Huberman LabMicronutrients for Health & Longevity | Dr. Rhonda Patrick
EVERY SPOKEN WORD
150 min read · 30,055 words- 0:00 – 3:12
Dr. Rhonda Patrick – Micronutrients, Cold & Heat Exposure
- AHAndrew Huberman
Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. (instrumental music) 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 FASEB. 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 rapt with attention throughout the discussion. And I think that you'll want to have a pen and paper handy, because she offers not only a very clear understanding of the biological mechanisms by which other micronutrients operate, but some very clear and actionable tools and items that we can all embark on if we are to optimize our brain and body health. We also discuss behavioral protocols. Dr. Patrick is well known for her understanding of the scientific literature on sauna and the use of heat and cold for optimizing things like metabolism, longevity, cardiovascular health, and I'm delighted to say that we discuss that as well, and how behavioral protocols can interface with supplement-based and nutritional protocols. I'm confident that you'll learn a tremendous amount of information from Dr. Patrick, much of which is immediately actionable. And if you're not already following and listening to her excellent podcast, you'll absolutely want to do that. It's foundmyfitness.com is the website where you can get access to that podcast. It's also on Apple and Spotify and YouTube as Found My Fitness. Dr. Patrick also has a terrific newsletter that I recommend signing up for. It's foundmyfitness.com/newsletter is where you'll find it, and it includes research on fasting, micronutrients, sleep, depression, fitness, longevity, and far more, along, of course, with actionable protocols.
- 3:12 – 4:27
Momentous Supplements
- AHAndrew Huberman
I'm pleased to announce that the Huberman Lab Podcast is now partnered with Momentous supplements. Our motivation for partnering with Momentous is to provide people one location where they can go to access the highest quality supplements in the specific dosages that are best supported by the scientific research, and that are discussed during various episodes of the Huberman Lab Podcast. If you go to livemomentous.com/huberman, you will see those formulations. I should mention that we are going to add more formulations in the months to come. And you will see specific suggestions about how best to take those supplements, meaning what dosages and times of day, and in fact, how to combine those supplements with specific behavioral protocols that have been discussed on the podcast and are science-supported in order to derive the maximum benefit from those supplements. And many of you will probably also be pleased to learn that Momentous ships not just within the United States, but also internationally. So once again, if you go to livemomentous.com/huberman, you will find what we firmly believe to be the best quality supplements in the precise dosages and the best protocols for taking those supplements, along with the ideal behavioral protocols to combine with those supplement formulations.
- 4:27 – 5:30
The Brain-Body Contract
- AHAndrew Huberman
I'm pleased to announce that I'm hosting two live events this May. The first live event will be hosted in Seattle, Washington on May 17th. The second live event will be hosted in Portland, Oregon on May 18th. Both are part of a lecture series entitled The Brain Body Contract, during which I will discuss science and science-based tools for mental health, physical health, and performance. And I should point out that while some of the material I'll cover will overlap with information covered here on the Huberman Lab Podcast and on various social media posts, most of the information I will cover is going to be distinct from information covered on the podcast or elsewhere. So once again, it's Seattle on May 17th, Portland on May 18th. You can access tickets by going to hubermanlab.com/tour, and I hope to see you there. 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
- 5:30 – 9:42
AG1 (Athletic Greens), Thesis, InsideTracker
- AHAndrew Huberman
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. With Athletic Greens, I get the vitamins I need, the minerals I need, and the probiotics to support my microbiome. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and claim a special offer. They'll give you five free travel packs, which make it easy to mix up Athletic Greens while you're on the road, plus a year's supply of vitamin D3 K2.There are a ton of data now showing that vitamin D3 is essential for various aspects of our brain and body health. Even if we're getting a lot of sunshine, many of us are still deficient in vitamin D3. And K2 is also important because it regulates things like cardiovascular function, calcium in the body, and so on. Again, go to athleticgreens.com/huberman to claim the special offer of the five free travel packs and the year's supply of vitamin D3, K2. Today's episode is also brought to us by Thesis. Thesis makes what are called nootropics, which means smart drugs. Now, to be honest, I am not a fan of the term s- nootropics. I don't believe in smart drugs in the sense that I don't believe that there's any one substance or collection of substances that can make us smarter. I do believe, based on science however, that there are particular neural circuits and brain functions that allow us to be more focused, more alert, access creativity, be more motivated, et cetera. That's just the way that the brain works, different neural circuits for different brain states. And so the idea of a nootropic that's just going to make us smarter all around fails to acknowledge that smarter is many things, right? If you're an artist, you're a musician, you're doing math, you're doing accounting, a different part of the day you need to be creative, these are all different brain processes. Thesis understands this, and as far as I know they're the first nootropics company to create targeted nootropics for specific outcomes. They only use the highest quality ingredients, which of course is essential. Some of those I've talked about on the podcast, things like DHA, ginkgo biloba, phosphatidylserine. They give you the ability to try several different blends over the course of a month, discover which nootropics work best for your unique brain chemistry and genetics and goals, and with that personalization, design a kit of nootropics that's ideal for the different brain and body states you want to access. I've been using Thesis for more than six months now and I can confidently say that their nootropics have been a total game changer. My go-to formula is the clarity formula or sometimes I'll use their energy formula be- before training. To get your own personalized nootropic starter kit go online to takethesis.com/huberman, take a three-minute quiz and Thesis will send you four different formulas to try in your first month. That's takethesis.com/huberman and use the code Huberman at checkout for 10% off your first order. Today's episode is also brought to us by InsideTracker. InsideTracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better understand your body and help you reach your health goals. I've long been a believer in getting regular blood work done, for the simple reason that many of the factors that impact your immediate and long-term health can only be assessed with a quality blood test. What's unique about InsideTracker is that while there are a lot of different tests out there for hormones and metabolic factors, et cetera, with InsideTracker you get the numbers back in terms of your levels, but they also give you very clear directives in terms of lifestyle, nutrition and supplementation that can help you bring those values into the ranges that are best for you and your health goals. And that's very different than a lot of the other programs where you get a lot of information but you don't really know what to do with that information. InsideTracker makes that all very easy to understand and very actionable based on the very easy to use dashboard at InsideTracker. If you'd like to try InsideTracker you can visit insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Just use the code Huberman at checkout. And now for my discussion with Dr. Rhonda Patrick.
- 9:42 – 16:38
Stress Response Pathways, Hormesis
- AHAndrew Huberman
Rhonda, welcome. This has been a long time coming.
- RPRhonda Patrick
(laughs)
- AHAndrew Huberman
Even longer than you know, because even before we discussed you coming on this podcast as a guest, I've been watching your content for a very long time. So I want to start off by saying thank you. You were the spearhead to break through from academic science to public education, so I consider you first in and, uh, the rest of us are just in your wake. So thank you for that. It's been...
- RPRhonda Patrick
Oh, that is so kind. Thank you. Thank you so much. (laughs)
- AHAndrew Huberman
Well, it's absolutely true.
- RPRhonda Patrick
I am so excited to be here having a conversation with you, so-
- AHAndrew Huberman
Thank you. Well, it's absolutely true. If anyone, uh, 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, uh, educators that have formal science training and, uh, do regular posting of content, um, came in several years after you initiated it. So we're all grateful. Uh, 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, 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.
- RPRhonda Patrick
I would love to. Let's take a step back and I think you brought up a really important point here and I think that point has to do with the intermittent challenging of yourself and, and whether that is through, you know, temperature changes like cold or heat or through other types of stressors like physical activity or perhaps even dietary compounds that are found in plants. These are things like polyphenols or flavanols. Humans were, you know, we evolved to intermittently challenge ourselves and before we had Instacart where you could basically just get your food delivered to you, before the industrial revolution, you know, occurred, we were out hunting.
- AHAndrew Huberman
Sure.
- RPRhonda Patrick
And I say we, not us, but humans. We were out...... you know, gathering, we were moving. Um, and we had to be physically fit. You couldn't, you know, catch your prey if you were a sedentary slob, right? You were moving and you had to like, you know, pick your berries. You had to move. And so physical activity was a part of everyday life. And caloric restriction or intermittent fasting was also a part of it. This is another type of, of, of challenge, you know? We, we didn't always, you know, have a prey that we caught or maybe temperatures were such that, you know, there was nothing for us to gather, right? So food scarcity was something common as well as eating plants, so getting these compounds that I mentioned. So this is, these, these are all types of stress, intermittent challenges that activate genetic pathways in our bodies. These are often referred to in science as stress response pathways because they respond to a little bit of stress, you know? Physical activity is strenuous. Fasting's a little bit stressful. Heat, cold, these things are all types of little intermittent challenges, and, um, there is a lot of crosstalk between these stressors and the genetic pathways that they activate, and these genetic pathways that are activated help you deal with stress. And, and, and they do it in a way that is not only beneficial to help you deal with that little stressor, exercise or heat, it's, 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, uh, a little bit of cha- stressful challenge that activates these stress response pathways in a beneficial way that is a net positive, that actually, you know, is, it has a very profound antioxidant, antiinflammatory response or, you know, or whatever the response is. It could be the production of more stem cells. These are cells that help regenerate different, um, cells within tissues. Or something like autophagy, which is a process that can clear away all the gunk inside of our cells, pieces of DNA, protein aggregates. So you'll find that these stress response pathways are activated, like, by a v- a variety of stressors. So for example, one pathway is called heat shock proteins. And as their name would imply, one would go, "Oh, they're activated by heat." Well, correct. They are activated very robustly by heat, and we can talk about that. But, you know, you can eat a p- a plant like broccoli sprouts, which is high in something called sulforaphane. This is a, a compound that, um, is, is sort of like a hormetic compound, or as David Sinclair likes to say, it's a xenohormetic compound. I love that. I love that term. Um, and it activates heat shock proteins among other things. It also ac- 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 gonna more robustly activate heat shock proteins from heat versus cold, but there is some overlap. Um, so I think that sort of forms the foundation there.
- AHAndrew Huberman
Mm-hmm. Yeah, that's very helpful. And, uh, you know, it brings to mind i- in the context of the nervous system, I always tell people, you know, you only have a small kit of neurochemicals to work with. There isn't dopamine for, um, Netflix and then dopamine for relationship and dopamine for work, et cetera. There, dopamine is a generic pathway by which motivation, craving, and pursuit emerge, et cetera, eh, just like adrenaline is a, a generic theme of many different behaviors. And I, it seems that it is the job of biological systems to be able to take a diverse range of inputs, even unknown inputs. Like we don't know what technology will look like in three years, but you can bet that some of those novel technologies will tap into the very systems that I'm talking about now, and, um, 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, uh, before we, uh, talk a little bit more about cold and heat. Y- y- you mentioned plants
- 16:38 – 21:12
Plants, Polyphenols, Sulforaphane
- AHAndrew Huberman
as a, 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. Um, the extreme version from the carnivore types, um, 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, uh, what's healthy for the planet, animals, and maybe for us. But if we set aside that argument and we just raise the hypothesis that plants have compounds that are bad for us, but maybe by consuming them in small amounts, they're creating this hormesis type scenario, so then I think we conceivably solve the problem. We could say, yes, uh, plants are bad for us, but in small amounts, they provide this hormetic response, and they're good for us, right? So it, in the same way that heat is, uh, 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 and these compounds? Do you think of them as good for us or as, um, bad for us, they're a very sharp blade and we want to use them potently?
- RPRhonda Patrick
I, I actually, I think that it's impo- almost impossible. I mean, you'd have to eat nothing but the same plant all day every day in lar- I mean, the bioavailability of these, these compounds in the plants, they're attached to a food matrix, um, you know? It's, it's not like taking it in a supplement form as well. Um, it, it's, it's such that, like, it's, it's very difficult to make it toxic. Now, there are some cases, for example, if you eat cabbage, and I think there's some group in Africa or somewhere that, like, that's all they eat is cabbage, and there is a goitrogen in cabbage. It's not sulforaphane. It's another compound, but that's all they eat every day, nothing but that, and they get-
- AHAndrew Huberman
They get goiter, the thick neck. Mm-hmm.
- RPRhonda Patrick
Yeah, and they're, like, iodine deficient on top of that. So, um, you know, I do think there's, there, you can, of course-... make... I mean, there are types of plants that are toxic in small quantities, right? I mean, that-
- AHAndrew Huberman
Hemlock.
- RPRhonda Patrick
Hemlock, exactly. So-
- AHAndrew Huberman
Will kill you. Folks, don't, don't play this game with hemlock.
- RPRhonda Patrick
(laughs) But you're not gonna get poisoned from eating, you know, your, your, your serving of broccoli at dinner, right? So, I mean, it, it depends on the plant.
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
It's, it's, I don't... These generalizations are kind of ... They're just not useful, and I think that a lot of people online, um, in the blogosphere, it, it, it, they gravitate towards them because it's just easier, and it's a lot more sensational. Um-
- AHAndrew Huberman
I eat plants, meat, and starches. I'm one of those rare omnivores out there now.
- RPRhonda Patrick
I do too. (laughs)
- AHAndrew Huberman
I feel like a r- a rare (laughs) or it's rare to be an omnivore, but I think once you step out of the social media, uh, as you said, the blogosphere, uh, most people, m- I would say 99% of people on the planet are probably omnivores.
- RPRhonda Patrick
Right.
- AHAndrew Huberman
And someone will probably correct me, but-
- RPRhonda Patrick
And I th-
- AHAndrew Huberman
... I doubt the number falls below 90, 98.
- RPRhonda Patrick
I think if you look at data, you know, um, and, and when we have carnivore data, I, like, I can't wait to see it, but, like, right now, it's a lot of, "Okay, well, this is a lot of anecdotal evidence," and there's, you know, there's a good... There's a lot of, uh, good starts with anecdotes, but, like, people change a thousand things at once, and they don't realize that, but they do. And so anecdotal data is only so good, right? It's a, it's a starting point. Um, and so we don't really know longterm what carnivore diets are gonna do, you know. They may be beneficial short-term. Um, they may, you know, be beneficial for reasons of elimination of other things. Like, who knows, right? Lots of possibilities. But I do think with respect to plants, um, you know, that there's n- that, that there's so much evidence, like for example, sulforaphane is one that I, I really like, because, um, uh, there's just evidence that sulforaphane 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, um, genes that are involved in detoxifying compounds that we're exposed to from our food, like heterocyclic amines. In fact, there have been GWA studies. So these are genetically ... Um, these are studies that are, um, genome-wide associated studies. For people listening, uh, that aren't familiar, people have a variety of versions of genes, and, um, we have a gene that's able to make, um, heterocyclic amines to basically de- detoxify it so it's not as harmful. Um, and, 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.
- 21:12 – 23:50
Tools 1: Sulforaphane - Broccoli Sprouts, Broccoli, Mustard Seed
- RPRhonda Patrick
But if they eat a lot of broccoli and cruciferous vegetables, it negates that risk because they're getting sulforaphane, which activates, uh, a lot of the glutathione transfer g- glutathione transferase and synthase genes. So glutathione is a major antioxidant in our brain and 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 sulforaphane or broccoli or broc- broccoli sprouts, which have like 100, up to 100 times more sulforaphane than broccoli, are activating glutathione in the brain. There's human evidence of that. I mean, that's amazing-
- AHAndrew Huberman
That is amazing. Can I just-
- RPRhonda Patrick
... um, in plasma. Yeah?
- AHAndrew Huberman
Uh, s- sorry to interrupt. I just want to make sure when ... Uh, so broccoli sprouts are different than broccoli. Um, and you just told us, uh, that they have much, they're much richer in these, um, these compounds. So note to self, I should have broccoli sprouts, not just broccoli. Uh, can we cook the broccoli and still get these nutrients, or do we have to eat it raw? I confess, eating raw broccoli is really aversive to me.
- RPRhonda Patrick
(laughs) Um, so there... The sulforaphane is formed from a compound called glucoraphanin, which is in the broccoli, and the enzyme that converts it into sulforaphane is myrosinase, and it's heat-sensitive. Uh, so you do somewhat lower the sulforaphane levels when you c- when you cook the broccoli. However, um, there was a study a few years back that showed adding one gram of mustard seed powder, ground mustard seed powder, which also contains the myrosinase enzyme, to your cooked broccoli increases the sulforaphane by fourfold.
- AHAndrew Huberman
So m-
- RPRhonda Patrick
So ...
- AHAndrew Huberman
Th- this is great 'cause I confess, I like broccoli if it's cooked to the appropriate density, um, not too mushy, but definitely not raw. The idea of eating raw broccoli to me just sounds horrible, but I, I l- like the way mustard seed sounds. So just a little bit of mustard seed powder added to the cooked broccoli can recover some of these compounds.
- RPRhonda Patrick
Yes.
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
So what I do is I will, you know, lightly steam my broccoli, and then I add a little bit of my Kerrygold butter, um, and then I add some mustard seed powder on the top of that.
- AHAndrew Huberman
And-
- RPRhonda Patrick
And it's got a little s- little kick. Like, it's just a little spice, you know?
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
And if you don't taste that, it's expired. Like, it should have a little kick.
- AHAndrew Huberman
And because I know people will want to know how often and how much, um, you know, are you eating this every day or most days of the week?
- RPRhonda Patrick
Well, I had shifted to supplementation with sulforaphane. I've, I have admitted, I'm, I'm admitting right now that I've been terrible about it the past, like, I don't know, six months or so.
- AHAndrew Huberman
The supplementation or the r-
- RPRhonda Patrick
Yes.
- AHAndrew Huberman
... or the broccoli?
- RPRhonda Patrick
Yes, the supplementation. And, um ... And, uh,
- 23:50 – 25:25
Tool 2: Moringa & Nrf2 Antioxidant Response
- RPRhonda Patrick
so there's another way to get... There's another compound, and it's actually called Moringa, and Dr. Jed Fahey, who's really the expert on sulforaphane, uh, he's a good friend of mine. He's been on the podcast a couple of times. He, um, h- he, he basically thinks, and, you know, has done a lot of research on Moringa as well, that it's, it's like a cousin, and it activates the Nrf2 pathway similarly to sulforaphane. And so I've been buying this Kuli Kuli Moringa powder. I don't have any affiliation with them, but-
- AHAndrew Huberman
Kuli Kuli is a brand?
- RPRhonda Patrick
Kuli Kuli's the brand.
- AHAndrew Huberman
Okay. That you have no affiliation to?
- RPRhonda Patrick
Sell it at Whole Foods. I have no affiliation.
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
But Jed Fahey, like, has researched it, like, like that specific brand. And so it's, like, legitim- it's legit, you know? It's, like, science-backed-
- AHAndrew Huberman
Yeah.
- RPRhonda Patrick
... um, in terms of actually containing Moringa and activating Nrf2. Uh, and I add it to my smoothies.... so that's what I've been doing, and-
- AHAndrew Huberman
What, what are some approp- um, dose ranges?
- RPRhonda Patrick
... I, so I-
- AHAndrew Huberman
Of course, we give the usual recommendations that people should talk to their physician, et cetera, et cetera, but, um, if people are going to ex- what do you take? That's always the, uh, "Let's take-"
- RPRhonda Patrick
A big heaping tablespoon.
- AHAndrew Huberman
"... the David Sinclairian approach."
- RPRhonda Patrick
(laughs)
- AHAndrew Huberman
"What do you..." Where he'll talk about what he does, um, as a way to, to deal with this. And of course, everybody's different and should, uh, in all seriousness, should, um, anytime you add or delete something from your, uh, uh, consumption should, uh, consult some trusted healthcare professional, trusted by you. Um, what, do you recall the, the dosages?
- RPRhonda Patrick
I do a big heaping tablespoon, um-
- AHAndrew Huberman
So Moringa, Kuli Kuli Moringa.
- RPRhonda Patrick
Yeah, and it's, it is-
- AHAndrew Huberman
It sounds like a song.
- RPRhonda Patrick
It's with a K.
- AHAndrew Huberman
Yeah.
- RPRhonda Patrick
I know, it does. (laughs)
- AHAndrew Huberman
(laughs)
- RPRhonda Patrick
Um, but, you know, for people
- 25:25 – 27:10
Sulforaphane: Antioxidants (Glutathione) & Air Pollution (Benzene Elimination)
- RPRhonda Patrick
also listening, it's like, "Well, why would I do that?" You know, I mentioned the glutathione in the brain. I, I mentioned it in, um, plasma. It's, it's been shown to lower DNA damage in people and, and white blood cells. Uh, it's also been shown... There's been several different studies in China. You know, in China, there's a lot of air pollution, and I mentioned that, you know, it's a very powerful activator of NRF2, and I know you're, you're familiar with NRF2. But NRF2 is like, it's a transcription factor that is... It is, it is binding to a little specific sequence in a variety of different genes, and it's, like, turning them on, uh, 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, um, some of the genes are, are basically these, these detoxifying pathways. We talked a little bit about the glutathione, but there's also ones that are involved in, um, air, airborne carcinogens like benzene. So benzene's found in air pollution, I mean, cigarette smoke. I mean, who... If you're c- if you're smoking cigarettes still, like, please try to quit, but-
- AHAndrew Huberman
Yeah, you're mutating your DNA.
- RPRhonda Patrick
I mean, yeah, it's, like, the worst.
- AHAndrew Huberman
Like, to say nothing of the lung cancer. You're mutating your DNA.
- RPRhonda Patrick
And heart disease risk, heart disease risk. But an- anyways, um, people, and this has been repeated in, in more than one study, that literally after 24 hours of taking, I can't remember off the top of my head what the dose of sulforaphane from broccoli e- extract, uh, broc- broccoli's, um, seed extract was, or broccoli, uh, sprouts extract, not the seed. It was the sprouts. Um, anyways, they started excreting like 60% benzene and acrolein. I mean, that's something that we get in cooked food.
- AHAndrew Huberman
It's coming out in their urine?
- RPRhonda Patrick
Coming out in their urine. Yeah, so-
- AHAndrew Huberman
Well, I'm not a smoker, and I have to be honest. It's rare that I hear of a supplement for the first time 'cause I've been, you know, deep-diving on supplements since I was in my teens. Uh, this is fascinating, and it brings me back to this question that we had before, and I, I, I appreciate
- 27:10 – 29:35
Plants & Stress Response Pathways, Intermittent Challenges
- AHAndrew Huberman
that you answered it very clearly. Plants have compounds that are good for us. They're not just stressing us. They're activating pathways that are reparative. That's what, that's what I'm taking away from w- everything you're telling me.
- RPRhonda Patrick
Right, and, and, and that our bodies were supposed to be getting that stress to have those pathways activated. Like, it is, like... You know? Right? I mean, this is conserved among different animals. Like, this is, this is, this is something that is, is suppo- it's supposed to happen, and in our modern day world, we don't have to eat plants. We don't have to move anywhere or exercise. We don't have to go through periods of not eating food because we can have it at our fingertips at any second, right? So, I mean, we've got this conundrum of, we're never activating these stress response pathways that we're suppo- that we're supposed to activate, we're supposed to.
- AHAndrew Huberman
I find that fascinating, and again, uh, drawing a parallel to the nervous system. Um, so what I'm hearing you say is that, historically, we would have to go through some stress, some... Confront cold, or con- confront heat, or confront effort, or, or hunger, and have to exercise, essentially, in order to obtain these compounds, and then those compounds are reparative. Yeah, I, I feel that resembles, uh, the dopamine pathway. I always say, you know, there's nothing wrong with dopamine. People think about dopamine hits as bad or dopamine is bad. There's absolutely nothing wrong with dopamine. The problem is, dopamine, especially high levels of dopamine released without the need for effort to access that dopamine, is problematic. So a line of cocaine gives you a ton of dopamine with no effort except to ingest the drug, whereas, um, working for four years or more to get your degree will release a lot of dopamine and a lot of cortisol along the way, as we know, and it's considered a healthy accomplishment in most cases. A tremendous amount of... If you... 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 re- we are rewarded with particular compounds that are reparative both for the challenge, but then it make us stronger. It is... Hormesis really is, it seems, a case of what doesn't kill us makes us stronger. Um, what other...
- 29:35 – 35:08
Traumatic Brain Injury, Sulforaphane, Nrf2
- AHAndrew Huberman
So you mentioned-
- RPRhonda Patrick
Can, can I add to that one thing you just said?
- AHAndrew Huberman
Yeah, please.
- RPRhonda Patrick
Because-
- AHAndrew Huberman
Please.
- RPRhonda Patrick
... because this has been shown with, for example, sulforaphane in animal studies. You precondition, give the animals sulforaphane, and then you expose them to, like, you know, hypoxia or some sign of i- ischemic stroke condition, whatever they do to induce that, and the sulforaphane, it basically protects them. Like, it... Their preconditioned, and their, their ra- their stress response pathways are primed, and so when they're then exposed to the ischemic stroke, they, their outcomes are so much better, so much better than the animals that didn't get the sulforaphane 48 hours before, whatever it was. You know, and, and this is, like, this has been shown in multiple animal studies with sulforaphane specifically in the brain. Um, I know Mark Mattson, uh, Dr. Mark Mattson. He's a lo- often thought of as the intermittent fasting king, but, you know, he's a neuro- neuroscientist, and he, um, he did publish some work and, and talks about sulforaphane as well.
- AHAndrew Huberman
I'm really glad you brought that up b- uh, that example up because many of the questions I get on social media and elsewhere are about traumatic brain injury and TBI, and, you know, is just one example. Um, and people always think, "Oh, sports. It's football." Whenever you say TBI, people always think football, and I want to just take a men- a moment to editorialize.90% or more of traumatic brain injury is construction work, at-home accidents. Football players are a ti- hockey players are a ti- 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, uh, concussion is, is prominent. People are always asking, "What can I do in order to offset brain injury? Uh, I had a concussion two years ago, what can I do?" And, 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, um, either should be explored in the context of brain injury, or I'm guessing are being explored in the context of brain injury.
- RPRhonda Patrick
Yeah, so a couple of things there. Um, one is that, I mean, traumatic brain injury, I mean, it's terrible, but it's also, it's so interesting, because it's also like literal real-time brain aging. Like, you know, like it's, you're able to, like, accelerate it and understand. So I, I often think of, when I think of traumatic brain injury, I think of so much overlap between Alzheimer's disease and dementia and these neurodegenerative diseases, because there is, there are, there are a lot of similarities there, you know? And so sulforaphane, I personally think, um, and I do think there's been some animal research with TBI, I mean, and, and, uh, sulforaphane, mostly preconditioning rather than, uh, treatment. Um, so again, it's like, well, I mean, if you're gonna, if you want a healthy lifestyle thing, and you're a construction worker or you're fill in the blank, that's, you know, gonna... I mean, anyone that drives a car, I mean, you're at risk to some degree, right?
- AHAndrew Huberman
Or bicycle.
- RPRhonda Patrick
Bicycle, yeah. I mean-
- AHAndrew Huberman
Around Stanford, we have, you know, I would say, uh, people demonize motorcycles, people demonize a lot of things, but moving fast through space on a small object next to a 3,000-pound vehicle, I mean, we've lost, we have a number of friends that have died. We have a number of people with traumatic brain injury. Um, I'm not against cycling or cyclists, but it, it is, um, it's a risky sport, uh, by any stretch. Um, 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, the mustard seed, uh, is there evidence that... Well, first of all, Nrf2 is expressed in neurons, right? So those, those cells should be protected. Are there other cells of the body that could possibly gain protection from these pathways?
- RPRhonda Patrick
Um, well, lungs for one, uh, but, you know, just even in plasma cells. I, I mean, I think it's pretty, Nrf2 is pretty ubiquitously expressed. Liver. Uh, so there's, I mean, there's, there's so many animal studies that have looked at all those things. I try to kind of gravitate towards human ones 'cause it's a li- little, a lot more relevant. Um, but, but I think, you know, overall, like I s- I mentioned, you know, DNA damage lower, I think, I think it was like 24, 24 or 34% lower in, um, human blood cells after broccoli sp- um, broccoli sprout powder supplementation.
- AHAndrew Huberman
Wow.
- RPRhonda Patrick
Um, and, and I made a video on this, like, years ago, 2016 maybe, and I think I have, like, the references on there to... Exact amounts, I can't remember.
- AHAndrew Huberman
We can link to the video, yeah.
- RPRhonda Patrick
But it was, it's kind of an old video. It's two th- 2016. But, um, I also had Jed on the podcast, uh, and he, he did talk about this. Um, but you know, it's also been shown in randomized controlled trials to help treat autism and autistic symptoms. And yet again, it's doing interesting things in the brain, and, um, I think it, I think it does have something to do with the oxidative stress and the glutathione, which would be relevant for TBI treatment. Uh, and it hasn't been shown empirically that that helps with treatment, but I do think, uh, someone could do that study. Um, I think that it s- it should be done (laughs) , honestly, because it's a low-hanging fruit, I mean, if there's any impact. And there is at least one preliminary study that glutathione is increased in the brain after humans are, you know, basically taking sulforaphane. So, um-
- AHAndrew Huberman
Which is really, uh, for people listening, that's so important, because a number of compounds that, uh, 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. Um, we will get back to heat and cold in this, uh, theme that I tried to surface, but I just find this too interesting to, to, uh, diverge at this point, um, from, from these themes.
- 35:08 – 48:40
Tools 3: Omega-3 Fatty Acids (ALA, EPA & DHA), Fish Oil, Oxidation
- AHAndrew Huberman
So are, what other compounds or micronutrients do you, uh, place in the top tier of useful, interesting... There are animal studies. Maybe there are hopefully also some human studies. Uh, we've talked about a few. Uh, I know you've talked a lot about omega-3 fatty acids. So if you had to do your kind of top three-
- RPRhonda Patrick
Yeah.
- AHAndrew Huberman
... um, your, your superstars of nutrients for the brain and body, sounds like we've got one, one set, what would you put in alongside them?
- RPRhonda Patrick
Omega-3, uh, the marine omega-3 fatty acids. So these are found in marine types of, uh, you know, animals, fish, cold water fish, fatty fish. Uh, so, so there's a, there's three fatty acids. There's one from a plant, and, and, um, that's often referred to as ALA, people call it short alpha-linolenic acid, and then there's eico- eicosapentaenoic acid, or EPA, and docosahexaenoic acid, which is DHA.
- AHAndrew Huberman
Two.
- RPRhonda Patrick
Yeah. But EPA-
- AHAndrew Huberman
I'm amazed you can pronounce two of the most difficult words to pronounce right next to, oh, and spell, and right next to ophthalmology, which if you can spell it... Um, I know people who have appointments in ophthalmology departments that don't know how to spell ophthalmology. Uh, a little secret, there's a, there's an extra P in there. Um, so the ALA, the... I'm not going to attempt to pronou- pronounce it, because your pronunciation was perfect, of both of these two compounds. Uh, and you said they're marine sources. So fish, so sardines, cod, this sort of thing, but what about krill? I've seen krill oil, and there was a, a few years back people were saying krill is a better source for omega-3s than, um, is, uh, fish oil. I took some krill oil capsules. Um, made me itch all over, so I stopped.
- RPRhonda Patrick
Do you have a shellfish allergy?
- AHAndrew Huberman
No, I don't think so.
- RPRhonda Patrick
No. Okay.
- AHAndrew Huberman
I don't think so. I'm not a big fan of shellfish, but I like, you know, I'll have oysters every now and again or shrimp or something and feel fine, so.
- RPRhonda Patrick
... yeah, we can talk about sources. So, um, krill is a, um, a, a source mostly of a type of DHA and EPA that's in phospholipo- lipid form. So it's a phosphatidylcholine omega-3 fatty acid, and, um, that's different than most, most of the... Well, if we're talking about s- fish oil supplements, that's a different story. But if you're talking about comparing fish to krill, eating krill, like, we're talking about the foods.
- AHAndrew Huberman
Oh, I would never eat krill.
- RPRhonda Patrick
Okay. Are we talking about the supplements? Okay, so fish oil supplements.
- AHAndrew Huberman
Yes. I apologize. Yeah, krill supplement versus fish o- fish oil supplement, and if you, if it fits in the conversation, talking about great sources of, of omega-3s in their whole form, I, I've a, I've a bad feeling you're going to tell me sardines, um.
- RPRhonda Patrick
Sardines are g- are, yeah, they're, they're awesome. Anyways, but-
- AHAndrew Huberman
Except for, except for the taste. (laughs)
- RPRhonda Patrick
... except for the, a- and, and for the potential contaminants, um, mercury I think was one. No. Joe was, 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 used to eat ser- sardines every day. And, um, and then he had, like, really high mercury levels, and I was really shocked because sardines are like, you know, low in the fish, you know, group. So they're, the, the higher up you get, like swordfish and sharks, like, really high mercury 'cause they're eating all the other fish, right? Um, but I think some brands, and if you look at like ConsumerLab, um, ConsumerLab, there's, it's like a third party site that I'm not affiliated with, but e- I use them because they, they do a lot of analysis of different foods and supplements. And so you can look at, like, some of their sardines, and they've like, they have a list of, like, ones that are pretty decent. But anyways, um, back to your question about fish oil supplements versus krill oil supplements. Uh, so the, one of the major differences is the, that fish oil supplements, if you get a high quality one, it's in a triglyceride form. Um, so you're, you've got like a, a glycerol backbone with three fatty acids, and, and that's attached, and those are either DHA or the EPA. And, um, or if you have a lower quality fish oil supplement, then you have what's called eth- ethyl ester form. And typically, um, the reason for that, it's, 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, reesterifying it, which costs more money. So you can get it in ethyl ester form, which, um, isn't as bioavailable, and in fact, if you don't take it with food, you're gonna be in trouble. You're not gonna absorb m- m- much of it at all. Um-
- AHAndrew Huberman
Would you see this on the packaging? Is it gonna say it's in this ethyl, ethyl form?
- RPRhonda Patrick
Some fish oil brands will put it on their website, perhaps on their packaging, but you, most of the time, um, you'll have to dig for it on the website and/or call them. Uh, but I think for the most part, ones that are, like, higher end will, will market it, like triglyceride form. And it's not that ethyl ester's bad. It just means take it with food. So, um, so, so the, one of the major prescription omega-3s out there is, both of 'em actually, Lovaza, which is a mixture of DHA and EPA, as well as Vascepa, which is a highly purified EPA. These are both prescribed by physicians to patients with hypertriglyceridemia, so high triglycerides, um, among other things, I think, um, m- maybe dysregulation of lipids as well, but-
- AHAndrew Huberman
This is amazing. So, uh, for people, 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.
- RPRhonda Patrick
Yes.
- AHAndrew Huberman
Just to really-
- RPRhonda Patrick
Well-
- AHAndrew Huberman
I just want to-
- RPRhonda Patrick
(laughs)
- AHAndrew Huberman
... push home, again, I'm not carnivore, keto, or anything. I'm an omnivore, but, but to just push home that, um, we, uh, one thing that's so wonderful that you've done over the years and that you continue to do is to move away from these very, um, broad sweeping statements about, you know, fat is bad. I mean, here's a case where we're saying fat is not only good, it can be used to combat issues with fat metabolism. And then there, you know, fats are not just one thing. They're many things. Um, so anyway, I just am, wanna put a little highlighter and, and a point of appreciation there and, and make sure that people are, are sensitized to the fact that, um, if you hear that fat is bad, you have to ask, "What kind of fat?" Right? And, and here we're talking about these omega-3s. Okay, so the triglyceride form can be taken with or without, uh, food, um, and there's prescription forms. What's w- uh, I can't get... I, I don't know if I can get ahold of the prescription form unless, um, you know I-
- RPRhonda Patrick
You have high triglycerides.
- AHAndrew Huberman
Or I have a friend with high triglycerides.
- RPRhonda Patrick
Or, you know. (laughs)
- 48:40 – 52:02
EPA Omega-3s & Depression
- AHAndrew Huberman
mainly based on the data that I'm aware of, uh, looking at comparison of people doing that, anywhere from two to four grams of EPA per day compared to, uh, SSRIs, serotonin, selective serotonin reuptake inhibitors, and, um, 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 are-... by my read are remarkable, people that take these things in sufficient doses, meaning the EPAs, are able to get by with much lower dosages of SSRIs for depression relief or, in some cases, to come off their SSRIs completely, um, or avoid going on antidepressant medication. Now, of course, this is not something people should cowboy. You know, mental health issues are serious. But, um, what other reasons ... I'd love your thoughts on that-
- RPRhonda Patrick
Yeah.
- AHAndrew Huberman
... on the mental health part. And, uh, 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?
- RPRhonda Patrick
So do you, do you know, um ... So I actually published a paper back in 2015 about the role of omega-3 and vitamin D in depression, bipolar disorder, bipolar disorder schizophrenia, and impulsive behavior. But, um, so, like, within that paper, like, the, doing background research ... And this was a review article, by the way. I was just connecting dots 'cause
- AHAndrew Huberman
No, I'm gonna, I'm gonna grab the-
- RPRhonda Patrick
But, um-
- AHAndrew Huberman
I, I confess I don't know the paper, but, eh, I love quality reviews-
- RPRhonda Patrick
(laughs)
- AHAndrew Huberman
... because the references therein are so useful.
- RPRhonda Patrick
Well, um, there's a huge role for inflammation, the cause of inflammation in depression. And, um, you know, I think we did a short animated video on this as well, like, years ago, back when I was, you know, publishing that, that work, where, you know, people are injected with lipopolysaccharide. I mean, this is something that we're, we're generating from our, from our gut, mostly from, you know, our gut permeability, which happens a lot. Um, endotoxin, it's also called. It's like there, it's endotoxin lipopolysaccharides. It's basically the outer membrane of bacterial cells-
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
... uh, when bacteria are di- die. So, like, when the immune cells in our gut come into contact with the bacteria because we drank, uh, alcohol five days in a row or whatever, um, we release endotoxin, or it's st- something stressed us out, we release endotoxin into our body, and that causes inflammation. And so you can inject people with lipo- lipopolysaccharide and cause depressive symptoms.
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
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?
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
Uh, it totally, the depressive symptoms, versus the placebo, so the placebo with saline control. So there was, this was a placebo control because obviously it's hugely important for depression. Um, it ameliorated the depressive symptoms-
- AHAndrew Huberman
Amazing.
- RPRhonda Patrick
... that was caused by lipopolysaccharide.
- AHAndrew Huberman
Amazing. And LPS, lipopolysaccharide, is no joke. I, uh, years ago, when I was working on thermal regulation, uh, we would inject animals with LPS to induce fever. It, there's a, the vagus nerve registers the presence of LPS signals to these, uh, particular hypothalamic areas and cranks up body temperature because basically it's a signal that the body is infected.
- RPRhonda Patrick
Mm-hmm.
- AHAndrew Huberman
Right? Um, amazing. Uh, 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 D- DHA in the same-
- RPRhonda Patrick
Yes.
- AHAndrew Huberman
... supplement. Is that okay?
- RPRhonda Patrick
Yes. Yeah. Yeah.
- AHAndrew Huberman
Yeah. Okay.
- RPRhonda Patrick
And, and, you know, to kind of
- 52:02 – 54:23
Krill Oil vs. Fish Oil Supplements?
- RPRhonda Patrick
... Boy, we have, we got a lot of things to hit back on because your, one of your original questions was krill oil versus fish oil.
- AHAndrew Huberman
Yes. It's still in the queue.
- RPRhonda Patrick
And DHA-
- AHAndrew Huberman
Yeah.
- RPRhonda Patrick
DHA specifically, um, is, it, it, it's, you know, in phospholipid form. It, it's more bioavailable, so our, our bodies, you know, if you're comparing exact quantity or concentration, you know, in triglyceride form versus, um, phospholipid form, you will get more in your plasma cells, or in your plasma, plasma cell, in your pl- in your plasma, uh, with krill oil. However, krill oil, uh, supplements are so low dose. Like, I mean, good luck getting two grams (laughs) -
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
... of omega-3 from krill oil. And, also, krill oil supplements are notoriously, like, rancid. I don't know, for whatever reason.
- AHAndrew Huberman
Maybe that's what made me itchy all over.
- RPRhonda Patrick
I, I think they're just ... I, I, like, I, I, I haven't found a good krill oil supplement. Um, I, I pretty, pretty much stay away from it. I mean, if you smell it too, I mean, it's just like, like it just smells rancid.
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
Um, so, but the thing is, and I also published a paper on this back in 2019, or, yeah, something like that, um, about DHA in phospholipid form getting into the brain, um, in a, through a different mechanism than DHA in triglyceride form, and so it's going through a transporter called the MFSD2A transporter, and I think it's very relevant for people with an ApoE e4 allele. So, uh, I've kind of-
- AHAndrew Huberman
People with, with an Alzheimer's susceptibility.
- RPRhonda Patrick
Right. So, so, like, 25% of the population has an allele in a gene called ApoE, uh, 4, and, um, basically it, uh, uh, it's ApoE, but the 4 is, is re- referred to as the, the, the bad kind of version of it. Um, this is something in our bl- our bodies. It's also in our brain, and it, if people have one of these versions, if they got one from their mom or their dad, they have a twofold increased risk for Alzheimer's disease. If they get two, which is much ... It's much more, um, less, less, it's less common. I think it's, like, 2% of the population or something has two alleles. But they have, like, a 10 or 11-fold increased risk of Alzheimer's disease. So, um, there is a role for phospholipid form, um, DHA in their brain, but you also make phospholipid DHA inside your body, and you can do that by taking in more triglyceride form. So two grams, like the magic, more, two grams or more is the magic number, I think. Um,
- 54:23 – 59:24
Benefits of Omega-3 Fatty Acids, Omega-3 Index & Life Expectancy
- RPRhonda Patrick
so, so kind of back to, like, the, the why for fish oil, and, and I, I personally think it is one of the most powerful anti-inflammatory, um, things, dietary lifestyle things, that we can, we can get easily, relatively easily-
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
... that, um, is, is gonna powerfully modulate the way you think, the way you feel, and the way you age. And, uh, a variety of different types of studies kind of led me to that conclusion. Uh, a, a variety of, you know, observational studies, so there's been lots of work by Dr. Bill Harris and his collaborators looking at what, it's called the omega-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, it's a long-term marker of omega-3 status. This is very different from-... 99.9% of any study you see or any, um, lab that you go to to get your omega-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 it like you went out to dinner? So, um, it's not a great biomarker for long term omega-3 status. It's kind of like the, you know, fasting blood glucose levels versus the HbA1c, which is like a long term marker, right, of your, of your blood glucose levels. So, the omega-3 index, he's done a variety of studies, uh, observational studies. So for people listening, these are studies. They're obviously flawed, because they're not establishing causality. They're, you know, you're looking at, um, people's lifestyles. But in the sa- in the case of, of Bill Harris' work, he's measuring something. So he's measuring the omega-3 index, and he's measuring the omega-3 index in people and then looking at their mortality risk, for example, or their cardiovascular disease risk. Uh, and what he has found is that most ... Fir- first of all, um, standard American diet has an omega-3 index of 5%. Japan, by contrast, has an omega-3 index of around 10 to 11%. Big, big difference there. And they also have about a five year increased life expectancy compared to people in the US. And that's-
- AHAndrew Huberman
Do you think that's mainly due to their fish intake, seafood intake?
- RPRhonda Patrick
So what he showed was ... I, I think it's a, a big part of it.
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
I mean, you can't o- say it's the only thing, but what he showed in his data was that in ... And I, I think it was Framingham study where he, he looked at the omega-3 index in people that had a omega-3 index of 4% or lower, so close to what the standard American is but a little bit lower. Um, they had a five year decreased life expectancy compared to people that had an 8% omega-3 index. And so, um, big difference there, right? Five vers- five years life expectancy. But here's the really interesting thing, Andrew. He also looked at smokers, and smokers and their omega-3 levels, and so he stratified it, right? And he found smokers that had no omega-3 were like the worst of all. I mean, it was like, it was just like worse, right? We, we all know smoking is bad for us and will take, take years off our life expectancy.
- AHAndrew Huberman
Absolutely.
- RPRhonda Patrick
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 o- low omega-3 index.
- AHAndrew Huberman
Wow.
- RPRhonda Patrick
Right?
- AHAndrew Huberman
Wow. And that's, that's amazing, um, and it's also amazing to me that people still smoke cigarettes. (laughs) But I see a lot of people vaping, and I, I, and I'm, and I know a lot of people consume cannabis, right? People love ... Has there been any studies of, uh, specifically of vaping or people, um, smoking marijuana and, uh, all cau- all-caused mortality?
- RPRhonda Patrick
Life expectancy? I haven't seen those.
- AHAndrew Huberman
Yeah.
- RPRhonda Patrick
I haven't seen those. Yeah.
- AHAndrew Huberman
They're not motivated enough to come in as research subjects.
- RPRhonda Patrick
(laughs) Okay.
- AHAndrew Huberman
That was, that was, again, a, a poor joke. Um, it is hard to study people, uh, 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. Um, but again, they're actually not very good research subjects in all seriousness, 'cause they are not very motivated or consistent and they forget their appointments. So, um, that's incredible. Um, and you mentioned the, 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. Um, food-
- RPRhonda Patrick
The omega-3s are, are, I mean, they are, they are resolving inflammation. They're, like, blunting inflammation. They're, they're doing so many different, like, a- they ha- they affect so many different parts of the inflammatory pathway, which is, I think it plays a huge role in, in the way we age, the way our brain ages, the way we feel, our mood, just our joints, all that. And so, it's ... It's amazing, but it's not, you know ...
- AHAndrew Huberman
I, I, 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
- 59:24 – 1:06:07
Tool 4: Food Sources of EPA Omega-3s
- AHAndrew Huberman
want to just touch on food sources for a moment. Um, first of all, are there plants that are rich in omega-3s? And second, my, 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 and eat high quality meats in relatively limited amounts. Um, but I do eat pretty often. But I've been told, uh, by these, uh, 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, 'cause 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 the, my steaks have omega-3s, or no?
- RPRhonda Patrick
Um, so there was a study published that compared conventional meat, so meat that is, you know, the, that animals are fed, you know, corn or soy or whatever it is.
- AHAndrew Huberman
Which, which is terrible.
- RPRhonda Patrick
Yeah.
- AHAndrew Huberman
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, (laughs) a joke, I read all the comments, but, um, the ... It seems to me that th- these animals would have to get, either be taking fish oil or eat plants that are very rich in omega-3s in order for the, the meat to actually contain sufficient omega-3s.
- RPRhonda Patrick
I ... So, so the meat, comparing the conventional meat to like the gra- grass fed or, you know, pasture raised cows, uh, or cattle, uh, there were higher levels of alpha-linoleic acid. And ALA is ... The, the ... It can be converted into EPA and DHA. Um, but the conversion is very inefficient and very dependent on a variety of factors, including genetics.... genetics, a b- a huge, you know, regulator. Like, some people can do it much better. Others, like, you're getting, like, 5% of conversion to EPA. Uh, estrogen is a major regulator of making that more efficient. And, and makes sense because pregnancy, when your estrogen just goes through the roof, I mean, y- y- these omega-3 fatty acids play a very important role in brain development. So you're, you know, eh, women are supposed to be converting any ALA they can into the longer chain omega-3 fatty acids, right? So, so, um, estrogen does affect that. But I would say plant sources... So if you're looking for the ALA, plant sources w- would be, you know, walnuts, flax seeds. Those are probably the highest. But if you're, if a person is a vegan or a vegetarian, their best bet is to actually get microalgae oil, and you can supplement with microalgae oil because microalgae do, it's, they do make the, the DHA. And so, um, that would be a better source for, for people that are, that are vegetarian and vegan rather than doing the, the flax seed oil, because of that conversion inefficiency, you know, the enzymes that convert ALA into, uh, EPA and DHA. Again, there's, it's inefficient.
- AHAndrew Huberman
And then for people that eat fish, um, sardines you said. Um-
- RPRhonda Patrick
Salmon.
- AHAndrew Huberman
... salmon, and you have to eat the skin, as I understand.
- RPRhonda Patrick
Uh, you don't have to but-
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
... it's good. I mean-
- AHAndrew Huberman
It's rich with, with omega-3s.
- RPRhonda Patrick
The oil, yeah. And, and, and the reason I say s- like, like I per- I think the best would be wild Alaskan salmon versus the farm-raised because the farm-raised, again, they're feeding 'em, they're feeding 'em corn, they're feeding 'em, like, grain and stuff-
- AHAndrew Huberman
Really?
- RPRhonda Patrick
... and then they give 'em astaxanthin. So astaxanthin is a carotenoid. It's the carotenoid that's in things like krill, crustaceans that make their red pigment.
- AHAndrew Huberman
Yeah, it's also being used now as a supplement, and there's a prescription form to try and rescue some age-related vision loss because of the, the role of the vitamin A pathway in photoreceptors. Uh-huh.
- RPRhonda Patrick
Yeah. Well, you know, actually the carotenoids themselves, so like lutein and zeaxanthin, they're really good at sequestering singlet oxygen, which is som- damaging, right?
- AHAndrew Huberman
Right.
- RPRhonda Patrick
So like-
- AHAndrew Huberman
Yeah, as we age, the, um, because the retinal cells, uh, the, uh, cells of the eye are so metabolically active, they accumulate a lot of reactive oxygen species, and, uh, mitochondrial repair and eliminating reactive oxygen species is, is a major, uh, theme of trying to rescue vision, I think that's-
- RPRhonda Patrick
Yeah. (laughs)
- AHAndrew Huberman
So that's, 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 from-
- RPRhonda Patrick
I've seen some. (laughs)
- AHAndrew Huberman
... Glen Sh- that's my, uh, good friend of many years and amazing scientist, Glen Jeffery's lab out of University College London. I'm del- we should talk about that at some point. If not today-
- RPRhonda Patrick
I, I saw that study, like 2020 was it?
- AHAndrew Huberman
Yeah. And now they have a second study.
- RPRhonda Patrick
Oh, do they? They've done- Okay.
- AHAndrew Huberman
Yeah. It's looking real. I mean, you know, they, they-
- RPRhonda Patrick
That's exciting.
- 1:06:07 – 1:10:22
Omega-3 Supplementation, Omega-3 Index Testing
- AHAndrew Huberman
- RPRhonda Patrick
And supplementation is a good way to get a, a high dose. And, and to get back to your dose point, uh, there was a, a couple of studies that, that basically, you know, sh- you know, I think there was so- 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. Uh, and that, and I think it was a little bit less if it was triglyceride form, but I think two grams is a, a good safe number. So most Americans that are not eating a lot of fish and they're not supplementing are probably around a 4 to 5% omega-3 index. And to get to the 8%, and, 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.
- AHAndrew Huberman
Yeah, I was gonna ask about, um, about testing.
- RPRhonda Patrick
Yes.
- AHAndrew Huberman
So, so where can somebody measure... Where and how can somebody measure their omega-3 index? Which, again, just to remind people is the, uh, 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?
- RPRhonda Patrick
Not the omega-3 index. Okay. So the omega-3-
- AHAndrew Huberman
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.
- RPRhonda Patrick
No, that was plasma.
- AHAndrew Huberman
Okay, I misunderstood.
- RPRhonda Patrick
That's okay.
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
So pla- 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.
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
The, the phospholipids. It's in a phospholipid, right? So your, your phospholipids are carrying thing, these are lipoproteins, like, they're carrying things like omega-3 and triglycerides and stuff and shuttling 'em around, so, um, the omega-3 index is actually in the red blood cells, and red blood cells take 120 days to turn over. So if you're gonna do a baseline test, um, if you wanna know before supplementing what your level is, you have to wait tw- 120 days before doing the second test after supplementing to know how much you, you went up. Because the o- that's how long it takes for your red blood cell to turn over. So, the omega-3 index, um, Bill Harris has a, um, a company that he, he co-founded. It's called m- Omega Quant, and they measure the omega-3 index. They have a variety of different index tests. You can do like a basic one or a little more advanced, but they-
- AHAndrew Huberman
This is from a blood draw.
- RPRhonda Patrick
It i- it, it's a little blood spot thing. Yeah.
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
And, um, you know, like, he uses money to, like, funnel back into doing lipid research, so he's, like, out there doing all sorts of interesting studies on omega-3s. It's great.
- AHAndrew Huberman
Great.
- RPRhonda Patrick
But I, uh, oh, the omega-3 index is great. Um, I think that, honestly, more people and more researchers should be using it because, uh, th- the conflicting data alway- it always comes down to what we're measuring, the sensitivity of it, a- y- you know, are we even measuring anything? So, you know, 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 omeg- the ome- omega-3 index? Did-
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
You know, there's all sorts of problems with randomized control trials, and I think that it just, we need to, like, as scientists, we need to come together and, like, make some progress. I mean, you know? Let's all talk to each other.
- AHAndrew Huberman
Mm-hmm.
- RPRhonda Patrick
Let's, let's, let's figure things out. Like, I, this, this test is out there. It should be used. It should be used not just by Bill's group, but, like, everyone.
- AHAndrew Huberman
Yeah. Well, and I'm learning so much from you b- and I agree we need more collaboration. I've always enjoyed really fruitful collaborations in my lab at Stanford, and, uh, collaborating is just so much more fun. Online, there seems to be a bias more towards creating silos as opposed to, um, bridges. But, uh, I appreciate that you bring up the need for more collaboration. And, and knowing which measures are best, and in this case, uh, now thank you for the clarification. I understand this omega-3 index is going to be best. You mentioned you, so basically right now when I look at you, I think you are 16% omega-3.
- RPRhonda Patrick
And dolphins are 19%. I'm almost dolph-
- AHAndrew Huberman
Is that your goal? You're trying (laughs) to get there?
- RPRhonda Patrick
It, it is. (laughs)
- AHAndrew Huberman
(laughs) To, to, uh, interesting. Um, actually they should probably do something where you're trying to achieve the omega-3, uh, uh, ratio of the, the, your favorite species. Um, now that we've covered a bit of how to get these things into one's system depending on what one eats, et cetera, and some of the better measurements,
- 1:10:22 – 1:14:40
Benefits of Omega-3s
- AHAndrew Huberman
w- how is omega-3 and some of these other related, uh, lipids, how are they having these positive effects? In my mind, and this i- 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. Um, 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?
- RPRhonda Patrick
Yeah.
- AHAndrew Huberman
I mean, what are some of the purported, reported, and known mechanisms?
- RPRhonda Patrick
I think some of the, the most well-known mechanisms, um, do have to do with the, 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, uh, from the metabolites, uh, 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 an inf- inflammatory response in a, a timely manner, right? And resolvins help do that. And, and so resolvins are one, and then there's these specialized m- um, pro-mediating molecules, the SPMs, that also help resolve the inflammation. Um, there's, like you mentioned, the leucotrienes and prostaglandins, and these things are being affected by EPA, and they do affect platelets and platelet aggregation and they e- you know, they do affect that whole pathway as well. And so there's just m- and there's, you know, I think there's just so many different ways and inputs. And so when we talk about inflammation, honestly it that, it's a big general term, but you're talking about, when you're talking about serotonin release, um, you know, at the level of neurons, you know, we know that these inflammatory molecules cross the blood-brain barrier. And I just mentioned ago about injecting people with lipopolysaccharide and causing depressive symptoms. Um, you know, it's known that that omega-3 p- s- and actually specifically EPA is able to help serotonin in f- 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 bl- you're not having so much inflammation getting into the brain and affecting serotonin release, right? That's one mechanism. And then another would be, well, DHA itself has been shown, it's, it's a very important, uh, 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, uh, are affected by the membrane fluidity, you know, like how sh- rigid and how fluid the cell membrane is. And DHA plays a role in that. And so, eh, for example, in animal studies, if you make an animal deficient in DHA, their serotonin receptors, dopamine receptors, they're affected because the structure of them is affected through the fluidity of the membrane. And so I think that's another mechanism. And, and I'm talking sort of general 'cause I'm not a neuroscientist.
- AHAndrew Huberman
No, but it makes perfect sense. I mean, th- we know for instance, l- uh, neuroplasticity and the r- eh,... almost always involves the recruitment of more receptors or an improvement in some feature of receptors to neurotransmitters, and they literally move laterally in the membrane. They kind of float around like little rafts. Sometimes they are, in fact, in lipid rafts. And so it makes perfect sense that these molecules like DHA, which are part of the structural fat of the neuron, because, of course, the outsides of neurons are basically fat, not just the myelin that people have heard of, but the actual membranes, that if getting that right, it, it, you wouldn't want it as rigid as concrete, but you wouldn't want it as soft as ... I need to come up with something here. What's that gooey stuff that kids play with? It's like that goo.
- RPRhonda Patrick
Uh-
- AHAndrew Huberman
Anyway, there's a-
- RPRhonda Patrick
Oh, yeah. Um-
- AHAndrew Huberman
Yeah. It's disgusting-
- RPRhonda Patrick
(laughs)
- AHAndrew Huberman
... and it's too soft to be a membrane for a neuron. That's what, that's what we know.
- RPRhonda Patrick
You get it in those machines, like the claw machines.
- AHAndrew Huberman
Someone will put it in the, someone will put it in the comments and tell me what that disgusting gooey stuff is. Uh, you don't want your neurons to be that gooey, and yet you don't want them to be like concrete either.
- RPRhonda Patrick
It's a balance.
- AHAndrew Huberman
It's a balance.
- RPRhonda Patrick
Yeah.
- AHAndrew Huberman
Um, and in mentioning DHA, I'm just gonna ... I realize I'm backtracking, but I wanna make sure that we close
- 1:14:40 – 1:17:07
Tool 5: Food Sources of DHA Omega-3s
- AHAndrew Huberman
all the hatches for people. Y- we talked a lot about, uh, EPA, but are food sources of DHA, um, that you find particularly attractive, either by taste or by, uh, potency for DHA, what, what are just a few that we could throw out? Because I am ma- 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?
- RPRhonda Patrick
Well, the fish is packaging the DHA and EPA in the ratio.
- AHAndrew Huberman
Right. Okay.
- RPRhonda Patrick
And, um, but I, I also do eat salmon roe, which is, um, very salty, and, um, it's a, it's a really high source of the phosphato- phosphatidylcholine DHA that we talked about.
- AHAndrew Huberman
So this is fish eggs?
- RPRhonda Patrick
It is.
- AHAndrew Huberman
Yeah.
- RPRhonda Patrick
Mm-hmm. Yeah, and actually, I d-
- AHAndrew Huberman
That I like for some reason.
- RPRhonda Patrick
Oh, do you?
- AHAndrew Huberman
Yeah. I'll eat the ... Uh, so I'm discovering something about myself. Um, th- this is, was not meant to be nutrit- nutritional psychotherapy, but you're doing that for me anyway. Um, I'm discovering that, yeah, I like eating embryonic fish. I just don't like eating the actual fish.
- RPRhonda Patrick
Okay, well-
- AHAndrew Huberman
Um, okay, so fish eggs are, are okay.
- RPRhonda Patrick
They're-
- AHAndrew Huberman
So caviar basically.
- RPRhonda Patrick
Caviar, yes.
- AHAndrew Huberman
Right.
- RPRhonda Patrick
And, and that's a good source of the phospholipid form.
- AHAndrew Huberman
Yum.
- RPRhonda Patrick
And I was consuming that a lot because I wanted to get the phospholipid form.
- AHAndrew Huberman
Yum.
- RPRhonda Patrick
Um, so, and it's actually really good. There's been some animal studies in piglets and rodents as well showing that consuming phospholipid DHA, uh, during fetal brain development, like gets w- like ten times more DHA in the brain. Again, it's-
- AHAndrew Huberman
Makes sense based on fetal development. Um, so do I need to inj- en- uh, buy beluga caviar? Stuff can get pretty expensive at $200 a tin.
- RPRhonda Patrick
I don't think you need to, no.
- AHAndrew Huberman
Okay.
- RPRhonda Patrick
I think it's a, it's a matter of preference, and, uh, you're, if you're supplementing with your, your two to four grams of fish oil, I mean, that, you're gonna get phospholipid form anyway 'cause your body's gonna make it.
- AHAndrew Huberman
Okay. I've s- I've seen some containers of, of what I assume to be quality fish eggs that are not at the caviar level you can find in, in the better grocery stores, that aren't super expensive.
- RPRhonda Patrick
Right.
- AHAndrew Huberman
I wouldn't dip as low as to go eat, for instance, like, um, fishing bait. Like when we were kids, we used to go fishing. You'd put the fish egg on the thing. That's probably not good.
Episode duration: 2:49:32
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