The Science of Eating for Health, Fat Loss & Lean Muscle | Dr. Layne Norton

Andrew Huberman 0:00 (instrumental music) Welcome to the Huberman Lab Podcast, where we discuss science, and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today my guest is Dr. Layne Norton. Dr. Norton is one of the foremost experts in protein metabolism, fat loss, and nutrition. He did his degrees in biochemistry and nutritional sciences, and is considered one of the world experts in understanding how we extract energy from our food, and how exercise and what we eat combine to impact things like body composition and overall health. Today we discuss an enormous number of topics under the umbrella of nutrition and fitness, including for instance, what is energy balance? That is, how do we actually extract energy from our food? We also discuss the somewhat controversial topic of artificial sweeteners, whether or not they are safe or not, and whether or not they are an effective tool for weight loss and particular for people suffering from obesity and different types of diabetes. We also talk about gut health, that is the gut microbiome, and how it's impacted by food and how it can actually impact the metabolism of the foods that we eat. We also discuss fasting or so-called intermittent fasting or time-restricted feeding, what it does and what it does not do in terms of how effective it is for weight loss, and perhaps even for health and longevity. We also talk about protein, and define very clearly how much protein each and all of us need depending on our daily activities and life demands. We discuss the various types of diets that you've probably heard about, including ketogenic diets, vegan diets, vegetarian diets, and pure carnivore diets as well as more typical omnivore diets, and how to make sure that you get all of the essential amino acids that are critical for healthy weight maintenance, weight loss, or directed muscle gain. We also talk about supplements, in particular the supplements for which there is an immense amount of science pointing to their safety and efficacy for fitness and for overall body composition. What I'm sure will become clear to you as you hear Layne talk about each and every one of these topics is that he has an incredible ability to both understand the mechanistic science but also the real-world applications of the various discoveries that are made in particular papers, and in particular, in the randomized control trials. That is, when a given scientific hypothesis has been raised, he's extremely good at understanding why it was raised, but also at evaluating whether or not it works in the real world, which is what I believe most everybody out there is concerned with. I think this is one of the things that really distinguishes him from the other voices in the nutritional landscape. I assure you that by the end of today's discussion, you will have a much clearer understanding about what the science says about nutrition, about fitness, and about how different diets and fitness programs combine to achieve the results that

Andrew Huberman 2:53 you want. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero cost to consumer information about science, and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is LMNT. LMNT is an electrolyte drink with everything you need and nothing that you don't. That means it contains sodium, potassium, and magnesium, the so-called electrolytes, but no sugar. As you may have heard me discuss before on this podcast, every cell in our body, and in particular cells within our brain, the so-called neurons or nerve cells, critically rely on the presence of electrolytes, sodium, magnesium, and potassium, in order to function properly. I myself am a big believer in consuming electrolytes any time I've been sweating a lot, so that could be after or during exercise, or after doing the sauna. So by drinking electrolytes in the form of LMNT electrolyte mix, I'm able to replenish those electrolytes and maintain mental clarity and energy throughout the day. LMNT contains a science-backed electrolyte ratio of 1,000 milligrams of sodium, 200 milligrams of potassium, and 60 milligrams of magnesium. If you'd like to try LMNT, you can go to drinklmnt, spelled L-M-N-T, dot com/huberman to get a free sample pack with your purchase. Again, that's drinklmnt.com/huberman to get the free sample pack. Today's episode is also brought to us by ROKA. ROKA makes eyeglasses and sunglasses that are of the absolute highest quality. The company was founded by two all-American swimmers from Stanford, and everything about ROKA eyeglasses and sunglasses were designed with performance in mind. I've spent a lifetime working on the biology of the visual system, and I can tell you that your visual system has to contend with an enormous number of challenges in order for you to see clearly, for instance when you move from a sunny area to a shady area and back again, whether or not you're looking at something up close or off into the distance. ROKA understands the biology of the visual system, and has designed their eyeglasses and sunglasses accordingly so that you always see with perfect clarity. ROKA eyeglasses and sunglasses were initially designed for activities such as running and cycling, and indeed they are very lightweight. Most of the time I can't even remember that they're on my face they're so lightweight. But the important thing to know about ROKA eyeglasses and sunglasses is that while they can be used during sports activities, they also have a terrific aesthetic and they can be used just as well for wearing to work or out to dinner, et cetera. If you'd like to try ROKA eyeglasses and sunglasses, you can go to ROKA, that's R-O-K-A dot com, and enter the code Huberman to save 20% off on your first order. Again, that's ROKA, R-O-K-A, dot com, and enter the code Huberman at checkout. Today's episode is also brought to us by InsideTracker. InsideTracker is a personalized nutrition program. They analyze the data from your blood and DNA to help you better understand your body and help you reach your health goals. Now, I've long been a believer in getting regular blood work done, for the simple reason that many of the factors that impact your immediate and long-term health can only be analyzed with a quality blood test. One of the major issues with a lot of blood and DNA tests out there, however, is that you get information back about levels of hormones, levels of lipids, levels of metabolic factors, but you don't know what to do about that information. With InsideTracker, they have a easy-to-use platform that allows you to assess those levels and then determine what sorts of behavioral changes, nutritional changes, maybe even supplementation changes you might want to make in order to bring those numbers into the ranges that are optimal for you.If you'd like to try InsideTracker, you can go to insidetracker.com/huberman to get 20% off any of InsideTracker's plans. Again, that's insidetracker.com/huberman to get 20% off. The Huberman Lab Podcast is now partnered with Momentous Supplements. To find the supplements we discuss on the Huberman Lab Podcast, you can go to livemomentous, spelled O-U-S, livemomentous.com/huberman. And I should just mention that the library of those supplements is constantly expanding. Again, that's livemomentous.com/huberman. And now for my discussion with Dr. Layne Norton.

Andrew Huberman 6:50 Layne, Dr. Norton, thank you so much for being here. This is a long time coming, and I have to say, I'm really excited because I've seen you in the social media sphere. I've also listened to a number of your other podcasts. And as a fellow PhD scientist, I feel a great kinship with you. I know you have tremendous experience in, in fitness and nutrition, a number of areas. We also got a lot of questions from our audience, and I'm really looking forward to talking with you today.

Layne Norton 7:17 Yeah, I'm excited too. I mean, it's, like you said, it's been something we've been talking about for a long time, so I was glad we were able to make it happen.

Andrew Huberman 7:23 Yeah, indeed. And, um, I think some of the audience, uh, has requested a debate or a battle, and I can tell you right now-

Layne Norton 7:29 (laughs)

Andrew Huberman 7:29 ... it's not going to happen. Actually, one of the things that, um, brought Layne and I together, uh, in conversation online and then via text, et cetera, was the fact that I love to be corrected. Um, and that's what happened.

Layne Norton 7:44 (laughs)

Andrew Huberman 7:44 I ma- I did a post about artificial sweeteners, which we will talk about a little bit later in the episode, and Layne pointed out some areas of the study that I had missed, um, or maybe even misunderstood, and I revised my opinions, and I think it's wonderful, and other studies have come out since then. So hopefully, our conversation will serve as a, as a message of how, uh, science and actionable science can, um, can be perceived and, and, and that it doesn't always have to be a battle. But hey, if we get into it, we get into it. Um, it won't get physical because we know you would win.

Layne Norton 8:18 (laughs)

Andrew Huberman 8:20 So, uh, in any case, I'd like to start, um, with something that's rather basic and yet, um, can be pretty complex, um, and that's this issue of energy balance and energy utilization. I think most people have heard of a calorie.

Layne Norton 8:32 Yeah.

Andrew Huberman 8:32 Um, I am assuming that most people don't actually know what that is in terms of, uh, how it works-

Layne Norton 8:39 Okay. Yeah.

Andrew Huberman 8:39 ... and what it represents. And so maybe you could just explain for people what happens when we eat food of any kind, and how is that actually converted into energy as a way of framing up the discussion around weight loss, weight maintenance, weight gain, and body composition?

Layne Norton 8:57 It's a great question. And like you said, this is one of those things where, you know, people use the term calories in, calories out, and they say, "Well, that's way too simplistic." I'm like, "If you look at what actually makes up calories in, calories out, it's actually very complicated," right? So let's deal with the, uh, what you mentioned first. What is a calorie? Because I think a lot of people don't quite understand this. So a calorie just refers to a unit of energy, of heat specifically. And so, well, what does that have to do with food? What does that have to do with, like, what we digest and eat? Really, what you're talking about is the potential chemical energy that is in the bonds of the macronutrients of food, right? And by digesting, assimilating, and metabolizing those nutrients, we're able to create energy. And the end product of that, mostly, is ATP, um, adenosine triphosphate, which is your body's, uh, energy currency. So to understand ATP, just try to think about if you're trying to power these various reactions in your body, um, we're talking about tens of thousands of enzymes that require ATP, um, you know, it doesn't make sense that you would have to create a bunch of micro explosions, (laughs) right? You want something that can transfer high energy phosphates to power these reactions, to give up, essentially, its energy to power something that might otherwise be unfavorable. So a lot of metabolism is simply creating ATP, which the end of the line of that, I'm going to kind of work backwards, is what's called oxidative respiration. So that happens in the mitochondria. Everybody's heard, mitochondria, powerhouse of the cell. And that is done, uh, through essentially creating a hydrogen ion gradient across the mitochondria, which powers the production of ATP by converting free phosphate plus ADP to ATP. Now, the way that hydrogen ion gradient is created is through, um, you know, creating hydrodoge- hydrogen ions that can be donated through the Krebs cycle. Now, the Krebs cycle is linked to glycolysis. So if we talk about carbohydrate metabolism, carbohydrates basically, other than fructose, get converted into glucose, which can go into glycolysis, and you can produce some ATPs through glycolysis, and then it boils down to pyruvate, then acetyl-CoA, which goes through the Krebs cycle, produces a lot more ATPs from that. Uh, if you talk about protein, protein's a little bit different because protein, uh, gets converted to amino acids, which can be used for muscle protein synthesis or protein synthesis in other tissues. Uh, but it also can be converted through gluconeogenesis to glucose, and there also are some ketogenic amino acids as well. Um, and so you can have a few different ways to get to the Krebs cycle, ei- either being through, um, acetyl-CoA or through glucose going through glycol- glycolysis to pyruvate. Then you have fatty acids, which, um, are able to create energy through what's called beta-oxidation, where essentially you're taking these fatty acids and you're lopping them off two carbons at a time to produce acetyl-CoA, which again can go into the Krebs cycle-... produce those hydrogen ions that can then power the production of ATP. So that's kind of like at the cellular level of how this stuff works. But

Layne Norton 12:36 stepping back and taking it back out, like, w- what does that have to do with weight loss or weight gain, right? Well, when you think about the balance of energy in versus energy out, sounds very simple. But let's look at what actually makes up energy in versus energy out. First of all, you've got to realize that the energy in side of the equation is more difficult to track than people think, right? So one, uh, food labels, which we like to think as being, you know, like, from upon high, uh, can have up to a 20% error in them.

Andrew Huberman 13:10 Really?

Layne Norton 13:11 Oh, yeah.

Andrew Huberman 13:12 So 100 calorie, something listed as 100 calories per serving, it could, what's actually in there could be-

Layne Norton 13:16 Could be 80 or-

Andrew Huberman 13:17 ... 80 or 120?

Layne Norton 13:18 Right, exactly.

Andrew Huberman 13:19 Huh.

Layne Norton 13:19 So that's one aspect of it. The second aspect is, there's what's called your energy, but then there's also metabolizable energy, right? So if you have, uh, food stuff with, say, a lot of insoluble fiber, typically, insoluble fiber, uh, is not really digestible, and so you could have, you know, quite a bit of carbohydrate, you know. But if you can't extract the energy from it, and typically, this is because insoluble fiber from, like, plant material, the carbohydrate or/and even some of the protein is bound up in the, uh, plant structure, which makes it inaccessible to digestive enzymes. And so this is what, like, adds bulk to your sch- stool and whatnot, but again, reduces the metabolizable energy in there. And there's some evidence that based on people's individual gut microbiome, that some people may actually be better at extracting energy out of fiber compared to other people. So just starting off right there, okay, there's, there's quite a bit of play in the energy in side of things. Now, one of the things people will say is, "Well, see, that's why you shouldn't worry about tracking calories, 'cause, you know, the food labels can be 20% off." And what I'll say is, "Okay. That's a, that's... I understand where you're coming from. But typically, if it's off, it's going to be consistently off. And if you're consistent with how you track it, e- eventually, y- you'll be able to know kind of what you're taking in." And it's kind of, that's kind of like saying, "Well, don't worry about tracking, you know, if you're..." I, I like to use financial, um, examples. You know, we know that to save money, or you have to earn more money than you spend. Well, you can't exactly know how much money you're earning at a time, you know, 'cause there's inflation and then there's, uh, if you have investments, those can be, you know, different interest rates and whatnot. It's like, okay, but you're, you know, if you have a budget, you have a reasonable idea of what it's going to be, you know? And you make, you make certain assumptions, but you can relatively guess.

Andrew Huberman 15:17 Yeah, that's a good example.

Layne Norton 15:18 Right.

Layne Norton 15:19 So now let's look at the energy out side of the equation, which is actually way more complicated, right? So your energy out is a few different, uh, buckets. The first one and the biggest one is your resting metabolic rate, so your RMR. And that, for most people, is anywhere from 50 to 70% of your total daily energy expenditure. Now people use the term metabolic rate and energy expenditure kind of interchangeably, but they're not the same thing. So your total daily energy expenditure is the summation of all the energy you expend in a day.

Andrew Huberman 15:53 Walking upstairs,-

Layne Norton 15:55 Everything.

Andrew Huberman 15:55 ... exercise, if you do it.

Layne Norton 15:56 Fidgeting.

Andrew Huberman 15:57 Aye.

Layne Norton 15:57 Yeah.

Andrew Huberman 15:58 Plus your resting metabolic rate.

Layne Norton 15:59 Right. So resting metabolic rate is a big part of that, but it's not the only thing. So that's usually about 50 to 70%. And sedentary people will be on the higher end of that, so it'll be a bigger proportion. Whereas people who are more active, it'll be a little bit lower, not because their metabolic rate is lower, but because they're expending a greater percentage of their calories from physical activity. Then you have something called the thermic effect of food, which is a relatively small percentage of your total daily energy expenditure. It's about 5 to 10%. Uh, and very difficult to measure and usually, what researchers do when they're kind of looking at this stuff is they just kind of make an assumption about it. They use a constant. Uh, but that's about 5 to 10% of your daily energy expenditure. And that refers to the amount of energy it takes to extract the energy out of food. So think about your body kind of like a car, right? You don't just have gas in your tank and it spontaneously starts up, right? Like, you have to have a battery so you put in energy so you can get the energy out of the, the petrol that you have in your car. Similar with, with food, you can't just eat food and then, you know, it just appears in your cells and you start doing stuff. It has to be systematically broken down and put into forms that can actually produce energy. And so you have to put some energy in to achieve that, and a lot of times people will say something like, "Well, not all calories are created equal." That's not true, because calorie's just a unit of measurement, right? That would be like saying not all seconds on a clock are created equal. Yes, they are. All sources of calories may have differential effects on energy expenditure and appetite. So if we look at something like, um, fat, for example. The TEF of fat is about 0 to 3%. Meaning if you eat 100 calories from fat, your net will be about 97 to 100.

Andrew Huberman 17:47 So the process of breaking down that fat e- essentially subtracts some of the, the calories away because you used it in creating energy-

Layne Norton 17:56 Correct.

Andrew Huberman 17:56 ... by breaking those chemical bonds to create ATP?

Layne Norton 17:58 Correct.

Andrew Huberman 17:58 Okay.

Layne Norton 17:58 Correct. So you have, like, for example, some enzymes that require ATP to run these processes. Now fat is actually the easiest thing to convert into energy. Then you have carbohydrate, which has a TEF of like 5 to 10%. So you eat 100 calories from carbohydrate, and obviously, like, the fiber content makes a big difference on this. But if you eat 100 calories, you'll net 90 to 95. Protein is about a 20 to 30% TEF. So if you eat 100 calories from protein, you're only netting 70 to 80. Now you still net, you know, people say, "Well, you can't eat too much protein." Well-... you know, people will ask, "Well, can protein be stored as fat?" The carbons from protein, it's unlikely it's gonna wind up in adipose tissue. But if you're eating a lot of protein, overall it's part of a lot of calories, it does p- it has to be oxidized and it can provide a calorie cushion for other things to be stored in fat. But protein itself does provide, you know, a net positive for calories, but less so than carbohydrate or fat. And tends to be more satiating. So again, when people talk about, you know, are all calories created equal? Yes, but all sources of calories may have differential effects on energy expenditure and appetite.

Layne Norton 19:05 So that's the TEF bucket and the BMR bucket. Then we go to physical activity and physical activity is essentially two parts. There's exercise, which is kind of your purposeful movements, like you go out for a walk, you do a training session, I mean, whatever. Any purposeful activity. And then you have what's called NEAT, which is Non-Exercise Activity Thermogenesis, which I think is actually a r- really cool.

Andrew Huberman 19:29 It's fascinating.

Layne Norton 19:30 Yeah, it is.

Andrew Huberman 19:30 Yeah.

Layne Norton 19:30 So it's, I was actually hanging out with somebody last night and I was noticing them and they, they were fidgeting their feet and their, their fingers and I said, you know, "Have you always, like, been pretty lean?" And they were like, "Yeah, I never really had a pr- problem maintaining leanness." And when you look at the obese resistant phenotype, people think they have high BMR or, you know, they exercise a lot and really what it i- it seems to be is NEAT. They tend to, if they overeat, they just spontaneously increase their physical activity. Now, people get NEAT confused. I've heard people say, "Well, I'm gonna go out for a walk to get my NEAT up." That's not NEAT. NEAT is not something you can consciously modify. What you're doing there, if it's purposeful, it's exercise. So for example, if I, when I'm talking, if I'm waving around my hands, if I'm tapping my feet, if I'm whatever, that's NEAT. But, you know, trying to, like, get yourself, "Well, I'm just gonna tap my foot more," well now, if I'm consciously having to do this, then my focus... I mean, you, you know how the brain works. Very hard to do, you know, you don't really do two things at once.

Andrew Huberman 20:36 Right.

Layne Norton 20:37 You kind of switch quickly between tasks, right?

Andrew Huberman 20:39 Absolutely. Can I quickly ask, uh, was the person that you're referring to our friend, uh, Ben Bruno?

Layne Norton 20:44 No. (laughs) No.

Andrew Huberman 20:44 (laughs)

Layne Norton 20:45 But he is fidgety too.

Andrew Huberman 20:46 He has amazing online fitness channel. Um, he's a freakishly strong individual.

Layne Norton 20:50 Oh, yeah.

Andrew Huberman 20:50 Yeah. And, uh, um, I can't remember whether or not, Ben, you're a fidgeter or not. But anyway, I'll have to go, go check and we'll measure your fidgeting. Um, a- about, uh, non-exercise induced thermogenesis, NEAT, um, my understanding of the old papers on this, old being, I guess, back to the mid '90s-

Layne Norton 21:08 Yeah.

Andrew Huberman 21:08 ... is that the calorie burn from NEAT is actually pretty significant. We're not talking about 100 calories or 200 calories per day, we're talking about in some cases h- hundreds of thousand, excuse me, hundreds to maybe even close to 1,000 calories per day.

Layne Norton 21:22 Yeah.

Andrew Huberman 21:22 Could you elaborate on that?

Layne Norton 21:23 Yeah. So there was actually a really classic study, I think from, I want to say it's from Levine in 1995, it was Metabolic Ward Study, and hopefully I don't butcher the study because I'm trying to, you know, pull it out of my brain.

Andrew Huberman 21:38 I don't expect you to have PubMed in your head.

Layne Norton 21:40 (laughs)

Andrew Huberman 21:40 Although I must say you have a, a, a quite extensive, uh, PubMed ID, um, grab bag in there. So-

Layne Norton 21:47 I try to bring the receipts.

Andrew Huberman 21:48 Yeah.

Layne Norton 21:48 I try to bring the receipts.

Andrew Huberman 21:49 We can put a, we will put a link to this study in the show note captions-

Layne Norton 21:52 Yeah.

Andrew Huberman 21:52 ... so, um, uh, people can peruse it if they like. Yeah.

Layne Norton 21:55 So I, I believe they had people overeat and I, I think it was by, like, 1,000 calories a day and I think for six weeks. And I mean, this is the Metabolic Ward, so they are, this is very tightly controlled. It's as tight as you get. And what was interesting is, of course, on average, people gained weight and gained fat mass, but some people gained more than expected and there was one person in particular who only gained, like, just over half a kilo, right? They should've gained, like, I think it was something like three to four kilos, it was, was predicted, and what they found is this indi- individual just spontaneously increased their physical activity. Like, he didn't purposefully do it, it, it just happened, and I mean, you know, anecdotally, I've seen people who are, again, you know, very lean even eat a meal, sit down, and start sweating, you know? And be very fidgety. There was a, a natural bodybuilder back in the day named Jim Cordova, and this guy was just very lean all the time and he was exactly that phenotype, you know? He would walk up a flight of stairs and all of a sudden he's sweating. Sit down to eat a meal, he's sweating, you know? He just...

Andrew Huberman 23:03 He's a furnace.

Layne Norton 23:04 Just expending energy.

Andrew Huberman 23:05 Mm-hmm.

Layne Norton 23:07 And what's very interesting about NEAT is that seems to be the most modifiable... I mean, exercise is very modifiable 'cause you can be intentional with that, but of, you know, BMR, TEF, and NEAT, NEAT seems to be far more modifiable. So even a body weight reduction of 10%, they've observed a decrease in NEAT of almost 500 calories a day.

Andrew Huberman 23:33 Wow.

Layne Norton 23:33 For, for a 10%, uh, reduction in body weight. Now, you also do get a decline in BMR when you lose weight. One, because you're just in a smaller body now and so it takes less energy to, uh, locomote, uh, but also there's what's called metabolic adaptation which is a r- further reduction in your BMR than expected from the loss of body mass, and that's on average usually around, like, 15%. But it does seem to be... There's new evidence coming out on the metabolic adaptation from BMR and it seems to be a little bit, um, kind of in the transition phases. So if you, if you start a diet, within the first few weeks, you will have a reduction in BMR that then kind of just aft- thereafter, any further reduction is mostly from the amount of body mass you lose. And then if you, like, for example, finish a diet and move your calories to maintenance, um, within a few weeks, BMR kind of starts to come back up. There is still a small reduction, uh, but I used to be somebody who thought the BMR...... you know, the metabolic adaptation was a big reason why people stopped losing weight or plateaued and now I think it's much more to do with NEAT.

Andrew Huberman 24:48 Interesting. And you said that it can't be conscious, um, because that will distract us from other activities. I don't know if you've had a chance to look at th- this study and I'll send it to you, maybe might be fun to do a kind of an online journal club about this at some point soon, but there's a study that came out of University of Houston recently having people do, now, this is a long period of time, four hours a day of basically a soleus pushup, which is basically a heel raise, kind of a seated calf raise-

Layne Norton 25:12 Hm.

Andrew Huberman 25:12 ... with one foot, uh, not weighted. And then they looked at a bunch of things about glucose metabolism and glucose clearance and insulin levels, and they didn't conclude that people burned a ton of calories but what they concluded was that, um, blood sugar regulation improved greatly.

Layne Norton 25:28 Mm-hmm.

Andrew Huberman 25:28 And I think, you know, there was a lot of excitement about this, um, at some level, but based on everything you're telling me, this, it fits perfectly with what's known about NEAT. So this sort of fell somewhere in between with, um, in between, excuse me, uh, sort of deliberate exercise-

Layne Norton 25:44 Yeah.

Andrew Huberman 25:44 ... and spontaneous movement. I guess they've tried to make that spontaneous movement a little bit more conscious.

Layne Norton 25:49 Well, what I'll tell people is if, if you're worried about NEAT, one thing you can do, like, these watches for example, people are like, "Oh, well it told me I burned this many calories." The- they are not accurate for energy expenditure. I mean, it is like, there is a meta-analysis in 2018 I want to say, between a 28 and 93% overestimation of energy expenditure by these watches.

Andrew Huberman 26:15 Fitness trackers. So for those-

Layne Norton 26:16 Yeah.

Andrew Huberman 26:16 ... of you listening, we're not gonna name the brand but, uh, fitness trackers, uh, so wrist-worn fitness trackers.

Layne Norton 26:21 And this is, and this is across the board.

Andrew Huberman 26:22 Okay.

Layne Norton 26:23 Um, so like, depending on the brand it could be, you know, more or less, but they all overestimated the amount of ex- the calories you burn from exercise. So this is actually a great example where people go, "Well, calories in calories out doesn't work for me 'cause I ate in a calorie deficit and I didn't lose weight." And, uh, when I talk to them, usually it's they went to an online calculator, it's one- it's a few things, they went to an online calculator, put in their information, it spat, it spat out some calories to eat and they ate that and didn't lose weight. And it's like, well, what do you think is more likely, that you're defying the laws of, you know, um, conservation of energy or that you're- you might have not gotten the right number for you?

Andrew Huberman 26:59 The r- the measurement tool was off.

Layne Norton 27:00 Yeah.

Andrew Huberman 27:01 Yeah.

Layne Norton 27:01 The next thing is a lot of people weigh very sporadically and I'll tell people like, "If you're gonna make intentional weight loss a goal," um, and again this can be different for different people but typically I tell people, "Weigh in first thing in the morning or after you go to the bathroom, do it every day and take the average of that for the week and then compare that to the next week's average."

Andrew Huberman 27:22 Can I ask one quick, sorry to interrupt-

Layne Norton 27:23 Mm-hmm.

Andrew Huberman 27:23 ... but one quick question about that.

Layne Norton 27:24 Mm-hmm.

Andrew Huberman 27:24 When you say go to the bathroom, not to get, um, uh, too detailed, uh, here for unnecessarily but are you talking about urination and, um, emptying-

Layne Norton 27:33 Both of them. Yeah.

Andrew Huberman 27:33 ... your bowels? Ideally-

Layne Norton 27:34 Yeah both of them, yeah.

Andrew Huberman 27:34 ... because you could have eaten a big meal the night before.

Layne Norton 27:36 Yeah.

Andrew Huberman 27:36 Yeah. Got it.

Layne Norton 27:36 Yeah.

Andrew Huberman 27:37 So wake up, uh, use the bathroom, um, in all, all forms that you're ready and then, and then get on the scale, take that measurement, average that across the week, and then maybe every Monday you'd take that value and see how you're progressing.

Layne Norton 27:51 Right, and, and the reason I, I recommend doing that is if you're just kind of sporadically weighing in, a- as somebody who weighs themselves pretty, pretty regularly, I mean, my weight will fluctuate, you know, five, six pounds and not seemingly changing much, you know? And that's just, you know, those short term changes are fluid so I'm- I've had it before where week to week my average didn't change but between the lowest weigh in from a previous week and the highest weigh in might have been like eight pounds, right? So if you're somebody who just randomly is weighing in and you're eating in a calorie deficit and you just weigh in one day where you've just, whatever reason holding some more fluid then you go, "Oh see, this isn't working," when in reality your average might be dropping. So that's one of the reasons and actually, um, believe it or not, uh, weight fluctuations are actually identified as a major reason why people get discouraged from weight loss. Um, that it, it kind of stops the buy-in.

Andrew Huberman 28:50 Mm-hmm.

Layne Norton 28:50 You know when they have a fluctuation up, so that's one of the reasons early-

Andrew Huberman 28:53 Great point.

Layne Norton 28:53 ... one of the reasons early on that low carb diets tend to work really well is 'cause people lose a lot of water weight really quickly and they get that buy-in, right? Say, "Oh, this is working."

Andrew Huberman 29:01 Yeah, we can return to that in a little bit-

Layne Norton 29:02 Yeah.

Andrew Huberman 29:02 ... because I have theories as to how that, um, you know, when people eat less carbohydrate they excrete more water and they'll see f- you know, for the first time they'll see some definition in their abs-

Layne Norton 29:12 Mm-hmm.

Andrew Huberman 29:12 ... and they'll go, "Oh my god, this diet's amazing."

Layne Norton 29:14 Yep.

Andrew Huberman 29:14 Um, and the fluid loss does hold that promise. I think fluid loss can do some other things, it might people litt- make people literally feel lighter, um-

Layne Norton 29:21 Yeah. Yeah.

Andrew Huberman 29:21 ... although it can do, uh, have some negative effects.

Andrew Huberman 29:24 I do have one quick question, and, and, um, I do want, we'll return to NEAT in a moment but when you say the caloric burn as a consequence of exercise-

Layne Norton 29:31 Mm-hmm.

Andrew Huberman 29:31 ... I want to ask about the caloric burn during that exercise. So for instance-

Layne Norton 29:35 Mm-hmm.

Andrew Huberman 29:35 ... if somebody's on the treadmill and they'll see, okay, they burned, you know, 400 calories. Actually, I think this is a month where a number of prominent podcasters like Bert Kreischer, Tom Segura, Joe Rogan, others-

Layne Norton 29:44 Yeah.

Andrew Huberman 29:45 ... are doing, they call it Sober October but in addition to avoiding alcohol they, they're burning 500 calories per day during the exercise.

Layne Norton 29:50 Yeah.

Andrew Huberman 29:50 They're me- they're measuring it. A lot of people do this. They think- they take track of whether, or excuse me, take stock of how many calories they burned. My understanding is that if that particular form of exercise is a muscle building form of exercise that at some point later there might be an increase in muscle if you did it, everything right, do everything right, and then you will burn more energy as a consequence of adding that tissue. That's a long process as, as you know and we will discuss, but I have heard about this post-exercise induced increase in oxidative metabolism. I'm probably not using the right, uh, languaging here.

Layne Norton 30:26 EPOC, yeah.

Andrew Huberman 30:27 So if I were to go out for instance and sprint, do some sprints, run hard for a minute, jog for a minute, run hard for a minute, do that ten times over, they'll- let's assume I burn 400 calories during that, um, exercise, um, bout.... but my understanding is that in the hours that follow, my basal metabolic rate will have increased. Is that true? And is it significant enough to care about?

Layne Norton 30:50 So I'll answer both those questions. Um, yes, there does seem to be a small increase, uh, in metabolic rate. And no, it does not appear to be enough to actually make a difference. So when they look at... and again, this is where, um, I tell people, I think I have a good perspective on this, because I- my undergraduate degree was a biochemistry degree, so I was very into mechanisms. You know what I mean? It was like, "Oh, if we just do this and this, we'll get this." Right? And then, I did nutrition as a graduate degree, and then my advisor was so great, because y- y- you could do something over here and he could tell you how it would affect vitamin D metabolism over here.

Andrew Huberman 31:26 This is Don Laymon.

Layne Norton 31:27 Yeah, Don Laymon.

Andrew Huberman 31:28 Yeah.

Layne Norton 31:28 So h- you know, he would always kind of say, "Yeah, but what's the outcome going to be?" Right? So this is actually one of the things I changed my mind on, was I used to be very much, well, I think, you know, high intensity interval training is probably better because you get this post-exercise energy burn, which they do see in some of these studies, but in the kind of meta-analyses and like more tightly controlled studies where they equate work between high intensity intervals and moderate or low intensity, uh, cardio, so equating work, uh, they don't see differences in the loss of body fat. And so to me, if I'm looking at it, that's the example of a mechanism which is, okay, we're seeing this small increase in basal metabolic rate, that should lead to increased loss of body fat. But again, remember, you're capturing a- a snapshot in time, right? But we don't see a difference in the loss of body fat. So what may be happening, and again, I'm just speculating, but a way to explain it could be, you might have an increase and then you might actually have a decrease that tends to just kind of wash it out. Right?

Andrew Huberman 32:33 I see. And I have to imagine some forms of exercise, this would be highly individual, but, um, will spike appetite more than others. So for instance, if I go out for a 45-minute jog or, which I do, a 45 to 60 minute hike or jog once a week, I just make it a point to do that, or ruck or something like that, throw on a weight vest and hike. After that, I find I- I'm very thirsty, I want to hydrate, but I'm not that hungry.

Layne Norton 32:56 Mm-hmm.

Andrew Huberman 32:56 And that's true of most all cardiovascular exercise for me. Um, but after I weight train, about 60 to 90 minutes later, I want to eat the refrigerator.

Layne Norton 33:07 (laughs) .

Andrew Huberman 33:08 And so obviously calories in calories out dictates that that will play an important role as to whether or not I gain or lose weight, et cetera. So is it safe to say that the specific form of exercise that people choose, uh, needs to be taken in consideration of calories in calories out? So how much is burned during the exercise? Also, how much that exercise tends to stimulate appetite?

Layne Norton 33:30 Mm-hmm.

Andrew Huberman 33:31 I don't know whether or not people explore this in- in the rigorous studies.

Layne Norton 33:33 Yep.

Andrew Huberman 33:34 And whether or not that form of exercise actually increases lean muscle mass or not. Um, so, uh, now we've taken exercise and split it into a number of different dimensions, but this is what, uh, you are so masterful at, is really parsing how the different components work individually and together. So if- if you would just, um, you know, expand on that, I- I'd love to know what you're thinking.

Layne Norton 33:55 Yeah. So this is actually a really fascinating thing. Um, so first thing I want to, I want to just go back to talking about like, for example, Bert and Tom and- and Joe, were going to do 500 calories a day on whatever. Um, so those apparatuses don't measure those things effectively either, right? Just like these watches. But the one thing I will say is if you are... like for example, if I do two hours of resistance training, typically this will say I burned about 1,000 calories, right?

Andrew Huberman 34:21 That's a lot of resistance training.

Layne Norton 34:23 Right.

Andrew Huberman 34:23 My w- my weight workouts are like s- are warm up for 10 minutes and then one hour of work, done. (laughing)

Layne Norton 34:28 I- I just, I love to train.

Andrew Huberman 34:29 Okay.

Layne Norton 34:30 It's a...

Andrew Huberman 34:30 And you- and you can recover from... My recovery quotient is pretty low.

Layne Norton 34:33 Mm-hmm.

Andrew Huberman 34:33 So I've been training for 30 plus years, and I found that if I do more than an hour of hard work in the gym, meaning resistance training, i- 75 minutes, maybe I'm okay, but past that, I have to take two, maybe even three days off before I can train.

Layne Norton 34:50 Mm-hmm.

Andrew Huberman 34:50 My nervous system just doesn't tolerate it well.

Layne Norton 34:52 Mm-hmm.

Andrew Huberman 34:52 So I- I limit it to an hour. Um, you know.

Layne Norton 34:55 Yeah.

Andrew Huberman 34:55 But, um, you know.

Layne Norton 34:55 And- and part of that to remember is like I've kind of built up to that over a long period of time, right?

Andrew Huberman 34:59 Mm-hmm.

Layne Norton 34:59 You know, so couldn't just throw somebody in and start having them do two hours a day. It's not going to go well for them.

Andrew Huberman 35:04 I'd like to take a quick break and acknowledge one of our sponsors, Athletic Greens. Athletic Greens, now called AG1, is a vitamin mineral probiotic drink that covers all of your foundational nutritional needs. I've been taking Athletic Greens since 2012, so I'm delighted that they're sponsoring the podcast. The reason I started taking Athletic Greens and the reason I still take Athletic Greens once or usually twice a day is that it gets me the probiotics that I need for gut health. Our gut is very important. It's populated by gut microbiota that communicate with the brain, the immune system, and basically all the biological systems of our body to strongly impact our immediate and long-term health. And those probiotics in Athletic Greens are optimal and vital for microbiotic health. In addition, Athletic Greens contains a number of adaptogens, vitamins and minerals that make sure that all of my foundational nutritional needs are met, and it tastes great. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman and they'll give you five free travel packs that make it really easy to mix up Athletic Greens while you're on the road, in the car, on the plane, et cetera, and they'll give you a year's supply of vitamin D3 K2. Again, that's athleticgreens.com/huberman to get the five free travel packs and the year's supply of vitamin D3 K2.

Layne Norton 36:18 What I

Layne Norton 36:19 will say about the calorie trackers is, so if I'm used to, okay, I usually burn about 1,000 calories according to this, it's not accurate, but if I go in tomorrow and I do 1,300-... it may not be accurate. I don't know what the exact number is, but I can be relatively confident that it's more than the previous session, right? And so, in terms of comparison, it might be okay, like, you know, kind of within subject. Um, and then the other thing that I was kind of circling around on was, if you're worried about NEAT, tracking your steps can be helpful, because people's step counts can spontaneously decrease when they're on a fat loss diet. They don't even realize it. So, uh, and, and that, again, not a complete measure of NEAT, but what we've had some clients do, uh, with our team bio-link coaches is they'll say, "Okay, you're at 8,000 steps right now. We're not gonna add any purposeful cardio. But whatever you need to do to maintain that 8,000 steps, do that." And sometimes they have to add, you know, 15, 20, 30 minutes of cardio because their spontaneous activity, that they're not even aware of, goes down.

Andrew Huberman 37:21 That's a really excellent point. I- I- I've heard, you know, the 10,000 steps per day number was, um, we all heard that.

Layne Norton 37:28 Yeah.

Andrew Huberman 37:28 And then I learned that 10,000 was just kind of thrown out as an arbitrary number. (laughs)

Layne Norton 37:32 Yeah. It is a good number.

Andrew Huberman 37:32 So like the eight-hour intermittent fasting thing, there's a story behind that, 'cause I actually, uh, spoke to Sauchin and it turns out that the graduate student in his lab that did that initial study, which was on mice by the way, um, was limited to being in the lab for about eight hours by their significant other. (laughs) So the eight-hour feeding window is actually the consequence of this r- person's relationship. Um, it's kind of a-

Layne Norton 37:53 That is a, that is a really great point that people don't realize when they, a lot of people will try to copy like scientific studies, and I'll, I'll tell people, like, "Listen, scientific studies are so confined. You, you need to be very careful with how broadly you apply what's in there." Right? Like they're, they're a very big hammer, is kind of the way I look at it. Okay? They're not a scalpel, they're a big hammer. And I think a lot of times in terms of coaching, scientific studies will tell you what not to do rather than what to do, right? Uh, but getting back to your question about like exercise appetite. So first off, I'm not really aware if there's, uh, evidence showing like differential effects of different forms of exercise on appetite. It's possible. Um, but, uh, again, it also could be like a placebo effect, right? Because we, like, for example, you and I grew up in an era where the muscle magazines, it was like, "Well, as soon as you finish your workout, you can have your biggest meal of the day."

Andrew Huberman 38:49 That's right.

Layne Norton 38:49 Right? And, you know, when I say placebo effect, I think people have the wrong idea of what the placebo effect is. They think that's just a feeling. Placebo effect can actually change your physiology. People don't, people don't realize this. Um, there's research showing that a placebo or the power of suggestion is basically as powerful as some pharmaceuticals. And one of the, the great examples I like to use is actually there was a study we just covered in our research review on creatine, where they did, um, four groups, not supplemented with creatine, told they weren't supplemented with creatine, not supplemented, told they were supplemented, supplemented, told they weren't, supplemented, told they were. Basically, it just matters what they told them.

Andrew Huberman 39:34 Really?

Layne Norton 39:35 Oh, yeah.

Andrew Huberman 39:35 This is incredible. Um, I have to get this study. We'll, uh ... So we can link to it.

Layne Norton 39:39 Yeah.

Andrew Huberman 39:39 Uh, a colleague of mine at, at Stanford, she's been on the podcast, I'd love to introduce you two, 'cause I think you guys would get, um, really riff. First of all, she was a former D1 athlete.

Layne Norton 39:47 Mm-hmm.

Andrew Huberman 39:47 Um, and then is, uh, runs a lab at Stanford in psychology, this is, uh, Leah Crum, and she's ... And grew up, um, in, in this, you know, very athletic obviously, and, and very, very smart. And her laboratory focuses on these belief/placebo effects, where if you tell people all the horrible things that stress do to you, in terms of your memory and cognitive functioning, and then you give them a memory test, they, they perform well below baseline. If you tell them that stress sharpens them in the short term, and that adrenaline is this powerful molecule that can, uh, (laughs) really tune up a number of memory systems, memory improves.

Layne Norton 40:19 Mm-hmm.

Andrew Huberman 40:19 And it, it's remarkable.

Layne Norton 40:21 Yeah.

Andrew Huberman 40:21 Um, and it's consistent. And, uh, and this, and they've done this for any number of different things and getting-

Layne Norton 40:26 And again, these are-

Andrew Huberman 40:27 ... food allergies, for instance, you know? Incredible results. In any case, I, I'm, I'm so glad you're bringing this up. Um, I take creatine monohydrate, uh, and I have for years, five grams a day. I don't love-

Layne Norton 40:38 And it's great.

Andrew Huberman 40:39 And, um, and it's great, and I believe it's great. So ... (laughs)

Layne Norton 40:42 (laughs) Well-

Andrew Huberman 40:42 So is there a compound effect of believing it's great and it actually, uh, being great?

Layne Norton 40:46 So not, not in this study, but, so I think the thing to point out, people will misinterpret that as creatine doesn't work. And that's not what that says. What it says is, your beliefs about what it does are probably just as powerful as what it does, right? So, uh, they actually did a study, and I don't have the citation, but it was, I think, within the last 10 years, where they told people they were putting them on anabolic steroids. And wouldn't you know it, they had better gains. Even though they weren't actually on anabolic steroids, they had better gains than people that they didn't tell were-

Andrew Huberman 41:17 Amazing.

Layne Norton 41:17 ... anabolic steroids. And that's like hard outcome, strength, lean body mass, you know, those sorts of things. So when people say, "Well, I wouldn't fall for, for the placebo effect." It's like, eh, you don't have to fall for it if, if you believe it to be true. The power of belief is very, very powerful, and as a scientist, I wish sometimes I was ignorant so that I could subject myself to the placebo effect more often. (laughs)

Andrew Huberman 41:41 Oh, yeah. Absolutely.

Layne Norton 41:42 Um, so kind of getting back to that's just a possible explanation of maybe why, you know, and I'm the same way. Like, I get done with a, a workout, like a resistance training session, I'm like, "I'm ready to eat." Right? Now, if you look at the literature overall on exercise and appetite, it's not always what you'd expect. Consistently, it seems to show that exercise actually has an appetite suppressant effect. So, um, people don't tend to compensate, at least fully, for the amount of movement they do. And there is some evidence that ... You've probably heard people say, "Well, exercise is a really poor weight loss tool." Right? Like it, like if you figure out how many calories you should be burning from it and you do that, you end up getting less weight loss than you, than you would predict.

Andrew Huberman 42:30 I have a family member who is perfectly happy to eat less, but-... doesn't loathe exercise-

Layne Norton 42:35 (laughs)

Andrew Huberman 42:35 ... but dislikes exercise.

Layne Norton 42:37 Yeah.

Andrew Huberman 42:37 And they, and they're of healthy weight-

Layne Norton 42:40 Mm-hmm.

Andrew Huberman 42:40 ... but I'm always encouraging them to exercise more. And so this is an ongoing battle in our, in our sibling relationship.

Layne Norton 42:46 Well, one thing I would say is that exercise, independent of anything that happens with your body weight, you will be healthier.

Andrew Huberman 42:52 Mm-hmm.

Layne Norton 42:52 So exercise is one of the only things that will actually improve your biomarkers of health without even losing weight. So there's, uh, like, it'll improve your insulin sensitivity, inflammation, all that stuff. So everybody out there looking for a hack to be healthier, exercise is the hack, right?

Andrew Huberman 43:08 Yeah. Crucial point. And our, um, uh, mutual friend, Dr. Peter Attia-

Layne Norton 43:14 Mm-hmm.

Andrew Huberman 43:14 ... I think has gone on record several times now saying that of all the things that one could take, NMN, et cetera, metformin, of all... Regardless of whether or not one takes those or doesn't take those, that the positive effects on longevity by way of bar- biomarkers from regular exercise is, y- you know, far outweighs all of those things combined. Not that those things don't necessarily work, but we're not going through them in detail now, but that exercise is by far the best thing we can do for our healthspan and lifespan.

Layne Norton 43:44 Yeah, absolutely. I, I,

Layne Norton 43:46 100% agree. And when you're talking about weight loss, people miss the point of exercise, I think. Y- uh, there's some work that came out from Herman Pontzer as well that basically showed, like, well, if you do 100 calories from exercise, you have a, like, 28 calorie reduction in your basal metabolic rate in response to that. So it's kind of like this constrained energy expenditure model, right? But what I would say is, okay, well, there's still a net of 72, right? So it's still, it's still-

Andrew Huberman 44:12 Mm-hmm.

Layne Norton 44:13 ... okay. And the other thing is I think the effects of exercise on weight loss are actually more due to what it does to appetite. Um, so if you look at people who lose weight and keep it off for a number of years, kind of outliers because most people don't keep it off for years, over 70% of them engage in regular exercise. Of people who do not keep weight loss, uh, like, maintain weight loss, less than 30% exercise regularly. So now, that's just a correlation, that doesn't necessarily prove causation, but there are some pretty compelling studies showing that exercise increases your sensitivity to satiety signals. So basically, you can have the same satiety signals, but you're more sensitive to them when you exercise. And there's actually a really classic study, um, from the 1950s in Bengali workers where they looked at basically four different quadrants of activity. So you had sedentary, lightly active, moderately active, heavily active, basically based on their, their job choice. And they didn't have an intervention, they just wanted to track them and, and see how much, you know, how many calories did they actually eat. So it was like a J-shaped curve. So the sedentary actually ate more food than the lightly active or moderately active, but from lightly active to heavily active, they almost perfectly compensated how many calories they should be eating. So to me, that suggests when you become active, you can actually rep- regulate your appetite appropriately, or much more appropriately than if you're sedentary.

Andrew Huberman 45:47 And do you think this has to do with changes in the brain, brain centers that respond to satiety signals from the periphery, um, and/or do you think it has to do with, uh, changes in br- blood sugar regulation? I, what I was taught, and I don't know if this is-

Layne Norton 46:02 Mm-hmm.

Andrew Huberman 46:02 ... still considered true is that, you know, spikes in blood sugar will trigger a desire to eat more, even though it's kind of exactly the opposite of what you need when you have a spike in blood sugar. And there's this kind of, and we'll get into this when we talk about artificial sweeteners, there's this idea in mind that I think I adopted perhaps falsely, that, you know, you eat something that's sweet or that tastes really good and, and you are suddenly on the train of wanting to eat more. Um-

Layne Norton 46:24 Yeah.

Andrew Huberman 46:24 ... and I could imagine how exercise, um, if it is increasing the satiety signals, uh, could be working in a number of different ways.

Layne Norton 46:32 Yeah. Uh, I, I think it's a m- m- I think the effect is probably mostly at the brain level. Um, you know, the, the effects on blood sugar, the research out there is not very compelling for blood sugar driving, uh, appetite. Now, if you become hypoglycemic, yes, you'll, you'll get hungry, but it's a different kind of hunger than, like, your normal, like, "I feel kinda empty and my stomach's growling." Like, those are, they can go together, but usually, like, the hypoglycemia is like, "I am hot. I feel like I'm gonna pass out." Like, you want to eat something not because your stomach's growling, but because y- you know that you just need some fuel.

Andrew Huberman 47:11 It's like you're getting pulled under.

Layne Norton 47:13 Oh, yeah.

Andrew Huberman 47:13 Yeah.

Layne Norton 47:13 Absolutely.

Andrew Huberman 47:13 I've been there.

Layne Norton 47:14 Yeah.

Andrew Huberman 47:14 I've been there when I've, uh, done longer fasts, something I don't do anymore, and drank a lot of black coffee.

Layne Norton 47:20 Mm-hmm.

Andrew Huberman 47:20 There was probably an electrolyte effect there because coffee has, you, uh, excrete sodium and other electrolytes.

Layne Norton 47:25 Yeah.

Andrew Huberman 47:25 And then just feeling like I needed something. This whole thing, like, I need something, this kind of desperation, I, I, I'm, I never want to be back here again.

Layne Norton 47:32 (laughs)

Andrew Huberman 47:33 (laughs) Hypoglycemia is very uncomfortable.

Layne Norton 47:34 Oh, it's not fun. So, you know, again, uh, when they, and when, then when they look at, you know, actual randomized control trials of implementing some exercise where they're, you know, pretty controlled environment, they typically see people, if, if anything, they eat less as opposed to eating more. Now, some people, again, that's, you know, studies report averages, right? And there's individual data points. So there are some people who at least anecdotally report that exercise makes them more hungry. That's completely valid. It's, now, it could be their beliefs around it, it could be a number of different things, but it's important to understand that there is individual variability. And I think one of the things that I've learned to appreciate more is not trying to separate psychology and physiology. We, we do this a lot and say, "Well, I want to know the physiology. I don't care about the psychology of it." And it, now I'm kind of appreciating more psychology is physiology. You know, that, like, with most things now, we have kind of the biopsychosocial model. L- and I'll give you an example of this. A lot of people get really caught up with appetite and-... if we could just suppress people's appetite. That's part of it, but people don't just eat 'cause they're hungry. They eat for a lot of different reasons, social reasons especially. So can you remember the last social event you ever went to that didn't have food?

Andrew Huberman 48:59 No.

Layne Norton 48:59 Right. Uh, if you look at dinner plates from the 1800s, they're about this big. Now how big are dinner plates?

Andrew Huberman 49:06 The whole buffet.

Layne Norton 49:06 Right. (laughs)

Andrew Huberman 49:07 (laughs) Yeah.

Layne Norton 49:08 Um, if you... Uh, there's, um, situational cues, right? You're sitting down to watch TV. Oh, grab some popcorn, grab some, you know, snack, whatever.

Andrew Huberman 49:17 I even see this with the, you know how, uh, one person will pick up their phone and then everyone picks up their phone?

Layne Norton 49:20 Mm-hmm.

Andrew Huberman 49:20 I think there's a similar effect with food.

Layne Norton 49:22 Yeah. A- and, and same thing, right? Like, (laughs) how many times have we either done it ourselves or been, uh, experienced people saying, "Oh, you should have something. You should have..." Or like, you know, a- alcohol especially, right? Like people will, um... Uh, I was hanging out with somebody last night and I had a beer and they just had, you know, a water. And I'm like, "Welp, I feel no need to try and convince them to do that with me." You know what I mean? But as humans, you know, we're, we're kinda herd animals. Like we don't want to be doing something out in isolation on our own. Now, I'm, I'm... This is a very tenuous, I guess, belief of mine, but, you know, doing things alone in isolation, you know, during kind of, you know, ancestral times, that's gonna set off your alarm system, you know? 'Cause if you don't have other people, you can't protect yourself, right? So typically, things were done together in groups and I think that's a lot of the reason why we tend to be just tribal in nature about a lot of things, right? So the whole point to that is, you know, on the list of reasons why people eat, I mean, I've gotten to the point where I think that hunger is actually not even the main reason people eat. Uh, you know, stress, um, lack of sleep.

Andrew Huberman 50:41 Boredom.

Layne Norton 50:41 Boredom.

Andrew Huberman 50:42 Yeah.

Layne Norton 50:42 Absolutely. So unless, you know, we can do something that addresses all those things, um... There's a, there's a line from a review paper. This review paper came out in 2011. It was by a researcher named McLean and it's the best review paper I've ever read. It was called, uh, Biology's Response to Dieting: The Impetus for Weight Regain. And basically, he went through all the mechanisms of these adaptations that happen during fat loss diets and how biology's response is to try to drive you back to your, your previous. And I'm gonna butcher the quote, but at the end of the study he said, basically, "The body's systems are comprehensive, redundant, and well-focused on restoring depleted energy reserves." And any attempt or any kind of strategy for weight loss that doesn't attempt to address a broad spectrum of these things is going to fail. And so that's why when people say, "Well, just do low carb, you won't be hungry," I'm like, "Yeah, but people don't just eat because they're hungry." So I think really, like, trying to get outside the box and, and think about these things, and especially when you read some of the literature. I, I recently read a, a systematic review of successful weight loss maintainers, which I thought was really interesting. Um, so they took people who had lost a significant amount of body weight and kept it off for s- for, I think it was three years, and they basically asked them questions and tried to identify commonalities. And there were some things that I expected, like cognitive restraint, self-monitoring, um, uh, you know, exercise. And then one of the things they said that I found really fascinating was pretty ubiquitous between people. They said, "I had to develop a new identity." So d- are you familiar with Ethan Suplee?

Andrew Huberman 52:33 No.

Layne Norton 52:34 So Ethan is a actor. He's been in, like, Remember the Titans and, uh, American History X. Um-

Andrew Huberman 52:39 I certainly saw American History X, yeah.

Layne Norton 52:41 Yeah. So he was, he was very large. Like, he was like 550 pounds and now he's, like, 230 and jacked. He l-

Andrew Huberman 52:48 Wait, he was fi- he was how much?

Layne Norton 52:49 550 pounds.

Andrew Huberman 52:51 Wow.

Layne Norton 52:52 Um, and he has it, whenever he puts a post on his Instagram of him training, it'll say, "I killed my clone today." And I asked him, like, "Is this what you're talking about? Like creating a new identity?" And he said, "This is exactly what I'm talking about. Because I had to kill who I was, because there was no way I was gonna be able to make long-term changes if I just didn't become a new person." Because there's, I mean... And addicts talk about this, right? Like, um, people f- who are alcoholics, they had to get new friends, they had to hang out at different places, because their entire life had been set up around this lifestyle for alcohol. And I would actually argue that eating disorders or disordered eating patterns is much harder to break than other forms of addiction. And you think about food addiction, well, in some ways, bulimia and anorexia are still addictions. You can't stop eating. If you're an alcoholic, you can abstain from alcohol. If you become addicted to, say, cocaine, you can abstain from that. You can never abstain from food. And so now imagine telling a gambling addict, "Well, you've got to play this slot, you know, a couple times a day, but no more." Like, that's, that's really challenging. So, um, yeah. I just... Like all this stuff, it's so important to be comprehensive with how we treat these things.

Andrew Huberman 54:20 All right. These are incredibly important points, and to my knowledge, I don't think anyone has really described it, uh, in a cohesive way the way that you're doing here. So important for people to understand this, because obviously as a neuroscientist, I think, you know, the nervous system is creating our thoughts, our thoughts are, and feelings are related to psychology, and therefore, of course our physiology and our psychology are one and the same. It's bidirectional. Now there's, nowadays, there's a lot of interest in brain/body, in particular gut.... brain, uh, access, and we, we can talk about that. But I, I really appreciate that you're spelling out how there are these different variables. Each one can account for a number of different things. Exercise clearly has a remarkably potent effect, both during the exercise in terms of caloric burn, overall health and biomarkers, and then, um, this is wonderful to learn that it can increase the sensitivity to, uh, to satiety signals. Uh, I think, uh, that makes, at least in my mind, places it very high on the list of things that people should absolutely do. But that there are other factors too, um, and the identity piece is fascinating. Um, it reminds me also, your story reminds me also of David Goggins, who is r-

Layne Norton 55:26 Mm-hmm.

Andrew Huberman 55:26 ... you know, you know, he talks about his former, very overweight self-

Layne Norton 55:29 Yup.

Andrew Huberman 55:29 ... almost as if it was a different person.

Layne Norton 55:31 Yeah.

Andrew Huberman 55:32 Um, and he uses language that I'm not gonna use here.

Layne Norton 55:35 (laughs)

Andrew Huberman 55:35 Um, but, you know, I've m- I know, met David, know David a bit, and he's, he's every bit as intense and driven as, and a remarkable human being as he appears to be, uh, online. He is that guy. Um, but it does seem like he had to more or less kill off a, a former version of himself and, and continues to do that every day. And I think what your point about th- this other fellow who did, um, does it, uh, does it through a similar process, I, the word today seems to really matter. It's not like you, uh, defeat this former version of yourself and then that per- that person is buried and gone. You said, you know, "I killed my clone today." And that's the way that David talks about it also, so this is a daily process. And I think, um, this is not just a small detail in tying together all these things. I think that what you are describing is, is fundamental, because we can pull on each one of these variables and talk about each one of them, but at the end of the day, we're a cohesive whole as a, as an individual. In, um, uh, sorry. You were about to say-

Layne Norton 56:31 No, that gets, that gets,

Layne Norton 56:32 actually, into one of my f- my favorite topics, which is, you know, why do we have such a hard time with losing weight, but more so keeping it off? Because of obese people, six out of every seven obese people will l- lose a significant amount of body weight in their life. So why do we still have an obesity problem? They don't keep it off. Why don't they keep it off? When you look at the research, basically what it suggests is because people think about, "I am going to do a diet and I'm gonna lose this weight," and they do not give any thought to what happens afterwards, right? It's like, think about if you have some kind of chronic disease or a diabetic, right? You, you can't just take insulin once and that's it, right? You got to take it continuously. Otherwise, you're gonna have problems. Um, if you do a diet and you lose, you know, um, 30 pounds, fantastic. But if you then just go back to all your old habits, y- you're gonna go back to where you were, if not more. Uh, you can't, you can't create a new version of yourself while dragging your old habits and behaviors behind you. So what I'll tell people is, 'cause people say, "Well, I'm doing m- a carnivore diet," or, "I'm doing this diet or that diet." And I'll say, "That's fine. Do you see yourself doing that for the rest of your life?" And if the answer is yes, if you, if you really believe that that's gonna be sustainable for you, and plenty of people, low carb, intermittent fasting, what, whatever, they say, uh, "Felt easy. You know, I could do this forever." Great. What, if you're going to lose weight, you have to invoke some form of restriction, whether it is a nutrient restriction, like low carb, low fat, a time restriction, intermittent fasting, any form of time-restricted eating, or calorie restriction, tracking macros, whatever. So you, you get, you get to pick the form of restriction. So pick the form of restriction that feels the least restrictive to you as an individual and also do not assume that it will feel the same for everybody else, because I made this mistake, whereas like, I, I track things. And so I, I allow myself to eat a variety of foods, I allow myself to eat some fun foods. Uh, but I track everything and I'm able to modify my body composition and be in good health doing that. Now, doesn't feel hard for me. Like, uh, part of it's I've just been doing it for so long. But to other people, that's very stressful. They don't wanna do, they say, "Well, I'd rather just not eat for, you know, 16 hours." If that feels easy for them, do that, because the one thing that, there was a couple of meta-analysis on, uh, popular diets, and basically what they showed was they were all equally terrible for, for long-term weight loss. But when they stratified them by adherence, and none of them were better for adherence overall, but when they stratified people just according from lowest adherence to best adherence, there was a linear effect on weight loss. So really what it says is, what is the diet that's gonna be easiest for you to adhere to in the long term? And you should probably do that. And people, w- again, this is where I step back and take the 10,000-foot view, somebody will say, "Well, I'm gonna do ketogenic because I wanna increase my fat oxidation and I wanna do this," and they're talking about all these mechanisms and everything, and that's great. Can you do it for the rest of your life, right? Is th- is this gonna be something sustainable for you? And if the answer is no, you probably need to rethink what your approach is gonna be.

Andrew Huberman 59:59 It's incredibly important message. Um, basically that. (laughs) You know?

Layne Norton 1:00:06 Yeah.

Andrew Huberman 1:00:06 If I could highlight, you know, if there was a, a version of highlight or boldface and underline in, uh, in the podcast space, I, I would highlight, boldface, and underline what you just said. Um, and for those of you that heard it, uh, listen to it twice and then go forward, because it's absolutely key. I think it also explains a lot of the so-called controversy that exists out there. I think, um, it also crosses over with the placebo effect. I almost want to say...... um, pick the, the nutrition plan that you think you can, uh, stick to for, for a long period of time, ideally forever, and pick your placebo too, because there j- there is a lot of placebo woven into each and every one of these things, intermittent fasting, uh, keto, probably even, um, vegan versus omnivore versus carnivore. Right?

Layne Norton 1:00:49 Well, they even talk about, um, you know, the diet honeymoon period, right, where, like, you go into a diet and you're all fired up about it, and, like, you're very adherent, and then what happens with every single diet, without exception in research studies, is once you get past a few months, adherence just starts waning.

Andrew Huberman 1:01:04 So then-

Layne Norton 1:01:04 And going off.

Andrew Huberman 1:01:05 ... here we are really talking about a form of relationship (laughs) , you know? I'm not- I'm not saying that to be tongue in cheek. Actually, we had a guest early on in the podcast, Dr. Karl Deisseroth. He's a psychiatrist and, um, bio engineer at Stanford, um, tremendously successful, Lasker Award winner, et cetera, and he talked about love as a sort of a, a, an interesting aspect of our psychology where it's a story that you co-create with somebody but that you live into the future of that story. You know, when you-

Layne Norton 1:01:34 Mm-hmm.

Andrew Huberman 1:01:34 ... t- pair up with somebody, that, we- he was referring to romantic love-

Layne Norton 1:01:36 Mm-hmm.

Andrew Huberman 1:01:37 ... that there's this sort of mutual agreement to create this, this idea that you're going to live into. So it's not just about how you feel in the moment. It's also that you project into the future quite a lot. I'm seeing a lot of parallels with, um, a highly functional and effective diet. And, um, and I love it. I'm not, uh, setting this parallel up artificially. I- I'm setting it up because I think that ultimately it, it boils, uh, down to what you said earlier, which is that the brain and our decisions about what we are going to stick to are tremendously powerful.

Layne Norton 1:02:05 And, and I think one thing I will say is, like, keep in mind, um, when you look at the, uh, research data, the meta-analyses on, say, time-restricted eating versus non, when calories are equated, doesn't seem to be a difference in, in weight loss, fat loss, and most biomarkers of health. Same thing for low carb versus low fat. If you equate calories and protein, there w- there was a meta-analysis done by Kevin Hall back in 2017 where they looked at the, and again, actual loss of body fat, and another important point was there was, I think there was 22 studies in this, but all of them provided food to the participants, right? That's important because that makes, m- ensures that adherence can be much higher in those studies, whereas, like, various free living studies, sometimes you can see funky results.

Andrew Huberman 1:02:47 People are sneaking food or, or they're just not really-

Layne Norton 1:02:51 It's very difficult.

Andrew Huberman 1:02:51 ... eating the way that the study would ideally have them eat.

Layne Norton 1:02:54 Unless, unless the person is getting, like, continuous support. Like, studies where they have a dietician talk to people, like, every week tend to actually have pretty good adherence. But, I mean, that's expensive to have done in a study, and again, like, what limits studies? Money, money, and money, right? Um, but the low carb versus low fat when protein and calories are equated, basically no difference in fat loss. Now some people get upset about this, but it's like, well, to me that's like, this is great because you get to pick the tool you want. The one tool, it doesn't seem to be that much better than another, so pick the one that works for you, right? Whatever lever you've gotta pull, you've got a bunch of different options.

Andrew Huberman 1:03:32 You

Andrew Huberman 1:03:33 mentioned, um, picking something you can stick to for a period of time. Is there ever a case for someone saying, "Look, I like to eat low carb or even keto for six months and then switch to a more standard omnivore, caloric maintenance type diet, and then switch back"? Is there any downside to doing that for sake of health or, or weight loss over time? Or weight maintenance over time? 'Cause I realize not everyone is trying to lose weight, um, and I definitely wanna talk about at some point how to eat to maintain weight.

Layne Norton 1:04:00 Yeah.

Andrew Huberman 1:04:00 'Cause I think there are a significant, um, fraction of people out there who are trying to do that. But yeah, is there anything, um, i- uh, is there any downside to being a dabbler? You know, keto for a few months and then, uh, omnivore for a few months, et cetera?

Layne Norton 1:04:14 I think that's actually, uh, a great thing, especially to, like, maybe find what you feel is easiest for you, right? Um, but in terms of, like, as a strategy, I mean, I guess, you know, some people, uh, this might get into dopamine, but, like, oh, change and get something new and, like, you know, you feel a bit more positive about it.

Andrew Huberman 1:04:31 The new partner model.

Layne Norton 1:04:32 Yeah, yeah, yeah.

Andrew Huberman 1:04:33 Right, right.

Layne Norton 1:04:33 Exactly.

Andrew Huberman 1:04:33 Exactly.

Layne Norton 1:04:33 So I don't think it's how I would usually set things up initially for somebody, but if somebody said, "Hey, I'd just like to have some variety and, and change it up," as long as they're still, like, you know, their behaviors and they're doing portion control or whatever it is, and they're able to sustain a calorie deficit or, you know, depending on whatever their goal is, I don't think there's really any downside to it. I, I do think the one thing to keep in mind is when you look at, like, going between extremes, so, like, um, low fat to low carb or, or vice versa, um, there can be in that transition period a little bit of weirdness for lack of a better term. Like, for example, if you've been on a ketogenic diet and all of a sudden you move to, like, a higher carb diet, you'll be, like, basically insulin resistant for, uh, just a short period of time. Now, is that gonna cause any health problems? Probably not in the long term, as l- as l- especially if you're still controlling calories. But just because your body has kind of, like, upregulated these systems dealing most w- mostly with fat and glucose production rather than glucose metabolism, so now if you start taking glucose or carbohydrate back in, like, for example, you give somebody an, uh, or a glucose tolerance test after they've been on keto, they'll do pretty terribly at it. Uh, but that doesn't last that long.

Andrew Huberman 1:05:50 About how long?

Layne Norton 1:05:52 Few weeks.

Andrew Huberman 1:05:53 I think that's, uh, important for people to know because I have a feeling during those first few weeks are the period of time when a lot of people go running back to what they were doing previously, which is not to say that they shouldn't, but, um, I've certainly done that. I try- I've tried, um, very low carbohydrate diet and I would have assumed, and now I know I'm completely wrong, but I assumed-

Layne Norton 1:06:12 (laughs) .

Andrew Huberman 1:06:13 ... that I was so carbohydrate starved for so long that my insulin sensitivity, which is a good thing by the way folks, uh, would have gone through the roof, and I would be able to just sponge up every bit of glucose that I would have ingested through carbohydrate. So I did indeed switch over and I felt like I had pretty terrible brain fog. I even got some jitters and I thought, "Wait, what is this?" You know, my blood sugar was low before. Now my blood sugar should be in more moderate territory. But based on what you just said, I'd upregulated the...... enzymes and systems in the body for fat metabolism on the keto diet and then switching over. Um, there was a, basically a ramping up of the, of the, the, the molecules involved in, uh, presumably in glycolysis.

Layne Norton 1:06:53 Transition period. I mean, think about like if you haven't weight trained before and you start weight training, you're gonna feel pretty terrible, right? Like, you're gonna be sore and stiff and all that kind of stuff. But I will say, you aren't necessarily wrong in what you said about being more insulin sensitive, because it depends on how you measure insulin sensitivity. So if you measure with something like, um, you know, fasting blood glucose or fasting insulin or even HOMA-IR, those tend to be pretty good on low carb. But then if you do an oral glucose tolerance test, it tends to be pretty bad. And so it, it depends on your specific measure, right? Um, so I, I think that, you know, the idea that keto makes you, you know, glucose intolerant or insulin resistant, I think, again, it's just a transition period. And I'm not too worried about it. But it is something important to keep in mind. And one of the reasons, like if somebody was to transition out of keto, typically if like I'm working with them or one of our coaches are working with them, we'll kind of instruct them to do it like slowly and kind of systematically over like a four to eight week period. That way hopefully, you know, they're not having that period of two weeks where they're like, "Oh man, why, why do I feel so terrible?"

Andrew Huberman 1:08:02 Very important point.

Andrew Huberman 1:08:03 I want to go to the other end, um, literally and figuratively, and talk about gut health.

Layne Norton 1:08:09 Mm-hmm.

Andrew Huberman 1:08:10 Because, uh, up until now, and certainly-

Layne Norton 1:08:12 I see what you did with that pun.

Andrew Huberman 1:08:13 (laughs) And certainly in the last, um, few minutes, we've been talking a lot about sort of top down processes. You know, the, the brain, the psychology, placebo effects, but the very real aspects of those. Not that I can imagine 2,000 calories is 1,000 calories and somehow change the law of thermodynamics. Can't do that. But we've been sort of top down in integrating a lot of different ideas into weight loss maintenance and, and weight gain. But gut health, at least the, the more popular studies on gut health, have kind of blown a lot of things out of the water. For instance, this idea that you could take obese mice and li- literally give them fecal transplants from lean mice, and yes that sounds like what it sounds like, um-

Layne Norton 1:08:56 Right.

Andrew Huberman 1:08:56 ... uh, fecal transplants definitely, um, inserted through the same end in which it comes out. And I point that out because a lot of people ask me, th- they, you know, and it was kind of scary to me. I thought, "Yes, y- you know, this is not about ingesting feces. This is they-"

Layne Norton 1:09:08 Oh. (laughs)

Andrew Huberman 1:09:08 "... they, they literally do a, a transplant of feces from lean mice into obese mice, and the obese mice get lean." And yes, this has been done in humans, limited number of studies, and observed, um, some pretty impressive effects on weight loss that I have to assume could be related to placebo effect. They might have told these obese people, "Hey, look, you're gonna get lean through this fecal transplant from lean people." But more likely, it had some effect on their core physiology. I don't know which aspects, although I can speculate which ones. And they became leaner. They lost weight. And that is, in some sense, miraculous, when y- especially given the important role of psychology and exercise and satiety signals, because I'm going to assume that they controlled for a number of those other variables, although no study is perfect.

Layne Norton 1:09:55 Right.

Andrew Huberman 1:09:55 What are your thoughts about gut health as it relates to metabolism, energy utilization, and balance?

Layne Norton 1:10:02 Yeah. So the first thing I'll say is I'm not a gut he- gut health expert, but I will, I feel relatively comfortable talking about it based on conversations I've had with people who are experts, uh, one being, um, Suzanne Devkota, who's, um-

Andrew Huberman 1:10:16 Oh, yeah.

Layne Norton 1:10:16 ... uh, are you familiar with her?

Andrew Huberman 1:10:17 I, well, she's sort of a phenom in this area, from what I understand.

Layne Norton 1:10:20 Yeah. So she was actually doing-

Andrew Huberman 1:10:21 Yeah.

Layne Norton 1:10:21 ... her master's when I was doing my PhD in Lehmann's lab. So she was one of my lab mates.

Andrew Huberman 1:10:24 Terrific.

Layne Norton 1:10:25 Um, and, you know, I, I, the other thing to say is, even gut health experts, and Suzanne will tell you this, they're like, "You know, talk to me in 20 years. We, we just know so little." And I, I think that's an overall thing that people don't understand is the scientific consensus moves very, very slow. And probably for good reason, because if we just flipped our scientific consensus based on one study, I mean, you, it would be a mess, right? So it's gonna take time before we really understand the implications of the gut and what it means. So when it comes to weight loss, there probably is a role in there. I mean, we've seen that there's something going on. Now, whether that's, is it, um, something where a gut bac- microbiome makeup that's more obese resistant, uh, perhaps it extracts less calories out of the food you eat, right? Or perhaps it's elevating BMR, although I, I think that that's probably somewhat unlikely.

Andrew Huberman 1:11:34 Do you think it could impact the way satiety signals are-

Layne Norton 1:11:37 So that's, that-

Andrew Huberman 1:11:38 ... I mean, back to the brain again is my question.

Layne Norton 1:11:39 So that's, we know that there's a link in the, the gut-brain axis, and so my suspicion is that it probably is, uh, working via appetite regulation. So tha- I mean, if we look at, um, if we look at the most effective, um, obesity treatments out there, which is like semaglutide, uh, I mean, you consistently see a, you know, 15%, you know, on average loss of body weight, which is massive, and people keep it off. Um, that is a GLP-1 mimetic, which is a gut hormone, and it basically just is a very, very powerful appetite suppressant.

Andrew Huberman 1:12:16 Uh, uh, not, well, I guess I'm interrupting but hopefully with a purpose, um-

Layne Norton 1:12:19 Go ahead.

Andrew Huberman 1:12:20 ... there's this really interesting study, and it's in mice admittedly, but, uh, published in a neuroscience journal recently, and the, basically the takeaway is that like so many things in neuroscience, it, the GLP-1 works in two parallel pathways. In the brain it seems to impact neurons in the hypothalamus that control satiety, so exactly what you're saying.... and in the gut, it seems to create a, um, the, an activation of the mechanosensors in the gut.

Layne Norton 1:12:43 Mm-hmm.

Andrew Huberman 1:12:44 So the perception is that the gut is full-

Layne Norton 1:12:47 Mm-hmm.

Andrew Huberman 1:12:47 ... even, or fuller, I should say, not full, because I think people who take, um, semaglutide don't feel bloated, unless, I don't know, m- they might. But that one feels as if their gut is actually fuller-

Layne Norton 1:12:58 Yeah.

Andrew Huberman 1:12:58 ... because these mechanosensors that send stretch, are sending signals to the brain, "Oh, like, I actually have some food. I'm not empty down there."

Layne Norton 1:13:04 Right.

Andrew Huberman 1:13:04 Um, anyway, I d- I, I'm tickled by this result, mostly because every time I hear about a, a drug or a, or a molecule having effect, we think it has an effect at one location.

Layne Norton 1:13:13 Mm-hmm.

Andrew Huberman 1:13:13 But it's kind of interesting that, especially for something like, um, appetite regulation, that it would be impacting body and brain in parallel. Anyway, forgive me, I, uh...

Layne Norton 1:13:21 That's okay.

Andrew Huberman 1:13:22 You can tell I'm, I'm, uh, ex-

Layne Norton 1:13:23 No, I think-

Andrew Huberman 1:13:23 ... really excited about this. And, and here you are telling a neuroscientist, me, that a lot perhaps circles back to these brain mechanisms of satiety.

Layne Norton 1:13:33 Yep. I mean, I, I think that, and especially looking at the research on leptin, you know, uh, like, we used to think, "Okay, metabolism is mostly like liver-based." And then, you know, there's, um, there's, uh, you know, metabolism in the adipocyte and skeletal muscle, but none of this stuff exists in isolation. There's so much crosstalk between these pathways. And that's, you know, when we get into mechanisms, th- one of the things... I love mechanisms, but one of the things I tell people is, keep in mind that when you're dealing with an outcome, right? So like, when I say outcome-based, we're talking about physical outcomes, like, uh, weight loss, fat loss, changes in blood markers, whatever. Tho- that is the summation of thousands of different mechanisms. So sure, sometimes you can affect a, a mechanistic pathway and you get just kind of straight down the line outcome, but not always. You know, whenever you make a treatment or, you know, kind of anything into the system, it's like throwing a pebble in a lake, right? It creates ripples. And we don't always know what those are gonna be, right? Um, and that's why, I mean, we've seen, you know, certain drugs, "Well, it works on this pathway." And then they list off all the side effects, and you go, "Well, how would it create that many side effects?" It's because nothing... For the most part, they don't just work in one place. There's multitude of places it works. Um, and, and to your point about, um, semaglutide and the effects on, uh, mechanosensors, it's probably why a lot of people report actually kind of like no- low grade nausea-

Andrew Huberman 1:15:12 Mm-hmm.

Layne Norton 1:15:13 ... um, when, when they're using semaglutide, uh, because of that. Because if you're, you know, f- that feeling is usually not like a real comfortable feeling, but, I mean, it will get you to not eat. So I think there's absolutely likely a connection, uh, but we haven't fully elucidated how that works, and we think about how complicated the gut is. I think I heard something like, there's more, you know, there's more cells in our microbiome by far than there are in our body. So we're actually more, in terms of a cell per cell level, we're actually more bacteria than we are eukaryote, right?

Andrew Huberman 1:15:48 (laughs) There's a, Justin Sonnenburg, who's one of the world experts on microbiome, he's in the lab upstairs from mine at Stanford, and, um, he has this idea, it's just an idea, that because we are indeed more bacteria than we are cells, the question is, who's the host and who's the passenger?

Layne Norton 1:16:02 (laughs)

Andrew Huberman 1:16:03 You know, like maybe we're-

Layne Norton 1:16:04 Yeah.

Andrew Huberman 1:16:04 ... we are just, maybe they are exploiting us to take them around and interact, because they interact and grow on one another-

Layne Norton 1:16:10 Yeah.

Andrew Huberman 1:16:10 ... and so this idea, this freaks people out. Lex Fridman will love this, that maybe human beings are just actually the vehicles for the microbiome-

Layne Norton 1:16:16 (laughs)

Andrew Huberman 1:16:17 ... and not the other way around. Anyway, kind of a, um, a scary thought. Um, do you do

Andrew Huberman 1:16:23 anything specifically to support your gut microbiome? Are you a-

Layne Norton 1:16:26 Mm-hmm.

Andrew Huberman 1:16:26 ... probiotic guy or a fermented foods guy or a fiber guy?

Layne Norton 1:16:30 So again, I'm gonna kind of go straight down the line from what I've heard from Suzanne and other experts. So if you want to improve gut health, one of the biggest levers, the three biggest levers you can pull is not eating too many calories, exercising, there's a, there is a connection between exercise and the gut, and fiber. So we, it is, of the things we know, dietary fiber seems to positively impact the gut, because it is a what's called a prebiotic. So your gut microbiota can take especially soluble fiber, although there's actually some evidence, at least in mice, that they, it might be able to use some insoluble fiber as well. Uh, I think Suzanne was doing a study looking at hemicellulose and actually seeing that some, like, specific forms of microbiota flourish with hemicellulose, suggesting that they