Dr. Rhonda Patrick on Huberman Lab: Why omega-3s extend life

1. 0:00 – 0:20

   Rhonda Patrick

   1. AHAndrew Huberman0:00

      Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Rhonda Patrick.

2. 0:20 – 3:43

   Physical Challenges, Stress Response Pathways, Hormesis, Temperature

   1. AHAndrew Huberman0:20

      Rhonda, welcome.

   2. RPRhonda Patrick0:21

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

   3. AHAndrew Huberman0:24

      Thank you. Uh, I have so many questions, but I wanna start off with a kind of a, 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 cold can stimulate a number of things like increases in metabolism, brown fat, et cetera, et cetera. 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?

   4. RPRhonda Patrick1:19

      Let's take a step back, and I think you brought up a really important point here. You know, we evolved to intermittently challenge ourselves, and before we had Instacart where you could basically just get your food delivered to you, we were out hunting, gathering. We were moving, and we had to be physically fit. You couldn't, you know, catch your prey if you were a sedentary slob, right? 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. There is a lot of crosstalk between these stressors and the genetic pathways that they activate, and these genetic pathways that are activated help you deal with stress. And they do it in a way that is not only beneficial to help you deal with that little stressor, exercise or heat, it'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 has a very profound antioxidant, antiinflammatory response, or, you know, whatever the response is. It could be the production of more stem cells or something like autophagy. 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. But you can eat a plant like broccoli sprouts, which is high in something called sulforaphane, 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. Cold also activates heat shock proteins. Now, you're gonna more robustly activate heat shock proteins from heat versus

3. 3:43 – 6:19

   Tool: Sulforaphane & Detoxification, Cruciferous Vegetables, Moringa

   1. RPRhonda Patrick3:43

      cold, but there is some overlap.

   2. AHAndrew Huberman3:45

      You mention plants 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.

   3. RPRhonda Patrick4:03

      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. But I do think with respect to plants, 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 g- GWAS 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. But if they eat a lot of broccoli and cruciferous vegetables, it negates that risk, because they're getting sulforaphane which activates glutathione transferase and synthase genes. So glutathione's a major antioxidant in our brain and in, in our, in our vascular system, in our body basically. There's evidence eating things like, you know, compounds that are like sulforaphane or broccoli or brock- 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.

   4. AHAndrew Huberman5:37

      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.

   5. RPRhonda Patrick5:44

      (laughs) 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 to your cooked broccoli increases the sulforaphane by fourfold.

   6. AHAndrew Huberman6:00

      Are you eating this every day, or most days of the week?

   7. RPRhonda Patrick6:03

      Well, I had shifted to supplementation with sulforaphane. There's another compound, and it's actually called Moringa...So it's like a cousin, and it activates the NRF2 pathway similarly to sulforaphane. And so I've been buying this Kuli

4. 6:19 – 8:16

   Tool: Marine Omega-3s Fatty Acids, Fish Oil Supplements

   1. RPRhonda Patrick6:19

      Kuli Moringa Powder, and I add it to my smoothies.

   2. AHAndrew Huberman6:22

      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?

   3. RPRhonda Patrick6:32

      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, there's three fatty acids. There's ALA, EPA, and DHA. 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 it's not that ethyl ester's bad, it just means take it with food, basically.

   4. AHAndrew Huberman7:09

      What's the dosage that you recommend people get?

   5. RPRhonda Patrick7:11

      I think two grams is, um, is a good threshold. Now, um, the International Fish Oil Standards, IFSO, they have a website where they do third-party testing of 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 measur- measure contaminants, so mercury, PCBs, dioxins, things that you'd find potentially in fish that are harmful to humans. Uh, 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. They give you a total oxidation number. It's called Toto- To- no T-O-T-O-X. To- TOTOX is what we call it for short, and, um, I like it to be at the least under 10, ideally under six. It's really hard to find all the right mixtures of things, but, um,

5. 8:16 – 10:34

   Benefits of Fish Oil Supplementation, Longevity, Tool: Omega-3 Index

   1. RPRhonda Patrick8:16

      people can go to this website and they can browse through the products.

   2. AHAndrew Huberman8:19

      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?

   3. RPRhonda Patrick8:26

      I personally think it is one of the most powerful anti-inflammatory dietary lifestyle things that we can, we can get easily that is gonna powerfully modulate the way you think, the way you feel, and the way you age. 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. He's done a variety of studies, uh, observational studies, so measuring 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 f- first of all, um, standard American diet has omega-3 index of 5%. Japan, by contrast, has an omega-3 index of around 10 to 11%, big, big difference there, and they also have about a five-year increased life expectancy compared to people in the US. What he showed in his data was that people that had a omega-3 index of 4% or lower, so close to what the standard American is, but a little bit lower, they had a five-year decreased life expectancy compared to people that had an 8% omega-3 index. 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.

   4. AHAndrew Huberman10:13

      Where and how can somebody measure their omega-3 index?

   5. RPRhonda Patrick10:15

      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 want to 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're, you went up, because

6. 10:34 – 13:14

   Omega-3s & Inflammation

   1. RPRhonda Patrick10:34

      the, that's how long it takes for your red blood cell to turn over.

   2. AHAndrew Huberman10:37

      How is omega-3 and some of these other related lipids, how are they having these positive effects? What are some of the purported, reported, and known mechanisms?

   3. RPRhonda Patrick10:47

      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, 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 the 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, um, pro-mediating molecules, the SPMs, that also help resolve the inflammation. Just so many different ways and inputs, and so when we talk about inflammation, honestly it, that, that'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. It's known that omega-3, actually specifically EPA, is able to help serotonin, inf- 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 b- 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 if, 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. There's been some animal studies in piglets and rodents as well showing that consuming phospholipid DHA, uh, during fetal brain development, it, like, gets way, like, 10 times more DHA in the brain. Uh, you're, if you're supplementing with your, your two to four grams of fish oil, I mean, that, you're gonna

7. 13:14 – 15:44

   Vitamin D; Health Benefits

   1. RPRhonda Patrick13:14

      get phospholipid form anyway 'cause your body's gonna make it.

   2. AHAndrew Huberman13:17

      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 brain and/or body health can really benefit from?

   3. RPRhonda Patrick13:32

      I mean, I think the most obvious would be vitamin D. 70% of the US population has inadequate vitamin D levels, 70 of the whole-

   4. AHAndrew Huberman13:41

      Amazing.

   5. RPRhonda Patrick13:41

      ... U- US. So this is everyone. And so I think that insufficient levels defined as less than 30 nanograms per milliliter, um, and, and that's sort of defined by the, the Endocrine Society. Um, there's been a, a lot of different meta-analyses of all cause mortality studies where vitamin D levels are, are, really seem to be ideal between 40 to 60 nanograms per milliliter. So basically, the point is that vitamin D is a steroid hormone, meaning it actually binds to a receptor and, um, another receptor dimerizes with it, vitamin, the, the retinoid receptor, and that complex goes into the nucleus of a cell, where your DNA is, and it recol- recognizes little sequences of DNA called vitamin D response elements, they're called VDREs, they're specific sequences of DNA that this complex, vitamin D recep- bound to the vitamin D receptor, goes inside and recognizes and turns on a whole host of genes, turns off a whole host of genes. I mean, this is, this is important stuff.

   6. AHAndrew Huberman14:41

      What sorts of things is it stimulating?

   7. RPRhonda Patrick14:44

      Okay, so first of all, it's r- it's regulating more than 5% of the protein-encoded human genome. One of the important things that you'll find interesting that I published on back in 2014 was that the VDREs and tryptophan hydroxylase 2... So for people listening, tryptophan hydroxylase is an enzyme that converts tryptophan into serotonin. So tryptophan is what we, uh, an amino acid that we get from our food. Um, you convert serotonin... Y- you convert tryptophan into serotonin into the gut, in the gut, but you also do it in the brain. However, serotonin does not cross the blood-brain barrier, so tryptophan has to get into your brain and then you have to convert it to serotonin in your brain. Well, the enzyme that does that in your brain is called tryptophan hydroxylase 2, and it's activated by vitamin D. But most people, I mean, this is regulating our immune, our immune cell, immune system, it's regulating, uh, our blood pressure, you know, all that, th- that water retention, you know, I mean, bone, of course, homeostasis. 5%, more

8. 15:44 – 19:09

   Tool: Vitamin D Supplementation, Bloodwork

   1. RPRhonda Patrick15:44

      than 5%. I mean, I can't tell you, like, so much.

   2. AHAndrew Huberman15:47

      Where and what is a good starting range for people to, to think about D3 supplementation, and again, foods that can increase D3?

   3. RPRhonda Patrick15:56

      Um, so vitamin D3 is a good way to supplement with it. Um, there, vitamin D2 would be a plant source. You often find it fortified in, like, foods like milk.

   4. AHAndrew Huberman16:04

      Okay.

   5. RPRhonda Patrick16:05

      Yeah, vitamin D is naturally, to some degree, in fatty fish, but you're not gonna correct a deficiency with eating vitam- with eating fish for your vitamin D. Like you, you're either gonna correct it with sun exposure, being in the right area, having the right amount of sun, and being the right age, um, because as you get old, you become very inefficient at making vitamin D3 in your skin. There've been, uh, a lot of these Mendelian randomization studies. So these are studies where scientists will look at people that have these common variations of a gene that's a little, more than 1% of the population. So it's not a random mutation, it's actually found in a, in a, uh, a sizable percent of the population. A lot of times, they'll look at genes that are also involved in SNPs that basically make the conversion of vitamin, either vitamin D precursor into D3 or in D3 into 25-hydroxyvitamin D or into the active steroid hormone, which is 1,25-hydroxyvitamin D. So you're not looking at vitamin D levels at all, you're looking at just the SNPs, and you know if they have it, they have low vitamin D. People, uh, randomly have these genes, and it's not like... There's no health status. So, um, these, these Mendelian randomization studies have found that people that can't convert, um, into the, the precursor, the 25-hydroxyvitamin D, which is usually what's measured, it's the most stable form of vitamin D in the body, um, they have a higher all-cause mortality if they can't do it. So people with, n- 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. They also are more likely to get multiple sclerosis. This has all been done with Mendelian randomization, and so, um, it really does hammer home the importance of measuring your vitamin D levels and, uh, being, being, uh, very proactive about that. I mean, you can, you can d- get it done anywhere. Your doctor will do it. You ask them to do it, you know. So, um, supplementation-wise, um, typically, if you don't have one of those SNPs, for, for the most part, taking 1,000 IUs 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 wanna get to 40.You're going to need at least 4,000 IUs.

   6. AHAndrew Huberman18:07

      Uh, so for people who are going to be stubborn and not get their D levels tested, and simply say, "Oh, I'll just take some D3." Is that reasonable, 1,000 to 5,000 IUs for most people will be reasonably safe?

   7. RPRhonda Patrick18:18

      If we look at the, the, the literature, the scientific literature, it is extremely hard to get like hypercalcemia, which would be the major concern with really high levels of vitamin D3 supplementation. I mean, we're talking like hundreds of thousands of IU a day for a long time. And by the way, there have been studies looking at, uh, people that are deficient in vitamin D. Um, in this case it was, uh, African Americans that were given a 4,000 IU a day vitamin D supplement to bring them back to sufficient levels. And, um, this was a, this was a smaller, smaller study than, um, 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.

   8. AHAndrew Huberman19:05

      So if I'm taking vitamin D3,

9. 19:09 – 21:23

   Tool: Magnesium, Dark Leafy Greens, Supplementation

   1. AHAndrew Huberman19:09

      I still need to get out into the sun, correct?

   2. RPRhonda Patrick19:11

      Absolutely.

   3. AHAndrew Huberman19:11

      Okay. Okay, so we've, we talked about these plant-based compounds, the omega-3s and D3. Is there anything that, um, f- to supplement-based or food-based compounds that you, you know, you think are especially useful for brain and or body health?

   4. RPRhonda Patrick19:27

      I do think magnesium is important in there as well.

   5. AHAndrew Huberman19:30

      Mm-hmm.

   6. RPRhonda Patrick19:30

      I mean, I think, you know, eh, 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. Magnesium's also involved in making ATP, the, the energetic currency of our cells. They're n- you know, basically all of our cells need ATP to do anything, and, um, they're als- 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, my gums are falling apart. I have scurvy," right? But like you can't see DNA damage. You can't see it, but it's happening. It's happening right now in my body and it's happening in your body. It's happening, normal metabolism is happening, you know, every day. Um, 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. Well, magnesium is at the center of a chlorophyll mole- molecule. Chlorophyll is what gives plants their green color. So dark leafy greens are high in magnesium. Basically, what does the 40% insufficien- insufficiency in the US tell us? People aren't eating their greens. They're eating their packaged food, they're eating their processed food, and standard American diet isn't really high in dark leafy greens.

   7. AHAndrew Huberman20:49

      So kale, what are some other examples, and-

   8. RPRhonda Patrick20:51

      Kale, spinach, chard, like Swiss chard-

   9. AHAndrew Huberman20:53

      Okay.

   10. RPRhonda Patrick20:53

       ... rainbow chard, um, romaine lettuce. So supplementation with magnesium, it can cause GI distress at like high doses. I personally like to take around 130 or 135 milligrams.

   11. AHAndrew Huberman21:05

       Mm-hmm.

   12. RPRhonda Patrick21:05

       That way it's not like a, a huge bolus to my gut. You can take like magnesium threonate, for example, and it doesn't affect the gut as much.

   13. AHAndrew Huberman21:12

       Oh, yeah, yeah.

   14. RPRhonda Patrick21:13

       I would say malate would be the best. That has to do with the short chain a- fatty acids being good for the gut. I think mala- malate's awesome, and I always tr- try to eat green apples. They're really high in malic acid.

   15. AHAndrew Huberman21:22

       Oh, good to know.

   16. RPRhonda Patrick21:22

       And,

10. 21:23 – 22:16

    Deliberate Cold Exposure, Mood & Dopamine

    1. RPRhonda Patrick21:23

       um, tart cherries. Tart cherries are really high in it as well.

    2. AHAndrew Huberman21:26

       Oh. You've talked a lot about the use of deliberate cold exposure. What sort of activity or stimulus do you, do you think is a reasonable and particularly potent one, uh, to use in terms of cold?

    3. RPRhonda Patrick21:38

       So today I did three minutes at 49 degrees Fahrenheit. I have a cold tub. I definitely do cold when I'm going to do a podcast, when I'm going to give a talk, or when I'm anxious. I feel good, I feel more focused, which is why I usually do it before po- any type of public speaking.

    4. AHAndrew Huberman21:55

       So the mood-enhancing effects that you report, those are almost certainly a consequence of having slowly elevating but significantly elevated dop- dopamine that goes on for hours. That's almost a dreamlike profile for dopamine, because most everything else, like an Adderall, a Ritalin, a cup of coffee, and a, um, and a workout drink, or pre-workout drink or something is going to give you a

11. 22:16 – 26:40

    Cold Exposure to Enhance Mitochondria, Shivering, Browning Effect

    1. AHAndrew Huberman22:16

       big spike in adrenaline and dopamine, and a big crash. 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. I, 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. Uh, but if you get cold adapted, then it certainly blunts the, some of the effect.

    2. RPRhonda Patrick22:39

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

    3. AHAndrew Huberman22:48

       Mm-hmm.

    4. RPRhonda Patrick22:48

       Shivering is a very inefficient way to produce heat, which is what your body's trying to do when it's exposed to cold. And your muscles are basically contracting and, and, and, um, and producing heat from that, but that's just not very efficient. So, uh, the, the more eloquent way to do it, or elegant I guess, uh, way to do it is, you know, to basically have your mitochondria produce tons and tons of heat. So mitochondria are these little organelles inside of your cells that are responsible for producing energy. Usually that's in the form of adenosine triphosphate, ATP, and that's what lets everything function inside of your body, from your neurotransmitter production, to your heart beating, et cetera. Basically, your mitochondria, um, they're like a little battery. So they have eh, they have, well, they have a double membrane, first of all, their structure, but they have a negative charge on the inside, and they have a positive charge on the inner membrane. Basically, you can uncouple that, that charge, and so that positive charge protons start leaking out of the mitochondria, and your mitochondria freak out, so this is called uncoupling it.... and they start to, hmm, it's maximum respiration as we call it. They try to make as much energy. They're like, "I got to get those, that, that, that proton back, that gradient, you know, electrochemical gradient." And so they just go insane and they, um, in this case, it's uncoupled energy, so the energy they're making is actually heat not ATP. Uh, but heat is ... But you're essentially burning substrate so who cares? You're burning, you're burning glucose. Uh, you're burning your lipids, you know, you're, you're basically burning things and making heat. And so, um, that's what uncoupling it does, and that is a much more efficient way of producing heat than shivering. And so as you become more adapted, um, maybe the, the, the longer duration that you've, you've stayed in the cold or the more times you've done it, you'll no longer shiver anymore. You will start to then just do this uncoupling type of thermogenesis as it's called. And, um, another type of adaptation that occurs is you actually produce more mitochondria in your adipose tissue. And, um, and that actually happens also regulated by norepinephrine or noradrenaline through a protein called PGC-1alpha. And what that protein does is it makes more mitochondria in your adipose cell. So per adipose cell, you're getting more mitochondria. It's a beautiful way to basically make more heat when you're ... It's, it's one of those things where it's like, it's, it, it, your body's going, "Okay, I'm gonna be exposed to this cold next time, how can I make sure I don't die? Oh, I can have more mitochondria and I'm gonna make more heat." And so you're making more mitochondria in your adipose tissue, and, and this is often ret- referred to as, like, the browning of fat. And the reason for that is because if you look under a microscope at a lipid droplet, like you're, you know, basically, um, uh, a fat cell, uh, not a lipid droplet, an adipocyte, um, you'll find that it looks darker because there's more mitochondria in there. So it's referred to as browning fat. That's awesome, you want more mitochondria in your muscle, it's associated with, um, improved muscle mass, improved endurance. I mean, mitochondria are essentially, they're making energy in your cell.

    5. AHAndrew Huberman25:49

       Mm-hmm.

    6. RPRhonda Patrick25:50

       And we, you know, we don't make more mitochondria normally. Like, you have certain inputs, ex- high intensity interval training, exercise can do it. Your cells are turning over, you make new cells, you replace old ones. With your mitochondria, um, you don't really do that for the most part. You can, mitochondrial biogenesis does happen but you have to stimulate it to happen. And, um, the way your mitochon- like, what happens with your mitochondria is they essentially are bobbing around inside of your cells and then they, they fuse with other mitochondria, exchang- exchange all their content, mitochondrial DNA and then fizz back apart, and that's how they kind of stay young-ish. But, like, as you age, you, you keep doing that with the same pool of mitochondria, then you're gonna get a bunch of old mitochondria mixing old stuff together, right? So why wouldn't you want to, like, bring up new healthy young mitochondria into that pool, right? So in my mind, when I hear mitochondrial biogenesis, I'm like, aging. Like, that's the first thing

12. 26:40 – 28:36

    Tool: High-Intensity Interval Training, Tabata Workout, Sauna, Memory

    1. RPRhonda Patrick26:40

       I think of.

    2. AHAndrew Huberman26:41

       Mm-hmm.

    3. RPRhonda Patrick26:41

       Uh, so anyways, cold exposure does that.

    4. AHAndrew Huberman26:43

       What sort of, um, cardiovascular or other types of training do you do? Uh, do you do HIIT? I imagine you'd, are doing high intensity interval training.

    5. RPRhonda Patrick26:50

       I do a lot of high intensity interval Tabatas on a stationary cycle three times a week, and I do a 10 minute, just 10, uh, because it's efficient and I push my ass. I push myself really hard.

    6. AHAndrew Huberman27:02

       That's the Tabata?

    7. RPRhonda Patrick27:03

       It's a t- 20 seconds on, 10 seconds off, and it's 10 minutes.

    8. AHAndrew Huberman27:06

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

    9. RPRhonda Patrick27:08

       You're maxing it. And then, um, I always have my sauna on pre-heating up. I get it to about 189 degrees Fahrenheit.

    10. AHAndrew Huberman27:14

        Mm-hmm.

    11. RPRhonda Patrick27:15

        I hop right in the sauna after my Peloton. I literally, like, down a bunch of water and then I get in and, and then I, like, either, um, read a science paper or prepare for a presentation or a podcast, or I, um, hash over things in my mind. And it's interesting because I would use the, uh, sauna to memorize things. I don't know if it has to do with the, th- like, the stress response. Like, when you, when you have an emotional s- trigger-

    12. AHAndrew Huberman27:40

        Mm-hmm.

    13. RPRhonda Patrick27:40

        ... like, you remember things better, right? I mean ...

    14. AHAndrew Huberman27:42

        Absolutely. The idea that being in this semi-stressful environment would aid in the learning and, and retention of information is, is really well substantiated by this b- beautiful work by a guy named James McGaugh. He was at UC Irvine for a while, and then I think at, uh, University of Arizona as well. They have a great memory group at both places, very strong in learning and memory, um, both places. And he was the one that really defined this, um, kind of, uh, inverted U-shaped function for the relationship between adrenaline and memory. Basically if you're too relaxed and not stressed enough, you're not going to remember any information. At peak levels of stress, you actually are a memory machine, at least within the context of whatever it is you're trying to learn. So very well s- you know, what you're describing is, uh, very well matches with that. And then of course, it tapers off as you really increase adrenaline to the point where people are l- starting to lose autonomic function,

13. 28:36 – 34:10

    Sauna, Cardiovascular & Cognitive Heath; Tool: Sauna Duration & Frequency

    1. AHAndrew Huberman28:36

       where they're just, they're panicking basically. The other thing that, that I would like to ask you about is in the sauna, of course, there's vasodilation, and profusion of blood to the brain is a wonderful way to enhance cognition.

    2. RPRhonda Patrick28:46

       The vasodilation does occur. So there's a lot of overlap between moderate intensity aerobic exercise and heat stress, and as you can imagine when you're exercising, you're eleva- elevating your core body temperature, you're, you're sweating. And, um, when you're actually in the sauna, blood does get redistributed to the skin to facilitate sweating. But much like exercise, blood flow in general is improved.... to the brain, to the muscles, everywhere. So, um, you know, I think generally speaking that, um, and- and this, you know, there's studies showing that sauna use is associated with a much lower risk of dementia and Alzheimer's disease. Like people, we know people that use it four to seven times a week have greater than 60% reduction in dementia risk and Alzheimer's disease risk compared to people that use it only one time a week. Um, people that use it two to three times a week have something like a 20, a little greater than 20% reduction in risk. There's a dose dependent effect on dementia risk and Alzheimer's disease risk. Uh, it also, uh, has a profound, like there's a- there's a big link between the cardiovascular system and the brain. Obviously blood flow, a big one, right? You know, like you- you need to get blood to your brain. Um, but cardiovascular mortality, so mortality from cardiovascular disease, if people use, or actually this was men, if men use the sauna four to seven times a week, it's a 50% reduction in cardiovascular related mortality compared to one time a week. Uh, again, dose dependent manner, two to three times a week is something like 24% lower car- um, death from cardiovascular disease. There's also lower, you know, sudden cardiac deaths, like a heart attack. That's like 60 something, greater than 60% lower if- if men use it four to seven times a week versus once. Again, a dose dependent thing. And this is all work from Dr. Jari Laukkanen. He's in, um, the University of Eastern Finland, and just one of the- the- the world's experts on sauna use. The more you do the sauna or any sort of heat stress, whether it's a hot tub or jacuzzi, um, you- you become adapted. You're- you basically start to sweat at a lower core body temperature to cool yourself down. All these sort of physiological changes start to happen earlier. Uh, and so, um, I stay in for like 30 minutes. Like I mean, so I stay in a long time. That's a lot. You have to listen to your body. Um, most of the studies, uh, that I just talked about were from, um, the- the duration, the time spent in the sauna when I said 50% reduction in cardiovascular disease related death, uh, what was shown was that men that were in the sauna for only 11 minutes, even if they used it four to seven times a week, that reduction was only like 8% instead of 50. It had to be greater than 19 minutes, so like 20 minutes is the sweet spot, at about 174 degrees Fahrenheit. To me, that's very strong data that this is more causal than some, you know, corollary thing, because that's always the problem with observational studies and including these, which they corrected for a whole host of factors like cholesterol, you know, exercise, just everything. Everything under the sun. I mean, they corrected for those. And on top of that, you have the dose dependent nature of the duration, the time spent in the sauna, and the frequency. So to me, it's like something's going on here.

    3. AHAndrew Huberman31:53

       Yeah.

    4. RPRhonda Patrick31:53

       Plus there's been studies, intervention studies, where it's like, you know, comparing directly head to head moderate or intensity aerobic exercise on a stationary cycle to 20 minutes in a sauna. They're- they're physiologically the same things happen, so heart rate elevates while you're doing the activity, blood pressure increases while you're doing the activity, but then after heart rate decreases, resting heart rate decreases below baseline, blood pressure is improved. So it decreases below baseline. This is happening the same in moderate intensity cycling versus sauna. So again, the sauna, like this heat stress, there's something about it that really mimics this moderate intensity aerobic exercise, which is really great for people that can't go for a run, that can't even get on a bike. Um, so you know, disabled people, granted there are some safety concerns, they're- they're pretty mild. Uh, but they do exist. Uh, you know, so people that had a recent heart attack or have some rare kind of heart disease or problem, drinking alcohol, never do that. Elderly people, low, uh, prone to low blood- blood pressure, always talk to a physician before doing the sauna. It is- it is stressful. Um-

    5. AHAndrew Huberman32:57

       Pregnant.

    6. RPRhonda Patrick32:58

       Pregnant women. Oh yeah, I definitely, um, avoided saunas when I was pregnant. So for those healthy fit people out there already exercising, there's a synergistic effect by also adding a sauna into that routine. And to me, that's great. And, um, there's so many beneficial things happening, uh, with the- with the heat stress in addition to like mimicking aerobic exercise. There's the heat shock proteins that we talked about earlier. Many animal studies have been done looking at Alzheimer's disease, uh, you know, like all- all, uh, a human-like Alzheimer's disease in a rodent and heat shock proteins protecting from it, you know. So, um, heat shock proteins are robustly activated in humans. Um, this has been shown to, uh, even or, you know, 50% higher over baseline levels after just 30 minutes at 163 degrees Fahrenheit in the sauna. So, um, and they stay activated at least in rodents for, you know, 48 hours at least. Um, so, you know, having these heat shock proteins around, making sure they're- they're properly taking care of our- our protein, so they're not aggregating in our brains and in our- in our plaques could be another potential way that sauna is protecting from Alzheimer's disease and, um, other, you

14. 34:10 – 35:36

    Tool: Hot Bath; Acknowledgements

    1. RPRhonda Patrick34:10

       know, cardiovascular health, as well as longevity.

    2. AHAndrew Huberman34:13

       I know people are probably desperate to know what if they don't have a sauna? I could imagine that a hot bath would work almost as well. Is that right?

    3. RPRhonda Patrick34:20

       Yeah. So there's been some studies looking at, for example, activation of heat shock proteins, also brain-derived neurotrophic factor increases with heat stress. Um, and so, uh, the sa- uh, the- the hot bath at around 104 degrees Fahrenheit, which is typically what studies will use for temperature, and, um, it's, uh, 20 minutes from the shoulders down. And- and that is like a very robust activation in heat shock proteins and in, uh, brain-derived neurotrophic factor.

    4. AHAndrew Huberman34:43

       Great.

    5. RPRhonda Patrick34:43

       And then heat shock proteins are also protecting against muscle atrophy, so that's also having to do with the protein structure and the muscle tissue as well, and this has been studied in animal, you know, animal data, um, as well as, um, uh, recent human data as well. It was local hyperthermia or local heat treatment, but, um, essentially it showed that it protected, I mean, it was like there was a study where, um, they were looking at muscle disuse and it was- it was something like the local heat treatment prevented like almost 40% of the muscle atrophy from disuse.

    6. AHAndrew Huberman35:12

       We covered a lot of- of territory, but, uh, I just want to thank you again. It was extremely thorough and extremely informative. On behalf of the listeners and, uh, just directly from me, thank you so much for your time. I learned a ton.

    7. RPRhonda Patrick35:24

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

    8. AHAndrew Huberman35:28

       Let's do it again.

    9. RPRhonda Patrick35:30

       Totally. (laughs)

    10. AHAndrew Huberman35:31

        Great.

Episode duration: 35:36