that bisglycinate can be neuroprotective. But Malle, I take during the daytime. I, it, for me, and again, this is subjective, it has a tangible effect in improving the recovery time from exercise. So it, I don't know that I've been sore from a workout since I started taking Malle and I used to get very sore. From even kind of trivial workout. So I don't know what's going on there, but I keep taking it.

• 1:45:07Dr. Rhonda Patrick?

  Malate, again, the short chain fatty acid. And I mean, you know, when you do have a, when you do intense exercise, you release endotoxin from your gut. I'm just going back to the interesting work because the malate being the short chain fatty acid. And, you know, you know, Mark Sugeanaga showing, this is all in animal research, by the way. But, I mean, it was like, you know, feeding these animals malate, I mean, it really protected the gut endotoxin release. And it affected metabolic syndrome and all sorts of things. But I think malate, malate is awesome. And I always try to eat green apples. They're really high in malic acid.

• 1:45:39Andrew D. Huberman?

  Oh, good to know.

• 1:45:40Dr. Rhonda Patrick?

  And tart cherries, tart cherries are really high in it as well.

• 1:45:43Andrew D. Huberman?

  It also tastes really good.

• 1:45:44Dr. Rhonda Patrick?

  But I, I, I was really interested in the magnesium 3-8 stuff. I take a supplement called Magnesium by Moon Juice. And it's like a little powder. It's got a little bit of monk fruit, but it tastes good. So I, I do it a little bit before bedtime as well. Probably several more hours though, because I don't like to drink tons and tons of fluids before I go to bed. And it has magnesium 3-8 and a variety of other versions of magnesium in it as well. And I really like it. But I thought the magnesium 3-8 stuff was super interesting. I, you know, would love to see more clinical data as well. But I think, you know, once we get it, it'll probably be like, oh yeah, it's getting into the brain and it's awesome. So, you know, why wait?

• 1:46:20Andrew D. Huberman?

  Right. I, and along those lines, I once put out a, a post that said, you know, I, I feel like there are a number of different categories of health, health information consumers online and understanding which one you're in for which topic can alleviate a lot of the strain and stress of finding the information. There's some people that are perfectly comfortable with data from a mouse study. It's like, if it's done in mice, great, I'll try it. Other people say, no, it has to be done in humans, double-blind placebo-controlled studies, you know, randomized clinical trials, et cetera. Then other people are just say, you know what? I don't even care about any of that. Just tell me what you do. And then other people are saying, you know, I don't even care what you do. Just tell me what to do. And then there's this other category, which are if it's in pill form or powder form, they'll take it.

• 1:47:02Andrew D. Huberman?

  And so I think a lot of the battles of people picking apart people's posts and things have to do with the fact that, that people don't realize that. People are showing up to the table in one or some combination of those stances. We know people that will try anything and we know people that won't take anything. So the idea here is to create an array of possibilities for people. And I think the animal data are very impressive. We should have you back on.

• 1:47:28Dr. Rhonda Patrick?

  I take it with the hope of, because I feel like the animal data is very promising. And so I'm like, it probably is, so why not?

• 1:47:35Andrew D. Huberman?

  Well, and obviously you're doing things right. So cold and heat converge on some common pathways related to what you called intermittent challenge, which I love. I think if, you know, intermittent fasting, cold, heat, exercise, I mean, maybe even intermittent sleep deprivation. I keep waiting for the intermittent sleep deprivation movement. I will say I pull a few all-nighters per year, just for work demands and procrastination and deadlines. And I'm the worst combination of academic, because I'm both a procrastinator and a perfectionist. So you end up pulling some all-nighters. The sleep I get the next night is pretty amazing, I must say. It's the sleep of gods, but I don't recommend anyone use sleep deprivation for that.

• 1:48:19Andrew D. Huberman?

  But I could imagine that we also evolved having some sleepless nights. So this idea of intermittent challenge is a really attractive one. And I want to make sure that we credit you with the phrase intermittent challenge.

• 1:48:29Dr. Rhonda Patrick?

  No, credit Dr. Mark Mattson.

• 1:48:31Andrew D. Huberman?

  Okay, Dr. Mark Mattson.

• 1:48:32Dr. Rhonda Patrick?

  Who has published and he has used that.

• 1:48:34Andrew D. Huberman?

  He used those words, that phrase. Okay, great, we'll make sure.

• 1:48:36Dr. Rhonda Patrick?

  Just like Dr. David Sinclair, I love the xenohormesis. He was in like one of his publications just so many years ago. I just love it. It's brilliant, a brilliant term. So, Dr. Mark Mattson.

• 1:48:45Andrew D. Huberman?

  Those Harvard guys are pretty smart. You know, I mean, it's a good school, I guess. Of course, it's a good school. We will credit the appropriate people. Thank you for that clarification. So you've talked a lot about the use of deliberate, what I call deliberate cold exposure, only to distinguish it from cold that you might just be accidentally exposed to. But it's sort of obvious when we say cold exposure. There are some amazing data on cold. The other day I saw a post from you and you've included this in talks before. I did not know this until I learned it from you, so credit to you, that even 20 seconds of immersion in, I think it was four degree.

• 1:49:25Dr. Rhonda Patrick?

  Forty-nine degrees Fahrenheit.

• 1:49:26Andrew D. Huberman?

  Forty-nine degree Fahrenheit. Okay, I was translating in Celsius, but forty-nine degree Fahrenheit water, so cold water can lead to long-lasting increases in epinephrine adrenaline. And I have to presume other neuromodulators and neurochemicals as well. What are some cold protocols that you find particularly interesting or attractive from the standpoint of, I don't know, pick your favorite, metabolism, neuro slash mood effects, brown fat stimulation, which of course weaves back to metabolism. You know, we could, we could do an entire episode all about cold, but what I'd love to know is what sort of activity or stimulus do you, do you think is a reasonable and particularly

• 1:50:11Andrew D. Huberman?

  potent one to use in terms of cold?

• 1:50:14Dr. Rhonda Patrick?

  So today I did three minutes at forty-nine degrees Fahrenheit. I have a cold tub.

• 1:50:19Andrew D. Huberman?

  So you're getting it up to your neck?

• 1:50:20Dr. Rhonda Patrick?

  Well, I try, I keep floating up. And so I'm like, it's like really hard. So the, like, I, I, I would say like, maybe most of my shoulder. I mean, really, I'm floating up. I was telling, I was telling my husband, I was like, there's too much water in here for me.

• 1:50:35Andrew D. Huberman?

  Or too much salt in there? Is it like the Dead Sea where you float on top?

• 1:50:38Dr. Rhonda Patrick?

  Is there salt in there? I don't know, he takes care of all the stuff that, you know, it's, it's, it's, it's the plunge.

• 1:50:44Andrew D. Huberman?

  Yeah, they make, and by the way, the podcast nor I am sponsored by Plunge, they did give me one. That thing is fantastic, also because it circulates the water.

• 1:50:52Dr. Rhonda Patrick?

  It does.

• 1:50:52Andrew D. Huberman?

  Which makes sure that you break up the thermal layer and it's even colder.

• 1:50:55Dr. Rhonda Patrick?

  It is even colder, it sucks. Anyways, so look, I'll, I'll, I'll give, I'll give it, I'll be honest here, I wish I did more cold than I do. I do cold when I'm gonna go on a podcast. I definitely do cold when I'm gonna do a podcast, when I'm gonna give a talk, or when I'm anxious. I need to make it more of a ritual. I love doing the sauna. Hate it unless it's summertime. It's a lot easier for me to get in the cold in the summertime. But um, what I do love about the cold is how I feel after and um, I feel less anxious. I feel good. I feel more focused, which is why I usually do it before any type of public speaking.

• 1:51:37Dr. Rhonda Patrick?

  Or in just when I'm just anxious, um, I'll just get in there. And so um, the twenty seconds at forty nine degrees, I think it was forty nine degrees Fahrenheit was really a good number because time and temperature do, time or duration, I guess would be a better word and temperature do matter. But but you know, you can, you can do twenty seconds at a colder temperature, which is I prefer. Or you can do a minute or longer at a warmer temperature. I think there was another study showing fifty nine degrees Fahrenheit at one hour. It was like two, three, four, but who wants to do one hour?

• 1:52:13Andrew D. Huberman?

  Yeah, I'm familiar with that study. I, I love, this is really, it reveals just how absolutely nerdy I am and maybe why sometimes and relationships in my life were challenged. I love reading the methods sections of papers. So you know, people can come at me with a number of things about papers and I might miss something. Surely I miss certain things like anybody does, but the methods I sort of, I relish in reading the methods. And that paper is really interesting because they had people sit in lawn chairs, basically in swimming pools. So for an hour and it wasn't real, it was chilly. It wasn't super cold. I mean, sixty is not, it's not warm, but it's not ice cold, obviously.

• 1:52:51Andrew D. Huberman?

  But an hour is ridiculous at some level, but the increases in dopamine were massive and lasted hours. So it's, it's really, so the mood enhancing effects that you report are, they're not, you're not imagining that. Those are almost certainly a, you know, the consequence of having slowly elevating but significantly elevated dope dopamine that goes on for hours. That's almost a dream like profile for dopamine. Because most everything else, like an Adderall, a Ritalin, a cup of coffee and a, and a workout drink, or pre-workout drink or something is going to give you a big spike in adrenaline and dopamine and a big crash. And somehow it creates this really nice contoured profile.

• 1:53:33Andrew D. Huberman?

  So I, whatever you're experiencing there is very nicely supported by the data.

• 1:53:38Dr. Rhonda Patrick?

  Well, I need to get, I need to get doing it more. I've, I've had a couple of scary experiences going from hot to cold.

• 1:53:45Andrew D. Huberman?

  Can you explain?

• 1:53:46Dr. Rhonda Patrick?

  Where blood pressure changes, I think where I basically went straight from a really hot jacuzzi. I was in there for like thirty minutes. I mean, I was, I was doing heat.

• 1:53:55Andrew D. Huberman?

  Jacuzzi, okay.

• 1:53:56Dr. Rhonda Patrick?

  Yeah, a hundred and four degrees Fahrenheit.

• 1:53:58Andrew D. Huberman?

  That's toasty.

• 1:53:58Dr. Rhonda Patrick?

  And then I, for thirty minutes. And then I went straight into, at the time, it was our pool. It was in like February, it was like wintertime and it was fifty, it was in the fifties. It was cold. And, and I was in there and I was like listening to Simon Garfunkel. I was like trying to stay in a long time, get on my cold and I was trying to press Dan because he like goes in there for like, he'll stay in there for like fifteen minutes. But I started to feel really like blinky, like low blood pressure or something and I got scared. So I got out and then I couldn't stand, like I had vertigo or something and I was so scared. I was so scared. And so, and I've, I've had a couple of times too where just going straight from the sauna to it, to the cold plunge, where I'm starting to feel, I'm like, ooh,

• 1:54:43Dr. Rhonda Patrick?

  I feel a little blood pressure change or something. And it makes sense. The sauna is causing vasodilation and the cold plunge is, or cold exposure is causing vasoconstriction. It feels like a very, you know, just shock to my system. And so now I wait, like I wait like a few minutes before going in. But I do need to kind of like make it more, the cold more routine because I talk all about the science. I'm familiar with all the science and, you know, the, the norepinephrine or noraadrenaline, you know, it's affecting brain and mood and, and you know way more about that than I do. I know how I feel and I, you know, know it's a neurotransmitter and, you know, it is, it is released, at least in rats they've shown, or was it mice? I think it might've been rats.

• 1:55:25Dr. Rhonda Patrick?

  But multiple studies showing in that it's released from the cold in the brain.

• 1:55:29Andrew D. Huberman?

  And now in humans as well.

• 1:55:31Dr. Rhonda Patrick?

  Oh, in the brain.

• 1:55:32Andrew D. Huberman?

  So in that study, that's the, we can put a link to this. It's published in two thousand, European Journal of Physiology, that big dopamine increase. They also looked at epinephrine and cortisol and saw some really, yeah, so this has been done.

• 1:55:43Dr. Rhonda Patrick?

  They did brain. Oh, I didn't.

• 1:55:44Andrew D. Huberman?

  Oh, no, no.

• 1:55:45Dr. Rhonda Patrick?

  The plasma.

• 1:55:45Andrew D. Huberman?

  No, yeah. Yeah, yeah, very, very hard to measure dopamine directly from the brain unless you're doing microdialysis. No, unfortunately, there's. Unfortunately, their skulls were intact. Fortunately for them, unfortunately for the research committee, their skulls were intact. So they couldn't measure directly in the brain. But obviously, there's a correlate there. You know, it's a very real effect. I think that, but the advantage of not doing it too often is that you're not cold adapted. Now, it's very hard for anyone to get truly cold adapted. Some people start to look forward to the cold. And what I think they're looking forward to is the feeling afterward, that dopamine rush. But if you get cold adapted, then it certainly blunts the, some of the effect.

• 1:56:28Dr. Rhonda Patrick?

  But I want to be cold adapted because that means I have more mitochondria in my adipose tissue and perhaps even muscle, like that's been shown.

• 1:56:37Andrew D. Huberman?

  So maybe there's a good opportunity to, so cold and UCP1, if you could educate us on UCP1, I find this really interesting, and I learned about it from you, so.

• 1:56:45Dr. Rhonda Patrick?

  Yeah, well, so norepinephrine actually released in the plasma, it does act as a hormone. Basal constriction is one thing it does, but it also regulates a variety of molecular functions that have to do with adaption to cold. One happening to be, you know, shivering is a very inefficient way to produce heat, which is what your body's trying to do when it's exposed to cold. And your muscles are basically contracting and producing heat from that, but that's just not very efficient. So the more eloquent way to do it, or elegant, I guess, way to do it is, you know, to basically have your mitochondria produce tons and tons of heat. So the way it does this is by activating a gene called UCP1, uncoupling protein 1,

• 1:57:30Dr. Rhonda Patrick?

  norepinephrine is upstream without activating it. So what that does is essentially, so mitochondria are these little organelles inside of your cells that are responsible for producing energy. Usually that's in the form of adenosine triphosphate, ATP, and that's what lets everything function inside of your body, from your neurotransmitter production to your heart beating, et cetera. However, you can uncouple your mitochondria, basically your mitochondria, they're like a little battery, so they have, well, they have a double membrane, first of all, their structure, but they have a negative charge on the inside and they have a positive charge on the inner membrane, so in between the outer membrane and inside, the inside part.

• 1:58:12Andrew D. Huberman?

  Like a neuron.

• 1:58:13Dr. Rhonda Patrick?

  Like a neuron, yeah. So I guess it's like a neuron. It's like a battery, negative and positive. Well, basically you can uncouple that that charge. And so that positive charge protons start leaking out of the mitochondria. And your mitochondria freak out. So this is called uncoupling it. And they start to, it's maximum respiration, as we call it. They try to make as much energy. They're like, I gotta get those, that, that, that proton back, that gradient, electrochemical gradient. And so they just go insane. And they, in this case, it's uncoupled energy. So the energy they're making is actually heat, not ATP. But heat is, but you're essentially burning substrates. Who cares? You're burning, you're burning glucose, you're burning lipids, you know, you're, you're basically burning things and making heat.

• 1:58:56Dr. Rhonda Patrick?

  And so that's what uncoupling it does. And that is a much more efficient way of producing heat than shivering. So as you become more adapted, maybe the, the, the longer duration that you've, you've stayed in the cold or the more times you've done it, you'll no longer shiver anymore. You will start to then just do this uncoupling type of thermogenesis, as it's called. And another type of adaptation that occurs is you actually produce more mitochondria in your adipose tissue. And, and that actually happens also regulated by norepinephrine or nora adrenaline through a protein called PGC1 alpha. And what that protein does is it makes more mitochondria in your adipose cells. So per adipose cell, you're getting more mitochondria.

• 1:59:41Dr. Rhonda Patrick?

  It's a beautiful way to basically make more heat when you're, it's, it's one of those things where it's like, it's, it's, your body's going, okay, I'm going to be exposed to this cold next time. How can I make sure I don't die? Oh, I can have more mitochondria and I'm going to make more heat. And so you're making more mitochondria in your adipose tissue. And, and this is often referred to as like the browning of fat. And the reason for that is because if you look under a microscope at a lipid drop, you know, basically a fat cell, not a lipid drop, adipocyte, you'll find that it looks darker because there's more mitochondria in there. So it's referred to as browning fat. And so we, I don't want to get into the whole beige fat brown. You know, there's this whole, I'm sure you've had experts on that talk all about that.

• 2:00:26Andrew D. Huberman?

  No, not yet. I mean, I always think of white fat, beige fat, brown fat. And beige is kind of intermediate. White can be converted into beige, but.

• 2:00:32Dr. Rhonda Patrick?

  Right. And beige can take on thermogenic characteristics essentially. And so. So you can activate beige fat so that it's thermogenic in the sense that it's burning glucose and/or, you know, fatty acids and, and producing heat. So, um, so the more you expose yourself to cold, the more you can brown your fat, so to speak, and, and therefore, um, you can tolerate the cold for longer periods, which people do notice, and you can, uh, then have the thermogenic qualities of having more brown adipose tissue or beige, activated beige adipose tissue, which is, um, you know, you'll get a lot of naysayers out there saying, oh, brown fat doesn't regulate metabolism at all.

• 2:01:14Dr. Rhonda Patrick?

  The reality is, there's like thousands of researchers trying to build, pill up brown fat and thermogenic, like, they're trying to make it a, a pill because it does affect metabolism. Um, you know, it's not the only thing. It's certainly if you're obese and trying to lose weight, you're not gonna like do that just by doing cold exposure. You need to do dietary and exercise, um, changes, you know, predominantly, but it does, it does affect metabolism and, um, you know, this is, this has been shown in human studies. So, uh, it is a, a interesting, another, it's another possible mechanism for, um, affecting metabolism, um, and that's in adipose tissue, but you also make more mitochondria and muscle tissue.

• 2:01:55Dr. Rhonda Patrick?

  And this is regulated not via norepinephrine, but it is still PG2-1 alpha, interestingly, um, not like, not that anyone else really cares but me, and maybe you do, Andrew.

• 2:02:04Andrew D. Huberman?

  I, I'm, I'm eating this up.

• 2:02:06Dr. Rhonda Patrick?

  So PG2-1 alpha, uh, is, is respond, is response to norepinephrine in adipose tissue to make more mitochondria, but in, uh, in muscle tissue, it's unclear what the regulator is. Cold exposure does it. So this is, this was shown, um, at least in a couple of studies I've seen where, uh, like people that were exercising, I believe, or maybe, may have been men only that were exercising, did some sort of training, and then did cold water immersion, something like 50 degrees Fahrenheit, 15 minutes, and PG2-1 alpha, which is a biomarker for mitochondrial biogenesis, which is the generation of new mitochondria. By the way, that's awesome. You want more mitochondria in your muscle. It's associated with, um, improved muscle mass, improved endurance. I mean, mitochondria are essentially

• 2:02:50Dr. Rhonda Patrick?

  Either they're making energy in your cell and we, you know, we don't make more mitochondria normally, like you have certain inputs, high intensity interval training, exercise can do it.

• 2:02:58Andrew D. Huberman?

  And actually make more mitochondria.

• 2:03:00Dr. Rhonda Patrick?

  Yes. Yeah. And that's been shown in people and.

• 2:03:03Andrew D. Huberman?

  Weight training or just high intensity interval training?

• 2:03:06Dr. Rhonda Patrick?

  I haven't seen weight training. I've seen it in, in high intensity interval training and endurance training, um, but that doesn't mean that it hasn't been shown. I just haven't seen it or that it hasn't been looked at. So.

• 2:03:17Andrew D. Huberman?

  Good to know. I'm, I'm always looking for reasons to finally do more HIIT type, high intensity interval training work. I do weight training and I do low intensity cardio.

• 2:03:26Dr. Rhonda Patrick?

  There was a brilliant study by, um, at the time he was a postdoc, Matthew Robinson, and, um, he's now gone on to start his own lab at the University of Oregon Health Science Center.

• 2:03:39Andrew D. Huberman?

  Great place.

• 2:03:39Dr. Rhonda Patrick?

  Um, and, and he did a study where, uh, both young and old, older people were, they had this whole high intensity protocol, which I can't remember what it was, but their protocol, um, for X amount of time. I'm, I'm sure it was at least a month. Uh, they then measured biomarkers of mitochondrial biogenesis in their muscle tissue and, uh, the, the amount of mitochondrial biogenesis in old people specifically, it happened in both young and old from HIIT, from the high intensity interval training was, I mean, it was like enormous, at least 50% I think. So, I mean, it was just like, whoa. And so like, why would you want that? Well, you know, mitochondria, your, your mitochondria, you don't make, your cell, your cells are turning over, you make new cells, you replace old ones with your

• 2:04:23Dr. Rhonda Patrick?

  mitochondria. Um, you don't really do that for the most part. You can, mitochondrial biogenesis does happen, but you have to stimulate it to happen. And, um, the way your mitochondria, like what happens with your mitochondria is they essentially are bobbing around inside of your cells and then they, they fuse with other mitochondria, exchange, exchange all their content, mitochondrial DNA, and then fizz back apart. And that's how they kind of stay young-ish. But like as you age, you, you keep doing that with the same pool of mitochondria and you're going to get a bunch of old mitochondria, mixing old stuff together, right? So why wouldn't you want to like? Bring up new, healthy, young mitochondria into that pool, right? So in my mind, when I hear mitochondrial biogenesis, I'm like aging. Like, that's the first thing I think of. So anyways, cold exposure does that.

• 2:05:07Andrew D. Huberman?

  Amazing.

• 2:05:07Dr. Rhonda Patrick?

  Other things as well, so.

• 2:05:08Andrew D. Huberman?

  No, I did, and please, thank you for offering to, you know, somehow filter the, the level of detail. But I assure you that listeners of this podcast are, are familiar with getting, um, drinking from the fire hose of mechanism. And that was really helpful. And again, this is just one example of maybe four or five other things that you've said at least that are going to inspire me to change my behaviors. I'm going to start doing some high intensity interval training. Dr. Andy Galpin was on this podcast recently and he told me that, that the subtle zone two cardio and the weight training is great, but that I really should be doing some max heart rate work per week. You know, going into max heart rate for 90 seconds and resting and repeating that, maybe even mild repeats. I'm just curious, as a brief aside, before we, we talk about heat,

• 2:05:54Andrew D. Huberman?

  what, what sort of cardiovascular or other types of training do you do? Do you do HIIT? I imagine you are doing high intensity interval training. If you could just give us a sense of the contour of your, your week as it relates to exercise and, and because you've been very gracious in sharing some of what you do for supplements and food. What about exercise?

• 2:06:12Dr. Rhonda Patrick?

  So I, um, it all depends on my week, of course, and, and, and what I've got going on with my son and, and my work schedule. But I typically, I do a lot of high intensity interval Tabata's on a stationary cycle. I use Peloton because, um, I just like that instructor there, like telling me what to do and then me competing with everyone else. I'm like, you know, so, um, it works.

• 2:06:33Andrew D. Huberman?

  You're revealing something about your psychology. This is what we just learned about. So this podcast is actually just a decoy for, for, uh, psychological assessment of the guest. No, I'm kidding. Um, but so now we know you're competitive. Good.

• 2:06:43Dr. Rhonda Patrick?

  Yeah.

• 2:06:43Andrew D. Huberman?

  Uh, that explains a lot of how you got through graduate school and then to do, do what you do. So you're getting on the Peloton and what does it look like for someone who's not familiar with Peloton? I know what they are, but I've never been on one. You are peddling against the instructor for how many seconds?

• 2:06:59Dr. Rhonda Patrick?

  So, um, you're, there's a bunch of people that are online, either doing the class with you at the same time or have all time doing it. So you can, you can kind of toggle on what you want and like, you can try to compete against the all time number.

• 2:07:11Andrew D. Huberman?

  Really competitive?

• 2:07:11Dr. Rhonda Patrick?

  Oh, yeah.

• 2:07:12Andrew D. Huberman?

  Okay.

• 2:07:12Dr. Rhonda Patrick?

  And the instructor is just there to like whip you, like. Like, you know, make you, there's, there's a part of, the brilliance with Peloton is, um, like, I used to do Rush, what's called Rush Cycle, and I used to go in, it's basically you go in and group, group cycle and have an instructor there and you do all this high intensity interval training stuff. And I loved it because there was a competitive aspect to it that had me working harder than I would work if it was just me in the room, like, without an instructor or anyone there. And it was just like, I'm at a gym, any gym, and I'm just on a stationary cycle, listening to a podcast, doing something, which is fine if that's your groove, right? But there is something about that group setting that kind of make, holds you accountable too, right? And, and the Peloton

• 2:07:57Dr. Rhonda Patrick?

  made it somehow virtual. It was amazing. And I remember being back at Rush Cycle, this is before pandemic, and people talking about Peloton in my class. And I'm like, oh, that's ridiculous. Why would I do that? Like, that's never gonna work. I need to, like, be here. And then the pandemic hit and I was like, all over the Peloton. And it works for me really well. So I tend to do that at least three times a week. Sometimes I do it more, like, you know, I'll do four. And I do a 10 minute, just 10, because it's efficient and I push my ass. I push myself really hard.

• 2:08:28Andrew D. Huberman?

  That's the Tabata.

• 2:08:29Dr. Rhonda Patrick?

  It's a 20 seconds on, 10 seconds off, and it's 10 minutes.

• 2:08:32Andrew D. Huberman?

  And on means you're pedaling like your life depended on it.

• 2:08:34Dr. Rhonda Patrick?

  You're maxing it.

• 2:08:35Andrew D. Huberman?

  And there's a lot of resistance in the pedals?

• 2:08:37Dr. Rhonda Patrick?

  Yeah, well, so you basically, there's a part where you're, I always do resistance. I'm like, the power, I do the power for, there's a part where you're, you're sitting cycling, you're trying to go really fast, but I always crank the resistance up. I always go above what they give me. And then, and then there's a part where you're standing and you really crank the resistance up, which I really do. And like, you feel it in your glutes.

• 2:08:55Andrew D. Huberman?

  It's like going up a hill.

• 2:08:55Dr. Rhonda Patrick?

  Yeah, exactly. And so they like, break it up. And most of the time you'll have like, those two, two, two parts. And I love the efficiency of it. You, you just, you get it done. And people sometimes hear me go 10 minutes, or really, you think you work, and I'm like, look, like, you max, you do max, you have Tabata for 10 minutes, and it's like, it's, it's intense.

• 2:09:13Andrew D. Huberman?

  Yeah, most people can't sprint for the, for the gate of an airplane they're about to miss, carrying a backpack. So if you think about, if I think about that, and then I just described myself, sprinting through the airport and going, all right, Andy Galpin, I got my 90 seconds max heart rate in for you, carrying this thing. But 20 seconds on, 10 seconds off. Repeating that over and over for 10 minutes. So by the time you're done, you're cooked.

• 2:09:37Dr. Rhonda Patrick?

  And then I, because I'm competitive during the recovery that they give you at the minute at the end, I'm pushing it max.

• 2:09:42Andrew D. Huberman?

  Great.

• 2:09:43Dr. Rhonda Patrick?

  The number is higher.

• 2:09:44Andrew D. Huberman?

  Great. So three times a week?

• 2:09:46Dr. Rhonda Patrick?

  Yeah, three times a week. And then I always have my sauna on preheating up. Takes about an hour and a half. And I get it to about 189 degrees Fahrenheit. I hop right in the sauna after my Peloton.

• 2:09:58Andrew D. Huberman?

  So the elevated heart rate continues? Is that the rationale?

• 2:10:00Dr. Rhonda Patrick?

  Yeah, I mean, I literally like down a bunch of water and then I get in and then I like either

• 2:10:07Dr. Rhonda Patrick?

  read a science paper, prepare for a presentation or a podcast, or I hash over things in my mind. And it's interesting because something about getting in the sauna, I think the stress, the heat stress of it, I used to, so I started doing the sauna in 2009 in graduate school.

• 2:10:26Andrew D. Huberman?

  Okay, and you're an early adopter.

• 2:10:27Dr. Rhonda Patrick?

  I started doing it every day. I lived across the street. I lived in a studio apartment with Dan. We live in the like small studio apartment, the smallest apartment you could ever imagine. And it was across the street from a YMCA because I was poor in graduate school, very poor, very poor. I mean, so you know.

• 2:10:42Andrew D. Huberman?

  I recall, I recall.

• 2:10:43Dr. Rhonda Patrick?

  Yeah, okay.

• 2:10:44Andrew D. Huberman?

  I lived in my lab.

• 2:10:46Dr. Rhonda Patrick?

  Wow.

• 2:10:47Andrew D. Huberman?

  But then again, I lived in my lab as a postdoc and as a, I admit, I lived in my lab with my bulldog as a faculty member for other reasons. But I get it. When you're a graduate student, you're poor, basically.

• 2:10:59Dr. Rhonda Patrick?

  And so I used to, I used to go to the sauna before going into the lab and I would, and I would, I started noticing that I was all of a sudden able to handle stress better. Like the stress of my six month setback because of failed experiment, which is crushing. On top of the pressure from your, my advisor and my own pressure because I'm very competitive with myself and I put a lot of pressure on myself. So I was having a hard time. I mean, I was very stressed out in graduate school and the sauna started to really noticeably affect my anxiety and my ability to handle stress. And I was like, what is going on here?

• 2:11:40Dr. Rhonda Patrick?

  So I started looking into the literature and you know, started getting interested in the effects on the brain. And in fact, at the time I had a friend who was not actually experimentally, but theoretically looking into the

• 2:11:55Dr. Rhonda Patrick?

  Opioid system and basically so when you get in the sauna you release a lot of endorphins. Endorphins are the feel-good hormones, feel-good opioids that you know make you feel good. But you also release something called dynorphin. And dynorphin is an endogenous opioid that binds to a receptor called the kappa opioid receptor, which dynorphin is responsible for that dysphoric feeling when you're in the sauna and you're hot or when you're running, doing exercise and you're like, you feel uncomfortable. Well, I think that's dynorphin, I'm speaking absolutely.

• 2:12:29Andrew D. Huberman?

  No, I think it is. I mean, there's evidence in alcoholics that some of the symptoms of withdrawal that they experience are related to dynorphin and dynorphin is known to negatively impact the dopamine receptor system. So basically, it's the feel like garbage pathway.

• 2:12:46Dr. Rhonda Patrick?

  Right, you feel like garbage and so you think that that would not be good. But this is where my friend comes in. He was looking at the effects of like treating morphine or heroin addiction and you know, people that are using those drugs, they basically, the endorphins or the you know, morphine or you know, heroin, they bind to a receptor in the brain called the mu opioid receptor. And as they take these drugs, that mu opioid receptor becomes downregulated and so you need more and more of the drug to feel as good as you did, right? Well, endorphins also bind to that receptor and he was looking into some of the other

• 2:13:26Dr. Rhonda Patrick?

  drugs that are like salvinor- salvinor- salvinorum or something, salvia it's called. It binds to the kappa opioid receptor. It also makes you kind of feel uncomfortable. Anyways, he had put some studies in front of me that showed basically binding of the, you know, either dynorphin or you know, whatever ligand to the kappa opioid receptor basically sensitizes the mu opioid receptor to the feel-good endorphins and also changes, I think it also. Upregulates it or something. So basically, there's a lasting effect of feeling good. So the endorphins that you release later from hugging someone or a joke you're laughing at or whatever, you feel it for longer, right?

• 2:14:07Dr. Rhonda Patrick?

  And so anyways, this is a with the sauna, with respect to the sauna, it's a big sort of hypothesis of mine. I did kind of publish that part of my hypothesis in a review article. But I do, I do wish more people would kind of look into that. That'd be amazing. But, but what I was getting at, I think, was I would use, I would use the sauna to memorize things. This is way back in the day and I still do it. And I wanted to talk to you about this because you're, you're a neuroscientist, that there's something about being in the sauna, like, and I think, I don't know if it has to do with the, like, the stress response, like, when you, when you have an emotional trigger, like, you remember things better, right?

• 2:14:48Andrew D. Huberman?

  Absolutely. There is a clear and known explanation for, mechanism for this.

• 2:14:53Dr. Rhonda Patrick?

  So, in the sauna, I mean, you also release norepinephrine, just like you do in the cold. There's a lot of overlap. You know, you're, I mean, it is a stressor, but I, like, use it to remember things. Like, I'm going through something. I want to go through a presentation, or a talk, or a podcast, or whatever. And I go in that sauna, and, I mean, you should try it, like, if you haven't already. I don't know if you have.

• 2:15:14Andrew D. Huberman?

  I have a sauna and a cold plunge now, and I haven't tried, prepare, I read books in the sauna in the evening. It's a, it's a time I insist on having my phone out of there, mostly because I, initially because I thought I'd cook the phone, but also just to get some separation from the phone and screens in the evening. So I read books. The only challenge sometimes is you're dripping sweat onto the books, but I'm willing to forego a few pages of a book. The, the, the idea that being in this semi-stressful environment would aid in the learning and retention of information is, is really well substantiated by this beautiful work by a guy named James McGaw. I don't know if his lab's still active, but he was at UC Irvine for a while, and then, I think, at University of Arizona as well. They have a great memory

• 2:15:56Andrew D. Huberman?

  group at both places, very strong in learning and memory, both places. And he was the one that really defined this kind of inverted U-shaped function for the relationship between adrenaline and memory. Basically, if you're too relaxed and not stressed enough, you're not going to remember any information. At peak levels of stress, you actually are a memory machine. At least within the context of whatever it is you're trying to learn. So very well, what you're describing is very well matches with that. And then, of course, it tapers off as you really increase adrenaline to the point where people are starting to lose autonomic function, where they're just, they're panicking, basically. But obviously, you're keeping it in range. The other thing that I would like to ask you about is in the sauna, of course, there's vasodilation.

• 2:16:41Andrew D. Huberman?

  And perfusion of blood to the brain is a wonderful way to enhance cognition. There's even some really nice data showing that during inhales, as opposed to exhales, people are better at learning information. Believe it or not, during the inhale, you're taking in and absorbing and remembering more than during exhales. And these are beautiful studies done in humans, of course. So I can imagine that vasodilation, getting more perfusion of blood to the brain, plus a little bit of stress, or maybe a lot of stress, from the epinephrine. And yet, it's, and then, of course, there's going to be the, I don't want to call it placebo, but there's going to be the context, the condition-place context of it. Like, if we, if we had a good experience remembering something in the sauna once, we tend to, the positive association effect of that location is real.

• 2:17:24Andrew D. Huberman?

  Just like if people go to a new city and they get robbed. Like, if you go to Cincinnati, I've never been to Cincinnati, but you get robbed in Cincinnati, your purse gets taken, your wallet gets taken. You kind of hate Cincinnati as a tourist. But that could happen in any number of different cities, right? The opposite is also true. So if something good happens someplace, I'm imagining that it's a combination of those effects. But I'll start, it would be very hard to do this in the cold. I feel like the cold is a very potent, I think it takes you too far down that curve, the McGaw curve.

• 2:17:51Dr. Rhonda Patrick?

  I have to sing songs or something when I'm in there.

• 2:17:53Andrew D. Huberman?

  Distract yourself.

• 2:17:53Dr. Rhonda Patrick?

  Oh, yeah, I sing songs.

• 2:17:54Andrew D. Huberman?

  But afterward, you're very efficient at learning.

• 2:17:56Dr. Rhonda Patrick?

  After I am. And with respect to the sauna, the vasodilation does occur. So there's a lot of overlap between moderate intensity aerobic exercise and heat stress. And as you can imagine, when you're exercising, you're elevating your core body temperature, you're sweating. And when you're actually in the sauna, blood does get redistributed to the skin to facilitate sweating. But much like exercise, Blood flow in general is improved to the brain, to the muscles, everywhere. So, you know, I think generally speaking that, and this, you know, there's studies showing that sauna use is associated with a much lower risk of dementia and Alzheimer's disease. Like, people, you know, people that use it four to seven times a week have greater than

• 2:18:38Dr. Rhonda Patrick?

  60% reduction in dementia and Alzheimer's disease risk compared to once.

• 2:18:42Andrew D. Huberman?

  Amazing. Oh, sorry. I didn't mean to cut you off. You said, people who use it, I apologize, but maybe you could tell us again. People who use it four to seven times per week have?

• 2:18:51Dr. Rhonda Patrick?

  They have a greater than 60% reduction in dementia risk and Alzheimer's disease risk compared to people that use it only one time a week. People that use it two to three times a week have something like a 20, a little greater than 20% reduction in risk. There's a dose-dependent effect on dementia risk and Alzheimer's disease risk. It also has a profound, like, there's a, there's a big link between the cardiovascular system and the brain. Obviously, blood flow, a big one, right? You know, like, you need to get blood to your brain. But cardiovascular mortality, so mortality from cardiovascular disease, if people use, or actually, this was men, if men use the sauna four to seven times

• 2:19:31Dr. Rhonda Patrick?

  a week, it's a 50% reduction in cardiovascular-related mortality compared to one time a week. Again, dose-dependent, man, or two to three times a week is something like 24% lower death from cardiovascular disease. There's also lower, you know, sudden cardiac deaths, like a heart attack. That's like 60 something, greater than 60% lower if, if men use it four to seven times a week versus once. Again, a dose-dependent thing. And the thing that's so profound there also to me, when, again, looking at the methods, when I look at the data, and this is all work from Dr. Yari Laukonen. He's in the University of Eastern Finland, and just one of the, the world experts on sauna use, especially with respect to cardiovascular

• 2:20:12Dr. Rhonda Patrick?

  health. What some of his data has also shown is that if you look at the duration, the time spent in the sauna, so a lot of the, so I mentioned the temperature I do is about, I do like 189 degrees Fahrenheit. Typically, I go in there, I'm pretty heat adapted. And so the more you do, the more you do the sauna or any sort of heat stress, whether it's a hot tub or Jacuzzi, you, you become adapted. You're, you're basically start to sweat at a lower core body temperature to cool yourself down. All these sort of physiological changes start to happen earlier. And so I stay in for like 30 minutes. Like, I mean, so I stayed a long time. That's a lot. You have to listen to your body. Um, most of the studies that I just talked about were from the, the duration, the time spent in the sauna.

• 2:20:56Dr. Rhonda Patrick?

  When I said 50% reduction in cardiovascular disease related death, what was shown was that men that were in the sauna for only 11 minutes, even if they used it four to seven times a week, that reduction was only like 8% instead of 50. It had to be greater than 19 minutes. So like 20 minutes is the sweet spot at about 174 degrees Fahrenheit. Um, and so, and, and most, most of the saunas in Finland, by the way, they're, they're, they're humid. So they, they, they put hot water, hot, not hot, they put water on hot rocks to create steam. And so it's some usually between 10 to 20% humidity in the Finnish sauna. So those, those studies were, I would say, most of the time you're going to find that their humidity is also elevated.

• 2:21:39Dr. Rhonda Patrick?

  But to me, the, the dose dependent nature of it and the duration, knowing like, you know, to me, that's a very strong data that this is more causal than some, you know, corollary thing. Because that's always the problem with observational studies, including these, which they corrected for a whole host of factors like cholesterol, you know, exercise, just everything, everything under the sun. I mean, they corrected for those. And on top of that, you have the dose dependent nature of the duration, the time spent in the sauna and the frequency. So to me, it's like something's going on here. Plus, there's been studies, intervention studies where it's like, you know, comparing directly head to head, moderate intensity aerobic exercise on a stationary cycle to 20 minutes in a sauna.

• 2:22:22Dr. Rhonda Patrick?

  They're, they're physiologically, the same things happen, so. Heart rate elevates while you're doing the activity. Blood pressure increases while you're doing the activity. But then after, heart rate decreases. Resting heart rate decreases below baseline. Blood pressure is improved, so it decreases below baseline. This is happening the same in moderate intensity cycling versus sauna. So again, the sauna, like this heat stress, there's something about it that really mimics this moderate intensity aerobic exercise, which is really great for people that can't go for a run, that can't even get on a bike. So, you know, disabled people, granted, there are some safety concerns, they're pretty mild, but they do exist. You know, so people that had a recent heart attack or have some rare kind of heart disease

• 2:23:07Dr. Rhonda Patrick?

  or problem, drinking alcohol, never do that. Elderly people prone to low blood pressure, always talk to a physician before doing the sauna. It is stressful. Pregnant? Pregnant women, oh yeah, I definitely avoided saunas when I was pregnant. But it is, I think it's very relevant for disabled people and also people like that are sedentary, I've been sedentary most of my life, like my mother. I've been able to get her in the sauna because she's not, I mean, I did get her on the Peloton once, but it's really much easier. She feels like it's a spa treatment and it's like she can listen to her music in there. And like, I care about her health, but she's mostly been a sedentary person. And so I find it much easier to convince her to get in the sauna than to get on Peloton. Ideally, you do both.

• 2:23:52Dr. Rhonda Patrick?

  The question would be, well, I exercise, I run, I do my high intensity interval training, why do I need to get in the sauna? And the reality is, and so I published all this in a review in the Experimental Gerontology last year, I guess, early, late last year. And basically cardiorespiratory fitness, which is a marker of, it's a marker of health. You know, cardiorespiratory fitness is improved.

• 2:24:20Dr. Rhonda Patrick?

  In people that do exercise and sauna compared to exercise alone or sauna alone. So for those healthy, fit people out there already exercising, there's a synergistic effect by also adding a sauna into that routine. And to me, that's great. And there's so many beneficial things happening with the heat stress. In addition to mimicking aerobic exercise, there's the heat shock proteins that we talked about earlier. And those, it kind of brings me back to my early days of science when I was at the Salk Institute for Biological Studies doing research on little nematode worms that we or someone else injected amyloid

• 2:25:01Dr. Rhonda Patrick?

  beta 42, the peptide, the 42 amino acid peptide that is involved in amyloid plaques found in the brain, correlated with Alzheimer's disease and other, you know, brain disorders. We injected those into the muscle tissue of worms. And basically, these worms become paralyzed with age because the aggregated proteins, these proteins aggregate. Well, heat shock proteins, one of the main things they do is they basically make sure the proteins inside of your cells maintain their proper three-dimensional structure and are folded right. And so they don't, they're not prone to aggregating and forming these plaques

• 2:25:41Dr. Rhonda Patrick?

  in your arteries and also in the brain. And there's, back to my worm studies I was doing, I would elevate heat shock proteins in those worms and it would totally, you know, correct the problem where they would no longer become paralyzed. They'd move around like they were young. So many animal studies have been done looking at Alzheimer's disease, you know, like a human-like Alzheimer's disease in a rodent and heat shock proteins protecting from it, you know. So heat shock proteins are robustly activated in humans. And this has been shown to even, you know, 50% higher over baseline levels after just 30 minutes at 163 degrees Fahrenheit in the sauna. So, and they stay activated at least in rodents

• 2:26:25Dr. Rhonda Patrick?

  for, you know, 48 hours at least. So, you know, having these heat shock proteins around.

• 2:26:32Dr. Rhonda Patrick?

  Making sure they're they're properly taking care of our our proteins so they're not aggregating in our brains and in our in our plaques could be another potential way that sauna is protecting from Alzheimer's disease and other, you know, cardiovascular health as well as longevity. So, um, you know, there's, there's people that have SNPs in heat shock protein factor 70 that if they have one of them, so they got one from their parents where they have more active heat shock protein 70, they live on average one year longer than people that don't have that SNP. And if they have two versions, they got one from their mom and one from their dad, they live on average two years longer than people that don't have that SNP. So it's also

• 2:27:09Andrew D. Huberman?

  Wow.

• 2:27:09Dr. Rhonda Patrick?

  been associated with human longevity as well as in lower organisms. So you can heat shock a worm or a fly and they live 15% longer. This is just worked on by Gordon Lithgow at the Buck Institute years and years ago. Um, so anyways, I guess what I was getting at was, um, the heat shock proteins are are part of that stress response pathway that we talked about earlier. And, uh, you know, they're also activated by cold as well. Cold shock does activate heat shock proteins, not as robust. Sulfurapatride activates them. Again, it's one of the reasons I think we should get all of these things because they are more robust inputs. You know, their input activating mechanisms are more robust for, you know, different ones. So there is crosstalk. There is, you know, I mean, I guess I get,

• 2:27:51Dr. Rhonda Patrick?

  it'd be more accurate to say there's, um, overlap. But, but, you know, it's also like you want to get the most robust from all of them, right? I do. So, I mean, that's why I want to do the sauna and exercise and eat my, you know, my broccoli sprouts and, and, um, all that stuff. So.

• 2:28:08Andrew D. Huberman?

  All right. It's super interesting. A couple, a couple of questions came up for me. Um, one is, you mentioned these, uh, SNPs, these, um, nucleotide repeats, basically genes that some people have more of or less of, uh, than others that can predict longevity in some sense. Is that the Fox 03 pathway?

• 2:28:28Dr. Rhonda Patrick?

  That's one that can, yeah, I mean, Fox 03 is, in fact, if you go back to the worm studies I was talking about, that was like one of the first things, when you see it with your own eyes, you can take these worms that you basically decrease their insulin signaling pathway and their IGF-1. Worms have what are called homologous genes, so they have a lot of similarities to humans. They have an insulin-like receptor, they have an IGF-1-like receptor, and they make something like Fox 03, which we have. And basically, if you decrease that insulin signaling pathway, their Fox 03 is always active in those worms. And they live like 100% longer. And not only do they live longer, I mean, they are like a very young worm. I mean, they are like, you look at this thing and you're like,

• 2:29:13Dr. Rhonda Patrick?

  this looks like the worm that was just born like hours ago. What's going on? This thing's at the end of its life. Now, as a side note, the thing that always got me on this was, by the way, this was discovered by Cynthia Kenyon, and this was like back in the 90s, and honestly, I'm not sure that anything has been as exciting in the worm world since then, but I thought, I mean, it was a really big finding. The only caveat there is that the worms go through this dour, it's called a dour, stage when this happens, when you decrease their insulin signaling and stuff. And they like go into this like metabolic stasis, like they're not eating as much or moving. And so it's like, okay, well, they live 100% longer, but like, they go into this weird state, you know?

• 2:29:54Andrew D. Huberman?

  I know people like this, some in the longevity community, they know who they are. But they'll get the last laugh because I'll be dead, well-fed, but dead, and they'll still be going. So in terms of the many data on sauna, and I also just want to acknowledge these Finnish groups that did this work is really pioneering, right? When you think 20 years ago, long before social media or any of this, and they're out there, up there, I should say, measuring cortisol and growth hormone and all this stuff, and people getting in and out of sauna, very, very interesting. So 20 minutes seems like the threshold at 170 degrees Fahrenheit.

• 2:30:36Andrew D. Huberman?

  More times per week seems to be better than fewer when you think when in terms of all cause mortality cardiovascular risk according to what what I just learned from you.

• 2:30:44Dr. Rhonda Patrick?

  Four would be a good, I think, minimum effective dose.

• 2:30:47Andrew D. Huberman?

  Four times a week and you combine it with the cold. I've also seen a protocol where is a very extreme protocol. I don't recommend this to people right off the bat where they had subject, human subjects get into the sauna for 30 minutes, get out for five, 30 minutes, get out for five, 30 minutes for a total of two hours of exposure. But that was what led to these massive 16 fold increases in growth hormone. I actually have a so I and they had to do it very seldom. So it sounds like these protocols you're describing 20 minutes done four times per week, far more reasonable for most people to access. But I know people are probably desperate to know what if they don't have a sauna? You know, a sauna is a kind of a unique item. So I have a couple of questions.

• 2:31:27Andrew D. Huberman?

  Can people use hot baths with the appropriate warning, of course, that without getting into a description of the the mechanics and the underlying biology, it's pretty obvious that the testes, if they get too warm, you'll you'll kill sperm. That's the reason why the testes are housed in a structure called the scrotum that can move around. So just to be, you know, we are biologists just talking about realities here. So if you're trying to conceive children or keep your sperm healthy, guys should probably stay out of warm hot baths.

• 2:31:58Dr. Rhonda Patrick?

  For at least six months. That's been shown.

• 2:32:00Andrew D. Huberman?

  Six months.

• 2:32:01Dr. Rhonda Patrick?

  So sperm product, so sperm motility goes down and sperm production goes down, but that is completely like corrected if they stay out of the sauna for six months. So so through six months later, it's back to normal.

• 2:32:12Andrew D. Huberman?

  Great. That's very useful information, I'm sure, to a number of people out there. So there if people don't have access to a sauna, and we get this about cold too, you always say, what about cold showers? And I always say, well, the studies may have mainly been done on immersion because it's hard to keep things controlled in cold showers. It just doesn't make for a very good experiment because how you get a bigger person, less of them is under the shower. And so it doesn't make for a good experiment. So it's a it's not as good as immersion. But with the with heat, I could imagine that a hot bath would work almost as well.

• 2:32:43Dr. Rhonda Patrick?

  Yeah, so there's been some studies looking at, for example, activation of heat shock proteins, also brain drive neurotrophic factor increases with heat stress. And so the hot bath at around 104 degrees Fahrenheit, which is typically what studies will use for temperature, which is actually cooler than when I crank my bath hot, it's so hot.

• 2:33:01Andrew D. Huberman?

  But you're very heat adapted.

• 2:33:03Dr. Rhonda Patrick?

  I'm very heat adapted, yeah. And it's 20 minutes from the shoulders down. And that is like a very robust activation in heat shock proteins and in brain drive neurotrophic factor. And then heat shock proteins are also protecting against muscle atrophy. So that's also having to do with the protein structure in the muscle tissue as well. And this has been studies in animal, you know, animal data, as well as some recent human data as well. It was local hyperthermia or local heat treatment. But essentially it showed that it protected. I mean, it was like, there was a study where they were looking at muscle disuse and it was, it was something like the local heat treatment prevented like almost 40% of the muscle atrophy from disuse. So like, and it's funny because I used to use the sauna when I was injured and stuff.

• 2:33:45Dr. Rhonda Patrick?

  I would go in the sauna because I like, I didn't know at the time because I was a graduate student, but I knew like just from experiments that like, you know, like, I'm not losing as much muscle, I feel better. Like I, you know, like at the time I was reading all about the growth hormone and stuff back then. But, and I knew about heat shock proteins and so I kind of knew, but that data wasn't around yet. And so now we have the data. And I've always like felt like I wasn't losing my muscle like I should have been when I was doing the sauna. And I was doing it literally seven days a week. It was like hardcore.

• 2:34:19Andrew D. Huberman?

  This is also during graduate school?

• 2:34:21Dr. Rhonda Patrick?

  Yeah, now, now I'm doing, I'm doing the sauna. Like a bare, bare minimum, I do three, but I try to do four because of the, it all depends on my schedule. I also like to do long runs. I really, it's like long being like three miles, not like Cam Haynes. It's too long. But I really, for me, and we were talking about this earlier, like off camera, that The runs for me are for my brain and I get this mind wandering effect where I daydream and I think about things. I work through problems. I get creative. I come up with ideas and this is all happening on the runs. And so I just, I miss my runs if I don't do them and I miss it because of the brain effects I get from it. And when I exercise,

• 2:35:06Dr. Rhonda Patrick?

  it's funny because I'm a female and you think that I'd be exercising, you know, to stay fit and in shape and care about my figure. But when I exercise, literally what I'm thinking about is my brain and I'm like, this is the best longevity drug there is. This is it right here, Rhonda. Like you're always wondering, you're always wanting to know, you're wanting to do the best. Like if you don't exercise, you're missing that essential dose. And so that for me is motivation, the dopamine seeking thing I'm looking for. Admittedly, I need to, I do not do enough strength training and I have to do it. I have to, I have to, I have to. I'm like, I'm just, I'm so after the endurance and the hit and I really need to add that in because muscle mass is also extremely important for aging as well, you know. So that's my, that's my fault.

• 2:35:52Andrew D. Huberman?

  Well, the, the brain effects are really interesting. I also run. I try and get one longer run per week and a few other runs and I do it without a phone. I don't listen to podcasts. I occasionally will listen to music, but I really try not to. I also find that my mind solves problems. I feel like it washes out the cobwebs, so to speak. Some of the most brilliant and prolific neuroscientists that I know who've had very long careers, Eric Kandel, Nobel Prize winner at Columbia, comes to mind for all his work on memory, used to swim a mile a day and now I think swims half a mile a day, but he's in his late 90s and he's still sharp, which is incredible. And his lab has done some work showing that any load bearing exercise repeated, so endurance work, unlike the Peloton or

• 2:36:37Andrew D. Huberman?

  cycling, that's really load bearing, although you're cycling really hard with the resistance, but causes the release of osteocalcin from the bones, which acts in an endocrine way, sort of like a hormone. Can actually travel to the hippocampus and at least in these animal studies induce the proliferation of neurons, growth of synapses, BDNF, a number of downstream things, which kind of makes sense if we were to put a just so evolutionary story on this. You know, a body that's active can signal to the brain that the body still needs cognition. You know, an inactive body in some ways is depriving the brain of any signal of what the body is doing, right? This is, obviously, I'm making this up as conjecture, but we know in ocean and various

• 2:37:21Andrew D. Huberman?

  ocean animals that they'll swim around for some period of their life and then they'll have a completely stationary portion of their life. And basically, the brain degenerates. You don't need much of a nervous system if you're not moving. So I think there's really something there and also just letting your ideas in mind drift. I love that you, and I appreciate that you shared your protocols because I think right now we're in an interesting time in public health information history where people are just kind of getting bombarded with cold is good, heat is gold. Cold is good, heat is good, excuse me, I misspoke. There are all these micronutrients and of course, macronutrients are important too. And today, you've really enriched us with the description of the underlying mechanisms

• 2:38:04Andrew D. Huberman?

  and the logic behind them, but also sharing what you do is really informative because I think people need a jumping off place and obviously, they need to start someplace and getting heat adapted, etc. Takes time, but I really appreciate that you're willing to share your protocols and that you do the things that you that you teach and educate people about. As a final question, because I have have have to ask, red light sauna or no red light sauna? I've been a little bit vocal about my feelings that none of the red light saunas I've ever been in got hot enough and it was frustrating. So like, I feel like it's neither here nor there. However, I do acknowledge that red light and low level light therapies are now known to do a number of interesting things. It was the Nobel Prize in 1908 for phototherapy for lupus.

• 2:38:49Andrew D. Huberman?

  So, you know, it's not like a new thing, the idea that light and light could do things positive for our biology, but do you have a red light in your sauna? Do you think it's useful? And I mention this because this is the number one question I get about sauna, red light or no red light? Or some, some intermediate answer.

• 2:39:07Dr. Rhonda Patrick?

  Um, so I don't have a, an infrared sauna, um, but I do have, like, I have a sauna that has lights. It makes red light, but I don't think it's the red light that you're talking about.

• 2:39:17Andrew D. Huberman?

  Okay.

• 2:39:17Dr. Rhonda Patrick?

  It's not activating it at a specific wavelength, which is.

• 2:39:21Andrew D. Huberman?

  It's usually so that the range that seems to be helpful, and I have, I confess, I use a red light panel for other things. Is 670 nanometer out to about 720 nanometer. So it looks like red and very dim pant, uh, light, dim red and bright red. And the idea is that red light can travel, the photon energy is such that it can travel down through the, uh, deep layers of the dermis of the skin.

• 2:39:48Dr. Rhonda Patrick?

  I, you know, I, I don't have a red light in my sauna. I don't know if it's essential or not. I don't think so, based on all the studies I've talked about. I think that would be, is, you know, the, the, the potential effect on mitochondria is interesting. I do think there's, um, a lack of really good, solid evidence in, you know, humans. But I do, that not, might only be because it's just not studied enough. And that's usually the case. So perhaps, you know, like there's the Juve, right? The Juve, they have those pant, red light panels and stuff.

• 2:40:20Andrew D. Huberman?

  Cozy are the two ones I know, K O Z E and Juve. They're, they're, as far as I know, I'm probably going to insult both companies at the same time. But I'd rather insult them both at the same time than, than just compliment one or insult one. Both of them seem excellent for getting the appropriate wavelengths of red light. And I do not have a relationship to either of those.

• 2:40:38Dr. Rhonda Patrick?

  Well, I, I personally think that the, the sauna in and of itself, it's about the heat stress. And typically the question I get is infrared sauna or regular sauna? And, um, there are some differences as well. Infrared saunas, maybe the infrared saunas are the ones that have the red light that you're talking about. Infrared saunas only get up to around 140 degrees Fahrenheit. So as I mentioned, the studies were about 174 degrees Fahrenheit. And so, um, you really have to. Stay in a longer period of time. However, there have been some studies coming out of Japan. They they use infrared sauna. They have this whole protocol. It's called way on therapy. And they they they they get people in infrared saunas and they wrap them in a towel and like

• 2:41:22Dr. Rhonda Patrick?

  they stay warm for X amount. So it's like the whole protocol ends up being like an hour long. But again, it's 140 degrees Fahrenheit. So it's an infrared sauna. And it's been shown to improve a variety of like coronary heart disease and conditions, heart related conditions, like there have been some improvements. So obviously, there's there's evidence that infrared saunas can be beneficial for cardiovascular health. I do, I've used infrared saunas many times at my my in-laws. They have infrared sauna and I have to crank that thing up for a while until it's maxed. And then I have to sit in there for an hour at least. I do sweat a lot, and that's another thing we didn't talk about. You do sweat some heavy metals and some some heavy metals are excreted predominantly through sweat and others through urine.

• 2:42:07Dr. Rhonda Patrick?

  So so for example, cadmium, there's like 125 fold increase in cadmium excretion from sweat. When you get in the sauna, also lead is something like 17 fold excretions higher. Another one is aluminum. It's about four fold higher. So infrared, you do sweat a lot too. And that's because the main difference is that you're heating your body up through thermal radiation versus the ambient hair air, like a standard, you know, sauna is a heater and the heater is heating up the air and and that's how you're heating yourself up. So it is a little bit of a different mechanism. I prefer regular saunas. Most of the data out there is from from the heat stress itself, like the your heart rate's elevating when you're in there. You're feeling hot. You're getting that cardiovascular. I

• 2:42:51Dr. Rhonda Patrick?

  mean, that's what you're feeling when you're in a hot sauna. And that for me takes a really long time in the infrared sauna. I get at the very end. But I do think there are some benefits from infrared and they are more affordable. They're less of a fire hazard. But again, hot baths are, I think, a good alternative modality for heat stress compared to like a regular sauna. So.

• 2:43:11Andrew D. Huberman?

  Great. That's a really helpful answer. I like I said, I use the red light, but not in the sauna. And and thank you for reminding us of that 174 degree Fahrenheit threshold that was mainly used in all these studies. We covered a lot of territory, but I just want to thank you again. It was extremely thorough and extremely informative. I now have, my notes are, always look a little bit like they were drawn out by a macaque monkey who has no knowledge of the English language, but I can decipher this to tell you that there are at least 10 additions to my current protocols that I'm gonna add, and I'll have lots of questions, so I apologize in advance for that. But on behalf of the listeners,

• 2:43:53Andrew D. Huberman?

  and just directly from me, thank you so much for your time. I learned a ton.

• 2:43:58Dr. Rhonda Patrick?

  My pleasure. Thanks for having me on. It was really awesome conversation, so I enjoyed it a lot.

• 2:44:03Andrew D. Huberman?

  Let's do it again.

• 2:44:04Dr. Rhonda Patrick?

  Totally.

• 2:44:05Andrew D. Huberman?

  Great. Thank you for joining me for my discussion with Dr. Rhonda Patrick. I hope you found it as interesting and as actionable as I did. Once again, if you'd like to learn more about Dr. Patrick's work, sign up for her newsletter, and to listen to her excellent podcast, go to foundmyfitness.com. You'll find links to the newsletter as well as the podcast there, or you can go direct to the podcast by going to Found My Fitness on YouTube, Found My Fitness on Apple, or Found My Fitness on Spotify. And once again, the newsletter is foundmyfitness.com/newsletter. If you're enjoying and/or learning from the Huberman Lab podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please subscribe to

• 2:44:46Andrew D. Huberman?

  the podcast on both Spotify and Apple. And on Apple, you have the opportunity to leave us up to a five-star review. If you have suggestions of topics, or guests, or feedback of any kind, please put that in the comment section on our YouTube page. In addition, please check out the sponsors mentioned at the beginning of today's podcast. That's the best way to support this podcast. As also mentioned at the beginning of the episode, we are now partnered with Momentous Supplements. So if you go to livemomentous.com/huberman, you'll find what we firmly believe to be the highest-quality supplements available, in the specific dosages that match the peer-reviewed science and recommendations made on various episodes of the Huberman Lab podcast. You will also find specific protocols of how much to take and when,

• 2:45:30Andrew D. Huberman?

  what time of day, what time of night, et cetera. And you will also find behavioral tools that can synergize with those supplements. Many of you will also be pleased to learn that Momentous Supplements, of course, ships within the United States, but also internationally. If you're not already following us on Instagram and Twitter, please do so. It's Huberman Lab on both Instagram and Twitter. There, I teach science and science-based tools, some of which overlap with the content of the Huberman Lab podcast, but much of which is distinct from the content of the Huberman Lab podcast. Thank you once again for joining me for my discussion with Dr. Rhonda Patrick. And as always, thank you for your interest in science.