Dr. Rhonda Patrick on Huberman Lab: Why gut LPS harms health

Dr. Rhonda Patrick 0:00 There's lots of data now showing that people that are doing these like short bursts at, at least a minute long, but up to three minutes, they're moving faster with intent, and it's having outsize effects on, 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, that's associated with a 40% reduction in all-cause mortality, 40% reduction in cancer-related mortality, a 50% reduction in cardiovascular-related mortality.

Andrew Huberman 0:37 Wow.

Dr. Rhonda Patrick 0:37 Nine minutes a day.

Andrew Huberman 0:39 Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. [guitar music] I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Rhonda Patrick, a biomedical scientist and leading public health educator. For over a decade, Rhonda has been one of the most trusted voices in building science-based health protocols. Today, we discuss what the latest and best research says we should all be doing to improve our health and vitality and avoid disease. Rhonda shares with us her exact exercise, nutrition, supplementation, and sauna protocols, and we get really detailed about the mechanisms and logic behind each one. We also discuss the things that science say you can do to significantly reduce your cancer and cardiovascular risk, including how to reduce visceral fat and arterial plaque. Today's discussion truly leaves no stone unturned. We discuss how eating can increase inflammation, believe it or not, ways to support your gut health, creatine, vitamin D, why broad vitamin and mineral and fiber support is crucial, as well as the different forms of magnesium and each of their unique effects. We also discuss omega-3s and why prescription sources of omega-3s may be the cleanest and most cost-efficient way to obtain sufficient omega-3 intake. We also discuss the importance of prioritizing regular resistance training and HIIT workouts over protein. You still need protein, but emphasizing the exercise component is crucial. And we discuss fiber, micronutrients, and why short-term fasting can be beneficial. Dr. Rhonda Patrick is a true wealth of knowledge, and today she generously provides us a master class on how you can design and adjust the exact health protocols to meet your specific needs. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Rhonda Patrick.

Andrew Huberman 2:40 Welcome back, Dr. Rhonda Patrick.

Dr. Rhonda Patrick 2:43 Excited to be here.

Andrew Huberman 2:44 It's been a while. I'm so excited. There's so much to go into. And I'll start off the same way I started last time because it's even more true. Thank you for being first person into this public science health education business. I don't know if everyone's aware of it, but you were the first person in, which is why I didn't say first man in, because the first person in was and is a woman, and you've done a marvelous job of educating people on science, how to parse papers and data, health practices, and, um, you know, the rest of us are just trying to follow in your wake. So thank you very much. I just want to thank you for being first.

Dr. Rhonda Patrick 3:21 Oh, man. Thank you so much for that. And also thank you for doing what you do. I mean, you really do a great service for science communication, um, you know, education, helping people love science and get healthier.

Andrew Huberman 3:33 Thank you. Well, uh, you're the pioneer. It's not always easy being a pioneer, but we all benefit, so. Let's jump in at exercise because, um, lately you've actually been posting your workouts, which is awesome, and, uh, you're clearly very fit. I learned before talking to you today that, uh, you were a competitive athlete. You were a long jumper or triple jumper?

Dr. Rhonda Patrick 3:54 I was a long jumper.

Andrew Huberman 3:55 Uh-huh.

Dr. Rhonda Patrick 3:55 But I would say my real competitive athleteness comes from my jump roping. [laughs]

Andrew Huberman 4:00 Okay. All right.

Dr. Rhonda Patrick 4:02 I was on a professional jump roping team.

Andrew Huberman 4:04 Professional?

Dr. Rhonda Patrick 4:05 Yes.

Andrew Huberman 4:05 Okay.

Dr. Rhonda Patrick 4:05 Yeah. It was, it was... We would compete. So I s- my friend and I started the team when we were in second grade, and it was called the San Diego Sandskippers. It was part of the International Rope Skipping Organization, which was actually started by her uncle. But there's jump rope teams all around the world, and, you know, now I think there's a new name, but, like, it got taken over by the Universal Jump Rope Team or something like that. I don't know exactly what it is. But, um, so I was on a team, and every year we would compete in, in Boulder, Colorado. There was competitions for all kinds of, you know, jumping rope, and, um, I would perform and start jump rope teams around the school-- around different schools in San Diego. So I, I used to get out of school, um, you know, get out of school free card and, uh, my partner and I would go and, and start to, um, do workshops at other schools and help them start jump rope teams and the idea was cardiovascular health, healthy heart, and, uh, yeah. So, so that's really, I, I would say my, my, my roots with, uh, being a competitive athlete.

Andrew Huberman 5:03 Awesome. I love skipping rope. Is it okay to say skipping rope or is jumping rope the-

Dr. Rhonda Patrick 5:07 Yeah. Yeah.

Andrew Huberman 5:07 Okay.

Dr. Rhonda Patrick 5:07 Skipping rope, jumping rope.

Andrew Huberman 5:08 And actually, it's a great opportunity for me to ask you what your thoughts are about, um, exercise that isn't just linear, right? I know, like, real jump ropers can do crossovers and, um, and these days I'm seeing a lot more about rope flow. I think it's David Weck and others online are, you know, stuff that's getting people out of the standard, you know, curls, bench presses, lunges, you know, and getting movements that are more, just for lack of a better term, across the body. Do you think there's something to that in terms of real physical benefits? I mean, I imagine there is.

Dr. Rhonda Patrick 5:39 Sure. I mean, I wouldn't be the expert to be able to give you a good answer on that, but I do think that jumping rope in general has unique benefits.

Andrew Huberman 5:47 Mm-hmm.

Dr. Rhonda Patrick 5:47 In addition to, obviously it's a great cardiovascular exercise. You're getting the weight bearing aspects as well-

Andrew Huberman 5:54 Mm-hmm

Dr. Rhonda Patrick 5:54 ...for building bone density, and I think that earlier for me, you know, I was doing it as a, a young girl, so important, right? 'Cause you're kind of banking that, that bone density early on-

Andrew Huberman 6:03 Yeah

Dr. Rhonda Patrick 6:03 ...which is important 'cause at some point, you know, menopause will hit and, and, uh, estrogen goes down and, and so you start to lose more bone. But, um, yeah, I'm sure there's a lot of benefits to jumping rope beyond what I'm describing as cardiovascular benefits and bone benefits that-Someone else could answer. [laughs]

Andrew Huberman 6:20 Well, I'm certainly gonna get back to jumping rope now that we, you know, resurrected it in this conversation. And I have to say, um, uh, bone density measurements aside, you have awesome posture. I notice people's posture.

Dr. Rhonda Patrick 6:31 Oh, really?

Andrew Huberman 6:32 Yeah. I didn't, didn't mean to put you on the spot here, but yeah, when I walked in, I was like, if you ever interacted with Rhonda in person, which I, I have, you have amazing posture. And these days, good posture is rare. So who knows, maybe the things, uh, uh, are related. I imagine they probably are, uh, bone health and, and posture and so forth. In terms of the

Andrew Huberman 6:49 sorts of exercise that people are more familiar with, what's your routine look like and what sorts of things in your routine are non-negotiables, and where's the place for experimentation and kinda what you're exploring now?

Dr. Rhonda Patrick 7:03 So for me, exercise is part of my personal hygiene, as you and I were discussing.

Andrew Huberman 7:08 Mm-hmm.

Dr. Rhonda Patrick 7:08 It, it really is a non-negotiable.

Andrew Huberman 7:10 Mm-hmm.

Dr. Rhonda Patrick 7:11 I absolutely have to do exercise just like I have to brush my teeth. And, um, you know, I kinda got that from Dr. Ben Levine, who's a, you know, probably one of the world leading cardiovascular exercise physiologists. He's at UT Southwest in Dallas. Just wanna shout out his name because I've really learned a lot from him. But the non-negotiables for me really are getting cardiovascular exercise and getting my, my resistance training, so building muscle, maintaining muscle strength as well. So my routine for me, I, I work out probably about five to six hours a week.

Andrew Huberman 7:46 Mm-hmm.

Dr. Rhonda Patrick 7:46 And those workouts, I largely am doing a combination of high intensity interval training that's not necessarily like the Norwegian 4x4, where I'm going as hard as I can for one min- or four minutes, and then recovering for three minutes and doing that four times. It's really, you know, the Norwegian 4x4 is a hard workout. Um, it's really good for improving your cardiorespiratory fitness, which I think is one of the best markers for longevity, and we can talk about that.

Andrew Huberman 8:10 Mm-hmm.

Dr. Rhonda Patrick 8:11 Um, I do a lot of... You know, it's a, it's a mixture of doing, you know, rowing machine, getting on the assault bike, and then doing, mixing in, mixing it in with lifting weights, doing some deadlifts, you know, doing squats. Um, so it's really for me a non-negotiable to, to do my, my vigorous intensity exercise, is what I would call it. So you're really kind of getting your heart rate up to, you know, 80% max heart rate at, at points. Not always, but especially during the intervals. I would say that's a non-negotiable for me.

Andrew Huberman 8:44 How many days a week are you doing that?

Dr. Rhonda Patrick 8:46 I do my, my longer HIIT workouts... So I have four days a week where I'm doing at least an hour. So two of those, two of those sessions are more of a CrossFit type of training-

Andrew Huberman 8:56 Mm-hmm

Dr. Rhonda Patrick 8:56 ... where I'll do the first 30 minutes will be strength training.

Andrew Huberman 8:58 Mm-hmm.

Dr. Rhonda Patrick 8:59 So I'll just be lifting heavier with, like, you know, fewer reps. And-

Andrew Huberman 9:02 What's the rest between sets? Sorry to get granular, but people-

Dr. Rhonda Patrick 9:05 Um

Andrew Huberman 9:05 ... will wonder.

Dr. Rhonda Patrick 9:05 What's funny is I typically rest about two minutes-

Andrew Huberman 9:08 Okay

Dr. Rhonda Patrick 9:08 ... between my sets.

Andrew Huberman 9:09 Mm-hmm.

Dr. Rhonda Patrick 9:10 I, I, I recover pretty quick.

Andrew Huberman 9:11 Mm-hmm.

Dr. Rhonda Patrick 9:12 Um, and my c- I do it with a coach, and my coach usually tells me that I'm spot on and I'm, like, ready to go, and it's been about two minutes.

Andrew Huberman 9:18 Mm-hmm.

Dr. Rhonda Patrick 9:19 So I, I usually, that's my recovery time.

Andrew Huberman 9:21 Mm-hmm.

Dr. Rhonda Patrick 9:22 And so the first 30 minutes is strength training, and that'll be, like, deadlifts. It'll be, you know, squats. I'll be cleaning. I'll be doing front squats. Sometimes I do the barbell or back squats, right? Like, it's a mixture-

Andrew Huberman 9:31 Mm-hmm

Dr. Rhonda Patrick 9:31 ... of different types of-

Andrew Huberman 9:33 Mm-hmm

Dr. Rhonda Patrick 9:33 ... strength training. And then the last 30 minutes is more of a high intensity interval training sessin- session. So it'll be like, you know, where I'm, I'm getting my heart rate up. So I'm mixing in the row machine. And then I have, like, maybe I'm doing cleans, but they're lighter, right?

Andrew Huberman 9:45 Mm-hmm.

Dr. Rhonda Patrick 9:46 So it's, like, more reps-

Andrew Huberman 9:47 Mm-hmm

Dr. Rhonda Patrick 9:47 ... but lighter load, right?

Andrew Huberman 9:48 Mm-hmm.

Dr. Rhonda Patrick 9:49 So, um, that's, I do that twice a week, and that each is an hour session. And then I do also twice a week about an hour and 20 minutes of... It's also more high intensity, but I have more recovery time 'cause I'm doing it with my girlfriends and we kind of-

Andrew Huberman 10:03 Mm-hmm

Dr. Rhonda Patrick 10:03 ... chitchat a little bit.

Andrew Huberman 10:04 Mm-hmm.

Dr. Rhonda Patrick 10:04 And so, um, but it's a very similar. We do, you know, rowing machine, assault bikes. We do s- the skier. You know, Rowperfect has that skier.

Andrew Huberman 10:12 Mm-hmm.

Dr. Rhonda Patrick 10:12 And then we mix it in with, you know, chest presses, and we do, you know, assisted pull-ups, and we do, you know, lighter squats with, like, larger-

Andrew Huberman 10:21 Mm-hmm

Dr. Rhonda Patrick 10:21 ... you know, more reps.

Andrew Huberman 10:22 Mm-hmm.

Dr. Rhonda Patrick 10:22 So that's another, you know, two hours a week. So I have four hours a week of just doing m- a lot of that sort of CrossFit, HIIT type of training. And then I mix that in with my more, like, runs that I do, which I would say are still, they're still considered vigorous intensity. They're just not quite as high intensity.

Andrew Huberman 10:41 Mm-hmm.

Dr. Rhonda Patrick 10:41 And I, I do probably, I run in, like, maybe six miles a week, so maybe, maybe at, uh, at my max, but these days I'm mostly running probably four, like, four miles a week. So, um, those runs tend to be, like, sometimes they're two miles, sometimes they're three miles.

Andrew Huberman 10:57 Okay.

Dr. Rhonda Patrick 10:57 And, you know-

Andrew Huberman 10:58 Do you enjoy running?

Dr. Rhonda Patrick 10:59 I do.

Andrew Huberman 10:59 Mm-hmm.

Dr. Rhonda Patrick 10:59 I do. And I think it's important as well, and sometimes I'll run with my husband and we just kinda, like, chill out and talk, and-

Andrew Huberman 11:05 Mm-hmm

Dr. Rhonda Patrick 11:06 ... you know, it's, it's a nice time for me as well just to kind of do that with him.

Andrew Huberman 11:10 Mm-hmm.

Dr. Rhonda Patrick 11:11 Um, and then on weekends I'll probably do, like, a hike with my family. And sometimes we'll do, like, a sprint up the hill and, you know, but it's more just enjoyable time in nature, um, still moving, but, you know, it's, it's kinda family time too.

Andrew Huberman 11:27 Weight vests on the run or hike?

Dr. Rhonda Patrick 11:28 No, I don't-

Andrew Huberman 11:29 Yeah.

Dr. Rhonda Patrick 11:29 Not... I mean, I'm kind of wanting to experiment with that-

Andrew Huberman 11:32 Mm-hmm

Dr. Rhonda Patrick 11:32 ... but not really.

Andrew Huberman 11:33 Mm-hmm.

Dr. Rhonda Patrick 11:33 I'm just kind of... Sometimes we bring our puppy and, you know, so it's, it's more about the experience, I think, than, like-

Andrew Huberman 11:39 Mm-hmm

Dr. Rhonda Patrick 11:39 ... I'm like, I get, I get a lot of workout throughout the week.

Andrew Huberman 11:41 Sure.

Dr. Rhonda Patrick 11:42 But it's, like you said, it's non-negotiable for me. And, and times when I'm like s- like today, so, you know, I had a long drive and so I, I got on my Peloton and I did a 10-minute s- you know, I did a 10-minute Tabata back to back. So it was, like, two back to back Tabatas, right? So it was... It ended up being 10 minutes. There's, like, 30-second recovery in between the two Tabata sessions. Two to one ratio, 20 seconds on, 10 seconds off. But, like, I have to do something every day, and if I'm traveling or I have, like, an early podcast or something, I'll, I'll just jump on the bike, and I have to get that blood flow. Sometimes I'm in my hotel room and I don't wanna go to the gym, I don't have time, and I just in my room, you know, I do, I do the air squats, I'll do high knees, jumping jacks, and I then repeat for 10 minutes.

Andrew Huberman 12:23 Mm-hmm.

Dr. Rhonda Patrick 12:23 I'm getting my heart rate up and I'm, you know, I've got sweat on my brow. Like, I'm not--

Andrew Huberman 12:26 Mm-hmm

Dr. Rhonda Patrick 12:26 ... it's not, like, the most intense workout, but it's so important for me.

Dr. Rhonda Patrick 12:30 You know, it... There's, there's a variety of brain benefits that have been shown with even just 10 minutes of this vigorous type of intensity of workout you do, you know, where you're-I mean, you probably have seen this, this data where it's like just 10 minutes of this vigorous type of exercise, you're immediately increasing neuronal connections. Um, th- there's been studies showing that you have an improvement in executive function by like 14%, which is pretty big. I think it was like a fif- 50-millisecond improvement processing speed or something, which doesn't sound a lot, but actually it translates to a big improvement in executive function. So my brain works better, I feel better, you know, better mood. Um, there's even studies that have compared impulse control after various types of intensity of workouts. So like there's one study that compared a more low intensity versus moderate intensity versus high intensity. So you're talking about like walking versus maybe, you know, jogging slowly where you can still have a conversation versus like you're doing a HIIT workout, right?

Andrew Huberman 13:29 Mm-hmm.

Dr. Rhonda Patrick 13:29 You're on. When you're on, you're not really talking 'cause you're going as hard as you can during that interval. And it was the high intensity, you know, vigorous intensity exercise that really increased plasma serotonin, which has been shown to associate with brain serotonin. The studies have been done. And serotonin is very important for, as you know, for impulse control. I mean, a lot of people think about serotonin with respect to mood-

Andrew Huberman 13:51 Mm-hmm

Dr. Rhonda Patrick 13:51 ... because we have these selective serotonin reuptake inhibitors, SSRIs, that are used to treat, you know, depression, major depressive disorder. But serotonin, as you know, does so much more, more than that. And impulse control is one of the, the, the big things that serotonin plays a role in. And so the studies show that plasma serotonin increased in the higher intensity group and that correlated with improved impulse control. So of course, for us now in the modern day society that we live in, we're constantly being bombarded with, you know, social media and all these things and like you have to be able to kind of like filter that out and not like just go with the impulse. Like check my social media, check my, you know, and how many likes did I get or whatever. You need to just be able to focus and so that for me, you know, serotonin is important.

Andrew Huberman 14:36 Mm-hmm.

Dr. Rhonda Patrick 14:36 And so I like to get that vigorous intensity exercise as well.

Andrew Huberman 14:39 I'd

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Andrew Huberman 17:03 I love that you mentioned other, 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, um, the impulse control piece is, I think, is a non-trivial aspect to, uh, the effects of exercise and just generally. I'm curious, do you, um, 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 ch- maybe text here or there if you need to, but are you able to compartmentalize or, um, do you struggle with the, the phone during workouts?

Dr. Rhonda Patrick 17:36 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-

Andrew Huberman 17:42 Mm-hmm

Dr. Rhonda Patrick 17:42 ... that, you know, if there's like an emergency I'll get a text message.

Andrew Huberman 17:45 Mm-hmm.

Dr. Rhonda Patrick 17:45 Oftentimes I put it on silent, like I, on no notifications because I don't want to be bothered. But I don't, I don't really check my phone. Um, I, I, I don't really like checking things like social media. For me it's just a distraction and frankly, I think it's ter- terrible for people's [chuckles] brains even though like my business kind of depends on it somewhat. I think ter- I think social media is not really good for people, to be honest.

Andrew Huberman 18:10 Mm-hmm.

Dr. Rhonda Patrick 18:10 Uh, so I don't really check my phone or bring my phone to my workouts. My workouts are... I like to chat with my friends when I'm working out with them-

Andrew Huberman 18:18 Mm-hmm

Dr. Rhonda Patrick 18:18 ... and that's fun. Yeah.

Andrew Huberman 18:19 That's in real life.

Dr. Rhonda Patrick 18:20 Yes. That's in r-

Andrew Huberman 18:21 IRL as the-

Dr. Rhonda Patrick 18:22 That's in, that's in, yeah [laughs]

Andrew Huberman 18:22 ... as the kids say.

Dr. Rhonda Patrick 18:24 That's in real life.

Andrew Huberman 18:25 Mm-hmm.

Dr. Rhonda Patrick 18:25 And, um, yeah, phones, phones for me are not something that I bring to my workout.

Andrew Huberman 18:30 Great. Yeah. I've, um, 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, um, sounds like you were already there and I'm just arriving. So

Andrew Huberman 18:45 I have a couple other specific questions about your workouts because, uh, for my own interest, and I know many people will wonder, for the dedicated weight workoutsAre these whole body workouts? And you said low reps. Uh, maybe you could just tell us what low reps is for you, and then the, uh, seems like the, the ever-present question is to failure, close to failure? I mean, um, just to, you know, round out that, that portion of the, of the workout picture.

Dr. Rhonda Patrick 19:08 The workouts that I'm doing with my strength training workouts with my coach, you know, it, it really depends. Most of those workouts are... They're, they're 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 lake- the weight goes down if I'm doing-- if I'm cleaning it, 'cause it's hard to clean.

Andrew Huberman 19:31 Mm-hmm.

Dr. Rhonda Patrick 19:31 It's also the har- Like, it's the thing that I hate doing the most. [laughs]

Andrew Huberman 19:35 Cleans.

Dr. Rhonda Patrick 19:35 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 cleans since, you know, February twenty twenty-four. 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 like-- I used to like to go long runs and, you know, races and stuff like that, so for me that's like my safe spot, right? That's what comes easy to me. Uh, weight training and resistance training, strength training, definitely not something that I've done my whole life. 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.

Andrew Huberman 20:27 Mm-hmm.

Dr. Rhonda Patrick 20:27 Where it was, like, unbelievable 'cause it was so hard, and I, I just didn't wanna do these cleans, you know, and, and, and these front squats. Um, 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, um, I do a variety of, um... 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. Right.

Andrew Huberman 20:55 Oh, you're doing singles?

Dr. Rhonda Patrick 20:56 We do. Mm-hmm.

Andrew Huberman 20:57 Okay.

Dr. Rhonda Patrick 20:57 I kn- Yeah. Yeah.

Andrew Huberman 20:58 Awesome.

Dr. Rhonda Patrick 20:58 And that's the hardest.

Andrew Huberman 20:59 Mm-hmm.

Dr. Rhonda Patrick 20:59 It's the hardest. But then there's, there's, like, my coach be like, "It's just one. It's just one." You know, sometimes we'll do like six, five, and then we do four twice-

Andrew Huberman 21:08 Mm-hmm

Dr. Rhonda Patrick 21:08 ... and then we do three twice, right?

Andrew Huberman 21:09 Mm-hmm.

Dr. Rhonda Patrick 21:09 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? Where I'm just like, it's, "This is the day for me. I, I'm, I'm stressed. I'm not, I'm not here." Like...

Andrew Huberman 21:25 Right.

Dr. Rhonda Patrick 21:25 So you kind of have to modify your workout, right? According to how you feel that day. Um, but I would say that those, the majority of my strength training workouts are, are deadlifting. You know, I love deadli- deadlifting. I think I'm pretty good at, at pulling that weight up, lifting that weight up.

Andrew Huberman 21:41 It's a straight bar, hex bar-

Dr. Rhonda Patrick 21:42 I do straight bar

Andrew Huberman 21:43 ... mixed grip. There's so many variables, but yeah.

Dr. Rhonda Patrick 21:44 Straight bar.

Andrew Huberman 21:45 Yeah.

Dr. Rhonda Patrick 21:45 Straight bar.

Andrew Huberman 21:46 All right.

Dr. Rhonda Patrick 21:46 And, um, th- it's the same deal with that. 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'll, 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?

Andrew Huberman 22:03 Mm-hmm.

Dr. Rhonda Patrick 22:03 So those, those are typically my strength training sessions are multi-joint. Sometimes I'll do accessory set, sessions, you know-

Andrew Huberman 22:09 Mm-hmm

Dr. Rhonda Patrick 22:09 ... where I'm working. I do, you know, the dips-

Andrew Huberman 22:13 Mm-hmm

Dr. Rhonda Patrick 22:13 ... um, or the Bulgarian, you know, the Bulgarian split squats. I mean, just the accessory stuff-

Andrew Huberman 22:20 Mm

Dr. Rhonda Patrick 22:20 ... that you're working the, like, smaller stabilization muscles and stuff like that.

Andrew Huberman 22:23 I love that you call Bulgarian split squats, uh, accessory smaller muscles.

Dr. Rhonda Patrick 22:27 [laughs]

Andrew Huberman 22:27 For a lot of people, that's the compound work. Which is just, I have to say, I, I am, inside I'm just, like, so delighted because, I mean, obviously, uh, 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, uh, working down to singles on multi-joint, like real mul- multi-joint. Like, you know, deadlifts, cleans. I know they're out there, but it's not that common to see in gyms. And, uh, this is going to n- uh, 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, um, pass 35, that they shouldn't do squats, that they shouldn't do deadlifts and certainly shouldn't do them heavy because it i- 'cause of this whole thing of, you know, you can do higher reps and you go to failure and still get hypertrophy. 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.

Dr. Rhonda Patrick 23:30 Yeah.

Andrew Huberman 23:30 And triples and doubles and singles, that's awesome.

Dr. Rhonda Patrick 23:34 It's-

Andrew Huberman 23:34 Yeah

Dr. Rhonda Patrick 23:34 ... hard.

Andrew Huberman 23:35 That's awesome.

Dr. Rhonda Patrick 23:35 It's so hard.

Andrew Huberman 23:36 Mm-hmm.

Dr. Rhonda Patrick 23:36 And it's the part that I, I'm like all about let's, like the last 30 minutes wherein it's hit and then that's hard. It's a different kind of hard.

Andrew Huberman 23:43 Mm-hmm.

Dr. Rhonda Patrick 23:44 But for me, the strength training is the hardest and there's definitely a mental component, right?

Andrew Huberman 23:48 Yeah.

Dr. Rhonda Patrick 23:48 Where I do not wanna do it. It's like you talk about with cold plunging, right? Like you-

Andrew Huberman 23:53 Mm-hmm

Dr. Rhonda Patrick 23:53 ... you just, it's so unpleasant and you don't wanna do it, and like you do it and it's like that mental toughness that you're building, right? I-- that's what I experience when I'm doing these, you know, strength training exercises that I'm doing.

Andrew Huberman 24:05 Mm-hmm.

Dr. Rhonda Patrick 24:06 And, and I don't know if it's gonna get easier. Maybe it will. It's hasn't yet. [laughs] I still, I still dread it, but I do it and, uh, I'm proud of myself for doing it, but it is, it's definitely hard and I am getting stronger, I think mentally and obviously physically as well. But, um, have to add in the aerobic as well, though. I think that's really important. It's nice not all-

Andrew Huberman 24:26 That's your base. Yeah.

Dr. Rhonda Patrick 24:28 Y- yeah.

Andrew Huberman 24:28 That's your... You love it.

Dr. Rhonda Patrick 24:29 I love it-

Andrew Huberman 24:30 Yeah

Dr. Rhonda Patrick 24:30 ... and I do think cardiorespiratory fitness is very important-

Andrew Huberman 24:32 Mm-hmm. Sure

Dr. Rhonda Patrick 24:32 ... you know, for, for long-term health as well as, you know, obviously building muscle and strength.

Andrew Huberman 24:36 Mm-hmm. 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'tBecause of this literature, I'm sure you're familiar with it, but, uh, the anterior midcingulate cortex, this brain area that is hyperplastic throughout the lifespan, which is rare for a brain area, and it enlarges, um, when we do things we don't want to do. I mean, it, it's so clear it's not just about doing hard things, about... it's about doing the hard thing you hate.

Dr. Rhonda Patrick 25:05 [laughs]

Andrew Huberman 25:05 [laughs] And, and for you, that sounds like the, 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. I just think it's a sh- it's a surefire stimulus that I hate to ma- get mentally stronger. And I think, um, having something that you really despise, that you know is good for you, seems to keep this anterior midcingulate cortex volume either increasing or the same, and that's actually the, 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, uh, easier-

Dr. Rhonda Patrick 25:40 Well-

Andrew Huberman 25:40 ... 'cause it's still... it's gonna be so much more beneficial.

Dr. Rhonda Patrick 25:42 I have a coach-

Andrew Huberman 25:43 Mm-hmm

Dr. Rhonda Patrick 25:43 ... who can tell when it's getting easier, and she will definitely up the weight.

Andrew Huberman 25:49 Mm-hmm.

Dr. Rhonda Patrick 25:49 I, I, I mean, it keeps-

Andrew Huberman 25:50 Yeah

Dr. Rhonda Patrick 25:51 ... I mean, it keeps going up, and so it doesn't-

Andrew Huberman 25:53 Mm.

Dr. Rhonda Patrick 25:53 It, it gets easier in a sense, but it doesn't, right?

Andrew Huberman 25:55 Mm.

Dr. Rhonda Patrick 25:56 So I mean, I, I think that's, that's the whole point is you're building strength, and you keep making it heavier, and it-

Andrew Huberman 26:02 Mm

Dr. Rhonda Patrick 26:02 ... becomes harder again because now it's heavier.

Andrew Huberman 26:04 Awesome.

Dr. Rhonda Patrick 26:04 But, um... And I haven't gotten injured, so that's also, you know, knock on wood. [laughs]

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

Dr. Rhonda Patrick 26:16 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. [laughs]

Andrew Huberman 26:26 Well, and the fact that you're working down into triples, doubles, and singles I think is, um, something that I'm trying to do more of. And I think, um, this notion that you can get hypertrophy with higher reps if you take it to failure, sure, I, I totally agree. Read the studies, totally agree with the data, but not everything is about hypertrophy.

Dr. Rhonda Patrick 26:42 Mm.

Andrew Huberman 26:42 I think that's what people forget. It's not all about growing muscle. [laughs] Um, and VO2 max, which is great, but it's just, it's not all about, um, the top contour. And I... What I love about the way you approach everything is you're, you go through multiple layers of, of the, the health stratus, as it were. This

Andrew Huberman 27:00 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.

Dr. Rhonda Patrick 27:19 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-

Andrew Huberman 27:36 Mm

Dr. Rhonda Patrick 27:36 ... 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, been doing more intermittent fasting, and what I mean by that is just really just eating less. And, um, the reason for that is because I noticed that everything that I was doing, which was, you know... I mean, I eat healthy, I exercise a lot, and yet I was sort of gaining more fat in the, the belly section, right, the visceral fat. And the only thing that really helped me stop that, put the, put the brakes on, was c- getting more in a caloric deficit. Um, 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, which for me-

Andrew Huberman 28:36 Per kilogram, okay

Dr. Rhonda Patrick 28:36 ... per kilogram, which is probably a little bit less than the pound.

Andrew Huberman 28:39 Mm-hmm. You know, it's, it's a kind of a throwaway, uh-

Dr. Rhonda Patrick 28:42 A gram per-

Andrew Huberman 28:42 ... statement. A gram-

Dr. Rhonda Patrick 28:43 ... per pound

Andrew Huberman 28:43 ... of quality protein, um, as defined as something with, you know, lots of the essential amino acids and, uh, uh, so forth, uh, per pound or per lean pound of body mass. Um-

Dr. Rhonda Patrick 28:56 Yeah. So-

Andrew Huberman 28:57 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.

Dr. Rhonda Patrick 29:04 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-

Andrew Huberman 29:10 Mm

Dr. Rhonda Patrick 29:10 ... 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 gaining, gaining more weight because I think-

Andrew Huberman 29:20 Mm

Dr. Rhonda Patrick 29:20 ... I was consuming more calories at the same time.

Andrew Huberman 29:22 Mm.

Dr. Rhonda Patrick 29:22 If s- if, if you're getting it from whole foods, right, like, that's just kind of naturally gonna happen. Uh, and so I had to slide down. Um, but I'm still, 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, and it's really, it's really worked well for me. But, like, people are different, and you have different goals-

Andrew Huberman 29:44 Mm

Dr. Rhonda Patrick 29:44 ... 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.

Andrew Huberman 29:58 Mm.

Dr. Rhonda Patrick 29:58 And as you mentioned, if you're training, perhaps your appetite for protein will increase, and so you'll start to eat, you know, more protein and less refined carbohydrates. I already wasn't eating a lot of refined, ultra-processed foods in the first place.

Andrew Huberman 30:11 Mm.

Dr. Rhonda Patrick 30:12 Probably not the answer [laughs] you were expecting, but it's, it's really, uh, for me, like, I, I just... Focusing on getting more protein was, was not working for my body, um, in terms of... But then again, I'm 47 years old. You know, that perimenopause phase, very different than someone who's 37 maybe.

Andrew Huberman 30:31 I don't know the answer to that. I, I, um, 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.

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

Andrew Huberman 30:45 Exactly. So I'm actually really pleased with your answer, uh, not because I have an agenda here, but because I-I and many other people seem to feel like unless there's a lot of resistance training or tremendous demands like hiking, you know, while backpacking, where if you burn tons of calories, you're carrying... You're basically rocking like nine hours a day, right?

Dr. Rhonda Patrick 31:04 Right.

Andrew Huberman 31:04 That, um, they have a hard time getting that much protein down. Um, 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, you know, it sounds like you eat starches, right?

Dr. Rhonda Patrick 31:18 I do eat oatmeal too.

Andrew Huberman 31:19 Mm-hmm.

Dr. Rhonda Patrick 31:19 It does satiate you.

Andrew Huberman 31:20 Mm-hmm.

Dr. Rhonda Patrick 31:21 These days, because I really kind of more focused a little bit on... I, I did want to, to calorically restrict somewhat without, you know, being unhealthy. Obviously, you can take every stressor to a-

Andrew Huberman 31:33 Mm

Dr. Rhonda Patrick 31:33 ... bad, unhealthy place, right? You don't want to starve yourself. You don't want to, like, not eat enough food. But, um, my, my meals are mostly, like, healthy protein. So I have homemade turkey burgers. Eat a lot of... I eat a lot of those. And then I eat chicken. You know, I... Pasture-raised chicken. I do, I do still eat wild Alaskan salmon, and then I'll, um, also mix in some, like, filet mignon. Like, I like grass-fed steak as well.

Andrew Huberman 31:58 Yum.

Dr. Rhonda Patrick 31:59 Those are my protein sources.

Andrew Huberman 32:00 Mm-hmm.

Dr. Rhonda Patrick 32:00 And always I pair it with greens.

Andrew Huberman 32:03 Ooh.

Dr. Rhonda Patrick 32:04 So... Or like some sort of vegetable. Most of the times it's, it's greens 'cause they're the most, most micronutrient dense. And so these days I'm eating a lot of sautéed collard greens that are, like, pre-prepared, has garlic and onion, and I'll put that... You know, I'll have that with my meal, or I'll have some, you know, sautéed kale. Sometimes I'll have a salad with it. But the portions are smaller, and like I said, I, 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. Sometimes I'll eat the high protein oats. They have those high protein oats.

Andrew Huberman 32:37 Mm.

Dr. Rhonda Patrick 32:38 That... Have you, have you seen those?

Andrew Huberman 32:39 No.

Dr. Rhonda Patrick 32:39 They're pretty good.

Andrew Huberman 32:39 I eat oatmeal, but I, I like protein foods. I like vegetables. I like fruit. I feel very lucky to like those foods mainly.

Dr. Rhonda Patrick 32:45 Yeah.

Andrew Huberman 32:46 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-

Dr. Rhonda Patrick 32:54 Yeah

Andrew Huberman 32:54 ... 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, and I just feel lousy. Get kind of sleepy afterwards. There's... So I... Uh, so it sounds like we eat pretty similarly, although I probably eat more starches than you do.

Dr. Rhonda Patrick 33:09 It's the more processed types-

Andrew Huberman 33:11 Mm

Dr. Rhonda Patrick 33:11 ... of carbohydrates-

Andrew Huberman 33:12 Mm

Dr. Rhonda Patrick 33:12 ... that, as you mentioned, it's like you typically, you don't feel good after you eat them.

Andrew Huberman 33:16 Mm-hmm.

Dr. Rhonda Patrick 33:16 And, you know, part of that's the postprandial inflammatory response-

Andrew Huberman 33:19 Yeah

Dr. Rhonda Patrick 33:19 ... 'cause some of those foods are a little more inflammatory.

Andrew Huberman 33:21 Mm.

Dr. Rhonda Patrick 33:21 I mean, a lot of additives and stuff that are affecting the gut, gut permeabilization. You're leaking lipopolysaccharide into the bloodstream, right?

Andrew Huberman 33:28 Yikes.

Dr. Rhonda Patrick 33:28 That's activating the immune system.

Andrew Huberman 33:30 We used to inject...

Andrew Huberman 33:32 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, um, 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, um, hearing that some starches will stimulate LPS, that's, uh, interesting. And it-

Dr. Rhonda Patrick 34:01 Well, let me clarify

Andrew Huberman 34:02 ... squares with my experience.

Dr. Rhonda Patrick 34:02 Let me clarify. [laughs]

Andrew Huberman 34:03 I'm not challenging. No, no, no. I'm, 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. [laughs] But if I eat certain starches, I'll be like, "Ugh," like I feel lousy, and I'm wondering if it's this.

Dr. Rhonda Patrick 34:17 So we have about a gram of LPS in our gut.

Andrew Huberman 34:19 Mm-hmm. Sure.

Dr. Rhonda Patrick 34:19 Like, that's on average, 'cause, you know, l- lipopolysaccharide is the outer component of a cell membrane of-

Andrew Huberman 34:24 Mm-hmm

Dr. Rhonda Patrick 34:25 ... gram-negative bacteria, right?

Andrew Huberman 34:26 A yeast. Yeah.

Dr. Rhonda Patrick 34:27 We have a lot of bacteria in our gut.

Andrew Huberman 34:28 Yeah. Mm-hmm.

Dr. Rhonda Patrick 34:28 Gram-negative bacteria, right?

Andrew Huberman 34:29 Yeah.

Dr. Rhonda Patrick 34:29 Trillions of bacteria in our gut.

Andrew Huberman 34:31 Sure.

Dr. Rhonda Patrick 34:31 So, um, when, when we eat food, typically, like, our gut epithelial cells, they ha- 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?

Andrew Huberman 34:44 Yeah.

Dr. Rhonda Patrick 34:44 Um, the, the... I would say the opposite end of the spectrum of that would be, like, celiac, where-

Andrew Huberman 34:49 Mm

Dr. Rhonda Patrick 34:49 ... they eat gluten or something. 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-

Andrew Huberman 35:02 Mm

Dr. Rhonda Patrick 35:02 ... LPS response from a meal.

Andrew Huberman 35:03 Mm-hmm.

Dr. Rhonda Patrick 35:04 Now, the type of meal does matter, so when I, when I say refined carbohydrates, it's not necessarily, like, healthy, you know, car- 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, it's, it's inflammation. It's bad.

Andrew Huberman 35:25 Mm.

Dr. Rhonda Patrick 35:25 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. I mean, it's like, it's very energy consuming-

Andrew Huberman 35:38 What?

Dr. Rhonda Patrick 35:38 ... to activate your immune system, right? Which is why... That's why when you're sick, you're so sleepy too, right?

Andrew Huberman 35:42 Mm-hmm.

Dr. Rhonda Patrick 35:42 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.

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

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

Andrew Huberman 36:29 Got it

Dr. Rhonda Patrick 36:30 ... that's been shown. [laughs]

Andrew Huberman 36:31 My niece, when she was little... Now she's all grown up, but when she was little, I, uh, 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, we'd

36:42 We do that. Um, we won't do that anymore.

Dr. Rhonda Patrick 36:45 I mean, a little bit's fine.

Andrew Huberman 36:46 Yeah.

Dr. Rhonda Patrick 36:46 But like I'm, I mean-

Andrew Huberman 36:47 So good

Dr. Rhonda Patrick 36:47 ... there's, there's studies showing that it does... Like saturated fat is hard on the gut.

Andrew Huberman 36:50 Yeah.

Dr. Rhonda Patrick 36:51 Like I said, it's a sliding scale. Like meals in general do it, but it's like you would... It's, it's like you would think.

Andrew Huberman 36:55 Mm-hmm.

Dr. Rhonda Patrick 36:56 The healthier foods that you're eating, like whole foods, you're getting less of that-

Andrew Huberman 36:59 Mm-hmm

Dr. Rhonda Patrick 36:59 ... LPS response. And then of course there's gluten, and that complicates the whole story, especially for people that are celiac, right? 'Cause that's, that's-

Andrew Huberman 37:06 Which is a small percentage-

Dr. Rhonda Patrick 37:08 It is

Andrew Huberman 37:08 ... of people are actually celiac.

Dr. Rhonda Patrick 37:09 Yeah.

Andrew Huberman 37:09 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.

Dr. Rhonda Patrick 37:16 I'm sure there's some people that are sensitive to gluten that do feel worse.

Andrew Huberman 37:19 Mm-hmm. Mm-hmm.

Dr. Rhonda Patrick 37:20 And then I'm sure some of that's the nocebo effect, right?

Andrew Huberman 37:22 Mm-hmm.

Dr. Rhonda Patrick 37:22 That's been shown with gluten in, in particular. Did you... Have you seen that study where people... There's been... So, so there were people that think they're, you know, glu- gluten sensitive.

Andrew Huberman 37:33 Mm-hmm.

Dr. Rhonda Patrick 37:34 And so they were en- enrolled in this study, and, um, these individuals were separated into two groups. One group was getting, 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 res- 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.

Andrew Huberman 37:58 Mm-hmm.

Dr. Rhonda Patrick 37:59 So it was thought that there's a nocebo effect where it's like the opposite of a placebo effect-

Andrew Huberman 38:03 Mm-hmm

Dr. Rhonda Patrick 38:03 ... where you just, you're, you, you're, you've got that phenotype where you think things negative are gonna happen-

Andrew Huberman 38:08 Mm-hmm

Dr. Rhonda Patrick 38:08 ... 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-

Andrew Huberman 38:16 Mm-hmm

Dr. Rhonda Patrick 38:16 ... with that regard.

Andrew Huberman 38:17 Mm-hmm.

Dr. Rhonda Patrick 38:17 In addition to like the, the lethargy, so we're ta- 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, and I do think that is part of that reason for feeling sleepy.

Andrew Huberman 38:29 Mm-hmm.

Dr. Rhonda Patrick 38:29 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-

Andrew Huberman 38:57 Yeah

Dr. Rhonda Patrick 38:57 ... up to a 50% increase-

Andrew Huberman 38:58 Ooh

Dr. Rhonda Patrick 38:59 ... o- over baseline, right?

Andrew Huberman 39:00 Mm-hmm. Mm-hmm.

Dr. Rhonda Patrick 39:00 So high amounts of inflammation, which makes sense. LPS is activating the immune-

Andrew Huberman 39:03 Sure. Sure

Dr. Rhonda Patrick 39:03 ... 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-

Andrew Huberman 39:08 Mm-hmm

Dr. Rhonda Patrick 39:08 ... 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.

Andrew Huberman 39:27 Mm-hmm.

Dr. Rhonda Patrick 39:28 Not in all cases, but there's a subset, right, 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 is 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, um, 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?

Andrew Huberman 39:59 Mm-hmm.

Dr. Rhonda Patrick 39:59 Um, interesting. So, so the LPS is affecting not only our, our energy levels, but also our mood.

Andrew Huberman 40:06 Mm-hmm.

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

Andrew Huberman 40:41 Yeah.

Dr. Rhonda Patrick 40:41 And so it actually binds to LDL particles on the ApoB protein. So ApoB is a protein that is on these lipoproteins, and it's a, a very important protein because that is what's used by the LDL receptors present on our liver to recycle LDL particles. And so what happens is these, these LPS particles are now bound to, you know, our, our lipoproteins, and our lipoproteins are still doing their function, right? They're going around and they're, they're, they're giving, you know, triglycerides and, and, you know, fatty acids and s- to some degree cholesterol to our cells that need it, right? We're constantly making new cells and repairing, and we, 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?

Andrew Huberman 41:28 Mm-hmm.

Dr. Rhonda Patrick 41:28 Like that's a very dangerous type of LDL particle, and that's one that's kind of been donating along, getting rid of trig- triglycerides and, um, whatever. If you think about a train with cargo, it's donating the, you know, dropping off the cargo. And so, um, when it's time to get recycled back into the liver, what do you know? The ApoB protein's 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? Comes and chews it up, right? Gets rid of the problem. So macrophages come in 'cause 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-

Andrew Huberman 42:17 I see

Dr. Rhonda Patrick 42:17 ... that came from the gut.

Andrew Huberman 42:18 Mm-hmm.

Dr. Rhonda Patrick 42:18 Tries to engulf it, but it can't 'cause it's not bacteria.

Andrew Huberman 42:21 Mm-hmm.

Dr. Rhonda Patrick 42:21 And you get the macrophage stuck to that lipoprotein LPS, you know, complex, and you get the formation of a foam cell. You probably heard of a foam cell.

Andrew Huberman 42:30 Mm-hmm. Mm-hmm.

Dr. Rhonda Patrick 42:31 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? Gut permeability, getting that LPS into our circulation's actually not a very good thing because you're, you're basically re-You know, dr- slow dripping in that infla-inflammation, that inflammatory signal, and it's wreaking havoc in our arteries, on our brain

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Andrew Huberman 44:21 Thank you for explaining that so clearly 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 it, uh, 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, with the brain and other organs that is critically dependent on the, uh, some threshold level of, of, of LPS. Um, thank you also for reminding us that LPS is present in the gut because we have yeast in our gut, some amount of, of yeast. You mentioned tight junctions, and the way I think about tight junctions, please correct me because I'm gonna get some or all of this wrong, is that essentially, uh, they form a, like a, a cellular 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 into the bloodstream. So now we're 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, at the brain level.

Dr. Rhonda Patrick 45:34 It's LPS, which is like the outer component of bacteria that have died.

Andrew Huberman 45:39 Mm-hmm. Mm-hmm.

Dr. Rhonda Patrick 45:40 Um, 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 gl-glial, glial cells and stuff in the, in the brain, um, 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 of 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. So, um, it's the inflammation, I think, that's really, um, it's, it's really powerful in terms of it's, it's a driver of the aging process in general. Like this inflammation, inflammaging, you've heard, you've heard of inflammaging. You know, I think, 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 y- 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, a component of it, but there's other things as well, right? I mean, you can have stress, um, cr- you know, any emotional stress, like that can lead to inflammation, um, s- not getting enough sleep, right? There's a lot of things that can, that can lead to inflammation. And, um, so it is kind of an important point to think about is, is really like trying to have your inflammation low, right? And how do you do that?

Andrew Huberman 47:25 I'm gonna

Andrew Huberman 47:26 take three different jumping-off points here, all related to what you said. So, um, don't think I'm a random, uh, 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, um, been interested in, uh, L-glutamine as a way to reinforce tight junctions in the gut.

Dr. Rhonda Patrick 47:50 Mm-hmm.

Andrew Huberman 47:50 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, and indeed, I didn't get sick as much as the imaginary control experiment that I never got to do [chuckles] . Meaning, I don't know if it helped or not, but I continue to take, uh, L-glutamine, uh, when I'm feeling run down. 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, uh, reinforcing the immune system?

Dr. Rhonda Patrick 48:25 There's not a ton of evidence in terms of like what's in the scientific literature supporting these statements, but there is some.

Andrew Huberman 48:32 Mm-hmm.

Dr. Rhonda Patrick 48:33 You know, and it's enough to kind of go, "Well, I'm gonna try to maybe experiment with it." So, you know, I first became interested in, 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, okay, 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. Um, and, and so glutamine can be converted into many things. So glutamine can be an amino acid, right? It's amino acid. Glutamine can be converted into the, um, i- 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, um, became interested in, in that because it was like, oh, glutamine's important for the survival of these cancer cells. Um, then I was doing a lot of activating immune cell studies as, you know, ob- uh, my, my graduate advisor, uh, is an im-immunologist by training, and so I was also doing that. 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 Shigenaga, 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. 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-

Andrew Huberman 50:25 Mm-hmm

Dr. Rhonda Patrick 50:25 ... for the gut. Now, these are all animal studies, right? So take it with a grain of salt, right? Like, 'cause at some point, you know... In my, in my opinion, animal studies are, are k- 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, um, not necessarily... I mean, with the gut health, it's, it's, you know, it's sparse-

Andrew Huberman 50:54 Mm-hmm

Dr. Rhonda Patrick 50:54 ... with humans. Um, I found more compelling with respect to glutamine in 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-

Andrew Huberman 51:17 Yeah

Dr. Rhonda Patrick 51:17 ... for a marathon, right?

Andrew Huberman 51:18 Yeah.

Dr. Rhonda Patrick 51:18 And so they're really, like, th- they're putting a lot of demand, right, energetic expenditures happening at a really high rate. So, um, they're, they're more prone to respiratory infections, 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-

Andrew Huberman 51:39 Interesting

Dr. Rhonda Patrick 51:39 ... compared to the ones that weren't doing it. And then I went back to my, "Oh, I know that glutamine's really important for T cell activation," and I was like, "I'm gonna take this," because being, being a, being a mom and having a child that's, it, bringing everything home like a vector, you know, you're, like, desperate. So-

Andrew Huberman 51:54 You're the experiment.

Dr. Rhonda Patrick 51:55 Yeah, exactly. And, and I never used to get sick, ever.

Andrew Huberman 51:58 Yeah.

Dr. Rhonda Patrick 51:58 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?" Like, I, I literally was, like, worried.

Andrew Huberman 52:05 Mm-hmm.

Dr. Rhonda Patrick 52:05 Um, and, 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.

Andrew Huberman 52:20 All at once? 'Cause it can be a little-

Dr. Rhonda Patrick 52:21 No

Andrew Huberman 52:21 ... hard on the gut.

Dr. Rhonda Patrick 52:22 No.

Andrew Huberman 52:22 Right?

Dr. Rhonda Patrick 52:22 Not all at once.

Andrew Huberman 52:23 Yeah.

Dr. Rhonda Patrick 52:23 Not all at once. I usually do it, like, in fives.

Andrew Huberman 52:25 Mm-hmm.

Dr. Rhonda Patrick 52:26 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.

Andrew Huberman 52:35 Mm-hmm.

Dr. Rhonda Patrick 52:35 But, like, I really don't get sick. I'm not getting sick, and even, 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-OKAY with that, because-

Andrew Huberman 52:45 Mm-hmm

Dr. Rhonda Patrick 52:45 ... placebo effect is real-

Andrew Huberman 52:46 Mm

Dr. Rhonda Patrick 52:46 ... as long as I'm not getting sick. Um, 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, it's overwhelming, and with confidence that it's improving gut health and it's improving immune... You know, it's gonna 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. Um, perhaps maybe if someone has colon cancer, that would be more of a concern, 'cause 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. 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-

Andrew Huberman 53:30 It's an abnormal growth.

Dr. Rhonda Patrick 53:31 Any-

Andrew Huberman 53:31 So anything that's associated with growth.

Dr. Rhonda Patrick 53:32 Yeah, it's proliferating.

Andrew Huberman 53:32 MTOR. I saw the recent study on taurine, which scared a lot of people-

Dr. Rhonda Patrick 53:36 Mm-hmm

Andrew Huberman 53:36 ... 'cause taurine's in a lot of energy drinks.

Dr. Rhonda Patrick 53:38 Mm-hmm.

Andrew Huberman 53:38 But that was an in vitro study. Um, yes, I was going to ask, you know, um, is, is there increased cancer risk if you're supplementing with glutamine because cancer cells love-

Dr. Rhonda Patrick 53:47 Okay

Andrew Huberman 53:47 ... glutamine?

Dr. Rhonda Patrick 53:48 So my personal opinion, I'm obviously not a-

Andrew Huberman 53:51 Yeah

Dr. Rhonda Patrick 53:51 ... medical physician. This is not a prescription. It's just my opinion. I, I personally am not scared of getting cancer from taking glutamine. If I had a colon tumor, i- a tumor in my colon, the, the first site that the glutamine is seeing, maybe the liver as well, since that's also-

Andrew Huberman 54:07 Mm

Dr. Rhonda Patrick 54:07 ... the next step. But, uh, barring, like, having a tumor already in my liver or in my colon-

Andrew Huberman 54:14 Mm

Dr. Rhonda Patrick 54:14 ... those would be the only, you know, types of situations that I would be worried about taking glutamine. I don't think it's gonna cause cancer.

Andrew Huberman 54:20 Mm-hmm.

Dr. Rhonda Patrick 54:20 Right? Now, I guess the question is, like, what if you don't know you have [laughs] it?

Andrew Huberman 54:23 Well, hopefully the cost will come down on whole body MRIs. Actually, the cost is coming down on whole body MRIs. 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, like panels of blood testing, you only got them if you really needed them. Now the cost of blood draws is really-

Dr. Rhonda Patrick 54:40 Right

Andrew Huberman 54:41 ... low.

Dr. Rhonda Patrick 54:41 Right.

Andrew Huberman 54:41 So hopefully-

Dr. Rhonda Patrick 54:42 Yeah

Andrew Huberman 54:42 ... uh, people will be more aware. Yeah, I, 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.

Dr. Rhonda Patrick 54:54 Yes.

Andrew Huberman 54:54 Before we

Andrew Huberman 54:55 went on mic, we were talking about NAC, N-acetylcysteine. Um-I take it once a day, uh, consistently, but I'll take it three times a day if I'm traveling a lot and, because I'm around sick people when I travel, especially in winter, um, or if I feel like I'm getting run down. And there, the data are pretty interesting. There's at least one study, uh, showing that it reduced flu transmission, um, where people were deliberately exposed to flu. I think it took the number of people that contracted flu compared to the placebo group somewhere from the high 70% area, um, don't remember the exact number now, we'll put a link to the study, down to maybe high 20s.

Dr. Rhonda Patrick 55:30 Yeah.

Andrew Huberman 55:30 Which is pretty impressive. And an ER doc came on this podcast, uh, Roger Seheult, who, um, and said he was a big proponent of, of, uh, N-acetylcysteine for people that are around sick people.

Dr. Rhonda Patrick 55:41 Mm-hmm.

Andrew Huberman 55:41 Do you take NAC?

Dr. Rhonda Patrick 55:42 Uh, so my only concern with taking it on a daily basis is it is a pretty powerful antioxidant.

Andrew Huberman 55:48 Mm-hmm.

Dr. Rhonda Patrick 55:49 And, you know, I think that we need to understand, like, antioxidants and the opposite, which would be generating oxidation, right?

Andrew Huberman 55:59 Mm-hmm.

Dr. Rhonda Patrick 56:00 Like, it's not, it's not like oxidation is bad. It's bad when it's constant slow drip oxidation-

Andrew Huberman 56:06 Mm-hmm

Dr. Rhonda Patrick 56:06 ... that's damaging, you know, other parts of our body, DNA, proteins, lipids. Some oxidation you want, like if you're exercising, right?

Andrew Huberman 56:13 Sure.

Dr. Rhonda Patrick 56:14 There's a burst of oxidation.

Andrew Huberman 56:15 To get the adaptation.

Dr. Rhonda Patrick 56:16 To get the adaptations.

Andrew Huberman 56:17 Mm-hmm.

Dr. Rhonda Patrick 56:17 And so my concern would be, for one, maybe timing it around your exercise-

Andrew Huberman 56:21 Mm-hmm

Dr. Rhonda Patrick 56:21 ... so not taking it close to when you're exercising. And these studies come out of, you know, 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.

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

Dr. Rhonda Patrick 57:01 The SELECT trial was done.

Andrew Huberman 57:03 Yeah. Mm-hmm.

Dr. Rhonda Patrick 57:03 So the SELECT trial was, um, was looking at selenium and vitamin E and if it could slow the progression of prostate cancer, and it turned out that, um, the opposite was found, and it was really kind of due to this high dose of alpha-tocopherol, which also has other effects of, um, 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?

Andrew Huberman 57:30 Mm-hmm.

Dr. Rhonda Patrick 57:31 So anyways, um, the point here is that with NAC, my only concern would be y- you know, blunting the, the oxidation that you're getting from beneficial... 'Cause I know you're highly active.

Andrew Huberman 57:43 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, um, illnesses around me, or I feel like maybe I'm coming down with something.

Dr. Rhonda Patrick 57:53 So that's when I, that's when I take it, but it's mostly because of... I wasn't f- familiar with the flu, influenza data. That's interesting. I was just, it's good for lung health too.

Andrew Huberman 58:02 Mm-hmm.

Dr. Rhonda Patrick 58:03 Like, so although if smokers take it, I think it has the opposite effect where, again, it's like the can- the, the pre-cancerous 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.

Andrew Huberman 58:15 Mm-hmm.

Dr. Rhonda Patrick 58:15 And it turns out it's not the case, right? Like, 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?

Andrew Huberman 58:33 Mm-hmm.

Dr. Rhonda Patrick 58:33 And so that's kind of... And 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, you know, you're, you're, again, you're, you're causing these, 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 a, uh, is like the opposite of that. So it's like too much of the, um, reducing equivalents like the, you know, the NADH, the NADPH, the, you know, so... And it, it also has negative effects, so you kind of don't want to go too far on either ends of the, of the spectrum. But also you want to, instead of having this like slow leaking effect of these pro-oxidants where, 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, and it's off, right? And the adaptation, the ada- adaptation happens within the recovery period, right? When you're, for example, if you exercise, that's a big burst of reactive oxygen species that is beneficial.

Andrew Huberman 59:43 Mm-hmm.

Dr. Rhonda Patrick 59:43 And you want it, right? And you don't want to blunt those adaptations and so that's, that's kind of my concern with daily dosing of NAC.

Andrew Huberman 59:50 Great. I don't cold plunge, uh, in the six to eight hours after a resistance training for exactly the reason you're talking about.

Dr. Rhonda Patrick 59:56 Exactly.

Andrew Huberman 59:56 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, uh, and that's also when I'll, I'll take glutamine. If you take L-glutamine

Andrew Huberman 1:00:08 regularly, I, I personally observe that I get stronger, um, at a steady state of, of starch intake. And, uh, I don't like dropping starches too low 'cause I get weak.

Dr. Rhonda Patrick 1:00:18 Yeah.

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

Dr. Rhonda Patrick 1:00:24 Yeah.

Andrew Huberman 1:00:24 Mm-hmm.

Dr. Rhonda Patrick 1:00:24 There's a, there was a new study on, on eating starches and improving sleep.

Andrew Huberman 1:00:28 Yeah, and I'm so grateful for that.

Dr. Rhonda Patrick 1:00:30 Did you read about it? [laughs]

Andrew Huberman 1:00:30 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 r- running like crazy, I'll hear from marathoners and ultra people and people who 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? They're like, "Oh, no, I don't eat pasta." And they're like... And then they'll have some rice or some pasta, they're like, "Oh, I slept like a baby." And they, they were having it at lunch.

Dr. Rhonda Patrick 1:00:56 Yeah.

Andrew Huberman 1:00:57 And I just think that the, the brain doesn't shut down well when you have high levels of cortisol, and the cortisol/starch thing is an interesting one.

Dr. Rhonda Patrick 1:01:03 I'm so glad you brought this up because I thinkUm, this is something that I did wanna 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 study, 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? You're di- it, it... That's activating the sympathetic nervous system.

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

Dr. Rhonda Patrick 1:01:33 Yeah.

Andrew Huberman 1:01:33 Yeah.

Dr. Rhonda Patrick 1:01:33 And even as you're digesting, so if you think about it, like, you digest in, what it takes, like, five or so hours to fully finish about di-

Andrew Huberman 1:01:40 Yeah, depending on the meal. Yeah

Dr. Rhonda Patrick 1:01:41 ... Depending on the meal, right. So if you're eating, you know, right before you go to bed, you are, you are, you are not in that parasym- sympathetic activity, you know-

Andrew Huberman 1:01:50 Mm

Dr. Rhonda Patrick 1:01:50 ... s- part of the, part of the, you know, the cycle that you wanna be in. So, um, there was a new, even a new study that I shared, like, I don't know, couple days ago even, showing that if you stop eating three hours before bed... So these people were actually, um, it's interesting. Their... They had their blood pressure measured for starting in the mid-afternoon all the way throughout the night. This is the first study that really not just one endpoint looking at-

Andrew Huberman 1:02:14 Mm

Dr. Rhonda Patrick 1:02:14 ... blood pressure, but just mea- measuring it continuously. I don't know if it was every 15 minutes or something like that. But, um, it was found that their, 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.

Andrew Huberman 1:02:30 Mm.

Dr. Rhonda Patrick 1:02:30 So you get that, you know, that baroreflex dipping, right? So this is, like, part of the parasympathetic activation. As you know, very important for, you know, 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. I think what was found was it was something like, um, translated to, like, 20% lower risk of cardiovascular events, like heart attacks. So it's really pretty significant.

Andrew Huberman 1:02:55 That's impressive.

Dr. Rhonda Patrick 1:02:55 Yeah. And it really is an easy thing to do to think about stopping eating, you know, th- three hours before you go to bed. Like, that's, that's something I think that is not that hard to implement.

Andrew Huberman 1:03:05 Mm.

Dr. Rhonda Patrick 1:03:06 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... It was subjective, and I don't think it really was i- improved more.

Andrew Huberman 1:03:15 Mm.

Dr. Rhonda Patrick 1:03:15 But other studies have found that as well.

Andrew Huberman 1:03:16 Mm.

Dr. Rhonda Patrick 1:03:17 That sleep does improve. I know Satchin Panda, he's been on my podcast, your podcast. He's had studies showing that it seemed like-

Andrew Huberman 1:03:23 Mm

Dr. Rhonda Patrick 1:03:23 ... stop, stop eating three hours before bed really does seem to improve sleep. But this parasympathetic activation, you know, you don't wanna have a meal right before you bed because you want, you wanna be in the rest and recovery part, right?

Andrew Huberman 1:03:34 Mm-hmm.

Dr. Rhonda Patrick 1:03:35 So.

Andrew Huberman 1:03:36 Yeah, I think people hear, uh, and I understand why the nomenclature and the buzzwords of, you know, fight or flight for sympathetic and rest and digest for parasympathetic, but-

Dr. Rhonda Patrick 1:03:45 Yeah

Andrew Huberman 1:03:46 ... yeah, the evidence shows eating stimulates the sympathetic nervous system.

Dr. Rhonda Patrick 1:03:49 It, yeah. Digests.

Andrew Huberman 1:03:49 It's not a stress event, but it, it's a... It requires energy.

Dr. Rhonda Patrick 1:03:53 It's a-

Andrew Huberman 1:03:53 Anything that requires energy raises body temperature, and your body's doing work, and you-

Dr. Rhonda Patrick 1:03:56 It's an awake event, right?

Andrew Huberman 1:03:57 An awake event.

Dr. Rhonda Patrick 1:03:57 It's an awake event.

Andrew Huberman 1:03:58 Right, yeah.

Dr. Rhonda Patrick 1:03:58 You, you don't eat-

Andrew Huberman 1:03:58 That's a great way to put it

Dr. Rhonda Patrick 1:03:59 ... while you're-

Andrew Huberman 1:04:00 Yeah

Dr. Rhonda Patrick 1:04:00 ... sleeping.

Andrew Huberman 1:04:00 Yeah, and that's why these phrases, while I don't demonize anyone for creating the, you know, fight or flight, m- 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-

Dr. Rhonda Patrick 1:04:15 Yeah

Andrew Huberman 1:04:15 ... 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, 'cause on a given day, you just do what you can, right?

Dr. Rhonda Patrick 1:04:34 And that's what you want, right?

Andrew Huberman 1:04:36 Yeah.

Dr. Rhonda Patrick 1:04:36 I mean, so cortisol is circadian dependent-

Andrew Huberman 1:04:38 Mm

Dr. Rhonda Patrick 1:04:38 ... as you know. I mean, in the m- like, early morning of, early hours of the morning, that's when you want it to peak, right?

Andrew Huberman 1:04:44 Mm.

Dr. Rhonda Patrick 1:04:44 The part of the awakening response.

Andrew Huberman 1:04:46 Mm-hmm.

Dr. Rhonda Patrick 1:04:46 Like, you want it to go up. And it's, it's interesting, I, I, I... The, the reason I'm going on this is 'cause it's a little bit of a, um, soapbox for me, but so with, with the, with the cortisol activation, um, people don't realize this. You know, obviously it's a hormone, and it's binding to dif- two different receptors. There's the glucocorticoid receptor, and then there's the mineralocorticoid receptor. And both of those, um, when cortisol binds to it, they go into the nucleus of the cell, and they're changing the expression, 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 it's... It- cortisol has a very important role, and you want that peak. You want that spike, right?

Andrew Huberman 1:05:29 Mm.

Dr. Rhonda Patrick 1:05:29 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 ex- like, like, intensity, intense exercise can switch it on. Um, but what's interesting... And so can intermittent fasting, that it... What's interesting is there's studies from Mark Mattson's lab showing that, you know, the types of s- of, of stressors that are beneficial, these hormetic stressors, like exercise, like, you know, intermittent fasting, um, perhaps even cold exposure, like, these types of exposures change the receptor density of the res-

Andrew Huberman 1:06:09 Mm

Dr. Rhonda Patrick 1:06:09 ... receptors. So if you, if you look at what activates cortisol in a negative way, chronic stress, let's say emotional, financial, psychological, um, chronic sleep deprivation, right, that bad type of stress, you're getting... 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.

Andrew Huberman 1:06:30 Interesting.

Dr. Rhonda Patrick 1:06:31 There's a different biological response in the brain, in the hypothalamus, but also in, uh, you know, oth- other organs as well when you're, when you're activating cortisol through a beneficial type of stress, the hormetic stressors like, like intermittent fasting, like exercise, um, I believe probably deliberate cold exposure as well, where, um, it's a different biological response. 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 of genes.

Andrew Huberman 1:06:59 Mm.

Dr. Rhonda Patrick 1:06:59 That's what it's supposed to do, right?

Andrew Huberman 1:07:00 Mm.

Dr. Rhonda Patrick 1:07:00 The problem is, is when you have that slow drip, then, you know, not only are you're, you're 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're... You know, cortisolRepresses inflammation, right? It's, it suppresses the immune system. But like, so you're not getting that anti-inflammatory effect from cortisol. It's being dysregulated, and that's what you don't want. 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, um, anyways, I- 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 could always take something-

Andrew Huberman 1:07:50 Sure

Dr. Rhonda Patrick 1:07:50 ... to the extreme.

Andrew Huberman 1:07:50 Sure.

Dr. Rhonda Patrick 1:07:50 Okay, with that caveat, obviously I'm not talking about that. But with that caveat, like you do... You, you want your body to be able to turn it on and then turn it off and have the adaptation, have the response, right?

Andrew Huberman 1:08:01 Yeah.

Dr. Rhonda Patrick 1:08:01 And like I said, it's a different biological response than, than the chronic type of cortisol activation that you get with the bad types of stress.

Andrew Huberman 1:08:09 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, and this-

Dr. Rhonda Patrick 1:08:29 Yeah

Andrew Huberman 1:08:30 ... this sort of, um, 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 what? In a very appropriate way, um, that I appreciate, uh, Dr. Stacy 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, the, the message got contorted, right?

Dr. Rhonda Patrick 1:09:12 Mm-hmm.

Andrew Huberman 1:09:13 As it does.

Dr. Rhonda Patrick 1:09:13 Yes.

Andrew Huberman 1:09:14 Right?

Dr. Rhonda Patrick 1:09:14 Yes.

Andrew Huberman 1:09:14 And then it became women shouldn't train fasted. And then we had, uh, Lauren Clemso-Semple on this podcast who's a, you know, trained as a PhD. She has a background in nutrition, physiology, strength training coach, et cetera. 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, um, 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-

Dr. Rhonda Patrick 1:09:44 Yeah

Andrew Huberman 1:09:44 ... and peripheral dopamine, and probably, I'll go on record here, probably central dopamine, although we don't have as good evidence for that yet. But the evidence points to the fact that deliberate cold exposure lowers cortisol.

Dr. Rhonda Patrick 1:09:57 Mm.

Andrew Huberman 1:09:57 So this then, you know, because... And again, I think Stacy 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," [chuckles] right? And that's what Lauren's saying, and I'm guessing, um, that's what you'll say as well. Um, 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. You want it high in the morning, you want it low at night, um, in general. Um, it sounds like you train fasted?

Dr. Rhonda Patrick 1:10:37 I listen to how I feel.

Andrew Huberman 1:10:39 Yeah.

Dr. Rhonda Patrick 1:10:39 That's exactly what I do.

Andrew Huberman 1:10:40 Mm-hmm.

Dr. Rhonda Patrick 1:10:40 So what, what your podcast guest and-

Andrew Huberman 1:10:42 Mm-hmm

Dr. Rhonda Patrick 1:10:42 ... 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."

Andrew Huberman 1:10:50 Mm-hmm.

Dr. Rhonda Patrick 1:10:50 And I do. Um, but I oftentimes do train fasted, for 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.

Andrew Huberman 1:11:10 Mm-hmm.

Dr. Rhonda Patrick 1:11:11 Um, but the second reason is I love the cognitive benefits I have in the morning with it.

Andrew Huberman 1:11:15 Mm-hmm.

Dr. Rhonda Patrick 1:11:15 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, 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.

Andrew Huberman 1:11:33 Mm-hmm.

Dr. Rhonda Patrick 1:11:34 And you do burn a little bit more fat if you train fasted. I mean, that's known.

Andrew Huberman 1:11:38 Mm-hmm.

Dr. Rhonda Patrick 1:11:39 Um, you will, if it is a longer session, you will take an a per- performance enhancement hit. That is also known, right? So I think it really does come down to like what is your goal, how do you feel, and, and then you kind of go with that. And I, 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 ti- other times when I'm like, "I don't feel good. Like I'm gonna, I'm gonna take it easier." But I still train, I just... You listen to your body and I- that's a pretty easy-

Andrew Huberman 1:12:08 Mm-hmm

Dr. Rhonda Patrick 1:12:08 ... I think, rule of thumb.

Andrew Huberman 1:12:09 Mm-hmm.

Dr. Rhonda Patrick 1:12:10 Sometimes people like to complicate things, you know? I don't-

Andrew Huberman 1:12:12 Mm-hmm.

Dr. Rhonda Patrick 1:12:13 There's lots of reasons why. I don't... We don't need to get into that. [laughs]

Andrew Huberman 1:12:15 Yeah. I have theories.

Dr. Rhonda Patrick 1:12:16 But-

Andrew Huberman 1:12:16 Yeah, I have theories, but they're not important right now.

Dr. Rhonda Patrick 1:12:18 No, it's not important.

Andrew Huberman 1:12:18 Yeah, yeah, yeah.

Dr. Rhonda Patrick 1:12:19 Yeah. So, so yeah, I do, I do train fasted and it is, um, for me, it has, 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, I didn't have to train fasted. It was, it, it was, it was easy to keep, you know, the, the belly fat, the visceral fat lower. Um, hormonal changes are, 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, the fat that we see. The visceral fat, that's that deep fat that's lining your organs. It's often belly fat, you know, and it's lining the intestines, the liver. You know, it's, it's, it's, it's an, it's almost like an endocrine organ. I mean, 'cause 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. Um, people that have high visceral fat have 44% higher chance of having cancer, many different types of cancers.

Andrew Huberman 1:13:23 Wow.

Dr. Rhonda Patrick 1:13:23 It's huge. It's huge. You know, and, and, and of course insulin resistance is the number one problem [chuckles] with visceral fat, right?

Andrew Huberman 1:13:30 Yeah.

Dr. Rhonda Patrick 1:13:30 And I'd love to, to talk about that, but, um, if you want, I mean, we can, we can get into that.

Andrew Huberman 1:13:35 Please. Yeah.

Dr. Rhonda Patrick 1:13:35 Yeah. It's, it's... 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 gonna 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 higher amount of visceral fat. It's also that belly fat. Like, you can, you can... You just know, right? Um, interestingly, like, 70% 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, the years before menopause, and menopause, it, th- 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? I mean, that's something that I think it's, it's hard to deny. But, um, it's, it's one of the reasons why I kind of went back to practicing intermittent fasting because there's a, there's a f- 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. Uh, I've mentioned it's secreting these inflammatory molecules, its, 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 it up glucose into your liver, uh, muscle, adipose tissue. Lipolysis shuts down, right? It's like, okay, no longer am I gonna 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, uh, it's, it's essentially atta- 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-

Andrew Huberman 1:16:34 Hmm

Dr. Rhonda Patrick 1:16:34 ... we can talk about those studies. Like, people, people are skinny and can have high amounts of visceral fat. You've, you've heard of, like, lean... 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, um, 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. So we talked about-

Andrew Huberman 1:17:08 Mm-hmm

Dr. Rhonda Patrick 1:17:08 ... lethargy, right? So, you know, the inflammation that's being generated from these, this visceral fat constantly making these, you know, pro-inflammatory compounds are-

Andrew Huberman 1:17:18 Mm

Dr. Rhonda Patrick 1:17:18 ... an e- it's an energy sink, right? 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, I, we gotta get this blood glucose out of our system, right? It can cause a lot of damage if it sits around there. And so you make more insulin, and then what happens is you, your blood glucose goes way low 'cause it was, like, this overcompensation, right? And then you feel a crash. You feel, like, this crash, and that signals to the, you know, hypothalamus part of the brain, uh, I need energy, right? So then you, 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-

Andrew Huberman 1:18:02 Mm-hmm

Dr. Rhonda Patrick 1:18:02 ... you know, insulin resistance.

Andrew Huberman 1:18:04 Mm-hmm.

Dr. Rhonda Patrick 1:18:04 And what's interesting is that you can cause someone to gain visceral fat and, 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, um, insulin's 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, um, stop eating, be satiated. Like, I took a meal in, okay-

Andrew Huberman 1:18:39 Mm

Dr. Rhonda Patrick 1:18:39 ... like, I'm gonna be satiated. But it also plays a role in energy storage and telling the, 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, in a recent newsletter. It was a really interesting study 'cause it was healthy young men, and researchers put them on a, a little bit of a calorically dense, so it was like they were eating 1,200 to 1,500 more calories a day, and it was high saturated fat, high sugar, so it was, uh, processed foods, ultra-processed foods, like, you know, ultimate, right?

Andrew Huberman 1:19:19 That's a lot of ca- extra calories.

Dr. Rhonda Patrick 1:19:20 That's a lot of extra calories. For five days. It is. But what happened was their, they did cause their brain to become insulin resistant, and they didn't gain weight, but they gained visceral fat.

Andrew Huberman 1:19:31 Mm.

Dr. Rhonda Patrick 1:19:32 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? So you get this non-alcoholic, you know, fatty, fatty liver. But... And that happened after five days. I mean-

Andrew Huberman 1:19:46 In-

Dr. Rhonda Patrick 1:19:46 ... without gaining-

Andrew Huberman 1:19:47 In otherwise young, healthy-

Dr. Rhonda Patrick 1:19:48 Yeah. But, you know, they were eating a lot of calories, extra calories.

Andrew Huberman 1:19:52 Yeah, that's like a, a 1,200... That's like a half a pizza

1:19:57 e-extra above your m-maintenance calories per night

Dr. Rhonda Patrick 1:19:59 And that's probably what they were doing. They were eating lots of... They were eating, like, saturated fat and, and refined sugar, so-

Andrew Huberman 1:20:03 Burritos and french fries

Dr. Rhonda Patrick 1:20:04 Yeah. I mean, obviously, if you're gonna do the study, you wanna kind of do it to a h-

Andrew Huberman 1:20:07 Sure

Dr. Rhonda Patrick 1:20:07 ... a degree where you're gonna see some change, right?

Andrew Huberman 1:20:09 Mm-hmm.

Dr. Rhonda Patrick 1:20:09 So, so maybe, like, maybe it's not gonna happen in five days if you're-

Andrew Huberman 1:20:14 Mm

Dr. Rhonda Patrick 1:20:14 ... if you're only eating 500 more calories a day, but over time you will be gaining visceral fat, right? So it, it's not gonna be the same degree. It's something to be concerned about.

Andrew Huberman 1:20:23 Mm-hmm.

Dr. Rhonda Patrick 1:20:23 It's something to think about, and also because you can gain it and not really even know it.

Andrew Huberman 1:20:28 Mm.

Dr. Rhonda Patrick 1:20:28 Like, you know, without gaining a pound. And there are other things that cause it, not just, you know, eating too many calories or diet composition. I mean, you mentioned cortisol. I mean, chronic elevated cortisol makes you store the fat around, 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 a 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 gonna see on the scale.

Andrew Huberman 1:20:58 Mm.

Dr. Rhonda Patrick 1:20:58 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. It's a vicious cycle 'cause you start to eat more calories, right? And then it just becomes this vicious cycle of then you start to gain more visceral fat.

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Andrew Huberman 1:22:33 Such an important point that you can either not be gaining much or not gaining any, uh, total body weight, but gaining visceral fat. I think that's, uh, 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. You mentioned elevated... chronically elevated cortisol, sleep deprivation will increase visceral fat. Once again, I know I'm beating a drum here, um, 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 elevated cortisol in the morning, but especially in the hours before sleep. And I, 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.

Dr. Rhonda Patrick 1:23:27 Mm.

Andrew Huberman 1:23:27 And so-

Dr. Rhonda Patrick 1:23:28 Mm-hmm

Andrew Huberman 1:23:28 ... and we can't tease those apart.

Dr. Rhonda Patrick 1:23:29 No.

Andrew Huberman 1:23:29 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-

Dr. Rhonda Patrick 1:23:49 Mm-hmm

Andrew Huberman 1:23:49 ... in that, certainly in that last hour before sleep, ideally three, um, I feel like that small change can make a, an outsized positive difference.

Dr. Rhonda Patrick 1:23:57 That's interesting, like, the, the, the correlation between the high cortisol affecting your sleep and maybe that's also... Like, they're, they're related, and so the sleep loss really does make you... We know, we know from-

Andrew Huberman 1:24:09 Mm

Dr. Rhonda Patrick 1:24:09 ... you know, you probably know who the researchers are that have done those studies on sleep loss and it affecting appetite, right? I mean, like, people-

Andrew Huberman 1:24:15 Oh, everything gets dysregulated.

Dr. Rhonda Patrick 1:24:16 Right.

Andrew Huberman 1:24:16 I mean, uh, I don't want to take us off course-

Dr. Rhonda Patrick 1:24:18 No [laughs]

Andrew Huberman 1:24:18 ... 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, um, 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 f- uh, you're... Then you're just like a... It almost looks like somebody's ketogenic at one. Basically, the, the middle of the night when we're s- well, it should be at night, when you're sleeping is a, is kind of a test run of all the systems, but they get recalibrated, 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 1 carcinogen, um, as classified by the Wo- World Health Organization on a... I think most of the negative effects of drinking are because of the negative effects of alcohol on sleep. I'm not telling people-

Dr. Rhonda Patrick 1:25:03 Yeah

Andrew Huberman 1:25:03 ... drink in the morning, but-

Dr. Rhonda Patrick 1:25:04 Yeah

Andrew Huberman 1:25:04 ... uh, you know, i- and so I, I think that if you get your sleep right, you're not 90% of the way there, but you're halfway there.

Dr. Rhonda Patrick 1:25:11 Yeah.

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

Dr. Rhonda Patrick 1:25:16 Right.

Andrew Huberman 1:25:16 Yeah.

Dr. Rhonda Patrick 1:25:16 You're mo- you're mo- more motivated to exercise, for one. [laughs]

Andrew Huberman 1:25:19 More motivated to exercise, your food choices, I mean, and on and on.

Dr. Rhonda Patrick 1:25:23 Food choices. Yeah.

Andrew Huberman 1:25:23 The, the problem with talking about sleep as 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. These... No one gets it perfect. Yes, you'll survive. Like, without one poor night's sleep or an all-nighter, you're not gonna die. Like, you know, just get good at it on average-

Dr. Rhonda Patrick 1:25:40 Yeah

Andrew Huberman 1:25:40 ... right? That's what I'd say. Could you

Andrew Huberman 1:25:42 tell us what the structure of the intermittent fasting is for you? Does that mean skipping breakfast, skipping lunch, skipping dinner? 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-

Dr. Rhonda Patrick 1:25:54 Mm-hmm

Andrew Huberman 1:25:54 ... as, like, not the best way to lose fat or it is a... I think it's a terrific way to do the sorts of things that you're describing, and I'm learningToday more about the th- positive things it can do, um, 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?

Dr. Rhonda Patrick 1:26:14 For me, it-it-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 with actually-- 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.

Andrew Huberman 1:26:44 Mm-hmm.

Dr. Rhonda Patrick 1:26:44 As you mentioned, insulin sensitivity. And the metabolic switch is something that Dr. Mark Mattson coined, and I love it because I feel like, you know, thinking about intermittent fasting in that way makes it a little more clear as to the benefits of it.

Andrew Huberman 1:26:59 Mm-hmm.

Dr. Rhonda Patrick 1:26:59 It depends on the meal you have and how much exercise you do, right? But on average, let's say eleven, twelve 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 not... You're going from using carbohydrates as fuel to using fatty acids and making ketone bodies as fuel. And that's something that, you know, throughout human evolution was ingrained, right? Like we-

Andrew Huberman 1:27:29 Mm-hmm

Dr. Rhonda Patrick 1:27:30 ... didn't always have access to Uber Eats and Instacart, and you just at a swipe, you get food, right? I mean, there were many times when, you know, people had to not eat [laughs] 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.

Andrew Huberman 1:27:48 Yeah.

Dr. Rhonda Patrick 1:27:48 So this metabolic flexibility is something that's really ingrained in, in our, in our, our DNA in a sense, right?

Andrew Huberman 1:27:54 Mm-hmm.

Dr. Rhonda Patrick 1:27:55 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... They're clean, a clean way to burn energy.

Andrew Huberman 1:28:05 Mm-hmm.

Dr. Rhonda Patrick 1:28:05 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, you know, to signal to other parts of the body like, "Hey, this is a stressful time. There's no food. I'm, you know, burn... I'm, I'm in, in ketosis, um, let's, let's make you stronger," right? 'Cause 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? And so that's, that's kind of at the, I'd say, core of, 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, re-re- synapse formation and stuff. This hugely important for some, um, neuroplasticity. So it's activating beneficial compounds like that and again, um, it-it-it-it's not gonna happen if you're never going into this metabolic switch. And there's other ways to get there, right? So you can limit your, 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, there's different ways to get to this metabolic switch.

Andrew Huberman 1:29:38 Mm-hmm.

Dr. Rhonda Patrick 1:29:38 It doesn't necessarily have to be intermittent fasting.

Andrew Huberman 1:29:40 Got it.

Dr. Rhonda Patrick 1:29:41 And I'm telling you this because you're-you... I wanna tell you why I'm, I'm sort of back-

Andrew Huberman 1:29:45 Mm-hmm

Dr. Rhonda Patrick 1:29:45 ... 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, um, for me, intermittent fasting works. And so what I do typically is I will do most of the time my fast, my workouts will be fasted, not all the time. It do- it does depend on how I feel.

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

Dr. Rhonda Patrick 1:30:04 So I wake up like s- between 6:00 and 7:00.

Andrew Huberman 1:30:07 Mm-hmm.

Dr. Rhonda Patrick 1:30:07 And if I didn't have a family, like, you know, getting my son ready and I would probably work out right away, but I don't end up working out until like 8:30. So I'm, you know, and I-

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

Dr. Rhonda Patrick 1:30:21 I'm, I'm asleep, like I'm asleep by 10:00.

Andrew Huberman 1:30:24 Mm-hmm.

Dr. Rhonda Patrick 1:30:25 I'm usually in bed at 9:00. Takes an um, an hour of just like, you know, hanging out.

Andrew Huberman 1:30:29 Sure.

Dr. Rhonda Patrick 1:30:29 And yeah, so, so, um, or 9:30 sometimes. But yeah, usually 10 o'clock's when I'm sleeping. That's my, my bedtime. And, uh, so I do stop eating. I try to stop eating by 7:00 PM.

Andrew Huberman 1:30:42 Okay.

Dr. Rhonda Patrick 1:30:42 But typically my first meal on, it depends on the day, but it'll usually be like around 11:00, maybe sometimes 12:00. If I'm doing a podcast, it'll be later. And, um, I do like to be fasted in the morning because the cognitive benefits is, is really what I'm interested in with that metabolic switch, and it does come down to ketones, and I know that, uh, Mark Mattson's talked a lot about this. I had him on my podcast a couple year, 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, you know, 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 GABA's calming in a way. I don't, I don't know exactly. You could probably describe it better than I can. All I know is that I really like it.

Andrew Huberman 1:31:36 Mm-hmm.

Dr. Rhonda Patrick 1:31:36 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 hon-hon-honestly, I'm skipping the quote-unquote breakfast.

Andrew Huberman 1:31:58 Mm-hmm.

Dr. Rhonda Patrick 1:31:59 But, uh, some days I do haveThree meals, and, you know, oftentimes they're, 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 a or a three-fourths of a turkey burger or something. So it's, it's mostly protein, and it's not heavy.

Andrew Huberman 1:32:21 Mm-hmm.

Dr. Rhonda Patrick 1:32:22 But so I would say I'm, you know, usually eleven to seven-

Andrew Huberman 1:32:26 Mm-hmm

Dr. Rhonda Patrick 1:32:26 ... probably is when I'm eating-

Andrew Huberman 1:32:27 Mm-hmm

Dr. Rhonda Patrick 1:32:27 ... my meals most, most days. Some days it's, you know, I, I fast for a shorter period of time.

Andrew Huberman 1:32:31 Mm-hmm.

Dr. Rhonda Patrick 1:32:32 Some days I wake up in the morning because I, I did too early of, of like a, you know, I'd stopped eating like, like four or five hours before bed, and I'm like, "I need to eat."

Andrew Huberman 1:32:40 Sure.

Dr. Rhonda Patrick 1:32:40 And guess what? I eat, and then I work out, and it's like that's... You know, you kind of just listen to the, to what your body's doing. Actually, Mark Mattson just published a study very, very recently showing that he did a f- I think he was doing a five-two intermittent fasting protocol where it's like two days you're getting pretty severe caloric restriction. Like, you're eating one meal, but it's like five hundred calories, you know, for that, for the day, and it's twice, two days, two days out of the week. The other five days you're eating normal. And compared that to calorie re- like eating, 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 they had-- The fasting group had massive cognitive benefits, like twenty percent improvement in a battery of tests that were done.

Andrew Huberman 1:33:19 He attributes that to the ketones and the e- the effect of ketones-

Dr. Rhonda Patrick 1:33:22 He does

Andrew Huberman 1:33:22 ... on GABA.

Dr. Rhonda Patrick 1:33:23 He, he attributes it to the ketones.

Andrew Huberman 1:33:24 Mm-hmm.

Dr. Rhonda Patrick 1:33:25 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's key.

Andrew Huberman 1:33:34 Mm-hmm.

Dr. Rhonda Patrick 1:33:34 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 gonna get that. Like, that-

Andrew Huberman 1:33:42 Right

Dr. Rhonda Patrick 1:33:42 ... those studies have been done. And I think, you know, Courtney Peterson was some of the, one of the first ones to really show that effect on blood pressure, you know, like s- really significant in fact. If you, if you do early time restricted eating and stop eating, you know, I don't know how early in the day it was, maybe 6:00 PM.

Andrew Huberman 1:33:57 Mm-hmm.

Dr. Rhonda Patrick 1:33:57 Maybe it was 8:00 PM. But, you know, there was, like, a blood pressure drop that was, like, ten, you know, ten, I think it was, um, uh, points or something, millimeters of mercu-mercury.

Andrew Huberman 1:34:08 Significant.

Dr. Rhonda Patrick 1:34:09 What is it? Is it-

Andrew Huberman 1:34:09 Yeah. Yep.

Dr. Rhonda Patrick 1:34:10 Yeah.

Andrew Huberman 1:34:10 Yep.

Dr. Rhonda Patrick 1:34:11 So, I mean, that's very significant. It's on, 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.

Andrew Huberman 1:34:19 Right.

Dr. Rhonda Patrick 1:34:19 I would never say for someone to do that, but I'm just saying it's significant.

Andrew Huberman 1:34:22 Mm-hmm.

Dr. Rhonda Patrick 1:34:22 And that's not something that you'd typically see if you're eating, you know-

Andrew Huberman 1:34:25 Right

Dr. Rhonda Patrick 1:34:25 ... 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. Then, you know, that's, that's the way you can, you can do it. But I like it for the metabolic switch as well.

Andrew Huberman 1:34:45 Mm-hmm.

Dr. Rhonda Patrick 1:34:45 Um, if I were an endurance athlete running, you know, ten, fourteen miles a day, I wouldn't have to do this. That would be my metabolic switch.

Andrew Huberman 1:34:53 Mm-hmm.

Dr. Rhonda Patrick 1:34:53 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, and then burning, bur- using fat, 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, of time, 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-

Andrew Huberman 1:35:25 Sure

Dr. Rhonda Patrick 1:35:25 ... fasting. The problems with fasting and the people that are like, "Oh, fasting's 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.

Andrew Huberman 1:35:39 Mm-hmm.

Dr. Rhonda Patrick 1:35:39 Number two, they're afraid of losing muscle, and I think we have enough data now that it's like if you're training, if you're doing resistance training, you're not gonna be losing muscle. Now, maybe you won't gain as much as if you were eating more protein, but, um, you could. You could just eat more protein, um, within the window that you're eating and be fine, right?

Andrew Huberman 1:35:58 Mm-hmm.

Dr. Rhonda Patrick 1:35:59 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.

Andrew Huberman 1:36:08 Mm-hmm.

Dr. Rhonda Patrick 1:36:08 And it, it's like this clean feeling.

Andrew Huberman 1:36:10 Mm-hmm.

Dr. Rhonda Patrick 1:36:10 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 fasted, don't train while you're fasted. You don't have to, you know? I, 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, that's, that's what works well. But, um, 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.

Andrew Huberman 1:36:47 Yeah, I think the, uh, the known increase in adrenaline from being slightly fasted is awesome for cognitive function. Um, I think it allows people to ingest fewer stimulants in the form of caffeine. You can, you know, you don't need as much caffeine when you're-

Dr. Rhonda Patrick 1:37:02 Mm-hmm

Andrew Huberman 1:37:02 ... doing some fasting. I... What you describe is, um, 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, you know, coming a little bit earlier in the day and further from sleep. And also that thermogenic effect of eating raises core body temperature and, and you know to fall asleep you want your body temperature dropping. So it all starts to... What, you know, what I think is kind of, uh, 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, the, what works best for sleep, what, what you're describing, certainly today you really, in addition to many other things, really clarified the relationship between gut and inflammation and, 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. 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, I-"And I think I can train faster. I like to train faster. That might seem like a, 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, 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, is, uh, is so crucial because it's about feel that fits into a logic. And, uh, I have to say, uh, that's initially what drew me to your work, is there's a logic be- you're not just saying, "Okay, this study said this, so I'm gonna do this." It fits into a broader logic that comes from your training. So I just... That's a, just a point of gratitude, and I hope it'll 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-

Dr. Rhonda Patrick 1:38:49 Right

Andrew Huberman 1:38:50 ... and that w- 'cause 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.

Dr. Rhonda Patrick 1:38:57 Yeah, it's about the habit. Exactly.

Andrew Huberman 1:38:59 Mm-hmm.

Dr. Rhonda Patrick 1:38:59 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.

Andrew Huberman 1:39:04 Mm-hmm.

Dr. Rhonda Patrick 1:39:04 Exactly, where you, you, you know. And there are days when I... Nights when I ha- when I'm eating later because of social obligations, and I don't freak out about it-

Andrew Huberman 1:39:12 Mm-hmm

Dr. Rhonda Patrick 1:39:12 ... because it's about the habit.

Andrew Huberman 1:39:13 I like the idea of one metabolic switch, uh, per day. You know, you said you could get it from exercise-

Dr. Rhonda Patrick 1:39:20 Yeah

Andrew Huberman 1:39:20 ... and I thought, you know, I can really imagine that in five years a concept of, 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.

Dr. Rhonda Patrick 1:39:33 Yeah.

Andrew Huberman 1:39:33 Maybe you just exercise. Maybe you just fast 'cause you can't exercise because people's schedules are constrained, but the notion of the metabolic switch as being... Here's where it fits in exactly. The logic is you want the metabolic switch.

Dr. Rhonda Patrick 1:39:45 You do, and it's not just, you know... Th- 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?

Andrew Huberman 1:39:57 Mm-hmm.

Dr. Rhonda Patrick 1:39:57 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?

Andrew Huberman 1:40:04 Mm-hmm.

Dr. Rhonda Patrick 1:40:05 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, you know, when, when you're in a nutrient depriv- deprived state, right? When you're in that metabolic switch. And autophagy, and that's another one that people, some, it's a buzz, it's a buzzword now, but it is something that is activated. It's... First of all, we have basal amount of autophagy going on at any point, right? Like that's happening. Like it's-

Andrew Huberman 1:40:38 You don't have to fast-

Dr. Rhonda Patrick 1:40:39 You don't have to fast

Andrew Huberman 1:40:40 ... to get it.

Dr. Rhonda Patrick 1:40:40 Exactly.

Andrew Huberman 1:40:40 Or be in a caloric deficit, which will also-

Dr. Rhonda Patrick 1:40:42 Right

Andrew Huberman 1:40:42 ... exacerbate it.

Dr. Rhonda Patrick 1:40:43 Right.

Andrew Huberman 1:40:43 Yeah.

Dr. Rhonda Patrick 1:40:43 You do have fasted activated autophagy, and certain tissues are more sensitive, like the liver and the brain actually.

Andrew Huberman 1:40:51 Mm-hmm.

Dr. Rhonda Patrick 1:40:51 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, a g- 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 ac- you know, to access if you're gonna measure autophagy in humans, right?

Andrew Huberman 1:41:18 Mm-hmm.

Dr. Rhonda Patrick 1:41:18 Muscle biopsies have been done. That's... The muscle's also respons- uh, responsive to, to fasting induced autophagy. It's as responsive to exercise induced autophagy. By the way, the exercise, again, it's increasing energy expenditure, so at this, the end of the day, you're, you're getting into that sort of ketosis, right, state, the metabolic switch. So, um, there are studies showing that there's a signal there, uh, 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 gonna be hard to go get a liver. I mean, maybe we'll have some tools soon that we can easily access a, you know, liver biopsy, and that'd be great for many reasons, right? Not just looking at autophagy.

Andrew Huberman 1:41:58 Mm-hmm.

Dr. Rhonda Patrick 1:41:58 But I think that it, to some degree, you kind of just have to know that, okay, autophagy's happening right now in our, in our cells. Like so we know that it's activated by like fasting, by exercise, by these types of stress, and so why wouldn't it be increased somewhat?

Andrew Huberman 1:42:15 Mm-hmm.

Dr. Rhonda Patrick 1:42:15 And, and when I say autophagy, I'm talking about clearing out gunk that's built up in your cell, you know, 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? All sorts of stuff, right? And it's important. This is a cleanup process.

Andrew Huberman 1:42:35 Mm-hmm.

Dr. Rhonda Patrick 1:42:35 It's important. And so again, that's another part of the metabolic switch that I think is i- it's important to think about because we are really obsessed with anabolic, anabolic, is it anabolic? It's great. You do wanna... You definitely wanna grow muscle, right? You do, you do wanna grow new brain cells and stuff too, but, but you also wanna repair and you wanna have recovery and, and that's, that's another, you know, f- it's like the yin and the yang, right? You kinda want both.

Andrew Huberman 1:43:00 Mm-hmm.

Dr. Rhonda Patrick 1:43:00 So I think that's important to think about as well. Um, and fasting, intermittent fasting, I do... I like the daily metabolic switch. 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? Um, it helps if you're trying to lose visceral fat. It's one of the main ways you can do it, intermittent fasting, caloric restriction, exercise, aerobic exercise that helps lose visceral fat. But I mean, obviously we don't always wanna be in a caloric deficit, but we always don't wanna be constantly eating either.

Andrew Huberman 1:43:35 Mm-hmm.

Dr. Rhonda Patrick 1:43:35 And that's why it comes down to, I think, the simple rule for people, like if they're gonna 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 gonna 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 Jacobowitz, Jacobowitz and Froy. They're two researchers. Um, I mean, Satchin 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 like com- 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, you s- your melo- your melatonin levels naturally rise, right? And as you know, you know, melatonin is important for the onset of sleep and, 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. 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 wanna be eating a, particularly a carbohydrate-rich meal, but a meal you're not gonna be as, as insulin sensitive.

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

Dr. Rhonda Patrick 1:44:59 Yeah.

Andrew Huberman 1:44:59 Yeah.

Dr. Rhonda Patrick 1:44:59 When you're starting to get into that melatonin rising phase of-

Andrew Huberman 1:45:03 Mm-hmm

Dr. Rhonda Patrick 1:45:03 ... you know, of, of your cycle.

Andrew Huberman 1:45:06 Yeah. It's interesting. I, 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 befo- 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 it... to me, it's very simple. Uh, 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, [laughs] right?

Dr. Rhonda Patrick 1:45:31 Mm-hmm.

Andrew Huberman 1:45:31 Sometime during the day. And also, if you exercise fasted or after a small snack... It's kind of interesting when Stacy Sims said, "Not everyone should exercise fasted." 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 it, and it... 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 i- it told me something really important about the kind of sociology of what we do, which is when something validates people's experience, they, they love it. But it doesn't mean that the things that work for other people don't work, and I think that that's the, 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? [laughs] So, um, you do the best you can.

Dr. Rhonda Patrick 1:46:23 Right.

Andrew Huberman 1:46:23 Right? I think is what it comes down to. In fact, I b- meant to ask you earlier, and this is a good time to, um, to talk about this. Uh, you've described that if you are slightly sleep deprived, so not f- four hours per night or an all-nighter, but if you've only slept five, or let's say you're getting a, an hour or two less than your normal ration of sleep, there's some pretty significant inflammation that's, that, that occurs that's not good. But I've heard you cover that exercising can actually offset some of that inflammation. This answers a, a, an important and common question, which is, if I have to pick between sleep and exercise, what do I do? [laughs]

Dr. Rhonda Patrick 1:46:59 Yeah.

Andrew Huberman 1:46:59 Um, and it sounds like if it's one night poor sleep, exercise.

Dr. Rhonda Patrick 1:47:04 Yeah.

Andrew Huberman 1:47:04 But you, but you don't wanna make it a habit. That's... Uh, do I have that right?

Dr. Rhonda Patrick 1:47:07 Right. Yeah. I mean, so this, this data, a lot of it actually comes from you can cause even acute insulin resistance after, like, a night of, of sleep deprivation, certainly after-

Andrew Huberman 1:47:18 Mm-hmm

Dr. Rhonda Patrick 1:47:18 ... two to three nights of-

Andrew Huberman 1:47:19 Mm-hmm

Dr. Rhonda Patrick 1:47:19 ... sleep deprivation. And, you know, again, a lot of that's coming down to some of the th- things we've already talked about. And, um, 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, uh, and when I was a new parent. Of course, you're not getting enou- enough sleep, and so that's... I learned it... Before I actually dove into the science about it, I l- 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 don't really... you're not really exercising much at all.

Andrew Huberman 1:47:54 Yeah. Evolution wants the-

Dr. Rhonda Patrick 1:47:56 Yeah

Andrew Huberman 1:47:56 ... the baby to survive.

Dr. Rhonda Patrick 1:47:57 You're, you're recovering too.

Andrew Huberman 1:47:58 Yeah. Yeah.

Dr. Rhonda Patrick 1:47:58 I mean, childbirth is a very-

Andrew Huberman 1:48:00 Sure

Dr. Rhonda Patrick 1:48:00 ... it, it's a very traumatic process on the body. And so, um, I noticed that my, my glucose response was like... it was like pre-diabetic, and I was like, "What is going on?" And, um, 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, my glucose being, my fasting glucose-

Andrew Huberman 1:48:31 Wow

Dr. Rhonda Patrick 1:48:31 ... being really high, and also my postprandial glucose being higher than, than usual. And so, um, I looked into the studies, and there's now... You can, 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, 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?

Andrew Huberman 1:49:01 Mm-hmm.

Dr. Rhonda Patrick 1:49:01 If you're, 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? There's... So there's lots of ways around some of these rules that we hear about.

Andrew Huberman 1:49:13 Mm-hmm. Mm-hmm.

Dr. Rhonda Patrick 1:49:13 But with the, with the sleep loss, it really is... it's, it's interesting because people, like, when they don't get sleep, the last thing they wanna do is work out. And obviously, like, you don't wanna 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... So obviously poor sleep is a problem, you know, in the United States. I mean, a lot of people are, are sleeping fewer than seven hours a night. And, um, 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 and you don't wanna be on either end of the spectrum. And usually, like, sleeping long, there's, like, other disease states associated with it, right?

Andrew Huberman 1:50:02 Mm-hmm.

Dr. Rhonda Patrick 1:50:03 But, um, 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. And the same for, like, more than 10. They have a higher all-cause mortality than people getting between seven and, and nine. ButIf 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.

Andrew Huberman 1:50:28 Right. Well, 'cause 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, ah, cardio, like getting your heart rate elevated, and then doing addition to that, and then you're hiking, I mean, that-- it's just, ah, I think the guidelines are a good jumping off place for people to think about.

Dr. Rhonda Patrick 1:50:50 Well-

Andrew Huberman 1:50:51 Um.

Dr. Rhonda Patrick 1:50:51 ... we can talk about that because there's a new study that kind of throws-

Andrew Huberman 1:50:54 Yeah, you only-

Dr. Rhonda Patrick 1:50:55 ... that on the head.

Andrew Huberman 1:50:55 Yeah.

Dr. Rhonda Patrick 1:50:55 But, but the point is, is that if they were-- if people were exercising within the guideline range-

Andrew Huberman 1:50:59 Mm-hmm

Dr. Rhonda Patrick 1:51:00 ... that they basically, if they weren't getting enough sleep, if they were getting fewer than seven hours of sleep per night, that they, 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.

Andrew Huberman 1:51:18 So find the time to exercise, folks.

Dr. Rhonda Patrick 1:51:20 Yeah.

Andrew Huberman 1:51:21 But of course, periods of time, like after a new child or a new job or a particularly stressful time, I don't know any human being, I don't care how driven, um, okay, there's pro- Doggins and Cam Haynes being probably exceptions and a few others.

Dr. Rhonda Patrick 1:51:37 Outliers.

Andrew Huberman 1:51:37 You know, um [laughs] , I know you can ride out on a few others, but people who-- everybody ha- else, um, seems to have periods of time where they need to just back off a bit.

Dr. Rhonda Patrick 1:51:47 Mm-hmm.

Andrew Huberman 1:51:48 I know I certainly do, and I feel like I'm doing pretty well for myself, uh, despite, you know. And, and I think that it, it's important that people not hold themselves to a standard that is gonna make them sick or injured or miserable beyond... Yeah, you also wanna continue to enjoy health-promoting activities, right? [laughs]

Dr. Rhonda Patrick 1:52:06 Right.

Andrew Huberman 1:52:06 Yeah.

Dr. Rhonda Patrick 1:52:06 I mean, you gotta 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 it's s- you're sacrificing your happiness too, I mean, then that's a problem, right?

Andrew Huberman 1:52:22 Yeah.

Dr. Rhonda Patrick 1:52:22 'Cause that's part of the equation. Happiness is part of that healthy equation.

Andrew Huberman 1:52:25 Yeah. Health is a daily and lifelong thing, but sometimes it means taking a day off. I think that's what people don't say. Um, 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, uh, you know, coming off the accelerator can be really useful.

Dr. Rhonda Patrick 1:52:47 Yeah. Well, I also wanna just mention because, you know, we, we talked about my... You know, I, I work out a lot, and I am sort of addicted to it, but, like, not everyone has the time-

Andrew Huberman 1:52:57 Yeah

Dr. Rhonda Patrick 1:52:57 ... and motivation to, to go spend an hour block of time working out, and this is where I think the-- 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 and, you know, counting towards adding up to, to their, uh, physical activity, you know, requirements for the, for the week. And so there's these-- there's a lot of studies now. There's on something called, um, vigorous intermittent lifestyle physical activity, VILPA studies. Have you heard of those?

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

Dr. Rhonda Patrick 1:53:38 They're unstructured.

Andrew Huberman 1:53:39 Ex-

Dr. Rhonda Patrick 1:53:40 Uh, they're unstructured, and n-not everyone likes the word exercise snacks. I mean, I, I kinda like it, but the unstructured exercise, they're, they're the, they're the, 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.

Andrew Huberman 1:53:57 Mm-hmm.

Dr. Rhonda Patrick 1:53:57 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, um, 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, n- extremely unreliable. 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, when you're trying to recall that. So these accelerometers are, are worn on people's wrists, and they're me- 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 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 up. They're actually not measuring their heart rate in these studies. They're moving faster with intent, right? They're, they're jogging or they're, um, you know, they're not... Of course, there's the cases where they're actually exercising, but-

Andrew Huberman 1:55:00 Mm-hmm

Dr. Rhonda Patrick 1:55:00 ... but the short bursts of it, um, they're doing the things that I just mentioned, and it's having outsize effects on, 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, and it's considered more vigorous because of your-- the intent to move, right? It'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.

Andrew Huberman 1:55:39 Wow.

Dr. Rhonda Patrick 1:55:39 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. The people that just-- they're just take-- they're, they're doing those things, right? They're playing with their grandkids or their kids or their puppies or whatever. And so, um, these moments, they add up. And I'm, 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 th- 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-

Andrew Huberman 1:56:13 Mm-hmm

Dr. Rhonda Patrick 1:56:13 ... after another after another.

Andrew Huberman 1:56:14 Yeah.

Dr. Rhonda Patrick 1:56:14 I mean, it's, it's undeniable that these short moments of, you know, getting physically active, active do add up. AndStructured exercise snacks can be part of that. Like maybe you don't have a puppy, maybe you don't have a kid yet, maybe you work from home and you're not taking these... You know, maybe your situation's 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 m- two s- 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 workday 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.

Andrew Huberman 1:57:01 Mm-hmm.

Dr. Rhonda Patrick 1:57:01 So being sedentary means, like, 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.

Andrew Huberman 1:57:14 Mm-hmm.

Dr. Rhonda Patrick 1:57:14 But I just like to mention that as well. I would say being sedentary is a disease, actually. That's, that's something-

Andrew Huberman 1:57:20 Mm

Dr. Rhonda Patrick 1:57:20 ... I mean, people aren't thinking about it, but...

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

Dr. Rhonda Patrick 1:57:33 We do have data, for one, measuring cardi- cardiorespiratory fitness, which is a marker of cardiovascular health-

Andrew Huberman 1:57:40 Mm-hmm

Dr. Rhonda Patrick 1:57:40 ... being physically fit, right?

Andrew Huberman 1:57:41 Mm-hmm.

Dr. Rhonda Patrick 1:57:41 Obviously the gold standard of that would be measuring VO2 max, your maximal oxygen uptake during maximal exercise.

Andrew Huberman 1:57:48 Mm.

Dr. Rhonda Patrick 1:57:48 A lot of studies do not actually directly measure VO2 max.

Andrew Huberman 1:57:51 Mm.

Dr. Rhonda Patrick 1:57:51 They'll do, you know, maybe sub- 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? So, like, a 12-minute run would be an example. People do that. You, you run as fast as you can and maintain that pace for 12 minutes. So you're not going all out, obviously.

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

Dr. Rhonda Patrick 1:58:18 Yeah, yeah.

Andrew Huberman 1:58:19 Yeah.

Dr. Rhonda Patrick 1:58:19 And then, and there's a calculation out there that's done to kind of estimate your VO2 max. And so some studies-

Andrew Huberman 1:58:24 Mm

Dr. Rhonda Patrick 1:58:24 ... or a lot of studies are actually doing sort of an estimation of cardiorespiratory fitness.

Andrew Huberman 1:58:28 Mm-hmm.

Dr. Rhonda Patrick 1:58:28 So cardiorespiratory fitness, um, is really important, I think, for, you know, m-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?

Andrew Huberman 1:58:43 Mm-hmm.

Dr. Rhonda Patrick 1:58:43 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, you're not, um, obese, but you have a low cardiorespiratory fitness, it is as bad or worse in terms of your all-cause mortality, your, you know, 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, I'm stretching it a little bit.

Andrew Huberman 1:59:18 Mm-hmm.

Dr. Rhonda Patrick 1:59:18 But cardiorespiratory fitness is a marker of, I would say, fitness.

Andrew Huberman 1:59:22 Mm.

Dr. Rhonda Patrick 1:59:22 And so, um, that's why I think being sedentary is an, 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. If you go from low to, um, high normal, you know, that's, like, almost a three-year increase in life expectancy. And if you go up to high, then you're talking about a five-year increase in life expectancy compared to where you were at with low.

Andrew Huberman 1:59:50 Wow.

Dr. Rhonda Patrick 1:59:50 But again-

Andrew Huberman 1:59:50 Mm

Dr. Rhonda Patrick 1:59:51 ... I'm, I'm not talking about VO2 max, I'm talking about cardiorespiratory fitness.

Andrew Huberman 1:59:53 Mm.

Dr. Rhonda Patrick 1:59:53 And it's, it's really important. Here's another reason why I think that it's, it's really bad. So these, 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, 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.

Andrew Huberman 2:00:14 A slow, steady state.

Dr. Rhonda Patrick 2:00:14 Mm-hmm. Yeah. About 40% of people don't respond.

Andrew Huberman 2:00:16 Mm.

Dr. Rhonda Patrick 2:00:16 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 min- a minute running around chasing your, your grandkid or your puppy or your child, you know, that's, that's, that's a HIIT session.

Andrew Huberman 2:00:32 Or taking the stairs. That's amazing. I was traveling with my team-

Dr. Rhonda Patrick 2:00:34 Sprinting up the stairs

Andrew Huberman 2:00:35 ... oh, sprinting up the s- the stairs, or if you're carrying a lot of luggage in the airport, like, going up the stairs or down the stairs.

Dr. Rhonda Patrick 2:00:40 Right.

Andrew Huberman 2:00:41 It's wild. When you go to the airport, I, I, I like to notice this, um, nobody takes the stairs.

Dr. Rhonda Patrick 2:00:48 Yeah.

Andrew Huberman 2:00:49 Down or up.

Dr. Rhonda Patrick 2:00:50 Yeah.

Andrew Huberman 2:00:50 Like, the escalators are there.

Dr. Rhonda Patrick 2:00:51 It's the luggage. It's the luggage.

Andrew Huberman 2:00:51 And I'm always like, "Oh, this is a great opportunity to get some extra steps and some extra work." But I realize that's me. Um, but it's just, it's striking. Um, and if you're in DC ever, you know, they have these long stairwells that go, um, up from the, from the public transport, and that's a workout, you know? [laughs] And, and-

Dr. Rhonda Patrick 2:01:07 Carrying your luggage. [laughs]

Andrew Huberman 2:01:07 ... and I'm always like, "Oh, free workout."

Dr. Rhonda Patrick 2:01:09 Yeah, yeah.

Andrew Huberman 2:01:09 Like, you know, I 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 gonna be?" All the mice are going up the automatic elevator. It makes sense. And then why they would wanna do that, but these opportunities for exercise are clearly there. I, I feel like-

Dr. Rhonda Patrick 2:01:29 Yeah

Andrew Huberman 2:01:29 ... this is also, I, I would be remiss if I didn't do a quick shout-out to Steve Magness. Do you fo- ever see his content?

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

Andrew Huberman 2:01:37 Yeah.

Dr. Rhonda Patrick 2:01:37 I mean...

Andrew Huberman 2:01:37 I've never met him, but, um, people should, uh-

Dr. Rhonda Patrick 2:01:39 On, on Twitter. I've interacted with him on X.

Andrew Huberman 2:01:41 Yeah. Uh, people should, um, I think give him a follow. He's an, a very accomplished runner, uh, in his past, a running coach, I believe, as well, and, um, and a scientist, and I think has the best take on sort of measuring VO2 max. It's kind of interesting. You know, 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.

Dr. Rhonda Patrick 2:02:05 Mm.

Andrew Huberman 2:02:06 And he says people are generally surprised how easy the easy stuff should feel and how hard the hard stuff should feel. So I wa- just wanna credit Steve for saying that. So I try and keep that in mind around my cardio and do some high... I do a less of what you do, I, I confess, um, some high-intensity interval training, Tabata-type stuff, and then some wa- a lot of walks, a lot of hikes.

Dr. Rhonda Patrick 2:02:24 Yeah.

Andrew Huberman 2:02:25 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"

Dr. Rhonda Patrick 2:02:35 [laughs]

Andrew Huberman 2:02:35 ... like, that's accomplishing what you want, but actually there's a much easier pathTo better health, which is what you do and more or less what Steve is describing as well.

Dr. Rhonda Patrick 2:02:44 Yeah.

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

Dr. Rhonda Patrick 2:02:46 Yeah.

Andrew Huberman 2:02:47 Yeah.

Dr. Rhonda Patrick 2:02:47 I think so. I mean, I do, I do mix in quite a bit of probably more, more high-intensity interval training but, um, you know, I don't feel... Like, if I felt like it was, like, if I didn't feel good-

Andrew Huberman 2:02:58 Mm-hmm

Dr. Rhonda Patrick 2:02:58 ... I would, I would toggle down the, the pedal, right? I wouldn't keep-

Andrew Huberman 2:03:00 Mm

Dr. Rhonda Patrick 2:03:00 ... keep going on it.

Andrew Huberman 2:03:01 Right.

Dr. Rhonda Patrick 2:03:01 So I think you have to, again, just listen to your body. You know, you don't wanna overdo things. And I am-- I mean, there are people out there that are really, like, ah, endurance athletes that are, you know, like, that's not me. I'm a committed exerciser. I'm not, I'm not necessarily an athlete. Um, but, but yeah, so that would-- that's-- there's different, I think, levels here.

Andrew Huberman 2:03:21 Mm-hmm.

Dr. Rhonda Patrick 2:03:22 Steve is obviously athlete.

Andrew Huberman 2:03:23 Anyway, I've, I've learned from him around this topic.

Dr. Rhonda Patrick 2:03:26 Yeah.

Andrew Huberman 2:03:26 Uh, it's been, it's been helpful. I'd like to take a quick break and acknowledge one of our sponsors,

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Andrew Huberman 2:05:16 I wanna ask you about creatine.

Dr. Rhonda Patrick 2:05:17 Yeah. [laughs]

Andrew Huberman 2:05:18 Uh, I'm 50. I started taking-- weight training and running when I was like 16 maybe. Yeah. And I started taking creatine 'cause back then I was skinny, I wanted to put on muscle. I think creatine was sort of first discussed or released back then [laughs] when I was maybe eighteen or something like that. Something like that. Eighteen, nineteen. Um, so I've been taking it a long, long time.

Dr. Rhonda Patrick 2:05:40 Sure, yeah.

Andrew Huberman 2:05:41 Five to ten grams. But the original protocol, which nobody does anymore, but I confess I still do it 'cause 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 'cause the idea was you were supposed to spike your insulin, and then you get more into the muscles.

Dr. Rhonda Patrick 2:06:01 Mm-hmm.

Andrew Huberman 2:06:01 And then you had a, a maintenance dose, which was five grams per day. Um, and the idea back then was that you needed to do a washout every twenty weeks or so where you just stop taking it, you urinate out a bunch of water, and then you re-reload. And I confess, I've continued to do this minus the grape juice, but occasionally I'll do the grape juice thing. 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, um, stronger. Um, I did-- I wasn't aware of the cognitive benefits.

Dr. Rhonda Patrick 2:06:35 They weren't being studied back then.

Andrew Huberman 2:06:36 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 [laughs] of the year. We should start a supplement of the year thing.

Dr. Rhonda Patrick 2:06:47 I know.

Andrew Huberman 2:06:47 Right? For a while, I think vitamin D and melatonin came first. Um, we'll have to figure out what years those were. Then, uh, I feel like creatine got supplement of the year for 2026 un-unless something else comes along. So creatine, supplement of the year, 2026, even though it's been around for a long, long time. What do you think happened?

Dr. Rhonda Patrick 2:07:06 Well, so first I wanna talk about your loading phase, and I-- like, 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 crea- for your muscle creatine stores to become saturated.

Andrew Huberman 2:07:20 Mm-hmm.

Dr. Rhonda Patrick 2:07:20 And researchers aren't gonna [laughs] do a study where they wait that long. So the loading phase really was just-

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

Dr. Rhonda Patrick 2:07:27 Yeah.

Andrew Huberman 2:07:27 Oh, okay.

Dr. Rhonda Patrick 2:07:27 It was-- It's in this isolated bubble of in the experimental protocol. But like-

Andrew Huberman 2:07:32 Mm

Dr. Rhonda Patrick 2:07:32 ... in the real world-

Andrew Huberman 2:07:33 Got it

Dr. Rhonda Patrick 2:07:33 ... you have three weeks. Or if you're like an athlete-

Andrew Huberman 2:07:35 Mm-hmm

Dr. Rhonda Patrick 2:07:35 ... and you hadn't, you know, taken the creatine, you don't have your creatine stores up, and you have to quickly, rapidly-

Andrew Huberman 2:07:40 Got it

Dr. Rhonda Patrick 2:07:40 ... like, just fix your-

Andrew Huberman 2:07:40 I was just amazed at how quickly it worked. I g- I, I might be a hyper responder, but I legitimately put on... I realize some of it was water, or most of it was water, but somewhere between probably four and eight pounds of-

Dr. Rhonda Patrick 2:07:53 Of lean?

Andrew Huberman 2:07:53 ... of water in the muscle mass. I don't wanna call it lean mass because it's-

Dr. Rhonda Patrick 2:07:57 Yeah

Andrew Huberman 2:07:57 ... you know, it's water in the muscle. Um, but I, I just was-- I was like, "Oh my goodness, this is crazy," you know? And um, 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. Um, pretty remarkable molecule.

Dr. Rhonda Patrick 2:08:14 Yeah.

Andrew Huberman 2:08:14 Mm.

Dr. Rhonda Patrick 2:08:15 I mean, obviously creatine is stored as creatine phosphate in our, in our cells.

Andrew Huberman 2:08:19 Mm-hmm.

Dr. Rhonda Patrick 2:08:19 We make, to some degree, uh, you know, 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 en-energetically demanding. So having the creatine stores higher in your muscle is beneficial because, one, you're gonna 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.

Andrew Huberman 2:08:49 Mm-hmm.

Dr. Rhonda Patrick 2:08:49 It's just helping you train more, getting more reps in, you know, and whatever it is, training, train- your training volume's going up, and because your training volume's going up, then you're obviously putting more stress on your muscles, which is gonna lead to increased muscle protein synthesis.

Andrew Huberman 2:09:04 Mm-hmm.

Dr. Rhonda Patrick 2:09:04 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, um, as I started to get into resistance training, I was like, "I better start taking this." [laughs] This is... I'm, like, in this, in this world now, and started doing some research and taking it. So I was taking the five grams a day-

Andrew Huberman 2:09:30 Mm-hmm

Dr. Rhonda Patrick 2:09:30 ... 'cause that's really what most of the studies show. Creatine monohydrate, that's w- the most well-researched form of creatine. And I was taking five grams a day because I was interested in improving my, my training volume and, and getting the, the, the benefits of it, right? Um, and then I had Darren Cando on the podcast, uh, that was in 2024, I think it was, and, um, once I had started getting into the creatine research, I... The brain stuff started-- has been coming out over the past, you know, few years.

Andrew Huberman 2:10:02 Mm-hmm.

Dr. Rhonda Patrick 2:10:03 And that's, for me, become very interesting. I remember the first time I heard about it years ago, it was like, "Oh, it's, it's helping improve cognitive function in older, older p- you know, people."

Andrew Huberman 2:10:11 Yeah, the phosphocreatine system seems to be somewhat, um, biased towards forebrain structures. You know, I mean, obviously it's in lots of brain areas-

Dr. Rhonda Patrick 2:10:20 Yeah

Andrew Huberman 2:10:20 ... but that there might be a heavier reliance on it for brain areas that are associated with strategic planning and, you know-

Dr. Rhonda Patrick 2:10:27 Oh, interesting

Andrew Huberman 2:10:27 ... working memory and... Yeah.

Dr. Rhonda Patrick 2:10:28 Interesting.

Andrew Huberman 2:10:28 If you, if you were to sort of just map the, the, the sort of density of usage of the phosphocreatine system, you'd, you'd see a frontal bias for sure.

Dr. Rhonda Patrick 2:10:36 Okay.

Andrew Huberman 2:10:36 Yeah.

Dr. Rhonda Patrick 2:10:37 Um, well, anyways, that's kind of where my interest in, in-

Andrew Huberman 2:10:41 Mm-hmm

Dr. Rhonda Patrick 2:10:41 ... you know, kinda diving deeper. Anything that's helping the brain is interesting to me-

Andrew Huberman 2:10:46 Mm-hmm

Dr. Rhonda Patrick 2:10:46 ... as I know it to you as well.

Andrew Huberman 2:10:47 Mm-hmm.

Dr. Rhonda Patrick 2:10:48 And, um, and so I learned a lot from this podcast I did with Darren Cando. 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... 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, um, it's not like... So it's kinda like the muscle, right? You're not just gonna... If you take creatine and you don't work out, you're not gonna, you're not gonna get any increase in lean mass, right? It's not gonna 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 gonna 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. 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, we're learning, we're thinking. I mean, it is stressful on the brain, right?

Andrew Huberman 2:11:58 Mm-hmm. Mm-hmm.

Dr. Rhonda Patrick 2:11:58 So I mean, I am obviously speculating here and taking, taking... I'm extrapolating, right? I'm not, 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... You know, again, it's like, I think, between one to three grams or something. I'm not exactly sure how much, but it makes its own creatine. And it's kind of resistant to taking up the creatine that you're supplementing with, um, 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, in particular, right, your muscles are kind of consuming that because that's... They're very greedy for it, right? Uh, and, 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, and they're going higher than, than what you would get from just your brain normally making its own creatine. So the 10 grams of creatine a day, which is now what my baseline [laughs] is, is based off of that. But there's studies now showing that, um, if you're in this sort of stressed state, your brain is stressed, like for sleep, 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 have a... When I travel internationally, I never really sleep good on a, 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, cognitively.

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

Dr. Rhonda Patrick 2:13:44 Right. [laughs]

Andrew Huberman 2:13:44 Yeah.

Dr. Rhonda Patrick 2:13:45 Well, some people can sleep great on a plane, but I'm not one of those people. So, um, there have now been at least one study showing that if you give someone, it's like something like .35 grams per kilogram body weight of creatine, which comes out to a lot. I mean, it's like 20, 25. Depends on your body weight, right? Like y- you... 20, 25 grams-

Andrew Huberman 2:14:05 Yeah

Dr. Rhonda Patrick 2:14:05 ... perhaps even more. I mean-

Andrew Huberman 2:14:07 I mean, I'm 100 kilograms.

Dr. Rhonda Patrick 2:14:08 Yeah.

Andrew Huberman 2:14:08 That's a lot of creatine.

Dr. Rhonda Patrick 2:14:08 So it would be a lot.

Andrew Huberman 2:14:09 Yeah.

Dr. Rhonda Patrick 2:14:09 So for me-

Andrew Huberman 2:14:10 Yeah

Dr. Rhonda Patrick 2:14:10 ... 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, you know, 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, and when your sh- brain stre- cells are stressed out, right, I mean, like, energy, energetic demand goes up, and if you have more creatine, it's gonna 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.

Andrew Huberman 2:15:04 Mm-hmm.

Dr. Rhonda Patrick 2:15:04 This is all early.Early data.

Andrew Huberman 2:15:07 Mm-hmm.

Dr. Rhonda Patrick 2:15:07 Like, 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.

Andrew Huberman 2:15:19 You spread it out?

Dr. Rhonda Patrick 2:15:21 I do it in two doses.

Andrew Huberman 2:15:22 Mm-hmm.

Dr. Rhonda Patrick 2:15:22 I mean, some people are very sensitive to a 10 gram-

Andrew Huberman 2:15:24 Mm-hmm

Dr. Rhonda Patrick 2:15:24 ... dose where they might, like, get a GI irritation effect.

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

Dr. Rhonda Patrick 2:15:30 Diarrhea.

Andrew Huberman 2:15:30 Yeah.

Dr. Rhonda Patrick 2:15:30 Exactly, yeah. So the very scientific way [laughs] putting it.

Andrew Huberman 2:15:34 Yeah.

Dr. Rhonda Patrick 2:15:34 But I mean, that... So I, I do spread it out, and I take it-- I don't take it at night. I like to take mine in the morning.

Andrew Huberman 2:15:40 Mm-hmm.

Dr. Rhonda Patrick 2:15:40 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, a-- My brain is under a lot of stress 'cause I'm constantly learning. I'm reading papers.

Andrew Huberman 2:15:49 Mm-hmm.

Dr. Rhonda Patrick 2:15:49 And like I said, I'm, 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 five to 10, really does seem to affect my brain functioning, like, later in the day, where I seem to keep, keep going better, where I-

Andrew Huberman 2:16:08 Great

Dr. Rhonda Patrick 2:16:09 ... I'm not getting as tired. And it could be placebo, which is fine. Like I said, I am fine with placebo [laughs] effects. As long as what I'm ingesting is not actually bad for you-

Andrew Huberman 2:16:18 Mm-hmm

Dr. Rhonda Patrick 2:16:18 ... placebo's fine with me.

Andrew Huberman 2:16:19 Mm-hmm.

Dr. Rhonda Patrick 2:16:19 Um, 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, I'm always sleep deprived. I mean, I, 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 'cause that's brilliant, 'cause that's like one of my... that's one of my problems. 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 they're of c- it's like, you know, it's not all the time.

Andrew Huberman 2:16:53 Mm-hmm.

Dr. Rhonda Patrick 2:16:53 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 gonna be beneficial for the brain," if it's gonna improve cognitive function, that's really something that people are interested in.

Andrew Huberman 2:17:11 Right.

Dr. Rhonda Patrick 2:17:11 Now, again, I don't know that it's like if you're just some young, healthy person that gets all their s- you're getting... You're sleeping well, 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 it may be helpful for that as well. There's been some studies with children looking at creatine supplementation after, um, a, a TBI, and it seems to help with their, their recovery. Um, I am probably experiencing brain aging. So I'm just kind

Dr. Rhonda Patrick 2:17:43 of-

Andrew Huberman 2:17:43 Uh, I'm gonna 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, the, uh, people tend to, uh, 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, uh, 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, Torsten Wiesel, who, uh, co-recipient the Nobel Prize for brain plasticity and vision, he's still alive, and he, he was... I think he still runs. He's in his late 90s. And he paints, and he's, and he's sharp. So I just... I, I, I made a point to only interrupt here. People can check the, the data on the previous portions of the podcast, but and just say, I actually think that cognitively s- I'm using biologists as an example, it's possible in aspects of life where you're, um, 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.

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

Andrew Huberman 2:18:53 I... There's a theory, but I see you as that. And I'm, again, I'm not just saying it to be complimentary, although it is a compliment. I... It seems like you're, you're picking up steam. You're s- thinking about things. You're not forgetting things from way back when. You're building on the, the concepts and knowledge from way back when. So I, I find it reassuring that you, um, biologists in particular seem to have this, you know, up and to the right trajectory for cognition.

Dr. Rhonda Patrick 2:19:15 It's interesting. My, my late mentor, um, Dr. Bruce Ames-

Andrew Huberman 2:19:18 Mm-hmm

Dr. Rhonda Patrick 2:19:19 ... was every bit of that. I mean, you know, he passed away a little over a year ago. He was 96. But, you know, some of his most... He claims some of his b- best work was done, you know, in his late 80s.

Andrew Huberman 2:19:29 Right.

Dr. Rhonda Patrick 2:19:29 You know, where-

Andrew Huberman 2:19:29 You don't see that in math or physics.

Dr. Rhonda Patrick 2:19:31 Very... Yeah.

Andrew Huberman 2:19:31 Yeah.

Dr. Rhonda Patrick 2:19:31 So it'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 physic- physics as you're, as you're... Like, I, I, I just don't know.

Andrew Huberman 2:19:42 I don't know. I don't either.

Dr. Rhonda Patrick 2:19:42 But, like, with biology and, I mean, we're constantly learning new things and, 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? Like, that's like you're, you're inc- you're increasing synaptic connections and neuroplasticity-

Andrew Huberman 2:19:59 Mm-hmm

Dr. Rhonda Patrick 2:19:59 ... and you're keeping your brain younger in that way too, right?

Andrew Huberman 2:20:01 Mm-hmm.

Dr. Rhonda Patrick 2:20:01 So, uh, I, I think the learning process is-

Andrew Huberman 2:20:04 Mm-hmm

Dr. Rhonda Patrick 2:20:05 ... is super important, whether it's biology or whatever you're passionate about, right? Like, you learn new languages, what... Like, the learning process itself is something that is so important for, for brain aging as well. Um, and yeah, so I, I, I would agree with you that... But brain aging in general, yeah, I'm o- obviously chronologically aging, and there is some degree [laughs] of aging going on in my brain. But, you know, so that's, that's I think where the creatine craze has come from is the interest in... And I, and I've definitely played a role in some of this, you know, by-

Andrew Huberman 2:20:34 Yeah

Dr. Rhonda Patrick 2:20:34 ... by-

Andrew Huberman 2:20:34 Yeah

Dr. Rhonda Patrick 2:20:34 ... you know, talking, talking about my experience and, and, and being super interested in it because it's like it's felt good for me, and I've noticed-

Andrew Huberman 2:20:43 Mm-hmm

Dr. Rhonda Patrick 2:20:43 ... this experience, and this is completely anecdata again, but in addition with the small studies, and they are small. Uh, like, I don't know if you've looked at them, but they're, they're... You can, you can-

Andrew Huberman 2:20:53 Subject numbers are not huge.

Dr. Rhonda Patrick 2:20:54 Yeah. They're small, and you can poke holes in them, and, uh, you would be completely, you know, okay poking holes because it's-

Andrew Huberman 2:21:01 Mm-hmm

Dr. Rhonda Patrick 2:21:01 ... they're small s- 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, um, maybe there's something here. I think that more research is gonna come out on it, and I feel great.doing it.

Andrew Huberman 2:21:17 Mm-hmm.

Dr. Rhonda Patrick 2:21:17 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.

Andrew Huberman 2:21:24 Oh, yeah?

Dr. Rhonda Patrick 2:21:24 Yeah. But again, it could be that, you know, placebo-

Andrew Huberman 2:21:28 Mm

Dr. Rhonda Patrick 2:21:28 ... nocebo thing where... Who knows? Who knows?

Andrew Huberman 2:21:30 Sure.

Dr. Rhonda Patrick 2:21:30 But, you know, let's just say it is real, you know, for me, I gotta have, I gotta have my, my 10 grams of creatine for my brain. Um, you know, who knows? I may, in five years, be like, "I was wrong. We'll see new data come out."

Andrew Huberman 2:21:41 Sure.

Dr. Rhonda Patrick 2:21:41 But I don't think so.

Andrew Huberman 2:21:42 Mm-hmm.

Dr. Rhonda Patrick 2:21:43 I think, I think we're gonna have... I think this is, like, the next... A lot of people doing creatine research, it's, it's the new thing. They're really-

Andrew Huberman 2:21:50 Mm-hmm.

Dr. Rhonda Patrick 2:21:50 'Cause there's been a lot of work on exercise physiology and, you know, training volume-

Andrew Huberman 2:21:53 Yeah, the safety data are there, so it's not like they have to get a lot of cl-

Dr. Rhonda Patrick 2:21:57 The, the-

Andrew Huberman 2:21:57 ... you know, human subjects clearance

Dr. Rhonda Patrick 2:21:58 ... safety data is there. The safety data-

Andrew Huberman 2:21:59 Yeah

Dr. Rhonda Patrick 2:21:59 ... is... I mean, it's the most well-studied, you know, one of the w- most well-studied supplements out there, like you said.

Andrew Huberman 2:22:05 Mm-hmm.

Dr. Rhonda Patrick 2:22:05 I mean, you were taking it when you were 18, and it was-

Andrew Huberman 2:22:07 Yeah, ages ago

Dr. Rhonda Patrick 2:22:07 ... studied back then. Yeah. And it's just been studied the, you know, for all the years that- [laughs]

Andrew Huberman 2:22:11 Mm-hmm

Dr. Rhonda Patrick 2:22:11 ... that you've been taking it. So, I mean, if it was unsafe, like, we really would know.

Andrew Huberman 2:22:15 Mm-hmm.

Dr. Rhonda Patrick 2:22:16 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 gonna go, like, mainline 50 grams a day, I mean, I don't know, that's a little much. But-

Andrew Huberman 2:22:27 Someone on the internet will do it

Dr. Rhonda Patrick 2:22:28 ... there's always... Yeah. There's always the extreme.

Andrew Huberman 2:22:29 People dry... What do 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 gonna 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. Uh, you know what? As we're talking about creatine, I want to talk about some other s- uh, supplements. Um, 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