The Best Vitality & Health Protocols | Dr. Rhonda Patrick

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16:58Andrew Huberman:Terms and conditions apply. Again, that's hellolingo.com slash Huberman. I love that you mentioned other functions of serotonin because, as you point out, it is so heavily associated with this mood aspect and certainly has a role there. But the impulse control piece is, I think, is a non-trivial aspect to the effects of exercise. And just generally, I'm curious, do you bring your phone or feel compelled to check your phone during workouts? Or are you able to just say, I'm compartmentalizing now. This is the workout. You might put on music or maybe text here or there if you need to. But are you able to compartmentalize or do you struggle with the phone during workouts?

17:36Dr. Rhonda Patrick:Oh, I don't bring my phone to my workout at all. Like I don't – now I do have a watch that I wear that, you know, if there's like an emergency, I'll get a text message. Oftentimes I put it on silent, like on no notifications because I don't want to be bothered. But I don't really check my phone. I don't really like checking things like social media. For me, it's just a distraction. And frankly, I think it's terrible for people's brains even though like my business kind of depends on it somewhat. But I think social media is not really good for people, to be honest. So I don't really check my phone or bring my phone to my workouts.

18:14Dr. Rhonda Patrick:My workouts are – I like to chat with my friends when I'm working out with them, and that's fun.

18:19Andrew Huberman:That's in real life. Yes. IRL, as the kids say.

18:23Dr. Rhonda Patrick:That's in real life. And, yeah, phones for me are not something that I bring to my workout.

18:30Andrew Huberman:Great. Yeah, I've been experimenting with not allowing the phone in my gym and just the workouts go so much better. And I find that the mental and physical resetting aspect of working out just seems to be enhanced. But it sounds like you were already there and I'm just arriving. So I have a couple other specific questions about your workouts because for my own interest, and I know many people will wonder, for the dedicated weight workouts, are these whole body workouts? And you said low reps. Maybe you could just tell us what low reps is for you. And then the – it seems like the ever-present question is to failure, close to failure.

19:04Andrew Huberman:I mean just to round out that portion of the workout picture.

19:08Dr. Rhonda Patrick:The workouts that I'm doing with my strength training workouts with my coach, it really depends. Most of those workouts are their multi-joint workouts. So I am most of the time doing, you know, some either front squat, back squat, or I'm cleaning it as well, right? Which obviously the weight goes down if I'm cleaning it because it's hard to clean. It's also the hard, like, it's the thing that I hate doing the most.

19:35Andrew Huberman:Cleans.

19:35Dr. Rhonda Patrick:Oh, yeah. Cleans with front squat because it's really hard. And for me, I mean, for others who've been doing it for years, I'm sure it's like, you know, they love it. But for me, it's very hard. I've only been doing clean since, you know, February 2024. So I'm pretty new to it. And so it's mentally like I have to overcome that challenge, which, by the way, once I started doing all this sort of weight training, I've always been an endurance junkie. Like I used to go long runs and races and stuff like that. So for me, that's like my safe spot, right? That's what comes easy to me. weight training and resistance training, strength training, definitely not something that I've done my whole life.

20:18Dr. Rhonda Patrick:I'm so glad that I started doing it, but very, very challenging for me. And so I would say the biggest effect was on my brain and the ability to handle stress better, where it was like unbelievable because it was so hard. And I just didn't want to do these cleans, you know, and these front squats. And then the rest of my day was not as hard. And that to me was like the biggest surprise for this type of training. But anyway, so I do a variety of, if I'm doing, if I'm going heavier, then it, you know, depends. Sometimes I'll start off, it's like, okay, we start off, we do five reps and then we go down to four and then we go down to three and then we go down to one.

20:55Dr. Rhonda Patrick:Right.

20:55Andrew Huberman:Are you doing singles?

20:56Dr. Rhonda Patrick:We do. Yeah. Yeah. And that's the hardest. It's the hardest. But then there's, there's like my coach will like, it's just one, it's just one. You know, sometimes we'll do like six, five, and then we do four twice and then we do three twice. Right. And So it all depends, you know, also on the day. There's some days where I'm just like, you know, can we do lower reps and like lighter weight, right? I'm just like, this is the day for me. I'm stressed. I'm not here. So you kind of have to modify your workout, right, according to how you feel that day. But I would say that the majority of my strength training workouts are deadlifting.

21:36Dr. Rhonda Patrick:You know, I love deadlifting. I think I'm pretty good at pulling that weight up, lifting that weight up.

21:41Andrew Huberman:Just a straight bar, hex bar. I do a straight bar. Mixed grip. There's so many variables. Straight bar, straight bar. And it's the same deal with that.

21:50Dr. Rhonda Patrick:Like most of the time with strength training we'll do, you know, we start off at like five or six and then work our way down. And then I usually do a drop set after, you know, any of those sessions where I'll do 10 and then it's like a lot lighter, right? So those are typically my strength training sessions are multi-joint. I mean, sometimes I'll do accessory sessions, you know, where I'm working. I do, you know, the dips or the Bulgarian, you know, the Bulgarian split squats. I mean, just the accessory stuff that you're working with, like, smaller stabilization muscles and stuff like that.

22:23Andrew Huberman:I love that you call Bulgarian split squats accessory smaller muscles. For a lot of people, that's the compound work, which is just I have to say I am inside. I'm just like so delighted because, I mean, obviously weight training is something that's caught on broadly for men and women now. But I don't know many women, and I know they're out there, but I don't know many women who are working down to singles on multi-joint, like real multi-joint, like, you know, deadlifts, cleans. I know they're out there, but it's not that common to see in gyms. And this is going to no doubt spark a debate because, you know, some of the older, slightly ornery, but very credentialed strength training folks have been online recently saying that as people pass 35, that they shouldn't do squats, that they shouldn't do deadlifts and certainly shouldn't do them heavy because of this whole thing of, you know, you can do higher reps and you can go to failure and still get hypertrophy.

23:20Andrew Huberman:but what I love is that you're not necessarily talking about hypertrophy maybe some hypertrophy but this is about strength this is about building more strength and triples and doubles and singles

23:33Dr. Rhonda Patrick:that's awesome it's hard that's awesome it's so hard and it's the part that I'm like all about let's like the last 30 minutes we're in it's hit and then that's hard it's a different kind of hard but for me the strength training is the hardest and there's definitely a mental component right where I do not want to do it. It's like you talk about cold plunging, right? Like you just, it's so unpleasant and you don't want to do it. And like you do it and it's like that mental toughness that you're building, right? That's what I experience when I'm doing these, you know, strength training exercises that I'm doing.

24:06Dr. Rhonda Patrick:And I don't know if it's going to get easier. Maybe it will. It hasn't yet. I still dread it, but I do it. And I'm proud of myself for doing it, but it is definitely hard. And I am getting stronger. I think mentally and obviously physically as well. But I have to add in the aerobic as well, though. I think that's really important. That's your base. Yeah.

24:28Andrew Huberman:You love it.

24:29Dr. Rhonda Patrick:I love it. And I do think cardiorespiratory fitness is very important for long-term health, as well as obviously building muscle and strength.

24:37Andrew Huberman:Well, on the one hand, I want for you as a friend to for you to hate the heavy work less. On the other hand, I don't because of this literature, I'm sure you're familiar with it, but the anterior mid-cingulate cortex, this brain area that is hyperplastic throughout the lifespan, which is rare for a brain area. And it enlarges when we do things we don't want to do. I mean, it's so clear. It's not just about doing hard things, it's about doing the hard thing you hate. And for you, that sounds like the heavy compound movements. For me, yeah, I don't like the cold plunge, which is why I do it. I don't think it's magic.

25:13Andrew Huberman:I just think it's a surefire stimulus that I hate to get mentally stronger. And I think having something that you really despise, that you know is good for you, seems to keep this anterior mid-singulate cortex volume either increasing or the same. And that's actually the thing in these so-called superagers that is the strongest anatomical correlate that we have. So on the one hand, I hope it gets easier. On the other hand, for your sake, I hope it doesn't get easier because it's going to be so much more beneficial.

25:42Dr. Rhonda Patrick:I have a coach who can tell when it's getting easier and she will definitely up the weight. I mean, it keeps going up. And so it gets easier in a sense, but it doesn't, right? So, I mean, I think that's the whole point is you're building strength and you keep making it heavier and it becomes harder again because now it's heavier. Awesome. And I haven't gotten injured. So that's also, you know, knock on wood.

26:09Andrew Huberman:Yeah. No, knock on wood. But thank you for rounding out that picture. It's super inspiring for men and women, you know, so.

26:16Dr. Rhonda Patrick:It's not easy to post on social media because obviously I'm a newbie. So I have all sorts of, you know, things that I can, ways I can improve. But I'm posting it, you know.

26:26Andrew Huberman:Well, and the fact that you're working down into triples, doubles, and singles, I think is something that I'm trying to do more of. And I think this notion that you can get hypertrophy with higher reps if you take it to failure. Sure, I totally agree, read the studies, totally agree with the data, but not everything is about hypertrophy. I think that's what people forget. It's not all about growing muscle. And VO2 max, which is great, but it's not all about the top contour. And what I love about the way you approach everything is you go through multiple layers of the health status, as it were.

26:59Andrew Huberman:This is probably a good opportunity to talk about protein because I have a very specific question about protein. We all hear one gram of quality protein per pound of body weight or lean body weight. That's sort of what we're kind of what's thrown at us. By doing the heavier weight training, do you notice that your protein appetite has increased? Like appetite specifically for protein foods?

27:18Dr. Rhonda Patrick:I don't know that I have. You know, I interestingly have been doing a little bit more intermittent fasting in which, you know, people think about intermittent fasting. They think about it as just one thing, one intervention. I think it's two. There's a behavioral aspect to it where it's a tool to sort of lower the amount of calories you're taking in. The other one would be this metabolic switch. But so I've actually since, I don't know, September maybe, last September of 2025, been doing more intermittent fasting. And what I mean by that is just really just eating less. and the reason for that is because I noticed that everything that I was doing, which was, I eat healthy, I exercise a lot, and yet I was sort of gaining more fat in the belly section, right, the visceral fat.

28:10Dr. Rhonda Patrick:And the only thing that really helped me stop that, put the brakes on, was getting more in a caloric deficit. So maybe my drive to do that kind of is skewing whether or not my appetite for protein would go up. But I personally am on the scale of 1.2 to 1.6 grams per kilogram body weight. Per kilogram, okay. Per kilogram, which is probably a little bit less than the pound.

28:39Andrew Huberman:You know, it's a kind of a throwaway statement. I mean, a gram of quality protein as defined as something with, you know, lots of the essential amino acids and so forth per pound or per lean pound of body mass. Yeah. Which is something I think I and many other people shoot for, but I'm curious how religious you are about the, you know, getting a certain protein amount or per meal.

29:04Dr. Rhonda Patrick:Basically, it wasn't working for me in terms of like I was really trying to get aim for like the higher end of the for me, you know, 1.6 grams per kilogram body weight or even a little bit above that. And what I found what was happening is that I was actually getting gaining more weight because I think I was consuming more calories at the same time. If you're getting it from Whole Foods, right, like that's just kind of naturally going to happen. And so I had to slide down. But I'm still, like I said, I'm still getting within that range of like probably on average maybe 1.3, 1.4 grams per kilogram body weight.

29:39Dr. Rhonda Patrick:And it's really worked well for me. But like people are different and you have different goals, right? You know, like I'm gaining muscle mass and I feel like all my training is like the most important thing. And I think that we need – generally speaking, I think people should become more obsessed with training and less obsessed with protein. Like the protein will complement the training. And as you mentioned, if you're training, perhaps your appetite for protein will increase. And so you'll start to eat more protein and less refined carbohydrates. I already wasn't eating a lot of refined ultra-processed foods in the first place.

30:11Dr. Rhonda Patrick:Probably not the answer you were expecting. But it's really, for me, focusing on getting more protein was not working for my body in terms of – but then again, I'm 47 years old. that perimenopause phase very different than someone who's 37 maybe?

30:31Andrew Huberman:I don't know the answer to that. I do know that I hear from more and more people these days that they are having a hard time getting that one gram of protein per pound of body weight. It feels like a lot to them is what they're saying. They feel like they're kind of forcing themselves to do it.

30:44Dr. Rhonda Patrick:You shouldn't feel that way.

30:45Andrew Huberman:Exactly. So I'm actually really pleased with your answer, not because I have an agenda here, but because I and many other people seem to feel like unless there's a lot of resistance training or tremendous demands like hiking while backpacking, where if you burn tons of calories you're carrying, you're basically rocking like nine hours a day, right? Right. That they have a hard time getting that much protein down. And I think that's also the case if people are eating starches. Like I eat rice and oatmeal and some breads and things like that. Not a lot of bread, but it sounds like you eat starches.

31:17Andrew Huberman:I do eat oatmeal too.

31:19Dr. Rhonda Patrick:It does satiate you. So these days, because I really kind of more focused a little bit on – I did want to calorically restrict somewhat without being unhealthy. Obviously, you can take every stressor to a bad, unhealthy place, right? You don't want to starve yourself. You don't want to like not eat enough food. But my meals are mostly like healthy proteins. So I have homemade turkey burgers. I eat a lot of those. And then I eat chicken. You know, I eat pasture-raised chicken. I do still eat wild Alaskan salmon. And then I'll also mix in some like filet mignon, like I like grass-fed steak as well.

31:58Dr. Rhonda Patrick:Those are my protein sources. And always I pair it with greens or like some sort of vegetable. Most of the times it's greens because they're the most micronutrient dense. And so these days I'm eating a lot of sauteed collard greens that are like pre-prepared, has garlic and onion. and I'll put that, you know, have that with my meal or I'll have some, you know, sauteed kale. Sometimes I'll have a salad with it, but the portions are smaller. And like I said, I also do a little bit of intermittent fasting. We can talk about that as well, but that's kind of these days what I'm doing for my meals. I haven't eaten as much.

32:34Dr. Rhonda Patrick:Sometimes I'll eat the high protein oats. They have those high protein oats that have you, have you seen those? They're pretty good.

32:39Andrew Huberman:I eat oatmeal, but I like protein foods. I like vegetables. I like fruit. I feel very lucky to like those foods mainly. And then the starch for me has to be very clean. I like oatmeal rice, homemade pastas I'll eat. Like if I go out, I'll have, sometimes I'll have some homemade pasta or a sourdough bread or something. But I find that most starches that are out there in the world have a bunch of other junk in them, but I just feel lousy, get kind of sleepy afterwards. So I, so it sounds like we eat pretty similarly, although I probably eat more starches than you do.

33:09Dr. Rhonda Patrick:It's the more processed types of carbohydrates that, as you mentioned, it's like typically you don't feel good after you eat them. And, you know, part of that's the post prandial inflammatory response because some of those foods are a little more inflammatory. I mean, a lot of additives and stuff that are affecting the gut, gut permeabilization, you're leaking lipopolysaccharide in the bloodstream, right? That's activating the immune system.

33:30Andrew Huberman:We used to inject, I don't do any animal experiments anymore, and I'm actually grateful to not do them. So I didn't like working on animals, but it was what we did until I decided to work on humans, but we used to inject LPS to stimulate an inflammatory response to kind of prime a regeneration response that you could get through macrophages and things like that. And so LPS is a very potent way to generate local or even systemic inflammation. I think hearing that some starches will stimulate LPS, that's interesting. Well, let me clarify. It squares with my experience. Let me clarify. I'm not challenging.

34:04Andrew Huberman:No, no, no. I'm not challenging. It squares with my experiences. I'm one of these, I never get stomach aches, I never get headaches. If I do, something's badly wrong with my stomach or my head. But if I eat certain starches, I'll be like, oh, like I feel lousy. And I'm wondering if it's this.

34:16Dr. Rhonda Patrick:So we have about a gram of LPS in our gut. Like that's on average because, you know, lipopolysaccharide is the outer component of a cell membrane of gram-negative bacteria, right? Yeast. We have a lot of bacteria in our gut, gram-negative bacteria, right? Trillions of bacteria in our gut. But so when we eat food, typically like our gut epithelial cells, we have a tight junction that's holding them together. When we eat food, they transiently open and then close. Like it's kind of a normal response, right? I would say the opposite end of the spectrum of that would be like celiac where they eat gluten or something.

34:51Dr. Rhonda Patrick:It opens up and stays open. And so you get like a ton of LPS leakage into the system, which causes massive inflammation. It just happens with meals in general. you do get somewhat of a LPS response from a meal. Now, the type of meal does matter. So when I say refined carbohydrates, it's not necessarily like healthy, you know, carbohydrates like vegetables. It's like you're eating something that is refined sugar, typically with saturated fat. So those types of foods really cause like LPS response. You know, it's inflammation. It's bad. It's hard on the gut. But the postprandial inflammatory response essentially is that LPS getting into the system, activating the immune system, which draws the energy.

35:34Dr. Rhonda Patrick:I mean, it's like it's very energy consuming to activate your immune system. Right. That's why when you're sick, you're so sleepy, too. Right. Well, there's also cytokines that are somnogenic and promoting sleep. But like activating your immune system requires a ton of energy. And so when you're constantly activating the immune system, you know, that's an energy sink. Right. And so you do feel tired. And that's why a lot of times after a meal, you're feeling kind of lethargic.

36:00Andrew Huberman:Do protein foods of the sort that you listed off before, do they cause less opening of the tight junctions of the gut?

36:08Dr. Rhonda Patrick:I think that the big deal with the opening of the tight junctions in the gut is, you know, I mean, eating a big meal will do it. Eating a very, like, ultra-processed food meal will do it. But interestingly enough, just eating a bunch of saturated fat without a fiber matrix, so like butter. You're just like eating butter. Don't ever do that. But like if you just eat butter, that's been shown.

36:31Andrew Huberman:My niece, when she was little, now she's all grown up. But when she was little, I taught her how to eat like a little bit of Kerrygold butter, and she loved it. So then we would do this thing where we'd do that. We won't do that anymore.

36:45Dr. Rhonda Patrick:I mean, a little bit's fine. But like, I mean, there's studies showing that it does like saturated fat is hard on the gut.

36:50Andrew Huberman:Yeah.

36:51Dr. Rhonda Patrick:Like I said, it's a sliding scale. Like meals in general do it, but it's like you would think. The healthier foods that you're eating, like whole foods, you're getting less of that LPS response. And then, of course, there's gluten and that complicates the whole story, especially for people that are celiac, right? Because that's.

37:06Andrew Huberman:Which is a small percentage of people are actually celiac, right? But a lot of people seem to believe, and I believe them, that when they eat gluten, they feel worse than when they don't eat gluten.

37:16Dr. Rhonda Patrick:I'm sure there's some people that are sensitive to gluten that do feel worse. And then I'm sure some of that's the nocebo effect, right? That's been shown with gluten in particular. Have you seen that study? Where people, there's been, so there were people that think they're, you know, gluten sensitive. And so they were enrolled in this study. And these individuals were separated into two groups. One group was given the gluten, bread with gluten, and the other group was given the bread without gluten. and the people that were given the bread without gluten had a terrible, you know, abdominal response.

37:52Dr. Rhonda Patrick:Like they were bloated. They felt terrible. I mean it was all – and there was no gluten in the actual bread, but they thought there was. So it was thought that there's a nocebo effect where it's like the opposite of a placebo effect where you've got that phenotype where you think things negative are going to happen, and you can make them happen. You can change your immune system. You can change your brain signaling and, you know. So probably a combination of both. with that regard. In addition to like the lethargy, so I was talking about in the context, that's why it sparked my, you know, interest is like you were talking about feeling tired after a meal.

38:26Dr. Rhonda Patrick:And I do think that is part of that reason for feeling sleepy. But, you know, what's interesting about LPS, you talked about injecting it to mice, and I've also done experiments injecting LPS into mice. There have been studies where people have been injected with an amount of LPS that is, you know, similar to what you would find your gut releasing into your bloodstream or a placebo control, which in this case was saline. And individuals that were injected with the LPS, high amounts of inflammatory markers like TNF alpha. I mean, we're talking like up to

38:57Andrew Huberman:50 % increase over baseline, right?

39:00Dr. Rhonda Patrick:So high amounts of inflammation, which makes sense. LPS is activating the immune system. Your immune system is like there's a foreign invader, right? It's not a foreign invader. It's just the food you ate that caused transient gut permeability. And those individuals also feel depressive symptoms and feelings of like social withdrawal. So the inflammation is affecting the brain, right? These inflammatory factors are getting in the brain, crossing the blood-brain barrier and affecting the way we feel. And we know now that inflammation plays a big role in major depressive disorder and depression, not in all cases, but there's a subset, right?

39:29Dr. Rhonda Patrick:Where it's really like it does, it seems to play a big role. In fact, interestingly, there's been some studies showing that people that are, that don't respond to SSRIs are, have very high amounts of C-reactive protein. So this was the biomarker for a classical biomarker for inflammation. I would argue it's not that sensitive, but nonetheless, it is a biomarker for inflammation. And so people that don't respond to SSRIs have high amounts of inflammation, which kind of raises this question of, is there like this subset of depression that's really inflammatory driven, right? Interesting. So the LPS is affecting not only our energy levels, but also our mood.

40:06Dr. Rhonda Patrick:And then, you know, there's also evidence that – so we know that LPS binds to LDL particles through lipid-lipid interactions. And in fact, it's kind of part of the adaptive response. It's why you don't want to ever go get your cholesterol measured like right after you're sick or had a very stressful event, something that causes inflammation because you will increase – VLDL production increases and LDL production increases. And it's sort of an adaptive response to bind that LPS to prevent it from causing more damage. And so it actually binds to LDL particles on the ApoB protein. So ApoB is a protein that is on these lipoproteins.

40:51Dr. Rhonda Patrick:And it's a very important protein because that is what's used by the LDL receptors present on our liver to recycle LDL particles. So what happens is these LPS particles are now bound to, you know, our lipoproteins. And our lipoproteins are still doing their function, right? They're going around and they're giving, you know, triglycerides and fatty acids and to some degree cholesterol to our cells that need it, right? We're constantly making new cells and repairing and our cells need that. As they donate triglycerides and fatty acids, they get smaller in size. The lipoproteins, you probably heard of small, dense LDL, right?

41:28Dr. Rhonda Patrick:Like that's a very dangerous type of LDL particle. And that's one that's kind of been donating along, getting rid of triglycerides and whatever. If you think about a train with cargo, it's donating, you know, dropping off the cargo. And so when it's time to get recycled back into the liver, what do you know? The ApoB protein is obscured by that LPS and it's not recycled. And so it gets lodged into the arterial wall. and because there's an LPS bound to this, you know, small dense LDL particle, macrophages, which are, as you mentioned, it's like the first line of defense against something like a bacterial invader, right?

42:06Dr. Rhonda Patrick:It comes and chews it up, right? Gets rid of the problem. So macrophages come in because they're seeing this signal of LPS and think it's a foreign invader when it's actually just a small dense LDL particle bound to LPS that came from the gut, tries to engulf it, but it can't because it's not bacteria. And you get the macrophage stuck to that lipoprotein LPS, you know, complex, and you get the formation of a foam cell. You've probably heard of a foam cell. It's the beginning of atherosclerosis. And so this is where gut health and the food we eat is sort of, it's linked to cardiovascular health, right?

42:41Dr. Rhonda Patrick:Gut permeability, getting that LPS into our circulation is actually not a very good thing because you're basically, you know, slow dripping in that inflammation, that inflammatory signal, and it's wreaking havoc in our arteries, on our brain.

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44:21Dr. Rhonda Patrick:Thank you for explaining that so clearly,

44:23Andrew Huberman:because I don't think anyone has ever explained how exactly gut health is signaling cardiovascular health or pushing or pulling down on or raising cardiovascular health. as a neuro guy, I think about the vagus nerve as the primary conduit between gut and brain. And I was recalling that LPS injected into the gut is how you actually experimentally induce a fever because the, and if you cut the vagus, no fever. So there's this, there seems to be something about the way that the gut communicates with the brain and other organs that is critically dependent on some threshold level of LPS. Thank you also for reminding us that LPS is present in the gut because we have yeast in our gut, some amount of yeast.

45:04Andrew Huberman:You mentioned tight junctions. And the way I think about tight junctions, please correct me because I'm going to get some or all of this wrong, is that essentially they form like a cellar fence in the gut. And that transient opening or partial opening of these is a normal process. But it sounds like after a meal, some bacteria, when you say leaks out into our system, it's literally going to the bloodstream. So now we have bacteria circulating. And if some of that is small enough to get across the blood-brain barrier, that's another way that bacteria can start to cause inflammation at the brain level?

45:34Dr. Rhonda Patrick:It's LPS, which is like the outer component of bacteria that have died. Actual live bacteria getting in, I don't know as much about that, perhaps as well, but I know that the LPS is getting in. And I do know that the LPS, you know, activating the immune system and stuff and the resident glial cells and stuff in the brain does break down the blood-brain barrier. It's like the early – like we know neuroinflammation is really some of the early parts of breaking down in the blood-brain barrier, which is the early stages of neurodegenerative disease. It is how the gut is – gut health is linked to the brain and to neurodegenerative disease as well.

46:14So it's the inflammation I think that's really – it's really powerful in terms of – it's a driver of the aging process in general.

46:23Dr. Rhonda Patrick:Like this inflammation, inflammaging, you've heard of inflammaging. You know, I think now it's pretty clear to me that is, if you're thinking about the molecular events that are leading to these hallmarks of aging, which lead to the phenotypes and, you know, frailty and the diseases, right? Like type 2 diabetes, cancer, Alzheimer's disease, like go upstream of that. And the inflammation is at the core of it. And so we hear this word inflammation a lot. And it's like, what does it mean? You know, and it's a lot. It means a lot of things. It's not just the gut. The gut is a component of it. But there's other things as well, right?

47:03Dr. Rhonda Patrick:I mean, you can have stress, you know, any emotional stress, like that can lead to inflammation, not getting enough sleep, right? There's a lot of things that can lead to inflammation. And so it is kind of an important point to think about is really like trying to have your inflammation low, right? And how do you do that?

47:25Andrew Huberman:I'm going to take three different jumping off points here, all related to what you said. So don't think I'm a random subject generator here. We will get back to fasting, I promise. Lately, you've posted a bit about glutamine as a potential tool to perhaps buffer the immune system under times of stress. I've also been interested in L-glutamine as a way to reinforce tight junctions in the gut. I don't know if that literature is robust or not. I have to say I started taking L-glutamine years ago in times when I was working a lot and not sleeping enough because someone told me it would help me not get sick.

48:01Andrew Huberman:And indeed, I didn't get sick as much as the imaginary control experiment that I never got to do. Meaning I don't know if it helped or not, but I continue to take L-glutamine when I'm feeling run down. And I take a couple of other things too, but could you tell us about how or if or how L-glutamine is important for gut health and if and how L-glutamine might be helpful for reinforcing the immune system? There's not a ton of evidence in terms of like what's in the scientific literature supporting these statements, but there is some, you know, and it's enough to kind of go, well, I'm going to try to maybe experiment with it.

48:36Dr. Rhonda Patrick:But so, you know, I first became interested in glutamine because when I was doing my graduate research, I was doing a lot of cancer metabolism studies. And I would do nutrient withdrawal and I would, you know, remove glucose from cancer cells and see what would happen. And it's like, OK, well, I would get I would remove glucose from from, you know, lymphoma cancer cells in the Petri dish. And a lot of them would die, but they wouldn't all die. And I was like, why aren't they all dying? Turns out, well, they had glutamine there. So glutamine was enough to sustain them. and so glutamine can be converted into many things.

49:07Dr. Rhonda Patrick:So glutamine can be an amino acid, right? It's amino acid. Glutamine can be converted into the Krebs cycle. So it can be converted into intermediates that are used to make energy by the mitochondria and glutamine can be converted into glutamate, right? Neurotransmitter, right? So there's a lot of pathways and different fates for glutamine. So I became interested in that because it was like, oh, glutamine's important for the survival of these cancer cells. Then I was doing a lot of activating immune cell studies. As, you know, my graduate advisor is an immunologist by training. And so I was also doing that.

49:42Dr. Rhonda Patrick:Turns out glutamine was essential for the activation of immune cells. So that was kind of always in the background of my mind. And then in my postdoc, I did my postdoc with Dr. Bruce Ames and my colleague, Dr. Mark Shigunaga, was doing a lot of gut work. And this is why I know a lot about the LPS and the gut. Like it's from him. Like brilliant guy. He's now a photographer, like not in science at all, but brilliant guy and did a lot of really amazing experiments looking at, you know, gut permeability and things that can help buffer, you know, gut permeability. And one of those things were glutamine.

50:14Dr. Rhonda Patrick:So glutamine can get converted into these intermediates that are used by mitochondria in the gut epithelial cells. And so that's like an easy source of energy as well for the gut. Now, these are all animal studies, right? So take it with a grain of salt, right? At some point, you know, in my opinion, animal studies are really important for understanding the mechanism behind why things work. And we need human studies, you know, as well. Looking at the totality of evidence is important. It's the human studies that we're lacking. There's not a ton of them there. The ones that I have found more compelling, not necessarily, I mean, with the gut health, it's, you know, it's sparse with humans.

50:57Dr. Rhonda Patrick:I found more compelling with respect to glutamine and human studies was the immune system. And this is where I started putting connecting the dots, right? Where I started coming across this literature of these endurance athletes who do get a higher amount of respiratory tract infections. You know, like when I mean endurance athletes, I mean, these guys that are like out running marathons all year, like they're just constantly training for a marathon. Right. And so they're really like they're putting a lot of demand. And, right, energetic expenditure is happening at a really high rate. So they're more prone to respiratory infections.

51:29Dr. Rhonda Patrick:And there's a few studies out there showing that if these athletes take a higher dose of glutamine, I think it's like 30 grams or something high like that, that they had a lower incidence of respiratory tract infections than once they weren't doing it. And then I went back to my, oh, I know that glutamine is really important for T cell activation. and I was like, I'm going to take this because being a mom and having a child that's bringing everything home like a vector, you know, you're like desperate.

51:54Andrew Huberman:You're the experiment.

51:55Dr. Rhonda Patrick:Yeah, exactly. And I never used to get sick ever. Like I would never get sick. And then all of a sudden I was getting sick like three times a year. And I was like, do I have cancer? Like what's going on? I literally was like worried. And then I started taking glutamine. Now I take it just, I only take five grams on a daily basis. But if, if my son's sick, if there's any exposure, if it's like during the season, if I'm traveling, I go up to 15, I go up to 20. All at once?

52:20Andrew Huberman:Cause it can be a little hard on the gut. No, not all at once.

52:23Dr. Rhonda Patrick:Not all at once. I usually do it like in fives. So I do five grams, five grams, five grams. And, you know, I have to, with the caveat of I do that, but I also take a lot of creatine as well. And so I don't know which one or both, but like, I really don't get sick. I'm not getting sick. And even if it's brought home in my house, I'm not getting sick. And maybe it's a placebo. And you know what? I am A-OK with that because placebo effect is real as long as I'm not getting sick. So I do think, I think with the glutamine, you know, it's not something that I would feel comfortable saying that it's, there's a lot of evidence.

52:55Dr. Rhonda Patrick:It's overwhelming and with confidence that it's improving gut health and it's improving immune, you know, it's going to help give your immune cells energy, particularly if they need to be activated, you know, upon exposure to any pathogen. But I feel like it's worth experimenting with. Perhaps maybe if someone has colon cancer, that would be more of a concern because I did mention that cancer cells, cancer cells love everything, anything that's good for you, right? Folate, I mean, if you don't have enough folate, you can cause double-stranded breaks to your DNA, which lead to mutations that lead to cancer.

53:24Dr. Rhonda Patrick:But if you have cancer and you take a bunch of folate, you need folate to make new DNA. And so they like the folate, right? So it's like -

53:30Andrew Huberman:It's an abnormal growth. So anything that's associated with growth. I saw the recent study on taurine, which scared a lot of people because taurine is in a lot of energy drinks. But that was an in vitro study. Yes, I was going to ask, you know, is there increased cancer risk if you're supplementing with glutamine because cancer cells love glutamine?

53:48Dr. Rhonda Patrick:So my personal opinion, I'm obviously not a medical physician. This is not a prescription. It's just my opinion. I personally am not scared of getting cancer from taking glutamine. If I had a colon tumor, a tumor in my colon, the first site that the glutamine is seeing, maybe the liver as well, since that's also the next step. But barring like having a tumor already in my liver or in my colon, those would be the only, you know, types of situations that I would be worried about taking glutamine. I don't think it's going to cause cancer, right? Now I guess the question is like what if you don't know you have?

54:23Andrew Huberman:Hopefully the cost will come down on whole body MRIs. Actually, the cost is coming down on whole body MRIs. that hopefully more people are able to get those. It's not just such a high-end exclusive thing in the near future. Kind of like blood draws. Used to be like panels of blood testing. You only got them if you really needed them. Now the cost of blood draws is really low.

54:41Dr. Rhonda Patrick:Right, right.

54:41Andrew Huberman:So hopefully people will be more aware. Yeah, I will take a tablespoon of glutamine once or twice or three times a day if I'm feeling run down. You mentioned being exposed to pathogens from vectors of different sorts. Before we went on mic, we were talking about NAC, N-acetylcysteine. I take it once a day consistently, but I'll take it three times a day if I'm traveling a lot because I'm around sick people when I travel, especially in winter, or if I feel like I'm getting run down. And there the data are pretty interesting. There's at least one study showing that it reduced flu transmission where people were deliberately exposed to flu.

55:18Andrew Huberman:I think it took the number of people that contracted flu compared to the placebo group somewhere from the high 70 % area. I don't remember the exact number now. We'll put a link to the study. down to maybe high 20s, which is pretty impressive. And an ER doc came on this podcast, Roger Schwelt, and said he was a big proponent of NSEAL cysteine for people that are around sick people. Do you take NAC?

55:42Dr. Rhonda Patrick:So my only concern with taking it on a daily basis is it is a pretty powerful antioxidant. And, you know. I think that we need to understand like antioxidants and the opposite, which would be generating oxidation, right? Like it's not like oxidation is bad. It's bad when it's constant slow drip oxidation that's damaging, you know, other parts of our body, DNA, proteins, lipids. Some oxidation you want, like if you're exercising, right? There's a burst of oxidation.

56:15Andrew Huberman:To get the adaptation.

56:16Dr. Rhonda Patrick:To get the adaptations. And so my concern would be, for one, maybe timing it around your exercise, so not taking it close to when you're exercising. And these studies come out of studies that have been done with high-dose vitamin E plus vitamin C. I haven't seen a lot of vitamin C studies alone that are blunting exercise adaptations. There's maybe one at a high dose. Most of the time it's vitamin C and vitamin E, vitamin E, alpha-tocopherol. When I say high-dose, usually it's 400 IUs. just to give you a reference point, the RDA is like 24 IUs or something. So we're talking high dose.

56:47Andrew Huberman:But a supplement can be 200 to 800. So it wouldn't be hard to blunt that exercise effect accidentally. Yeah, I don't take vitamin E. It spiked my prostate-specific antigen, which I was told is a known effect among urologists.

57:01Dr. Rhonda Patrick:The SELECT trial was done. So the SELECT trial was looking at selenium and vitamin E and if it could slow the progression of prostate cancer. And it turned out that the opposite was found. And it was really kind of due to this high dose of alpha tocopherol, which also has other effects of lowering another type of vitamin E in the body called gamma tocopherol, which is anti-inflammatory. And I think that has something to do with inflammation actually can increase the PSA, right? So anyways, the point here is that with NAC, my only concern would be, you know, blunting the oxidation that you're getting from beneficial because I know you're highly active.

57:43Andrew Huberman:I'm training hard. I don't want my training to be short-circuited from NAC. I'm perfectly happy to only take NAC if I'm feeling run down or exposed to illnesses around me.

57:53Dr. Rhonda Patrick:So that's when I take it, but it's mostly because I wasn't familiar with the influenza data. That's interesting. I was just, it's good for lung health too. Like, so although if smokers take it, I think it has the opposite effect where, again, it's like the precancerous cells are using it to their benefit. You know, we used to think antioxidants, oh, it's so good, you know, just more, more, more. And it turns out it's not the case, right? And that's why a lot of these other types of hormetic stressors or plant phytochemicals, they're actually generating an antioxidant response endogenously in our body by activating these antioxidant pathways, which are so much more powerful than what you would get from an antioxidant, right?

58:33Dr. Rhonda Patrick:And so that's kind of – it's not like you don't want some antioxidants. It's just like you don't want to overdose on taking too much NAC and too much vitamin C and too much vitamin E because there's also something called reductive stress. So we know about oxidative stress. Oxidative stress is when you're, again, you're causing these reactive oxygen species to damage things like your DNA, for example. And over time, eventually that happens in a part of the gene that can be oncogenic and lead to cancer. Well, reductive stress is like the opposite of that. So it's like too much of the reducing equivalents like the NADH, the NADPH.

59:12Dr. Rhonda Patrick:And it also has negative effects. So you kind of don't want to go too far on either ends of the spectrum. But also you want to, instead of having this like slow leaking effect of these pro-oxidants that are happening from eating a bad diet, from, you know, inflammation, things like that, you want it to be a short burst where you switch it on. You have the adaptation. It's off, right? And the adaptation happens in the recovery period, right? When you're, for example, if you exercise, that's a big burst of reactive oxygen species. That is beneficial. And you want it, right? and you don't want to blunt those adaptations.

59:46Dr. Rhonda Patrick:And so that's kind of my concern with daily dosing of NAC.

59:50Andrew Huberman:Great. I don't cold plunge in the six to eight hours after resistance training for exactly the reason you're talking about. Yeah, I want the inflammation. I want the increased blood flow. I don't want to short circuit that. I'm perfectly happy to only take NAC under conditions where I'm a bit run down. And that's also when I'll take glutamine. If you take L-glutamine regularly, I personally observe that I get stronger at a steady state of starch intake. And I don't like dropping starches too low because I get weak.

1:00:18Dr. Rhonda Patrick:Yeah.

1:00:18Andrew Huberman:And I also can't sleep as well if my starches are too low. I just am too wired.

1:00:23Dr. Rhonda Patrick:Yeah. There was a new study on eating starches and improving sleep.

1:00:28Andrew Huberman:Yeah, and I'm so grateful for that because for several years I talked about that on the podcast and people said, oh, you know, he's gorging himself with pasta and then passing out and that's the worst time. I wasn't saying that. I'm saying that if you're not, if you're running like crazy, I'll hear from marathoners and ultra people and people are doing a million things. They'll say, I'm not sleeping well. And they're exercising like crazy. It's like, well, when was the last time you had a bowl of pasta? Like, oh, no, I don't eat pasta. And then they'll have some rice or some pasta. Like, oh, I slept like a baby.

1:00:55Andrew Huberman:And they were having it at lunch. And I just think that the brain doesn't shut down well when you have high levels of cortisol. And the cortisol starch thing is an interesting one.

1:01:03Dr. Rhonda Patrick:I'm so glad you brought this up because I think this is something I did want to talk about really, and it has to do with stop eating three hours before bed for that very reason. So there was a new – even a new – but there's been several studies now really showing that this is important for that cardiovascular reset, right? Your parasympathetic activity is supposed to go higher. You're in your rest and recovery phase, right? When you're eating food, that's the sympathetic activity, right? That's activating the sympathetic nervous system.

1:01:32Andrew Huberman:As you're eating, yeah. Yeah.

1:01:33Dr. Rhonda Patrick:And even as you're digesting. So you have to think about it. Like you digest and what it takes like five or so hours to fully finish about. Yeah, depending on the meal. Depending on the meal. Right. So if you're eating, you know, right before you go to bed, you are not in that parasympathetic activity, you know, part of the cycle that you want to be in. So there was even a new study that I shared like, I don't know, a couple days ago even, showing that if you stop eating three hours before bed. So these people were actually – it's interesting. They had their blood pressure measured for starting in the mid-afternoon all the way throughout the night.

1:02:11Dr. Rhonda Patrick:This is the first study that really not just one endpoint looking at blood pressure but just measuring it continuously. I don't know if it was every 15 minutes or something like that. But it was found that during sleep, if they had stopped eating three hours before bed versus the group that did not stop eating three hours before bed, their blood pressure dipped like lower. So you get that baroreflex dipping, right? So this is like part of the parasympathetic activation. As you know, very important for the blood pressure to go down. Heart rate went down like, you know, much, much lower. And that reset is so, so important for cardiovascular health.

1:02:46Dr. Rhonda Patrick:I think what was found was it was something like translated to like 20 % lower risk of cardiovascular events like heart attacks. So it's really pretty significant. Yeah. And it really is an easy thing to do to think about stopping eating, you know, three hours before you go to bed. Like that's something I think that is not that hard to implement. And it will improve your sleep as well as your cardiovascular health. Although I think in that study, I don't know that sleep was really subjective and I don't think it really was improved more. But other studies have found that as well, that sleep does improve.

1:03:17Dr. Rhonda Patrick:I know Sachin Panda, he's been on my podcast, your podcast. He's had studies showing that it seemed like stop eating three hours before bed really does seem to improve sleep. But this parasympathetic activation, you know, you don't want to have a meal right before you bed because you want to be in the rest and recovery part, right? Right.

1:03:35Andrew Huberman:So, yeah, I think people hear and I understand why the nomenclature and the buzzwords of, you know, fight or flight for sympathetic and rest and digest for parasympathetic. But yeah, the evidence shows eating stimulates the sympathetic nervous system. It's not a stress event, but it's a it requires energy. Anything that requires energy raises body temperature and your body's doing work. It's an awake event.

1:03:57Dr. Rhonda Patrick:An awake event. It's an awake. You don't eat while you're sleeping.

1:04:00Andrew Huberman:Yeah, and that's why these phrases, while I don't demonize anyone for creating the fight or flight, well, I mean, there's ways that you want your sympathetic nervous system activated that are not about fight or flight. Like I actually think if people just got the first hour of their day more active and energized, bright light, exercise, caffeine, if you're me, and Lord knows I'm grateful that caffeine exists, in the first hour of the day or first hours if you can't manage that because of schedule. And then the last hour of the day was strongly parasympathetic. I mean, everything would get better without having to think a ton about exactly how you're doing that because on a given day, you just do what you can.

1:04:34Dr. Rhonda Patrick:And that's what you want, right? I mean, so cortisol is circadian dependent, as you know. I mean, in the, like, early morning of – early hours of the morning, that's when you want it to peak, right? Part of the awakening response. Like, you want it to go up. And it's interesting. The reason I'm going on this is because it's a little bit of a soapbox for me. But so with the cortisol activation, people don't realize this. You know, obviously it's a hormone and it's binding to two different receptors. There's the glucocorticoid receptor and then there's the mineralocorticoid receptor. And both of those, when cortisol binds to it, they go into the nucleus of the cell and they're changing the expression.

1:05:15Dr. Rhonda Patrick:So they're activating genes and deactivating genes, like 20 % of the human genome. It's a large percentage, right? And this is on multiple different organs. So cortisol has a very important role. And you want that peak. You want that spike, right? That's what you want. And then you want it to shut off. And there are things that can activate it, obviously, like in the morning, going out, bright light exposure, as you mentioned. Like that's very important for that cortisol awakening response. But you can also – like intense exercise can switch it on. But what's interesting, and so can intermittent fasting, that what's interesting is there's studies from Mark Mattson's lab showing that, you know, the types of stressors that are beneficial, these hormetic stressors like exercise, like, you know, intermittent fasting, perhaps even cold exposure, like these types of exposures change the receptor density of the receptors.

1:06:09Dr. Rhonda Patrick:So if you look at what activates cortisol in a negative way, chronic stress, let's say emotional, financial, psychological, chronic sleep deprivation, right, that bad type of stress, you're not getting a big spike. You're getting a slow drip of it. And so what happens is when you have that type of stress, you're increasing the glucocorticoid receptors and you're decreasing the mineralocorticoid receptors. There's a different biological response in the brain, in the hypothalamus, but also in other organs as well. when you're activating cortisol through a beneficial type of stress, the hormetic stressors like intermittent fasting, like exercise, I believe probably deliberate cold exposure as well, where it's a different biological response.

1:06:52Dr. Rhonda Patrick:And also if you think about it, you know, you actually want cortisol to do its, you know, function. You want it to change the expression. That's what it's supposed to do, right? The problem is when you have that slow drip, then, you know, not only are you increasing, They're changing the receptor, you know, activation, but also they become resistant to the cortisol. And so you're not getting the benefits. You know, cortisol represses inflammation, right? It suppresses the immune system. So you're not getting that anti-inflammatory effect from cortisol. It's being dysregulated. And that's what you don't want.

1:07:22Dr. Rhonda Patrick:You don't want cortisol to be dysregulated in terms of, like, the genes that it's supposed to activate or deactivate. You want it to be doing what it's supposed to. It's supposed to regulate. We're supposed to have the cortisol, you know, activation response. So anyways, that's something that I kind of want to clear in people's minds because I feel like a lot of people get worried about, oh, my gosh, I'm doing, you know, HIIT and it's activating my cortisol. Well, that's fine. It's like, you know, I mean, I guess if you do too much HIIT, right, you can always take something to the extreme. With that caveat, obviously, I'm not talking about that.

1:07:53Dr. Rhonda Patrick:But with that caveat, like you do, you want your body to be able to turn it on and then turn it off and have the adaptation, have the response, right? And like I said, it's a different biological response than the chronic type of cortisol activation that you get with the bad types of stress.

1:08:09Andrew Huberman:Yeah, I guess same goes for intermittent fasting. And maybe you could share with us what your intermittent fasting protocol is. I know that recently cortisol has been like increasingly demonized as the stress hormone, stress hormone. And people saw pictures of people with Cushing's disease, which is, you know, a drastically elevated cortisol and the moon face and the excessive visceral fat. And this sort of fear mongering around cortisol was particularly directed toward women. And this entered the health fitness space because I think in an appropriate way, I'll just be very direct here. I don't like, I no longer tap dance around who said, you know, in a very appropriate way that I appreciate, Dr.

1:08:49Andrew Huberman:Stacey Sims came on the podcast and she said, listen, some women shouldn't train fasted because they don't feel well when they train fasted. and their cortisol is too high and so forth. That captured a lot of people's experience. A lot of women in particular, but some men certainly were like, yes, oh my God, thank you. Thank you, thank you, thank you. But then the message got contorted, right? As it does, right? And then it became women shouldn't train fasted. And then we had Lauren Colenso Semple on this podcast who's trained as a PhD. She has a background in nutrition, physiology, strength training coach, et cetera.

1:09:24Andrew Huberman:And she said, no, listen, you can train fasted or not fasted as a woman or a man, it's kind of your preference, but that we don't need to fear these cortisol spikes. And forgive me for going long here, but I think it is important that people hear this again, which is there's also this idea that deliberate cold exposure increases cortisol. But when you look at the data, it definitely increases adrenaline and peripheral dopamine, and probably, I'll go on record, probably central dopamine, although we don't have as good evidence for that yet. But evidence points to the fact that deliberate cold exposure lowers cortisol.

1:09:58Andrew Huberman:So this then, you know, because, and again, I think Stacey appropriately said, a lot of women who want to use cold shouldn't go as cold, but the message got contorted and it became women shouldn't do deliberate cold exposure because of the cortisol increase. And so part of the reason I'm going long here is I'm trying to correct the narrative on her behalf. She said, do what works for you, right? And that's what Lauren's saying. And I'm guessing That's what you'll say as well. But I just need to get that out there because the message has gotten totally pretzel twisted up. And cortisol is neither good nor bad.

1:10:31Andrew Huberman:You want it high in the morning. You want it low at night in general. It sounds like you train fasted.

1:10:37Dr. Rhonda Patrick:I listen to how I feel. That's exactly what I do. So what your podcast guests and the researchers are talking about is exactly there are times when I wake up in the morning and I'm like, I need to eat something before I work out. And I do. But I oftentimes do train fasted, one, because I am practicing intermittent fasting again. But I do it, I'm not like starving myself. And like I said, the reason, there's multiple reasons I do it. One reason is because it really did help me lose the belly fat, which is the visceral fat, which is like the worst kind of fat you can have. And we can talk more about that.

1:11:11Dr. Rhonda Patrick:But the second reason is I love the cognitive benefits I have in the morning with it. And it's the main reason I do it. And so there are many times when I do train fasted, but I am not out running 15 miles. Most of my, like I said, my sessions are about an hour long. And am I taking a little bit of a performance hit with the high intensity? Probably. Probably, yes. But it's not much to matter for me. And you do burn a little bit more fat if you train fasted. I mean, that's known. You will, if it is a longer session, you will take an important performance enhancement hit. That is also known, right?

1:11:44Dr. Rhonda Patrick:So I think it really does come down to, like, what is your goal? How do you feel? and then you kind of go with that. And I completely agree. Like there are times when, you know, I'm on my cycle and I feel fine and I'm working out just fine. And there are other times that I'm like, I don't feel good. Like I'm going to take it easier. I still train. I just, you listen to your body. And that's a pretty easy, I think, rule of thumb. Sometimes people like to complicate things. You know, I don't, there's lots of reasons why. I don't, we don't need to get into that. I have theories.

1:12:16Andrew Huberman:Yeah, I have theories, but they're not important right now. No, it's not important. Yeah.

1:12:19Dr. Rhonda Patrick:So, yeah, I do train fasted and it is – for me, it has helped me tremendously change my body composition. Like I said, I'm in a different part of my life than perhaps a 30-year-old woman is, right? So when I was 30, I mean like I didn't have to train fasted. It was easy to keep, you know, the belly fat, the visceral fat lower. Hormonal changes do play a role in the way your body – so estrogen plays a role in telling your body how to store fat. So subcutaneous fat would be the kind of fat that you can just like pinch, right? The fat that we see. The visceral fat, that's that deep fat that's lining your organs.

1:12:56Dr. Rhonda Patrick:It's often belly fat, you know, and it's lining the intestines, the liver. You know, it's almost like an endocrine organ because it is secreting hormones. It's secreting inflammatory factors. It's metabolically active. It's constantly breaking down triglycerides. It's associated with double the increased risk, double the risk of early death. People that have high visceral fat have 44 % higher chance of having cancer, many different types of cancers. Wow. It's huge. It's huge. You know, and of course, insulin resistance is the number one problem with visceral fat, right? And I'd love to talk about that.

1:13:32Dr. Rhonda Patrick:But if you want, I mean, we can get into that. Yeah. So with the visceral fat, and like I said, you know, visceral fat is something if you really directly want to measure it, you do a DEXA scan. But, you know, for the average person that isn't going to go out and do a DEXA scan, waist circumference is a proxy. It's used in a lot of studies. So women that have a waist circumference of 35 inches or above are considered to have a higher amount of visceral fat. Men that have a waist circumference of 40 inches or above are considered to have a higher amount of visceral fat. It's also that belly fat.

1:14:02Dr. Rhonda Patrick:Like you can – you just know, right? Interestingly, like 70 percent of women over the age of 50 have high visceral fat. 50 % of men over the age of 50 do. You know, again, coming down to women go through menopause, estrogen plays an important role in telling the body, you know, to store the fat subcutaneously rather than viscerally deep around organs. And so as women transition to perimenopause, you know, the years before menopause and menopause, their estrogen goes down, and that does change the way the body stores fat. And any woman that's going through either of those stages knows it. And it's also why you see often women over the age of 50 with more belly fat, right?

1:14:45Dr. Rhonda Patrick:I mean, that's something that I think it's hard to deny. But it's one of the reasons why I kind of went back to practicing intermittent fasting because there's a couple of ways that you can really powerfully lose visceral fat. And one of them is doing aerobic exercise, high-intensity interval training, also really powerfully can do it, but also being in a caloric deficit. And I think when you start to get the combination of both, that's what really worked for me. It's crazy how quickly you can gain it based on your diet as well. So it is different from the subcutaneous fat in many ways. I've mentioned it's secreting these inflammatory molecules.

1:15:25Dr. Rhonda Patrick:It's, you know, hormones. But it's also constantly breaking down triglycerides into free fatty acids. And the location of it is very dangerous because it's right surrounding the liver, right? It's this deep organ fat. And that's very close to the portal vein. And so you're constantly getting this sort of mainlining free fatty acids to the liver. And visceral fat is very different from subcutaneous fat because it doesn't respond to insulin like subcutaneous fat does. In other words, when you have a meal, you eat a carbohydrate meal, and you basically your body increases insulin to help take up glucose into your liver, muscle, adipose tissue.

1:16:03Dr. Rhonda Patrick:Lipolysis shuts down, right? It's like, okay, no longer am I going to break down these fats. It's time to use this energy, right? Visceral fat doesn't respond to insulin, so it just keeps going, right? And these free fatty acids, because they're going right to the liver, it's essentially antagonizing the insulin receptors. So it causes insulin receptors to become more resistant to insulin. And this is part of why people with high visceral fat, by the way, you can gain visceral fat without gaining a pound. and we can talk about those studies. Like people are skinny and can have high amounts of visceral fat.

1:16:40Dr. Rhonda Patrick:You've heard of like metabolically unhealthy but lean individuals. Those people exist. And so you can have a high amount of visceral fat but not really look like you do. So when, you know, obviously the insulin resistance is a problem for many reasons, but it also plays a role in those energy crashes that you experience, right? And that's kind of like some of the first signs of insulin resistance actually have to do with what you're feeling. We talked about lethargy, right? So, you know, the inflammation that's being generated from this visceral fat constantly making these, you know, pro-inflammatory compounds are – it's an energy sink, right?

1:17:19Dr. Rhonda Patrick:So you do constantly feel tired. But also because your cells are becoming insulin resistant, when you have a high glucose meal and you're not responding, the body kind of overcompensates and produces more insulin. So it's like we got to get this blood glucose out of our system. It can cause a lot of damage if it sits around there. And so you make more insulin. And then what happens is your blood glucose goes way low because it was like this overcompensation. And then you feel a crash. You feel like this crash. And that signals to the, you know, hypothalamus part of the brain. I need energy, right?

1:17:53Dr. Rhonda Patrick:So then you sort of crave, you get those cravings for those calorically energetic dense foods. What I'm talking about is like the experience of like, you know, insulin resistance. And what's interesting is that you can cause someone to gain visceral fat and their brain can become insulin resistant. So we think a lot about insulin resistance in the muscle, liver. your brain also can become insulin resistance quite quickly, actually. So insulin is very important in the brain for a lot of reasons, as you know. But, you know, a couple of the things relative to what we're – or relevant to what we're talking about would be one is it does act on the hypothalamus and help, you know, tell it to basically stop eating, be satiated.

1:18:38Dr. Rhonda Patrick:Like I took a meal in, okay, like I'm going to be satiated. But it also plays a role in energy storage and telling the body how to store the energy. And so when your brain becomes insulin resistant, it's not doing that. And so you're not being satiated. So you eat more and you're storing the fat more viscerally. And there was a study that was published actually quite recently. I covered this in a recent newsletter. It was a really interesting study because it was healthy young men. And researchers put them on a little bit of a calorically dense. So it was like they were eating 1 ,200 to 1 ,500 more calories a day.

1:19:13Dr. Rhonda Patrick:and it was high saturated fat, high sugar. So it was the processed foods, ultra processed foods, like, you know, ultimate, right? That's a lot of extra calories. That's a lot of extra calories. They're five days. It is. But what happened was they did cause their brain to become insulin resistant and they didn't gain weight, but they gained visceral fat and they started gaining fat around their liver. And that's something that happens as well because visceral fat is surrounding liver. You're getting a lot of free fatty acids and they're going right to the liver. So the liver has to store it, right?

1:19:40Dr. Rhonda Patrick:So you get this non-alcoholic fatty liver. And that happened after five days. I mean, without gaining -

1:19:47Andrew Huberman:In otherwise young, healthy. Yeah.

1:19:49Dr. Rhonda Patrick:But they were eating a lot of calories, extra calories. Yeah, that's like a half a pizza extra above your maintenance calories per night.

1:19:59Andrew Huberman:And that's probably what they were doing.

1:20:00Dr. Rhonda Patrick:They were eating lots of - They were eating like saturated fat and refined sugar.

1:20:03Andrew Huberman:Burritos and french fries. Yeah.

1:20:04Dr. Rhonda Patrick:I mean, obviously, if you're going to do the study, you want to kind of do it to a degree where you're going to see some change, right? So maybe it's not going to happen in five days if you're only eating 500 more calories a day. But over time, you will be gaining visceral fat. So it's not going to be the same degree. It's something to be concerned about. It's something to think about. And also because you can gain it and not really even know it without gaining a pound. And there are other things that cause it, not just eating too many calories or diet composition. I mean, you mentioned cortisol.

1:20:36Dr. Rhonda Patrick:I mean, chronic elevated cortisol makes you store the fat around, you know, visceral fat. Sleep loss. I mean, there's also studies showing that you take healthy men, sleep-deprive them for a couple of weeks. I think four hours, they're getting four hours of sleep. At night, they can start gaining visceral fat, I mean, pretty rapidly with only like a pound, gaining a pound of weight. So, again, it's like not necessarily something that you're going to see on the scale, but it's happening, right? And it's affecting your short-term mood. I mean, how you feel, your energy. It's affecting, you know, the way you're eating.

1:21:05Dr. Rhonda Patrick:It's a vicious cycle because you start to eat more calories, right? And then it just becomes this vicious cycle that you start to gain more visceral fat.

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1:22:16Andrew Huberman:In fact, I love them all. I love the watermelon, the raspberry, the citrus, and I really love the lemonade flavor. So if you'd like to try element, you can go to drinkelement.com slash Huberman to claim a free element sample pack with any purchase. Again, that's drinkelement.com slash Huberman to claim a free sample pack. Such an important point that you can either not be gaining much or not gaining any total body weight, but gaining visceral fat. I think that's the first time I've heard that, and it's a vital message for people to hear because this visceral fat sounds like one of the major health hazards we need to worry about.

1:22:50Andrew Huberman:You mentioned chronically elevated cortisol, sleep deprivation will increase visceral fat. once again, I know I'm beating a drum here, almost to death, but having high cortisol early in the day and low cortisol in the evening is the definition of not chronically high cortisol. The definition of chronically high cortisol is somewhat elevated or elevate cortisol in the morning, but especially in the hours before sleep. And I actually have a theory that is not a stretch that one of the main reasons why it's so detrimental to our mental and physical health in the short and long-term is because of the ways it disrupts sleep.

1:23:27Andrew Huberman:And so, and we can't tease those apart. You can't do a study where you spike cortisol late in the day. Even if you can fall asleep just fine after the end of a really stressful day, the sleep is different. And people say, well, life has stress. And I totally agree. I mean, Lord knows I've experienced life has stress, but getting that last hour of the day, doing things to push down on cortisol, push down on stress, lower heart rate, not eating in that, certainly that last hour before sleep, ideally three. I feel like that small change can make an outsized positive difference.

1:23:57Dr. Rhonda Patrick:That's interesting, like the correlation between the high cortisol affecting your sleep, and maybe that's also like they're related. And so the sleep loss really does make you, we know, we know from, you know, you probably know who the researchers are that have done those studies on sleep loss and it affecting appetite, right? I mean,

1:24:15Andrew Huberman:Oh, everything gets dysregulated. I don't want to take us off course, but I think you might find it interesting that there's a beautiful study where they look measured metabolism during sleep. They basically had people breathe into a tube during sleep. They had a mask on. And it turns out that the brain cycles through all the different forms of metabolism during sleep. There's a phase of sleep where you're essentially running on sugar. There's a, then there's like a, it almost looks like somebody's ketogenic at one. Basically the middle of the night when we're, well, it should be at night when you're sleeping is a, it's kind of a test run of all the systems, but they get recalibrated.

1:24:47Andrew Huberman:and it's so important. I actually think, you know, most of the negative effects of alcohol that people talk about, yes, it's a poison. It's a class one carcinogen as classified by the World Health Organization. I think most of the negative effects of drinking are because of the negative effects of alcohol on sleep. I'm not telling people drink in the morning, but, you know, and so I think that if you get your sleep right, you're not 90 % of the way there, but you're halfway there.

1:25:11Dr. Rhonda Patrick:Yeah.

1:25:11Andrew Huberman:I really do believe that. And then getting your sleep right makes you do a bunch of other things.

1:25:15Dr. Rhonda Patrick:Right. You're more motivated to exercise, for one.

1:25:19Andrew Huberman:More motivated to exercise your food choices. I mean, and on and on. The problem with talking about sleep is so important is people will get sleep anxiety. So we tap dance around this. Like, oh, we don't want people stressed. Learn how to fall asleep. Learn how to fall back asleep. No one gets it perfect. Yes, you'll survive. Like, without one poor night's sleep or an all-nighter, you're not going to die. Like, you know, just get good at it on average, right? That's what I'd say. Could you tell us what the structure of the intermittent fasting is for you? Does that mean skipping breakfast, skipping lunch, skipping dinner?

1:25:47Andrew Huberman:Because I know a number of people are sort of getting drawn back to intermittent fasting after a couple years of it getting beat up on. It's like not the best way to lose fat. I think it's a terrific way to do the sorts of things that you're describing, and I'm learning today more about the positive things it can do for insulin sensitivity and so forth. If you're on a bout of intermittent fasting, are you doing it by the clock? Are you doing it by feel? What does it look like?

1:26:14Dr. Rhonda Patrick:For me, it really does depend on the day. And I really do try to stop eating three hours before I go to bed. It doesn't always happen, you know, with family obligations, social obligations. But it's the habit that's important, right? So intermittent fasting, you know, it's more than just one intervention. As I mentioned, it's a behavioral tool that you can use to limit your calorie intake without actually having to count all the calories, which some people like to do. Some people don't, right? So it's a tool, but also it's really important for a metabolic switch, as you mentioned, insulin sensitivity.

1:26:46Dr. Rhonda Patrick:And the metabolic switch is something that Dr. Mark Mattson coined, and I love it because I feel like thinking about intermittent fasting in that way makes it a little more clear as to the benefits of it. It depends on the meal you have and how much exercise you do, right? But on average, let's say 11, 12 hours to deplete your liver glycogen levels. And once that happens, you do start to burn fat and use fatty acids as fuel and make ketone bodies. So you go into ketogenesis, right? And that's a metabolic switch. Metabolic flexibility. You're going from using carbohydrates as fuel to using fatty acids and making ketone bodies as fuel.

1:27:24Dr. Rhonda Patrick:And that's something that throughout human evolution was ingrained, right? Like we didn't always have access to Uber Eats and Instacart and you just add a swipe, you get food, right? I mean, there were many times when people had to not eat because they couldn't forage their foods, maybe the time of year, or they couldn't hunt their food because they didn't get a win or whatever. I don't know. So this metabolic flexibility is something that's really ingrained in our DNA in a sense, right? I mean, one of the reasons I like to do that is the ketone production. And why is that? You know, ketones are really clean.

1:28:03Dr. Rhonda Patrick:They're a clean way to burn energy. So they generate less oxidative stress, less oxidative products, but they also are energetically favorable in that it takes less energy to use them to make energy than glucose does. So it takes more energy to use glucose as energy than it does ketones. But they're also a signaling molecule. So it's a way for the body to signal to other parts of the body like, hey, this is a stressful time. There's no food. I'm in ketosis. let's make you stronger, right? Because that's kind of what evolution wants. Like if you're not able to find or eat food, you have to be stronger to be able to do it, right?

1:28:44Dr. Rhonda Patrick:And so that's kind of at the, I say, core of this metabolic switch and why it's important. And I think that I really like Mark Mattson being the pioneer in this. And as a neuroscientist, really looking at the benefits in the brain as well, you know, these ketones like beta-hydroxybutyrate are activating, you know, growth factors like brain-derived neurotrophic factor in the brain. As you know, it's very important for, you know, learning memory, you know, synapse formation and stuff that's hugely important for neuroplasticity. So it's activating beneficial compounds like that. And, again, it's not going to happen if you're never going into this metabolic switch.

1:29:24Dr. Rhonda Patrick:And there's other ways to get there, right? So you can limit your food, go into this ketosis, right, where you're basically depleting your liver glycogen. or you can exercise a lot, right? So your energy expenditure goes up. So there's different ways to get to this metabolic switch. It doesn't necessarily have to be intermittent fasting. And I'm telling you this because I want to tell you why. I'm sort of back on the intermittent fasting. And by the way, it's not for everyone. Like I said, I mean, I think that you can find other ways to get this metabolic switch. And for me, intermittent fasting works.

1:29:55Dr. Rhonda Patrick:And so what I do typically is I will do most of the time my workouts will be fasted, Not all the time. It does depend on how I feel.

1:30:03Andrew Huberman:What time do you typically wake up?

1:30:04Dr. Rhonda Patrick:So I wake up like between 6 and 7. And if I didn't have a family, like, you know, getting my son ready, I would probably work out right away. But I don't end up working out until like 8.30. So I'm, you know.

1:30:19Andrew Huberman:It's still pretty early. What time do you go to sleep, if you don't mind me asking?

1:30:21Dr. Rhonda Patrick:I'm asleep. Like I'm asleep by 10. I'm usually in bed at 9. It takes an hour of just like, you know, hanging out. Yeah. Yeah, so – or 9.30 sometimes. But, yeah, usually 10 o 'clock is when I'm sleeping. That's my bedtime. And so I do stop eating. I try to stop eating by 7 p.m. But typically my first meal on – it depends on the day, but it will usually be like around 11, maybe sometimes 12. If I'm doing a podcast, it will be later. And I do like to be fasted in the morning because the cognitive benefits is really what I'm interested in with that metabolic switch. And it does come down to ketones.

1:31:00Dr. Rhonda Patrick:And I know that Mark Mattson's talked a lot about this. I had it on my podcast a few years ago, actually. I learned so much. But the ketones like beta-hydroxybutyrate are increasing GABA. They're like balancing the glutamate, the excitatory neurotransmitter with the inhibitory one, GABA. And I think the increase in GABA is what helps me and what I love the most because it does help, I think, quiet down some of the other, I don't know, chitter-chatter in my brain. and help me focus because it's like somehow the gap is calming in a way. I don't know exactly. You could probably describe it better than I can.

1:31:33Dr. Rhonda Patrick:All I know is that I really like it. And so in the mornings, I like to be, you know, I like to be fasted. I like to be cognitively aware. It's when I get most of my productive work done and I feel smarter. So I'm doing it. And that's why I typically like to shift my breakfast to later. Now, I do, I would say some days I do only eat two meals where I am, I'm honestly, I'm skipping the quote unquote breakfast, but some days I do have three meals and, you know, oftentimes there are like different sized meals. Right. And usually my, if I do have three meals, the, the, the third one will be the in between the first meal and the second meal will be like a very, like a half or three fourths of a turkey burger or something.

1:32:18Dr. Rhonda Patrick:So it's, it's mostly protein and it's not heavy, but so I would say I'm, you know, usually 11 to 7 probably is when I'm eating my meals most days. Some days it's, you know, I fast for a shorter period of time. Some days I wake up in the morning because I did too early of like, you know, I'd stopped eating like four or five hours before bed and I'm like, I need to eat. And I guess what? I eat and then I work out and it's like, that's, you know, you kind of just listen to what your body's doing. Actually, Mark Mattson just published a study very, very recently showing that he did a, I think he was doing a 5-2 intermittent fasting protocol where it's like two days, you're getting pretty severe caloric restriction.

1:32:57Dr. Rhonda Patrick:Like you're eating one meal, but it's like 500 calories, you know, for the day. And it's twice, two days out of the week. The other five days, you're eating normal. And compared that to calorie, like eating like a healthy diet. And they were somewhat calorie restricted, but not quite as much as the people that were doing the fasting. And the fasting group had massive cognitive benefits, like 20 % improvement in a battery of tests that were done.

1:33:19Andrew Huberman:He attributes that to the ketones and the effect of ketones on GABA.

1:33:23Dr. Rhonda Patrick:He attributes it to the ketones. And like, can you get that to some degree with caloric restriction? Probably, especially the more severe caloric restriction you do, you can. If we're talking about weight loss, caloric restriction is key, right? You have to have that. If we're talking about the cardiovascular reset, like caloric restriction, if you're eating meals right before bed, you're not going to get that. Like those studies have been done. And I think, you know, Courtney Peterson was one of the first ones to really show that effect on blood pressure, you know, like really significant. In fact, if you do early time-restricted eating and stop eating, you know, I don't know how early in the day it was, maybe 6 p.m., maybe it was 8 p.m.

1:33:58Dr. Rhonda Patrick:But, you know, there was like a blood pressure drop that was like 10, you know, 10, I think it was, points or something, millimeters of mercury.

1:34:08Andrew Huberman:Significant. What is it? Yeah. Yeah. Yeah.

1:34:11Dr. Rhonda Patrick:So, I mean, that's very significant. You know, it's on magnitude of what you'd see with like some of the first line, you know, drugs that are used to treat hypertension. I would never say for someone to do that, but I'm just saying it's significant. And that's not something that you typically see if you're eating, you know, fewer calories, but you're eating constantly throughout the day. So I do think there are special benefits that can be had. But again, it's also a tool that people use. I use it as a tool as well. I don't like to count calories. Like I don't, you know, some people do. And that's fine.

1:34:39Dr. Rhonda Patrick:Then, you know, that's the way you can do it. But I like it for the metabolic switch as well. If I were an endurance athlete running, you know, 10, 14 miles a day, I wouldn't have to do this. That would be my metabolic switch. And it's not that I'm not metabolically flexible. I mean, I do. I think you can just training itself, you know, does to some degree help with metabolic flexibility, right? The ability to switch between burning glucose and carbohydrates and then using fat and fatty acids as your energy source. It's that I really, I want that, I want that real switch to be on. And I want it to be on for a little bit of time.

1:35:19Dr. Rhonda Patrick:And then I want to turn it off by eating. You know, I'm not starving myself. And I think you can go too far with exercise and with fasting. The problems with fasting and the people that are like, oh, fasting is terrible for you. I mean, it comes down to one, they were all about, it's like the weight loss is not just due to intermittent fasting itself. It's due to calorie restriction. Guess what? They were right. They were right. Number two, they're afraid of losing muscle. And I think we have enough data now that if you're training, if you're doing resistance training, you're not going to be losing muscle.

1:35:47Dr. Rhonda Patrick:Now, maybe you won't gain as much as if you were eating more protein. But you could. You could just eat more protein within the window that you're eating and be fine, right? So I think that's the other thing that people are worried about is muscle loss, including myself. And I train so much now. And it just works well for me. And I feel good. And it's this clean feeling. You feel cognitively sharp and it works. And I think that the metabolic switch is something to not be scared of as long as you're not, again, going to the extreme, right? And if you don't want to train while you're fast, don't train while you're fasted.

1:36:23Dr. Rhonda Patrick:You don't have to, you know. I think there's a little bit of an added benefit that works for me in terms of burning fat, which is what I, you know, particularly visceral fat. And to me that's what works well. But you can obviously like if you're training hard and a lot and really fasting, maybe that's too much. It's too much of a stress. So you have to kind of figure it out for yourself.

1:36:47Andrew Huberman:Yeah, I think the known increase in adrenaline from being slightly fasted is awesome for cognitive function. I think it allows people to ingest fewer stimulants in the form of caffeine. You don't need as much caffeine when you're doing some fasting. What you describe is similar to what I do, although I notice these days I'm waking up hungrier and hungrier, and I attribute that actually to my last bite of food coming a little bit earlier in the day and further from sleep. And also that thermogenic effect of eating raises core body temperature, and you know to fall asleep, you want your body temperature dropping.

1:37:22Andrew Huberman:So it all starts to – what I think is very exciting to me is that for a few years there, it seemed like there were just so many things, so many protocols, so many studies. But when I think about cortisol high in the morning, low in the evening, bracketing the day, what works best for sleep, but what you're describing, certainly today you really, in addition to many other things, really clarified the relationship between gut and inflammation and brain and other tissues. Things start to fall into bins that it's, you know, like all of biology, so beautifully organized that it doesn't mean long lists of things for people to do.

1:37:56Andrew Huberman:I love the idea that while it sounds like you're just saying, oh, if I wake up and I'm hungry, I eat. And if I'm not, and I think I can train fast, I like to train fast. That might seem like an obvious thing to some, but I think it's so critical because the mechanism that you're chasing in both cases is the same. You're trying to get great sleep, great workouts, but you're not trying to optimize the workout to the point where, you know, you disrupt your sleep or you insist on doing something like eating or fasting, whatever it is. So the find out what works for you thing is so crucial because it's about feel that fits into a logic.

1:38:30Andrew Huberman:And I have to say that's initially what drew me to your work is there's a logic. You're not just saying, okay, this study said this, so I'm going to do this. It fits into a broader logic that comes from your training. So that's just a point of gratitude, and I hope it will frame in people's minds that, yes, do what you feel, do what works for you, but try and frame it in a certain logic. Right. Because that's actually what gives you flexibility over time. Like, oh, you're traveling, you have to eat a little later. Okay, the next morning maybe train fasted or vice versa.

1:38:58Dr. Rhonda Patrick:Yeah, it's about the habit. Exactly. It's about the habit. And there are days when I just like I can't train fasted or there are days where I wake up and I have to eat. Exactly. And there are days when I – nights when I'm eating later because of social obligations and I don't freak out about it because it's about the habit.

1:39:13Andrew Huberman:I like the idea of one metabolic switch per day. You know, you said you could get it from exercise. And I thought, you know, I can really imagine that in five years, a concept of health that hopefully everyone understands out there is that find a way to generate the metabolic switch once per day. Maybe you fast and exercise. Maybe just exercise. Maybe just fast because you can't exercise because people's schedules are constrained. But the notion of the metabolic switch is being – here's where it fits in exactly. The logic is you want the metabolic switch. You do.

1:39:45Dr. Rhonda Patrick:And it's not just, you know, there's other components to this metabolic switch that we haven't even discussed, which is like when you're in that fasted state, when you're in the ketosis, like that's also repair mode for your body, right? So there's the fed state, the grow, anabolic, and of course we're all obsessed with anabolic now because they're associated with muscle growth, right? But there's also the repair and recovery state, right? And so you don't always want the growth on, right? You want to repair damage. And repairing damage can be damage to DNA. A lot of these genes are activated when you're in a nutrient-deprived state, right, when you're in that metabolic switch.

1:40:25Dr. Rhonda Patrick:And autophagy, and that's another one that people – it's a buzzword now, but it is something that is activated. First of all, we have basal amount of autophagy going on at any point, right? Like that's happening. You don't have to fast.

1:40:39Andrew Huberman:You don't have to fast, exactly. Or be in a caloric deficit, which will also exacerbate it. Right.

1:40:43Dr. Rhonda Patrick:You do have fasted-activated autophagy, and certain tissues are more sensitive, like the liver and the brain, actually. And so, you know, we don't have a lot of human data on that in terms of, like, fasting. Exercise also activates it. We don't have a lot of great quality human data, and that's for a lot of reasons. One is the tissues that are most responsive to fasting-induced autophagy are not blood cells. In fact, like, blood cells are pretty restricted in their response to fasted-induced autophagy. But that's the easiest cell to access if you're going to measure autophagy in humans, right?

1:41:18Dr. Rhonda Patrick:Muscle biopsies have been done. Muscle is also responsive to fasting-induced autophagy. It's responsive to exercise-induced autophagy. By the way, the exercise, again, it's increasing energy expenditures. At the end of the day, you're getting into that sort of ketosis state, the metabolic switch. So there are studies showing that there's a signal there. But, you know, for some people, it's not enough. Well, it's not enough. We don't really know. And you can't go off the animal data. And, you know, I think to some degree it's going to be hard to go get a liver. I mean, maybe we'll have some tools soon that we can easily access a liver biopsy.

1:41:54Dr. Rhonda Patrick:And that'd be great for many reasons, right? Not just looking at autophagy. But I think that to some degree you kind of just have to know that, okay, autophagy is happening right now in our cells. So we know that it's activated by fasting, by exercise, by these types of stress. And so why wouldn't it be increased somewhat? And when I say autophagy, I'm talking about clearing out gunk that's built up in your cell throughout the day. We're talking about pieces of DNA, fragments of DNA. We're talking about protein aggregates that didn't get – they're either properly, like, not properly folding or they're not being degraded, right?

1:42:32Dr. Rhonda Patrick:All sorts of stuff, right? And it's important. This is a cleanup process. It's important. And so, again, that's another part of the metabolic switch that I think is – it's important to think about because we are really obsessed with anabolic, anabolic. Is it anabolic? It's great. You do want to – you definitely want to grow muscle, right? You do want to grow new brain cells and stuff too. But you also want to repair and you want to have recovery. And that's another, you know, it's like the yin and the yang, right? You kind of want both. So I think that's important to think about as well. And fasting, intermittent fasting, I do – I like the daily metabolic switch.

1:43:06Dr. Rhonda Patrick:It may not be for everyone, you know. I mean like I said, it's not – I do think that you can find other ways to get there, exercise being the big one. Some people do, caloric restriction. Some people don't need to. Caloric restriction is something that helps if you're trying to lose weight, right? It helps if you're trying to lose visceral fat. It's one of the main ways you can do it. Intermittent fasting, calorie restriction, exercise, aerobic exercise that helps lose visceral fat. But I mean, obviously, we don't always want to be in a caloric deficit, but we always don't want to be constantly eating either.

1:43:35Dr. Rhonda Patrick:And that's why it comes down to, I think, the simple rule for people. Like if they're going to do some sort of metabolic switch, some sort of intermittent fast, it would be like, okay, let's try to at least stop eating three hours before bed. Because then you're at least going to be extending that fast somewhat by three hours, right? So I think that's – and plus you're getting that, the cardiovascular benefits that are really – they seem to be important. And then not eating at night. So there's all these studies that have come out of Israel. I think it's – is it Jacobitz? Jacobitz and Freud, they're two researchers.

1:44:06Dr. Rhonda Patrick:I mean, Sachin Panda, I remember years ago, showed me one of the studies. It was like published in Science showing that if you have the same exact meal, same calorie intake, same composition, macronutrient composition in the morning, the afternoon, in the evening, the insulin response is different. Like you're the most insulin sensitive early in the morning as you start to go towards the evening and particularly three hours before your natural bedtime, your melatonin levels naturally rise, right? And as you know, you know, melatonin is important for the onset of sleep and preparing the body for sleep, but it's also preparing the other organs for rest and recovery, including the pancreas, which is making insulin.

1:44:44Dr. Rhonda Patrick:And so you're not making as much insulin when it's closer to your natural bedtime because of the melatonin levels that are rising. And so you don't want to be eating, particularly a carbohydrate-rich meal, but a meal, you're not going to be as insulin sensitive.

1:44:57Andrew Huberman:In the last three hours before sleep.

1:44:59Dr. Rhonda Patrick:Yeah, when you're starting to get into that melatonin rising phase of your cycle.

1:45:06Andrew Huberman:Yeah, it's interesting. I think when people hear, okay, you're most insulin sensitive in the morning, that would be the time to eat your biggest meal. But then people say, wait, but then I'm trying to fast and I'm trying to exercise. And like, how do I do this? I think that's where for them, the confusion comes in. And to me, it's very simple. Just because your insulin sensitivity is highest first thing in the morning, doesn't mean you have to eat right away. I mean, it just means avoid eating too close to bedtime, right? Sometime during the day. And also if you exercise fasted or after a small snack, it was kind of interesting when Stacey Sims said, not everyone should exercise fasted.

1:45:39Andrew Huberman:She said, especially a lot of women don't like to do that. She didn't say eat a meal. She said like, have a scoop of whey protein with some, I think she said with like some almond milk in it. And you couldn't believe the response on the internet. It was like vindication, right? And I get it. It was like it vindicated people's experience. Like, oh, thank you, thank you. And it told me something really important about the kind of sociology of what we do, which is when something validates people's experience, they love it. But it doesn't mean that the things that work for other people don't work.

1:46:11Andrew Huberman:And I think that that's the part that gets lost. And so if a study shows that insulin sensitivity is highest in the morning, but you can only exercise first thing in the morning, what do you do? You know, so you do the best you can. Right. I think it's what it comes down to. In fact, I meant to ask you earlier, and this is a good time to talk about this. You've described that if you are slightly sleep deprived, so not four hours per night or an all-nighter, but if you've only slept five, or let's say you're getting an hour or two less than your normal ration of sleep, there's some pretty significant inflammation that occurs that's not good.

1:46:46Andrew Huberman:But I've heard you cover that exercising can actually offset some of that inflammation. This answers an important and common question, which is if I have to pick between sleep and exercise, what do I do? And it sounds like if it's one night, poor sleep, exercise. But you don't want to make it a habit. Do I have that right?

1:47:07Dr. Rhonda Patrick:Yeah. I mean, so this data, a lot of it actually comes from you can cause even acute insulin resistance after like a night of sleep deprivation, certainly after two to three nights of sleep deprivation. And, you know, again, a lot of that's coming down to some of the things we've already talked about. and but exercise can help basically negate a lot of that and I learned that firsthand through experience when I was wearing a continuous glucose monitor and when I was a new parent of course you're not getting enough sleep and so that's I learned it before I actually dove into the science about it I learned about it through my own data where I was you know I wasn't exercising as much and particularly in the first month really like you're kind of in a cave as a new mom you You don't really, you're not really exercising much at all.

1:47:54Andrew Huberman:Evolution wants the baby to survive.

1:47:57Dr. Rhonda Patrick:You're recovering too. I mean, childbirth is a very, it's a very traumatic process on your body. And so I noticed that my glucose response was like, it was like pre-diabetic. And I was like, what is going on? And that's when I started looking into the literature and happened to be around the same time when I was then starting up my, at the time I was doing spin classes. And then it was very clear to me. It was like I do these high-intensity interval training classes even just twice a week. And it was like almost completely negating what I had seen previously of my fasting glucose being really high and also my postprandial glucose being higher than usual.

1:48:35Dr. Rhonda Patrick:And so I looked into the studies and there's now – you can find many studies out there. And it really, I mean, obviously exercise is one of the best thing you can do to improve insulin sensitivity and to also bring glucose into your cells, right? And so that's part of what you were talking about with, oh, you're more insulin sensitive during the morning, at least during the evening. And I also mentioned that. But guess what? There's levers you can pull that like change the equation. And exercise is a big one, right? If you're exercising, you're becoming more insulin sensitive. You're increasing more glucose transporters on your muscle that's causing glucose to go in easier, right?

1:49:08Dr. Rhonda Patrick:So there's lots of ways around some of these rules that we hear about. But with the sleep loss, it really is – it's interesting because people like when they don't get sleep, the last thing they want to do is work out. And obviously like you don't want to do like the hardest thing, especially if you're really like sleep deprived a lot. But it really does help negate the inflammation and the insulin insensitivity that can happen after even just a single night of sleep. And there's studies out there showing that. And then there's also these longitudinal studies that have been done looking at, you know, people.

1:49:42Dr. Rhonda Patrick:So obviously poor sleep is a problem, you know, in the United States. I mean, a lot of people are sleeping fewer than seven hours a night. But there's studies out that have looked at people that sleep either shorter, so fewer than seven hours a night, or they're sleeping more than 10, right? So you don't want to be on either end of the spectrum. And usually like sleeping long, there's like other disease states associated with it, right? But so people that are sleeping, you know, not getting enough sleep, they have a higher all-cause mortality than people that are getting at least seven to nine hours of sleep.

1:50:11Dr. Rhonda Patrick:And the same for like more than 10. They have a higher all-cause mortality than people getting between seven and nine. But if people exercise, if they're meeting the physical activity guidelines right now, which is 75 minutes of vigorous intensity exercise and 150 minutes a week of moderate intensity exercise.

1:50:28Andrew Huberman:Right. Well, because the guidelines are helpful, but they're just guidelines because, I mean, doing the sort of workout that you're doing, working up to doubles and triples and singles on compound lifts and then doing cardio, like getting your heart rate elevated and then doing addition to that and then your hiking. I mean, it's just – I think the guidelines are a good jumping off place for people to think about.

1:50:50Dr. Rhonda Patrick:Well, we can talk about that because there's a new study that kind of throws that on the head. But the point is that if people were exercising within the guideline range, that they basically, if they weren't getting enough sleep, if they were getting fewer than seven hours of sleep per night, that they basically had the same mortality rate as people that were getting enough sleep. So it's offsetting some of that unhealthy stuff, the insulin resistance, you know, the inflammation that we know, you know, can lead to diseases and early mortality.

1:51:18Andrew Huberman:So find the time to exercise, folks. But of course, periods of time like after a new child or new job or particularly stressful time, I don't know any human being. I don't care how driven. Okay, there's probably – Duggins and Cam Haynes being probably exceptions and a few others. The outliers. I don't know. You can ride out and a few others. But people who – everybody else seems to have periods of time where they need to just back off a bit. I know I certainly do. I feel like I'm doing pretty well for myself despite, you know, and I think that it's important that people not hold themselves to a standard that is going to make them sick or injured or miserable beyond.

1:52:02Yeah, you also want to continue to enjoy health promoting activities.

1:52:06Andrew Huberman:Right.

1:52:06Dr. Rhonda Patrick:I mean, you got to say, like, what's your goal? Like, your goal is to be healthy, to be happy. if you're taking it to this extreme where you're trying to just go to the extreme, like go hard, go home, and you're sacrificing your happiness too, I mean, that's a problem, right? Because that's part of the equation. Happiness is part of that healthy equation.

1:52:25Andrew Huberman:Health is a daily and lifelong thing, but sometimes it means taking a day off. I think that's what people don't say. And I think it's in a time when perhaps a lot of people aren't exercising enough. So promoting the no days off thing can be helpful. But for those that are already, you know, forward center of mass, you know, coming off the accelerator can be really useful.

1:52:47Dr. Rhonda Patrick:Well, I also want to just mention because, you know, we talked about my, you know, I work out a lot and I am sort of addicted to it. But like not everyone has the time and motivation to go spend an hour block of time working out. And this is where I think that people can sigh a sigh of relief because there's now so much emerging data that have been coming out, you know, over the last decade on these short bursts of physical activity that add up. They add up and people aren't really thinking about them, you know, counting towards adding up to their physical activity, you know, requirements for the week.

1:53:28Dr. Rhonda Patrick:And so there's a lot of studies now. There's on something called Vigorous Intermittent Lifestyle Physical Activity, VILPA studies. Have you heard of those?

1:53:36Andrew Huberman:Are these the exercise snacks?

1:53:38Dr. Rhonda Patrick:They're unstructured. They're unstructured and not everyone likes the word exercise snacks. I mean, I kind of like it. But the unstructured exercise, they're the moments in your life where you're taking advantage of everyday situations to get your heart rate up to move. And so that could be I'm playing with my new puppy and I'm sprinting around with my new puppy. I'm, you know, chasing my grandkid around. I'm playing tag or my child. I'm sprinting up the stairs to get to my office. I'm running to catch the bus. I'm moving, right? And so researchers, and there have been several studies on this now, researchers use accelerometers rather than just relying on these questionnaires, which are, as you know, you know, extremely unreliable.

1:54:19Dr. Rhonda Patrick:I mean, it's very hard for people to remember how much exercise. You sitting here asking me about my exercise. I mean, there's always so much, you know, that you can be accurate when you're trying to recall that. So these accelerometers are worn on people's wrists and they're measuring like fast movement, the movement, right? And so thousands and thousands, like hundreds of thousands of participants, there's lots of data now showing that people that are doing these like short bursts at least a minute long, but up to three minutes, right? Where they're getting their – they're moving. I'm saying they're getting their heart rate.

1:54:49Dr. Rhonda Patrick:They're actually not measuring their heart rate in these days. They're moving faster with intent, right? They're jogging or they're, you know, they're not – of course, there's the cases where they're actually exercising. But the short bursts of it, they're doing the things that I just mentioned, and it's having outsized effects on health outcomes. So, for example, individuals that do on the high end, so they're doing, you know, three minutes of this short burst of an unstructured type of exercise snack, and they do it three times a day. So it's a total of nine minutes a day, okay, this type of activity.

1:55:25Dr. Rhonda Patrick:And it's considered more vigorous because of the intent to move, right? That's more vigorous even though they're not measuring heart rate. That's associated with a 40 % reduction in all-cause mortality, 40 % reduction in cancer-related mortality, a 50 % reduction in cardiovascular-related mortality. Wow. Nine minutes a day. And this is even in people that don't identify as exercisers. So they're not the kind of people like you and I that go and intentionally set out time to go to the gym. They're people that just, they're doing those things, right? They're playing with their grandkids or their kids or their puppies or whatever.

1:55:55Dr. Rhonda Patrick:And so these moments, they add up. And I'm citing one study, but, you know, it was a dose-dependent effect even doing three minutes a day. You know, there's a study in women showing, you know, three and a half minutes a day. I mean, they were having pretty profound benefits on all-cause mortality and cancer-related mortality as well. And multiple studies now have shown this. I mean, this is like one study after another after another. It is undeniable that these short moments of, you know, getting physically active do add up. So, structured exercise snacks can be part of that. Like maybe you don't have a puppy.

1:56:26Dr. Rhonda Patrick:Maybe you don't have a kid yet. Maybe you work from home and you're not taking this. You know, maybe your situation is different than what I described, but you can take these moments to do exercise snacks. And that can be a minute long. And it can be like there was there's studies showing that two studies and I'll talk about one showing that getting up and doing 10 body weight squats every 45 minutes over a seven and a half hour work day is better at regulating blood glucose levels than a 30 minute walk. Right. So you get up and you do 10 body weight squats. Pretty easy. I mean, it's also very good to break up that sedentary time.

1:57:01Dr. Rhonda Patrick:So being sedentary means that you're not moving. That also is an independent risk factor, even if you do exercise for things like cancer being a big one. Although I would say if you're doing a lot of exercise, you're doing pretty good. But I'd just like to mention that as well. I would say being sedentary is a disease, actually. That's something, I mean, people aren't thinking about it, but.

1:57:22Andrew Huberman:Even in the absence of what Lynn Norton calls energy toxicity, like even if somebody is at maintenance or below maintenance calories, if they're sedentary, that's problematic.

1:57:32Dr. Rhonda Patrick:We do have data for one measuring cardiorespiratory fitness, which is a marker of cardiovascular health, being physically fit, right? Obviously, the gold standard of that would be measuring VO2 max, your maximal oxygen uptake during maximal exercise. A lot of studies do not actually directly measure VO2 max. They'll do, you know, maybe a submaximal treadmill test or they'll estimate it, right? There's a calculation out there. You can do kind of what you're, if you wear like an Apple watch or some sort of fitness tracker, what they do is, which is, you know, it's looking at the distance that you run and the amount of time it takes, right?

1:58:08Dr. Rhonda Patrick:So like a 12-minute run would be an example. People do that. You run as fast as you can and maintain that pace for 12 minutes. You're not going all out, obviously.

1:58:17Andrew Huberman:You see how far you can go. Yeah.

1:58:19Dr. Rhonda Patrick:And then there's a calculation out there that's done to kind of estimate your VO2 max. And so some studies or a lot of studies are actually doing sort of an estimation of cardiorespiratory fitness. So cardiorespiratory fitness is really important, I think, for, you know, marking your health and longevity. And, you know, if you have a low cardiorespiratory fitness, most of the times you are not physically active, right? And there are studies showing that if you don't have any, you know, diagnosable diseases, so you're not insulin resistant, you don't have cardiovascular disease, you don't have cancer, all that stuff, right?

1:58:51Dr. Rhonda Patrick:You're not obese, but you have a low cardiorespiratory fitness. It is as bad or worse in terms of your all-cause mortality, you're predicting mortality, than having cardiovascular disease or smoking or having hypertension or these things that we know that are really bad for health, right? So being sedentary, as I'm saying, it's a low cardiorespiratory fitness. I guess it's not exactly correct. It's a little bit, I'm stretching it a little bit. But cardiorespiratory fitness is a marker of, I would say, fitness. And so that's why I think being sedentary is a disease. And people with a low cardiorespiratory fitness, I mean, if you go anywhere above that, you know, from low to like low normal, that's associated with a two-year increase in life expectancy.

1:59:37Dr. Rhonda Patrick:If you go from low to high normal, you know, that's like almost a three-year increase in life expectancy. And if you go up too high, then you're talking about a five-year increase in life expectancy compared to where you were at at low. But again, I'm not talking about VO2MX. I'm talking about cardiorespiratory fitness. And it's really important. Here's another reason why I think that it's really bad. So these studies were done. By the way, cardiorespiratory fitness is improved by aerobic exercise in general. That's great. And then, you know, if you add in high-intensity interval training in their mix, that also really helps because there are some people that don't respond necessarily to just doing cardiovascular.

2:00:14Dr. Rhonda Patrick:Slow, steady state. Yeah, about 40 % of people don't respond. So mixing in the high intensity is good. If you're physically active and doing that, that's great. If you're doing these short bursts of physical activity, also good because it's a little bit of a high intensity, you know, exercise, right? A minute running around chasing your grandkid or your puppy or your child. You know, that's a hit section.

2:00:32Andrew Huberman:Taking the stairs, that's amazing. I was traveling with my team. Sprinting up the stairs. Sprinting up the stairs or if you're carrying a lot of luggage in the airport, like going up the stairs or down the stairs. Right. It's wild when you go to the airport. I like to notice this. Nobody takes the stairs.

2:00:48Dr. Rhonda Patrick:Yeah.

2:00:49Andrew Huberman:Down or up. Like the escalators are there. And I'm always like, oh, this is a great opportunity. You get some extra steps and some extra work. But I realize that's me. But it's just, it's striking. And if you're in D.C. ever, you know, they have these long stairwells that go up from the public transport. And that's a workout, you know. Carrying your luggage. And I'm always like, oh, free workout. Like, you know, like get it in my day. I mean, it sucks to arrive a little bit more sweaty than you would otherwise. But I just think if this were an experiment and we were looking at mice and we were videotaping from above, I always think to myself, like, which mouse am I going to be?

2:01:21Andrew Huberman:All the mice are going up the automatic elevator. It makes sense. And then why they would want to do that. But these opportunities for exercise are clearly there. I feel like this is also I would be remiss if I didn't do a quick shout out to Steve Magnus. Do you ever see his content?

2:01:36Dr. Rhonda Patrick:I've interacted with him. Yeah. Yeah.

2:01:37Andrew Huberman:I've never met him, but people should - On Twitter.

2:01:40Dr. Rhonda Patrick:I've interacted with him on X.

2:01:41Andrew Huberman:Yeah. People should, I think, give him a follow. He's a very accomplished runner in his past, a running coach, I believe, as well, and a scientist, and I think has the best take on sort of measuring VO2 max. It's kind of interesting. He has a theory, which I think is strongly backed, that most measures of VO2 max are not measures of VO2 max at all. But one of the best measures of cardiorespiratory fitness is how fast can you run a mile? And he says people are generally surprised how easy the easy stuff should feel and how hard the hard stuff should feel. So I just want to credit Steve for saying that.

2:02:14Andrew Huberman:So I try and keep that in mind around my cardio and do some high. I do less of what you do, I confess, some high intensity interval training, Tabata type stuff, and then a lot of walks, a lot of hikes. Yeah. And I haven't formally measured my VO2 max in a while, but I think he just nails it with that. Because I think people think the 30-minute jog on the treadmill where you get sweaty and you're like, ah, like that's accomplishing what you want. But actually there's a much easier path to better health, which is what you do and more or less what Steve is describing as well.

2:02:44Dr. Rhonda Patrick:Yeah. Yeah.

2:02:44Andrew Huberman:Does that square with your experience? Yeah, I think so.

2:02:47Dr. Rhonda Patrick:I mean, I do mix in quite a bit of probably more high-intensity interval training. But, you know, I don't feel – like if I felt like it was like if I didn't feel good, I would toggle down the paddle, right? I wouldn't keep going on it. So I think you have to, again, just listen to your body. You know, you don't want to overdo things. And I am, I mean, there are people out there that are really like endurance athletes that are, you know, like that's not me. I'm a committed exerciser. I'm not necessarily an athlete. But yeah, so that's those different, I think, levels here. And Steve is obviously athlete.

2:03:23Andrew Huberman:Anyway, I've learned from him around this topic. Yeah. It's been helpful. I'd like to take a quick break and acknowledge one of our sponsors, Function. Last year, I became a Function member after searching for the most comprehensive approach to lab testing. Function provides over 100 advanced lab tests that give you a key snapshot of your entire bodily health. This snapshot offers you with insights on your heart health, hormone health, immune functioning, nutrient levels, and much more. They've also recently added tests for toxins, such as BPA exposure from harmful plastics, and tests for PFASs or forever chemicals.

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2:05:03Andrew Huberman:Function currently has a wait list of over 250 ,000 people, but they're offering early access to Huberman podcast listeners. Again, that's functionhealth.com slash Huberman to get early access to Function. I want to ask you about creatine. I'm 50. I started taking weight training and running when I was like 16, maybe. Yeah. And I started taking creatine because back then I was skinny. I wanted to put on muscle. I think creatine was sort of first discussed or released back then when I was maybe 18 or something like that. Something like that. 18, 19. So I've been taking a long, long time. Yeah. Five to 10 grams.

2:05:42Andrew Huberman:But the original protocol, which nobody does anymore, but I confess I still do it because I enjoy it, was to take five grams three to five times per day. There was this loading phase. And you would mix it with a little bit of grape juice because the idea was you were supposed to spike your insulin and then you get more into the muscles. And then you had a maintenance dose, which was five grams per day. And the idea back then was that you needed to do a washout every 20 weeks or so, where you just stop taking it, you urinate out a bunch of water, and then you reload. And I confess, I've continued to do this minus the grape juice, but occasionally I'll do the grape juice thing.

2:06:20Andrew Huberman:I don't think there's any real merit to the loading phase, maintenance phase idea. But back then and still now, I feel like creatine has made me feel great. Stronger, I wasn't aware of the cognitive benefits. They weren't being studied back then. They weren't being studied back then. But what are your thoughts on why creatine suddenly has become this like banner supplement? It's like supplement of the year. We should start a supplement of the year thing, right? For a while, I think vitamin D and melatonin came first. We'll have to figure out what years those were. Then I feel like creatine got supplement of the year for 2026 unless something else comes along.

2:07:00Andrew Huberman:So creatine, supplement of the year, 2026, even though it's been around for a long, long time. What do you think happened?

2:07:06Dr. Rhonda Patrick:Well, so first I want to talk about your loading phase. And that was really for the studies that were being done, right? Because if you're taking five grams a day of creatine, it takes about three to four weeks for your muscle creatine stores to become saturated. And researchers aren't going to do a study where they wait that long. So the loading phase really was just—

2:07:25Andrew Huberman:Oh, so that's what inspired it.

2:07:26Dr. Rhonda Patrick:Yeah, it's in this isolated bubble of in the experimental protocol, but like in the real world, you have three weeks. Or if you're like an athlete and you hadn't, you know, taken the creatine, you don't have your creatine stores up and you have to quickly, rapidly.

2:07:40Andrew Huberman:Got it. I was just amazed at how quickly it worked. I might be a hyper responder, but I legitimately put on, I realized some of it was water or most of it was water, but somewhere between probably four and eight pounds of water in the muscle mass. I don't want to call it lean mass because, you know, it's water in the muscle. But I just was like, oh, my goodness, this is crazy, you know. And then people thought maybe it was a steroid. It's not a steroid. Maybe it's bad for your kidneys. Turns out it's safe for your kidneys and most everyone. Pretty remarkable molecule.

2:08:14Dr. Rhonda Patrick:Yeah. I mean, obviously creatine is stored as creatine phosphate in our cells. We make, to some degree, between one to three grams of creatine a day, our liver. Our brain also makes it. it's used to make energy. And so your muscles, if you're working out, you're really consuming a lot of energy, right? It's very energetically demanding. So having the creatine stores higher in your muscle is beneficial because one, you're going to be able to increase your training volume, right? So it's not like creatine is anabolic in the sense that protein or amino acids are, right? It's not like directly affecting muscle protein synthesis.

2:08:49Dr. Rhonda Patrick:It's just helping you train more, getting more reps and, you know, whatever it is, your training volume is going up. And because your training volume is going up, then you're obviously putting more stress on your muscles, which is going to lead to increased muscle protein synthesis. And, you know, obviously there's water probably as well. That said, you know, you asked me, you know, what happened. So I got interested in creatine back in 20, when I started basically weight training. And obviously I'd heard about it forever, never took it. And as I started to get into resistance training, I was like, I better start taking this.

2:09:24Dr. Rhonda Patrick:This is, I'm like in this world now and started doing some research and taking it. So I was taking the five grams a day because that's really what most of the studies show, creatine monohydrate. That's the most well-researched form of creatine. And I was taking five grams a day because I was interested in improving my training volume and getting the benefits of it, right? And then I had Darren Kando on the podcast. That was in 2024, I think it was. And once I had started getting into the creatine research, the brain stuff has been coming out over the past few years. And that's, for me, become very interesting.

2:10:05Dr. Rhonda Patrick:I remember the first time I heard about it years ago. It was like, oh, it's helping improve cognitive function in older people.

2:10:11Andrew Huberman:Yeah, the phosphocreatine system seems to be somewhat biased towards forebrain structures. I mean, obviously it's in lots of brain areas, but there might be a heavier reliance on it for brain areas that are associated with strategic planning and working memory. Yeah. Interesting. If you were to sort of just map the sort of density of usage of the phosphocreatine system, you'd see a frontal bias for sure.

2:10:36Dr. Rhonda Patrick:Okay. Yeah. Well, anyways, that's kind of where my interest in, you know, kind of diving deeper. Anything that's helping the brain is interesting to me, as I know it to you as well. And so I learned a lot from this podcast I did with Darren Kanda. He, you know, researches creatine and collaborates with a lot of different researchers that are doing, you know, research on the brain and muscle and, you know, lots of the bone. It turns out it's beneficial for the bone as well. But the brain, it's interesting that we also make creatine in the brain, but it's not like – so it's kind of like the muscle, right?

2:11:11Dr. Rhonda Patrick:You're not just going to – if you take creatine and you don't work out, you're not going to get any increase in lean mass, right? It's not going to do much of anything because you're not putting in the work. I think the same goes with the brain as well where it's like researchers started to find out that, well, you can't just take creatine and it's going to enhance cognitive function. It's in the background of stressing the brain, right? You're stressing your muscles by workout. Same goes for the brain. It's like in these situations of stress, whether that's sleep deprivation, whether it's, you know, a traumatic brain injury.

2:11:44Dr. Rhonda Patrick:I mean, I would argue, you know, there's a lot of psychological stress, depression, constantly using your brain like you and I right now in this conversation. We're learning, we're thinking, I mean, it is stressful on the brain. Right. So, I mean, I'm obviously speculating here and taking – I'm extrapolating, right? I'm not saying that there's studies showing that. But it does seem as though that that's when creatine seems to shine in the brain. And you might go, well, your brain makes it. And it's true. Your brain does make – again, it's like between one to three grams or something. I'm not exactly sure how much, but it makes its own creatine.

2:12:20Dr. Rhonda Patrick:And it's kind of resistant to taking up the creatine that you're supplementing with, particularly because, for one, the muscle is very greedy. So when you're getting to that five gram range, muscles are really consuming. If you're working out in particular, right, your muscles are kind of consuming that because they're very greedy for it, right? And there have now been, I think, a handful of studies showing that when you start to get above that, there was a study out of Germany showing this. And it's a small study. This needs to be replicated. Like this is all new, you know, emerging data. But that study showed that once you start to get to, you know, 10 grams, then if you look by MRI, you can start to see that creatine levels are increasing in certain brain regions and perhaps in the brain regions that you were talking about.

2:13:04Dr. Rhonda Patrick:And they're going higher than what you would get from just your brain normally making its own creatine. And so the 10 grams of creatine a day, which is now what my baseline is, is based off of that. But there's studies now showing that if you are in this sort of stressed state, your brain is stressed, like for sleep deprivation, for example, you're sleep deprived for 21 hours and your brain's not working very good after not sleeping for 21 hours, right? I mean, that's obviously when I travel internationally, I never really sleep good on an international flight. And so I'm like not – if you were to come find me after that flight, I'd be like not working very good, right?

2:13:43Andrew Huberman:You and everybody else. Right. Yeah.

2:13:45Dr. Rhonda Patrick:Well, some people can sleep great on a plane, but I'm not one of those people. So there have now been at least one study showing that if you give someone – it's like something like 0.35 grams per kilogram body weight of creatine, which comes out to a lot. I mean it's like 20, 25 – it depends on your body weight, right? Like 20, 25 grams, perhaps even more.

2:14:06Andrew Huberman:I mean, I'm 100 kilograms. Yeah, so you would be a lot.

2:14:09Dr. Rhonda Patrick:So for me, it's more like 20, 25 grams, right? But if you give individuals that high dose in that, you know, sleep deprived state, that they're cognitively not only performing normal, but they're performing better than their baseline. And that, of course, generated a lot of interest. There have been studies coming out since then showing that, okay, if you give older adults with mild cognitive impairment, perhaps mild early stage Alzheimer's disease, again, 20 grams. You're giving them the 20-gram range of creatine. It's improving their cognitive function. Why is that? Well, creatine is important to make energy.

2:14:47Dr. Rhonda Patrick:And when your brain cells are stressed out, right, I mean, like energy, energetic demand goes up. And if you have more creatine, it's going to make things easier. There's also some inflammation that's being generated in that stress state. And it seems as though creatine is also having both an indirect and direct effect on inflammatory processes as well. This is all early, early data. Like more needs to be done. But I think there's enough safety data out there now where it's like, well, it's really not harmful to take 10 grams a day. I take 10 grams a day every day. You spread it out. I do it in two doses.

2:15:21Dr. Rhonda Patrick:I mean, some people are very sensitive to a 10-gram dose where they might, like, get a GI irritation effect.

2:15:27Andrew Huberman:It can give some people diarrhea. Diarrhea, exactly.

2:15:31Dr. Rhonda Patrick:Yeah.

2:15:31Andrew Huberman:So the very scientific way of putting it.

2:15:33Dr. Rhonda Patrick:But, I mean, so I do spread it out. And I take it – I don't take it at night. I like to take mine in the morning. And I don't know, Andrew, this might be a placebo. I feel like I'm constantly in a stress – I'm constantly in a – my brain is under a lot of stress. I'm constantly learning. I'm reading papers. And like I said, I'm extrapolating here. This isn't sleep deprivation. That's obviously a much more extreme type of stress. But I have noticed that taking my 10 grams, going from 5 to 10, really does seem to affect my brain functioning like later in the day where I seem to keep going better, where I'm not getting as tired.

2:16:11Dr. Rhonda Patrick:And it could be placebo, which is fine. Like I said, I am fine with placebo effects. As long as what I'm ingesting is not actually bad for you, placebo is fine with me. But it is working for me. when I travel, I do when I'm going to the East Coast. I mean, I'm on the West Coast. So when I go anywhere and I have to give a talk early in the morning and I never sleep good in a hotel, I'm always sleep deprived. I mean, I don't know that a time that I haven't been traveling and I'm gonna start traveling with my pillow like you do because that's brilliant. Because that's like one of my, that's one of my problems.

2:16:40Dr. Rhonda Patrick:But there's many problems in hotel rooms that lead to me not sleeping as good, right? So I take 20, sometimes 25 grams of creatine in those situations. And it's like, you know, it's not all the time. But it seems to help me again. And like I said, I'm okay with placebo, which is fine. But we do have some evidence that it might. And I think this is kind of where people are already interested in creatine. And so when you start to go, well, maybe it's going to be beneficial for the brain. If it's going to improve cognitive function, that's really something that people are interested in. Now, again, I don't know that it's like if you're just some young, healthy person that gets all their – you're getting – you're sleeping well.

2:17:17Dr. Rhonda Patrick:You're exercising. Everything's great. You know, and I mostly sleep well and exercise great. I'm extrapolating here, but like, you know, Alzheimer's disease on the extreme end, TBI also on the extreme end. That's real-time aging, right? And there's some evidence that may be helpful for that as well. There's been some studies with children looking at creatine supplementation after a TBI, and it seems to help with their recovery. I am probably experiencing brain aging. So I'm just kind of—

2:17:43Andrew Huberman:I'm going to interrupt there. I don't think so. I'm not trying to just be complimentary. You know, I paid close attention to the data and it seems like in certain fields like math and physics, people tend to peak with their contributions early. There's a reason why the Fields Medal is only given to people, you know, like I think it's 40 or younger. My dad's a physicist, so he can check me on this one. But biologists, at least the ones I know that took good care of themselves, they're known to make great discoveries be cognitively sharp, intellectually strong, well into their 70s and 80s. I mean, Torrenson Weasel, co-recipient of the Nobel Prize for Brain Plasticity and Vision, he's still alive and he was – I think he still runs.

2:18:22Andrew Huberman:He's in his late 90s and he paints and he's sharp. So I just – I made a point to only interrupt here. People can check the data on the previous portions of the podcast. But just say, I actually think that cognitively, I'm using biologists as an example, it's possible in aspects of life where you're building a base of data to pull from, which is what biology really is. It's just an example here. That to get cognitively stronger and stronger with age.

2:18:52Dr. Rhonda Patrick:Right.

2:18:52Andrew Huberman:There's a theory. But I see you as that. And again, I'm not just saying it to be complimentary, although it is a compliment. It seems like you're picking up steam. You're thinking about things. You're not forgetting things from way back when. You're building on the concepts and knowledge from way back when. So I find it reassuring that biologists in particular seem to have this, you know, up and to the right trajectory for cognition.

2:19:15Dr. Rhonda Patrick:It's interesting. My late mentor, Dr. Bruce Ames, was every bit of that. I mean, you know, he passed away a little over a year ago when he was 96. But, you know, some of his most – he claims some of his best work was done, you know, in his late 80s. Right. You don't see that in math or math. physics. Yeah. So that's interesting. And, and, you know, I don't know exactly the difference. I mean, I don't know how much learning goes into math and physics as you're, as you're like, I, I just don't know, but like with biology and I mean, we're constantly learning new things and reading new papers. And then I think even just the novelty of learning new things, I mean, that's brain-derived neurotrophic factor, right?

2:19:53Dr. Rhonda Patrick:Like that's like you're, you're, you're increasing synaptic connections and neuroplasticity and you're keeping your brain younger in that way too, right? So I think the learning process is super important, whether it's biology or whatever you're passionate about, right? Like you learn new languages, like the learning process itself is something that is so important for brain aging as well. And yeah, so I would agree with you that, but brain aging in general, yeah, I'm obviously chronologically aging and there is some degree of aging going on in my brain. But, you know, so that's, I think where the creatine crazes come from is the interest in, and I've definitely played a role in some of this, you know, by, you know, talking about my experience and being super interested in it because it's like, it's felt good for me and I've noticed this experience and this is completely anecdata again.

2:20:46Dr. Rhonda Patrick:But in addition with the small studies, and they are small, like, I don't know if you've looked at them, but they're, you can - Subject numbers. Yeah, they're small and you can poke holes in them and you would be completely, you know, okay poking holes because they're small, you know, sample sizes. But it is kind of a consistent trend line where we're seeing more studies come out and show the same thing, same thing. And it's like, okay, you know, to a certain point, maybe there's something here. I think that more research is going to come out on it. And I feel great doing it. So, I mean, and even to the point where if I don't have my 10 grams and it's only five, like I'll notice.

2:21:24Andrew Huberman:Oh, yeah?

2:21:24Dr. Rhonda Patrick:Yeah. But again, it could be that, you know, placebo, nocebo thing where who knows? Who knows? But, you know, let's just say it is real. You know, for me, I got to have my 10 grams of creatine for my brain. You know, who knows? I may in five years be like, I was wrong. We'll see new data come out. But I don't think so. So I think we're going to have – I think this is like the next – a lot of people doing creatine research, it's the new thing. They're really – because there's been a lot of work on exercise physiology and training volume. Yeah, the safety data are there.

2:21:55Andrew Huberman:So it's not like you have to get a lot of human subjects clearance. The safety data is there.

2:21:58Dr. Rhonda Patrick:The safety data is – I mean it's the most well-studied, you know, one of the most well-studied supplements out there. Like you said, you were taking it when you were 18. A lot of years ago. Yeah, and it's just been studied for all the years that you've been taking it. So, I mean, if it was unsafe, like we really would know. And again, I don't want to get into all the data on the safety, but I think that it's pretty, pretty solid that it's now, of course, like if you're going to go like mainline 50 grams a day, I mean, I don't know. That's a little much. Someone on the Internet will do it. Yeah.

2:22:29Andrew Huberman:People dry, what are they, dry scoop? I mean, people have died dry scooping energy drinks. I mean, there's always a moron or two out there that are going to take things to the extreme and harm themselves doing something that no one else is dumb enough to do. But I think we look at the center of mass for things. You know, as we're talking about creatine, I want to talk about some other supplements. But it occurs to me that if there's some data, ideally from animal studies and humans, and something is safe, I think the question nowadays, because of how broadly health and supplement and other kinds of information goes in the world, I think the question that everyone should ask themselves is, okay, do I want to be in the experimental or the control group?

2:23:17Andrew Huberman:That's how I think about it. So like if there's a study about creatine or some new molecule, I'm going to ask you about magnesium in a moment, right? I look at the safety margins on magnesium. Okay, I'm comfortable with those safety margins. So that should always be question number one. And then it's, do I want to be in the experimental or the control group? And I think that these days people who are against supplements or against something, they'll say, well, the effect isn't nearly as big as you get from exercise. Totally. Absolutely. But that's not really what we're talking about. People love this in the cannabis and alcohol thing.

2:23:49Andrew Huberman:Whenever I make a point about alcohol or cannabis, they'll say, well, alcohol is worse. I'm like, yeah, and? I mean, these are two separate entities. So I think that people should just ask themselves, are you comfortable with the safety margins? And do you want to be in the experimental or the control group? And then, of course, there's the can I afford to be in the experimental group if I do something? But those are really the only questions. There's no one saying that creatine is better than anything else or worse than anything else. Right. But somehow the messaging gets all messed up. And then all these news articles get generated about what creatine is and it isn't.

2:24:26Andrew Huberman:And I find it like kind of frustrating because that's – the issue is not whether or not creatine is better than exercise and good sleep. The question is do you want to be in the experimental or the control group and can you afford to be in the experimental group?

2:24:42Dr. Rhonda Patrick:Right. I like that. I like that framework especially if it's like, well, we know it's safe. Okay. So I can potentially be in the experimental group because that's question number one. You have to have that answer first, right? At least in my book. But, yeah, I mean, there's flaws with all sorts of studies and creatine studies included, right? And people make all sorts of claims about it. And, you know, you got to tone it down a little bit. I mean, it's not like the best performance enhancer ever.

2:25:08Andrew Huberman:Right.

2:25:09Dr. Rhonda Patrick:But it seems pretty good at, you know, improving exercise volume recovery as well. I mean, that's like also something that's been shown. And then helping with the stressed out brain.

2:25:17Andrew Huberman:On the basis of our last conversation some years ago on this podcast, I started taking Lovaza, which is, as you know, a prescription omega-3, so very high concentration omega-3 because I was getting it from standard sources. And I thought, well, I'm hitting 50 and my omega-3 and I want clean omega-3. I don't want it contaminated with mercury and other things. So I'll take omega-3s in the form of Lovaza. It's available generic form now. So it's pretty inexpensive. And I have to say my blood profiles were pretty good, but they improved pretty dramatically when I started taking Levaza. So I'm grateful to you for encouraging the omega-3, you know, take the omega-3 path.

2:26:02Dr. Rhonda Patrick:Have you ever had an omega-3 index test done?

2:26:04Andrew Huberman:No.

2:26:04Dr. Rhonda Patrick:To measure the...

2:26:05Andrew Huberman:Oh, if it's on the function test, then it would be... I think it is. Then it's in normal range. I know it wasn't flagged, but I don't recall what the level was.

2:26:13Dr. Rhonda Patrick:Yeah. You want to be in the high index, not the low, right? Well, obviously, if you're taking it, you're not going to be in the low. Usually, it's around two grams a day to get you from low to high. And I do think that's one of the low-hanging fruits in terms of, like, something powerful and having an outsized effect on your health that people can do that's not that much effort. It's not like an exercise, an exercise effort.

2:26:33Andrew Huberman:Or eating salmon. I don't like fish. No.

2:26:36Dr. Rhonda Patrick:Yeah. And, you know, a lot of people don't like fish. And also, there's now microplastic contamination in our, you know, seafood sources. There's the heavy metals. PCBs, contaminants. I mean, I still eat salmon, but like, you know, it's not like it used to be. So there are other cleaner ways to get your omega-3 levels higher. And omega-3 is very important for cardiovascular. It's one of the most important, I would say the most powerful, naturally occurring dietary compounds for suppressing inflammation and resolving inflammation would be a better way of putting it, right? I mean, and that's, again, at the core of aging.

2:27:15Dr. Rhonda Patrick:And if you look at any sort of measure of aging, whether it's even these epigenetic aging clocks, they're very sensitive to inflammation. And that's why there's so many studies coming out now showing omega-3 can slow this biological aging as measured by these epigenetic aging clocks. And that's, I think, even in randomized controlled trials showing this, that it's doing that. And that leads to functional outcomes as well. So even if you're only slowing the clock, let's say, by three months, you're still having outcomes like where, for example, three months slowing the epigenetic age and clock by omega-3 only is going to get you like, you know, 16 % lower pre-frailty.

2:27:55Dr. Rhonda Patrick:Or if you add in vitamin D and resistance training, because the study showed a synergy between the three, then you're talking about like lowering the chance of invasive cancer by 66%, even though you're only getting - Yeah. Even though you're only getting -

2:28:07Andrew Huberman:So vitamin D resistance training and - And omega-3. And omega-3.

2:28:10Dr. Rhonda Patrick:Yeah, and this was – the trial was actually out of Switzerland, I believed, and it looked at omega-3, vitamin D alone or resistance training alone. And the only thing that actually slowed the aging of the clocks was omega-3. Now, I'll say that with a caveat, okay? The baseline exercise in this Switzerland group, 88 % of these people were physically active, like doing exercise. So adding, you know, 30 minutes, three times a week of resistance training on top of that didn't slow the clock more. And I wouldn't expect it to, to be honest, when you're already physically active and that's your baseline.

2:28:48Dr. Rhonda Patrick:Clearly, they weren't eating enough omega-3 because that did slow the epigenetic age and clock. Other studies have shown if you're vitamin D deficient, severely vitamin D deficient, like African-Americans, for example, who are obese or overweight. if they add in vitamin D and supplement with 4 ,000 IUs a day for six weeks, they can actually slow their epigenetic, reverse their epigenetic aging as well. So I think, again, it's all like where you're starting from. But the point is that the omega-3 alone did slow the aging of these clocks. And you add in the resistance training and vitamin D, those alone didn't do it.

2:29:23Dr. Rhonda Patrick:But when you add it with the omega-3, there was synergy. So it kept going down. and when the three combined, it slowed the epigenetic aging by like 3.8 months, but that translated to like 66 % less likely to get invasive cancer. And then the pre-failty was the omega-3 alone. And there was another marker I can't remember. I covered this in a newsletter a while back. And this isn't the first study to show this with omega-3. Omega-3s are really – I went on this tangent. I'm sorry, Andrew. You got me on one of my favorite topics. I mean, I'm excited because I take Levaza.

2:29:57Andrew Huberman:I take vitamin D, D3. Yeah. I take a lot. I take 5 ,000 to 8 ,000 IUs per day, and I get sunlight. People actually ask me. This is just a quick window into the messaging around sunlight. Some people will say, if I take vitamin D, do I still need sunlight? And, you know, a big part of my messaging is trying to tell me that sunlight does a bunch of other things. But I take vitamin D at that level. I take the Levaza, and, of course, I have resistance train. and the Levaza move and actually increasing the vitamin D was on the basis of, yes, blood work, but also our prior conversation. I feel much better.

2:30:28Dr. Rhonda Patrick:Yeah.

2:30:29Andrew Huberman:Much better. I take about 5 ,000

2:30:31Dr. Rhonda Patrick:IUs a day as well. And I do get sunlight. And I agree with you, sunlight's important for sunlight's not, and vitamin D production is not the only thing that sunlight is doing. Obviously, you've talked in great depth about that. I'm going to go into the grave.

2:30:44Andrew Huberman:I actually want a little window over my grave. It'll be a little morbid so I can get morning sunlight. I'm just kidding, folks. When I'm in the ground, I'm in the ground. No, I think the omega-3 literature has been greatly assisted by your messaging around it because it got pretty confusing out there for a while. There was the usual pushback that comes after supplement to the year is released. It's a joke, folks. Is the, oh, no, it's actually bad for us. You know, there's always a few of those. And then we eventually arrive at sanity again. And you go, no, the bulk of studies point in the direction of this being healthy.

2:31:16Dr. Rhonda Patrick:Right. and improves cardiovascular health, lowers the incidence of cardiovascular events, including heart attacks and strokes, right? These are the gold standard. We've got the observational data. We have now looking at the molecular events, we're like, you know, epigenetic aging. We know that it's really good at resolving inflammation because you want your immune system to be active, but you don't want it to be overactive. You want it to be active and then turn off, right? And so the omega-3 fatty acids like DHA and EPA, which are in Lavasa or Lavasa, are what the, when they're metabolized, they're forming these molecules, resolvins, protectants, these things are resolving inflammation.

2:31:52And so I think that it's just,

2:31:55Dr. Rhonda Patrick:it's one of the easiest ways that you can increase your anti-inflammatory response and exercise obviously being another very powerful one. But the omega-3s, it's always easier to take a supplement. And so like I have my parents taking it, you know, anyone that I care about, it's like, you know, easy, easy, done. You know, take your two grams a day. I say two grams a day because, you know, LaVey's is prescribed at four grams a day. You know, so two grams is pretty on the conservative side, and that's really what's been shown by Dr. Bill Harris and some of his colleagues that can basically you can take someone from a low omega-3 index of 4 % up to a high omega-3 index of 8 % by supplementing with about two grams a day.

2:32:33Dr. Rhonda Patrick:So, and by the way, there's all sorts of data on that front with the omega-3 index, and I think we talked about this last time, but, you know, five-year increased life expectancy if you're on the high end. You're talking about 90 % reduction in sudden cardiac death.

2:32:47Andrew Huberman:Brain weight in children if pregnant women are taken.

2:32:51Dr. Rhonda Patrick:I mean, it's important throughout the lifespan. It's, you know, from in utero development throughout childhood all the way through adult life and into old age. You know, these omega-3 fatty acids are, I'm talking about the resolving inflammation, but they're also very important for, they are incorporated into our cell membranes, DHA and to some degree EPA. and that has a very important role in the fluidity of our cell membranes. And this is important for if you think about our endothelial cells lining our vascular system, our arteries, you want them to be fluid and more flexible, right? That's very important for being able to respond to a stressful situation.

2:33:27Dr. Rhonda Patrick:In fact, the stiffening of our heart with age, you know, the collagen that surrounds our pericardium, that's surrounding our heart, pericardium and our myocardium, Like that increases the risk of a heart attack, you know, a cardiovascular event. You want your cells to be more flexible. So that's what, you know, these omega-3s are also doing. And that's why they're also really important for cardiovascular health in addition. And the brain as well. I mean, all of our transporters, all of our receptors, right, they're embedded in the cell membrane. And the fluidity of that membrane is important for the structure and function of these things.

2:34:00Dr. Rhonda Patrick:And that's why omega-3 affects dopamine, serotonin, right? it's why it's affecting, it's not the only reason inflammation is also, but part of the reason is because it's changing the way our cell is like, you know, structurally composed. And if you think about trans fats, like that's, they do the opposite, right? They stiffen the cell membranes. And that's why it's like the worst thing you could do for your cardio, one of the worst things that you could do for your cardiovascular health is eat a bunch of trans fats. Smoking is another one. Smoking is terrible for your cardiovascular health.

2:34:30Andrew Huberman:Do people still eat trans fats? No. I feel like trans fats got executed in – when was it that trans fats got executed?

2:34:38Dr. Rhonda Patrick:When they all became – I think it was 2018. When they're all like –

2:34:42Andrew Huberman:Yeah, they were sentenced to death. Yeah.

2:34:43Dr. Rhonda Patrick:No, it's – the point is that we all know trans fats are bad for our heart, but we don't think about why. And they stiff – I mean, the researchers doing it know. I mean, it's stiffening your cell, your endothelial cells.

2:34:57Andrew Huberman:Well, donuts, right? As in, like, if you go get a donut, isn't a donut have a bunch of fried foods? Fried foods.

2:35:02Dr. Rhonda Patrick:There's probably some amount of trans fat that's like below the threshold of being.

2:35:08Andrew Huberman:It's the only bad food I miss.

2:35:09Dr. Rhonda Patrick:Yeah.

2:35:10Andrew Huberman:The late night donut.

2:35:11Dr. Rhonda Patrick:I had so much margarine as a kid. My mom used to buy it by the tub. I remember it. It's like this. She used to go to Costco and get like this big yellow tub of margarine. I remember those tubs. And everything was cooked in it. And I mean, it was like on our toast. This was a battle in my home.

2:35:26Andrew Huberman:Actually, I'm going to resurrect some family battles of the butter. The butter margin battle was a battle.

2:35:33Dr. Rhonda Patrick:Yeah.

2:35:35Andrew Huberman:Butter won.

2:35:36Dr. Rhonda Patrick:Yeah, it doesn't taste the same. But, you know, that was the craze. It was the loaf, like the fat was bad and butter was bad and margin was good. And it turns out, nope, trans fats are really bad. But the point I was trying to make was to help contrast for people to understand. Sometimes when I talk self-fluidity, people are like, what?

2:35:53Andrew Huberman:No, it's good that people, I mean, I think it's very important that people understand some of the cellular and molecular underpinnings of protocols, because I strongly believe that understanding mechanism, even just a little bit, or striving to understand it, embeds the information for people, makes it more likely that they'll do the behaviors, and gives them a logic to work from when they have to make choices, because life isn't perfect. I know that to be certain.

2:36:23Dr. Rhonda Patrick:I completely agree with you. It's certainly for me, but that is also my hope. I think that if people kind of understand somewhat of the why, it's motivating to try to adopt the healthy habit. But also, I think it helps them remember why it's important, right?

2:36:38Andrew Huberman:It's how the brain learns. The secret is context. The way to remember something is context. People always say it's story. No, it's context. And anyway, you and I know that to be true from our background. If I may, I'd like to ask about magnesium. I'm very bullish on magnesium, in particular magnesium 3 and 8 before sleep. For sleep, I take AGZ because I help them build it. It just has a bunch of things like magnesium 3 and 8 and saffron and tart cherry, the things that have either been shown or are, you know, gradually they're amassing research data to other people, studies out there to support that it can facilitate either transition to sleep or sleep.

2:37:19Andrew Huberman:But magnesium threonate and magnesium bisglycinate, to me, are interchangeable with respect to sleep. But magnesium threonate, I'm aware there are some studies that there may be some cognitive benefits. So magnesium obviously could be split into a number of things, but maybe we just start there with threonate bisglycinate. I have a feeling that you're aware of some additional differences between them, and I'd like to know what you prefer for sleep or for cognitive benefits, and then maybe we get into the other magnesiums.

2:37:46Dr. Rhonda Patrick:Yeah, I think so. If we if we're comparing magnesium bisglycinate or magnesium glycinate, depending on how many molecules of glycine are attached to the magnesium, compared to magnesium L3 and 8, the main difference here, and this is based on very limited amount of data, a lot of it, animal data, with respect to the magnesium 3 and 8, is that that form of magnesium is supposed to get into and cross the blood-brain barrier more readily and get into the brain better. And in the brain, it's, you know, helping facilitate neurotransmission, et cetera, right? Helping improve cognitive function. And so, whereas magnesium glycinate or bisglycinate, you're having the magnesium attached to the glycine.

2:38:31Dr. Rhonda Patrick:Glycine also is great to take for sleep. So, I like to take magnesium bisglycinate or glycinate for sleep. And so that I would say, if you're interested in more the cognition aspect.

2:38:44Andrew Huberman:Well, the studies I think you're referring to, the Gursang-Luz data, you know, show some in mice, some cognitive enhancement or at least some offsetting of cognitive decline. Those are different but related, obviously. In anticipation of today's discussion, I was able to find one study, seems okay, it's not a huge sample size, showing a positive reports on sleep quality after magnesium L3 and 8. So the studies are starting to show up. Right, starting to show up. But there aren't a lot of studies on magnesium for specific outcomes in humans. And I think it's because it hits like, what, 3 ,000 plus pathways?

2:39:23Andrew Huberman:There's a lot of pathways. Yeah.

2:39:25Dr. Rhonda Patrick:It's a cofactor for many enzymes.

2:39:27Andrew Huberman:So if you're taking bisglycinate before sleep, are you taking it a half hour or 60 minutes before sleep?

2:39:32Dr. Rhonda Patrick:I'm usually taking it, I would say, like a couple hours before bed. You know, sometimes I add a little bit more magnesium in the mix. depends on the day and if I exercise more because you do sweat out magnesium. And so if you're pretty athletic, your requirements can go up by even as much as 20%. But yeah, the magnesium L3, it's interesting. I very recently got interested in experimenting with it. You know, there's a little bit of human evidence as well that it improves cognition. Not strong, but again, it's that, you know, we just don't have a lot of people researching it. And we have the animal data.

2:40:05Dr. Rhonda Patrick:The animal data is a little stronger. Don't have a lot of human data, but it seems to signal it might be important. It might help with cognition, right? And so I kind of got interested in experimenting with the magnesium L3N8, which I haven't usually, it's a new thing for me. I've been doing magnesium glycinate for a while.

2:40:22Andrew Huberman:I think the study actually looked at the MagTene. Yes. I have no financial relationship to MagTene. I want to be very clear. I just mentioned that because that's a common one out there. And as far as I know, I'll double check, but they weren't paid by MagTene.

2:40:34Dr. Rhonda Patrick:I think the MagTene did fund the study.

2:40:36Andrew Huberman:Oh, they did? So, yeah. Okay. All right. We'll put a link to it.

2:40:39Dr. Rhonda Patrick:Doesn't discredit it unless there's some, you know, bad things going on, which I like to think not. I mean, you know.

2:40:46Andrew Huberman:It's supposed to be done independently. I mean, when they pay for a group to do it. I mean, by law, they're supposed to blind the data and not bias the outcomes. One hopes that's what they do. Yeah.

2:40:56Dr. Rhonda Patrick:And I think for the most part, you're probably okay. But it is something to consider if there's a potential COI, right? But, yeah, so I don't know. So that was the first part of your question was the difference between the glycinate and the ethylene. And then the concern that I might have, which might be something you're not thinking about, is, okay, well, I need to fulfill my magnesium requirements, right? And so our daily magnesium requirements, again, based on our gender and our physical activity, it's a range. It's a sliding scale. So, you know, women, 300, 350 milligrams a day. Men, 350, 400 milligrams a day, really depending on how physically active you are.

2:41:33Dr. Rhonda Patrick:And this is just, you know, your daily requirements to have enough magnesium to run, you know, repairing DNA damage to run. You need magnesium to make energy, to utilize energy. You need it for neurotransmission. Like there's so many different, you know, important functions in our body that require magnesium to work to make vitamin – to convert vitamin D3 into the active steroid hormone. And this to me is like to some degree vindicating, but also I'm super annoyed by it because, you know, we have all these different studies out there on vitamin D supplementation and is it important? And I mean there's so many negative data out there.

2:42:13Dr. Rhonda Patrick:Well, it doesn't do what we thought. It's not doing anything. But half the U.S. population doesn't get enough magnesium. And so those enzymes that are important for converting the D3 that you're taking into the active steroid hormone are not working properly. So anyways, I'm not going to go on that tangent, but I'm just saying magnesium is doing a lot of things. So if you are taking the magnesium threonate and let's say it is getting – it's going into the blood more – sorry, the brain more readily, then the concern would be, well, not enough of it is around for DNA repair and other organs and stuff.

2:42:48Dr. Rhonda Patrick:And so you might want to get another source of magnesium. It's all theoretical, right? And like that's not – there's no data on that. So just mostly because no one's looking at it. No one's investigating it.

2:42:59Andrew Huberman:There's not a lot of incentive. It's funny when people will always say, well, there's no incentive because the drug companies can't make a lot of money on it. And sometimes that's true. But I have to chuckle because as scientists, I will tell you folks. And, like, I wish I could just, like, paint this across the sky. But then I get accused of being, like, a chemtrail person or something. The reason there's no studies on BPC-157, the reason there's no like RCTs on a randomized control on different forms of magnesium and large sample sizes because we barely have enough money to fund the current research.

2:43:33Andrew Huberman:Like I'm not trying to make this political like we just had a 1 % increase in the NIH budget. But like there isn't an infinite amount of money to run studies. And so scientists are, if they already work on magnesium or it becomes interesting to them because it came up in a screen of pathways, people aren't, there are not a lot of scientists sitting around going, oh, like maybe I should study, compare magnesium, malate, bisglycinate, threonate in sleep, in 2000 subjects, male, female, like pregnant and perimenopause. Like, no, no, there's no money to do it. Like, so that's where I get back to, is it safe?

2:44:08Andrew Huberman:Do you want to be in the experimental or the control group? Can you afford to be in the experimental or the control group?

2:44:14Dr. Rhonda Patrick:Yeah.

2:44:14Andrew Huberman:I feel like that's, that's like all we've got. And I'm only, I'm chuckling out of, it's sort of like a laughter of pain because I get where people are coming from. But the drug companies are not like avoiding studying magnesium because there's no money to make. It's because, I don't know, what would that even look like? Like what endpoint, what disease, what like, yeah, anyway, forgive me for editorializing. Yeah.

2:44:36Dr. Rhonda Patrick:You're not going to cure, you know, cardiovascular disease or cancer by taking a magnesium supplement. I mean, these nutraceuticals, these vitamins and minerals, they're about prevention really. And giving your body the right nutrients that it needs to do and function properly, you know, whether that is, you know, getting enough sleep. You know, when you're stressed, when your cortisol goes up, you know, chronically, you're depleting magnesium. You know, it's very like magnesium is being used to deal with that stress, right? So there's a reason that we need things like magnesium and, you know, vitamin D.

2:45:11Dr. Rhonda Patrick:It gets converted into steroid hormone, changing 5 % of our, you know, our genome. So, yeah, it's different. It's not like a pharmaceutical where you don't need this, you know, to function optimally. But it might – it's the whole like, okay, I'm sick and now I need this – or I'm overweight, right? We got the GLP ones, right? I'm fat. I'm obese. And I need to help fix that. And so that's kind of a different paradigm.

2:45:40Andrew Huberman:Specific endpoint type stuff.

2:45:42Dr. Rhonda Patrick:Yeah, exactly.

2:45:42Andrew Huberman:Yeah, I think that's super important for people to hear that. Oh, by the way, I should just say, for your sake and for the listeners, I divide supplements into basically four categories, like food replacement, like whey protein or a protein bar, you know, obvious sort of general support, specific effects, and then experimental maybe. Yeah, yeah. And so I think what we're talking about here with magnesium is kind of a combination of maybe helps with sleep, some specific effects that you're aware of, like required, and you're trying to top off. You're trying to make sure that you're covering a deficiency.

2:46:16Dr. Rhonda Patrick:Yes.

2:46:17Andrew Huberman:Okay. Yes. Got it.

2:46:18Dr. Rhonda Patrick:You're trying to make sure you're getting enough of the magnesium. Exactly. Are there any other things that you take that are just trying to make sure that you're not deficient anywhere or for specific reasons?

2:46:28Andrew Huberman:We've talked about a few along the way here, glutamine, vitamin D, omega-3s, creatine.

2:46:33Dr. Rhonda Patrick:I take a multivitamin and that is to cover my bases because, you know, there's a lot of things in a multivitamin. You have to find it obviously a good quality one. And anyone that tells you that multivitamins are useless, they're wrong. I'm going to tell you that. They're wrong because I think now we have pretty strong data, three very large randomized controlled trials, part of the COSMOS trials. Have you heard of these studies? And it's really, I think, pretty clear that in these studies, older adults, we're talking 65 years and older, that are taking a multivitamin supplement for, you know, was it a year?

2:47:12Dr. Rhonda Patrick:I think it was. It could be two, but I think it was a year. And it was, by the way, Centrum Silver. It was like your standard, you know, anyone could afford to get it at Walmart type of vitamin. And after a year of taking this multivitamin, it globally reduced brain aging by about 2.1 years. Three trials. Globally reduced brain aging by 2.1 years. Battery of tests that are done, right? I mean, it's, you know, I'm just talking about general here. And it also reduced episodic brain aging by 4.9 years. So that would be, you know, as people probably are already familiar with that listen to this podcast, you know, episodic memory.

2:47:50Dr. Rhonda Patrick:That's the part of memory that's involved in like remembering events and people and like experiences. Am I right? I mean, it's part of like not as much. A sequence of things. Sequence of things. Yeah. And so, you know, that's a big effect for just a daily multivitamin, you know. And so for that reason, you know, I mean, I've been taking it before these studies came out. But my parents, you know, anyone that's older adult should be taking a multivitamin. So that's another one that I take. and I take it to cover my bases as well. I'm obviously not an older adult and who knows, it might not have the same effect on me, but it's one of those that it's not harmful.

2:48:30Dr. Rhonda Patrick:It's a little bit of an expensive urine, fine, but it is covering some of my bases in terms of some of the micronutrients in it, right? The other ones that I take in besides the one that you mentioned, which is vitamin D, omega-3, I do creatine, magnesium. I do magnesium glycinate. I should look into the bisglycinate because I definitely would like another molecule of glycine I like for my sleep. But I also sometimes take another form of magnesium, which is it's like a mixture of magnesium malate and tarate, I think, and glycinate is also in that. But sometimes I take that for sleep. And then I take ubiquinol for mitochondrial health.

2:49:10Andrew Huberman:You like the data on that, obviously, if you're taking it.

2:49:13Dr. Rhonda Patrick:There's stronger data, I think, on ubiquinone, which is the oxidized form. It's more stable. There's just, when I say stronger, I mean more data.

2:49:20Andrew Huberman:Do you take coenzyme Q10?

2:49:22Dr. Rhonda Patrick:So coQ10 is ubiquinol.

2:49:26Andrew Huberman:Okay.

2:49:26Dr. Rhonda Patrick:Yeah. And so I'm taking the reduced form of it, which is ubiquinol. The more stable form would be ubiquinone.

2:49:32Andrew Huberman:Are those trademark names? Because I take coenzyme Q10.

2:49:36Dr. Rhonda Patrick:Yeah, you're taking -

2:49:37Andrew Huberman:I'm guessing if I took a closer look at the bottle, I'd say the ubiquinone.

2:49:40Dr. Rhonda Patrick:It's ubiquinone, yeah.

2:49:42Andrew Huberman:Ubiquinone.

2:49:42Dr. Rhonda Patrick:The ubiquinol is a little bit more bioavailable, but yeah. So I'm pretty convinced that that helps with mitochondrial function. You know, it's not like you could always have more data, right? So we'll just leave it at that. The other one I take is now I'm taking urolithin A in the form of – I'm taking mitopir, by the way. I have nothing to do with these companies. But there's now – I've just been over the years increasingly interested. So urolithin A is something that is formed from a type of polyphenol that's found in some fruits, like pomegranate being the main one. I think raspberries may also have some.

2:50:19Dr. Rhonda Patrick:I think walnuts also. But it's elagitannin is the polyphenol. And these elagitannins get metabolized by the gut microbiome and the metabolites that are formed. One of them is called urolithin A. And so urolithin A is a compound that seems to stimulate the process of mitophagy, which is a very specific form of autophagy that's only for mitochondria. And, you know, that's been shown in – there have been randomized control trials showing this in humans. It does stimulate mitophagy, blood cells as well as muscle biopsy. but that's an important cleanup process for how our mitochondria repair themselves.

2:51:02Dr. Rhonda Patrick:There's no repair enzymes, right? Part of that repair process is mitophagy, where they're getting rid of selectively can get rid of parts of mitochondria that are damaged. So it's really a rejuvenation. And some of the clinical data, I would say, is emerging. More needs to be done, but it seems to, in some cases, improve endurance performance, which makes sense because they rely heavily on mitochondria, but even also help with the immune system and this whole inflammation. So it helps keep immune cells. It seems like it's helping keeping immune cells, quote unquote, younger. So again, emerging data, but it's, I'm in that, I'm like, I'm the experiment group.

2:51:39It seems to be safe and I'm not taking too high of a dose.

2:51:42Dr. Rhonda Patrick:So that's another one that I'm supplementing with. The other one that I'm taking also is a very, a form of, I would say, I'm going to call it sulforaphane, but it's not sulforaphane. It's the precursor to sulforaphane, glucoraphanin, because that's more stable. And so I take something called Avmacol, which the reason I take that one is because there's, oh, it's 13 now. A new study just came out, 13 studies using that form. And sulforaphane is also one of those plant phytochemicals. It's formed. It's found in crucifix vegetables. As you know, we've talked about this before, so I'll try to make it brief.

2:52:18Dr. Rhonda Patrick:But so glucoraphanin is in these cruciferous vegetables like broccoli. Broccoli sprouts are a really, really great source of it. And when the plant is crushed, you know, like when you eat it, eat broccoli or chew it, whatever, an enzyme is activated that converts glucoraphanin into sulforaphane. The reason I take it is because I've been now convinced by, I would say, the limited number of human studies, clinical studies, but also the totality of evidence looking at cruciferous vegetables in general and then also animal data, that it's really important. It's probably the best naturally occurring dietary activator of a stress response pathway that is important for detoxification.

2:52:57Dr. Rhonda Patrick:And that pathway is the NRF2 pathway. I'm sure you've heard of that pathway. Sulforaphane is a very, very powerful activator of that pathway. And what I mean by pathway is that gene is turning on and turning off many, many other genes. What we know about it is that it's very important for activating the detoxification genes that are involved in detoxifying things that are harmful to us. And so the classic studies that have been done, some of them, most of them in China where air pollution is very high, is that if you take, you know, this broccoli sprout sulforaphane extract, you can start to excrete compounds that are found in air pollution like benzene that are carcinogenic, right?

2:53:35Dr. Rhonda Patrick:And you can start to excrete it after 24 hours by like 60%. Great. What about plastics? So that's my thing. That's why I'm taking it in my whole family. Because the same enzymes that are activated by the sulforaphane that detoxify benzene. So basically you're detoxifying it. What I mean is you're basically making it water soluble so you can excrete it through urine. Okay. The same ones, that's exactly what those enzymes do to BPA. They make it water soluble and help you excrete it through urine. There's no human data showing this yet. I want someone to do the study. But we do have animal evidence where, you know, animals are given a high dose of BPA and sulforaphane and it protects against the toxicity.

2:54:21Dr. Rhonda Patrick:I basically think that someone's going to show it and it's going to be clear because the enzymes that are involved are activated by this, by sulforaphane. That's been shown with benzene and acrylene excretion, right? So why wouldn't it be BPA? You never know.

2:54:34Andrew Huberman:The mechanistic logic is there.

2:54:35Dr. Rhonda Patrick:Yeah, yeah, exactly, exactly. So that's another reason why also it increases. It's been shown in human studies to very powerfully increase glutathione in both the plasma and the brain. And that's also through the Nrf2 pathway. It activates the powerful antioxidant pathway. It also deactivates phase one biotransformation enzymes. Those are involved in turning a pro carcinogen into a carcinogen. So those are things like you're eating, you know, you're grilling your meat at a high temperature and you're getting heterocyclic amines, right? I mean, these things can be harmful. But our body can deal with it.

2:55:09Andrew Huberman:We had a cancer doc on here recently and I was scared to ask him the question because I didn't want the answer. But I did want the answer of, you know, the char on meat. Yeah. And he's like, it's a pretty serious carcinogen. That's real. I mean, the occasional thing isn't going to be a problem. You'll be relieved to know, and this is not a promotional, that the can that you're drinking out of, these are intentionally BPA, BPS, and PFAS free. We attest to my be happy to send you the results. I already know. I already knew about that. Because I know that you and I are both, I am wary of the BPAs and the rest.

2:55:38Andrew Huberman:I think it's wild that 10 years ago, people like Charles Poliquin were saying, don't handle receipts. and everyone was like, this is really kooky. Actually, back then, no one even heard what he was saying. It was such a niche thing. Then people were very, I think, disparaging of people saying, be wary of receipts. Now, I think the microplastics and the BPA, BPS, PFAS concern is really taking hold more broadly. And I think that, you know... The tables have turned.

2:56:10Dr. Rhonda Patrick:Yeah. And really, obviously, you can't eliminate them completely. It's impossible. They're everywhere. Yeah. They're everywhere. I mean, we're—

2:56:18Andrew Huberman:Clothing, I heard, is the main—

2:56:19Dr. Rhonda Patrick:It's the main source of microplastics in the ocean, right? Because we're washing our clothes, and this cute shirt that I'm wearing, I mean, it's got microplastics in it for sure. And so every time you're washing your clothes, all the microplastics are coming out and getting into the ocean. And also then when you put your clothes in the dryer, and if your dryer is ventilating anywhere in your house, you're breathing those in, the microplastics.

2:56:46Andrew Huberman:They sell these traps. When I did the episode of microplastics, I found out that online you can – I think it costs – it's not cheap, cheap. But it's like considering they last a while, I think they're somewhere with refill somewhere in the neighborhood of – I want to say something like$70. but it traps, supposedly traps the microplastic.

2:57:01Dr. Rhonda Patrick:In the washing machine. In the washing machine.

2:57:03Andrew Huberman:And in Europe, I think this is actually built in or is required in a number of countries. Like they're way ahead of us. They're way ahead of us on a number of things. I mean, a few things are really, they're far behind, I must say, with respect to health, but on many things, they are way ahead of us.

2:57:19Dr. Rhonda Patrick:Yeah, well, clearly with the Switzerland, people in Switzerland being 80, like 88 % of them being physically active, they're way ahead of us on that.

2:57:25Andrew Huberman:I'm excited to share with you that Matina, the yerba mate drink that I helped create is now available at Sprouts Market nationwide. Long-time listeners of the Huberman Lab podcast know that yerba mate is my preferred caffeine source. It provides a smooth energy lift without giving you the jitters, and it has many other benefits, such as helping regulate blood sugar, improving digestion, mild appetite suppression, and more. Matina is my absolute favorite of all the yerba mate brands out there. And believe me, I've tried them all. The flavors are fantastic. I drink at least three cans of Matina every single day.

2:57:59Andrew Huberman:You'll often see them on the table during our podcast recordings. I absolutely love the product and I'm proud to now have it sold at Sprouts Market. Also, there's a great new offer. They are giving away a free can of Matina to anyone who buys it at Sprouts and sends in a photo of their receipt. To learn more about how you can get a free can of Matina, go to drinkmatina.com slash offer. Again, that's drinkmatina.com slash offer to get a can of Matina for free at your local Sprouts Market. What is your threshold for you? And what do you think is kind of reasonable levels of what's actionable for you?

2:58:36Andrew Huberman:Like how do you set that? I think it will help people kind of understand how you're approaching stuff.

2:58:41Dr. Rhonda Patrick:What's actionable in terms of improving what I'm interested in improving my health.

2:58:44Andrew Huberman:Yeah, like, I mean, without picking any specific example, like when you look at the literature and you see, let's say, let's say BPC-157 is kind of a fun one because everyone's excited about this now except the physicians who don't like working with peptides besides GLPs or other FDA-approved peptides, they're like freaking out online from them all the time. Compounding pharmacies just got the green light that they're going to be able to do basically whatever except sell retitrutide, which is under patent. So there are many, many animal studies on BPC-157 showing accelerated cartilage growth, nerve growth after injury, and on and on and on and on, and angiogenesis.

2:59:24Andrew Huberman:So there's some potential cancer risk there, right? But basically zero human data. There's one study, weak study, self-report. There's actually a clinical trial where they, I'm not making this up, folks, is BPC enemas, very high dosage for some sort of bowel disease or bowel inflammation. And the study was like, I don't think the study was completed or something like that. Don't ask me why. No, I'm not making this up. But that's pretty much the only human data that I'm aware of. but tons of people injecting and swallowing BPC and saying, yeah, it helped me recover, you know, heal more quickly.

3:00:04Andrew Huberman:How do you think about something like that? Like that current condition?

3:00:08Dr. Rhonda Patrick:First of all, if you're not doing it, you're not going to be doing this every day forever, right? Like this is a short defined period of time where you're going to do your injection. Oh, really? Okay. I know. I know.

3:00:17Andrew Huberman:I mean, I don't know what people do. Unfortunately, I think some people like to take it every day, but let's assume two months maximum to work around an injury or through an injury. Yeah.

3:00:26Dr. Rhonda Patrick:For people that I know that have experimented with it, it's been like three months and a period of time, and they did have improvements. And they could have been through placebo, which I will say is possible. But for me, it really comes down to like, is it safe? Is it safe? Okay. If it's safe, you obviously have to get the good source because if it's all these pharmacies now, I mean, that's a problem. because we do know that that's a big area of, I would say, concern with any sort of nutraceutical, you know, sort of thing. And I would put this into that category is that, you know, people are putting things in the products that are not necessarily what's supposed to be in there.

3:01:04Dr. Rhonda Patrick:And they're not really paying attention to quality because it's not regulated. Right. So so if you can get a good source of it and you trust the source of it and you have maybe someone who is qualified to prescribe it to you, because there are naturopaths and stuff like that, functional medicine practitioners. There are people that are prescribing them.

3:01:24Andrew Huberman:And some MDs, some board certified. And some MDs, yeah, some MDs are. Did their residency, did all the things. I know because I'm friends with some of them. And a lot of doctors are happy to prescribe peptides sort of off-label, like Sermorelin for purposes other than what it was FDA approved for. I mean, I'm not taking it, as I mentioned earlier. But you've tried it. It very quickly spiked my PSA and nuked my REM sleep and increased my deep sleep. So I was like, I don't want to, I don't, I'm not interested in those effects. And, and I do worry about tickling the growth hormone pathway too much or too long because

3:02:00Dr. Rhonda Patrick:of, you know, I don't, you know, hopefully I don't have any tumors sitting around, but

3:02:04Andrew Huberman:if I do, I don't want to vascularize them or grow them.

3:02:06Dr. Rhonda Patrick:Right. Yeah. So for me, I mean, I'm always more on the cautious side, to be honest. And so for me, the safety thing has to be checked first. and then at that point if i can check the safety thing then it's like you said i mean i can't i'll try it like i mean i'm doing like some of these supplements that like mitopure for one like the urolithin a i mean it's not like tons and tons of data on it but it seems to be safe and you know i'm experimenting with it i'm also experimenting experimenting with a lot of other things so it's hard to know what's working sure nicotinamide riboside is another one i take um back on to the what I take.

3:02:40Andrew Huberman:Is that for a longevity effect? I mean, I take a sublingual NMN, no relationship to any company that sells NMN. At least the one I take is from, they hate it when I do this, but from Renew by Science, it's the cheapest version. That's not why I take it. I just like the powder put under my tongue. I like the energy effect. I will say this, and I've done the control experiment on myself, and I have family members who've done it too. It makes my hair grow crazy fast and my nails grow crazy fast. I know it's because if I stop, that halts. Those aren't really effects I'm looking for. And it worries me a little bit because what else is it making grow crazy fast?

3:03:15Andrew Huberman:Again, I don't think I have a tumor, but what else is it, you know, if I have like a polyp or something, is it making that grow crazy fast? I don't know.

3:03:21Dr. Rhonda Patrick:I asked that question to Dr. Charles Brenner when I had him on podcast because there was a study on NMN in mice that the mice had tumors and then they, you know, gave them, I think they injected them with NMN or maybe was orgalovage. I don't remember which way it was, but it accelerated the growth of those rare types of pancreatic cancer cells. And so I was, you know, obviously energy, yes, cancer cells love energy too, right? Brennan doesn't like NMN.

3:03:47Andrew Huberman:And I will take NR sometimes. I do take true knowledge. Right.

3:03:50Dr. Rhonda Patrick:Well, it doesn't, I mean, either way. So the same endpoint here, we're increasing NAD, right? So the question is then, okay, well, should I be worried about cancer? And he pointed me to some study out of Australia where I think it was, maybe it might have been nicotinamide that basically prevented some kind of, it wasn't melanoma, but it was another type of skin cancer. And so I was like, okay, well, that seems sort of to the point here. I am experimenting with it. Why? First of all, I became interested in it because the effects on mitochondrial health, there is effects on fertility, you know, energy recovery when I started.

3:04:27Dr. Rhonda Patrick:It just, you know, and then again, you can find a couple of studies where like, maybe, you know, you're not as insulin sensitive. And who knows? Like, it's not – there's not enough data there. So I would say I'm cautiously experimenting with it. But so far, I love it. And I don't – again, you never know what's placebo here.

3:04:43Andrew Huberman:So I do take – they don't pay me. I buy it. I do take TruNiagen, NR. That's what I take, yeah. NR. And on the data sheet, they include some human studies. I have a family member. I'll just say my sister takes it. She, like, loves it. Yeah. She's convinced. Now, that could be placebo. But she is so convinced. She texts me about it. I feel so much better. I have so much better. I have no idea. She has no idea if it's placebo, but Brenner's a very good scientist. I will say he's, he's a, he's what, you know, what we call in our business, you and me, a serious scientist. I just don't think any of that's going to make me have a direct effect on living longer.

3:05:20Dr. Rhonda Patrick:I don't know that it is. I don't know that it's the, it's not one of my, like, if I had to like, you know, shrink down to my core supplements, like it wouldn't be in there. And, you know, there's many other things that are important, I think, for.

3:05:32Andrew Huberman:So if you were budget limited, it wouldn't get above the above threshold. Like if someone out there had like just like 100 bucks or 200 bucks to spend on supplements, which is a lot for a lot of people.

3:05:43Dr. Rhonda Patrick:I don't know that it's going to help you live longer either. Now, it might help with your exercise recovery a bit. Right. It might help improve mitochondrial function. I mean, maybe it's going to help with repleting some of the NAD stores. I mean, if you can improve mitochondrial health and, you know, you're improving things like on a small scale. Right. So mitochondrial health is at the core of everything. So that's something to consider. But yeah, I'm not convinced it's the end olbio either, but I do take it. And it is something I'm experimenting with. I think it seems to be safe. And there's a lot of emerging data that caught my interest.

3:06:17Dr. Rhonda Patrick:But omega-3 is the top, right? There's nothing NAD, the nictinamide riboside, or NMN, if you can find a good source of it, that's not comparable in my books.

3:06:27Andrew Huberman:Have you experimented with L-carnitine because of the mitochondrial effects? Because I was able to find some good studies on sperm and egg quality, which are thought to be downstream of mitochondrial health. Right. That's the idea.

3:06:41Dr. Rhonda Patrick:If you can improve mitochondrial health, fertility, which is why NR is now involved with fertility, seems to be improving fertility. It's right. If you can improve mitochondrial health, then you're going to improve fertility, sperm health, right, egg health, right? Yeah. L-carnitine, a lot of those studies came out of my mentor's lab were the same. So he looked at the combination of L-carnitine and alpha-lipoic acid, improving mitochondrial health, and came up with a supplement that – it's called Juvenon now, but it's L-carnitine with alpha-lipoic acid.

3:07:09Andrew Huberman:It's a pill.

3:07:10Dr. Rhonda Patrick:It's a supplement, yeah.

3:07:11Andrew Huberman:Yeah.

3:07:11Dr. Rhonda Patrick:And so, yes, I have experimented with that. And, in fact, my husband takes it. But, I mean, I just can't take so many supplements.

3:07:21Andrew Huberman:Yeah. I was just curious.

3:07:23Dr. Rhonda Patrick:We have our, yeah, but it is, you know, you can find evidence that it improves mitochondrial health. So, you know, it's just a matter of, again, like what are you looking for? I feel like I'm doing a lot of high-intensity interval training too, and I'm taking the urolithin A. That's a lot, you know, I'm doing a lot of stuff to optimize mitochondrial health. I mean, at some point you have to like not, you can't do everything there is. Sure.

3:07:47Andrew Huberman:No, of course not. But yeah, L-carnitine. And then it's budget limited too.

3:07:49Dr. Rhonda Patrick:But maybe, you know, maybe I should add the L-carnitine in. Oh, no, I'm not saying that. It's possible, right?

3:07:53Andrew Huberman:I started experimenting with it, but I take it in injectable form.

3:07:57Dr. Rhonda Patrick:Really?

3:07:57Andrew Huberman:It's going to shock some people. You can get away with taking much lower milligram count. Otherwise, you have to take a lot of it because a lot of it just isn't absorbed if you take it orally. And then I was told that if you take it orally, you also have to do something to offset the increase in TMAO. And that worried me. So I figured needles don't scare me. I'll just inject it.

3:08:16Dr. Rhonda Patrick:Interesting. Yeah. Yeah, the TMAO thing. I mean, so not – it depends on your gut bacteria, whether or not you're metabolizing L-carnitine into TMAO.

3:08:23Andrew Huberman:There's actually a lot of complexity involved in that whole thing.

3:08:26Dr. Rhonda Patrick:But you can get your TMAO measured. So if you're supplementing with it – I mean, the same goes for choline. Yeah, sure. Like if you're worried, like choline can be converted into TMAO.

3:08:34Andrew Huberman:Yeah, I'll take alpha-GPC before a workout sometimes or if I need to – if I ever need to focus late in the day, I don't want caffeine because it impedes my sleep. But I'll take alpha-GPC because this is kind of a cool effect. Alpha-GPC actually will improve your REM sleep. It's not a huge effect, but you'll notice you'll get more REM sleep. So it's one of the few things I've found that can increase energy late in the day. Do a workout or work if I have to work later into the day. Still sleep just fine and actually sleep better.

3:09:00Dr. Rhonda Patrick:What does work later into the day mean for you? Like working until like 8, 9 o 'clock?

3:09:04Andrew Huberman:Yeah, well, I do that often. But I don't like to work out after 2 p.m. because I like caffeine before I work out. But I'll do some cardio in the afternoon or something. But if I really have to push, push, push, or if I've traveled and I really need exercise and I want to get a 6 p.m. workout, but I also want to fall asleep at 1030, I'll take some alpha GPC.

3:09:25Dr. Rhonda Patrick:I used to take that. Like, I don't know. It's been maybe like 10 years. But it's interesting. I might try experimenting with that again. I'm always looking for things that I find a little bit safer.

3:09:36Andrew Huberman:Like I don't do the nicotine, as you know. It is shocking how many young people are taking nicotine now. Oh, I know. Yeah. I've never tried it. First of all, it's highly addictive. Forget the blood pressure and the vasoconcer. That's all bad. You know, I think the big issue is that if I take it, I start getting the spasming in my throat when I don't take it. And that's because of it. I have a friend who works on these pathways and it's because of the activation of the muscarinic receptors. So on smooth muscle, you start getting a tick and kind of a clearing of your throat. And then you take more nicotine, you feel fine.

3:10:05Andrew Huberman:So I didn't want to become dependent on it.

3:10:07Dr. Rhonda Patrick:Yeah.

3:10:07Andrew Huberman:And I don't like it. I think it's a bad habit that a lot of people are going to be seeking to quit later. A lot of young people. Older people might benefit from it because of the cognitive enhancement, but that's a whole other story.

3:10:19Dr. Rhonda Patrick:Well, maybe the alpha GPC and the creatine and magnesium L3.

3:10:24Andrew Huberman:Yeah. Alpha GPC is very helpful if you need to really lock in for a few hours and do something physically. What does? I take 600 milligrams. You can take up to 900, but I do just fine on 600. So I think I just take it in pure form and capsule. Yeah. Any of them out there that come from a reputable brand is, like, going to work.

3:10:41Dr. Rhonda Patrick:What about, like, before a podcast or something like that? Does that have any effect or why? Oh, yeah. It does.

3:10:46Andrew Huberman:Yeah, it'll put you into – you know, I mean, if you feel like you want to be heightened focus. But I rely on water, caffeine, electrolytes, and good sleep. There's this wild study. We don't want to – I don't want to take us too far off track here. But there's a study out of WashU recently, really, really talented researcher. I want to bring him on this podcast. does brain imaging, and he compared essentially the effects of drugs for ADHD versus a good night's sleep and basically found that there's no focus enhancement of Adderall, Vyvanse, Ritalin-type drugs. They mainly looked at Ritalin. All it's doing is increasing alertness to the level that you would get after a good night's sleep.

3:11:25Andrew Huberman:It may be that these drugs just increase alertness, which allows you to dial in focus. But if you're sleeping well and enough, you make up the gap, And people with ADHD might just be having some serious sleep defects. So, you know, it speaks to this thing. Like, I don't know that there's a single drug that can actually increase cognition and focus. Most of them probably just get you in the plane of alertness that allows you to dial in your focus. Some people will be like, that's BS. They take modafinil. But this is just another form of increasing alertness.

3:11:55Dr. Rhonda Patrick:Well, reducing anxiety, I think, things that are anxiolytic help with that as well. And I think I was talking about, I don't know if I was telling you or someone else before the podcast. One of the reasons why I also like that metabolic switch with the ketosis and the beta-hydroxybutyrate. And sometimes I'll take exogenous ketones too. Although if you take them in a fasted state, it kind of shuts down the lipolysis. But anyways, it's because it increases GABA. The beta-hydroxybutyrate increases GABA. And for me, it's beneficial because I am the phenotype where I like, you know, I can have other things going on in my mind.

3:12:27Dr. Rhonda Patrick:that it's, I don't want to, it's not anxiety, but it's more of that anxious phenotype, if that makes sense. And so the increase in GABA really does help me with focus because it's quieting down, I think.

3:12:40Andrew Huberman:I actually think that a lot of people who are very intellectually engaged, which clearly you are over many, many years and very physically active and healthy, there's a lot of capacity there. And unless there's something to really absorb all that capacity, you can get multiple tracks going. And we sometimes think of that as anxiety or even some people will say it's ADHD. I don't necessarily think it's that, but it's an uncomfortable state to be in. It's so pleasureful to be like where all one's resources, physical or cognitive or both are harnessed. It's a very pleasant state. Earlier you were saying the GABA increase from the ketosis.

3:13:14Andrew Huberman:I think more and more we're just realizing that people have differing levels of excitatory to inhibitory balance in the brain. And so some people like things that bring GABA up. Some people like things that bring glutamate up, broadly speaking. And finding that sweet spot is where you go, oh, like I'm alert, but calm.

3:13:31Dr. Rhonda Patrick:Right. And that's what it does for me. Alert, but calm. Great. And for me, I'm like, and I noticed that there was a few years ago, I really experimented with a ketogenic diet. I just can't do that type of diet, but I did experiment with it. And that was one of the main things that I noticed is like, I'm alert, but calm. And it's like, I liked it.

3:13:49Andrew Huberman:Well, then don't take nicotine because the reason people like nicotine is it's a stimulant that calms you down. So I do think that one of the reasons it's so habit forming is because I know of nothing else that puts you in that plane of focus of alert but calm that is reasonably low cost, that is legal. I've never done amphetamine or cocaine, so I wouldn't want to. And clearly that's a path to destruction. So the reason so many young people are taking it is because it gets them right in that plane of alert but calm, but it has all these negative effects that go with it.

3:14:24Dr. Rhonda Patrick:Yeah, and that's why I have stayed away from it because I know I quite love it.

3:14:28Andrew Huberman:I've asked some young folks who ask me about nicotine, how many milligrams are you taking? They'll say nine milligrams. I'll say how many times per day? They'll say eight times per day. I'm like, oh, my God. Like, that's crazy.

3:14:40Dr. Rhonda Patrick:But they didn't start there.

3:14:41Andrew Huberman:No, you just quickly get there. You adapt. Yeah, so I don't want to sound like that curmudgeon that's like don't drink and don't take nicotine and this kind of thing, but it's a slippery slope.

3:14:52Dr. Rhonda Patrick:Right, yeah. It's a really slippery slope. I mean, there's other things that you can do that maybe it's not going to be as potent. Alpha GPC. Alpha GPC. For me, I like doing my metabolic switch and my ketones.

3:15:03Andrew Huberman:Nice. Well, I'd be curious to hear how you feel in the alpha GPC.

3:15:07Dr. Rhonda Patrick:I remember liking it. I don't know why. I think I stopped taking it because I got pregnant is probably what it was. It's a good reason. It's one of those things where you just forget. You go back to the basics and then like the - Different experiment. Yeah.

3:15:20Andrew Huberman:Before I came on here, I did put out a call for some questions to the world. Okay. Rapid fire Q &A from the land of X and Instagram. These are the students of the class, of your class. And this way I think about it. Actually, I wanted to ask about this. So I'm so grateful that this person asked about natto kinase for improving blood lipid profiles. Is it something you're interested in or have experimented with?

3:15:48Dr. Rhonda Patrick:It's not something that I've experimented with. And I've been more interested in natto, the natto kinase. I know some, I really would have to say I don't have enough data to really have an opinion on it.

3:16:01Andrew Huberman:Okay. Well, I don't have enough data to have an opinion on it, but I take it anyway. A lot of questions about things we already talked about. So cold plunge, et cetera, but an exceptional number of questions about microplastics. And I know we touched into it, but on a scale of 1 to 10, 10 being like you're really concerned, how concerned are you about microplastics for mental and physical health, longevity, just broadly speaking?

3:16:25Dr. Rhonda Patrick:I would say I am less concerned about microplastics than I am about not getting the right nutrients and micronutrients from our foods. because our body can detoxify at least some of the chemicals associated with them, the microplastics themselves. I mean, I guess it's not – we don't really know what they're going to do long term. But I'm concerned enough to try to avoid – to, sorry, limit my exposure to them as much as possible.

3:16:52Andrew Huberman:So you don't drink out of plastic water bottles?

3:16:54Dr. Rhonda Patrick:I mean, I try not to as much as possible. I mean, you know, I definitely have to at some points. But I try not to, yes. And when I do, I just realize it's the habit. and you kind of have to let go. I mean, I know some people that like don't drink and like they're gonna get their water from their food, their fruits while they're traveling. Pretty extreme. Yeah. But I think mental health is important. So I mean, it's like, is the stress of avoiding the microplastics worse than the actual little bit of microplastics you're being exposed to might be?

3:17:25Andrew Huberman:TSA is going to hate me, but I lost a bet two days ago to a member of our podcast team. He bet me, we bet, that I said one couldn't bring a Mountain Valley spring water bottle through security at the airport. And he said that you absolutely can. And I said, there's no way. So I made him a bet and I lost. He brought it through.

3:17:47Dr. Rhonda Patrick:Full of water?

3:17:48Andrew Huberman:Full of water. You tell them it's for medical reasons. You don't have to state what they are. They open the cap. They take a sample out. They test it. So there's a time constraint and it's going to create more jobs for TSA. sorry that was sort of a joke sort of not a joke TSA has been you know in tricky circumstances lately and he showed up at the at the gate with it and was like here's your water you absolutely can bring water through in glass vessels or whatever vessel but they're going to test it and it helps if it's a commercial vessel it's not like your own glass water bottle can I pause for

3:18:22Dr. Rhonda Patrick:a minute because you mentioned a specific brand which I also when I when I don't make money from

3:18:27Andrew Huberman:Right. Same.

3:18:28Dr. Rhonda Patrick:When I'm traveling, that's the brand that I go to. And there was a study that came out showing that there's actually a larger volume of microplastics within this study from glass bottles versus plastic bottles, which was a very shocking finding. So there's more microplastic number coming from the glass bottles. It turns out this was a study out of France. There was a study out of France and also in the U.S. it's the paint on the lids. You mentioned the lid. And so it's the paint on the lid that's getting contaminated in the whole bottling of this water that is getting into the water. But I do want to mention that the size was shown to be larger from the glass bottles versus the plastic.

3:19:13Dr. Rhonda Patrick:So the microplastic size was larger. And as you probably know, larger microplastics are not well absorbed through the gut epithelial cells. So when you're taking them in, in the gut, But they're coming out, they're being excreted through your feces and less likely to be taken up into your gut and then get into your body. And that's actually well known. And so I'm actually more concerned about the size of microplastics. And it wasn't like the huge orders of magnitude difference between the water from glass versus the plastic. It's so counterintuitive. You think, wait, what? Why is it? So it's the paint that's on the list.

3:19:47Dr. Rhonda Patrick:But anyways, I just want to mention that I still drink when I'm traveling. I still go for the glass, not the plastic, because of the size of the microplastics. And knowing, because the size was much bigger, that it's very, I would say, more data is going to come out on this. But I would be surprised if you're absorbing more of the larger particles because it's known that you absorb the smaller ones.

3:20:06Andrew Huberman:Thank you for that. And if you want, you can now take your glass bottle through security. Full seed oils, the dreaded seed oil debate. Where do you land on this?

3:20:17Dr. Rhonda Patrick:I try to avoid them. mostly because, one, if you're avoiding seed oils, you're going to avoid a lot of the processed packaged foods that they come in, which I know are terrible for you. Two, because I think that cooking them or heating them, I mean, is more of my concern because they are, you know, polyunsaturated fatty acids, which are very prone to oxidation. And when you're heating something that's prone to oxidation, you're accelerating that whole process. I don't want to consume oxidized lipids. I've seen, I've looked into that literature, And the last time I looked into it was, I think, 2024.

3:20:53Dr. Rhonda Patrick:At that time, I was pretty convinced that if you are heating and reheating oils like they do in fast food, for sure, you're increasing inflammatory markers. That's been shown. And I think also when you're really having a higher level of omega-6s and stuff around, I'm not as concerned because I'm getting a lot of omega-3. But it does also increase your vitamin E requirements as well because of the oxidation of these polyunsaturated fatty acids. So do I think it's like the worst ever? I mean, you can find all this data out there showing that, you know, if you replace, you know, saturated fat with some of these seed oils, there's improvements in lipid profiles.

3:21:32Dr. Rhonda Patrick:But at the end of the day, the question is really what if like you had olive oil instead or avocado oil instead, would it be even better? I think possibly. So if you're really trying to go for the optimum, I avoid them as much as I can for that reason. But I think there's a little bit more hype when it comes to the seed oil. But if that makes sense, you know, I'm kind of, that's my take.

3:21:55Andrew Huberman:Makes sense to me for what it's worth. I stick to olive oil and small amounts of butter. And that's because I also think seed oils taste terrible. How come no one talks about that? But anyway, and olive oil and butter are delicious. It's been so long since I've actually, like, I mean, had the seed oil, but yeah. Well, you know, and no one can convince me that they don't taste bad to me. So then the debate just kind of falls away. How often are you doing the sauna nowadays and what is the top contour of that protocol look like?

3:22:27Dr. Rhonda Patrick:So I've taken a little pause on the sauna right now, but typically I am doing, I was doing it like I would say five nights a week. And I say nights because I was usually doing them in the night. and it was mixed, a mixture between either getting in the sauna or hot tub. So I like, I like getting in the hot tub, head out under the stars there with my husband. It's like our time. So yeah, usually it's like 20 minutes and temperature wise, you know, I don't go that hot. I honestly, I'm like 180.

3:22:57Andrew Huberman:Five nights a week is great. I need to get back on a five night a week sauna or hot tub protocol.

3:23:03Dr. Rhonda Patrick:I do like the hot tub, especially, I don't know, there's something about being outside. And I think now there's evidence that the benefits are really like the same. It's the deliberate heat exposure, right? You're getting that through the hot tub or through the sauna.

3:23:15Andrew Huberman:Creatine for kids, like young kids, like younger than 16, any data and or ideas about this, good or bad? Yeah.

3:23:23Dr. Rhonda Patrick:So there is data in the literature showing that if you give younger children that are doing like, for example, sports like soccer, it does seem to improve their agility and it seems to be safe, I do give my son two and a half grams of creatine a day.

3:23:40Andrew Huberman:Cool.

3:23:41Dr. Rhonda Patrick:So that's how I feel.

3:23:43Andrew Huberman:There's no better indication of how one feels and what they're willing to deliberately give their kids. I don't know where this stems from, and we can cut it if you want. Someone asked, why did you single-handedly ruin bananas for this person? Yes. Did you ruin bananas?

3:24:00Dr. Rhonda Patrick:So I used to put bananas in my smoothies. And there's an enzyme that is produced in bananas that break down polyphenols, particularly ones that are found in blueberries. And the reason I was getting my smoothies was one for the greens, but two for the blueberries because the polyphenols have been shown to improve cognition. Love blueberries. So sorry, sorry, don't mix the blueberry with the banana smoothie because it has been shown to decrease the polyphenols, which are important.

3:24:24Andrew Huberman:Yeah, yeah. Well, the alcohol industry will come for me someday and the banana industry will come for you. and I think we're safe for a while. Should we ignore studies that have less than X number of subjects? I think that's a really good question. Like, obviously it depends, but when we're talking about human studies, where's the line for small study versus large meaningful study for you? Obviously how strongly it's powered, but how do you think about that?

3:24:53Dr. Rhonda Patrick:Well, I'll tell you, when I was first looking at the sauna literature, all the studies that I was looking at were like N of 10 or smaller. And it's really the aggregate of those studies and then looking at like animal data. And then you start to, you know, you start to look at observational data and the totality of evidence. And you put together this picture. I don't think you should ignore studies that are small. I think that it's part of the story. I think we're getting a little too caught up and it's got to be the randomized placebo-controlled trial. It's got to have lots of participants. and I mean, that's great if we have that data, but we don't always have that data.

3:25:29Dr. Rhonda Patrick:And I don't know that we will always have that data with everything that we're interested in understanding, right? So the way I look at it is if it's like just one study with an N of 10, okay, interesting. Like with the creatine, right? Like, I mean, these studies have been small sample sizes. Now there's more than one, but at the end of the day, it's still very, I would say in this pilot study phase, right? We have just small studies. So I do not ignore them, but I also don't hedge all my bets on them either. I do know that there were a lot of people that were criticizing me on my sauna. I mean, back in, you know, 2014, published an article on Tim Ferriss' blog, went on Joe Rogan's podcast and talked about, you know, the benefits of sauna.

3:26:12Dr. Rhonda Patrick:And I had people that were going, your sample sizes are too small. And now we have so much data that has come out since then really kind of validating everything and showing even more benefits. You kind of have to look at the totality of evidence and what endpoints are you looking at and how can you gather data from different sources, whether it's clinical studies or observational studies or animal studies, and try to come up with the bigger picture, right? But then also don't be too confident in your statements.

3:26:40Andrew Huberman:I'm very gratified to know that pretty much every other question you addressed the answer to en route to where we are now in the podcast truly and I'll leave them up so you can see them later if you choose. cold plunges notwithstanding, vitamin D, exercise in all its contours, specificity, fasting, magnesium, lots of questions about supplements, which we covered, creatine, lots of questions about inflammation, longevity. And so I just have to say, first of all, on behalf of everybody, thank you so much. This was really an incredible tutorial and so much of it is actionable. and as you are known for, it was incredibly thorough in terms of setting the context within mechanisms of what we know, what we still don't know and I also personally want to thank you because when you speak, I learn and when you speak, I also learn things that change my behavior and that's a whole other level.

3:27:38Andrew Huberman:Since our last conversation, I can think of at least four and probably as many as a dozen things that I do on a daily basis as a consequence of that conversation and just the gut inflammation, health, brain, body access conversation that we had earlier. I'm going to listen to this again and take notes because there's just so much there. And the metabolic flexibility thing has an input that can come from multiple sources and just on and on. So thank you for doing what you do. Thank you for being you, for being first in and still going and doing things with such rigor. And really so much grace. It's just awesome.

3:28:15Andrew Huberman:People love you. So I certainly do and appreciate you. And it's just it's a wonderful thing for me to have a colleague like you. And you really set the standard. So thank you so much for coming here and doing this marathon. And can't wait to do it again.

3:28:30Dr. Rhonda Patrick:Thank you so much, Andrew. It's really been great. I learned so much from you as well and appreciate everything.

3:28:36Andrew Huberman:Thank you. Thank you for joining me for today's discussion with Dr. Rhonda Patrick. To learn more about her work, please see the links in the show note captions. If you're learning from and or enjoying this podcast, please subscribe to our YouTube channel. That's a terrific zero-cost way to support us. In addition, please follow the podcast by clicking the follow button on both Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five-star review. And you can now leave us comments at both Spotify and Apple. Please also check out the sponsors mentioned at the beginning and throughout today's episode.

3:29:06Andrew Huberman:That's the best way to support this podcast. If you have questions for me or comments about the podcast or guests or topics that you'd like me to consider for the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. For those of you that haven't heard, I have a new book coming out. It's my very first book. It's entitled Protocols, an Operating Manual for the Human Body. This is a book that I've been working on for more than five years, and that's based on more than 30 years of research and experience. And it covers protocols for everything from sleep to exercise, to stress control, protocols related to focus and motivation, and of course, I provide the scientific substantiation for the protocols that are included.

3:29:46Andrew Huberman:The book is now available by presale at protocolsbook.com. There you can find links to various vendors. You can pick the one that you like best. Again, the book is called Protocols, an operating manual for the human body. And if you're not already following me on social media, I am Huberman Lab on all social media platforms. So that's Instagram, X, Threads, Facebook, and LinkedIn. And on all those platforms, I discuss science and science-related tools, some of which overlaps with the content of the Huberman Lab podcast, but much of which is distinct from the information on the Huberman Lab podcast.

3:30:17Andrew Huberman:Again, it's Huberman Lab on all social media platforms. And if you haven't already subscribed to our Neural Network newsletter, the Neural Network newsletter is a zero-cost monthly newsletter that includes podcast summaries as well as what we call protocols in the form of one-to-three-page PDFs that cover everything from how to optimize your sleep, how to optimize dopamine, deliberate cold exposure. We have a foundational fitness protocol that covers cardiovascular training and resistance training. All of that is available completely zero cost. You simply go to HubermanLab.com, go to the menu tab in the top right corner, scroll down to newsletter and enter your email.

3:30:51Andrew Huberman:And I should emphasize that we do not share your email with anybody. Thank you once again for joining me for today's discussion with Dr. Rhonda Patrick. And last, but certainly not least, thank you for your interest in science. Thank you.