Huberman Lab - Dr. Rhonda Patrick: Micronutrients for Health & Longevity

Starting point is 00:00:00 Welcome to the Huberman Lab podcast where we discuss science and science-based tools for everyday life. 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

Starting point is 00:00:45 health. Dr. Patrick did her formal training in cell biology, exploring the links between mitochondrial 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

Starting point is 00:01:21 premier journals in the world, including science, nature cell biology, trends in cell biology, and facep. Indeed, Dr. Patrick is an expert in an extraordinarily broad range of topics that impact our health. 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 wrapped 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

Starting point is 00:02:00 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 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.

Starting point is 00:02:35 I'm confident that you'll learn a tremendous amount of information from Dr. Patrick, much of which is immediately actionable. 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 slash newsletter is where you'll find it. And it includes research on fasting, micronutrient sleep, depression, fitness longevity, and

Starting point is 00:03:09 far more, along, of course, with actionable protocols. I'm pleased to announce that the Hubertman Lab podcast is now partnered with Momentus Supplements. Our motivation for partnering with Momentus 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 Uberman Lab podcast. If you go to livemomentus.com slash Uberman, you will see those formulations.

Starting point is 00:03:38 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 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 drive

Starting point is 00:03:58 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 live momentous.com slash Huberman, you will find what we firmly believe to be the best quality supplements in the precise dosages and 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.

Starting point is 00:04:33 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. Our first sponsor is Athletic Greens. Athletic Greens is an all-in-one vitamin mineral probiotic drink. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or twice today is that it helps me cover all of my basic nutritional needs. It makes up for any deficiencies that I might have. In addition, it has probiotics, which are vital for microbiome health.

Starting point is 00:05:10 I've done a couple of episodes now on the so-called gut microbiome and the ways in which the microbiome interacts with your immune system, with your brain to regulate mood, and essentially with every biological system relevant to health throughout your brain and body. With athletic greens, I get the vitamins I need, the minerals I need, and the probiotics to support my microbiome. If you'd like to try athletic greens,

Starting point is 00:05:32 you can go to athleticgreens.com slash huberman and claim a special offer. They'll give you five free travel packs, plus a year supply of vitamin D3K2. There are a ton of data now showing that vitamin D3 is essential for various aspects of our brain and body health, even if we're getting a lot of data now showing that vitamin D3 is essential for various aspects of our brain and body health, even if we're getting a lot of sunshine, many of us are still deficient in vitamin D3.

Starting point is 00:05:51 And K2 is also important because it regulates things like cardiovascular function, calcium and the body, and so on. Again, go to atletagreens.com slashubramin to claim the special offer of the 5 free travel packs and the year supply of vitamin D3 K2. Today's episode is also brought to us by Element. Element is an electrolyte drink that has everything you need and nothing you don't. That means the exact ratios of electrolytes are an element

Starting point is 00:06:15 and those are sodium, magnesium, and potassium, but it has no sugar. I've talked many times before on this podcast about the key role of hydration and electrolytes for nerve cell function, neuron function, as well as the function of all the cells and all the tissues and organ systems of the body. If we have sodium, magnesium, and potassium present in the proper ratios, all of those cells

Starting point is 00:06:36 function properly and all our bodily systems can be optimized. If the electrolytes are not present and if hydration is low, we simply can't think as well as we would otherwise. Our mood is off, hormone systems go off, our ability to get into physical action to engage in endurance and strength, and all sorts of other things is diminished. So with element, you can make sure that you're staying on top of your hydration and that you're getting the proper ratios of electrolytes. If you'd like to try element, you can go to drinkelement.lmentNT.com slash Huberman, and you'll get a free element sample pack with

Starting point is 00:07:08 your purchase. They're all delicious. So again, if you want to try element, you can go to elementlmnt.com slash Huberman. And now, from my discussion with Dr. Rhonda Patrick. Rhonda, welcome. There'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.

Starting point is 00:07:43 So thank you for that. That's been... Oh, that is so kind. Thank you. Thank you so much. Well, it's absolutely true. I am so excited to be here having a conversation with you. 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.

Starting point is 00:08:14 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 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, etc., etc., hopefully you'll tell us more about those.

Starting point is 00:08:52 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 lead us to some point of convergent understanding. So, if you would. 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

Starting point is 00:09:30 challenging of yourself. And whether that is through temperature changes like cold or heat, or through other types of stressors, like physical activity, or perhaps even dietary compounds that are bound in plants. These are things like polyphenols or flavanols. 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, and I say we, not us, but humans, we were out gathering,

Starting point is 00:10:09 we were moving, and we had to be physically fit. You couldn't 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 error, in a minute fasting was also a part of it. This is another type of challenge. We didn't always have a prey that we caught or maybe temperatures were such that

Starting point is 00:10:36 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 these are all types of stress, with something common as well as eating plants. So getting these compounds that I mentioned. So these are all types of stress, intermittent challenges that activate genetic pathways in our bodies.

Starting point is 00:10:53 These are often referred to in science as stress response pathways because they respond to a little bit of stress. 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 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 normal metabolism,

Starting point is 00:11:32 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 has a very profound antioxidant anti-inflammatory response 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 a topogy, which is a process that can clear away all the gunk inside of ourselves, pieces of DNA, protein aggregates. So you'll find that these stress response pathways are activated by a variety of stressors. So for example, one pathway is called heat shock proteins.

Starting point is 00:12:18 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 can eat a plant like broccoli sprouts, which is high in something called sulfurophane. This is a compound that is sort of like a whormedic compound.

Starting point is 00:12:35 Or as David's clear likes to say, it's a Xenohormedic compound. I love that term. And it activates heat shock proteins, among other things. It also activates a very powerful detoxification pathway called NRF2, which helps you detoxify things like carcinogens that you're exposed to. Well, guess what? Heat activates that.

Starting point is 00:12:54 So what I'm getting at is there is overlap. Like cold also activates heat shock proteins. You're like, really cold? Yes, it activates. These are stress response pathways. And they are activated by various types of stressors. Now, you're going to more or more blessedly activate heat shock proteins from heat versus cold, but there is overlap. So I think that forms a foundation

Starting point is 00:13:18 there. Yeah, that's very helpful. And it brings to mind in the context of the nervous system, I always tell people, 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. Dopamine is a generic pathway by which motivation, craving, and pursuit emerge, et cetera. Just like adrenaline is a generic theme of many different behaviors. It seems that it is the job of biological systems to be able to take a diverse range of inputs,

Starting point is 00:13:52 even unknown inputs. 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 plants are trying to kill us.

Starting point is 00:14:25 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 than 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 hormisist type scenario. So then I think we conceivably solve the problem.

Starting point is 00:14:56 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 heat is bad for us, too much cold is bad for us, but in small amounts, they provide this hormetic response, and they're good for us. So in the same way that heat is, too much 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 scenario can be good for us. Is that how I should think about plants in these compounds? Do you think of them as good for us?

Starting point is 00:15:19 Or as bad for us, they're a very sharp blade and we want to use them, potently? I sharp blade and we wanna use them politely. I actually think that it's almost impossible. I mean, you'd have to eat nothing but the same plant all day, every day in the lot. I mean, the bioavailability of these compounds in the plants, they're attached to a food matrix. It's not like taking it in a supplement form as well.

Starting point is 00:15:47 It's such that, it's not like taking it in a supplement form as well. It's such that like, 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 sulfur, and it's another compound, but that's all they eat every day. Nothing but that. And they get, yeah, and they're like iodine deficient on top of that. So, 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, a hamlock, exactly. So, don't play this game with with him. But you're not going to get poison from eating, you know, you're serving a broccoli at dinner, right? So I mean, it depends on the plant.

Starting point is 00:16:33 It's, I don't, these generalizations are kind of, they're just not useful. And I think that a lot of people online in the blogosphere, they gravitate towards them because it's just easier and it's a lot more sensational. I plants meat and starches. I'm one of those rare omnivores out there now. I feel like a 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, most people, I would say 99% of people on the planet

Starting point is 00:17:02 are probably omnivores. Right. And someone will probably correct me, but I doubt the planet are probably omnivores. Right. And someone will probably correct me. But I doubt the number falls below 98. I think if you look at data, you know, and when we have carnivore data, I can't wait to see it, but right now it's a lot of, okay, well this is a lot of anecdotal evidence and there's a good, there's a lot of good starts with anecdotes, but like people change a thousand things at once

Starting point is 00:17:28 and they don't realize that, but they do. And so anecdotal data is only so good, right? It's a starting point. And so we don't really know long-term what carnivore diets are gonna do. They may be beneficial short-term, they may be beneficial for reasons of elimination may, you know, be beneficial for reasons of elimination of other things like who knows, right? Lots of possibilities. But I do

Starting point is 00:17:49 think with respect to plants, you know, that there's, that there's so much evidence like, for example, sulfur, is one that I really like because there's just evidence that sulfur afraid is a very powerful activator of the NRF2 pathway. 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 were exposed to from our food, like heterocyclic amines. In fact, there have been GWAS studies.

Starting point is 00:18:20 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 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 cruciferate vegetables, it negates that risk because they're getting sulfuric fain, which activates a lot of the glutathione transfer, glutathione

Starting point is 00:18:59 transferase and synthase genes. So glutathione is a major antioxidant in our brain and in our vascular system and ourase genes. So glutathione's a major antioxidant in our brain and in our vascular system and our body, basically. So there's evidence that eating things like compounds that are like sulfuraphane or broccoli, or broccoli spouts, which have like a hundred, up to 100 times more sulfuraphane than broccoli,

Starting point is 00:19:22 are activating glutathione in the brain. There's human evidence of that. I mean, that's amazing. That is amazing. Impatient. Yeah. Sorry to interrupt. I just want to make sure when so broccoli sprouts are different than broccoli.

Starting point is 00:19:33 And you just told us that they have much richer in 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. So the sulfuricane is formed from a compound called glucoraphanin, which is in the broccoli. And the enzyme that converted into sulfuricane is myrocinase, and it's heat-sensitive. So you do somewhat lower the sulfuricane levels when you cook the broccoli.

Starting point is 00:20:08 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. Two of your cooked broccoli increases the sulfurophane by fourfold. So, 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,

Starting point is 00:20:35 but I like the way mustard seeds sound. So just a little bit of mustard seed powder added to the cooked broccoli can recover some of these compounds. Yes, so what I do is I will lightly steam my broccoli and then I add a little bit of my carigold butter and then I add some mustard seed powder on the top of that. It's just a little spice and if you don't taste that, it's expired. It should have a little kick.

Starting point is 00:21:02 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? Well, I had shifted to supplementation with sulfurophane. 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. The supplementation or the broccoli? Yes, the supplementation. And so there's another way to get, there's another compound and it's actually called meringa. And Dr. Jed Fey, who's really the expert on sulfur, fein, he's a good friend of mine, he's been on the podcast a couple of times.

Starting point is 00:21:43 He basically thinks and has done a lot of research on Moringa as well, that it's like a cousin and it activates the NRF2 pathway similarly to Stolferrfain. And so I've been buying this Koolie Koolie Moringa powder. I don't have any affiliation with them. Koolie Koolie is a brand. Koolie Koolie is a brand. You have no affiliation. I'm no affiliation.

Starting point is 00:22:02 But Judfe, he has researched it like that specific brand, and so it's like legit. It's legit, you know, it's like science back in terms of actually containing maringa and activating NRF2, and I added to my smoothies. So that's what I've been doing. What are some of those ranges? So of course we give the usual recommendations that people should talk to their physician, et cetera, et cetera.

Starting point is 00:22:24 But if people are going to, what do you take? That's always the, let's take that. Let's take the table. The David St. Clairion approach. What do you, where he'll talk about what he does as a way to deal with this? 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? I do a big heaping tablespoon. So maringa, cool and cool and maringa,

Starting point is 00:22:55 it sounds like a song. It's with a K, I know. But for people also listening, it's like, well, why would I do that? 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.

Starting point is 00:23:13 There's been several different studies in China. In China, there's a lot of air pollution. And I mentioned that it's a very powerful activator, NRF2. And I know you're familiar with NRF2. But NRF2 is like a transcription factor. That 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.

Starting point is 00:23:34 It's regulating what's being activated or what's not being activated or being turned off. And some of the genes are basically these detoxifying pathways. 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,

Starting point is 00:23:53 if you're smoking cigarettes still, like please try to quit. But I mean, yeah, it's just one of the lung cancer you're mutating your DNA. 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 sulfur, or fein from broccoli extract, broccoli seed extract was, broccoli sprouts extract, not

Starting point is 00:24:21 the seed, it was the sprouts. Anyways, they started excreting like 60% benzene and acralene. I mean, that's something that we get in cooked food. It's coming out in their urine. Coming out in their urine. Yeah. So 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

Starting point is 00:24:40 teens. This is fascinating. And it brings back to this question that we have before and 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 I'm taking away from everything you're telling me. Right. And that our bodies were supposed to be getting that stress to have those pathways activated. Like it is, you know, right?

Starting point is 00:25:08 I mean, this is conserved among different animals. Like this is something that 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 to activate. We're supposed to.

Starting point is 00:25:38 I find that fascinating and again, drawing a parallel to the nervous system. 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 hunger, and have to exercise, essentially, in order to obtain these compounds. And then those compounds are reparative.

Starting point is 00:25:59 I feel that resembles the dopamine pathway. I always say, 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 to ingest the drug.

Starting point is 00:26:24 Whereas 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, different types of intermittent

Starting point is 00:26:58 challenge. And we can re, we are rewarded with particular compounds that are reparative, both for the challenge, but then it make us stronger. It is, or me since it really is, it seems a case of what doesn't kill us, makes us stronger. So you mentioned. Can I add to that one?

Starting point is 00:27:13 Please. Please. Please. Please. Please. Please. Please. Please.

Starting point is 00:27:21 Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. Please. give the animal sulfurerfain and then you expose them to like, you know, hypoxia or some kind of exchemic stroke condition, whatever they do to induce that. And the sulfurerfain, it basically protects that, like, their precondition and their stress response pathways are primed. And so when they're then exposed to the exchemic stroke, their outcomes are so much better, so much better than the animals that didn't get the sulfurerfane 48 hours before or whatever it was. And this has been shown in multiple animal studies, with sulfur-erfane, specifically,

Starting point is 00:27:51 in the brain. I know Mark Mats and Dr. Mark Mats, and he's often thought of as the intermittent fasting king, but he's a neuroscientist, and he did publish some work and talks about sulfur-erfane as well. 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.

Starting point is 00:28:17 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, many of them, 75% or more, experience those. So it's salient within those communities, but concussion is prominent. People are always asking,

Starting point is 00:28:49 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 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.

Starting point is 00:29:12 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. You're able to accelerate it and understand. So 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 neurodegenneries because there are a lot of similarities there.

Starting point is 00:29:41 So for a fein, I personally think, and I do think there's been some animal research with TBI, I mean, and so for a fein, mostly preconditioning rather than treatment. So again, it's like, well, I mean, if you're going to, if you want a healthy lifestyle thing and you're a construction worker or you're filling the blank, that's, you know, going to, I mean, anyone that drives into car, I mean, you're at risk to some degree, right? Or bicycle.

Starting point is 00:30:05 Bicycle, yeah. 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 3000 pound vehicle, I mean, we've lost, we have a number of friends who've died, we have a number of people with traumatic brain injury. I'm not against cycling or cyclist, but it is, it's a risky sport by any stretch.

Starting point is 00:30:30 So in taking things like maringa 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, NRF2 is expressed in neurons, right? So those cells should be protected. Are there other cells of the body that could possibly gain protection from these pathways? Well, lungs for one, but just even in plasma cells, I mean, I think it's pretty, NRF2 is pretty

Starting point is 00:31:01 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, I was like 24, 24, 34% lower in human blood cells after broccoli, broccoli sprout powder supplementation.

Starting point is 00:31:25 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. You can relate to the video, yeah. But it was kind of an old video, it was 2016. But I also had jet 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 it does have something to do with the oxidative stress and the glutathione,

Starting point is 00:31:55 which would be relevant for TBI treatment. It hasn't been shown empirically that that helps with treatment. But as you 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 is any impact, and there is at least one preliminary study that glutathione is increased in the brain after humans are, you know, basically taking sulfuraphane. So- Which is really, for people listening, that's so important, because a number of compounds that people take in sub-platform Don't cross the blood-brain barrier or they get metabolizing ways that what's listed on the bottle almost becomes irrelevant for what your cells actually experience

Starting point is 00:32:33 So that's very reassuring We will get back to heat and cold in this theme that I tried to serve as bi just fine It's 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 hopefully also some human studies. We've talked about a few. I know you've talked a lot about omega-3 fatty acids.

Starting point is 00:33:02 So if you had to do your top three, your superstars of nutrients for the brain and body, sounds like we've got one set. What would you put alongside them? Omega-3, the marine omega-3 fatty acids. So these are found in marine types of animals, fish, cold water fish, fatty fish. So there's three fatty acids.

Starting point is 00:33:26 There's one from a plant, and that's often referred to as ALA. People call it short, afolinolate acid. And then there's a co sapentinoic acid or EPA and doca hexanoic acid, which is DHA. Yeah. But EPA. Two of the most difficult words to pronounce right next to 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 have a spell ophthalmology, a little secret. There's an extra P in there. So the ALA,

Starting point is 00:33:57 I'm not going to attempt to pronounce it because your pronunciation was perfect of both of these two compounds. And you said there are marine sources. So fish, so sardines caught 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.

Starting point is 00:34:24 Do you have a shellfish allergy? 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. Yeah, we can talk about sources. So, um, krill is a, um, a source mostly of a type of DHA and EPA

Starting point is 00:34:42 that's in phospholipid form. So it's a phosphatidal colon omega-3 fatty acid. And that's different than 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 eatin' krill, like we're talking about the food. Oh, I would never eat krill.

Starting point is 00:35:00 Okay, are we talking about the supplements? Okay, so fish oil supplements. Yes, I apologize. Krill supplement versus fish oil supplement. And if you, if it fits in the conversation, talking about great sources of omega-3s in their whole form, I have a bad feeling you're gonna tell me Sardines. Sardines are, yeah, they're awesome.

Starting point is 00:35:20 Anyways, except for the taste. And for the potential contaminants, Mercury, I think, was, no. Show was, yeah, it was Mercury. And Joe was telling me about like he used to eat Sardines every day. Joe Rogan was telling me that he used to eat Sardines every day.

Starting point is 00:35:36 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, groups. So 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, consumer lab, there's, it's like a third party site that I'm not affiliated with, but I'll use them because they, they do a lot of analysis of different foods

Starting point is 00:36:06 and supplements, and so you can look at like some of their sardines and they have like they have a list of like ones that are pretty decent. But anyways, back to your question about fish oil supplements, for sure it's krill oil supplements. So one of the major differences is that fish oil supplements. If you get a high quality one, it's in a triglyceride

Starting point is 00:36:25 form. So you've got like a glycerol backbone with three fatty acids and that's attached. And those are either DHA or the EPA. And or if you have a lower quality fish oil supplement, then you have what's called ethylester form. And typically 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,

Starting point is 00:36:52 and then it's just kind of easier to leave it like that than like re-stairifying it, which costs more money. So you can get it in ethylester form, which isn't as bioavailable. And in fact, if you don't take it with food, you're gonna be in trouble, you're not gonna absorb much of it at all. Would you see this on the packaging?

Starting point is 00:37:10 Is it gonna say it's in this Ethel form? Some official brands will put it on their website, perhaps on their packaging, but most of the time, 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 market it like triglyceride form. And it's not that ethyl ester is bad.

Starting point is 00:37:30 It just means take it with food. So one of the major prescription omega-3s out there is both of them, actually, LaVaza, which is a mixture of DHA and EPA, as well as Vesipa, which is a highly purified EPA. These are both prescribed by physicians to patients with hyper-traglissaridemia, so high triglycerides, among other things,

Starting point is 00:37:51 I think maybe dysregulation of lipids as well. This is amazing. So these are prescription drugs that are essentially very high potency purified omega-3s, but they're given to people for lipid issues. So this is the treatment of issues with fat metabolism by giving people fat. Just to really, I just want to push home.

Starting point is 00:38:11 Again, I'm not carnivore keto or anything. I'm an omnivore, 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 their, you know, fats are not just one thing, there are many things. So anyway, I just want to put a little highlighter and a point of appreciation there and make

Starting point is 00:38:42 sure that people 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-3s. 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, you know, or I have a friend with high triglycerides. No, it's illegal folks don't share prescription drugs But 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, what's the dosage that you recommend people get?

Starting point is 00:39:17 So one way or another all right, okay, so the the dosage that physicians prescribed for high triglycerides for example is Okay, so the dosage that physicians prescribed for high triglycerides, for example, is four grams a day. Four grams of EPA? Of, yes, of the Vesipa. I think Lavazas also prescribed at four grams a day. And you can get either those from your physician. My father-in-law just got one of them describing us. He was, we were buying our own omega-3 for years and years. It's like, hey, you can actually get this and health insurance can cover it.

Starting point is 00:39:47 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. Anyways, so normally I ask about mechanism and then I talk about protocols, but in the or the why or the why, but we haven't gotten there yet. 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 just raising the importance of omega-3s, and then we'll definitely get to the Y in the underlying mechanism. Yeah. I think four grams is, I mean, and in fact, like, you know, Bill Harris,

Starting point is 00:40:19 Dr. Bill Harris is just one of the pioneers on Omega-3 fatty acid research. She was on her podcast last August. And he was saying that reason FDA chose that was literally just because how much they could get people to take. 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 just purely like cost and 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. I'm smiling because our good friend, Souching Panda at the Saul

Starting point is 00:40:56 Institute, who's done a lot of important work on intermittent fasting and other incredible work on circadian rhythms, et cetera. When I was talking to him in preparation for an episode on Intermin 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, 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.

Starting point is 00:41:26 It was eight hours of feeding window plus some measurements, time to walk into the lab, park the car, etc. The eight hour feeding window that everyone holds so wholly was actually just born out of this relationship between these two graduate students. Had they been single, I was single all through graduate school or most of it anyway, and I lived in the lab. If it be me, we'd all be intermittent fasting would mean eating 14 hours a day. That was a joke, not a good one, but just want to make clear I'm joking.

Starting point is 00:41:52 But the point that you're making is a really good one, that the 4 gram amount is not a threshold based on anything except the threshold of people's willingness to actually take the stop. 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, you know, 150 minutes of cardio, and it's really a question of what you can reasonably do in a study. So I take four grams a day.

Starting point is 00:42:19 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. You split them. I do. I don't know if, I don't think it's necessary, not necessarily.

Starting point is 00:42:32 I just happen to buy, I happen to get a certain fish oil supplement that separates them. And so, like, Lavazza, Lavazza's a great one, and it's all like in one, and it's easier. What if someone doesn't have a prescription? So I take over the counter, fish oil.

Starting point is 00:42:46 I know I feel better, because I've done the experiment of going on and off. I take that mainly for, I don't have depression, but my mood is better, my joints feel better, I just feel better. And I like to think that my platelets are slippery and they're cruising through any little obstructions in my veins or arteries.

Starting point is 00:43:05 That's the image I have in my head, but I don't have any data to support that part. Yeah, I mean, so if you're asking for like, where do people get these? Well, let's say I look at the bottle and it says, two grams per serving, but then I look and it's 750 milligrams of EPA, right? Or a thousand milligrams of EPA. Let's Or a thousand milligrams of EPA.

Starting point is 00:43:26 Let's say half of it is EPA. Then do I want to hit a threshold of EPA or a threshold of what's listed on the bottle, right? 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? I think two grams is a good threshold. Now, the international fish oil standards,

Starting point is 00:43:52 IFSO, they have a website where they do third-party testing of 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, doxins, 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 well in the refrigerator because it's colder.

Starting point is 00:44:35 Yeah, they're extremely prone. Mine's in the cupboards, and now I know. The shelf life's increased lower oxidation. It makes perfect sense. Right. So anyways, they measure that. And I typically like to look for, they give you a total oxidation number. It's called toe toe toe toe, no, T O T O X toe toe,

Starting point is 00:44:54 toe tox is what we call it for short. And I like it to be at the least under 10 ideally under six. 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.

Starting point is 00:45:22 They do have up to like 20, 27 or something. 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.

Starting point is 00:45:43 No, I'm glad you did the work. I'm going to put a tweet every week, Oh, no. 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. And I chose five brands from each,

Starting point is 00:45:59 and I tried to find one in like Europe and one in Canada, so there's a great selection of them. No, thank you for doing that work. I don't want to do that like Europe and one in Canada. So there's a great selection of them. No, thank you. You and other. I don't want to do that work. And I trust you. So yeah, I try and get two grams per day of EPA from supplementation. I'll now put it in the refrigerator.

Starting point is 00:46:14 Moot 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 SSRI, serotonin selective serotonin re-uptake 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 reader 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 that are SSRIs

Starting point is 00:46:50 completely or avoid going on antidepressant medication. Now, of course, this is not something people should cowboy mental health issues are serious, but what other reasons, I'd love your thoughts on that, on 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 in the rest of our body? So do you know, so I actually published a paper back in 2015 about the role of Omega-3 and vitamin D

Starting point is 00:47:20 in depression by polar disorder, bipolar disorder schizophrenia and post-alcoholic behavior. But, so, like, within that paper, like, doing background research, and this was a review article, by the way, I was just connecting dots, because that was... No, I'm going to grab that. But... I confess I don't know the paper, but I love quality reviews, because the references they're

Starting point is 00:47:41 in are so useful. Well, there's a huge role for inflammation, the cause of inflammation and depression. And I think we did a short animated video on this as well, like here to go back when I was publishing that work, where people are injected with lipopolar saccharide. I mean, this is something that we're generating

Starting point is 00:48:01 from our gut, mostly from our gut permeability, which happens a lot. Endotoxin, it's also called, it's endotoxin lipopolysaccharide. It's basically the outer membrane of bacterial cells when bacteria die. So when the immune cells in our gut come into contact with the bacteria because we drink alcohol five days in a row or whatever, we release endotoxin or something stressed us out. We release endotoxin into our body and that causes inflammation. 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

Starting point is 00:48:40 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 control because obviously it's hugely important for depression. It emulated the depressive symptoms of the cause by lipopolysaccharide. Amazing. And LPS, lipopolysaccharide, is no joke.

Starting point is 00:49:02 I, years ago when I was working on thermal regulation, we would inject animals with LPS to induce fever. There's the vagus nerve registers the presidents of LPS signals to these particular hypothelamic areas and cranks up body temperature, because basically it's a signal that the body is infected. Amazing. So I will continue with my two grams per day. Maybe I'll

Starting point is 00:49:28 ramp it up to four. I'm not doing the DHA separately. There is DHA in the same supplement. Is that okay? Yes, yeah, yeah. And you know, to kind of, boy, we have, we got a lot of things to hit back on because you're, one of your original questions was krill oil versus fish oil and DHA. DHA specifically is it's you know in fossil lipid form it's more bioavailable so our 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, or in your plasma cell, in your plasma, with krill oil.

Starting point is 00:50:11 However, krill oil supplements are so low dose, like I mean, good luck getting two grams of omega-3 from krill oil. And also krill oil supplements are notoriously rancid. I don't know for whatever reason. Maybe that's what made me itchy all over. I think there's just, like I haven't found a good krill oil supplement.

Starting point is 00:50:34 I pretty much stay away from it. I mean, if you smell it too, I mean, it just like, like it just smells rancid. So, but the thing is, and I also published a paper on this back in 2019 or something like that, about DHA and phospholipid form getting into the brain through a different mechanism than DHA in triglyceride form.

Starting point is 00:50:59 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 4 allele. So I kind of- With an Alzheimer's susceptible. Right, so like 25% of the population has an allele and a gene called APOE 4. And basically it is APOE, but the 4 is referred to as the bad kind of version of it. This is something in our bodies. It's also in our brain.

Starting point is 00:51:26 And if people have one of these versions, if they got one from their mom or their dad, they have a two-fold increased risk for Alzheimer's disease if they get two, which is much more, it's less common. I think it's like 2% in the population, so he has two alleles. But they have like a 10 or 11-fold increased risk

Starting point is 00:51:42 of Alzheimer's disease. So there is a role for phospholipid form, a DHA in the brain, but you also make phospholipid DHA inside your body. And you can do that by taking in more triglyceride forms. So two grams are more, is the magic number, I think. So, so kind of back to like the, the Y for fish oil and I personally think it is one of the most powerful anti-inflammatory things, dietary lifestyle, things that we can we can get easily, relatively easily,

Starting point is 00:52:17 that 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 types of studies kind of led me to that conclusion. 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-3 index. So this is actually the omega-3 level in red blood cells. So red blood cells turn over about every 120 days. So it's a long-term marker of omega-3 status.

Starting point is 00:52:50 This is very different from 99.9% of any study you see or any lab that you go to to get your omega-3 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 days before? Oh, I had fish. My omega-3 levels are great, but did you eat fish like that every week? 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 HBA-1C, which is like a long-term marker, right, of your blood glucose levels. So, the omega-3 index, he's done a variety of studies, observational studies, so for people listening, these are studies

Starting point is 00:53:35 that are obviously flawed because they're not establishing causality. They're, you know, you're looking at people's lifestyles, but in the case of Bill Harris's work, he's measuring something. So, he's measuring omega-3 index, and he's measuring omega-3 index in people and then looking at their mortality risk, for example, or their cardiovascular disease risk. 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%.

Starting point is 00:54:12 Big difference there. And they also have about a five-year increased life expectancy compared to people in the US. Do you think that's mainly due to their fish intake, seafood intake? So what he showed was, I think it's a big part of it. I mean, you can't 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 looked at the omega-3 index and people that had a omega-3 index of 4% or lower, so close to what this standard American is, but a little bit lower.

Starting point is 00:54:44 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 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 we stratified it, right?

Starting point is 00:55:03 And he found smokers that had no omega-3 were like the worst of all. I mean, it was like, it was just like a worse, right? We all know smoking is bad for us and we'll take years off our life expectancy. But smokers that had the high level, like smokers that were taken their fish oil or eating fish or whatever 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. Right? Wow. And that's amazing. And it's also amazing to me that people still smoke cigarettes,

Starting point is 00:55:35 but I see a lot of people evaping. And I know a lot of people consume cannabis, right? People, a lot. There have been any studies of specifically evaping or people smoking marijuana and All-cause mortality and I haven't seen those. I haven't seen those 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

Starting point is 00:56:05 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. The Omega-3s are, I mean, they are resolving inflammation, they're like, blunting inflammation. They're doing so many different, like, they affect so many different parts

Starting point is 00:56:40 of the inflammatory pathway, which is, I think it plays a huge role 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 amazing, but it's not, you know. I love fish oil. I feel better when I take it. I try to eat some fatty fish a couple 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-3s?

Starting point is 00:57:08 And second, I have some friends who are really into meat, and I like meat a lot. Dad's Argentine, but I don't eat very much of it. I try to eat high quality meats in relatively limited amounts, but I do eat pretty often. But I've been told by these sources of a questionable authority that if an animal grazes on really good grasses, for instance, that the meat can contain a lot of omega-3s, which in principle makes sense based on this omega-3 index, because you're telling me that a lot of this omega-3 is sequestered into the red blood cells. So if I'm eating high-quality grass-fed meat and the grasses had omega-3s, do my steaks have omega-3s or no?

Starting point is 00:57:51 So there was a study published that compared conventional meat, so meat that is, that animals are fed in a corn or soy or whatever it is. Which is terrible. Yeah. But for animals and people, as far as I can tell, I'm sure I'll get some attacks, but that's okay. I won't read those comments. Again, a joke, I read all the comments,

Starting point is 00:58:14 but it seems to me that these animals have to get either be taking fish oil or eat plants that are very rich in omega-3s in order for the meat to actually contain sufficient omega-3s. So the meat comparing the conventional meat to the grass-fed, or going to pasture-raised cows, or cattle, there were higher levels of alpha, linoleic acid. And ALA is, it can be converted into EPA and DHA.

Starting point is 00:58:46 But the conversion is very inefficient and very dependent on a variety of factors, including genetics, huge regulator. Like some people can do it much better. Others, like you're getting like 5% of conversion to EPA. Estrogen is a major regulator of making that more efficient others, like you're getting like 5% of conversion to EPA. Estrogen is a major regulator of making that more efficient and it makes sense because pregnancy when your estrogen just goes through the roof.

Starting point is 00:59:14 I mean, these omega-3 fatty acids play a very important role in brain development. So your, you know, women are supposed to be converting any ALA they can into the longer chain omega-3 fatty acids, right? So estrogen does affect that, but I would say plant sources, so if you're looking for the ALA, plant sources would be wallnuts, flaxseeds, those are probably the highest. But 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, they do make the DHA. And so that would be a better source for people that are vegetarian and vegan rather than

Starting point is 01:00:01 doing the flaxseed oil because that conversion inefficiency, you know, the enzymes that convert ALA into EPA and DHA. Again, there's it's inefficient. And then for people that eat fish, um, sardines, you said, um, salmon, and you have to eat the skin as I understand. I, you don't have to, but it's good. It's rich with, with the oil. Yeah, and, and the reason I say like, like, I, I, I think the best would be wild Alaskan salmon versus the farm rays because the farm rays, again, they're feeding them corn. They're feeding them like green and stuff. Really?

Starting point is 01:00:36 And then they give them astazanthin. So astazanthin is a carotenoid. It's the carotenoid that's in things like krillacrystations that make their red pigment. 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 role of the vitamin A pathway

Starting point is 01:00:55 and photo receptors. Yeah, well, you know, actually the crottenoids themselves, so like ludonies, azanth, and they're really good at sequestering singlet oxygen, which is some damaging, right? Yeah, as we age, because the retinal cells, the cells of the iris, so metabolically active, they accumulate a lot of reactive oxygen species

Starting point is 01:01:15 and mitochondrial repair and limiting reactive oxygen species is a major theme of trying to rescue vision. I think so. That's a whole other podcast in story. There's some really interesting data now on the use of red light to try and trigger these pathways. From Glen, that's my good friend of many years and amazing scientist Glen Jeffries Labata,

Starting point is 01:01:35 University College London, I'm, we should talk about that at some point. I thought that study, like 2020, was it? I think like, oh, do they, they've been on a track. Yeah, it's looking real. I mean, you know, they're cautious They've done a test. Yeah, it's looking real. I mean, you know, they're cautious. They're appropriately British and cautious about it.

Starting point is 01:01:49 You know, I always joke if those studies have been done over here, everyone had already know about it. Glenn is a very conservative guy, but they've done this stuff now in pigs and rodent models and now also two studies in humans. It's looking pretty, pretty interesting. So Sardines, but also anchovies. By the way, I hate all the food items that I'm describing. I can barely tolerate salmon.

Starting point is 01:02:11 I don't like fish at all. I like live fish. The fish well, fish tanks when I was a kid. I just don't know. I find fish, unless it's in sushi form, I find it absolutely repulsive. And I don't know why I probably have some mutation. So raw fish is actually higher in mercury than cooked. Okay, well that's good. I don't really like sushi that much anyway.

Starting point is 01:02:28 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 best. I eat certain my like every day my like first meal almost is like I can't assert beans and an avocado with like Avocado is good. Yeah, with a little bit of lemon and then some little hot sauce. Like, you know, this avocado omega threes. Avocado is very good in monoinsaturated fat. It's normally high in polyinsaturated fat. Omega three really, I mean, it's either the DHA and EPA

Starting point is 01:02:58 that's in the marine sources fish or it's the plant ALA source, which is like the flax seed or the walnuts. So it's the plant ALA source, which is like the flax seed or the walnuts. So it's rough. I mean, all these companies now are making these plant-based products that taste like meat. My wish is that they would just make a fish that tastes like a steak. But that's... The fish come out albino, the ones that they farm raised because they don't eat any of the... I'm joking. I don't want a genetically modified fish

Starting point is 01:03:25 that tastes like a steak. You know, I love the taste of steak. The point here is that if one doesn't see themselves regularly consuming these fish sources of omega-3s, it seems to me that the only way to really get them is from supplementation. And supplementation is a good way to get a high dose and to get back to your dose point. There was a couple of studies that basically, I think there was some way they showed that people

Starting point is 01:03:57 that are in the 4% omega-3 index range in order to get to the 8%, the five-year increased life expectancy for comparing the two groups was to supplement with at least two grams, it was about two grams a day. 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-3 index.

Starting point is 01:04:24 And to get to the 8 percent. And I think that's a good empirical way of thinking about it, right? Okay, well, I want to get to that 8 percent. By the way, I'm almost 16 percent omega-3 index. Yeah, I was going to ask about testing. So where can somebody measure, where and how can somebody measure their omega-3 index?

Starting point is 01:04:42 Which again, just to remind people, is essentially the percentage of omega-3s 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. No. No, the omega-3 index. Okay, so the omega-3-

Starting point is 01:04:58 I thought you said in red blood cells, if I ate salmon two days ago, my omega-3 index is gonna go up. No, that was plasma. I misunderstood. Okay. So most people are measuring, like if you look at a lot of studies, Sam and two days ago, my omega-3 index is going to go up. No, that was plasma. I misunderstood. That's the point. 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

Starting point is 01:05:15 omega-3 levels. Okay. The phospholipids, it's in a phospholipid, right? So your phospholipids are carrying thing, 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 going to do a baseline test, if you want to know before supplementing what

Starting point is 01:05:38 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 is called Omega Quant. And they measure the Omega 3 Index. They have a variety of different index tests. You can do like a basic one or a little more advanced. It's from a blood draw. It's a little blood spot thing.

Starting point is 01:06:07 Yeah. And he uses money to funnel back into doing lipid research. Like he's out there doing all sorts of interesting studies on omega-3. It's great. But the omega-3 index is great. I think that honestly, more people and more researchers should be using it because the conflicting data, it

Starting point is 01:06:26 always comes down to what we're measuring, the sensitivity of it. Are we even measuring anything? So you're giving someone 500 milligrams 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? There's all sorts of problems with randomized control trials, and I think that we need to, like, as scientists, we need to come together and, like, make some progress. I mean, you know, let's all talk to each other. Let's figure things out. Like, this test is out there. It should be used. It should be used, not just by Bill's group, but, like, everyone.

Starting point is 01:07:02 Yeah. Well, and I'm learning so much from you, 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 in mega three index is going to be best.

Starting point is 01:07:31 You mentioned you, so basically when now I look at you, I think you are 16% omega three. And dolphins are 19%. I'm almost down. Is that your goal? You're trying to get there. It is. To do the interesting.

Starting point is 01:07:43 Actually, they should probably do something where you're trying to achieve the omega-3 ratio of your favorite species. Now that we've covered a bit of how to get these things into one 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

Starting point is 01:08:11 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 more transmitter, like serotonin and dopamine? it through the synthesis of membrane on neurons that allows neurons to release more transmitter like serotonin and dopamine. I mean, what are some of the purported, reported, and known mechanisms? I think some of the most well-known mechanisms do have to do with the omega-3 fatty acids being

Starting point is 01:08:39 very powerful regulators of 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 resolve ends help do that.

Starting point is 01:09:07 And so resolve ends are one. And then there's these specialized, um, promediating molecules, the SPMs that also help resolve the inflammation. Um, there's, like you mentioned, the leukotreans and prostate landings 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. And so there's just, and there's, I think there's just so many different ways

Starting point is 01:09:33 and inputs. And so when we talk about inflammation, honestly, that's a big general term, but you're talking about, when you're talking about serotonin release, at the level of neurons, we know that these inflammatory molecules cross the blood brain barrier. And I just mentioned ago about injecting people

Starting point is 01:09:49 with lipopryllic saccharide and causing depressive symptoms. It's known 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 resolvings and stuff. 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?

Starting point is 01:10:20 That's one mechanism. And then another would be, well, DHA itself has been shown. 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 ourselves, including neurons, are affected by the membrane fluidity,

Starting point is 01:10:43 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, they're affected because the structure of them is affected through the fluidity of the membrane. And so I think that's another mechanism.

Starting point is 01:11:06 And I'm talking sort of general, because I'm not a neuroscientist. No, but it makes perfect sense. I mean, we know, for instance, neuroplasticity, and 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,

Starting point is 01:11:26 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 the neurons are basically fat, not just the myelin that people have heard of, but the actual membranes that, if getting that right,

Starting point is 01:11:44 you wouldn't want it as rigid as concrete, but you wouldn't want it as soft as, maybe come up with something here. It's like gooey stuff that kids play with. It's like that goo, anyway. Oh, yeah. Yeah. It's disgusting and it's too soft to be a membrane for a neuron.

Starting point is 01:11:58 That's what that's all we know. Get in those machines. 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. It's about. It's about. Yeah. And in mentioning DHA, I'm just going to 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 our food sources of DHA that you find particularly attractive either by taste or by potency for DHA?

Starting point is 01:12:31 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? Well, the fish is packaging the DHA and EPA in the ratio. Okay. But I also do eat salmon row, which is very salty,

Starting point is 01:12:53 and it's a really high source of the phosphatile colonine DHA that we talked about. So this is fish eggs. It is. Yeah, and actually, it is. That I like for some reason. Of do you? Yeah, I'll eat, so I'm discovering something about myself. It is. Yeah. And actually, it is. That I like for some reason. Oh, do you?

Starting point is 01:13:05 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. Okay, well. Okay, so fish eggs are okay, so caviar based. Caviar, yes. And that's a good source of the phospholipid form.

Starting point is 01:13:23 And I was consuming that a lot because I wanted to get the phospholipid form. 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... Make sense based on fetal development. So do I need to, in, by Beluga caviar, stuff can get pretty expensive at $200 a day.

Starting point is 01:13:52 I don't think you need to. Okay. I think it's a matter of preference and if you're supplementing with your two to four grams of fish oil, I mean, that you're gonna get phospholipid form anyway, cause your body's gonna make it. Okay, I mean, that you're gonna get phospholipid form anyway, because your body's gonna make it. Okay, I've seen some containers of what I assume

Starting point is 01:14:09 to be quality fish eggs that are not at the caviar level that you can find in the better grocery stores. That aren't super expensive. 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.

Starting point is 01:14:27 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, DHA, and then you mentioned there's a third category. What would you place in your third category of foods or supplement-based nutrients that our health, brain and or body health can really benefit from? 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

Starting point is 01:15:05 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. And as I understand, there's an inverse relationship with the darker, the more darker, the darker your skin is, naturally, the more vitamin D you need to consume, is that right? 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

Starting point is 01:15:32 at African Americans and compared African Americans to Caucasians with light skin, the pair of skin, and how well they could make vitamin D from sun exposure, and how long they had to be in the sun to make X amount, right? And it turns out that African-Americans with 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 of that natural sunscreen. So I think the take home there is a lot of people with a darker skin living in sub-Saharan Africa or people living in India with darker skin or in the Philippines, these equatorial

Starting point is 01:16:15 regions where there's their eutennicity darker skin because it's protection from the burning raises. In adaptation. They are in the sun war. And they're getting more vitamin D, but people that maybe move to the United States from the burning raises. In adaptation. They are in the sun war. Right. Yeah. And they're getting more vitamin D, but people that maybe move 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 their four months, for example.

Starting point is 01:16:38 Or even living in our modern day society where people just don't go outside anymore. I mean, we're inside, we're in our laptops in school, we're at work, we're in our keep-it-go, whatever. So supplementation does play a major role, not only for people with, you know, darker skin that are now tied all the time, but for everyone, 70% of the US population has inadequate vitamin D levels, 70 of the whole US. So this is everyone.

Starting point is 01:17:02 And so I think that insufficient levels defined as less than 30 nanograms per milliliter. And that's sort of defined by the the endocrine society looking looking looking at a lot of different aggregate studies and all cosmotality for example. There's been a lot of different meta analyses of all cosmotality studies where vitamin D levels are really seem to be ideal between 40 to 60 nanograms per milliliter. And so in order to get to that level, if you are not outside all the time living in Southern California where you're always outside without sunscreen on, I always wear sunscreen because I'm trying to protect my skin from so many wrinkles and stuff, right? But also skin cancer is, you know, somewhat of an issue as well. So, so basically the point is that vitamin D is steroid hormone, meaning it actually binds to a receptor and another receptor dimerizes with it, vitamin, 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.

Starting point is 01:18:14 There are specific sequences of DNA that this complex vitamin D bound with the vitamin D receptor goes inside and recognizes and turns on a whole host of genes, turns off a whole host of genes, turns off a whole host of genes. I mean, this is important stuff. Like, imagine 70% of the population having insufficient testosterone, right? It's a steroid hormone. Which might be headed there, but probably not. No, I think that it's names are very important.

Starting point is 01:18:40 And I think that one of the issues is that vitamin D is called vitamin D. It's not called DHA or, you know, variant blah, blah, blah. It doesn't sound like a hormone. I also, I'm glad that you're mentioning 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.

Starting point is 01:19:16 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 to 30 minutes a day three times a week, exposing a culturally acceptable yet substantial amount of their skin during that time and saw big increases in testosterone and estrogen. And this is through a correct and a sight linked pathway involving P53 that 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. The idea that sun could trigger the activation of a production of a hormone is really interesting and makes total sense.

Starting point is 01:19:54 When vitamin D gets into cells and it's binding to these VDR ease, what sorts of things are they triggering? For testosterone, we know it's going to trigger protein synthesis, muscle growth, tendons, strength, et cetera. With estrogen, it's going to be a keep your neurons going. Your joints feeling good. I always remind people that by the way, because the 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.

Starting point is 01:20:28 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? Okay, so first of all, it's regulating more than 5% of the protein encoded human genome. And this was, I say more than because when I was looking at this data really in depth back in starting in 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 big published database where someone had you know published all these genes they found VDRE's in and

Starting point is 01:21:14 Basically, I found that Triptophan hydroxylase one and Triptophan hydroxylase two was on there And so then I started looking at the sequence and I was doing some in silica work. And it turns out that the VDREs 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

Starting point is 01:21:50 barrier. So, triptophan 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 triptophan hydroxylase 2, and it's activated by vitamin D. The one in the gut is actually tryptophan hydroxylase 1. Some of my published work hypothesized that it might actually be repressed by vitamin D because it has a sequence itself. This 12 nucleotide sequence can determine, in some degree, whether it's going to be activated or turned off. I was able to look at that and think, oh, maybe this and that.

Starting point is 01:22:25 And so since then, there have been some groups that have confirmed more with In vivo and or in vitro studies, because I'm mind was all in silicone and all that stuff. But anyways, so serotonin, a really important one. But most people, I mean, this is regulating our immune cell, immune system, it's regulating our blood pressure, you know, all that, that water retention, you know, I mean bone, of course, homeostasis, 5% more than 5%. I mean, I can't tell you like so much.

Starting point is 01:22:55 I mean, and with 7, 7, 0% of the U.S. population deficient, I mean, I think that this could be the linchpin and a number of really important issues. So supplementing vitamin D3 is what I normally hear is the, I do, I think I end up taking 5,000 IUs, sometimes 10 IUs of vitamin D3 per day. Just done that for a long time and I've had my levels tested in their 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

Starting point is 01:23:28 off a little low. I had some digestive issues. This went on a long period of time. Was taking on my recommendation, 15,000 IUs of D3 and was still deficient in D3. Now takes, and I'm not suggesting anyone do this, is a special case perhaps, but no chronic illness that we're aware of, needs to take 30,000 IUs per day in order to bring their D3 range just into normal, which is to me it's striking because they eat quite well, they're a healthy weight, et cetera, but it's made a tremendous difference

Starting point is 01:24:00 in terms of their mood. Now of course, it's 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 and what is a good starting range for people to think about D3 supplementation?

Starting point is 01:24:18 And again, foods that can increase D3. 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. Does anyone still drink milk besides kids? Oh, here is that you can't find cow's milk. I mean, all the milk is that you're getting milk.

Starting point is 01:24:41 Yeah, like they're fortified in those as well. Oh, they are. Okay. Yeah, they're fortified in those as well. Oh, they are. They are. Yeah, they're fortified in. I have a hard time finding out. I'm a 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.

Starting point is 01:24:56 You think about cod liver oil, right? It has vitamin D, but it's not. You're not going to correct a deficiency 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 that converting vitamin D,

Starting point is 01:25:18 making vitamin D three in your skin. Well, that's probably what was going on here, because this person is getting up in their area. There's a lot of single nucleotide polymorphisms. We talked about apoi for previously, but there's a variety of genes that people have, very common actually. In fact, I've had many people that have done that exact same thing. So measuring your vitamin D levels before and after supplementation is the only way you're

Starting point is 01:25:43 going to figure that out, right? 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, there's a variety of SNPs that basically make that conversion inefficient. And, in fact, there have been a lot of these Mendelian randomization studies. So, these are studies where people, scientists will look at common Snips people that have these common variations of a gene that's a little more than 1% of the population

Starting point is 01:26:12 So it's not a random mutation. It's actually found in a sizeable percent of the population and then they've looked at various outcomes And a lot of times they'll look at genes that are also involved in some kind of lifestyle factor, so vitamin D and SNPs that basically make the conversion of vitamin, either vitamin deprecursure into D3 or in D3 into 25-vitamine D or into the active steroid hormone, which is 125-vitamine D. And there's a variety of different SNPs that show people. So you're not looking at vitamin D levels at all. You're looking at just the SNPs and you know if they have it, they have a low vitamin D, okay? So it's really a way of doing a beautifully randomized controlled trial with an observational study because you're not biased. Vitamin D levels are also associated with health. People that

Starting point is 01:27:01 are have higher vitamin D are either outside more, they're more physically active, or they're aware of their health and their supplementing, right? So you always have to worry about that when you're doing an observation, but ideally in a randomization, it's beautiful for that reason where you now just randomly people are randomly have these genes and it's not like there's no health status. Like if you have the SNP, like your family member was healthy and all that, you know, they were healthy and yet they. They were healthy and yet they couldn't get their D levels up. So these Mendelian randomization states have found that people that can't convert into the precursor, the 25 hydroxy vitamin D, which is usually what's

Starting point is 01:27:36 measured. It's the most stable form of vitamin D in the body. They have a higher all-cause mortality if they can't do it. So people with that don't have it have a lower all-cause mortality. 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 To me now, why did I get on this rant? Oh because you're your family member So basically they also are more likely to get multiple scrocs This is all been done with Mendelian randomization. And so it really does hammer home the importance of measuring your vitamin D levels

Starting point is 01:28:08 and being very proactive about that. I mean, you can get it done anywhere. 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 five nanograms per milliliter

Starting point is 01:28:28 So let's say you're deficient your 20 nanograms per milliliter and you want to get to 40 You're gonna need at least 4,000 I use if you are Normal don't have any of these snips that change your metabolism of vitamin D, right? Does it matter when you take it relative to sun exposure, time of day with or without food? I've seen some not so great preliminary evidence suggesting maybe time of day is important. I don't think it real.

Starting point is 01:28:56 Like I can't seem to, you know, to find anything that really suggests because like, the fur to actually be converted into the hormone, I mean, it's stored. Just sure that the steroid hormones are slow actually. Yeah, it's not like a immediate thing right. So like you know maybe we'll get some new data that's like otherwise but I just don't yeah It simplifies the problem anyway.

Starting point is 01:29:17 So for people who are going to be stubborn and not get their D3 levels test 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 I use 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 course way to approach it, but I feel fine and I'm still breathing in ambulatory. So is that reasonable, a thousand to five thousand, I use for most people will be reasonably safe. Again, we're not making

Starting point is 01:29:50 just assuming that people are going to just jump to it without the blood test. Of course, I think that if we look at the literature, the scientific literature, it is extremely hard to get hypercalcemia, which would be the major concern with really high levels of vitamin D3 supplementation. I mean, we're talking like hundreds of thousands of IU a day for a long time. So hundreds of thousands. Yes. Yes. Now, the upper tolerable intake was set by the medicine institute to be 4,000. It was just like the safe, it was kind of like one of those things where it's safe.

Starting point is 01:30:29 I personally take 5,000, I use it as well. And my levels really hover around 50 nanograms per mil and I do out, I don't put sunscreen on all the time. I do put on my face and I wear a hat, but like some of my skin is being exposed. So I do make it from the sun as well. But I'm glad you brought up the fact that you keep arms exposed if you, because in these studies that I mentioned before,

Starting point is 01:30:55 looking at sun exposure on skin and increases in other hormones to 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 are you all covered up out in the sun?

Starting point is 01:31:18 Well, that might be great for setting your circadian rhythm by way of light to through the eyes, because that's the primary mechanism for that. But it seems to me that the more of your body surface that you can safely and appropriately, please, folks, appropriately expose to the sun, the more vitamin D you're going to create, right? So laying out 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. Absolutely.

Starting point is 01:31:48 Okay. Okay. Especially if you have sunscreen on your face. I know it almost seems like trivially simple, but I'm not sure that people are used to thinking about their skin as a interface to create these hormones. Yeah. So, surface area matters. And by the way, you know, there have been studies looking at people that are deficient

Starting point is 01:32:06 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 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'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 D binds to the receptor and then it complexes with the retinoid receptor and they go into the nucleus of the complex and turn on and turn off genes.

Starting point is 01:32:52 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 will 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 somehow, some hypermorphous. Which is basically geek speak for, a gene is very, is vastly reduced in its function, number in function, number people know what I mean,

Starting point is 01:33:23 but is eliminated completely. Yeah. Right, but, uh, but isn't eliminated completely. Yeah. Right. Well, these animals, um, if you look at them, uh, after the age of four months, I mean, the mice look like, I mean, they're accelerated aging, they're wrinkle, they have no hair. I mean, they just, I mean, their lifespan, lifespan shorter, I mean, they just, they, you can 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, my life spends around like two to and a half years, but like 500 years old. Right, it went to graduate school twice. Yeah.

Starting point is 01:33:54 Actually, graduate school is a lot of fun. I like to think I age 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 or the data, it's remarkable. So, I think it's, I'm definitely going to try and get my mega-3 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, I still need to get out into the sun. Correct?

Starting point is 01:34:25 I think a lot of people don't know that, or at least I have family members that have been a little bit resistance, 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 to be honest, I'm as scared of sunscreen

Starting point is 01:34:41 as I am of melanoma. That some of the things in sunscreen are really spooky. Mainly the compound, and here I'm not scared of sunscreen as I am of melanoma. Like that some of the things in sunscreen are really spooky. Mainly the compound. And here I'm not one of these. I drink tap water. Listen folks, I have like people cringe with it. I drink tap water, I have the occasional croissant or donut. I'm not, you know, I'm 90% of the time I'm doing the right things the right way.

Starting point is 01:34:59 I think, although I'm now going to improve on them with this new knowledge, but I don't like what I see in most sunscreens because if you look at these compounds, they cross the blood brain barrier. I don't want compounds crossing the blood brain barrier. Titanium dioxide. Dioxide, some of the triclosans that are also in these cleansers. I mean, once you know a little bit about neurons, folks, you realize that 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

Starting point is 01:35:30 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 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. I've always geared towards the ones with the minerals that are like reflecting it.

Starting point is 01:36:03 It is somewhat difficult to penetrate things all the way through the skin into the bloodstream, but I don't know maybe some of these compounds get in there easily. I have seen the evidence with some of those things. Yeah, there is some of them, they go transdermal. And they get in. Okay, well, I know that there's some of them react with the sun and while they do protect from the UVA and or B, they form massive reactive oxygen species and curcinogen. I mean, it's like, the very thing you're trying to protect yourself from might actually cause.

Starting point is 01:36:34 We don't know. I mean, it's completely speculation. But there is, 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 a lot of high end ones also have, you know, it's the chemical sunscreen ones, the chemical ones.

Starting point is 01:36:51 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 get papers and they get together and they pick apart the papers. There's a strong correlation between being an early graduate student and being the most critical, because once you've actually published some papers, you realize that most studies people are doing their best within the context of what they can do.

Starting point is 01:37:11 But it'd be great to do a journal club at some point about sunscreens, because I'd love to really figure out what's in these compounds up. 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, like I said, I drink tap water, I use commercial toothpaste, whatever. But when it comes to sunscreen, it freaks me out

Starting point is 01:37:29 because some of these compounds do go transdermal 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. We're at that. We're at. But get out in the sun and get your D3 levels up. Okay, so we've, we've talked about these plant-based compounds, the omega-3s and D3, unless there's

Starting point is 01:37:50 something else that you just absolutely must throw into the mix, I'd probably will return us to the conversation that I opened up with, which was about cold and heat, which admittedly I pulled us off that path. So I want to, I take full responsibility for that. But before I do that, I just want to offer you the opportunity. Is there, is there anything that fit to supplement based, or food based compounds that you, you know, you think are especially useful for brain and everybody.

Starting point is 01:38:20 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 it's involved in everything. It is. It's involved. It's also involved in vitamin D metabolism. And in fact, 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 percent. That's a big number. Now, you know, magnesium is also involved in making ATP, the energetic currency of ourselves.

Starting point is 01:39:05 There are basically all of our cells need ATP to do anything. And 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

Starting point is 01:39:36 right now and my body ends up happening in your body, it's happening normal metabolism, it's happening, you know, every day. But we repair that damage, we have repair enzymes in our body called DNA repair enzymes. They require magnesium. Magnesium is a cofactor for them. What that means is a cofactor means enzymes need it to function properly. And so without that cofactor, they're not doing it properly.

Starting point is 01:40:00 And the way I like to think about magnesium, it's easy because people call what food should I eat, right? Naturally, that's an 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. That's one of the, and basically, what is the 40% insufficiency in the U.S. 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. Standard American diet isn't really high in darkly-fee greens. So, so darkly-fee greens are how I like to get my magnesium.

Starting point is 01:40:34 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 silver or fame, right? As with broccoli, do I need to eat the dark leafy greens raw? 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?

Starting point is 01:41:02 It's obviously, I'm not- And the time looting and de-sammering. I'm gonna try a chromat, meaning I'm not, I'm not colorblind, but I, but I just want to make sure it falls under the strict category. Yes. Because everyone's in a while, I'm like, oh, I eat my vegetables. I like avocados and people worry about my non-cosmonaut vegetable. Okay.

Starting point is 01:41:14 I love vegetables, also, also. But so, Kale, what are some other examples? Kale spinach, charred, like Swiss charred, rainbow charred, um, romaine lettuce. I mean, is the bitterness and important component to this? Is it everything? For magnesium, no, but for sulfurophane, sulfurophane for cruciferous vegetables,

Starting point is 01:41:31 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, you get dreamt it. Like, yeah, you know, I personally don't worry about it.

Starting point is 01:42:05 I just don't worry. I think like, if you don't worry, I'm not going to. But I also like, I too supplement with magnesium. I do take around a, so supplementation with magnesium. I mean, this, we could go on and on. Let's keep this the shortens week because we're going to 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.

Starting point is 01:42:27 That way it's not a huge bolus to my gut. I think it depends on the form of magnesium too. Yes, you can take magnesium 3 and 8 for example, and it doesn't affect the gut as much. Magnesium citrate. Citrate is what I think. Yeah, it is a pretty, pretty potent gut stimulus.

Starting point is 01:42:48 I mean, I feel like it's a little bit harder to man. Well, I take 135 milligrams should be pretty good. And citrate actually, oh boy, do we want to go here? Sure. I mean, it's up to you and we can, we don't have to. I personally, I've been supplementing with magnesium

Starting point is 01:43:02 for a long time. Yeah. I use three and eight and bisclycinate and mallate for different reasons. So I, yes, I would love to go there if you were willing to. I would say mallate would be the best. And that, that has to do with the short chain at fatty acids being good for the gut and a lot of work done by a former colleague of mine and good friend Mark Schickenaga showing that the short-chain fatty at citrate, malate lactate,

Starting point is 01:43:27 but specifically malate really in lactate are the major ones that get into the gut epithelial cells and are energy source for the mitochondria and the goblet cells. So anyways, whole other... That's okay. I take malate because I was told that it would be helpful. I get first of all It doesn't make me sleepy like some of the other forms of magnesium which are act as a mild sedative for me

Starting point is 01:43:52 They do tap into the GABA or chick pathway neuro transmitter folks that in general Brought sweeping generalization here can have somewhat of a of a sedative quality Which is why I take magnesium 3 and 8 and or bisclice and 8 before sleep, 30 or 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 3 and 8 can be neuroprotective, although those are still, those studies are still ongoing.

Starting point is 01:44:23 I'm getting a sense that maybe you're a little more skeptical of that than I am. Yeah, I know, I've seen the studies with a three and eight. I think 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

Starting point is 01:44:42 their sample size was too small. Right. Yeah, I'm thinking, that paired with the, there's some work. Yeah, the song, the song, the song, so in that this is getting kind of

Starting point is 01:44:52 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, it goes on, and some of the other folks

Starting point is 01:45:02 with at that time in MIT, that I think very highly of their work. And 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 for me, I figured that given the safety profile of Mac3 and 8, given that it helps

Starting point is 01:45:24 me sleep better and sleeping better is just better for everything. Frankly, that's why I take it. And biscliscinated and 3 and 8 seem to be somewhat interchangeable. But I don't know of any reports that biscliscinate can be neuroprotective. But malate, I take it during the daytime, for me, again, this is subjective. It has a tangible effect in improving the recovery time from exercise.

Starting point is 01:45:47 So I don't know that I've been sore from a workout since I started taking Mally, 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. Mally, again, the short-chain fatty acid. And I mean, when you do intense exercise, you release endotoxin from your gut.

Starting point is 01:46:08 I'm just going back to the interesting work because the malay being the short-chain fatty acid and Mark Schringenagger showing this is all an animal research, by the way. But I mean, it was like feeding these animals malay. I mean, it really protected the gut, endotoxid release, and it affected metabolic syndrome and all sorts of things. But I think Malay, Malay, it's awesome.

Starting point is 01:46:27 And I always try to eat green apples. They're really high in malac acid. Oh, good to know. And tart cherries, tart cherries are really high in it as well. It also tastes really good. But I was really interested in the magnesium three and eight stuff. I take a supplement called magnesium by Moonjuice, and it's like a little powder. It's got a little bit of

Starting point is 01:46:45 monk fruit but it tastes good so 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 as flu is before I go to bed and it has magnesium 3 and 8 and a variety of other versions of magnesium in it as well and I really like it but I thought the magnesium 3 and 8 stuff was super interesting I you I would love to see more clinical data as well, but I think once we get it, it'll probably be like, oh yeah, it's getting into the brain and it's awesome.

Starting point is 01:47:10 So, you know, why wait? Right, I, along those lines, I once put out a post that said, you know, 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 that 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, randomized clinical trials, etc. Then other people are just say, you know what? I don't even care about any of that. Just tell me what you do.

Starting point is 01:47:45 And then other people are say, you know what? 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 pillform or powder form, they'll take it. 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 people don't realize that people are showing up to the table in one or some combination of those

Starting point is 01:48:05 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 top. 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. 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.

Starting point is 01:48:39 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 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 a, I'm the worst combination of, 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 who

Starting point is 01:49:09 used sleep deprivation for that. But I could imagine that we also evolved having some sleepless nights. So this idea of intermittent challenges is a really attractive one and I want to make sure that we credit you with the phrase intermittent challenge. No, no. Dr. Mark Matzen. Okay, Dr. Mark Matzen gets published and he has used that phrase. Okay, great, we'll make sure. Just like Dr. Dr. Mark Matzen. Okay, Dr. Mark Matzen gets published and he has used those words. Yes. Okay, great. We'll make just like Dr. David Sinclair. I love the Xenoharmesis. He was in like one of his publications. Just so many years ago. I just love it. It's brilliant, brilliant term. So Mark Matzen gets a lot of work. That's hard for guys. They're pretty smart. You know, I mean, it's a good school, I guess. Of course, it's a good school.

Starting point is 01:49:44 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.

Starting point is 01:50:04 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 4 degree. 49 degree Fahrenheit. 49 degree Fahrenheit, okay, I was translating this, I'll say about 49 degree Fahrenheit water, so cold water can lead to long lasting increases in epinephrine adrenaline. And I have to presume other neuromodulators

Starting point is 01:50:31 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 we used back to metabolism. We could do an entire episode all about coal, but what I'd love to know is, what sort of

Starting point is 01:50:57 activity or stimulus do you think is a reasonable and particularly potent one to use in terms of coal? you think is a reasonable and particularly potent one to use in terms of cold. So today I did three minutes at 49 degrees Fahrenheit. I have a cold tub. So you get in up to your neck? Well I try to keep floating up. And so I'm like, it's like really hard. So the like 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, I'm floating up, I was telling my husband, there's too much water in here for me, I can't.

Starting point is 01:51:27 Or too much salt in there, is it like the Dead Sea, where you float on top? Is there salt in there? I don't know, he takes care of all the stuff that, it's the plunge. Yeah, 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, which makes sure that you break up the thermal air and it's even colder. It is even colder. It sucks. Anyways, so look, I'll give it a be honest here. I wish I did more cold than I do. I do cold when I'm going to go on a podcast. I definitely do cold when I'm going

Starting point is 01:51:59 to do a podcast, when I'm going to give a talk or when I'm anxious. I need to make it more of a ritual. I love doing this on, I hate the cold, I hate it. Unless it's summertime, it's a lot easier for me to get in the cool in the summertime. But what I do love about the cold is how I feel after. And I feel less anxious, I feel good,

Starting point is 01:52:22 I feel more focused, which is why I usually do it before, any type of public speaking, or just when I'm just anxious, I'll just get in there. And so the 20 seconds at 49 degrees, I think it was 49 degrees Fahrenheit, was really a good number because time and temperature do, at time or duration, I guess it would be a better word and temperature do matter. But you can do 20 seconds at a colder temperature,

Starting point is 01:52:53 which is I prefer, or you can do a minute or longer at a warmer temperature. I think there was another study showing 59 degrees Fahrenheit at one hour. It was like two to three. But who wants to do one hour? Yeah, I'm familiar with that study. I love, so this is really, it reveals just how absolutely nerdy I am and maybe why sometimes in relationships in my life were challenged. I love reading the method sections of papers. So, you know, people can come at me with a number of things about papers and I might miss something,

Starting point is 01:53:21 surely I miss certain things like anybody is, 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 for an hour. And it wasn't real, it was chilly, it wasn't super cold. I mean, 60s is not, it's not warm, but it's not ice cold, obviously.

Starting point is 01:53:42 But an hour is ridiculous at some level. But the increases in dopamine were massive and lasted hours. So the mood enhancing effects that you report are you're not imagining that. Those are almost certainly a consequence of having slowly elevating, but significantly elevated dopamine that goes on for hours. That's almost a dream-like profile for dopamine,

Starting point is 01:54:09 because most everything else, like an Adderol, a Ritalin, a cup of coffee, and a pre-workout drink, or something, is gonna give you a big spike in adrenaline in dopamine and a big crash. And somehow, it creates this really nice contoured profile. So whatever you're experiencing there is very nicely supported by the data. and somehow it creates this really nice contoured profile. So whatever you're experiencing there is very nicely supported by the data. Well, I need to get doing it more.

Starting point is 01:54:32 I've had a couple of scary experiences going from hot to cold. Can you explain? Blood pressure changes, I think, where I basically went straight from a really hot Chakuzi. I was in there for like 30 minutes. I mean, I was doing heat jobs. Chakuzi, okay. Yeah, 104 degrees Fahrenheit. That's toasty.

Starting point is 01:54:50 And then I for 30 minutes. And then I went straight into, at the time, it was our pool, it was in like, February, it was like winter time, and it was 50, it was in the 50s. It was cold. And I was in there and I was was listening to Simon Garfunkel. I was like trying to stay in a long time, get on my cold,

Starting point is 01:55:08 and then I was trying to press Dan because he goes in there for like, he'll stay in there for like 15 minutes. But I started to feel really 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, so scared.

Starting point is 01:55:27 And so, and I've had a couple of times too where it's just going straight from the sauna to it to the cold plunge where I'm starting to feel like, I feel a little blood pressure change or something. And it makes sense. The sauna is causing vasodilation and the cold plunge is called, cold exposure is causing facial constriction until it's like a very, you know, just shocked 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

Starting point is 01:56:00 and, you know, the, the norapeneferin or noradrenaline, you know, it's affecting brain and mood, and I'm way more about that than I do. I know how I feel, and I know it's a neurotransmitter, and it is released, at least in rats they've shown, or was it mice, I think it might have been rats, but multiple studies showing in that it's released from the cold in the brain.

Starting point is 01:56:21 And now in humans as well. Oh, the brain they've shown. So in that study, we could put a link to this. It's at Publish in 2000 European Journal of Physiology. That big dopamine increase, they also looked at epinephrine and cortisol and it saw some really, yes, this has been done in human. They did brain. Oh, no, no, not plasma.

Starting point is 01:56:37 Yeah, yeah, very hard to measure dopamine directly from the brain unless you're doing micro dialysis. No, it's unfortunately, 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. It's a very real effect.

Starting point is 01:56:57 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 some of the effect. But I want to be cold-adapted because that means I have more mitochondria in my anapost tissue and perhaps even muscle like that's been shown.

Starting point is 01:57:28 So maybe it does 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 yeah, well so norup and effron actually released in the plasma does act as a hormone vasoconstriction is one thing it, 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 is trying to do

Starting point is 01:57:57 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, a way to do it is to basically have your mitochondria produce tons and tons of heat. So the way it does this is by activating a gene called UCP1 on coupling protein 1, or up and effort is upstream of that, activating it.

Starting point is 01:58:23 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 your body from your neurotransmitter production to your heart, beating, et cetera. However, you can uncouple your mitochondria.

Starting point is 01:58:47 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 part. Like a neuron. Like a neuron, yeah. So I guess it's like a neuron. It's like a battery, negative and positive.

Starting point is 01:59:08 Well, basically, you can uncouple that charge. And so that positive charge, Proton, start leaking out of the mitochondria. And your mitochondria freak out. So this is called uncoupling. 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 Prot proton back, that gradient, the electrochemical gradient.

Starting point is 01:59:29 And so they just go insane. And they, in this case, it's uncoupled energy so that energy they're making is actually heat, not ATP. But heat is, but you're essentially burning substrate, so who cares? You're burning, you're burning glucose, you're burning, you lipids, lipids, you're basically burning things and making heat. And so that's what uncoppling it does. And that is a much more efficient way of producing heat than shivering.

Starting point is 01:59:53 So as you become more adapted, maybe the longer duration that 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 uncoppling 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 that actually happens also regulated by Nora epinephrine or Nora adrenaline through

Starting point is 02:00:20 a protein called PGC1 alpha. And what that protein does is it makes more mitochondria in your adipose cell. So per adipose cell, you're getting more mitochondria. It's a beautiful way to basically make more heat when you're, it's one of those things where it's like, 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 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.

Starting point is 02:00:50 And this is often referred to as the browning of fat. And the reason for that is because if you look under a microscope at a lipid droplet, you know, basically a fat cell, not a lipid droplet at 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 I don't want to get into the whole beige fat brown. There's this whole, I'm sure you've had experts on that talk all about that. No, not yet. I mean, I always think of white fat, beige fat brown fat, and beige is kind of intermediate.

Starting point is 02:01:22 White can be converted into beige, but yeah. And beige can take on thermogenic characteristics, essentially. And so you can activate beige fat so that it's thermogenic in the sense that it's burning glucose and, or fatty acids and producing heat. So the more you expose yourself to cold, the more you can brown your fat, so to speak, and therefore you

Starting point is 02:01:47 can tolerate the cold for longer periods, which people do notice, and you can then have the thermogenic qualities of having more brown adipose tissue or beige, activated beige adipose tissue, which is, you know, you'll get a lot of naysayers out there saying, oh, brown fat doesn't regulate metabolism at all. And the reality is there's like thousands of researchers trying to build up brown fat and thermogen. Like they're trying to make it a pill because it does affect metabolism.

Starting point is 02:02:15 You know, it's not the only thing. It's certainly a fero beast and trying to lose weight. You're not gonna like do that just by doing cold exposure. You need to do dietary and exercise changes just, you know, predominantly, but it does affect metabolism. And, you know, this has been shown in human studies. So it is an interesting, it's another possible mechanism for affecting metabolism. And that's an adipose tissue, but you also make more mitochondria and muscle tissue. And this is regulated not by a Nora epinephrine, but it is still PGC1 alpha. Interestingly,

Starting point is 02:02:52 not like not that anyone else really cares about me, maybe you do. I'm eating this up. So PGC1 alpha is response to Nora epinephrine and adipose tissue to make more mitochondria, but in muscle tissue, it's unclear what the regulator is. Cold exposure does it, so this was shown at least in a couple of studies I've seen where people that were exercising, I believe, are maybe made of men, only that were exercising that some stuff were training.

Starting point is 02:03:20 And then did cold water immersion, something like 50 degrees Fahrenheit, 15 minutes. And PGC-1-1L, 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 improved muscle mass, improved endurance. I mean, mitochondria are essentially either the making energy in your cell and we don't make more mitochondria normally.

Starting point is 02:03:46 Like you have certain inputs, high intensity interval training, exercise can do it. And actually make more mitochondria. Yes, yeah, and that's been shown in people. And weight training or just high intensity interval training. I haven't seen weight training. I've seen it in high intensity interval training and endurance training.

Starting point is 02:04:04 But that doesn't mean that it hasn't been shown I just haven't seen it or that hasn't been looked at so. But you know, I'm always looking for reasons to finally do more Hit type high-intensity interval training work. I do weight training and I do low-intensity cardio There was a brilliant study by at the time he was a post-doc Matthew Robinson and At the time he was a postdoc Matthew Robinson and he's now gone on to start his own lab at the University of Oregon Health Science Center. Great place. And he did a study where both young and older people were, they had this whole high intensity protocol, which I can't remember what it was, but their protocol for X amount of time, I'm sure it was at least a month, they

Starting point is 02:04:47 then measured biomarkers of mitochondrial biogenesis in their muscle tissue. And the amount of mitochondrial biogenesis in old people specifically, it happened in both young and old from hit, 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, you're, you're, you're might account, you don't make your cell, your cells are turning over, you make new cells, you replace old ones where you're

Starting point is 02:05:14 mitochondria. 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 the way you're might, like what happens with your mitochondria is they essentially are bobbing around inside of your cells and then they fuse with other mitochondria exchange all their content and mitochondrial DNA and then fizz back apart. And that's how they kind of stay young-ish.

Starting point is 02:05:35 But as you age, you keep doing that with the same pool of mitochondria and you're gonna get a bunch of old mitochondria mixing old stuff together, right? So why wouldn't you wanna bring up new healthy 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. Other things as well. You know, I just, and police, thank you for offering to somehow filter the level detail, but I assure you

Starting point is 02:06:07 that listeners of this podcast are familiar with getting, drinking from the firehose 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 the subtle zone two that are going to inspire me to change my behaviors. I'm going to start doing some high intensity in real training. Dr. Andy Galpin was on this podcast recently, and he told me that the subtle zone to cardio

Starting point is 02:06:30 and the weight training is great, but that I really should be doing some max heart rate work per week, 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 talk about heat,

Starting point is 02:06:47 what sort of cardiovascular or other types of training do you do? Do you do hit? I imagine you are doing high-intensity interval training. If you could just give us a sense of the contour of your week as it relates to exercise and because you've been very gracious in sharing some of what you do for supplements and food, what about exercise? So it all depends on my week, of course, and what I've got going on with my son and my work schedule.

Starting point is 02:07:09 But I typically, I do a lot of high intensity interval tabatas on a stationary cycle. I use peloton because I just like that instructor there like telling me what to do and then me competing with everyone else. I'm like, yeah, you know, so it works. You were revealing something about your psychology. This is what we just learned about. So this podcast is actually just a decoy for psychological assessment of the guest.

Starting point is 02:07:31 No, I'm kidding. But so now we know you're competitive. Good. Yeah. That explains a lot of how you got through graduate school and then 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? So 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 kind of toggle on what you want and you can try to compete against it. So it's really competitive. Oh yeah.

Starting point is 02:08:03 Okay. And the instructor is just there to whip you. Like, you know, make you, there's a part of, the brilliance with Peloton is, 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 cycle and have an instructor there and you do all this high intensity interval training stuff.

Starting point is 02:08:21 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 group, right?

Starting point is 02:08:40 But there is something about that group setting that kind of make, hold to accountable too, right? And the Peloton made it somehow virtual. It was amazing. And I remember being back at Rush Cycle, this is before a 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 going to work. I need to 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 before and I do a 10 minute just 10

Starting point is 02:09:15 Because it's efficient and I push my ass like push myself really hard That's the tabata is that to 20 seconds on 10 seconds off and it's 10 minutes and on means you're peddling like your life Dependent you're maxing it and there's a lot of resistance and the 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 sitting set 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.

Starting point is 02:09:46 Like going up a hill. Yeah, exactly. And so they break it up and most of the time you'll have those two parts. And I love the efficiency of it. You just, you get it done and people sometimes hear me go, 10 minutes or really you think you work and like, look, you max, you do max, you would tovada for 10 minutes and it's intense. Yeah, most people can't sprint for the gate

Starting point is 02:10:08 of an airplane there about to miss carrying a backpack. So if you think about, if I think about that and then I just described myself, the other sprinting through the airport and going, all right, Andy Gallup, and 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

Starting point is 02:10:26 for 10 minutes. So by time you're done, you're cooked. 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. Right. Number. Right. So three times a week. Yeah, three times a week. And then I always have my sauna on pre-heating up. Takes about an hour and a a half and I get it to about 189 degrees Fahrenheit. I hop right in the sauna after my peloton. So the elevated heart rate continues? Is that the rationale? Yeah, I literally like down a bunch of water and then I get in and then I like either read a science paper, prepare for a presentation or a podcast, or I hash over things in my mind.

Starting point is 02:11:05 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. Okay, and I- You're an early adopter. I started doing it every day. I lived across the street. I lived in a studio apartment with Dan,

Starting point is 02:11:24 within the small studio part, the smallest apartment you could ever imagine. And it was across the street, I lived in a studio apartment with Dan, we lived in the small studio apartment, the smallest apartment you can ever imagine. And it was across the street from a YMCA because I was poor and very poor, very poor. I mean, so, you know, I, I recall, I recall me, I lived in my lab. Wow. But then again, I lived in my lab as a postdoc

Starting point is 02:11:40 and as 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. Yes. And so I used to go to the sauna before going into the lab. And I would start noticing that I was all of a sudden

Starting point is 02:12:01 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 advice, 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,

Starting point is 02:12:20 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? 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 opioid system. Basically, so when you get in the sauna, you release a lot of endorphins. Endorphins are the feel good opioids that make you feel good. But you also release something called dynorfen.

Starting point is 02:13:01 And dynorfen is an endogenous opioid that binds to a receptor called the capa opioid receptor, which Dinoirfen is responsible for that dysfork feeling when you're in the sun, on your hot, and when you're running, doing exercise, and you're like, you feel uncomfortable. Well, I think that's Dinoirfen speaking, absolutely. I think it is. I mean, there's evidence in alcoholics that some of the symptoms of withdrawal that the experience are related to dinorphin and dinorphin is known to negatively impact

Starting point is 02:13:33 the dopamine receptor system. So basically, it's the feel like garbage pathway. Right, you feel like garbage. And so you think that that would not be good, but this is where my friend that comes in. He was looking at the effects of like treating morphing that would not be good, but this is where my friend that comes in. He was looking at the effects of treating morphine or heroin addiction and people that are using those drugs.

Starting point is 02:13:52 They basically, the endorphins or the morphine or heroin, they bind to a receptor in the brain called the muobuoid receptor. And as they take these drugs, that muobuid receptor becomes down-regulated, and so you need more and more of the drug to feel as good as you do it, right? Well, Endorphins also bind to that receptor, and he was looking into some of the other drugs that are like salvinorium, salvinorium or salvia. It's called it binds to the capi-obio 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

Starting point is 02:14:34 either dynorphin or you know whatever ligand to the capi 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 out or whatever, you feel it for longer, right?

Starting point is 02:14:58 And so anyways, this is a, with the song, with respect to the song, 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 wish more people would look into that. That'd be amazing. But what I was getting at, I think, was, I would use the son to memorize things. This is way back in the day, and I still do it.

Starting point is 02:15:23 And I wanted to talk to you about this because you're a neuroscientist that there's something about being in the sauna. And I think, I don't know if it has to do with the stress response, when you have an emotional trigger, you remember things better, right? Absolutely. There is a clear and known explanation for mechanism for this. Yeah. So in the sauna, I mean, you also release Nora Peneffren, just like you do in the cold.

Starting point is 02:15:49 There's a lot of overlap. You know, you're really, you're, you, 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. I have a sauna and a cold punch now. 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 can.

Starting point is 02:16:05 I have a sauna and I call lunch now and I haven't tried prepare. I read books in the sauna in the evening. 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 the evening.

Starting point is 02:16:21 So I read books. The only challenge sometimes you're dripping sweat onto the books, but I'm willing to forgo a few pages of a book. The idea that being in this semi-stressful environment would aid in the learning and retention of information is really well substantiated by this. It's a beautiful work by a guy named James McGaw.

Starting point is 02:16:39 I don't know if his lab is still active, but you see your vine for a while, and then I think at University of Arizona as well. They have a great memory group at both places, very strong in learning and memory, both places. He was the one that really defined this inverted U-shaped function for the relationship between adrenaline and memory.

Starting point is 02:17:01 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 doing their panicking, basically. But obviously, you're keeping it in range. The other thing that I'd like to ask you about is in the sun, of course, there's vasodilation. And perfusion of blood to the brain is a wonderful way to enhance cognition.

Starting point is 02:17:35 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 exiles. And these are beautiful studies done in humans, of course. So I can imagine that phase of dilation, getting more perfusion of blood to the brain, plus a little bit of stress, or maybe a lot of stress

Starting point is 02:17:59 from the epinephrine. And yet, it's in, 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 conditioned place context of it. Like if we, if we had a good experience remembering something in the sauna once, we tended the positive association effect of that location is real. Just like if people go to a new city and they get robbed, like if you go to a Cincinnati, I've never been to Cincinnati.

Starting point is 02:18:21 If 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 at any number of different cities, right? The opposite is also true. So if it's something good happens someplace. So 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 address.

Starting point is 02:18:39 I think it takes you too far down that curve, the McGaw curve. I have to sing songs or something when I'm in. Distractions. Oh, yeah, I sing songs or something when I'm in. Distractions. Oh, yeah, I sing songs. But afterward, you're very efficient at learning. After I am. And with respect to the sauna, the basadialation does occur. So there's a lot of overlap between moderate intensity,

Starting point is 02:18:55 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, I think generally speaking, there's studies showing that sauna use is associated with

Starting point is 02:19:23 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 60% reduction in dementia and Alzheimer's disease risk compared to ones. I was sorry, I didn't mean to cut you off. You said, people who use it, I apologize, maybe you'd tell us again, people use it four to seven times per week have. 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.

Starting point is 02:19:51 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 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

Starting point is 02:20:19 actually this was men, if men use this on a 47 times a week, it's a 50% reduction in cardiovascular related mortality compared to one time a week. Again, dose dependent manner, two to three times a week is something like 24% lower, death from cardiovascular disease. There's also lower sudden cardiac death, it's like a heart attack. That's like 60 something greater than 60% lower.

Starting point is 02:20:42 If men use it 47 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 Lalkinin, he's in the University of Eastern Finland, and just one of the world experts on sauna use, especially with respect to cardiovascular health.

Starting point is 02:21:04 What some of his data has also shown is that, if you look at the duration, the time spent in the sauna, 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 sauna or any sort of heat stress, whether it's a hot tub or jacuzzi, you become adapted.

Starting point is 02:21:28 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. So I stay in a long time. That's a lot. You have to listen to your body. Most of the studies that I just talked about were from the duration, the time spent in the sauna when I said 50% reduction in cardiovascular disease related death. What was shown was that men that were in the sauna for only 11

Starting point is 02:21:55 minutes, even if they used it four to seven times a week, that reduction was only like 8% said 50. It had to be greater than 19 minutes. So like 20 minutes is the sweet spot. At about 174 degrees Fahrenheit. And so, and most of the sun is in Finland, by the way, they're humid, so they put hot water, they put water on hot rocks to create steam. And so it's usually between 10 to 20% humidity in the finish sauna. So those studies where I would say most of the time you're going to find that their humidity is also elevated. But to me, the the dose dependent nature of it and the duration knowing like, you know,

Starting point is 02:22:36 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, exercise, just everything, everything of 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 something's going on here. Plus, there's been studies, intervention studies, where it's like, you know, comparing directly

Starting point is 02:23:06 head-to-head, moderate intensity aerobic exercise on a stationary cycle to 20 minutes in a sauna. 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.

Starting point is 02:23:31 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 bite So you know disabled people granted there are some safety concerns. They're 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 or problem drinking alcohol never do that elderly people low prone to low blood blood pressure always talk a physician before doing this on it. It is stressful. Pregnant women.

Starting point is 02:24:08 Pregnant women. Oh, yeah, I definitely avoided sonas 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 their life. 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,

Starting point is 02:24:34 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 the Peloton. Ideally, you do both. 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

Starting point is 02:24:54 and I review in the experimental gerontology last year, I guess, late last year. And basically, cardio respiratory fitness, which is a marker of, it's a marker of health. Cardio respiratory fitness is improved in people that do exercise and sauna compared to exercise alone or sauna alone. So for those healthy, fit people out there

Starting point is 02:25:19 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 like mimicking aerobic exercise, there's the heat-check 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 Biolatial Studies doing research on little nematode worms that we are someone else injected Amaloid Beta 42, the peptide, the 42 amino acid peptide that is involved in Amaloid clacks found in the

Starting point is 02:26:00 brain, correlated with Alzheimer's disease and other 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 in your arteries and also in the brain and there's back to my my worm studies I was doing I would

Starting point is 02:26:39 I would elevate H.O.G. 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. Many animal studies have been done looking at Alzheimer's disease, a human-like Alzheimer's disease in a rodent, and H-Chach proteins protecting from it. H-Chach proteins are robustly activated in humans. This has been shown to even, you know, 50% higher over baseline levels after just 30 minutes at 163 degrees Fahrenheit in

Starting point is 02:27:12 the sauna. So, and they stay activated at least in rodents for, you know, 48 hours at least. So, you know, having these Hitchock proteins around, making sure they're properly taken care of our proteins so they're not aggregating in our brains and in our plaques, could be another potential way that Saunas is projecting from Alzheimer's disease and other cardiovascular health, as well as longevity. So there's people that have SNPs in heat shock protein factor 70 that if they have one

Starting point is 02:27:46 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 snip. And if they have two versions, if 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 snip. So it's also 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. Anyways, I guess what I was getting at was the heat shock proteins are part of that stress

Starting point is 02:28:18 response pathway that we talked about earlier. They're also activated by cold as well. Cold shock does activate heat shock proteins, not as robust, so for a free and active, activates them. Again, it's one of the reasons I think we should get all of these things because they are more robust inputs. They're input activating mechanisms

Starting point is 02:28:36 are more robust for different ones. So there is crosstalk, there is, I mean, I guess, I get, it'd be more accurate to say there's overlap, 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. I need myself, you know, my broccoli sprouts and all that stuff. So it's super interesting. A couple of questions came up for me. One is you mentioned these SNPs, these nucleotide repeats. Basically, genes that some people have, more or less of, than others that can predict longevity

Starting point is 02:29:16 in some sense. Is that the FOX-03 pathway? That's one that can. Yeah, I mean FOX-03 is, in fact, if you go back to the warm 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 receptor, they have an IGF-, like receptor, and they make something like FOXO3, which we have.

Starting point is 02:29:47 And basically, if you decrease that insulin signaling pathway, their FOXO3 is always active in those worms, and they live 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, 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

Starting point is 02:30:16 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 go into this metabolic stasis,

Starting point is 02:30:38 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? 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,

Starting point is 02:30:53 and they'll still be going. So in terms of the many data on sauna, and I also just wanna acknowledge these finish groups that did this work, it is really pioneering, right? When you think 20 years ago, along before social media or any of this, and they're up there, I should say, measuring cortisol and growth hormone and all this stuff

Starting point is 02:31:16 in people getting into ins sauna. Very, very interesting. So 20 minutes seems like the threshold at 170 degrees Fahrenheit. More times per week seems to be better than fewer when you went in terms of all caused mortality cardiovascular risk, according to what I just learned from you. Or would be a good, I think, minimum effect of dose. Four times a week. And you combine it with the cold.

Starting point is 02:31:40 I've also seen a protocol where it's a very extreme protocol. I don't recommend this to people right off the bat where they had 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, 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 kind of a unique item. So I have a couple questions.

Starting point is 02:32:18 Can people use hot baths? With the appropriate warning, of course, that without getting into a description of the mechanics and the underlying biology, it's pretty obvious that the testes, if they get too warm, 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, a re-arbiologists 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 baths. For at least six months, that's been shown. So sperm, so sperm,

Starting point is 02:32:54 motility goes down and sperm production goes down, but that is completely like corrected if they stay out of the sonnet for six months. So through six months later, it's back to normal. Great, that's very useful information. I'm sure to a number of people out there. So if people don't have access to a sauna, and we get this about cold too,

Starting point is 02:33:15 you always say, what about cold showers? And I always say, well, the studies 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 you get a bigger person, the less of them is under the shower. And It just doesn't make for a very good experiment because you get a bigger person, the less of them is under the shower, and so it doesn't make for a good experiment.

Starting point is 02:33:28 So it's not as good as immersion, but with heat, I could imagine that a hot bath would work almost as well. So there's been some studies looking at, for example, activation of heat shock proteins, also brain drive neurodegryphic factor increases with heat stress. And so the hot bath that around 104 degrees Fahrenheit,

Starting point is 02:33:47 which is typically what studies will use for temperature, which is actually cooler than when I crick my bath hot. It's so hot. But you're very heat-adapted. 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

Starting point is 02:34:03 and in brain drive nerve, perfect factor. And then heat shock proteins are also protecting against muscle atrophy. So that's also having to do with the protein structure and the muscle tissue as well. And this has been studies in 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.

Starting point is 02:34:22 I mean, it was like, there was a study where they were looking at muscle disused and it was something like the local heat treatment prevented like almost 40% of the muscle atrophy from dysused. So like, and it's funny because I used to use this on when I was injured and stuff. I would go in the sauna because I like, I didn't know at the time because I was a graduate student,

Starting point is 02:34:42 but I knew like just from experiments that like, you know, like I'm not losing as much muscle. I feel better like, you know, know at the time because I was a graduate student, but I knew just from experiments that I'm not losing as much muscle. I feel better. At the time, I was reading a lot about the growth hormone and stuff back then. I knew about heat shock proteins, so I knew that data wasn't around yet. Now, we have the data. I felt like I wasn't losing my muscle. I should have been when I was doing the song and I was doing it literally seven days a week. It was like hardcore.

Starting point is 02:35:10 This is also during graduate school. Yeah, now I'm doing I'm doing the song like a bare bare minimum I do three, but I try to do four because of that. 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 camhain, so 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, 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.

Starting point is 02:36:08 And I'm like, this is the best long-jagged, long-jabbedy drug there is. This is it right here, Ronda. You're always wondering. You're always wanting to know. You're wanting to do the best. If you don't exercise, you're missing that essential dose. And so that, for me, is the motivation. The dopamine seeking thing I'm looking for.

Starting point is 02:36:25 Admittedly, I do not do enough strength training and I have to do it, I have to have to have to, 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 fault. Well, 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

Starting point is 02:36:54 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 Kendall, 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 cycling that's really load-bearing, although your cycling really hard with the resistance, but causes the release of osteocalcin

Starting point is 02:37:36 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, a body that's active can signal to the brain that the body still needs cognition. 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 a conjecture. But we know in ocean animals that they'll swim around for some period of their life and then they'll have a completely stationary

Starting point is 02:38:17 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 you the ideas and mine 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'm a spoke, 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 and the logic behind them but also sharing what you do is really informative because I think people need a jumping off place and

Starting point is 02:39:01 obviously they need to start someplace and getting getting heat adapted, et cetera, takes time. But I really appreciate that you're willing to share your protocols and that you do the things 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 sauna's,

Starting point is 02:39:24 I've ever been in got hot enough and it was frustrating. So 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 a Nobel Prize in 1908 for photo therapy, for lupus, so it's not like a new thing,

Starting point is 02:39:42 the idea that red 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 intermediate answer. So I don't have an infrared sauna,

Starting point is 02:40:03 but 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, because it's not activating it at a specific wavelength, which is- It's usually so that the range that seems to be helpful, and I confess, I use a red light panel for other things, is 670 nanometer, out to about 720 nanometer.

Starting point is 02:40:25 670 nanometer out to about 720 nanometer. So it looks like red and very dim lights, dim red and bright red, and the ideas that red light can travel the photon and energy is such that it can travel down through the deep layers of the dermis of the skin. I, you know, 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 as, is the potential effect on mitochondria is interesting. I do think there's a lack of really good solid evidence in humans, but that might only

Starting point is 02:41:02 be because it's not studied enough. That's usually the case. So perhaps, there's the Juve, right? The Juve, they have those red light panels. Juve and Cozy are the two ones I know, K-O-Z and Juve. They're there as far as I know. I'm probably gonna insult both companies at the same time, but I'd rather insult them both at the same time

Starting point is 02:41:20 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 us. Yeah, well, I personally think that 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 there are some differences as well.

Starting point is 02:41:41 Infrared saunas, maybe the infrared saunas are the ones that have the red light that you're talking about. Infrared sonas, maybe the infrared sonas are the ones that have the red light that you're talking about. Infrared sonas only get up to around a 140 degrees Fahrenheit. So as I mentioned, the studies were about 170, 40 degrees Fahrenheit. And so you really have to stay in a longer period of time.

Starting point is 02:41:59 However, there have been some studies coming out of Japan. They use infrared sauna. They have this whole protocol. It's called way on therapy. And they get people in infrared suns and then they wrap them in a towel. And they stay warm for X amount. So the whole protocol ends up being like an hour long.

Starting point is 02:42:19 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 evidence that infrared zonas can be beneficial for cardiovascular health. I do, I've used infrared zonas many times that my in-laws, they have an infrared zona, 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.

Starting point is 02:42:50 You do sweat, some heavy metals, and some heavy metals are excreted predominantly through sweat and others through urine. So for example, cadmium, there's like 125 fold increasing cadmium excretion from sweat. When you get in the sauna also lead is something like 17 fold excretion's higher. Another one is aluminum. It's about four fold higher. So infrared, you do sweat a lot too.

Starting point is 02:43:16 And that's because the main difference is that you're heating your body up through thermal radiation versus the ambient air. Well, like a standard sauna is a heater and the heater is heating up the air 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 the heat stress itself, like that your heart rate is elevating when you're in there.

Starting point is 02:43:40 You're feeling hot, you're getting that cardiovascular. I mean, that's what you're feeling when you're in the hot sauna. And that, for me, takes a really long time and the infrared sauna to 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 a regular sauna. So. Great, that's a really helpful answer. I said I used the red light, but not in the sauna. And thank you for reminding us of that 174-degree Fahrenheit

Starting point is 02:44:11 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 Macak 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 going to add, and I'll have lots of questions, so I apologize in advance for that, but I'll be half of the

Starting point is 02:44:44 listeners and just directly from me. Thank you so much for your time. I learned a ton. My pleasure. Thanks for having on. It was really awesome conversation, so I enjoyed it a lot. Let's do it again. Totally. 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

Starting point is 02:45:17 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 slash newsletter. If you're enjoying and or learning from the Hubertman Lab podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please subscribe to the podcast on both Spotify and Apple. And on Apple, you have the opportunity to leave us up to a five star review.

Starting point is 02:45:44 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 in the beginning of the episode, we are now partnered with Momentus Supplements. So if you go to livemomentus.com slash Huuberman, 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.

Starting point is 02:46:17 You will also find specific protocols of how much to take and when, what time of day, what time of night, etc. 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

Starting point is 02:46:44 content of the Huberman Lab podcast, but much of which is distinct from the content of the Hubertman 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. you

Huberman Lab - Dr. Rhonda Patrick: Micronutrients for Health & Longevity

There aren't comments yet for this episode. Click on any sentence in the transcript to leave a comment.