Dr. Rhonda Patrick: Micronutrients for Health & Longevity

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 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 premier journals in the world, including Science,

Nature cell biology, trends in cell biology and FAFSAB. 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 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. I'm confident that you'll learn a tremendous amount of information from Dr. Patrick, much of which is immediately actionable.

And if you're not already following and listening to her excellent podcast, you'll absolutely want to do that. It's foundmyfitness.com is the website where you can get access to that podcast. It's also on Apple and Spotify and YouTube as found my fitness. Dr. Patrick also has

a terrific newsletter that I recommend signing up for. It's foundmyfitness.com slash newsletter is where you'll find it. And it includes research on fasting, micronutrient, sleep, depression, fitness, longevity, and far more, along of course with actionable protocols. I'm pleased to announce that the Huberman Lab podcast is now partnered with 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 Huberman Lab podcast. If you go to livemomentice.com slash Huberman, you will see those formulations. I should mention that we are going to add more formulations in the months to come.

And you will see specific suggestions about how best to take those supplements, meaning 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 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 livemomentice.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. 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 a day 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. 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.

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And now for my discussion with Dr. Rhonda Patrick. Rhonda, welcome. This has 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 spirit to break through from academic science to public education. So I consider you first in and the rest of us are just in your wake. So thank you for that. It's been.

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. So it's absolutely true. If anyone does their research, they will realize that the statement I just made is absolutely true. And there isn't even a close second, you know, any other public facing educators that have formal science training and do regular posting of content came in several years after you initiated it. So

We're all grateful. I have so many questions, but I want to start off with a kind of a new but old theme that you're very familiar with. So temperature is a powerful stimulus, as we know for biology. And you've covered a lot of material related to the utility of cold, but also the utility of heat. And as I learn more and more from your content and from the various papers, it seems that

There's a bit of a conundrum in that cold can stimulate a number of things like increases in metabolism, brown fat, et cetera, et cetera. Hopefully you'll tell us more about those. But heat seems to be able to do a lot of the same things. And I wonder whether or not the discomfort of cold, deliberate cold exposure and the discomfort of heat might be anchoring to the same pathway.

So would you mind sharing with us a little bit about what happens when we get into a cold environment on purpose, and what happens when we get into a hot environment on purpose? And I'm hoping that this might eventually 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 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 found in plants, these are things like polyphenols or flavonols.

humans were, you know, we evolved to intermittently challenge ourselves. And before we had Instacart where you could basically just get your food delivered to you, before the Industrial Revolution, you know, occurred, we were out

hunting, and I say, we, not us, but humans. We were out gathering, 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 pick your berries, you had to move. And so physical activity was a part of everyday life.

And caloric restriction 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 there was nothing for us to gather.

Food scarcity was 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. 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 cross talk 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, normal immune function happening, just life, aging, right? So this concept is referred to as hormesis, right? This is a little bit of stressful challenge that activates these stress response pathways in a beneficial way that is a net positive that actually, you know, has a very profound antioxidant anti-inflammatory response or, you know, or whatever the response is.

the production of more stem cells. These are cells that help regenerate different cells within tissues or something like autophagy, which is a process that can clear away all the gunk inside of our cells, pieces of DNA, protein aggregates.

So you'll find that these stress response pathways are activated by a variety of stressors. So for example, one pathway is called heat shock proteins. And as their name would apply, one would go, oh, they're activated by heat. Well, correct. They are activated, very robustly by heat. And we can talk about that. But you can eat a plant like broccoli sprouts, which is high in something called sulfurophane. This is a

A compound that is sort of like a hormetic compound, or as David so Claire likes to say, it's a xenohormetic compound. I love that. I love that term. And it activates heat shock proteins, among other things. It also activates a very powerful detoxification pathway called NRF2, which helps you detoxify things like carcinogens that you're exposed to. Well, guess what? Heat activates that.

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

Yeah, that's very helpful. And, you know, it brings to mind in the context of the nervous system, I was so people, you know, you only have a small kit of neurochemicals to work with. There isn't dopamine for Netflix and then dopamine for relationship and dopamine for work, et cetera. 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, even unknown inputs, like we don't know what technology will look like in three years, but you can bet that some of those novel technologies will tap into the very systems that I'm talking about now.

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. 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 plant 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 the swamiest type scenario so then i think we

conceivably solve the problem, we could say, yes, plants are bad for us, but in small amounts, they provide this hormetic response and they're good for us, right? So in the same way that heat is, too much heat is bad for us, too much cold is bad for us, can kill us, can kill neurons, but appropriately dosed in an intermittent challenge type of scenarios can be good for us. Is that how I should think about plants in these compounds? Do you think of them as good for us or as bad for us, they're a very sharp blade and we wanna use them potently?

I actually, I think that it's almost impossible. I mean, you'd have to eat nothing but the same plant all day every day in large. I mean, the bioavailability of these compounds in the plants, they're attached to a food matrix. You know, it's not like taking it in a supplement form as well.

It's such that 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 or somewhere that's all they eat is cabbage, and there is a goitrogen in cabbage. It's not sulforaphane, it's another compound, but that's all they eat every day. Nothing but that. And they get, yeah, and they're iodine deficient on top of that.

You know, I do think there's, you can, of course, make, I mean, there are types of plants that are toxic in small quantities, right? I mean, that- Hamlock. Hamlock, exactly. We'll kill you. Folks don't play this game with Hamlock. But you're not gonna get poisoned from eating, you know, you're serving of broccoli at dinner, right? So, I mean, it depends on the plant. 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. Plants meet and starches. I'm one of those rare omnivores out there now. I feel like I'm rare. It's rare to be an omnivore. But I think once you step out of the social medias, as you said, the blogosphere, most people, I would say 99% of people on 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, 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 people change a thousand things at once, and they don't realize that, but they do.

And so anecdotal data is only so good, right? It's a starting point. And so we don't really know long-term what carnivore diets are going to do. They may be beneficial short-term. They may be beneficial for reasons of elimination of other things like who knows, right? Lots of possibilities. But I do think with respect to plants, there's so much evidence, like for example, sulforaphane is one that I really like because

There's just evidence that sulfurophane is a very powerful activator of the NRF2 pathway. And this is a pathway that regulates a lot of genes and a lot of genes that are related to like glutathione production. Genes that are involved in detoxifying compounds that were exposed to you from our food like heterocyclic amines. In fact, there have been GWAS studies. So these are genetically, these are studies that are genome-wide associated studies for people listening

that aren't familiar, people have a variety of versions of genes. And we have a gene that's able to make heterocyclic amines to basically detoxify it so it's not as harmful.

And people that don't have a certain version of that that's doing it well are very prone to like colon cancer and increased cancer risk. But if they eat a lot of broccoli and cruciferous vegetables, it negates that risk because they're getting sulfurophane, which activates a lot of the glutathione transferase and synthase genes. So glutathione is a major

antioxidant in our brain in our in our in our vascular system in our body basically so um... you know there's there's evidence that it that that eating things like you know compounds that are like so far from or broccoli or blocked broccoli spouts which have like a hundred up to a hundred times more so far from them broccoli are activating glutathione in the brain there's human evidence of that i mean that's amazing that is amazing in plasma yeah uh... just already in trouble i just want to make sure when uh...

So broccoli sprouts are different than broccoli. 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 sulfurophane is formed from a compound called glucoraphanin, which is in the broccoli, and the enzyme that converted into sulfurophane is myrosinase, and it's heat sensitive.

So you do somewhat lower the sulfurophane levels when you cook the broccoli. However, there was a study a few years back that showed adding one gram of mustard seed powder, ground mustard seed powder, which also contains the myrosinase enzyme. Two year cooked broccoli increases the sulfurophane by fourfold.

So this is great because I confess, I like broccoli. If it's cooked to the appropriate density, not too mushy, but definitely not raw. The idea of eating raw broccoli to me just sounds horrible, but I like the way mustard 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 Kerrygold butter and then I add some mustard seed powder on the top of that. And it's got a little kick. It's just a little spice. And if you don't taste that, it's expired. It should have a little kick.

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

So there's another way to get, there's another compound, and it's actually called moringa. And Dr. Jed Faye, who's really the expert on sulforaphane, he's a good friend of mine, he's been on the podcast a couple of times. He 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 sulfurophane. And so I've been buying this Cooley Cooley Moringa powder. I don't have any affiliation with them. Cooley Cooley is a brand. Cooley Cooley is a brand that you have no affiliation to. I have no affiliation, but Jed Fahey has researched it like that specific brand. And so it's like legit, it's legit, it's like science back in terms of actually containing Moringa and activating NRF2. And I add it to my smoothies.

So that's what I've been doing. What are some of those ranges? So I. Of course, we give the usual recommendations that people should talk to their physician, et cetera, et cetera. But if people are going to it, what do you take? That's always the, let's take that. Let's say the St. Clairian approach. What do you, where he'll talk about what he does as a way to deal with this. And of course, everybody's different and should, in all seriousness, should,

Anytime you add or delete something from your consumption, should consult some trusted healthcare professional, trusted by you. What do you recall the dosages? I do a big, keeping tablespoon. So moringa, cooling, cooling, 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 in white blood cells.

It's also been shown, 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 at NRF2, and I know you're familiar with NRF2, but NRF2 is like it's a transcription factor that is binding to a little specific sequence in a variety of different genes, and it's like turning them on, or in some cases, turning them off. It's regulating what's being activated or what's not being activated or being turned off. And some of the genes are basically these

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's found an air pollution, I mean, cigarette smoke. If you're smoking cigarettes still, please try to quit. You're mutating your DNA. I mean, yeah, it's just like nothing 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 fame from broccoli extract, broccoli seed extract was a broccoli sprouts extract, not the seed, it was the sprouts. Anyways, they started excreting like 60% benzene and ackerelene. I mean, that's something that we get in cooked food. It's coming out in their urine.

Yeah. Well, I'm not a smoker, and I have to be honest, it's rare that I hear of a supplement for the first time, because I've been, you know, deep diving on supplements since I was in my teens. This is fascinating. And it brings me back to this question that we had 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. This is conserved among different animals. This is something that is supposed to happen. 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.

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, have to exercise essentially in order to obtain these compounds. And then those compounds are reparative. I feel that resembles the dopamine pathway. I always say, there's nothing wrong with dopamine.

people think that 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. 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 challenge and we can, we are rewarded

with particular compounds that are reparative, both for the challenge, but then it make us stronger. It is, ormesis really is, it seems the case of what doesn't kill us, makes us stronger. So you mentioned- Can I add to that one thing you just said? Please. Because this has been shown with, for example, sulfurophane in animal studies, you precondition and give the animal sulfurophane and then you expose them to hypoxia or some kind of exchemic stroke condition, whatever they do to induce that. And the sulfurophane, it basically

protects them, like their precondition and their stress response pathways are primed. And so when they're then exposed to the ischemic stroke,

Their outcomes are so much better, so much better than the animals that didn't get the sulforaphane 48 hours before, whatever it was. And this has been shown in multiple animal studies with sulforaphane specifically in the brain. I know Mark Matson, Dr. Mark Matson, he's often thought of as the intermittent fasting king, but he's a neuroscientist and he did publish some work and talks about sulforaphane 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 is just one example. And people always think, oh, sports, it's football. Whenever you say TBI, people always think football. And I just want to just take a moment to editorialize.

90% or more of traumatic brain injury is construction work at home accidents. Football players or hockey players or martial artists are a tiny fraction of the people who have TBI and concussion of various kinds. It just so happens that within those communities, many of them 75% or more experience those. So it's salient within those communities, but concussion is prominent. People are always asking, what can I do?

in order to offset brain injury. I had a concussion two years ago. What can I do? And it's been, it's been a tough question because we really don't have anything for them. I mean, you tell them sleep well, eat well, exercise, but it sounds like some of these reparative pathways either should be explored in the context of brain injury or I'm guessing are being explored in the context of brain injury. Yeah. So a couple of things there. One is that, I mean, traumatic brain injury, I mean,

It's terrible, but it's so interesting because it's also literal real-time brain aging. You're able to accelerate it and understand. I often think of, when I think of traumatic brain injury,

I think of so much overlap between Alzheimer's disease and dementia and these neurodegenerative diseases because there are a lot of similarities there. And so, sulforaphane, I personally think, and I do think there's been some animal research with TBI and sulforaphane, 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 a car, I mean, you're at risk to some degree, right? Or bicycle. 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 have died. We have a number of people of traumatic brain injury. I'm not against cycling or cyclists, but it is It's a risky sport by any stretch So in taking things like moringa 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 you know, just even in plasma cells. I mean, I think it's pretty, NRF2 is pretty ubiquitously expressed, liver. So there's, I mean, 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 I think, you know, overall, like I mentioned, you know, DNA damage lower, I think it was like 24 or 34% lower.

in human blood cells after broccoli sprout powder supplementation. And I made a video on this years ago, 2016, maybe, and I think I have the references on there to exact amounts. I can't remember. We can link to the video. 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 it's also been shown in randomized controlled trials to help treat autism and autistic symptoms.

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, which would be relevant for TBI treatment. It hasn't been shown empirically that that helps with treatment, but I do think someone could do that study.

I think that it should be done honestly because it's a low hanging fruit. I mean, if there 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 sulforaphane. So, um, which is really for people listening. That's so important because a number of compounds that people take in supplement form don't cross the blood brain barrier.

or they get metabolized in ways that what's listed on the bottle almost becomes irrelevant for what your cells actually experience. So that's very reassuring. We will get back to heat and cold in this theme that I tried to service, but I just find this too interesting to diverge at this point from these themes. So what other compounds or micronutrients do you place in the top tier of useful, interesting,

There are animal studies, maybe there are hopefully also some human studies. We've talked about a few. I know you've talked a lot about omega-3 fatty acids. So if you had to do your kind of top three, your superstars of nutrients for the brain and body, sounds like we've got one set. What would you put in 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. There's one from a plant.

And that's often referred to as ALA, people call it short, affilinolac acid. And then there's, I co-sapentanoic acid or EPA and Doka hexanoic acid, which is DHA. Yeah. I'm amazed you can pronounce two of the most difficult words to pronounce right next to and spell, right next to ophthalmology, which if you can spell it, I know people who have appointments in ophthalmology departments that don't know how to spell ophthalmology. A little secret, there's an extra P in there.

The ALA that I'm not going to attempt to pronounce it because your pronunciation was perfect of both of these two compounds and you said are marine sources. So fish, so sardines, cod, this sort of thing. But what about krill? I've seen krill oil and there was a few years back, people were saying krill is a better source for omega threes than is fish oil. I took some krill oil capsules, made me itch all over. So I stopped.

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.

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

to krill eating krill like we're talking about every krill are we talking about supplements yes i apologize yeah krill supplement versus fish or fish oil supplement and if you if it fits in the conversation talking about great sources of of omega threes in their whole form i have a bad feeling you're going to tell me sardines

Um, sardines are yeah, they're they're awesome. Anyway, except for the taste and and for the potential contaminants, um, Mercury, I think was want no show is yeah, it was mercury and, um, Joe was telling me about like he used to eat sardines every Joe Rogan was telling me that he sees sardines every day and, um, And then he had like really high mercury levels and I was really shocked because sardines are like, you know, low in

the fish, you know, group, so 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, it's like a third-party site that I'm affiliated with, but I'll use them because they do a lot of analysis of different foods and supplements, and so you can look at some of their sardines and they have a list of ones that are pretty decent. But anyways, back to your question about fish oil supplements versus krill oil supplements. One of the major differences is that fish oil supplements. If you get a high-quality one, it's in a triglyceride 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.

or if you have a lower quality fish oil supplement, then you have what's called ethyl ester 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, and then it's just kind of easier to leave it like that than like re-sterifying it, which costs more money. So you can get it an ethyl ester 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? Is it gonna say it's in this ethyl 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. 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 the SEPA, which is a highly purified EPA. These are both prescribed by physicians to patients with hyper triglycerideemia, so high triglycerides, among other things, 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, again, I'm not carnivore keto or anything, I'm an omnivore, but to just push home that

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 fats are not just one thing, they're many things.

Anyway, I just want to put a little highlighter and a point of appreciation there and make sure that people are sensitized to the fact that if you hear that fat is bad, you have to ask what kind of fat. Here we're talking about these omega-3s. The triglyceride form can be taken with or without food. There's prescription forms.

I can't get, I don't know if I can get ahold of the prescription form unless, um, you know, or I have a friend with high triglycerides. No, it's illegal folks. Don't share prescription drugs. Um, 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? Um, one way or another. All right. Okay. So the, the dosage that physicians prescribe for high triglycerides, for example,

is four grams a day. Four grams of EPA? Yes, of the Visipa. I think Lavazas also prescribed it four grams a day. And you can get either of those from your physician. My father-in-law just got one of them describing us to you. We were buying our own Omega-3 for years and years. It's like, hey, you can actually get this in health insurance and cover it. And it's a really purified form, but you have to take it with food. That was the bottom line.

I've totally gone on tangents, but like you're asking more interesting questions anyway So what 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 we're just raising the importance of omega-3s and then we'll definitely get to the why and the underlying yeah, I think four grams is I mean and in fact like you know

Bill Harris, 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 compliance. 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, Sachin Panda at the Salk 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 intermittent fasting, I said, why the eight hour feeding window? And he said, well, the graduate student who ran those studies had a partner, I think it was a girlfriend, as I recall, I hope I didn't get that backward. And the partner said, listen, you can be in lab.

10 hours a day, but you can't be in lab 14 hours a day if you want this relationship to work. And so it was eight hours of feeding window, plus some measurements, time to walk into the lab, park the car, et cetera. And so the eight hour feeding window that everyone holds so wholly was actually just born out of this relationship between these two graduate students. You know, had they been single, I was single all through graduate school, or most of it anyway, and I lived in the lab.

So if it 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. But the point that you're making is a really good one that the four gram

amount is not a threshold based on anything except the threshold of people's willingness to actually take the stop. And I think that's important for people to hear because so often we hear the eight hour feeding window, four grams of EPA, 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. 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. I'm, I just happen to buy, I happen to get a certain fish oil supplement that's like separates them. Um, and so, you know, like LaVaza, LaVaza is 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. I know I feel better because I've done the experiment of going on and off. I take the mainly for, I don't have depression, but, um,

My mood is better. My joints feel better. I just feel better. And I like to think that my platelets are slipperier and they're cruising through any little obstructions in my veins or arteries. 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 say half of it is EPA. Then do I want to hit a threshold of EPA or a threshold of

of what's listed on the bottle, right, on the 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, 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, dioxins, things that you'd find potentially in fish that are harmful to humans. And they also measure mercury and then oxidized fatty acids. So these omega-3 fatty acids are polyunsaturated fatty acids.

which are extremely prone to oxidation. So please keep your fish oil in the refrigerator because it's colder. Yeah, they're extremely prone. Mine's in the cover, so now I know. The shelf life's increased. Lower oxidation. Makes perfect sense. So anyways, they measure that. And I typically like to look for, they give you a total oxidation number. It's called TOTOX. TOTOX is what we call it for short.

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.

People can go to this website and they can browse through the products. I've 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 of the products. 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. No, I'm glad that you did the work. I'm going to put up a tweet every week.

with you tagged until this list is published online. Sorry, Rhonda, but I'm going to do it. I know it's very sadistic of me, but in service to the community and myself. And I chose five brands from you. And I tried to choose, I tried to find one in like Europe and one in Canada. So there was a great selection of US and other. Thank you for doing that work. I don't want to do that work. And I trust you. So yeah, I try and get two grams per day of EPA.

from supplementation. I'll now put it in the refrigerator. Mood is better. I made that decision mainly based on the data that I'm aware of, looking at comparison of people doing that anywhere from two to four grams of EPA per day compared to SSRI, selective serotonin, reuptake inhibitors.

treatment of depression and I don't want to take an SSRI if I don't have to and fortunately I don't have to but the data by my read are remarkable. People that take these things insufficient doses meaning the EPA's are able to get by with much lower dosages of SSRI's for depression relief or in some cases to come off their SSRI's completely or avoid going on antidepressant medication. Now of course this is not something people should cowboy you know mental health issues are serious but

What other reasons, I'd love your thoughts on that, on mental health part. And so maybe you could tell us what are some things that getting two to four grams of EPA per day is going to help with in our brain and the rest of our body.

So do you know, so I actually published a paper back in 2015 about the role of omega-3 and vitamin D in depression, bipolar disorder, schizophrenia and impulsive behavior. But so like within that paper, like the doing background research, and this was a review article, by the way, I was just connecting dots. No, I'm going to grab it. I confess I don't know the paper, but I love quality reviews because the references they're 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, a year 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 from our gut, mostly from

are 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 like 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. And so you can inject people with lipopolysaccharide and cause depressive symptoms. However, if you take those same cohort of people, give them EPA and I think it was somewhere around two grams and then inject them with lipopolysaccharide. We're establishing causation here, right?

It totally, the depressive symptoms versus the placebo. So the placebo was saline control. So this was a placebo controlled because obviously it's hugely important for depression. It emeliorated the depressive symptoms of the cause by lipopolysaccharide. Amazing. And LPS lipopolysaccharide is no joke. 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 hypothalamic areas and cranks up body temperature because basically it's a signal that the body is infected, right?

Amazing. So I will continue with my two grams per day. Maybe I'll ramp it up to four. I'm not doing the DHA separately. There's 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 specifically is it's, you know, in fossil lipid form.

It's more bioavailable, so our bodies, you know, if you're comparing exact quantity or concentration, you know, in triglyceride form versus phospholipid form, you will get more in your plasma cells, or in your plasma cells, in your plasma, with Creole oil. However, Creole oil supplements are so low dose, like, I mean,

good luck getting two grams of Omega-3 from Cril Oil. And also, Cril 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, I haven't found a good Cril Oil supplement. I pretty much stay away from it. I mean, if you smell it too, I mean, it just smells rancid. But the thing is, and I also published a paper on this back in 2020,

19 or yeah, something like that about DHA and phospholipid form getting into the brain in a through a different mechanism than DHA in triglyceride form. And so it's going through a transporter called the MFS D2A transporter. And I think it's very relevant for people with an APOE4 allele. So I kind of within Alzheimer's susceptible. Right. So like 25% of the population has an allele and a gene called APOE.

four, and basically it's APOE, but the four is referred to as the bad kind of version of it. This is something in our bodies. It's also in our brain, and if people have one of these versions, if they got one from their mom or their dad, they have a two-fold increase risk for Alzheimer's disease, if they get two, which is much more, it's less common. I think it's like 2% of the population, something has two alleles, but they have like a 10 or 11-fold increase risk of Alzheimer's disease.

So there is a role for phospholipid form DHA in the brain, but you also make phospholipid DHA inside your body. And you can do that by taking in more triglyceride form. So two grams are more is the magic number, I think. So kind of back to the why for fish oil. And I personally think it is one of the most powerful anti-inflammatory

things, dietary lifestyle, things that we can get easily, relatively easily, that 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 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. 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 HBA1C, 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 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 the 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%.

big, big difference there. And they also have about a five year increase 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 only say it's the only thing, but what he showed in his data was that

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 the standard American is, but a little bit lower. They had a five-year decrease 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? And he found smokers that had no omega-3 were like the worst of all. I mean, it was like, it was just like worse, right? We 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 taking their fish oil or eating fish or whatever it was, they were doing to get them up to 8%. They had the same life expectancy as non-smokers with the low omega-3 index, right?

And that's amazing. And it's also amazing to me that people still smoke cigarettes. But I see a lot of people vaping.

And I know a lot of people consume cannabis. There have been any studies specifically of vaping or people smoking marijuana and all cause mortality. You haven't seen those. I haven't seen those. They're not motivated enough to come in as research subjects. That was, again, a poor joke. It is hard to study people marijuana use unless I'm told by my colleagues that study this stuff, unless you offer people marijuana, in which case they'll do it.

But again, they're actually not very good research subjects in all seriousness because they are not very motivated or consistent and they forget their appointments. So that's incredible. And you mentioned that the data on pollution related to the plant compounds earlier. So it's almost like these things are, again, are acting in a reparative way.

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 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. Um, I do want to just touch on food sources for a moment. Um, first of all, are there plants that are rich in omega threes? And second by, um, I have some friends who are really into meat. And, um, I like meat a lot. My dad's Argentine, but I don't eat very much of it. I try to eat high quality meats and relatively limited

amounts, but I do eat pretty often. But I've been told by these sources of questionable authority that if an animal grazes on really good grasses, for instance, that the meat can contain a lot of omega-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?

Um, so there was a study published that compared conventional meat. So meat that is, you know, that animals are fed, you know, corn or soy or whatever it is. Which is terrible. Yeah. But for animals and people, as far as I can tell, I'm sure I'll get, I'll get some, um, attacks, but that's okay. I won't read those comments. The, um, the, again, a joke, I read all the comments, but, um, the,

It seems to me that these animals 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 like the grass fed or going to pasture raised cows or cattle, there were higher levels of alpha linoleic acid. And ALA can be converted into EPA and DHA.

But the conversion is very inefficient and very dependent on a variety of factors, including genetics. Genetics, a huge regulator. Some people can do it much better. Others, you're getting 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.

These omega-3 fatty acids play a very important role in brain development. Women are supposed to be converting any ALA they can into the longer chain omega-3 fatty acids. So estrogen does affect that. But I would say plant sources, so if you're looking for the ALA, plant sources would be walnuts, flax seeds, 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 doing the flaxseed oil because that conversion inefficiency, the enzymes that

convert ALA into EPA and DHA. Again, it's inefficient. And then for people that eat fish, sardines, you said salmon. Salmon, and you have to eat the skin, as I understand. You don't have to, but it's good. It's rich with the oil. Yeah, and the reason I say, I think the best would be wild Alaskan salmon versus the farm rays, because the farm rays, again, they're feeding them

They're feeding them like green and stuff. And then they give them as to Xanthin. So, as to Xanthin is a carotenoid. It's the carotenoid that's in things like chiral acoustations 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 in photoreceptors. Yeah. Well, you know, actually the carotenoids themselves. So, like, lutenines, azanthin, they're really good at sequestering singlet oxygen.

which is damaging, right? As we age, because the retinal cells, cells of the eye are so metabolically active, they accumulate a lot of reactive oxygen species and mitochondrial repair and limiting reactive oxygen species is a major

theme of trying to rescue vision. That's a whole other podcast and story. There's some really interesting data now on the use of red light to try and trigger these pathways. I've seen some. That's my good friend of many years and amazing scientist Glenn Jeffrey's lab at the University College of London. We should talk about that at some point. I saw that study in 2020, was it? Now they have a second study. Oh, do they? They've done it again. It's looking real. I mean, they're cautious. They're appropriately British and cautious about it.

I always joke if those studies have been done over here. Everyone had already.

know about it glen is a very conservative guy but they've done the stuff now in in pigs in rodent models and now also two studies in humans it's looking pretty pretty interesting uh... so sardines but also anchovies i mean all i'd by the way i hate all the food items that i'm describing i can barely tolerate salmon i don't like fish at all actually i like a lot of fish oil and 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. Now, I don't really like sushi that much anyway. You're giving me great reasons to not eat fish, but except I should eat these other fish sources or supplement more heavily. That's the message I'm getting. I eat sardines. My like every day, my like first meal almost is like a can of sardines 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 of Omega-3s? Avocado is very good in monoinsaturated fat. It's not really high in polyinsaturated fat. Omega-3 really, I mean, it's either the DHA and EPA that's in the marine sources fish, or it's the plant ALA source, which is like the flax seed or the walnuts.

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. 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 to genetically modify fish that tastes like a steak. All that, you know, I love the taste of steak. The point here is that if you don't, if you, if one doesn't see themselves regularly consuming these fish, these fish sources of omega threes, 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, you know, I think there was some way they showed that people that are in the 4% Omega-3 index range in order to get to the 8%, right? The five-year increased life expectancy if we're comparing the two groups was to supplement with at least two grams. It was about two grams a day.

And that and I think it was a little bit less if it was triglyceride form, but I think two grams is a good safe number so Most Americans that are not eating a lot of fish and they're not supplementing a probably around a four to five percent Omega-3 index and to get to the eight percent and I think that's a good

empirical way of thinking about it, right? Okay, well, I want to get to that 8%. By the way, I'm almost 16% 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? Which again, just to remind people is the 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. The omega-3 index. Sorry, I misunderstood. I thought you said in red blood cells, if I ate salmon two days ago, my omega-3 index is going to go up. No, that was plasma. I misunderstood. So most people are measuring, like, if you look at a lot of studies, and honestly, Andrew, I think a lot of the reason for conflicting data is because

people are measuring plasma omega-3 levels. Okay. The phospholipids, it's in a phospholipid, right? So your phospholipids are carrying things, these are lipoproteins, they're carrying things like omega-3 and triglycerides and stuff and shuttling them around. So the omega-3 index is actually in the red blood cells and red blood cells take 120 days to turn over. So if you're going to do a baseline test,

If you want to know before supplementing what your level is, you have to wait 120 days before doing the second test after supplementing to know how much you went up, because that's how long it takes for your red blood cell to turn over. So the Omega-3 index, Bill Harris has a company that he co-founded is called Omega Quant, and they measure the Omega-3 index. They have a variety of different

Index test you can do like a basic one or a little more advanced is from a blood draw it. It's a little blood spot thing Yeah, and you know like he uses the money to like funnel back into doing lipid research like he's like out there doing all sorts of interesting studies on omega-3 is great, but I know the omega-3 index is great. I think that Honestly more people and more researchers should be using it because

The conflicting data, it 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 controlled trials, and I think that we need to

as scientists, we need to come together and make some progress. Let's all talk to each other. Let's figure things out. This test is out there. It should be used. It should be used not just by Bill's group, but everyone.

Yeah. Well, 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 omega-3 index is going to be best. You mentioned you. So basically, when now I look at you, I think you are 16% omega-3. And dolphins are 19%. I'm almost done. Is that your goal? You're trying to get there? It is. To do the interesting. Actually, they should probably do something we were 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

how are they having these positive effects? In my mind, and this is incredibly elementary, but my understanding is that at some level, they're making platelets more slippery. Is that true or not? I hope I'm happy to be wrong. How is it possibly impacting my mood? Is it through the synthesis of membrane on neurons that allows neurons to release 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 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 resolvins help do that. And so resolvins are one. And then there's these specialized

pro-mediating molecules, the SPMs, that also help resolve the inflammation. There's, like you mentioned, the leukotrenes and prostaglandins, and these things are being affected by EPA, and they do affect

platelets and platelet aggregation. And they do affect that whole pathway as well. And so there's just so many different ways and inputs. And so when we talk about inflammation, honestly, it's a big general term. But 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 to go about injecting people with lipopolysaccharide and causing depressive symptoms.

Um, you know, it's known that, that omega three, 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 resolvins and stuff. And this then helps more serotonin be released because you're, you're not having so much inflammation getting into the brain and affecting serotonin release, right?

That's one mechanism. And then another would be, well, DHA itself has been shown. It's a very important fatty acid that makes up cell membranes, many cell membranes, including in our neurons. And as you very well know, Andrew, the structure and function of receptors of transporters, these membrane-bound proteins on the surface of our cells, including neurons, are affected by the membrane fluidity, you know, like how rigid and how fluid the cell membrane is.

DHA plays a role in that. And so, for example, in animal studies, if you make an animal deficient in DHA, they're 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. 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. They float around like little rafts. Sometimes they are, in fact, in lipid rafts.

And so it makes perfect sense that these molecules like DHA, which are part of the structural fat of the neuron, because of course the outsides of neurons are basically fat. Not just the myelin that people have heard of, but the actual membranes, that getting that right. You wouldn't want it as rigid as concrete, but you wouldn't want it as soft as

need to come up with something here. It's that gooey stuff that kids play with. It's like that goo. Anyway, there's a, yes, it's disgusting and it's too soft to be a membrane for a neuron. That's what that's what we know. Someone put it in the comments and tell me what that disgusting gooey stuff is. You don't want your neurons to be that gooey and yet you don't want them to be like concrete either. It's a balance. It's a balance. Yeah.

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.

Are food sources of DHA that you find particularly attractive either by taste or by potency for DHA? What are just a few that we could throw out? Because I am aware that there are supplements where you can get a nice ratio of EPA to DHA, or you take them separately as you do. But if I want to make sure that I'm getting enough DHA, what do I need to be sure I'm eating on a regular basis?

well the fish is packaging the d h a n e p in the ratio and uh... but i i also do eat salmon roe which is uh... very salty and uh... it's a it's a really high source of the phosphatolic whole lean d h a that we should expect

It is. Yeah. And actually, that I like for some reason. Oh, do you? Yeah, I'll eat that. 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 base caviar Yes, and that's a good source of the phospholipid form and I was consuming that a lot because I wanted to get the phospholipid form So and 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 weight like 10 times more DHA than the brain. Again, it's makes sense based on fetal development. So do I need to and by beluga caviar, stuff can get pretty expensive at $200. I don't think you need to. I think it's a it's a matter of preference. And if you're supplementing with your

you're two to four grams of fish oil. I mean that you're going to get phospholipid form anyway because your body's going to make it. I've seen some containers of what I assume 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.

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. 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 brain and our 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 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. There's a sliding scale on how efficient that process is. And as I understand, there's an inverse relationship with the darker your skin is, naturally, the more vitamin D you need to consume. Is that right?

The darker your skin is, the harder it is. So there was a study out of the University of Chicago. This was several years ago where they looked at African-Americans and compared African-Americans to Caucasians with light skin, fair skin, and how 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.

I 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, you know, 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, you know, these equatorial regions where there's, there, you tend to see darker skin because it's protection from the burning raisins. An adaptation.

They are in the sun war, and they're getting more vitamin D, but people that maybe move to United States, to Minnesota, or in a place where UVB radiation isn't getting to the atmosphere 12 months out of the year, it's only getting there four months, for example.

Um, or even living in our modern day society where people just don't go outside anymore. I mean, we're inside, we're at our laptops in school, we're at work, we're in our cubicle, whatever. So, um, supplementation does play a major role, not only for people with, um, you know, darker skin that aren't outside all the time, but for everyone, 70% of the U.S. population has inadequate vitamin D levels, 70 of the whole U.S. So this is everyone.

And so I think that insufficient levels defined as less than 30 nanograms per milliliter. And that's sort of defined by the endocrine society. Looking at a lot of different aggregate studies and all cos mortality, for example, there's been a lot of different meta-analyses of all cos mortality 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, live 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. But also skin cancer is somewhat of an issue as well.

So basically, the point is that vitamin D is steroid hormone, meaning it actually binds to a receptor and another receptor dimerizes with it, 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.

There are specific sequences of DNA that this complex, the vitamin D receptor goes inside and recognizes and turns on a whole host of genes, turns off a whole host of genes. I mean, this is important stuff, like imagine 70% of the population having insufficient testosterone.

Right. It's a steroid hormone, which might we might be headed there. Um, but probably not. No, I think that it's names are very important. And I think that one of the issues is that vitamin D is called vitamin D. It's not called, um, D H E A or, you know, variant blah, blah, blah. It doesn't sound like a hormone. I also, I'm glad that you're mentioning, um, skin as the major

kind of interface between the environment and vitamin D synthesis because a lot of people think of skin as just a protective sheath around us or something to adorn ourselves with earrings or tattoos or whatever, but skin obviously serves those roles, but the skin is an endocrine organ. It has the capacity to make things that impact hormones and to make hormones. 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 keratinocyte linked pathway involving P53. This was done in humans, but they did some knockout studies in parallel. And what this study told me reminded me is that skin is an endocrine organ. So the idea that sun could trigger the activation of

of a production of a hormone is really interesting and makes total sense. So when vitamin D gets into cells and it's binding to these VDR E's, what sorts of things are they triggering? So like for testosterone, we know it's going to trigger protein synthesis, muscle growth, tendon strength, et cetera. With estrogen, it's going to be keep your neurons going, your joints feeling good. I always remind people that

By the way, because guys are always seem to want to increase their testosterone and reduce their estrogen. Just remind people, if you reduce your estrogen, guys, your libido will plummet to near zero. Don't crush your estrogen. It'll also make you stupid. If you're not already stupid, it will make you stupid. So estrogen is vitally important for males and females. When vitamin D gets into cells, what sorts of things is it stimulating?

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 published all these genes, they found V-D-R-E's in. And basically I found that tryptophan hydroxylase 1 and tryptophan hydroxylase 2 was on there. And so then I started looking at the sequence and I was doing some in silico work, and it turns out that the V-D-R-E's and tryptophan hydroxylase 2, so for people

Listening tryptophan hydroxylase is an enzyme that converts tryptophan into serotonin. So tryptophan is what we, an amino acid that we get from our food. You convert tryptophan into serotonin into the gut, but you also do it in the brain. However, serotonin does not cross the blood brain barrier. So tryptophan has to get into your brain, and then you have to convert it to serotonin in your brain. Well, the enzyme that does that in your brain

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

Since then, there have been some groups that have confirmed more with in vivo and or in vitro studies, as mine was all in silico and all that stuff. But anyways, so serotonin, a really important one. But most people, I mean, this is regulating our immune cell, immune system. It's regulating our blood pressure, you know, all 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

I mean, and with seven, seven zero percent of the US population deficient, I'm beginning to think that this could be the linchpin and a number of really important issues. So supplementing vitamin D three is what I normally here is the, I do, I take, I think I end up taking 5,000 IU, sometimes 10, I use a vitamin D three per day.

Just done that for a long time and I've had my levels tested and they're in range, but I have a family member. I'll just mention this. I have a family member who was not feeling well, just kind of feeling off a little load. I had some digestive issues. This went on a long period of time was taking on my recommendation 15,000 I use 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 IU's per day in order to bring their D3 range just into normal.

Which is, to me, is striking because they eat quite well, they're a healthy weight, et cetera. And it's made a tremendous difference 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 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? And, again, foods that can increase D3.

Um, so vitamin D3 is a good way to supplement with it. Um, their vitamin D2 would be a plant source. You often find it fortified in like foods like milk, usually D2. There's been a- Does anyone still drink milk besides kids?

Oh, it's like you can't find cow's milk. I mean, all the lot is that you're getting one. Yeah, like they're fortified in those as well. Okay. Oh, they are. They are. Yeah, they're fortified in. I have a hard time finding cow's milk and all that stuff. Yeah, they're in all that stuff. Okay. Vitamin D is naturally to some degree in fatty fish. Like, you know, like 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 with eating fish for your vitamin D. Like you're either going to correct it with sun exposure, being in the right area, having the right amount of sun and being the right age. Because as you get old, you become very inefficient at doing that converting vitamin D, making vitamin D three in your skin. Well, that's probably what was going on here. Because this person is getting up in there. There's a lot of single nucleotide polymorphism. We talked about APOE4 previously, but there's a variety of

genes that people have very common actually. In fact, I've had many people that have to do done that exact same thing.

So measuring your vitamin D levels before and after supplementation is the only way you're gonna figure that out, right? Very important. If you don't measure it, like you don't know, like 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've been a lot of these Mendelian randomization studies. So these are studies where people, scientists will look at common

SNPs, people that have these common variations of a gene that's a little more than 1% of the population. So it's not a random mutation. It's actually found in a sizable 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 D precursor into D3 or into D3 into 25-5 droxy vitamin D or into the active steroid hormone, which is 125-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5-5

with an observational study because you're not biased. You know, vitamin D levels are also associated with health. People that have higher vitamin D are either outside more, they're more physically active, or they're aware of their health and they're supplementing, right? So you always have to worry about that when you're doing an observational study. But when dealing around a physician is beautiful for that reason where you now just randomly, people randomly have these genes and it's not like there's no health status. Like if you have the SNP,

like your family member was healthy and all that, you know, they were healthy and yet they couldn't get their D levels up, right? So these, these Mendelian randomization studies have found that people that can't convert into the, the precursor, the 25 hydroxy vitamin D, which is usually what's measured. It's the most stable form of vitamin D in the body.

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.

To me, now why did I get on this rant? Oh, because you're a family member. So basically, they also are more likely to get multiple sclerosis. This has all been done with Mendelian randomization. And so it really does hammer home the importance of measuring your vitamin D levels and being very proactive about that. I mean, you can get it done 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 IU's of vitamin D will raise blood levels by around five nanograms per milliliter. So let's say you're deficient, you're 20 nanograms per milliliter, and you want to get to 40. You're going to need at least 4,000 IU's. If you're normal, don't have any of these SNPs that change your metabolism of vitamin D, right? It doesn't 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 really like I can't.

seem to, you know, to find anything that really suggests because like, for it to actually be converted into the hormone, I mean, it's stored. Just slow acting. The steroid hormones are slow acting. Yeah, it's not like a media 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. 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 realized 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? 1,000 to 5,000 I use for most people will be reasonably safe. Again, we're not 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 scientific literature, it is extremely hard to get hypercalcemia, which would be the major concern with really high levels of vitamin D3 supplementation.

hundreds of thousands of a day for a long time. The upper tolerable intake was set by the Medicine Institute to be 4,000. It was just like one of those things where it's safe. I personally take 5,000 I use a day 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 it on my face and I wear a hat, but 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 because in these studies that I mentioned before, looking at sun exposure on skin and increases in other hormones, testosterone, estrogen, mainly.

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

Yeah. So surface area matters. And by the way, you know, there, there have been studies looking at people that are deficient in vitamin D. In this case, it was African Americans that were given a 4,000 IU a day vitamin D supplement to bring them back to sufficient levels. And so this was a smaller, smaller study than I would like, but it reversed their epigenetic aging by like three years because

Again, it's a hormone. It's regulating more than 5% of your protein encoding human genome. There'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.

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 you turn on and turn off genes. Well, if you get rid of that receptor, which is what you can do in animal studies, you can sort of determine like what effects there will be with no vitamin D, right? Like how do you study 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- Some hypomole. Yes. Which is basically geek speak for, a gene is vastly reduced in its function, number and function, number, people know what I mean, but isn't eliminated completely. Right. Well, these animals, if you look at them after the age of four months, I mean, the mice look

like, I mean, they're accelerated aging. They're wrinkled. They have no hair. I mean, they're life span shorter. I mean, 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, mice life spans around like two, two and a half years, but like,

500 years old. It went to graduate school twice. Yeah. 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 I'm definitely going to try and get my omega 3 percentage up there. I'm not going to 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? Okay. I think a lot of people don't know that, or at least I have family members that have been a little bit resistant. It's 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 as I am of melanoma. 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, people cringe when I drink tap water,

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, 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, it's 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 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. And 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. It is somewhat difficult to penetrate things all the way through the skin, into the blood stream, 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 evidence they go transdermal. And they get in. Okay, well, I know that there are some of them react with

the sun and while they do protect from the UVA and or B they like form massive reactive oxygen species and carcinogen I mean it's like the very thing you're trying to protect yourself from might actually cause right we don't know I mean like it's completely speculation but there is like I think some more 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 have

You know, it's the chemical sunscreen ones, the chemical ones. We should do, I'm proposing that we do a journal club. A journal club folks is where academics get together and read 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, you know,

Most studies, people are doing their best within the context of what they can do. But it'd be great to do a journal club at some point about sunscreens, because I'd love to really figure out what's in these compounds. I mean, people are using them like crazy. And I'm not one of these people who's like, oh, I won't use commercial toothpaste or anything like that.

I, like I said, I drink tap water, I use commercial toothpaste, whatever. But when it comes to sunscreen, it freaks me out because some of these compounds do go transdermal 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. Wear hat. Wear hat. But get out in the sun and get your D3 levels up.

Okay, so we've talked about these plant-based compounds, the Omega-3s and D3. Unless there's something else that you just absolutely must throw into the mix, I probably will return us to the conversation that I opened up with, which is about cold and heat, which admittedly I pulled us off that path. So I want to take full responsibility for that. But before I do that, I just want to offer you the opportunity.

Are 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 her body health? 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 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%. That's a big number. Now, magnesium is also involved in

making ATP, the energetic currency of our cells. Basically, all of our cells need ATP to do anything. 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 causes an insidious type of damage.

daily that you can't look in the mirror and see, like when you're deficient in vitamin C, you're like, my gums are falling apart. I have scurvy, right? But like, you can't see DNA damage. You can't see it, but it's happening. It's happening right now in my body and it's happening in your body. It's happening in 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. And the way I like to think about magnesium, it's easy because people go, what food should I eat? Naturally, that's the next question. Well, magnesium is at the center of a chlorophyll molecule. Chlorophyll is what gives plants their green color.

dark leafy greens are high in magnesium. Basically, what does the 40% insufficiency in the US tell us? People aren't eating their greens. They're not eating their greens. They're eating their packaged food, they're eating their processed food, standard American diet isn't really high in dark leafy greens. Dark leafy greens are how I like to get my magnesium. I think it comes along with all these other important, I mean, you get calcium in them, you get

That vitamin K1, you're getting a lot of other micronutrients, and you're getting other compounds that we don't know about, and ones that we know about, like sulforaphane, right?

As with broccoli, do I need to eat the dark leafy greens raw? And in this case, I'm a little more open to it because I actually like the taste of dare I say kale, and kale's a dark leafy green, right? It's obviously, I'm not. I'm a trichromat, meaning I'm not color blind, but I just want to make sure it falls under the strict category. Yes. Because every once in a while, I'm like, oh, I eat my vegetables. I like avocados. If you were my main avocados, not vegetable.

I love vegetables also. But so, kale, what are some other examples? Cale, spinach, chard, like Swiss chard, rainbow chard, romaine lettuce. Is the bitterness an important component to this? For magnesium, no, but for sulphurifane, sulphurifane, for cruciferous vegetables, that would be the brassica family. But your question about cooking them, so magnesium is, it is bound to the food matrix and

And it can be somewhat less bioavailable.

Um, but you know, so cooking it can somewhat release the, 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 with it. Like, yeah, you know, I personally don't worry about it. Okay. Just don't worry. I think like, if you don't worry, I'm not going to, but I also like, I do supplement with magnet. I do take around. So supplementation with magnesium.

I mean, we could go on and on. Let's keep this short and sweet because we're going to get back to the other stuff. But it can cause GI distress at high doses. I personally like to take around 130 or 135 milligrams. That way, it's not like a huge bolus to my gut. But I think it depends on the form of magnesium, too. Yes. Yeah. I mean, you can take magnesium three and eight, 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. I mean, I feel like it's a little bit harder to man. Well, I take 100 135 milligrams should be pretty good and situate actually.

Oh boy, do we want to go here? Sure. I mean, I, it's up to you and we can, we don't have to. I personally, I've been supplementing with magnesium for a long time. Yeah. I've, I use three and eight and bisclicinate and malate for different reasons. So I, yes, I would love to go there if you're, if you're willing to. I would say malate would be the best. And that, 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 Schigenaga.

showing that the short chain fatty at citrate malate lactate. But, but specifically malate really in lactate are the other 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. Yeah. I take malate because I was told that it would be helpful. First of all, it doesn't make me sleepy like some of the other forms of magnesium, which act as a mild sedative for me.

Um, they do tap into the GABAergic pathway, neurotransmitter folks that in general, broad sweeping generalization here can have somewhat of a, uh, of a sedative quality, which is why I take magnesium three and eight and or bisglycinate before sleep 30 to 60 minutes before sleep. Definitely enhances my transition time to sleep. Um, and the depth of sleep. No question in my, my experience, there's some data that three and eight can be

COG can be neuroprotective, although those studies are still ongoing. I'm getting the sense that maybe you're a little more skeptical of that than I am. Yeah, I know. I've seen the studies with the 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 their sample size was too small. Right. Yeah. I'm thinking that that paired with it. There's some work. The animal stuff. Yeah. The goal song lose work on with. So in the, this is getting kind of into inside ball of neuroscience, you know, that the quality of the labs matters, folks. And that's something that's not accessible to people outside of fields. And, you know, goal song Lou and some of the other folks with, at that time at MIT did, I,

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 MAG-3 and 8, given that it helps me sleep better and sleeping better is just better for everything. Frankly, that's why I take it in bisclicinate and 3 and 8 seem to be somewhat interchangeable.

But there's, I don't know of any reports that bisclicinate can be neuroprotective. But malate, I take care in the daytime. I, it, for me and again, this is subjective. It has a tangible effect in improving the recovery time from exercise. So it, I don't know that I've been sore from a workout since I started taking malate 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.

Malate, again, the short chain fatty acid and when you do intense exercise, you release endotoxin from your gut. I'm just going back to the interesting work because the malate being the short chain fatty acid and

You know, you know, Mark Shiganog is showing this is all in animal research, by the way. But I mean, it was like, you know, feeding these animals, Malay. I mean, it really protected the gut endotoxin release and it affected metabolic syndrome and all sorts of things. But I think Malay, it's awesome. And I always try to eat green apples. They're really high in malic 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 3 and 8 stuff. I take a supplement called Magnesium by Moonjuice and it's like a little powder. It's got a little bit of 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 of fluids 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 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. So why wait?

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 line placebo control studies, you know, randomized clinical trials.

et cetera. Then other people are just saying, you know what? I don't even care about any of that. Just tell me what you do. And then other people are saying, you know 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 pill form 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 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.

Uh, we should have you back on. 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. Um, so cold and heat.

converge on some common pathways related to what you called intermittent challenge, which I love. I think if, you know, intermittent fasting, cold, heat, exercise, I mean, maybe even intermittent sleep deprivation. I keep waiting for the intermittent sleep deprivation movement. I will say I pull a few all-nighters per year just for work demands and procrastination and deadlines and I'm 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 use 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 Mattson.

Okay, Dr. Mark Mattson. He has used that phrase. Okay, great. We'll make sure. Just like Dr. Davidson Claire, I love the Xenohormesis. He was in like one of his publications just so many years ago, and I just love it. It's brilliant, brilliant term. So Mark Mattson. Those harder guys are pretty smart.

I mean, it's a good school, I guess. Of course, it's a good school. We will credit the appropriate people. Thank you for that clarification. So you've talked a lot about the use of what I call deliberate cold exposure, only to distinguish it from cold that you might just be accidentally exposed to, but it's sort of obvious when we say cold exposure.

There are some amazing data on cold. The other day I saw a post from you, and you've included this in talks before, I did not know this until I learned it from you, so credit to you, that even 20 seconds of immersion in, I think it was four degree. 49 degree Fahrenheit. 49 degree Fahrenheit, okay, I was translating this out. 49 degree Fahrenheit water, so cold water can lead to long lasting increases in epinephrine adrenaline. And I have to presume other neurodegrees

neuromodulators and neurochemicals as well. What are some cold protocols that you find particularly interesting or attractive from the standpoint of, I don't know, pick your favorite metabolism, neuro slash mood effects, brown fat stimulation, which of course we use back to metabolism. We could do an entire episode all about cold, but what I'd love to know is what sort of

activity or stimulus do you 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 would say like,

Okay. Maybe most of my shoulder. I mean, really, I'm floating up. I was telling my husband, I was like, there's too much water in here for me. I can't. 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, you know, it's the plunge. Yeah, they may, then 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 layer and it's even colder. It is even colder. It sucks. Anyways, so look, I'll give it a, I'll 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 to do a podcast.

when I'm gonna give a talk or when I'm anxious, I need to make it more of a ritual. I love doing this on. I hate the cold, I hate it. Unless it's summertime, it's a lot easier for me to get in the cold in the summertime. But what I do love about the cold is how I feel after. And I feel less anxious, I feel good, 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, time or duration, I guess would be a better word, and temperature do matter. But you can do 20 seconds at a colder temperature, which is I prefer, or you can do a minute or longer at a warmer temperature.

There was another study showing 59 degrees Fahrenheit at one hour. It was like two or three full, but who wants to do one hour? Yeah, I'm familiar with that study. I love to. This is really reveals just how absolutely nerdy I am and maybe why some times and relationships in my life were challenged. I love reading the methods sections of papers. So, you know, people can come at me with a number of things about papers and I might miss something. Surely I miss certain things like anybody 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 really, it was chilly. It wasn't super cold. I mean, 60s, it's not warm, but it's not ice cold, obviously. 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

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, because most everything else, like an Adderall, a Ritalin, a cup of coffee, and a pre-workout drink or something, is gonna give you a big spike in adrenaline and dopamine and a big crash. And somehow, it creates this really nice contoured profile.

So I, whatever you're experiencing there is very nicely supported by the data. Um, well, I, I need to get, I need to get doing it more. I, I've, 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 chacuzzi. I was in there for like 30 minutes. I mean, I was, I was doing heat. Chacuzzi. Okay. Yeah. 104 degrees Fahrenheit. That's toasty.

And then I had 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 fifties. It was cold. And I was in there and I was like listening to Simon Garfunkel. I was like trying to stay in a long time, get on my cold and I was trying to press Dan because he like goes in there for like, he'll stay in there for like 15 minutes.

I started to feel really like blinky, like low blood pressure or something. And I got scared. So I got out and then I couldn't stand like I had vertigo or something. And I was so scared, so scared. And so, and I've, I've had a couple of times too, where just going straight from the sauna to it, uh, to the cold plunge, um, where I'm starting to feel, I'm like, ooh, I feel a little blood pressure change or something. And it makes sense. The sauna is causing vasodilation.

And the cold plunge is cold exposure is causing visual constriction. It feels like a very, you know, just shocked to my system. And so now I wait, like I wait like a few minutes before going in, but I do need to kind of like make it more the cold, more routine because I talk all about the science. I'm familiar with all the science and, you know, the, the NOR epinephrine or NORA adrenaline.

It's affecting brain and mood, and you know 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. And now in humans as well. Oh, in the brain, they've shown. So in that study, we can put a link to this. It's published in 2000, European Journal of Physiology.

that big dopamine increase. They also looked at epinephrine and cortisol, and it's awesome, really. Yeah, so this has been done. They did brain. Oh, I didn't know. The plasma. Yeah, yeah, yeah. Very hard to measure dopamine directly from the brain unless you're doing micro dialysis. No, unfortunately, there's, unfortunately, there's skulls were intact. Fortunately for them, unfortunately for the research committee, there's 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, 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 adipose tissue and perhaps even muscle like that's been shown. So maybe there's a good opportunity to, so cold and UCP one, if you could educate us on UCP one, I find this really interesting. And I learned about it from you. Yeah. Uh, well, so noroponaphrin actually released in the plasma does act as a hormone. Base of constrictions. One thing it does, but it also,

regulates a variety of molecular functions that have to do with adaption to cold. One happening to be, you know, shivering is a very inefficient way to produce heat, which is what your body is trying to do when it's exposed to cold. And your muscles are basically contracting and producing heat from that, but that's just not very efficient. So the more eloquent way to do it or elegant, I guess, way to do it is, you know, to basically

have your mito