Dr Layne Norton: The Science of Eating for Health, Fat Loss & Lean Muscle | Huberman Lab Podcast #97

Transcription for the video titled "Dr Layne Norton: The Science of Eating for Health, Fat Loss & Lean Muscle | Huberman Lab Podcast #97".


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Introduction Of Guest - Dr. Layne Norton

Dr. Layne Norton, Nutrition & Fitness (00:00)

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. Lane 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. In 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 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 Lane 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 controlled 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.

Discussion On Nutrition, Weight Loss And Caloric Intake

LMNT, ROKA, InsideTracker, Momentous (02:53)

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 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 Element. Element 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 in 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 anytime 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 element electrolyte mix, I'm able to replenish those electrolytes and maintain mental clarity and energy throughout the day. Element contains a science-backed electrolyte ratio of 1000 milligrams of sodium, 200 milligrams of potassium and 60 milligrams of magnesium. If you'd like to try Element, you can go to drinkelementspelledlmnt.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 ROCA. ROCA makes eyeglasses and sunglasses that are the absolute highest quality. The company was founded by two all-American swimmers from Stanford and everything about ROCA 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. ROCA understands the biology of the visual system and has designed their eyeglasses and sunglasses accordingly so that you always see with perfect clarity. ROCA 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 ROCA 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, etc. If you'd like to try ROCA eyeglasses and sunglasses, you can go to ROCA. That's ROKA.com and enter the code Huberman to save 20% off on your first order. Again, that's ROCA ROKA.com and enter the code Huberman at checkout. Today's episode is also brought to us by Inside Tracker. Inside Tracker is a personalized nutrition program that analyzes 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 Inside Tracker, they have an 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 Inside Tracker, you can go to insidetracker.com/huberman to get 20% off any of Inside Tracker's plans. Again, that's insidetracker.com/huberman to get 20% off. The Huberman Lab Podcast is now partnered with Momentus Supplements. To find the supplements we discuss on the Huberman Lab Podcast, you can go to LiveMomentus, spelled O-U-S, LiveMomentus.com/huberman. I should just mention that the library of those supplements is constantly expanding. Again, that's LiveMomentus.com/huberman.

Calories & Cellular Energy Production (06:50)

Now, for my discussion with Dr. Lane Norton. Lane, 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. As a fellow PhD scientist, I feel a great kinship with you. I know you have tremendous experience in fitness and nutrition and 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. I'm excited too. Like you said, it's been something we've been talking about for a long time. I was glad we were able to make it happen. Yeah, it needed. I think some of the audience has requested a debate or a battle and I can tell you right now. It's not going to happen. Actually, one of the things that brought Lane and I together in conversation online and then via text, etc. was the fact that I love to be corrected. That's what happened. I did a post about artificial sweeteners, which we will talk about a little bit later in the episode. Lane pointed out some areas of the study that I had missed or maybe misunderstood. I revised my opinions and I think it's wonderful and other studies have come out since then. Hopefully, our conversation will serve as a message of how science and actionable science can be perceived. It doesn't always have to be a battle. But hey, if we get into it, we get into it. It won't get physical because we know you would win. In any case, I'd like to start with something that's rather basic and yet can be pretty complex. That's this issue of energy balance and energy utilization. I think most people have heard of a calorie. I'm assuming that most people don't actually know what that is in terms of how it works, what it represents. Maybe you could just explain for people what happens when we eat food of any kind. 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. It's a great question. And like you said, this is one of those things where people use the term calories in calories out. They say, "Well, that's way too simplistic." And I'm like, if you look at what actually makes up calories in calories out, it's actually very complicated. Let's do 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 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. And by digesting, assimilating, and metabolizing those nutrients, we're able to create energy. And the in-product of that mostly is ATP. Adenosine triphosphate, which is your body's energy currency. So to understand ATP, just try to think about if you're trying to power these various reactions in your body. We're talking about tens of thousands of enzymes that require ATP. It doesn't make sense that you would have to create a bunch of micro-explosions. 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 to the mitochondria. Everybody's heard mitochondria powerhouse of the cell. And that is done through essentially creating a hydrogen ion gradient across the mitochondria, which powers the production of ATP by converting free phosphates to ATP. Now, the way that hydrogen ion gradient is created is through creating 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 ATP through glycolysis, and then it boils down to pyruvate, then the acetyl-CoA, which goes through the Krebs cycle, produces a lot more ATP's from that. If you talk about protein, protein's a little bit different because protein gets converted to amino acids, which can be used for muscle protein synthesis or protein synthesis in other tissues. But it also can be converted through gluconeogenesis to glucose, and there also are some ketogenic amino acids as well. And so you can have a few different ways to get to the Krebs cycle, either being through acetyl-CoA or through glucose going through glycolysis to pyruvate. Then you have fatty acids, which are able to create energy through what's called beta-oxidation, where essentially you're taking these fatty acids and you're lapping them off two carbons at a time to produce acetyl-CoA, which again can go into the Krebs cycle, produce those hydrodions that can then power the production of ATP.

Energy Balance, Food Labels, Fiber (12:35)

So that's kind of like at the cellular level of how this stuff works, but stepping back and taking it back out, like, 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 inside of the equation is more difficult to track than people think, right? So one, food labels, which we like to think is being, you know, like from up on high, can have up to a 20% error in them. Really? Oh, yeah. Yeah, 100 calorie is something listed as 100 calories per serving. What's actually in there could be 80 or 120. Right, exactly. 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 food stuff with, say, a lot of insoluble fiber, typically insoluble fiber 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 it's not a little fiber from like plant material, the carbohydrate or even some of the protein is bound up in the plant structure, which makes it inaccessible to digestive enzymes. And so this is what like adds bulk to your school stool or 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 quite a bit of play in the energy inside of things. Now, one of the things people will say is, well, see, that's why you shouldn't worry about tracking calories, because, you know, if 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, eventually you'll be able to know kind of what you're taking in. And that's kind of like saying, well, don't worry about tracking, you know, if you're, I like to use financial 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, because there's inflation, and then there's, if you have investments, those can be, you know, different interest. And whatnot, say, 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. Yeah, that's a good example.

Resting Metabolic Rate, Thermic Effect of Food (15:19)

Right. So now let's look at the energy outside of the equation, which is actually way more complicated, right? And so your energy out is a few different buckets. The first one and the biggest one is your resting metabolic rate, so your arm are. 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. Walking upstairs, exercise, if you do it. Fidgeting. Yeah. Plus your resting metabolic rate. 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 the 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 five to 10%. And very difficult to measure and usually what researchers do when they're kind of looking at this stuff as they just kind of making the assumption about it. They use a constant. But that's about five 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 petrol that you have in your car. Similar with food, you can't just eat food and then 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 calories 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 fat, for example, the TEF of fat is about zero to 3%, meaning if you get a hundred calories from fat, your net will be about 97 to 100. So the process of breaking down that fat, essentially subtracts some of the calories away because you used it in creating energy by breaking those chemical bonds to create ATP. Correct. So you have, 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're 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 going to wind up an adipose tissue. But if you're eating a lot of protein overall as part of a lot of calories, it does, 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 tend to be more satiating. So again, when people talk about, you know, are all calories created equal?

Exercise & Non-Exercise Activity Thermogenesis (NEAT) (19:04)

Yes, but all sources of calories may have differential effects on energy expenditure and appetite. 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, whatever, any purposeful activity. And then you have what's called meat, which is non-exercise activity thermogenesis, which I think is actually really cool. It's fascinating. Yeah, it is. So it's, I was actually hanging out with somebody last night and I was noticing them, they were fidgeting their feet and their fingers. And I said, no, have you always like been pretty lean? And they were like, yeah, I never really had a 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 seems to be as neat. They tend to, if they overeat, they just spontaneously increased their physical activity. Now, people get neat confused. I've heard people say, well, I'm going to go out for a walk to get my need up. That's not neat. Need is not something you can consciously modify. What you're doing there, if it's purposeful, it's exercise. So for example, if 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 going to tap my foot more. Well, now, if I'm consciously having to do this, then my focus, I mean, you know how the brain works. Very hard to do, you know, you don't really do two things at once. You kind of switch quickly between tasks, right? Absolutely. Can I quickly ask, was the person that you're referring to our friend Ben Bruno? No, no. But he is Fidgety too. Yeah, amazing online fitness channel. He's a freakishly strong individual. Oh, yeah. And I can't remember whether or not Ben, you're a fidgeter or not. But anyway, I'll have to go check and we'll measure your fidgeting. About non-exercise-induced thermogenesis, neat. My understanding of the old papers on this, old being, I guess, back to the mid-90s, 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, hundreds of thousands, excuse me, hundreds to maybe even close to 1000 calories per day. Could you elaborate on that? Yeah, so there was actually a really classic study, I think from, I want to say it's from Levine in 1995. It was a metabolic award study. And hopefully I don't butcher the study because I'm trying to, you know, pull it out of my brain. I don't expect you to have PubMed in your head, although I must say you have a quite extensive PubMed ID grab bag in there. I'm trying to bring the receipts. I'm trying to bring the receipts. We can put, we will put a link to the study in the show note captions. So people can prove it if they like. So I believe they had people overeat. I think it was by like 1000 calories a day, I think for six weeks. And I mean, this is the metabolic award. 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 have gained like, I think it was something like three to four kilos, it was predicted. And what they found is this individual just spontaneously increased their physical activity. Like he didn't purposely do it. It just happened. And I mean, 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 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 and eat a meal. He's sweating. You know, he just, he's a furnace, just expending energy. And what's very interesting about neat is that seems to be the most modifiable. I mean, exercise is very modifiable because you can be intentional with that. But of, you know, BMR, TEF and neat, neat seems to be far more modifiable. So even a bodyweight reduction of 10%, they've observed a decrease in neat of almost 500 calories a day for a 10% reduction in bodyweight. 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 locomote. But also there's what's called metabolic adaptation, which is a 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 kind of in the transition phases. So if you start a diet, within the first few weeks, you will have a reduction in BMR that then kind of just 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, within a few weeks, BMR kind of starts to come back up. There is still a small reduction, 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. Interesting. And you've said that it can't be conscious because of that will distract us from other activities. I don't know if you've had a chance to look at this study and I'll send it to you. Maybe it'd 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 soulliest pushup, which is basically a heel raise, kind of a seated calf raise with one foot, 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 blood sugar regulation improved greatly. And I think, you know, there was a lot of excitement about this at some level. But based on everything you're telling me, this fits perfectly with what's known about neat. So this sort of fell somewhere in between with, in between excuse me, sort of deliberate exercise and spontaneous movement. I guess they've tried to make that spontaneous movement a little bit more conscious.

Losing Weight, Tracking Calories, Daily Weighing (25:49)

Well, what I'll tell people is if you're worried about neat, one thing you can do, like these watches, for example, people like, oh, what told me I burned this many calories. They are not accurate for energy expenditure. I mean, it is like there was a meta analysis in 2018, I want to say, between a 28 and 93% overestimation of energy expenditure by these watches. Fitness track. So for those of you listening, we're not going to name the brand, but fitness trackers are so risk-worn fitness trackers. And this is across the board. So like depending on the brand, it could be, you know, more or less, but they all overestimated the amount of 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 because I ate an calorie deficit and I didn't lose weight. You know, 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 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, conservation of energy or that you might have not gotten the right number for you? The measurement tool was off. Yeah. The next thing is a lot of people weigh varies sporadically, and I'll tell people, like, if you're going to make an intentional weight loss a goal. And again, this can be different for different people, but typically I tell people, weigh in, first thing in the morning, or I have to 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. Can I ask one quick, sorry to interrupt, but one quick question about that. When you say go to the bathroom, not to get too detailed here for unnecessarily, but are you talking about urination and emptying your bowels? Ideally, because you did a big meal the night before. Yeah. Yeah. Got it. And then you're going to use the bathroom in all forms that you're ready, and then get on the scale, take that measurement, average that across the week, and then maybe every Monday you take that value and see the progression. Right. And the reason I recommend doing that is if you're just kind of sporadically weighing in, as somebody who weighs themselves 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'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 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, believe it or not, weight fluctuations are actually identified as a major reason why people get discouraged from weight loss. It kind of stops the buy-in, you know, when they have a fluctuation up. So that's one of the reasons early on that low carb diets tend to work really well, is because people lose a lot of water weight really quickly, and they get that buy-in, right? So all of this is working. Yeah, we can return to that in a little bit, because I have theories as to how that, you know, when people eat less carbohydrate, they screte more water and they'll see, you know, for the first time, they'll see some definition in their absol, you know, "Oh, my God, this diet's amazing." And the fluid loss does hold that promise. I think fluid loss can do some other things that might make people literally feel lighter, although it can do. We have some negative effects.

Post-Exercise Metabolic Rate, Appetite (29:24)

I do have one quick question, and I do want, we'll return to neat in a moment, but when you say the caloric burn as a consequence of exercise, I want to ask about the caloric burn during that exercise. So for instance, somebody's on the treadmill and they'll see, "Okay, they burn 400 calories." Actually, I think this is a month where a number of prominent podcasters like Bert Kreischer, Tom Segura, Joe Rogan, others, they call it sober October, but in addition to avoiding alcohol, they're burning 500 calories per day during the exercise. They're measuring it. A lot of people do this. They think they take track of whether, excuse me, take stock of how many calories they burn. 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 building. 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 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 language in here. So if I were to go out, for instance, and do some sprints, run hard for a minute, jog for a minute, run hard for a minute, do that 10 times over. Let's assume I burn 400 calories during that exercise, about. 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? So answer both of those questions. Yes, there does seem to be a small increase 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 I tell people, I think I have a good perspective on this because 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." And then I did nutrition as a graduate degree, and then my advisor was so great because you could do something over here, and he could tell you how it would affect vitamin D metabolism over here. This is Don Lehman. Yeah, Don Lehman. So he would always kind of say, "Yeah, but what's the outcome going to be?" So this is actually one of the things I changed my mind on, was I used to be very much, "Well, I think high intensity interval training is probably better because you get this post-exercise energy burn, which they do see in some of these studies." So I think in the kind of meta-analyses and more tightly controlled studies where they equate work between high intensity intervals and moderate or low intensity cardio, so equating work, they don't see differences in the loss of body fat. And so to me, if I'm looking at, 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 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. I see. And I have to imagine some forms of exercise, this would be highly individual, but we'll spike appetite more than others. So if I go out for a 45-minute jog, which I do a 45- to 60-minute hiker jog once a week, I just make it a point to do that, or rock or something like that, throwing a weight vest and hike. After that, I find that very thirsty, I want to hydrate, but I'm not that hungry. And that's true of most all cardiovascular exercise for me. But after I weight train, about 60 to 90 minutes later, I want to eat the refrigerator. So obviously calories in, calories out dictates that that will play an important role as to whether or not I gain or lose weight, etc. So is it safe to say that the specific form of exercise that people choose 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? I don't know whether or not people explore this in the rigorous studies. And whether or not that form of exercise actually increases lean muscle mass or not. So now we've taken exercise and split it into a number of different dimensions, but this is what you are so masterful at is really parsing how the different components work individually and together. So if you would just expand on that, I'd love to know what you're thinking. Yeah, so this is actually a really fascinating thing. So first thing I want to just go back to talking about, like for example, Bert and Tom and Joe, we're going to do 500 calories a day on whatever. So those apparatuses don't measure those things effectively either, 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 1000 calories. That's a lot of resistance training. My weight workouts are like warm up for 10 minutes and then one hour of work done. I just I love to train. Okay. And you can recover from my recovery quotient is pretty low. 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, 75 minutes, maybe I'm okay, but past that, I have to take two, maybe even three days off before I train my nervous system just doesn't tolerate it well. So I limit it to an hour. Yeah. But part of that to remember is like I've kind of built up to that over a long period of time, right? You know, so you couldn't just throw somebody in and start having to do two hours a day. It's not going to go well for them.

AG1 (Athletic Greens) (35:04)

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Exercise & Appetite, Calorie Trackers, Placebo Effects & Beliefs (36:19)

What I will say about the calorie trackers is so if I'm used to, okay, usually burned about 1000 calories according to this, it's not accurate. But if I go in tomorrow and I do 1300, 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. And so in terms of comparison, it might be okay, like, you know, kind of within subject. 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 not a fat loss diet. They don't even realize it. And that, again, not a complete measure of neat, but what we've had some clients do with our team biling coaches is they'll say, okay, you're at 8000 steps right now. We're not going to add any purposeful cardio, but whatever you need to do to maintain that 8000 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. That's a really excellent point. I've heard, you know, the 10,000 steps per day. Number was, we all heard that. And then I learned that 10,000 was just kind of thrown out as an arbitrary number. So we're like an eight hour intermittent fasting thing. There's a story behind that. It's actually spoke to Satchin. And it turns out that the graduate student in his lab that did that initial study, which was on mice, by the way, was limited to being in lab for about eight hours by their significant other. So the eight hour feeding window is actually the consequence of this person's relationship. 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 tell people like, listen, scientific studies are so confined, you need to be very careful with how broadly you apply what's in there, right? Like they're, they're a very big hammers, the 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? But getting back to your question about like exercise appetite. So first off, I'm not really aware if there's evidence showing like differential effects of different forms of exercise on appetite. It's possible. But 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, 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 realize this. There's research showing that a placebo or the power of suggestion is basically as powerful as some pharmaceuticals. And one of 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 four groups, not supplement with creatine, told they weren't supplement with creatine. Not supplementing, told they were supplementing, supplementing, told they weren't, supplementing, told they were. Basically, it just matters what they told them. Really? Oh, yeah. This is incredible. I have to get this study. So we can link to it. A colleague of mine at Stanford, she's been on the podcast. I'd love to introduce you to because I think you guys, we could really riff. First of all, she was a former D1 athlete and then runs a lab at Stanford in psychology. This is Leah Crumb. And she's in the very athletic, obviously, and very, very smart. And her laboratory focuses on these belief/posibo 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 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 really tune up a number of memory systems, memory improves. And it's remarkable and it's consistent. And they've done this for any number of different things, including food allergies, for instance, incredible results. In any case, I'm so glad you're bringing this up. I take creatine monohydrate and have for years, five grams a day. It's great. And it's great, and I believe it's great. So is there a compound effect of believing it's great and it actually being great? 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 they actually did a study, and I don't have the citation, but it was, I think, within the last ten 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 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 the placebo effect, it's like, eh, you don't have to fall for it 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. Yeah, absolutely. 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 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 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 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 would predict. I have a family member who is perfectly happy to eat less but doesn't loathe exercise, but just likes exercise. And they're of healthy weight, but I'm always encouraging them to exercise more, and so this is an ongoing battle in our sibling relationship. Well, one thing I would say is that exercise independent of anything that happens with your body weight, you will be healthier. So exercise is one of the only things that will actually improve your biomarkers of health without even losing weight. So there's like an improved insulin sensitivity, inflammation, all that stuff. So everybody out there looking for a hack to be healthier, exercise is the hack, right? And our mutual friend, Dr. Peter Ittya, I think has gone on record several times now saying that of all the things that one could take, and amend, et cetera, regardless of whether or not one takes those or doesn't take those, that the positive effects on the longevity by way of biomarkers from regular exercise is 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 health span and lifespan.

Exercise & Satiety Signals, Maintain Weight Loss & Identity (43:46)

Yeah, absolutely. I 100% agree. And when you're talking about weight loss, people missed the point of exercise, I think. There's some work that came out from Herman Ponser 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 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. 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, 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 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 job choice. And they didn't have an intervention, they just wanted to track them and see how much, you know, how many calories did they actually eat. So it was like a J shape 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 regulate your appetite appropriately, or much more appropriately than if you're sedentary. And do you think this has to do with changes in the brain, brain centers that respond to satiety signals from the periphery and/or do you think it has to do with changes in blood sugar regulation? What I was taught, and I don't know if this is 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. This is the idea in mind. I think I adopted, perhaps falsely, that, you know, you eat something that's sweeter, that tastes really good, and you are suddenly on the train of wanting to eat more. And I could imagine how exercise, if it is increasing the satiety signals, could be working in a number of different ways. Yeah, I think the effect is probably mostly at the brain level. You know, the effects on blood sugar, the research out there is not very compelling for blood sugar driving appetite. Now, if you become hypoglycemic, yes, you'll get hungry, but it's a different kind of hunger than like your normal, like I feel kind of empty and my stomach's growling. Like those are, they can go together, but usually like the hypoglycemic is like, I am hot, I feel like I'm going to pass out. Like you want to eat something not because your stomach's growling, but because you know that you just need some fuel. It's like you're getting pulled under. Oh, yeah, absolutely. I've been there when I've done longer, fast, something I don't do anymore, and drank a lot of black coffee. It was probably an electrolyte effect there because coffee as you excrete sodium and other electrolytes. And then just feeling like, I needed something, this whole thing, like I need something that's kind of desperation. I never want to be back here again. Hypoglycemic is very uncomfortable. Not fun. So, you know, again, then when they look at actual randomized control trials of implementing some exercise where they're pretty controlled environment, they typically see people, if anything, they eat less as opposed to eating more. Now, some people, again, 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. Now, it could be their belief surrounded. 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 do this a lot. And I said, "Well, I want to know the physiology. I don't care about the psychology of it." And now I'm kind of appreciating more. Psychology is physiology. You know, like with most things now, we have kind of the bio-psychosocial model. 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 because 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? Right. If you look at dinner plates from the 1800s, they're about this big. Now how big are dinner plates? The whole buffet. Right? Yeah. If you... there's situational cues, right? You're staying down to watch TV. Oh, grab some popcorn, grab some snack, whatever. I even see this with it, you know, how a one person will pick up their phone and then everyone picks up their phone. I think there's a similar effect with food. Yeah. And same thing, right? Like how many times have we either done it ourselves or been experienced people saying, "Oh, you should have something. You should have it." Like, you know, alcohol, especially, right? Like people will... I was thinking about somebody last night and I had a beer and they just had, you know, a water. And I'm like, "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 kind of herd animals. Like, we don't want to be doing something out on isolation on our own. Now, 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 going to set off your alarm system, you know, because 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 the point where I think that hunger is actually not even the main reason people eat. You know, stress, lack of sleep, boredom, boredom, absolutely. So unless, you know, we can do something that addresses all those things, there's a line from a review paper. This review paper came out in 2011 by a researcher named McLean, and it's the best review paper I've ever read. It was called "Biology's Response to Dieting, the Impedis for Weight Regain." And basically went through all the mechanisms of these adaptations that happened during fat loss diets, and how biology's response is to try to drive you back to your previous. And I'm going to 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." So 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." You have it, people don't just eat because they're hungry. So I think really like trying to get outside the box and think about these things, and especially when you read some of the literature, I recently read a systematic review of successful weight loss maintainers, which I thought was really interesting. So they took people who had lost a significant amount of body weight and kept it off 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, 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 are you familiar with Ethan Supley? No. So Ethan is an actor, he's been like, "Remember the Titans and American History X." I certainly saw American History X. Yeah, so he was very large, like he was like 550 pounds, and now he's like 230 and jacked. He was how much? 550 pounds. Wow. And whenever he puts a post on his Instagram of him training, it'll say, "I killed my clone today." And I asked him, "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 going to be able to make long-term changes if I just didn't become a new person." And addicts talk about this, right? Like people who were 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. They've got food addiction. Well, in some ways, bulimia and rx-e are still addictions. You can't stop eating. Like you're 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 tongue-gambling addict. Well, you've got to play this slot, you know, a couple times a day, but no more. Like that's really challenging. So, yeah, I just like all this stuff. It's so important to be comprehensive with how we treat these things. These are incredibly important points. And to my knowledge, I don't think anyone has really described it in a cohesive way, the way that you're doing here. It's 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 and feelings are related to psychology. And therefore, of course, our physiology and our psychology are one and the same. It's bi-directional. Now, there's nowadays, there's a lot of interest in brain body, in particular gut-brain access, and we can talk about that. But 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 burden, overall health and biomarkers. And this is wonderful to learn that it can increase the sensitivity to satiety signals. I think that makes, at least my mind places very high on the list of things that people should absolutely do. But that there are other factors too. And the identity piece is fascinating. It reminds me also, your story reminds me also of David Goggins, who is teaching, you know, he talks about his former very overweight self, almost as if it was a different person. And he uses language that I'm not going to use here. But, you know, I met David, no David a bit, and he's every bit as intense and driven as a remarkable human being as he appears to be online. He is that guy. But it does seem like he had to more or less kill off a former version of himself and continues to do that every day. And I think what your point about this other fellow who does it through a similar process, the word today seems to really matter. It's not like you defeat this former version of yourself and then 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 this is not just a small detail in tying together all these things. I think that what you are describing 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 were a cohesive whole as an individual. Sorry, you were about to say. That's good.

Weight Loss & Maintenance, Diet Adherence (56:32)

Actually, I know one of 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 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'm going to do a diet and I'm going to 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 can't just take insulin once and that's it, right? You got to take it continuously. Otherwise, you're going to have problems. If you do a diet and you lose, you know, 30 pounds, fantastic. But if you then just go back to all your old habits, you're going to go back to where you were, if not more. 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, because people say, well, I'm doing 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 really believe that that's going to be stable for you and plenty of people, low carb, intermittent fasting, whatever, they say, felt easy. You know, I could do this forever. Great. 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 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 track things. And so I allow myself to eat a variety of foods. I allow myself to eat some fun foods. But I track everything. And I'm able to modify my body composition and be in good health doing that. Now, it doesn't feel hard for me. Part of it's I've just been doing it for so long. But the other people, that's very stressful. They don't want to do this. 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 popular diets, and basically what they showed was they were all equally terrible 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, it was a linear effect on weight loss. So really what it says is, what is the diet that's going to be easiest for you to adhere to in the long term, and you should probably do that. And people, again, this is where I step back and take the 10,000 foot view, somebody will say, well, I'm going to do ketogenic because I want to increase my fat oxidation and I want to 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 this going to be something sustainable for you? And if the answer is no, you probably need to rethink what your approach is going to be. It's an incredibly important message. Basically that, you know, if I could highlight, you know, if there was a version of highlighter boldface and underline in the podcast space, I would highlight boldface and underline what you just said. And for those of you that heard it, 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 it also crosses over with the placebo effect. I almost want to say pick the nutrition plan that you think you can stick to for a long period of time, ideally forever, and pick your placebo too because there is a lot of placebo woven into each and every one of these things, intermittent fasting, keto, probably even vegan versus omnivore versus carnivore. And I think we even talk about, you know, the diet honeymoon period, right? We're like, you go into a diet and you're all fired up about it, 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 waiting and going off. Here we are really talking about a form of relationship, you know. I'm not saying that to be tongue in cheek. Actually, we had a guest early on in the podcast, Dr. Carl Diceroth. He's a psychiatrist and bioengineer at Stanford. He's a tremendously successful Lasker award winner, et cetera. And he talked about love as a sort of 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 pair up with somebody that we just referring to romantic love, that there's this sort of mutual agreement to create 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 not a pair of levels with a highly functional and effective diet. And I love it. I'm not setting this parallel up artificially. I'm setting up because I think that ultimately it was 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. And I think one thing I will say is like, keep in mind, when you look at the research data, the meta analyses on, say, time restricted eating versus non, when calories are equated, doesn't seem to be a difference in the way that we're going to stick to. It seems to be a difference in weight loss, fat loss, and most biomarkers of health. Same thing for low carb versus low fat. Few equate calories in protein. 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, I think there was 22 studies in this, but all of them provided food to the participants. Right? That's important because that ensures that adherence can be much higher in those studies, whereas like various free living studies, sometimes you can see people who are living in the future. Sometimes you can see funky results. People are sneaking food or they're just not really eating the way that the study would ideally have them. Unless the person is getting like continuous support, like studies where they have a dietitian talk to people like every week, tend to actually have pretty good adherence. But I mean, that's expensive to have done the studying again, like what limits studies, money, money, and money, right? 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, what 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 got to pull, you've got a bunch of different options.

Restrictive Diets & Transition Periods (01:03:33)

You mentioned 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 weight loss over time or weight maintenance over time? Because I realize not everyone is trying to lose weight. And I definitely want to talk about at some point how to eat to maintain weight. Because I think there are significant fraction of people out there who are trying to do that. Is there any downside to being a dabbler, keto for a few months and omnivore for a few months, etc. ? I think that's actually a great thing, especially to maybe find what you feel is easiest for you, right? But in terms of as a strategy, I guess some people, this might get into dopamine, but like, change and get something new and you feel a bit more positive about it. And you partner model. Yeah, yeah, exactly. So I don't think it's how I would usually set things up initially for somebody. But if somebody said, hey, I just like to have some variety 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 what their goal is, I don't think there's really any downside to it. I do think the one thing to keep in mind is when you look at like going between extremes, so like low fat to low carb or vice versa, 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 just a short period of time. Now, is that going to cause any health problems? Probably not in the long term, especially if you're still controlling calories. But just because your body has kind of like upregulated these systems dealing 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 get somebody or glucose tolerance test after they've been on keto, they do pretty terribly at it. But that doesn't last that long. About how long? A few weeks. I think that's important for people to know because I have a feeling during those first few weeks or 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 I've certainly done that. I've tried very low carbohydrate diet and I would have assumed, and now I know I'm completely wrong, but I assumed that I was so carbohydrate starved for so long that my insulin sensitivity, which is a good thing, by the way, folks, would have gone that way. I 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 a pretty terrible brain fog. I even got some jitters and I thought, "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 had upregulated the enzymes and systems in the body for fat metabolism on the keto diet and then switching over. There was basically a ramping up of the molecules involved in presumably in glycolysis. Transition period. I mean, think about if you haven't weight trained before and you start weight training, you're going to feel pretty terrible, right? Like you're going to 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 fasting bug 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 depends on your specific measure, right? So I think that the idea that keto makes you glucose intolerant or insulin resistant, I think, again, it's just a transition period. And I'm not too worried about it. But there 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 do I feel so terrible?

Talk On Gut Health, Cardiovascular Disease And Protein Importance

Gut Health & Appetite (01:08:03)

Very important point. I want to go to the other end, literally and figuratively, and talk about gut health. Because up until now, and certainly -- I see what you did with that point. And certainly in the last few minutes, we've been talking a lot about sort of top-down processes, you know, the brain, the psychology, placebo effects, but the very real aspects of those. Not that I can imagine 2,000 calories as 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 weight gain. But gut health, at least the more popular studies on gut health, have blown a lot of things out of the water. For instance, this idea that you could take obese mice and literally give them fecal transplants from lean mice. And yes, that sounds like what it sounds like. Fecal transplants definitely inserted through the same end in which it comes out. And I point that out because a lot of people asked me that, you know, it was kind of scary to me. I thought, yes, this is not about ingesting feces. This is -- they literally do a transplant if he's 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 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 going to 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 -- 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. What are your thoughts about gut health as it relates to metabolism, energy, utilization, and balance? The first thing I'll say is I'm not a gut health expert, but I feel relatively comfortable talking about it based on conversations I've had with people who are experts, one being Suzanne Devkota, who's -- are you familiar with her? Well, she's sort of a phenom in this area, from what I understand. So she was actually doing her masters when I was doing my PhD in layman's lab. So she was one of my lab mates. Terrific. And the other thing to say is even gut health experts -- Suzanne will tell you this. They're like, "Talk to me in 20 years. We just know so little." 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, it would be a mess. Right? So it's going to take time before you 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 something where a gut, microbiome makeup that's more obese resistant, perhaps it extracts less calories out of the food you eat, right? Or perhaps it's elevating BMR, although I think that that's probably somewhat unlikely. Do you think it could impact the way satiety signals are? So that's -- I mean, back to the brain again is that question. So that's -- we know that there's a link in the gut brain axis. And so my suspicion is that it probably is working via appetite regulation. So, I mean, if we look at -- if we look at the most effective obesity treatments out there, which is like semaglutide, I mean, you consistently see a, you know, 15 percent, you know, on average loss of body weight, which is massive, and people keep it off, that is a GLP1 mimetic, which is a gut hormone, and it basically just is a very, very powerful appetite suppressant. Not -- well, I guess I'm interrupting, but hopefully with a purpose. There's this really interesting study, and it's in mice, admittedly, but published in a neuroscience journal recently. And the basically the takeaway is that, like so many things in neuroscience, the GLP1 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 an activation of the mechanosensors in the gut. So the perception is that the gut is full, even -- or fuller, I should say, not full, because I think people who take semaglutide don't feel bloated. And I don't know what they might -- but that one feels as if their gut is actually fuller because these mechanosensors that stretch are sending signals to the brain. So I actually have some food. I'm not empty down there. Anyway, I'm tickled by this result mostly because every time I hear about a drug or a molecule having an effect, we think it has an effect at one location. But it's kind of interesting that especially for something like appetite regulation that it would be impacting body and brain in parallel. Anyway, forgive me. You can tell I'm really excited about this. And here you are telling neuroscientists me that a lot perhaps circles back to these brain mechanisms of satiety. Yeah. I mean, I think that -- and especially looking at the research on leptin, we used to think, "Okay, metabolism is mostly liver-based, and then there's metabolism in the adipocyte and skeletal muscle." But none of this stuff exists in isolation. There's so much cross talk between these pathways. And that's -- when we get into mechanisms, the 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 weight loss, fat loss, changes in blood markers, whatever. That is the summation of thousands of different mechanisms. So sure, sometimes you can affect a mechanistic pathway and you get 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 going to be, right? 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?" Because nothing -- for the most part, they don't just work in one place. There's multitude of places it works. And to your point about Semic luteid and the effects on mechanosensors, it's probably why a lot of people report actually kind of like low-grade nausea when they're using Semic luteid because of that. Because if you're -- you know, 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, 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. And we're actually more -- in terms of a cell per cell level, we're actually more bacteria than we are you carry out, right? There's Justin Sonenberg, who's one of the world experts on microbiome. He's in the lab upstairs from mine at Stanford. And 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? You know, like maybe we are just -- maybe they're exploiting us to take them around and interact because they interact and grow on one another. And so this idea that this freaks people out, Lex Friedman will love this, that maybe human beings are just actually the vehicles for the microbiome and not the other way around. Anyway, kind of a scary thought.

Tool: Supporting Gut Health, Fiber & Longevity (01:16:23)

Do you do anything specifically to support your gut microbiome? Are you a probiotic guy or a fermented foods guy or a fiber guy? So again, I'm going to kind of go straight down the line from what I've heard from Suzanne, other experts. So if you want to improve gut health, one of the biggest leavers -- the three biggest leavers you can pull is not eating too many calories, exercising. 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 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. 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 may actually be getting some kind of fuel out of it, which is really interesting. Again, in mice, so, you know, just huge caveat. So your gut microbiome can produce these short-chain fatty acids from -- by fermenting this soluble fiber. And there's quite a bit of evidence that these volatile fatty acids, which can be then actually reabsorbed into the liver, that they have some positive effects, like, for example, butyrate -- when they've done butyrate supplementation, they've actually seen positive effects on insulin sensitivity. So what we seem to understand is that more diversity seems to be better. Fiber seems to be positive. Prebiotics seem to work much better than probiotics. - Supplemented prebiotics. - Yes. So the problem with most of the probiotics is they're typically not concentrated enough to actually colonize. And even if you do colonize, what happens is, like, let's say you colonize some microbiota that you didn't really have much of. If you're not fueling it with the appropriate fiber, it's not going to stay anyway, because it's essentially going to starve. So the research seems to really clearly suggest that eating enough fiber, which is, again, a prebiotic, that that is a better way to get a healthier gut per se than probiotic. What fiber sources do you use? And I think -- I realize there's a huge array of choices out there, but people will want to have some ideas as to how they could perhaps mimic what you're doing. Yeah, and I would just say diversity, right? So, you know, there's various evidence from various different fiber sources. Fruit and vegetables, obviously, you know, grains, some whole grains, some cereals, and then various other sources. So this is one of the things where we don't really have a good idea if, you know, this one source of fiber is better than another source of fiber. We just know that fiber overall is pretty good. And one thing I'll tell people is, like, if you want a longevity hack, I mean, fiber is kind of the longevity hack. If you look at some of these cohort studies, there was actually a recent, really large meta-analysis of over a million subjects. And basically what it showed was that for every 10 gram increase in fiber, there was a 10% reduction in the risk of mortality. And that extended specifically also to cardiovascular disease and cancer. So one of the things I'll tell people when they get, like, really into, you know, whether it's intermittent fasting or, you know, all these other things, that's great. Are you eating, like, over 50, 60 grams of fiber a day? And I just, because it's a centralized 50 to 60 grams, so if I were to eat, like, a bowl, like a, let's just say a quarter plate of broccoli. And the broccoli isn't stacked to the ceiling. The broccoli is just reasonably stacked on there. Approximately how many grams of fiber is that? If it's like two cups of broccoli. Yeah, so if you're like 200 grams of broccoli per se, would probably be like five, six grams of fiber. And I need to get how much per day? Ideally. I would say, I would typically what the recommended dose is, is 15 grams per thousand calories intake. Because if you're eating, you know, low calories, it's difficult to get enough fiber in. But based on, and again, these are cohort studies, so, but you can't do 20-year-long randomized human control trials, unfortunately. That doesn't really appear to be a top end, at least for the benefits of fiber. It probably boils down to like how much you can tolerate without feeling uncomfortable, right? Because if you're eating, like, a ton of fiber, I mean, at some point, it's not going to be very comfortable. Exercise becomes uncomfortable. Or hazardous. Yeah. And actually, I'm kind of touching on that because I think it is important. You know, a lot of people have kind of, in the carnivore community, said, well, you don't need fiber, you poop just fine without it. And I always say, well, pooping is the last reason to have fiber. Like, yes, it does help. It does seem to make elimination easier. You can, you know, do it more frequently, adds bulk to stool. But that's not why you should eat fiber. Why you should eat fiber is because of the effects of mortality. And, you know, some of the pushback will be, well, this is healthy user bias. And what I'll say is... Meaning healthy people do this, and therefore it's working. Well, I'll leave you more fiber, and therefore... And I mean, yeah, there's something to that. But if it was just healthy user bias, typically you would see some disagreement between the studies. And a great example of that is like red meat. So not every study shows red meat has an association with cancer and mortality. There's differences depending on the population used, depending on what they define as high red meat, low red meat, whether it's processed, unprocessed. But I have not found a study on fiber and cardiovascular disease and cancer and mortality, where it did not show improvements from higher fiber. So to me, that suggests that that effect is real. And so again, you know, as much fiber as you can get in comfortably, I would try to do it. Because it seems to have some really powerful effects and is good for the gut microbiome. The other thing that may be a consideration for the microbiome is there's some evidence that saturated fat may not be great for the microbiome, that it reduces the prevalence of some of the more positive strains of bacteria. And that appears to be not so much from the saturated fat itself, but from the bile in products that combine with saturated fat. Seems to have a negative effect on some of these more healthier forms of gut microbiota. But again, this is really difficult because we don't even know necessarily yet which species of gut microbiota are positive or negative. And that's, I mean, this gets into some of these studies where they may call it dysbiosis. Sounds scary, but dysbiosis just means that the gut changed. It doesn't necessarily, I mean, it doesn't tell you anything qualitative about whether the change was bad or good. And so these are just things I think we need to keep in mind when we talk about this stuff. This stuff is still very much in its infancy. But in terms of the big levers, I mean, it pretty much fits with what we know about a healthy lifestyle. Exercise, don't eat too much, consume a good amount of fiber from diverse sources. Fantastic. Fantastic because it fits with what I like to think of as kind of the center of mass of evidence, right?

LDL, HDL & Cardiovascular Disease (01:23:59)

And I'm starting to get some window into what your process is around selection of studies and no one study being holy. But when you look at, as you mentioned, all the studies on fiber having a positive effect to some degree or another, it's pretty hard to refute that there isn't something really interesting there. And one thing I'll tell people is like, you know, one study, I mean, sometimes I'll change my opinion based on a single study when it's really well done and very powerful. But usually like one study is just going to move me just a little bit. All right, and maybe if another one comes out, it'll move me a little bit more, right? And then like very slowly I'm going to get some, I mean, my experience with LDL cholesterol, this is something I changed my mind on a while back. When I was younger, like circa 2005, getting into grad school, kind of the prevailing thought was, well, it's not so much the LDL. It's the ratio of LDL to HDL. That's what matters. And probably about five years ago, and I was pretty strong about that opinion. And then five years ago, looking at these Mendelian randomization studies, I kind of went, I can't hold this position anymore. What's your revised position on LDL? So if you look at the research, HDL is important because it's a marker of metabolic health. If you have high HDL, it suggests that you are metabolically quite healthy. You very rarely will you have high HDL and like high CRP, which is inflammatory marker, or dysregulated blood glucose, almost exclusively people who have high HDL will have good biomarkers of metabolic health. But if you take drugs that raise HDL, it doesn't reduce your risk for cardiovascular disease. And Mendelian randomization studies, which Mendelian randomization basically uses natural randomization. So some people are, in the case of HDL, naturally higher secretors or naturally lower secretors of HDL. And, you know, we talked about how you can't really do a 20-year human randomized control trial. And when you're trying to examine something like heart disease, I mean, that is a lifetime exposure issue. It's very unlikely that you're going to pick out differences between treatments in two years or even five years. I mean, people don't develop, typically don't develop heart disease until they're in their 50s, 60s, and 70s. But Mendelian randomization allows is to say, okay, we have these people who naturally secrete more or less, so we can stratify those and look at what is their risk. So if you look at people who are low secretors of HDL versus high secretors of HDL with holding some of the other key variables consistent, like LDL, you don't see an effect on heart disease, really. Of LDL. Of HDL. Got it. But when you look at LDL and you look at the lifetime exposure to LDL, it is like a linear effect on heart disease. And we know that it's actually not so much LDL, but it's more April, April, April protein B, but that tends to track with LDL, just in general. And if you look at the mechanism, I mean, we know that LDL can penetrate the endothelium. So there's the mechanism is present. If we look at the epidemiology, it supports that it's an independent risk factor. And then again, these Mendelian randomization studies where we can kind of look at people's exposure over a lifetime. And then we see that linear kind of dose dependent effect. To me, that was convincing enough to change my mind on that particular topic. And then if you look at like some of the Framingham data, look at high, if you like stratify like high HDL versus low HDL, both groups looking at high LDL and low LDL. So if you have high HDL, low LDL, you will still be lower risk factor than somebody who has high HDL and high LDL. Right? So the ratio does matter. So the ratio does matter. The same thing with inflammation. If you look at people who are low inflammation, low LDL, they'll have a lower risk than people who are low inflammation high LDL. So again, that was kind of sufficient for me to change my mind. But it took, it was like not just one study came out. It was okay, then there was another study and then another study and then another study. And at a certain point I go, okay, well now I either have to change my mind or I'm basically just going to be cognitively dissonant and say, nope, I don't believe all that. And so I think that's one of the things to keep in mind people will say, oh, you're saying this is a bad study. Very rarely will I call something a bad study because data is just data. But the issue becomes how it is presented and how broadly it's applied in the mainstream media or by people on fitness influencers. And what I'll do is try to step in and say, okay, let's consider X, Y and Z as well. And then it's not a bad study, but let's just be careful about how broadly we imply the interpretation. Yeah, well, and I think you were in a very unique and important position to be able to place things into their proper context because of this, for lack of a better word, holistic view of how the psychology placebo effects also core fat, core physiology relate to one another and so on. In fact, I think that your training as a biochemist and then training as a nutrition with somebody who, Don Layman, who was pushing you to focus on outcomes. I think that's a beautiful capture of the continuum at which one can look at something because for those of you who don't know out there, you know a lot of laboratory studies on mice and humans, for instance, in the realm of biochemistry or in vitro studies, you'll see a change in some molecule can be quite traumatic. And then the assumption is, oh, you just take the drug that will change that molecule in a particular direction and then you'll get the effect you want at the whole organism level. The person will lose weight. The person will gain muscle. The animal will not have Alzheimer's, et cetera, but it just doesn't work that way because of the redundancy and this interplay. Well, a great example of that is so my research was actually in rodents, all my studies on protein metabolism and in leucine in particular is what we were studying. Well, we know if you give leucine increases muscle protein synthesis, but we also know if you supplement with leucine, people don't get more muscular. I was right. All you have to do is supplement with leucine. Right. Right. And so how is that possible? Where muscle building is not just protein synthesis. It's also the balance between synthesis and degradation.

Leucine, mTOR & Protein Synthesis (01:30:31)

So, and degradation just happens to be very, very difficult to measure. But a great example, and again, one of the cool things about my PhD was actually change the way I ate, which I think is so important. Which I think is interesting. So before I had been like, I ate eight meals a day, eat every two hours, try the keels a day. Yeah, when I got to grad school, get that 30 grams of protein. Get that amino drip going in was the idea, right? Like just have an IV hooked up of amino acids. Not really folks. Not really. Yeah. But that was kind of the concept. But the first study I did, we basically looked at, okay, a lot of people had measured the amplitude of protein synthesis. In response to a meal, we wanted to see how long does this last and where does it peak? Right. And so my thought was, okay, well, it'll probably track with plasma leucine. You give, for those that are not familiar, leucine is the amino acid that is almost exclusively responsible for increasing muscle protein synthesis when you eat protein. So it's one of the branch chain amino acids. So we wanted to see, okay, how long does this affect last? We fed these animals away protein. And again, I thought, okay, well, however long plasma leucine stays up, that would be how long proteins of the cystays up. And so we got the proteins of the cyst data back and it was peaked at 90 minutes, or sorry, peaked from 45 to 90 minutes, and then was back down to baseline by 180 minutes. And so when I went to do the plasma leucine analysis, my shock was at three hours, plasma leucine was still plateaued out. And I said, okay, well, when I look at the initiation factors, that will show me something. So for those not familiar, this is part of the mTOR signaling pathway. So one of the two of the targets of mTOR, when it's stimulating, leucine stimulates mTOR, two of the targets of mTOR are a protein compound called 4EBP1. And then another one is called ribosomal protein S6K. So I don't want to get into the specifics about it because it's kind of beyond the scope. But basically, when these things are phosphorylated by mTOR, it increases the rate of transition initiation, which translation initiation is basically the process of the ribosome hooking on to the mRNA and then starting protein synthesis. So I was looking at the phosphorylation of 4EBP1 and RP S6, and I was like, okay, well, I'll probably see these things come down at three hours, still plateaued. And so then it was like, what is, what's going on here? So I actually kept rerunning the data and rerunning the data and rerunning the data. And I'll never forget, I went into layman's office, and this is like six months after we've done this study, because this analysis takes time. So where are we with this duration study? I said, well, I just got to run the plasma data again because it's not right. And he's like, well, why is it not right? And I said, well, it just doesn't make any sense, you know? And I kind of went through, he's like, well, like, describe to me your technique, like, how are you doing this? I described it. And he said, well, how's your standard error? I told him what the numbers were. He said, it sounds like it's good data. He said, it sounds like you are trying to get the data to fit your conclusion, and you need to change your conclusion to fit the data. And that statement, this is why we do PhDs. This is why, yeah, you need an advisor. This is why I'm so skeptical of everything, because I have had so many of my ideas crushed by my own data, right? So we actually ended up, this kind of effect, this phenomenon is called muscle protein synthetic refractory period. So basically, like once you trigger the system, it kind of runs for a defined period of time, and then it takes time to essentially reset for lack of a better term. It's also been referred to as the muscle full effect. But so I looked at that and said, why am I eating every two hours then? And there was even a study out of Wolf's Lab, like back in '99, I think, where they infused essential amino acids for six hours. Proteinsynthesis went up, peaked at 60 minutes, came back down 120, and never went back up again. Maybe I'm being naive, but I would have thought that if protein synthesis goes up and then comes back down, that eating more often would be exactly the thing you would want to do. If your goal was to get increased protein synthesis, because you'd be pinging the system periodically. But the problem is the plasma amino acids are still elevated. So it's essentially like eating the whole way through, from the perspective of losing. From the cells, yeah. So that was one of those things where I said, you know what, I'm actually going to eat less often, because if I'm eating in three hours later, I've still got, you know, capped out plasma amino acids. And we looked at all kinds of stuff, like we looked at intracellular leucine just to make sure that that wasn't falling off. We looked at all the plasma essential amino acids, because we were thinking, well, maybe protein synthesis is sucking some of these amino acids out of the plasma, and they're dropping, and that's causing it to kind of short circuit the system. That wasn't the case. It just essentially what the evidence suggests, I think we're the only ones to show this so far. So I'm not ready to say that this is a real effect, because I hold out the idea that data artifacts do exist, and you can't be totally sure. But we saw an increase in AMP kinase, kind of around this mark where protein synthesis started falling off. And we also saw a decrease in intracellular ATP, and protein synthesis is an ATP dependent process. And so what we think might be happening is you're consuming protein and you're increasing muscle protein synthesis, and then at a certain point, it has enough effect on your energy metabolism in your cells. That it kind of short, not short circuit, but it kind of cuts it off. So again, we're the only ones to show that that I'm aware of, and that was, again, in rats. So I always talk about data. Like there's data I'm willing to bet my toe on, my foot on, my leg on, and my life on. I'd probably barely bet the end of my little toe on that one. I'm not quite sure, but it's interesting nonetheless. So that's a great example of, okay, we're looking at this mechanism of inventory signaling, and if we just looked at that, we'd say, "Oh, well protein synthesis is going to stay elevated for past three hours." But that's not what we saw. So yeah, I think it's, again, that's why I really try to get people to say, "Well, mechanisms are important, and especially if you're seeing an outcome, it's important to identify mechanisms that may explain that." But let's step back from the mechanisms from trying to chase mechanisms, and let's look at, like, chasing outcomes in terms of what we recommend to people. Excellent point.

Tool: Daily Protein Intake & Muscle Mass (01:37:31)

In terms of chasing outcomes, a number of people I know are interested in weight loss or weight maintenance, and several times throughout today's conversation, we've come back to this issue of satiety signals. Whether or not they're brain-based, body-based, or both, not wanting to eat more is a great way to maintain or lose weight because you simply don't want to. I heard you mentioned earlier that protein and maybe specific types of protein or sources of protein may provide better satiety signals than other macronutrients. Could you briefly talk about how macronutrients, including protein, but also carbohydrates and fats, impact satiety? And from the standpoint of somebody who, for instance, would like to, quote-unquote, lose a few pounds, right, probably would be happy to gain a little bit of lean body mass provided it was in a particular location on their body. That seems to be a thing now, directed hypertrophy, if you will. And how much they should focus on protein as a core component of creating this diet, assuming everything else is being done correctly. They're going to hit the right number of calories relative to their output, meat, etc. How should we think about protein as a satiety signals and are animal sources of protein, indeed, more bioavailable? That's a tricky word. For sake of muscle building, but also for sake of somebody who just would like to lose body fat, they don't want to lose muscle and they'd like to bring their weight down a few pounds. So a lot of things to unpack there. Of the macronutrients, protein is definitely the biggest lever that you can pull because even if it doesn't take a ton of protein to get a lot of the muscle building benefits, I mean, I think, it's a big thing. I mean, I think the benefits really start to plateau out around 1.6 grams per kilogram of body weight. There's some evidence that maybe even up to like 2.4 or 2.8 grams per kilo may give like a little bit more benefit. I think it probably looks something like an asymptote in terms of a curve where as you put more into the system, you always get a little bit more, but it just gets to the point where it's so infinitesimally small benefit that it's for all intensive purposes, no benefit. But you mentioned 1.6 grams of protein per kilogram of body weight. Would you consider that a threshold that most people should try and achieve daily? I see very few downsides to hitting that. I mean, I know some people, and this is going to get into a separate conversation, but I know some people will say, "Well, I don't want to stimulate MTOR because that's going to make me die early." And I think one of the things to keep in mind is if you look at, there's kind of this thought process out there that if you're stimulating MTOR, the protein is going to make you die early. And first off, we have very little human outcome data to support that claim. And the second thing is if you look at any macronutrient isolation, I can make a mechanistic argument that it's going to kill you. So fat, if you take in fat, it decreases flow-mediated dilation. Flow-mediated dilation is important for heart health in the short term. Carbohydrates stimulate insulin, insulin, you know, pro-inflammatory, and you know, all these other things. And so I can make an argument for any single macronutrient to be negative for longevity. I really want people, this is something that even scientists get wrong. They look at an acute response of something and assume that that is going to relate to long-term outcomes and signaling. So let's just take exercise, for example. If you didn't know anything about exercise, and I said to you, Andrew, I'm going to do something that's going to make you your heart rate go up, your blood pressure go up, your inflammatory markers go up, your reactive oxygen species increase, you're going to say, and it's going to damage your muscles, you're going to say, "I'm not doing that. That sounds horrible," you know. But it does all those things in the short term. But what is the long-term effect of exercise? You actually get healthier. All those things improve. No, I'm not saying that protein is a longevity hack or anything like that. But what I'm saying is I think some of the arguments out there based on mechanistic, you know, this increases in-tour, therefore we don't want to do it. I think it is a much more complicated argument than just that. So there's that. So protein is the biggest lever. I would shoot for 1.6 grams per kilogram. If you can do more, great. There doesn't seem to be really downsides to it. Even up to very high levels of protein, Jose Antonio did a study. There was a year-long randomized control trial. And again, it's just one year. But they were looking at all sorts of different biomarkers. And basically, even up to like 4 grams per kilogram of protein, they couldn't really find any negative health outcomes from it. Other than people were just so satiated, they ended up eating less calories. So protein is a big lever because one, it has a higher thermic effect of food. So you're getting a little bit more calorie burn per day, even though it's not a ton because TEF is a pretty small percentage of your overall energy expenditure. But still a benefit. You're getting the effects on lean body mass. If you're in a diet that's going to help preserve lean body mass, if you're at maintenance, it's going to help build a preserved lean body mass. And if you're in a surplus, it's going to help build a preserved lean body mass. Then you get the effects on appetite. So now I want to be careful because appetite effects tend to be very specific to individual foods. So you can take a high protein food and make it not very, not very satiating. So take for example, like a really tasty protein bar, which back when we were getting into this, there was no such thing existed. Now you have protein bars actually take pretty darn good. But if you eat one of them, I mean, are you really satiated? I don't really feel satiated. That's my protein bar. That's my pre meal snack. Right. Right. So why? Because I mean, it's processed, refined, and made to be very palatable. Okay. But take something like a 200 gram chicken breast. Very satiating. Right. And that's why when people say, well carbohydrates aren't very satiating. It depends on the carbohydrate. I mean, when you look at the like the satiety index, a plain baked potato is about as satiating as it gets. If I eat a bowl of oatmeal, I feel pretty good afterward. Yeah. For a while. Right. I mean, I usually I'll eat that along with some other things, but I completely agree. The, so you're saying that the form that it comes in, maybe even how much chewing is required, how good it smells, that your psychological associations. Because to me, a steak is an incredible meal. I mean, if I had to pick one food that I could eat, even though I'm not pure carnivore, for the rest of my life, it would be that because I think it would get me where I need to go. And then I'd probably have to sneak some fiber. Yeah.

Protein & Fasting, Lean Body Mass (01:44:24)

You know, but to an excellent point, I have a question that I don't want to take us off track, but I'm hoping it relates enough that you could answer it now. In the context of this, if I'm going to eat, let's say two grams per kilogram of body weight protein, and I'm not eating multiple meals, maybe I'm eating two or three meals per day, I'm certainly going to be eating more than the 30 gram threshold that was thrown around for a long time that we can only assimilate 30 grams of protein per meal. Should I just not worry about that? Some of it is going to go towards the thermic effect of food. Some of that might be converted into glucose of all things through gluconeogenesis. So should I worry about this 30 gram cutoff? Because I think balancing the 1.6 gram per kilogram of body weight threshold with number of meals with the need to exercise and work and live my life and sleep, et cetera, pretty soon you run into bottlenecks where you just can't do it all. Or you're spending so much time trying to focus on it all. You can't optimize all the things at the same time. You lose your mind and your body. So what is necessary in terms of frequency if one is getting enough protein? And then I tied into that question, is there any reality to this idea that if you eat 1 meal per day or you're fasting and then you eat, let's say 200 grams of protein in a single feeding that you can assimilate more because you were sort of protein starved? Is that a real thing? So most of the studies with protein are after a fast, because to assess it with stable isotope you have to be in a steady state. So we haven't observed that. It doesn't appear that fasting really kind of allows you to assimilate more protein after a fast. So this gets into a core of one of the things I looked at in my PhD, which is does protein distribution matter because most Americans get about 65 to 70% of their protein at dinner. Breakfast tends to be pretty minimal protein foods. Do any cultures actually eat a big breakfast and not a big lunch and dinner? Some heard that that was ideal. We'll get into circadian timing in a little bit. Does anyone actually do that? Steak and eggs for breakfast and then taper off the rest of the day. I know German culture tends to have a big breakfast, but it also tends to be sugary foods and whatnot. As far as like teleologically, I'm actually not sure about that. So if you look at that and then you consider that protein doesn't really have a storage mechanism. People will say, "Well, lean tissue is a storage mechanism." That's like saying a house is a storage facility for wood. If the house has been out of wood, you could get wood out of it, but that's not why you build the house. You're building the house out of a demand, same thing for a muscle tissue. There is a free pool of amino acids, but it's very, very small. So when you consider things like fat, which basically has unlimited storage capacity, carbohydrate, a relatively large storage capacity, you can store 400-500 grams of carbohydrate between your liver and muscles. And then protein, which almost has no storage capacity, the idea that, okay, you could make up for a low protein at one meal by over-consuming another meal didn't make sense to me. So one of the studies we did, and again, in rats, we took both groups. We're getting whey protein, so high-quality protein. They were getting the exact same amount of calories, exact same amount of nitrogen, exact same macros. Everything was the same. The only difference was one group basically got kind of three meals of similar amounts of protein. Dinner was a little bit bigger because we wanted to keep it somewhat similar to how people eat, but each meal was going to be over the threshold to stimulate muscle protein synthesis. Whereas the other group, I constructed it so the first two meals of the day should not stimulate muscle protein synthesis. It should be under that threshold, and then the last meal was about 70% of their total daily protein. And so we had them eat those for 11 weeks, and I'll never forget this. This is how obsessive I became about it is there was 110 animals in this study, and I made all the diets, and I weighed out exactly every single meal for every single animal for 11 weeks. So I was in there at 6 a.m., I was in there at noon, and I was in there at 6 p.m., you know? I love it. So that's a kind of PhD student that professors dream of. You're a student. So at the end of 11 weeks, we looked at lean body mass, we looked at body fat, we looked at hind limb weights. We didn't really see differences in lean body mass, but what we did see was a difference in hind limb weights. It wasn't massive, but there was a significant difference in the size of the muscles of the hind limbs of these animals. And so it was interesting that there wasn't a difference in lean body mass, and what we found, at least with the liver, the animals that were eating the one meal with really high protein actually had bigger livers, not like a huge amount, and not something that I would consider unsafe, but it was a statistically significant difference. And so to me, at least, like I'm trying to explain like no difference in lean body mass, but a difference in these hind limb weights, maybe there's some like sequestering of, you know, like that's fueling a little bit more protein synthesis of the splintnik tissues rather than, you know, because you're capping out skeletal muscle protein synthesis. And we do know that the splintnik tissues are more sensitive or have a greater rate of protein synthesis per day. Like the rate of skeletal muscle protein synthesis in humans is about like 1% per day. So it takes like 100 days to turn over, you know, skeletal muscle, whereas like your entire gut, your entire GI will turn itself over in like 2 to 3 days. Right? So really, and the liver also has a very high amount of protein synthesis, which is one of the reasons. It's actually one of the most metabolically active organs. So all that to say, it has not, it's been, there's been one human study that showed something similar. And then there's been a couple others that didn't. And then in the intermittent fasting studies, which is maybe a good tool to look at compared to continuous feeding, it, one thing I will say is it looks like the 16-8 intermittent fasting style. There's been a couple studies with Grant Tinsley. And this is something I've changed my mind on as well. Grant Tinsley has done a couple studies where they did use the 16-8 protocol. They had them train during their feeding window and they had them eat, I think it was at least three protein containing meals during those eight hours. These are humans. And they saw no difference in lean body mass at the end of the study compared to people who were eating, you know, as many times as they wanted throughout the day. Now, if you look at some of the more extreme forms of fasting, like alternate day fasting or like 22-2 or 24, there are some studies where you do start to see differences in lean body mass. So my suspicion is, and I'm just guessing, so this is tenuous. My suspicion is probably if you're getting like two to three, like high quality protein meals in a day, you're getting the vast majority of the benefits of protein. The most important thing is getting enough total. And then, secondarily, trying to get at least two or three meals with high quality protein in. But if you're going like pretty extreme with like alternate day fasting or maybe only one meal a day, then I think there may be some effects on lean body mass. But again, these can be mitigated as well if you're doing, you know, hard resistance training. Typically, that is the biggest lever in terms of lean body mass. Yes, you know, protein distribution may make a difference, but I'm trying to put it in contact so people don't feel like they need to go out and eat four meals a day. But again, so what I would say is like some of the more milder forms of, you know, time-restricted eating appear to be fine for lean body mass. Now, the caveat is the following. One of the nice things about animal studies is when you consider if you want to have a high subject number, high level of control, in a long duration, it's pretty much your only option. Right, so I have in our research review reps, I created a VIN diagram, which basically is like three, you know, circles crossing over. One is study duration, one is level of control, and the other one is subject number. And to get all three of those circles to cross over, it almost has to be in animals. Right. So in this, in reps, it's a newsletter or a book. So it's our monthly research review. Great. So every month we review like five studies that come out in fitness and nutrition, like we'll usually do at least one nutrition, one training, and one supplement per month. We will put a link to where people can sign up. This is a sign up format. Yeah. Yeah. So it's a subscription-based service. So basically, when people might look at like my study, well, why did you see a difference in muscle weights, whereas some of these other studies don't see a difference. I weighed out every single meal for 11 weeks, and keep in mind that 11 weeks in a rodents lifespan is a really long time. That's about an eighth of their total lifespan. So is it that there's no effect, or is it that the effect is relatively small and would take a really long time and very high level of control to see in humans? I don't know, but I think what I would say relatively confidently is if you're going to do like a 16-8 intermittent fasting, you're probably fine, especially, and again, what is the goal? Right? Like if you're a bodybuilder looking to be the most massive person you possibly can, or you're a football player, and some field that having as much lean body mass as possible is really important for you, then I would say, well, you're not really gaining a whole lot by doing some form of time-restricted eating. I think most of the people listening to this do not fall into that category. I think most people want to maintain or lose weight. They'd like to perhaps add a bit of quote-unquote "shape" or muscle to specific areas of their body and lose body fat. Right, and I think your normal forms of time-restricted eating are probably perfectly fine for that, right? And again, I don't want somebody to think, well, I do, you know, alternate day fasting. There's no point to be resistance training because I'm going to lose muscle mass. No, no, no, no, no. You can still build muscle doing that. You just might not build as much muscle as you would if you were eating in a more traditional format. But if that's something that works for you and your goals, and especially if it's fat loss or, you know, controlling your calories, then again, it's about the hierarchy of what's important, right? So to answer your question, I do think that timing and frequency matters are not so much frequency, but distribution more so.

Segment On Plant-Based Proteins, Obesity And Artificial Sweeteners

Plant-Based Proteins: Whey, Soy, Leucine, Corn, Pea (01:55:38)

So I think the distribution matters, but it's a much smaller lever than just getting enough total protein in. And then as far as like animal versus plant, I used to be in the camp of there's no way somebody can build as much muscle on a plant-based diet. And now I think I've come back to, you can, it just requires a little bit more planning. And I don't want to say always, but it's very difficult to do without an isolated source of protein. So unless you're going to supplement with an isolated plant source of protein, it's very difficult to get enough without going over on total calories because you can figure that, especially like, take somebody who may be calorically restricted, trying to get enough protein from whole intact plant sources. So you've got a few different things working against you. One, the source is a protein you're consuming also have carbohydrate and/or fat. Two, it's a less bioavailable form of protein. And three, it's a lower quality of protein in terms of it has typically less leucine, less branched amino acids and less essential amino acids. You answered the question that I almost interrupted you to ask, which was, does it boil down to the leucine content? And it sounds like that is one of the components and that a lot of the vegan and vegetarian sources of excellent protein, that excellent protein, vegetarian or vegan source is co-packaged with calories from carbohydrates and/or fat that make it hard to stay under the clogged threshold. Whereas a steak is, I'm not, and obviously people might want to avoid that for ethical reasons, but that's a different matter entirely. But a steak or a piece of chicken or an egg is, well, an egg has a yolk, which is, there's fat there, but is almost a pure protein fat source. There's no carbohydrate along for the ride. Right. So I think what I would say is that you can do it, it takes a little more planning, and you're almost always, if you're a vegan, especially, you're going to be better off, like, suppling with some isolated form of protein, or vegan form of protein. Now, this word gets into people say, well, what about the limiting amino acids and those sorts of things? It's a consideration. Some of the better forms of vegan protein in terms of amino acid content are like soy. No, I can hear everybody screaming online about their testosterone levels. In terms of actual outcomes and looking at testosterone, there was a recent meta-analysis looking at soy, and I think if it's your only source of protein, then maybe the dosage is high enough to cause some weird effects. But if you're just using it like once or twice a day, it doesn't seem to have an effect on testosterone or estrogen. So that can be a decent source of protein because it is a complete protein source. It does have a PD cause of one, which PD cause is basically a measure of protein quality based on does it provide enough of all the amino acids so that none are limiting. And so soy is one of the only vegan sources that does that. Interestingly, potato protein isolate actually has a similar essential amino acid content to whey. So isolated potato protein, it's just really hard to find. But vegans take note, vegetarians take note because our vegans rather cause whey is vegetarian and whey is a very high quality protein source. And actually they're actually creating whey now out of, I think it's, I may mischaracterize this, but I believe they're able to produce it out of like yeast or something like that. Amazing. So for vegans, now this is a great option because you can have whey that's not animal based that is going to be every bit as good as an animal based whey. So I think that's great. Getting to the leucine, let me go back. Sorry. So another reason that the using an isolated protein can be helpful is because it's more bioavailable as well when it's been isolated out. When it's the protein bound up in the actual plant material, it tends to be less bioavailable. Now cooking can help increase the bioavailability because it breaks some of those bonds and whatnot. But it still seems to be lower and you don't, it's really interesting. There was a recent study where they did a corn, wheat and pea blend of protein versus whey. And basically the outcome was 30 grams of each stimulated protein synthesis to a similar degree. But the plasma amino acids in the plant-based protein still did not get as high as with whey. Now it may be that that's just, it doesn't matter because once you get to a certain level, you get all the benefits. So, but I still found it interesting nonetheless that it didn't quite get as high. The other thing to consider with the vegan sources of protein is the leucine content. So, one of the studies we did was we looked at wheat, soy, egg and whey. Isonitrogenous, meaning we equated protein between the groups. Isocaloric, we equated calories and we looked at muscle protein synthesis. And I think this was, the meals were 15% of total energy from protein. So, like a, like your food guide pyramid level of protein. And we saw that in the wheat and soy group, they did not increase muscle protein synthesis, but the egg and whey group increased muscle protein synthesis. Now, what's really interesting is we went back and we took wheat and added free leucine to match the leucine content of whey. And the protein synthetic response was identical. So, again, I don't like to simplify things too much, but leucine appears to really be driving this ship. And I'll never forget, layman called me in his office one day, and he would always do these like thought experiments of, he liked to think about why something occurs the way it does. Dangerous territory. Yeah, so he would say, one day I'll never forget, he's like, "Laine, why do you think the body evolved to just sense leucine for muscle protein synthesis?" And of course, I'm like, "Oh, I don't know, man, I just work here. I'm just trying to get my PhD." And he said, "Well, think about it. You would want something that really wasn't extensively metabolized by the gut and liver because you would want to show up in the blood in values that reflect what you just ate." Makes sense. And you would want it to have passive diffusion across the muscle cell because you'd want to be concentration dependent, which it is. So... Get into the tissues and cells that need it most. Right. So not having active transport, but rather passive transport. So yeah, I thought that that was really interesting the way you broke that down. So few different options for the vegan folks out there. You can use an isolated source of protein. And again, like there's going to be good options coming because this plant-based whey is going to be a great option for folks. You can add free leucine to it, to whatever your source of protein is. Just buy supplemented leucine powder. Just buy leucine. Now, it tastes horrible. Yeah, I think I've heard that. Maybe I've even tried it. It's completely non-polar. It does not dissolve in anything. It can be put into capsules. It can be put into capsules. Yeah. So you could take a capsule. Like, for example, if you're eating your normal meal, you could just take a capsule of like one gram of leucine. It's probably going to bump you up enough that you're going to be good to go. And then there's options like blends, especially with corn. Corn is actually very high in leucine as a percentage of its protein. Now, you've got to remember, like, you go eat corn on a cob and you're getting like two grams of total protein. So it's not that much leucine. But if you isolate out the protein, put it into a powder, well now, you know, when you're getting like 80, 90% of the weight is now protein, corn is actually about 12% leucine in terms of the protein. So a great source of leucine. It is like almost frank deficient in some other amino acids. But you can blend it with a few other sources of protein. Like you could blend it with a soy, a pea, and you can create these complimentary blends that would actually have quite a bit of leucine, but also some of the other essential amino acids. So there are options out there for plant-based folks. And I mean, we have seen people who are plant-based, you know, build impressive amounts of muscle. There's quite a few bodybuilders that are plant-based. And a lot of the endurance athletes like it. And even though when we talk about muscle, we think about muscle building often, performance in endurance sports and also just performance for the typical person who's doing some cardiovascular training, hopefully some resistance training also, and just living life. I mean, many more people now, it seems, are vegan or at least avoiding meat in particular red meat. I'm not one of those people. I limit the amount and I certainly focus on the quality of what I eat.

Processed Foods (02:04:28)

But I do eat red meat, which brings me to a question about, you know, just generally in terms of food choice. You know, can we come up with a relatively short summary of the following? Tell me if this is correct or not, that most of us should be focused on, for sake of health, health span and lifespan, should be focused on ingesting minimally, non-processed and minimally processed foods, you know, maybe even cooking our own food. You know, I realize that's heresy now, but ideally we do some of that. And really trying to avoid foods that are highly processed and have lots of sugar. And I'm using this as a segue to get into a question that I really want your answer to. I've been dying to ask you this, which is if sugar intake is not actually going up, as much as people think it is, why are people getting so much fatter? So what do you think about just a general statement that we should try and eat foods that are low to no, minimally to not processed for about 80% of our foods? Is that a number? It's hard to actually get, you know, completely unprocessed food, because almost everything goes through some form of processing. So I'm thinking that anything that wouldn't survive long without refrigeration, on a shelf, like an apple or a banana or like ground oats to me, as long as there isn't a bunch of other stuff, and there would be minimally processed, a steak is not really processed, although it's cut off the animal, so there's a few steps in there. But that's what I mean. I think everybody kind of gets the gist. I'm probably a little bit pedantic when it comes to this stuff. No, this is good. Actually, one of the things I appreciate about you is something that I get teased a lot by people close to me, which is the caveats and the insistence on precision is really important, because especially with online communications these days, it's like a runaway train. You know, people will, you know... It's too easy to misinterpret what you're saying. Very easy to misinterpret. And the misinterpretations are often used to leverage whole new ideas about what isn't true, mostly about what is true. So I really appreciate the nuance, and this is what a long-form podcast really allows us to do is catch every curve. Yeah. So I would 100% agree with what you said, that if you were going to make a broad stroke, that trying to focus on minimally processed foods is very important. The one caveat I would say is I think it's important to understand why, because otherwise people can make this weird association that, like if I eat any processed food, it's going to kill me, or like every time I eat it, it's like I'm smoking a cigarette in my health, you know, my longevity is declining. Based on the studies we have, it's mostly about the energy that processed food just gets people to spontaneously eat more. And Kevin Hull showed this in his study that was very... I mean, he designed some of the most elegant studies in nutrition. He's great. And they basically took people from a minimally processed food diet and then gave them access to ultra-processed foods, very few instructions just to feel satisfied, and they spontaneously increased their calorie intake by 500 calories a day. I mean, that's massive. So, and we quite haven't quite figured it out. People said, "Well, it's sugar. It doesn't appear to be sugar." In terms of just an isolation, well, it's fats. Doesn't appear to be fats in isolation. Well, it's the combination of sugar and fat. Partly, well, it's the combination of sugar, fat, and salt. Partly, but there's some kind of like overall magic to the texture and the mouth feel and just the overall palatability of stuff, which is always why I say there's like right and wrong ways to these different diets. Like for example, like there's a right way to do plant-based, and then there's, you know, like, what's in some of these documentaries where they're eating like plant-based mac and cheese. You know, and again, I love a good mac and cheese, but like that should not form, like that should not be pitched as a healthy diet just because it's plant-based, right? Because I mean, you're eating a highly processed food that's very palatable and easy to overeat. Same thing for keto. You've now got like keto ice creams and you've got, you know, keto cookies and all these sorts of things. And I'm like, yeah, and if you look at them, they actually have more calories than the normal stuff. And I'm like, yeah, this is completely missing the point here. Like you're actually just taking yourself, like the whole point of those diets is the reason you tend to lose weight is originally, like good luck, you know, 10 years ago doing a keto diet eating processed food, right? Like you just couldn't do it, really. Now you can. But the problem is it's not going to work because you're going to be still consuming too many calories because even though it's keto, what are they doing? Well, they're trying to make it more palatable. They're trying to make a better mouth feel, which I guess if you're being keto for the sake of being keto, great. But if there's, if you have hopes of body composition modification, it's going to, you know, really negatively impact. So yes, I think minimizing the amount of processed food you consume can be important. Now that being said, it depends on the individual and their goals. If your goal is to, for example, build muscle or maintain a high body weight for a sport, for example, like an NFL offensive lineman or something of that nature, or if you're, you know, I worked with an NBA team, they were kind of, I can't disclose anything, but they were looking at drafting a certain player. And, you know, like for them, processed foods may actually be a tool. Or teenagers, right? We all want young people to eat more healthfully, I think, develop great habits, but some of them, their caloric needs are so high. So high. That if they were eating what I eat, they're going to dissolve into, you know, they're just waste away. So I, I described this again with a financial example. It's like a budget, right? So if I make a million dollars a year, for example, is it okay for me to buy like a $100,000 sports car? Let's assume that loans don't exist, right? Is it okay for me to buy a $100,000 sports car? If I still am able to pay my mortgage and pay my utilities and like take care of my responsibilities, the things I should do, is it okay if I do that, if it like makes me feel good and it's fun? Yeah, it's fine, right? Like you fits in your budget. If I have, if I make, you know, 50 grand a year, should I be going out and buying a sports car? Probably not because I'm not going to be able to pay my mortgage and all these other responsibilities. So your, your protein, your fiber, your micronutrients, these are your responsibilities. But those become much easier to hit when you have higher calories, right? So if you're, if you're, you know, eating 4,000 calories a day for whatever goal you have, you're probably going to have some leftover and like good luck eating 4,000 calories from mentally processed foods. You, quite frankly, you'll be miserable because you're, you're going to have such gut fill that you're going to feel like you can't even move. And so again, now it becomes okay. Well, is there something inherent to that food processing? Is there something, you know, that we can pick out that we know, okay, well, this is going to be a negative effect on health, even like body composition stuff aside?

Obesity Epidemic, Calorie Intake & Energy Output (02:11:54)

And I would say there's not really great evidence of that so far. And a great example of that is sugar. I mean, I actually just wrote a really long article on my website about why I think sugar was not the root cause of the obesity epidemic. And you kind of mentioned like sugar intake in the last 20 years has actually gone down a little bit. Alcohol intake. Well, if you look on the hole, it might have gone up a little bit, but you know, certainly in the male sector, it's gone way down. Drinking used to be, there was a 5 o'clock. People drinking all day. People are smoking a lot less. I think it's a real puzzle. I'd love to know what your health pockets are. I was talking to actually be in opposition because nicotine is actually an appetite suppressant. And also increases focus. The problem is it often arrives in a delivery device that can kill you. But nicotine itself is a powerful agent. It also can offset age-related cognitive decline, not entirely, but it makes the brain work better. I've got a buddy who doesn't like caffeine and he just takes those nicotine pouches and basically has one in almost all day because he's a very stressful job and is a high performer, you know? Yeah, be careful how you deliver it. But there's a Nobel Prize winning neuroscientists that will chew 5 or 6 pieces of nicker at an hour, which I do not recommend. But when he quit smoking, he just simply couldn't function as well. And he was the one who pointed me to the literature on offsetting age-related cognitive decline, even neuron maintenance. It's pretty interesting. It's a pretty impressive new tropics, to be honest. The first thing I realized is when we're talking about consumption data, this is based on actual production, basically. They're assuming that, okay, we're producing this amount of these foods so we can assume the consumption is going to follow that. So it's not a direct measurement. But it has been validated in a few different studies. We know that oil consumption has gone up. That's one of the big ones. And this kind of forms the crux of the seed oils or the root of the... It's definitely a question that I'm going to ping you on. They're going to come into your house and kick your dog and punch your mom and all kinds of stuff. And I'm happy to address those. But so calories have still gone up. There's some people who claim that they've gone... they've kind of plateaued. I think the data seems to suggest that calorie intake is still increasing. And the other thing to keep in mind is, even if it's plateaued, it's still at a high enough level that obesity is probably going to continue to increase up to a point where it'll probably plateau if calories are plateaued. What about energy output? Leaving aside meat because that sounds highly individual. I mean, people we know are focusing on exercise. There are a lot of folks out there that don't exercise. And energy output has gone down over the years. I mean, it's very obvious when you look at how people work now compared to even 30, 40 years ago. It's much different. Less walking. Also, I learned recently that kids in high school don't take PE class in many schools. We had to suit up and run and suit up. And if you didn't bring your change of clothes or you didn't wash them, in which case you'd be better off just not wearing them, nothing like the smell of a boy's locker room after a weekend, you know, you can still remember it. And it's not pleasant. But you had to run and do your push-ups with everybody else or play volleyball in your regular school day clothes. So that... my understanding is that physical education is not part of the basic education any longer. It probably depends on the state, but I know many states have done away with it just because of budget cuts. So activities going down, caloric intake is going up, maybe plateauing. Is that sufficient to explain the obesity epidemic? Based on what I've seen, I think it's pretty sufficient. So it might not be that big of a mystery after all? No, I don't think it's a big mystery. I think that people don't like the concept of energy balance. And I think because they insert judgment into it, which is, okay, if you're gaining weight over time at a fundamental level, it means you are eating, you're consuming more energy than you're expending. People insert the judgment, which is you're lazy. You're a sloth. You're whatever it is. And I think there's a lot of people out there who actually think that. I actually remember talking to somebody who was like, "Well, I would never hire an obese person for a job because it's just obvious that they're lazy." And I just remember going, "Are you serious?" Like, there are plenty of very, very smart, high achieving people who are obese. Like, it's not, this is what happens when you just put people in buckets. You know, like, people are much more complicated than this. Yes, there is some personal responsibility. But then when you look through the data and you take, there was a study done in obese women where they found that women who are obese were 50% more likely to have had some problems. They had some form of sexual assault trauma in their past. Right? We know that people from lower income areas are more prone to be obese. There's several, like, people who have a higher ACE score, I believe, which is kind of measures like traumatic childhood events. I believe there was a study showing them more likely to be obese. So there's, yes, it is an energy imbalance problem. But, you know, just saying eat less, move more, that's like telling broke people, "We'll just earn more money than you spend." It's technically right, but it's very unhelpful, right?

Obesity, Sugar & Fiber, Restriction & Craving (02:17:33)

What is more helpful is to describe and implement the habits and behaviors that will allow them to achieve that, right? So, kind of, I realize we kind of got a track a little bit, but circling back to, like, sugar. Circa 2005, I believe that sugar was fattening and bad for your health independent of any other variable. So, independent risk factor. And again, I want to be very clear about what independent means. Independent means independent of all of the variables. This thing is bad for your health and body composition. So, on its own, independent of whether or not, for instance, it increases hunger and appetite. Right. Or, or caloric intake, right? I was in a graduate school mixer. And one of the professors there was somebody who had done research on high fructose corn syrup and fructose specifically as well. And he was talking to another professor. And he had done this study in groats where he'd fed like, I think it was like 60 or 70% of their calories from fructose. And they saw some really weird things happen in the liver with an oval epigenesis and all this kind of stuff. The other professor is saying to him, yeah, it's pretty obvious that high fructose corn syrup is, you know, fattening. And this professor who had done this research said, yeah, because it's people over eat. And he's like, don't you think there's something inherent to it? And he said, no, I think it's just calories. He was eating too many calories. He's like, we did a proof of concept looking at, you know, could we, like, try eating 70% of your daily calories from fructose? You actually can't do it. Like, high fructose corn syrup is only 55% fructose. So if you ate nothing but high fructose corn syrup, you would still not get to this level that they fed in this study. So that got me kind of like questioning my beliefs about it. So then I went through and I said, okay, like, let's take out the epidemiology. Not that epidemiology is useless, but people who eat more sugar are also likely to eat more calories. So then I looked for the randomized control trials where they, you know, match calories and vary the amount of sugar. And it doesn't seem to make a difference. At least from fat loss or fat game. But what about health? So for instance, if somebody, and I know somebody like this who loves sweets is thin, get some exercise, not a ton. But my concern is that a significant fraction of their calories are coming from these sugary foods, and therefore they're not getting enough fiber, maybe protein, et cetera. So let's look at epidemiology for a second, and I'll address this more directly. When we look at epidemiology, people who eat higher amounts of sugar tend to be more obese, and tend to have, you know, worse biomarkers of health. But people who eat fruit, a lot of fruit sugar don't have those same associations. So why is that? Well, because fruit has fiber with it, right? So I started to kind of believe, based on the data I was looking at, that high sugar intake was not the problem per se. The problem was that high sugary foods typically are very low in fiber. But if you're getting enough fiber is sugar a problem. So there was a classic study by SirWitt in 1997. I think it's still the best study to this day looking at this. I know those people say, "Well, it was done in 1997. It has no relevance." You know, I know. If it's a good study, it's a good study. Some studies are timeless. In fact, they have greater records. We're not going to go back and undo the discovery of DNA because it was, you know, 60 years ago, or whatever it is. So they looked at an 1100 calorie diet, so low calorie diet. One group was eating over 110 grams of sugar a day, like sucrose. The other group was eating about 10 grams of sugar per day. Calories, protein, carbs, fats, all matched, right? And they provided all the meals to these participants. So very tightly controlled. And it was over six weeks. Both groups lost the exact same amount of body fat. So it doesn't seem to matter for body composition in terms of like sugar per se. Then they also looked at some biomarkers of health, like blood lipids and, you know, blood sugar and some other things. Again, there was no real differences. The only difference was, so all the biomarkers improved in both groups. The only real difference was a small difference in LDL. So the group eating low sugar had a better improvement slightly in LDL. But that's probably because they were eating more fiber. And we know fiber can be a bind to cholesterol and lower LDL cholesterol. So is, now I want to caveat this, sugar probably doesn't have any like positive health effects. So there's that, right? And nutrition is an exchange. If you're eating one thing, you're not eating another thing, right? So I, but what I would tell people is focus probably less on sugar, focus more on fiber. So if you're eating 30, 40, 50, 60 grams of fiber a day, but your sugar is, you know, 80, 90 grams, I would not be that worried about it. Especially if you're controlling calories as well. You know, what I would be worried about is if you're eating, you know, just a decent amount of calories and not getting enough fiber and, in general, right? And even in studies, there's a few meta analyses out now looking at isoe energetic exchange of different carbohydrates with sugar carbohydrates. So fructose and glucose and sucrose. Now why is this important? Well, again, you know, if you're not equate, when I say isoe energetic, that means equal in energy, equal in calories. So basically when they exchange either sucrose or glucose or fructose for other forms of carbohydrate, do they see differences in these markers of health, like HBA1C, fasting blood glucose, you know, blood lipids, and with rare exceptions, and I can't remember all the data points exactly, but the take home is doesn't really seem to make a difference. Now, before anybody out there, straw man's argument, I am not advocating for sugar consumption, but I think it's important for people to not create weird associations in their minds because one of the things I've observed, especially in the fitness industry, is when people feel like they can't eat something, like it's one thing if you say, "I am choosing not to eat this just because I'm choosing to." But it's a very different thing when you're purposely restricting because you feel like something is bad. And this, I mean, you know, the human brain is in many ways amazing and in many ways really dumb. So when you purposely try to restrict something, what tends to happen is you're more prone to binge on it. So people who will try to, "Well, I'm never going to eat sugar again or I'm going to try and limit sugar." And this isn't the case for everybody, but they have actually shown now in studies, people who are purposely restricting a specific nutrient, they tend to crave more of that nutrient. And if they do get exposed to it, they're more likely to have what's called a disinhibition reflex, which is basically a binge response because the thinking goes, "Well, this is bad." And there's no context on dosage making the poison. This is just bad in general, so if I have it, I've already screwed up. I might as well just have as much as I want. And I like Spincinodolsky's, compared to this, that's like getting a flat and then going out and slashing your other three tires because you might as well. So I really, I try to come from that perspective of I've seen so many people struggle with, you know, maybe not an eating disorder, but disorder to eating patterns because of these kind of associations they've made in their mind. And so that's why I'm so pedantic and a stickler about saying, "Okay, yes, it's a good idea to eat a minimally processed food and try to avoid processed foods, but not because processed foods are bad per se, but what the outcome tends to be from a lot of processed food consumption, which is over consuming calories and then therefore, you know, energy toxicity negatively contributing to your health." Yeah, it seems like it again returns to this, the potential for a positive, negative, or neutral behavioral change or a perceptual change of like craving of food all the time that you can't have is terrible.

Artificial Sweeteners & Blood Sugar (02:25:57)

It's a terrible state to be in. And this I think is a perfect segue for something that first brought us together. Which was, you know, which was this thing about artificial sweeteners. And let me just for the record be very clear. I have long ingested foods with artificial sweeteners, so I, throughout graduate school, I didn't have the best habits. They're healthier now than they were back then. But I would drink, you know, Diet Coke or two per day. I still have the occasional Diet Coke. I'm not completely averse to drink something that has artificial sweetener. Although I do avoid sucralose for reasons that maybe I can get into a little bit later. But a lot of the things I consume contain Stevia, which is not artificial plant, but it is a plant-based non-calaric, or a local or a sweetener. And I don't have a problem with that. I became very interested in artificial sweeteners because of the animal data I'm pointing to the idea that they may disrupt the gut microbiome. And then disrupt the gut from microbiome as you pointed out is a very broad statement. I don't really know the percentage of lactobacillus, exobacillus, or whatever, psilence, illus in there. They all seem to end in illus is ideal. And in fact, a lot of these companies that are having people send in their stool samples for analysis of the microbiome. I mean, take note, we don't really know what a healthy microbiome looks like, but we know what an unhealthy microbiome might look like. And it's one that doesn't have a lot of diversity in there. I was interested in that. Then there's the recent human study, which we should definitely get into. But I was mostly interested in artificial sweeteners for the reason that there is this food conditioning effect. And you see it in animals and you see it in humans that if you ingest, well, coffee is a really good example. Coffee doesn't actually taste good, folks, even though I like it. But when you taste coffee for the first time, most people think it's bitter and disgusting. Most everybody, like 95% of people say this doesn't taste good. Wine beer is the same thing. Yep, but people learn to associate the state of being caffeinated, which most people like in order to just feel normal. Right? Caffeine's one of the few drugs we ingest just to feel ourselves enough that soon, myself included, really look forward to and enjoy a cup of coffee. So it's a powerful example, in my opinion, of the food conditioning effect. So it's like a Pavlovian thing instead of salivating you crave. Right. And it did seem that this study from Dana Smalls Lab, which admittedly was a small, no pun intended study itself, not very many subjects, showed that if you ingested artificial sweeteners along with food that contained glucose, that you could sort of maybe even get a heightened glucose response just from the artificial sweeteners after a while. You and I connected over this study on social media. You pointed out that the design of the study wasn't superb. There was co-consumption of glucose, which made it complicated. We can go into that. But the reason I'm spouting off all this context is artificial sweeteners are many things. So I'd like to talk about their effects on blood sugar in the acute sense and according to what we might ingest them with, and how they might be changing blood sugar regulation at the level of brain and/or body. And then the gut microbiome data, I think, are interesting enough to discuss. And I have changed my view on artificial sweeteners based on what you've taught me. So this is a case where I've completely changed my view, which is that now I don't have any problem with them whatsoever based on the current data, which is not to say that I'm, you know, gulping down cupfuls of sucralose. But I feel okay ingesting some stevia and some aspartame, and I'm not too worried about it. Yeah, so I think kind of stepping back from a broad view, we have to think about, again, the hierarchy of importance, right? And what are you replacing with, right? So there is no situation where it is not a net positive to take somebody who drinks sugar sweetened beverages and have them drink an artificially sweetened beverage. Like in the meta analysis, there was actually a recent network meta analysis looking at markers of out of posity, HBA1C, a bunch of different health markers. And when you substitute, we'll call it non-nutritive sweeteners, since stevia is not artificial. But so when you substitute in an S for the sugar sweetened beverages, you see improvements in a lot of different things. Okay, what was really interesting about this network meta analysis was they also looked at water substitution in place of sugar sweetened beverages. And the effect wasn't as powerful as these are randomized control trials. So artificial sweetener containing beverages are more beneficial? So they were better for improving out of posity, and then in the health markers, it was kind of a wash, water and non-nutritive sweetener beverages performed similar. But they were better than sugar sweetened beverages, obviously. So they then based on a network meta analysis is kind of where you can compare two things that didn't get compared directly. So there's not many studies comparing in an S versus water directly. But if you have a common comparator, so if you compare A to B and B gets compared to C, you can compare A to C based on how they interact with B. Buttering it a little bit, but that's kind of the crux of a network meta analysis. So they looked at in an S versus water and found that actually in an S was slightly better for improving out of posity. And then S, of course, being non-nutritive sweeteners. So now again, if you like drinking water and you don't want to, I'm not trying to convince anybody to do that, what that seems to suggest is there is a little bit of an appetite suppressant effect from these artificial sweeteners or non-nutritive sweeteners. Now, this gets a little more complicated because if these were people drinking sugar sweetened beverages, maybe they've already developed a sweet taste and trying to go to water is too much of a jump for them. And so going to having something like intermediate is a little bit better. Like there's a lot wrapped up in this. But these are the randomized control trials, which are a little bit more tightly controlled, which I tend to default to a little bit more than I do the epidemiology, which epidemiology is just so messy because sure, non-nutritive sweetener consumption may be associated with different things. But there's also a whole other set of lifestyle and habits that are tied up in that. So I tend to hang my hand a little bit more on the randomized control trials. So understanding that, okay, now all things being equal, understanding that this is a tool that may help some people, and whenever I post about non-nutritive sweeteners in the comments, there's always one or two or three people who say all I did was cut out soda, and I drank diet soda instead and I lost 50 pounds, or I lost 75 pounds. I even had one percent, I lost 100 pounds, that's the only thing I did. Wow. I mean, that's a pretty massive lever to pull. If you consider somebody who might be having like, I mean, five or six cokes a day, I mean, that's, you know, we're talking a serious amount of calories. And that also means that by replacing with artificial sweetener containing beverages, they did not replace the soda with food. Correct. So like, let's now, let's talk about, right, this is where we can get into the microanalysis, but is that obese person who lost 100 pounds by doing that? Do I really care about maybe a small alteration to their big gut microbiome? No, because their gut microbiome is actually much more healthy now by them having lost all that excess adipose tissue. So again, the ranking of what I'm worried about, you know, can change depending on the specific situation. Now, let's take somebody like me, who's lean and doesn't really have, you know, any health problems that I'm aware of. What about artificial sweeteners for me? Well, for me, I kind of got using them because of bodybuilding contest prep because it was about the only appetite suppressant that worked for me. But do I think that they are healthful? Probably not. Do I think they're unhealthy? I would say based on the current data, I don't think that they're unhealthy. Now, the information on blood glucose, so there's some of the problems with some of these meta analyses or these reviews is they kind of lump all the non-nutritative sweeteners together. And then they may say, well, there's no effect on this or there's an effect on this. Well, the problem is these probably are different molecules and they can interact differently. Aspartame very clearly seems to have no effect on blood sugar or insulin. That has been repeatedly shown. Stevia doesn't appear to have much effect. Saccharin and sucralose, the jury is kind of mixed. Now, there was the study that we first connected on, which I think their primary outcome measure was actually they were looking at like kind of the sweet taste, like how it affected sweet taste. So what they did was the group that was getting the sucralose was also paired with maltodextrin. The control group was getting sucrose, which is an appropriate way to compare the sweet taste because maltodextrin is not as sweet as sucrose. So when you're trying to combine sucralose, which is already sweet with another form of chroma hydrate, you'd want something less sweet compared to your control. But for the outcome measure of insulin and blood glucose, probably not as appropriate because we know maltodextrin has a much higher glycemic index than sucrose. Right, so they appropriately controlled for taste, but not for the effect of the sweeteners. And I think that that was a key component. And I think the part of that study that intrigued me actually was in a talk version of that because that study drove me to watch a talk that, and we'll get Dana Smalon on the podcast at some point, hopefully, was that they had kids do this study. And they actually had to cease the study because a couple of the kids became prediabetic. I mean, it seemed like there was something hazardous about, this was at Yale School of Medicine, it's a good place. I mean, you know, there's a range everywhere, but it just seemed like there's something about sweet taste that if taken to the extreme might be able to impact blood sugar. This has impacted my sort of behavior. And I try to avoid really sweet things unless they're exceptionally delicious or the occasion calls for them because I do think that it increases my craving for sweet things. Well, it might not be necessarily a craving, but it just programs you. So let's your taste buds are extremely adaptable. So take, for example, like Indian food. If you bring like Indian people over to America and have them eat some more food, they think it tastes extremely bland because they are used to such spicy food, unless they have a certain level of spice, hardly even taste it. If you've ever done a high sodium diet and then gone to a low sodium diet, it feels very bland. That's a styrofoam. But your over time, your taste buds adjust. So sweet is the same thing. If you're used to eating a lot of sweet, you get kind of desensitized to it. And then if you go to something less sweet, it can kind of taste bland at first. Over time, it'll get better. But so I think it's one of those things that, again, it depends on the situation, right? Like if somebody's obese and they said, well, this is going to help me, you know, eliminate sugar, sweet and beverage. Like, why would you want to take that tool away from them? Like, that's a great lever to pull. I mean, if somebody can lose literally 100 pounds from just one change in lifestyle that's not even really that inconvenient of a change, that is powerful. But again, is it the most healthy thing they could do? And I think that's kind of like what tends to get asked. We don't know. Is it healthier than water? Probably not. Maybe as healthy as it. Who knows? Now, the, but I really make all those caveats because you don't want to have people who could use this as a tool think, well, no, I can't do this because it's actually bad for me. Right. If it helps you lose 50 pounds or 75 pounds or whatever it is, it trusts me. It's not bad for you, right? Well, it doesn't seem to increase the satiety signals.

Artificial Sweeteners & Gut Microbiome, Sucralose, Blood Sugar (02:38:55)

What do you think about the microbiome effects in this recent study? Because the recent study, I think, had some nice features to it. Yeah. And you've done a detailed description of the study. So for those that want that. Is this two weeks study or the two weeks study? Yeah. And we will provide a link. You did an excellent video on this on your YouTube channel that really parses each piece. But they compared the various artificial sweeteners and looked at the glucose response, looked at microbiome, a number of different measures. What was your general takeaway? And this was in humans for the, for I think of the first time looking at microbiome in humans due to artificial sweetener. There's, there are a few studies on the microbiome in humans with artificial sweeteners. The first two that came out showed pretty much no effect. But they were a little bit shorter in duration. They were like two to four weeks. And again, it depends on like what, what bacteria are getting measured, right? Like there's, you know, many different kinds of bacteria. So they could just be measuring one that didn't change. And then there was a 10 week study that came out that got a lot of press. And they showed, I think it was sucralose, I think. They showed an effect of change on the microbiome. Now, what was interesting is when I went into the species that changed the species that changed the most, compared to control, was a species called, I'm a butcher of the name, but let's like, Blaudia cocoitus. I think it's cool. I must say for those that work on the microbiome, it's so difficult to pronounce. I mean, you need a nomenclature committee and you need acronyms. I'm sorry. Just do it. Enough. Enough already. You're killing us. We'll call it BC. Thank you. We're going to start the nomenclature committee without you if you don't do it soon. So they noticed that this went up by like three to fourfold. So I kind of went down the rabbit hole on this. So interestingly, that particular species of bacteria is actually associated with lower adiposity, better insulin sensitivity, and people who are obese and children who are obese tend to have less of it. So I said, well, based on that study, you can actually argue that maybe sucralose actually improved the gut microbiome. Now again, I'm not making that claim because, you know, we have a lot of problems. We have a hard time understanding what a healthy microbiome looks like already. What this last study that came out, my biggest take home was, I think it's safe to say that some of these non-nutritive sweeteners are not metabolically inert. There are some effects. Now, are those effects good, bad, or neutral, I think has yet to be fully elucidated? Now, I focused more on the blood glucose responses in my analysis. So in that 10-week study, they looked at, they did oral glucose tolerance tests. And their conclusion, I didn't really feel like fit their data. So their conclusion was that, and again, I think it was sucralose, that it elevated blood glucose. And this is where statistics can get kind of tricky. So my take home was the area under the curve, the incremental area under the curve, which is looking at the, basically, the entire glucose response was not different between the control and the sucralose group. To me, that's the biggest take home. There was one time point at the end of the study in the sucralose group, the 30-minute time point that was statistically significantly higher blood glucose than the control group. It's kind of one of those things where I go, okay, it was one time point. It's statistically significant, but even then we've seen things be statistically significant that end up being data artifacts because they're not reproduced. So I'm not saying that's what's happening here, but again, the overall area under the curve was not different. So to me, that was the biggest take home. And papers we should probably mention are published because of effects generally. Lack of effect, harder to publish. No hypothesis doesn't, it's actually really unfortunate because a null hypothesis is just as useful data as the non-null hypothesis, but you're right, there is a very strong publication bias towards showing an effect. Versus not. Unless you can flip a field on its head entirely by showing something did not happen. Typically the positive result out does the negative result in positive meaning you see a result. And then of course it's one study. And I think that as you talked about earlier, the center of mass of data in a given field are probably the best basis for what we should do in terms of. And so I'm not changing my behavior around the intake of artificial sweeteners. I personally am still going to consume stevia and aspartame in relatively small amounts. But now I'm thinking, well, okay, if something contains sucralose, I don't have to perhaps actively avoid it. Whereas before I was, I was actively avoiding it. So the new study I thought was very elegantly, very involved. I mean, be quite frank, some of the animal stuff they did was extremely impressive. So there was actually two arms to the study. One was a human arm, one was the animal arm. I focused much more on the human side of it. So basically this was a two week study and the really unique aspect of this, which I think is both a strength and a weakness. They had almost 1,400 people apply for this study. And they only had 120, I think, that actually went into it. Because they did a very detailed food analysis of these folks. All of these people said that they avoided artificial sweeteners or didn't consume them. And I think people don't realize how ubiquitous sweeteners are. Prior to the study, these people were like, it was like jury selection. It's like not ever hearing of the plaintiff and the defendant. These are these mutant people who have never had an artificial sweetener. Right. So the strength is now you don't have a lot of like preexisting, you know, affirming. You know, effects that may be clouding what would actually happen when you add it in. Like for example, if you have people who are already consuming artificial sweeteners and then you have them consume artificial sweeteners, the likelihood things are going to change is pretty low. Right. So I think that that's a strength. It's also a weakness. And I want to be really careful because I think people took my words a little bit too far, which means I probably didn't do a good job of being nuanced enough. There is the possibility for a placebo effect here. So to me, if somebody has gone through that much painstaking care to avoid artificial sweeteners, it's likely they have a preconceived notion that those are bad for you. Like to, because they're difficult to avoid. Yes, it's possible if they're eating a very minimally processed diet that they're just not exposed to them. And that's very true as well. But the other thing that the researchers acknowledged was they weren't able to blind the study. Because if you've never had an artificial sweetener before, you're only used to regular sugar and you have an artificial sweetener, you know. You taste it. You know. It's still sweet, but it's not the same sweet. And there's an interesting effect there where a lot of people don't like the taste of aspartame the first time. I actually quit drinking diet soda for a while, thinking I should, and then had one. It tasted really, I can only describe it as kind of artificial, chemical. And then pretty soon it tasted great again. Yep. And so there is some attenuation there. And whether or not that's central meaning within the brain or peripheral, I don't know, but very interesting. Well, I see you as playing a critical role in defining what is and what still needs to be determined in terms of this landscape and the entire landscape really of nutrition. And that study did change my opinion in terms of, okay, I think we can clearly say now that like these aren't neutral, or sorry, that they're not inert, right? Like that was the thought process before was, well, they're not digested or whatnot. So they must be inert. That doesn't appear to be the case. But again, like when we look at the blood glucose data, there's, and I'm not saying this is what happened. I want to be very clear. I'm not saying this is what happened. I'm saying it's possible this happened. And so this is why we need more studies to verify. If these people had a preconceived notion that artificial sweeteners were bad for them, it's possible knowing they're ingesting artificial sweeteners that they could have had a blood glucose response. Now, the, my pushback on my own point there would be, then we should have expected to see it in all the, in all the non-nutritous of sweeteners, which they didn't. It was just in sucralose and saccharin. It was kind of a graded effect where sucralose and saccharin showed the most dramatic change. Yep. And Stevia and a few of the others did not. And the other issue I took with it, maybe it's a ticky-tack thing, was their primary outcome measure was blood glucose of the old glucose tolerance test. But they had people administer their own old glucose tolerance test, which basically they gave them, they said, okay, drink this drink, and they were wearing continuous glucose monitors, which should have been fine. But again, to me, and I'm being ticky-tacky, and again, I know all studies are limited by funding, so I think overall this was a great study. But I would have liked to see them monitor the, the old glucose tolerance test to administer it. Yeah, and when they before after, yeah. You want to know that they didn't ingest this or didn't ingest that. Right. Yeah. So those two things, but the other one of the caveat is it was a two week study, right? So we got to be really careful how much we interpret in this, because it's also possible that this is a transient effect, right? And maybe it goes away over time. We don't know. But again, I think it's, we can clearly say it's not inert, right? Now, how much emphasis we put on that on a two week study, I'm, I still will say, okay, maybe if you're worried, don't consume sucralose, right? But if you're, you know, 100 pounds overweight, and you want to use some sucralose as a replacement to help you lose weight, I would say don't let this study deter you from doing that, because the net effect is still going to be more positive than you not losing the weight, right? So if it's tool that helps you, fine. But I do hold open the idea that, well, there could be negative effects from it as well. But again, we're looking at like, what's the, what is the overall outcome, right? And then when I looked at, they examined like some of the different things that were increased with these different sweeteners. And again, this work gets messy because one of the things I saw was a big increase in butyrate production from the change in the gut microbiome presumably. Well, as we discussed earlier, butyrate's actually associated with like positive outcomes in terms of insulin sensitivity inflammation and some other things. So I just, I want to be real cautious before people say, well, there's a change in the microbiome. It must be a bad change. We don't know. It's possible. And again, if we have, you know, 10 more studies come out and start to show this, then I will start to shift my personal opinion of artificial sweeteners.

Insights On Rapid Weight Loss, Diet Impacts On Females And Food Processing

Rapid Weight Loss, Satiety & Beliefs (02:50:19)

So in anticipation of sitting down today, I did solicit for questions on social media. And one of the questions that got a lot of upvotes, likes, if you will, was that one that I think raises interesting questions about short-term and long-term outcomes. Short-term and long-term health. And it's the following. I think it's a common scenario. A number of people want to know what is the healthiest way to approach a kind of rapid weight loss. And here what I think is happening is somebody has an event coming up or they're just tired of being the weight they are or carrying the amount of adipose tissue they are. And they wanted to know whether or not it is safe to, for instance, lose three pounds a week for a few weeks in anticipation of a wedding or some other event. And whether or not straight caloric restriction and increasing activity is the best way to approach that. With the understanding that they may gain back a little afterwards, they might think ideally they'd like to maintain it afterwards. But what do you think of that sort of approach? You know, cutting your caloric intake in half, for instance, and then doubling and also doubling your physical output. So it's interesting because you might be surprised by what I'm going to say, which is the research data actually tends to suggest that people who are obese, who lose a lot more weight early, are more likely to keep it off. Which seems a little bit kind of contradictory, right? Like, well, that doesn't seem very sustainable. But again, you're weighing competing things. So there's sustainability aspect within. There's also like buy-in is huge for sustainability, right? So for a lot of overweight or obese people, if they start a diet and they don't see something quickly, they kind of bail on it because it's, you know, it's not working. Whereas if they see some rapid results pretty quickly, they buy in even harder, right? And so I think the conversation, especially for if there's any coaches or trainers out there, is just presenting that as the, you know, one of my favorite lines is there are no solutions. There's only trade-offs. I think Thomas Sol said that. So you're having a trade-off here. It is, yes, you're going to lose fat faster. You might lose lean mass a little bit faster too, which can be a problem. But I will say the more adipose tissue you have, the more aggressively you can diet without negative consequences. Somebody like me doing a really aggressive diet is not going to be good for my lean mass. One, I have a higher lean mass than normal. Two, I have a lower body fat than normal. As your body fat goes down, the percentage of weight loss from lean mass goes up. So people who are very obese, because they have so much adipose tissue to pull from, there's very little reason for the body to metabolize lean tissue. Now, that being said, if you go on a people misinterpret, like, well, I got an in-body done or a dexadundant, I've lost two pounds of lean mass, and they've lost 20 pounds overall. Well, keep in mind, adipose tissue itself is 13% lean mass. So there's actually protein component to the structural component of the adipose tissue, and it does have some water. So it's about 87% lipid, but the other part is lean. So at minimum, you should expect a 13% reduction in lean mass when you diet. And then when you consider like you lose body water overall, which is registers as lean mass, and you lose your sphinctic tissues can shrink a little bit. So it's normal to lose, you know, for the average person to lose like 25 or 30% of the weight that they lose from lean mass, but that doesn't mean skeletal muscle tissue. And again, the more adipose you have, the more aggressively you can approach the diet without really negative long-term consequences to lean mass or your overall health. But balance that with, okay, if I'm going to do this, I need to understand that I'm not going to be dieting this way forever. I'm doing this to give myself a boost to the beginning, and I have to be okay at some point with transitioning to something that's a little more sustainable. Based on what you just said, it reminds me of the satiety signal effect of exercise you mentioned earlier, that exercising can improve our sense of when we've had enough to eat. I just want to briefly mention that when Ali Crum was on the podcast, she mentioned that they'd been doing a study that I have to pair you to and hear the conversation as a fly on the wall, because what she was telling me was that if people believe that a food is nutritious for them, then eating less of it registers as more satiating. Whereas if people view dieting as a deprivation system, you know, like, "Oh, dieting is hard, and the food sucks, and it's terrible." Well, then they crave all sorts of other things, whereas they actually observe in their studies where people report reduced craving if they are told, for instance, a chicken breast and broccoli and some olive oil and rice is actually quite nourishing. It's actually really good for you. Then people eat that and they feel like they've actually eaten more. The satiety signaling goes up. So it's just a point that Ali made of those, aren't my data. The satiety is so impressive because even the rate at which you eat and write down to the size of the plate and the color of the plate, like the contrast in color. Really? I can't remember exactly. I think it's if the plate is a similar color to the food, I think people eat more. Whereas if it's a bigger contrast, they eat less. So even like plate color can make a difference on how much you eat. So again, human brain, very amazing, but also very dumb in some ways, right? Not an optimized algorithm. I always joke with people, I'm like, just look at how stupid humans are. You put some water in front of them. Like, you know, the ocean. They're like, "Oh, yeah, I'll pay 10 times more for this." But it's just, we're kind of wired that way. The reward signaling pathways in the brain run one chemical mainly, dopamine. There are others, of course, and very few algorithms. It's sort of like a intermittent reinforcement is one random reinforcement, but in the end, there aren't many algorithms. And we are probably not optimized, certainly not optimized for our own health because people will eat themselves to death, drug themselves to death, etc. simply because something felt good at one point. It proves your point. One of the things I tell people, I said this on Andy Fersalen's podcast was, interestingly, the dichotomy of life is, if you do what's easy in the short term, your life will be hard. If you do what's hard in the short term, your life will get easier. It's very strange. And actually, Ethan Suplee had a great example of this. When he was over 500 pounds, he said, "The amount of work I had to do to construct my life that I could just live was so much more work than just going to the gym for a couple hours a day." He's like, "The gym work is hard." He's like, "But when I look back at how much work I had to do to sustain that lifestyle versus just going to the gym and restricting calories." He's like, "To maintain the lifestyle of being 500 pounds was infinitely more difficult than what I do now." And so, again, a great example, short term, hard, going to the gym, calorie restriction, long term, life's easier. Just really interesting dichotomy I think about a lot.

Seed Oils & Obesity, Saturated Fat, Overall Energy Toxicity (02:58:13)

And I can't be restated often enough. Seed oils. People want to ask about seed oils. And for those of you that are listening who are wondering why we're sort of chuckling already, I should mention that both in the Twitter sphere and Instagram and online, there are these very polarized views that probably aren't worth focusing on for too long. But there are a number of folks out there who are arguing that seed oils are the source of all the obesity epidemic, all inflammation, etc. Illuminating everything. And then there are those that would argue just the opposite, that meat is the source of all problems, etc. And I think we've, thanks to your nuance and expertise, we've hopefully appropriately framed things that it's never that black and white. It's simply not. And rarely, rarely. I love olive oil. I realize that doesn't fit exactly into the seed oil category. I love olive oil. I use it in moderation. I do also consume some butter in moderation, etc. But are there any data on seed oils? And here, a good example, I think would be like canola oil, which comes from the rape seed that literally was renamed canola oil because rape seed oil is not good marketing. No, no, exactly. So the first thing I'll say is, seed oils have negatively contributed to our overall health because people in the last 20, 30 years, what they have tend to add is that they're not going to be able to do it. They have tend to add into their diet that has increased the overall calorie load is oil, like these various, mostly from seed oils. But when we look at like one to one replacement with other fats. And so I, if you look at the epidemiology, yeah, you can find some epidemiology showing people who consume more seed oil have more negative health outcomes. And then you can find mechanisms and the idea is, well, these have their polyunsaturated, which means in the fatty acid chain, there's multiple double bonds, which those double bonds can be oxidized when they're exposed to heat and some other things. And so the idea is, well, when you cook with these things and they get oxidized and that's going to cause inflammation in your body. So that's a plausible mechanism. So as always, I defer to the human randomized control trials. And so what you tend to find is when you substitute polyunsaturated fats, or sorry, when you substitute saturated fats for polyunsaturated fats, it's either neutral or positive in terms of the effects on like inflammation is basically neutral. There's some studies that show a positive effect of doing polyunsaturated fats, but it probably depends on the individual polyunsaturated fat. And that's the other thing I don't really is difficult because you're categorizing like everything in this one bucket and there are some differences between individual fatty acids. Even with saturated fat, like, for example, a steric acid doesn't tend to raise LDL cholesterol, whereas, you know, saturated fat as a whole tends to raise LDL cholesterol, but there are some saturated fats that don't. So again, it's like we're putting things in buckets and it's a little more nuanced than that. Then if you look at like the effects of polyunsaturated fats on markers of cardiovascular disease, again, tends to either be a neutral or positive effect when you substitute saturated fat for polyunsaturated fat. Now, if you want to get into like monounsaturated versus polyunsaturated, there's some, there's quite a bit of disagreement between the studies. What I would say based on the human randomized control trials is that you're probably better off consuming monounsaturated and polyunsaturated in place of saturated fat. But again, if the idea is, well, that means polyunsaturated are good for me, so I'm just going to dump a bunch of oil on everything and now you're upping your calories. Well, that's a negative now, right? Because you have to deal with the bigger problem of overall energy toxicity. So I'm not somebody who likes to demonize individual nutrients. I just haven't seen really compelling evidence that seed oils are the root cause of the problems that are being suggested. And I think this is a good example of kind of like, whenever there's something that pops up in the fitness industry, there's always like the opposite thing that pops up. And it's like the reactionary, extreme reaction to whatever this thing was over here. And I think that's what we're seeing with some of the seed oil stuff is it's mostly people who are trying to kind of expose the virtues of saturated fat. And listen, I think it's fine to consume some saturated fat. But again, I think limiting it to 7% to 10% of your daily calorie intake is probably wise, again, based on all the consensus of the evidence I've seen. And so once again, we're struggling with this, OK, we've got this epidemiology and these mechanisms that sound good. But then what actually happens when we do some human randomized control trials, and so far I just haven't seen the evidence to suggest that seed oils are independently bad for you, independent of the calories they contain. You said the words overall energy toxicity. And I just want to highlight that I think that's a fabulous term. I don't think enough people think about that because they are primed or we are all primed to think, OK, seed oils might be bad or artificial sweeteners might be bad, or this particular component of blood work might represent something good or bad without taking into account overall energy toxicity of the toxicity of over consuming calories, energy. And thank you for pointing out that most of the data point to the fact that saturated fat should make up about no more than 7% to 10% of total daily caloric intake. Is there a lower end threshold that can be problematic? For instance, I've noticed that my blood profiles, especially in terms of hormones, improve when I'm getting sufficient saturated fat. I'm a mutant, but years ago, because I'm a product of growing up in the 90s, I tried a low fat diet. It certainly crushed my androgen levels. I started adding some butter back in and I was right back in the sweet zone where I wanted to be. So 7% to 10% of total daily caloric intake is, I'm guessing, is probably about what I do now. I'll have to check. But is there a danger to going too low in saturated fats? So again, no solutions, only trade-offs, right? What maximizes out testosterone might not be the best thing for longevity, right? And vice versa. I'm not making that claim specifically, but I think it's important to understand this, that I think we all have this idea that there's this one iconic diet out there that is going to be the best diet for building muscle and burning fat and preventing cancer and heart disease. And the reality is, there's overall healthy dietary patterns that we see that are good for those things. But when we get down into the weeds, there's probably some push and pull here as well, right? So when it comes to saturated fat, there is some evidence that if you're too low on it, yes, you can have a reduction in testosterone. Now, is that reduction in testosterone, let's say 15, 20%, whatever it may be, is that sufficient to actually cause loss of lean mass that we don't know? That's never been shown. Interestingly, I just remembered this, there was one study that was comparing polyunsaturated fat versus saturated fat, and they equated total fat. And one of the really interesting things was the group getting the polyunsaturated fat had more lean mass at the end of the study compared to the group getting saturated fat. Now, so only one study I've never seen this replicated, so I'm very, this is a situation where I say, I would like to find out what the mechanism of that is, because this could just be random. But if that gets shown over and over, what I might say is, okay, well, what's the, what are we, if polyunsaturated are somehow increasing lean mass compared to saturated fat, who cares when happens with testosterone, unless that reduction in testosterone is causing some kind of impudent impedance for your life, right? So, all that to say, I don't really know. And by the way, that's something for those watching and listening, real experts, every once in a while, you should hear them say the following words, I don't know. Exactly. My graduate advisor was exceptional at that, and she was brilliant, right? And then in terms of like cholesterol synthesis, you really need a very, very small amount of saturated fat for LDL cholesterol synthesis. Your liver can synthesize, like the amount of LDL cholesterol, or cholesterol that your body requires is so small, in terms of like just living and being healthy. So, I don't think you need to worry about that. And from a cardiovascular disease standpoint, there is some evidence that even taking people who have like quote unquote low LDL of like, you know, 80 or 90 and taking them down to like 30 or 40, that there is still a benefit for the risk of cardiovascular disease. So, again, you're weighing these two buckets, right? So, what I say, if you're doing 7 to 10% from saturated fat, you're probably fine.

Females, Diet, Exercise & Menstrual Cycles (03:08:15)

I received a lot of questions about whether or not there are female specific diet and exercise protocols. And I realize this is a vast landscape, but some of those questions related to menopause and pre-menopause and some related to the menstrual cycle, most related to variations across the menstrual cycle. So, in terms of, let's just say, diet, maintenance or subchloric diet, are there any things that you've observed? We'll talk a little bit later about this wonderful app that you've produced, this Carbon app, which helps people manage their energy and take and a number of other things. And so, there you have a sort of a database where Lisa can experience base. And then I'm guessing there are probably also studies exploring male versus female differences in terms of adherence and what sorts of diets work. Are there any general themes that one can extract from that? It's going to be a really unpopular segment for the women. It doesn't seem to make a big difference. Actually, they may be relieved to hear that. Because it would make sorting through the information space, and certainly the information we've covered in this podcast up until now, simpler. It means that everything isn't different for them. Yeah, so, if you look at the male versus female studies relation to diet, they seem to respond to some similar way. Like, some are calorie deficit, it seems to produce similar results. If you do low carb, high carb, regardless, it seems to boil down to the same principles. Now, training wise, we do know that female, like the muscle fibers, adapt a little bit differently to training, but without getting too far into the weeds, it doesn't really change the way you should train. Because for the most part, building muscle, there's a lot of different ways to build muscle. So, we know that, like, light loads up to maybe like 30 reps, as long as it's taken close to failure, have basically the same effect on building muscle, at least in the short term, as heavy loads for low reps. It's mostly about taking the muscle close to fatigue, or failure. You don't have to go to failure, but getting close within a few reps. If you're between one rep and 30 reps, if you're getting close to failure, seem to produce similar results. So, again, great, you can pick with whichever form of discomfort you prefer, right? When it comes to female-specific training, again, females, actually, this is one thing that a lot of people don't know. They actually put on a similar amount of lean mass as a percentage of their starting lean mass as men. In fact, there's no statistically significant difference in the amount of lean mass they put on. Now, the absolute amount of lean mass that's added will be greater for men because they started with a greater amount of lean mass. Relative increase in lean mass is pretty much the same from similar training. Now, females, there's some differences in fiber types. Females tend to be a little less fatigable than men. They can go a little bit harder, a little bit longer. And there's also some evidence that they recover a little bit better. But that also could be simply due to the fact that they're not able to use as heavy of loads to induce hypertrophy. So, I kind of have this theory that while, as a percentage of your one rep max, you can program things. I think absolute load matters. When you look at the most elite power lifters, the super heavy weights aren't squatting three or four times a week. Because they're squatting eight, nine hundred pounds. I think that there's an overall recovery effect there. Again, I've no data to back this up. This is just my observation. But when you get into the lighter weight classes, and this goes from men too, you do see quite a few people who do many training sessions at high RPEs and seem to be able to recover from that. So, I do think the absolute load makes a difference. Now, when it comes to like menstrual cycle, this is one of those things where I kind of tell people, you know, do what you prefer. So, there's some people who have said you should program, you should like kind of schedule your training around your menstrual cycle, which is whenever you're going through your menstrual cycle, you know, reduce the intensity, reduce the volume, because you're, you know, you're not going to feel as good. You're not going to train as well. What I would say is just auto regulate that. If you go in and you're on your period, but you feel good and you're doing well that day, then I don't think you necessarily need to back it off. And there was one study that kind of supported that notion. But if you go in and you feel terrible and, you know, you feel like you could use, you know, a reduction in intensity and volume, then it's totally fine to auto regulate that. And when I say auto regulation, I'm auto regulation means you are regulating the individual training session based on your performance. So, I auto regulate in so far as, like, I'm a super nerd, so I have a velocity device, so I can actually attach to the bar and see how fast the load moves. And I know it varies different, like, warm up weights, what velocities I should be hitting. So, if I hit my last warm up and my velocity is about 10% higher than usual, I can be pretty confident that that's going to be a good day for me. If it's lower, then I can back it off a little bit. In fact, at Worlds, when I hit my last deadlift, it was 30% my last, my last deadlift warm up. It was 30% faster than I usually hit in the gym and I turned and looked at my coach and I said, "Yeah, we're going to get this today." So, there's various forms of ways to auto regulate, but again, women, if you're on your period, but you feel good, I don't think there's any reason you need to back off.

Raw vs. Cooked Foods (03:14:05)

But if you're not feeling good, then it's totally appropriate to back off. Raw versus cooked foods, people wanted to know whether or not, for instance, you know, eating a raw apple versus, I don't know, does anyone cook apples? I guess people used to bake, they were baked apples was a dessert when I was a kid. It was kind of the let down dessert. Sorry. They were saying like, "Not awesome unless it had a scoop of ice cream in it." Even then, maybe not awesome. But anyway, raw versus cooked, obviously, if you burn a piece of meat to the point where it's pure charcoal, that's too much. And if there is a small movement surrounding eating raw meats, that's not something I particularly enjoy. Frankly, sushi is the only raw food I personally ingest and I'm very careful about the source, frankly. Reputable places. Is there anything real about this in terms of being able to extract the amino acids, vitamins and minerals from the food, raw versus cooked? It just looks cool for Instagram. So when you cook foods, they actually tend to become, in terms of protein containing foods, they tend to become more digestible, not less. Eggs are this way, meat is this way. People say, "Well, when you heat protein, you denature it." And I think they hear that word denature and they think destroy. And that is not what denature means. So proteins fold up into 3D dimensional structures. You know this, of course, based on their amino acid sequence and their specific energies of those amino acids. When you heat protein or add acid, it starts to unfold that protein structure. That happens during digestion anyway. So I always chuckle when I've seen some companies come out with a way that you can cook with. It's not going to destroy the amino acids. I'm like, so you mean like regular way. So typically cooking actually makes amino acids more bioavailable, not less. Now, I would stay away from charring your meat because there is some evidence that charring creates polyoramatic hydrocarbons, which at least in animals when they give those, they appear to be carcinogenic. So if you do charring your meat by accident, I would just cut off the charred portions and then you should be fine. The char is delicious. Not of his charred too much, but there is something about a charred crust on a meat.

Berberine & Glucose Scavenging (03:16:32)

My dad's Argentine and I would like to cut the charring bar with you. What about people referred to them in their questions as "harb blockers," but I think what they're referring to are things like burbereen and some of the glucose scavengers. One glucose scavenger I'd love for you to comment on is this assertion that taking a brisk walk after a meal or maybe even a slow walk after a meal, some movement can help downshift the amount of circulating glucose in some way. I've heard that not a lot of people, but some are starting to pay attention to this idea of taking things like burbereen or even metformin can scavenge glucose. I personally can't take burbereen. If I take it, I get massive headaches unless I've ingested tons of sugar and carbohydrates. So I just don't mess around with it. But I know there are a number of people out there that want to know whether or not these glucose scavengers can be useful. I think that is really majoring in the minors. If I'm being honest, as far as the char blockers, there's some white kidney bean extract and those sorts of things. They do block the digestion of carbohydrates. Some say block. Those watching or listening. Metabolism is typically not on and off switches. When we say things like block or attenuate or inhibit, typically we're not talking about just a switch on the wall that you press it and everything turns off. We're talking about a dimmer switch. It just changes the emphasis. But these car blockers can reduce the absorption of carbohydrate. Now, they don't seem to cause weight loss when you just do it a normal diet. Now, why is that? Well, all it does is once those carbohydrates get to the large intestine and your bacteria get ahold of them, they start fermenting them to volatile fatty acids which get reabsorbed into your liver. You don't get the increase in blood glucose, but you still get almost all the calories from it. It's just in a different form. If car blockers, if they actually worked really well, if you block something from being absorbed, your GI typically does not just let undigested material sit in there, you get diarrhea. That would be the outcome. It's also how I debunked the whole 30 grams of protein at a meal. You can't absorb any more than that. If that was the case, when you ate a steak, you would just start having diarrhea every time you went over that 30 gram threshold. I remember during college, so this would be early 90s, there was the olestra craze. This idea of putting in non-digestible thing into things like potato chips so that it would clear through the GI tract faster, not absorb as many calories.

Fiber & Gastric Emptying Time (03:19:12)

This went nowhere, obviously. You don't hear about this anymore, but it does raise an interesting question related to energy balance, which is gastric emptying time. Obviously, in the landscape of eating disorders, in particular, anorexia, use and abuse of laxatives is a way in which people will in an unhealthy way try and control their weight. There's a lot of problems with that approach. What about gastric emptying time? Is this one way that people could control their energy balance in a healthy way? Where does fiber come into play? Fiber tends to improve GI transit time because that's bulk. Your GI system is basically a tube and it has peristalsis, which is wave-like contractions that moves the food down through the tube. If you have more bulk to the food, like with fiber, you can move it through a little bit better. In the gastric, the stomach specifically, fiber tends to delay gastric emptying and slow it a bit, probably because it congeals a little bit. This gets into the glycemic index argument. If you do low GI foods, you'll have a slower release of glucose. It's a slower gastric emptying time. Does that affect energy balance? There are quite a few studies looking at low GI versus high GI foods. In the studies where they don't control calories, low GI tends to outperform high GI, but when they control calories, there's no difference. What I think suggests is low GI foods just by their nature tend to be higher in fiber. It just comes back to the fiber issue.

Information On Supplements And Resilience In Training

Supplements, Creatine Monohydrate, Rhodiola Rosea (03:21:00)

I'd like to ask you about supplements for a moment. It's an enormous landscape, but I believe there are a few things that you believe in, meaning they exist and there are decent data to support their use. Maybe even some anecdotal data based on your own experience. As long as we highlight it as such, it could be interesting. I've heard you talk about two in particular, one that I'm very familiar with, which is creatine monohydrate. Share your thoughts on that, not just for muscle building, but maybe any other purposes for it. The other one is one that, frankly, I'm learning more about all the time now, thanks to your prompt, which is "Ridolia Roséa." I think I pronounced that correctly. Why that might be interesting or of use to people. Yeah, so touching on creatine, it is the most tested, safe, and effective support supplement we have. There are thousands of studies on creatine monohydrate now. I would say very clearly, too, if you're using any other form of creatine, I think you're wasting your money. creatine hydrochloride has some hype around it. It's apparently a little more soluble. The claim is that you need less, but there's only a couple studies on it, and it's more expensive. And creatine monohydrate is not particularly expensive. I realize people have to bring budgets, but it doesn't land in it. It's gotten more expensive because of COVID and supply chain issues. There's forms of creatine that appear to be as good, like hydrochloride, but it's more expensive. And then things like creatine ethyl ester has been shown to be worse than creatine monohydrate. Buffered creatine is as good or worse, and it's much more expensive. So I tell people, just take creatine monohydrate. It is tried and true. It's been shown to saturate the muscle cells 100% with phosphocreatin, and that's what you want. So creatine works through three different methodologies, one through increasing phosphocreatin content, which helps improve exercise performance. It also appears to improve recovery, and it increases lean mass, a lot of which is through bringing water into the muscle cells, but that is -- I mean, muscle cells are mostly water. So when people say, "Well, it's just water," that's what muscle cells mostly are. And it also increases strength and some other metrics now. It also has been shown in studies that people tend to get a decrease in body fat percentage. Now, that's probably because they're getting an increase in lean mass, and so the relative is a decrease in body fat percentage. But there are a few studies to show a decrease in fat mass as well. I don't think that creatine is a fat burner. I think that people are able to train harder, build more lean tissue, and so that's probably having an effect on fat mass. Then they've actually shown more recently some cognitive benefits to creatine, which I find really interesting as well. But the only knock on creatine that anybody's been able to come up with, because they've debunked the kidney stuff, they've debunked the liver study. There's no evidence that a harm's healthy kidney or liver is hair loss. So what about hair loss? Because there was one study in 2009 that showed that creatine increased DHT. But they didn't really show an effect on any other sex hormone. So it's kind of strange. Like you would think if there was an increase in DHT, there would be something else that changes as well. And it's only one study, and again, didn't directly measure hair loss, measured DHT, which we know is involved in the loss of the follicle. So what I would say is that I am not convinced it's only one study, never been replicated to my knowledge, and it was looking at a mechanism rather than an outcome. So if you're somebody who's prone to hair loss and you want to avoid creatine because of that, I understand. But for most people, I don't think it's something to worry about. Do you emphasize the classic loading of creatine taking it a bunch of times per day and then backing off or just taking it consistently at the, I think, 5 grams per day is kind of the typical dose that people take. So again, no solutions, only trade-offs. You can load it and you will saturate your fossil creatine stores faster, like usually within a week. If you just take 5 grams per day, it'll take 2, 3, 4 weeks. But you will get to the same place. And you're probably going to have a much lower risk of GI issues. Some people, creatine can be a gut irritant. If it is for some folks, I recommend splitting it into multiple doses. So maybe like multiple to 1 or 2 gram doses per day. And definitely don't load it if you're somebody who has GI issues from it. As far as we're going to go to Rosia, the research is still in its infancy. I was just reading a new systematic review that kind of concluded that we need more high quality research. But the research that is out there seems to suggest that not only does it reduce physical fatigue, but it also reduces the perception of fatigue and may also enhance memory and cognition as well. And it's referred to as an adaptogen. So I really like it. My anecdotal experience is when I combine that with caffeine, it tends to kind of smooth out the effects of caffeine. It's a more pleasant experience. And there's also some evidence that if you're like coming off caffeine, that it can reduce the negative side effects to caffeine withdrawal. Which by the way, I didn't really believe in that until I actually did a cold turkey. So before I meet, I will cut out caffeine for 7 days because you can basically reset your caffeine tolerance in 7 days. And like 2 days in, I mean I'm groggy. I've got the headaches. Usually I'll get body aches that come up because caffeine is actually a mild analgesic. And yeah, so it's very interesting to say, "But I slept like a baby." I'll tell you that. And then you took caffeine prior to your event. To the meat. So you really want the maximum punch from it. That's why you do that. And like I said, Rodeola tends to, it doesn't eliminate those negative effects, but it tends to dampen them a little bit. So I really like it. Again, would like to see more research on it. But there's a lot more stuff coming out like ashwagandas. Another thing that looks pretty promising. Seems to increase testosterone modestly. Interesting. I don't think it's like they've shown increases in lean mass. I don't think the increase in testosterone explains the increase in lean mass. It's just not a big enough increase. Could it be the decrease in cortisol? People have talked about it. Possible. It does decrease stress, stress hormones. It also has been shown to help with sleep. But I would like to see more research looking at mechanistically how it's increasingly in mass before I kind of say conclusively that this is the next creatine. There's more research that needs to come out. And then there's some other things that have an effect. You know, citrulline malate. There was a new meta-analysis that showed that citrulline malate can reduce fatigue and increase, I think, time to fatigue. And it may actually have some small recovery benefits as well. Different forms of carnitine can actually have recovery benefits. And actually interesting, I think it's carnitine tartrate actually has been shown. Voloch published a study that actually showed that it increased angiogen receptor density in muscle cells. That's interesting. No. No. Carnitine and its other forms are pretty... I think there's good evidence that they can improve sperm and egg health for people who are looking to conceive. Interesting. Yeah. There are a surprising number of studies on this in humans. But yeah, androgen receptor density, and that's from oral L-carnitine people who are taking capsules, not injecting directly into a muscle. Yeah. And then you've got things like, obviously, like the other most effective supplement out there is probably caffeine. I mean, like, if you look at the research studies, caffeine produces very consistently improvements in performance. So that's another one. Some people don't like the effect of caffeine. That's okay. I wouldn't know because I'd never come off it. Exactly. Well, interestingly, they do show that the effect appears to be consistent, that even if you're a habitual caffeine user, you do still get a benefit every time you take it. But like you said, you're just used to it. You know? So, you know, there's those things. Then you've got things like beta-alanine, which for... It's in our pre-workout. Probably not super helpful for most people for resistance training. It does seem to have some benefits for like high intensity. Like if you get out, you know, more than like 45 seconds or 60 seconds of like really hard training, it does appear to help with delaying fatigue for that. And then you've got things like betaine, or also called trimethical lysine, which there's some evidence that can improve lean mass. There's some evidence that it can improve power output. So there's a few things out there. But, you know, most of the stuff is not very good. So, you know, I think that that's, you know, those kinds of supplements, you know, very useful. But again, I'll never tell people they need supplements. Like again, even like something like creatine is going to be a very small effect compared to like proper nutrition, recovery, and hard training.

Hard Training; Challenge & Mental Resilience (03:30:33)

You know, one of the things I was talking with Ben Bruno the other day, and I said, you know, like some people will ask me like, how does this person make progress because, you know, they're programming as, you know, it's not evidence based or, or you know, this guy, how's he like, his exercises are dumb. And I'll say, yeah, but they train really hard for 20 years. Like, you know, one commonality you see between like really successful athletes or bodybuilders is they train really hard. And one of the things I have observed is the more into the weeds people tend to get. And again, this is just my own anecdote and observation. The more in the weeds they tend to get, the less hard I see them train. And so one of the things I really like that Mike Israel-Tull said, who's got a PhD and is a bodybuilder himself, he said, you can't out science hard training that if you're looking to build muscle and you're looking to improve your body composition, the main thing is just doing the work. And so this is the end of the hard work. And I would add to that, and this is true of academic endeavors too, of course, I think I hope you'll agree. Absolutely. Which is that, yeah, you know, the other thing is given the mental side earlier, we were talking about how satiety signals in the brain and what you think about foods can be relevant, learning to really enjoy training hard in addition to learning to really enjoy eating well, not just for the effects that it has on body composition. Composition, excuse me, those two, of course, but just learning to really enjoy the process of training hard and a really hard workout or a really hard paper that you have to sort through or really digging through a book that's challenging. Learning to really enjoy that, I think, is a, if there is a power tool out there, it's the psychological end. And I think a lot of that is getting the confidence of doing something hard that there's a payoff at the end. You know, and a lot of people, I get asked a lot in my Q&A's, how do I get more confident? How do I become more confident? I'll tell people you have to do. There's no hack you can't read about. You got to get in the arena. And I don't mean like compete in sports necessarily, but like doing a PhD or doing something, just something hard where you're putting yourself out there and you're saying, this is my goal and I'm going to go for it. You just learn so much by doing that about yourself. And so just what you said, I will reframe things in my mind when bad things happen from, it's not to say I never get stressed out because I do. And it's not to say that I never get down because I do because I'm a human. But when something bad happens, I should post about this in my store today. When something bad happens, I very rarely anymore do I go, "Whoa is me? Why did this happen to me?" Because you're in the universe, random bad things are going to happen. So instead I say, "I'm not dead." Instead I say, "Well, what an exciting opportunity to overcome an obstacle." And I bet because in the experience of my life, the biggest lessons and the best things in my life have actually come out of the most challenging, worst things that have happened. And so again, I would never have been able to do these sorts of things if I hadn't taken up weightlifting because weightlifting taught me so much about perseverance, delayed gratification, overcoming obstacles. And that's why I love it even to this day. And I'll still get butterflies when I go in for a squat session, even though I've been doing it for 23 years. That's wonderful. It's clear that you embrace hard things and for people listening to this, obviously it doesn't have to be weightlifting. You know, thinking hard things, learning an instrument, learning a language. Challenge is an absolute builder. And they've actually shown those sorts of things, like when you challenge yourself and also mentally, that I think there was a new study that came out basically showing a reduction in the risk of Alzheimer's and other age-related cognitive decline. I mean, basically use it or lose it, right? Yeah, the desire and the will to persevere, no doubt translates to this thing that we call the will to live, right? It's related to the will to live. Well, I think that what you just said, you know, beautifully embodies what most people are aspiring to, which is to, I think most people actually want to do hard things. They don't just want to have the results. I think that most people deep down, have some understanding that their reward system works that way. I must say, this conversation for me has been tremendously rewarding. First of all, it allowed me to meet you in person for the first time, which I've really enjoyed. I'm certain this won't be our last interaction on this podcast and elsewhere. Also, the amount of knowledge that you contain inside you is astonishing. There's lost stuff right around up there. Well, and we all benefit because your ability to pull from the mechanistic side, again, I think not limited to, but related to your background in biochemistry all the way through to the impact in humans, animal studies, being able to understand where those sit relative to one another. And then you're obviously a practitioner of you practice what you preach and what you talk about pertains to men, to women, younger people, older people, people who are vegan, and women. You're vegan, keto, carnivore. You really are able to net a tremendous number of ideas while staying really nuanced and data-driven. And so, I just want to say for myself and on behalf of the listeners, I really appreciate you coming in here today and sharing with us your knowledge.

Carbon App (03:36:12)

We will absolutely point people in the direction of where they can learn more about you. One of the places that I definitely want to mention before we part, however, is this carbon app. And I should just mention I'm not, this isn't a paid promotion or anything of that. So, actually, one of our podcast team members has been using carbon for a long time. This is an app that you devised, which allows people to navigate the exercise, nutrition, energy balance space for weight loss, muscle gain, fat loss, weight maintenance. I would just like to briefly ask you about that before we conclude. Without necessarily telling us everything that's in the carbon app, I'd love to know what are the major things that it does and is good for. And then what were some of the key things that you wanted to make sure were in there when you built it? Like, what's the sort of logical backbone behind it? Because I think there are a lot of food counting, calorie counting, exercise apps out there. Everyone I've talked to that uses carbon, including our mutual friend, Sagar and Getty, this member of my podcast, et cetera, raves about it. So, what is carbon and what does it do and what was your mindset in building it? What did you really want to see there that you didn't see elsewhere? So, those those things may not know, but I really, I started online coaching people for nutrition back in 2005. And that was the vast majority of my business all the way up until like 2017. And I had a lot of success with that, whether it be just average folks looking to lose weight or build muscle and right up to elite level competitors in physique sport. So, I kind of had this idea like, I don't want to say I had the idea, a few people had the idea. What if we could take what I do in coaching and try to automate as much of that as possible? Because, you know, by the time I was becoming a really popular coach, I mean, I was expensive. You were looking at like me charging, I got to the point where I was charging about $1,000 a month for coaching, right? And not most people cannot afford that. And I would like to not just coach rich people, you know what I mean? I would like to be able to help other people. So, the idea was to create an app that could do some of this stuff. There's always a place for human interaction, but for people who can't afford that, our app is basically $10 a month. And basically what we wanted to do was set up an app where, think about if you went to a nutrition coach, what would they do? They would probably ask you some questions about your goals, take some anthropometrics, and they would use like that information, maybe dietary preference. And they'd use that information to kind of formulate a baseline plan. That's what carbon does. So, we ask you, I think there's eight questions in the sign up flow about like your activity, your exercise, your lifestyle, your body weight, your body fat percentage, and if you don't know it, we help you calculate it. It's not perfect, but it's better than nothing. And then your dietary preferences. And we use that to come up with kind of your baseline, and your baseline will be your calories, your protein, your carbohydrates and fats. And what's different about our app, because apps like My Fitness Power Web will do that as well. What's different about ours is we encourage people to log their weight daily for the reasons that we talked about earlier. And then you can also track your food in the app. And honestly, I think our food tracker is actually like way easier to use than most of them out there. What we typically get great rave reviews about is how user-friendly our interface is, that it makes intuitive sense. And so you track your food, try to hit these macros that you're prescribed, and each week you will be prompted to check in with the coach on your check-in day. And then you put in some information, and then based on how you're progressing, the app will adjust or not adjust based on how you're progressing. So, for example, if you're hitting a weight loss plateau, it will sense that, and it will reduce your calories, or if you're trying to gain weight, and you're hitting a plateau, it will increase your calories. And there's a lot of back-end algorithm stuff that takes care of this, but the fundamental crux of the app is we try to determine your total daily energy expenditure, because that's going to tell us the first big thing we need to know, which is how many calories do you need to be eating for your goal. Right? So, on the front end, we basically do our best guess based on your anthropometrics. It's not going to be perfect, but it will get us in the ballpark. And if you do know, like some people already know, well, I know what I maintain my body weight on, there's actually a spot where you can manually enter that during the sign-up flow. So that's helpful for people who are super nerds like me. But then if you're just, people will ask, well, do you take Apple Watch data, do you take this, do you take that, and know for the reasons we talked about that it overestimates energy expenditure. What our app does is it's an algebra equation. If you, because your body weight, your maintenance calories is your total daily energy expenditure, your average calories that you eat to maintain your body weight will be the same as your total daily energy expenditure. So, if we know how body weight is changing, and we know how many calories the person's consuming, we can actually solve for what energy expenditure is. And you can see in the app that there's a kind of a maintenance calorie tracker or energy expenditure tracker. And typically after about three to four weeks, even if the app was off at first, it will have you pretty darn close. Because, like let's say somebody comes on and their goal is to lose a pound and a half a week or something like that. And the first week, they lose three pounds. Now, the app actually accounts for the fact that you can lose more water weight the first weeks. They probably wouldn't get an adjustment. But let's say the next week they lose three pounds. The app will sense that and adjust their calories up because it will be estimating that their energy expenditures are actually higher than what it had previously estimated based on the amount of weight they're losing. And the same thing goes in reverse. If they're not losing the amount of weight that they're supposed to, it will lower them based on the fact that it may have overestimated their energy expenditure. But that's the first crux of it is tracking that energy expenditure. And then the next thing is protein. So when the back end algorithm stuff is happening, calories are set first based on your energy expenditure and your goal. So for example, if you're on an aggressive diet, your calories are going to be lower, even if your energy expenditure might be a little bit high. Just because if you're trying to lose two pounds a week, I mean you're going to be in a pretty aggressive calorie deficit. So it's going to set the calories first. Then it will set protein based on your lean body mass. Then the calories that are left over will be allotted to carbohydrate and fat depending on your dietary preference. And we have a few different dietary preferences. So you have a calorie balance, which is about 50, 50 to 60, 40 carbohydrate to fat of the remaining calories. Then you have low fat, which is obviously a higher ratio of carbohydrate. You have low carb. You have a ketogenic diet, which is very, very low carb. And then there's also a plant based option. And within each of those options still, you can go in and actually shimmy the macros a little bit within a certain range so that you can kind of dial in what you're doing. And then what your specific dietary preference is because again, if we go back to what is going to produce the best long term results, it's whatever the person can adhere to. So we really try to start with the concept of adherence by allowing people to have the dietary preference that they want. And there's some other apps out there that are good apps like, for example, we get asked a lot what's the their app and the Renaissance periodization app and they have a great app. So we're kind of the opposite. We want to give you maximum flexibility. Now, for some people, they would prefer the rigid structure at first. But we find that for most people, giving them more flexibility typically improves adherence over the long run. So that's kind of how the app works. And again, like there's multiple different goals. It's not just a weight loss app. There's a maintenance. There's a muscle building. So you've got all kinds of different goals that can be accommodated, different rates of each of those goals. And I mean, I've used the app for over three years now to do my body weight. And I mean, like when I say that it's dialed me in because I'm very regimented with logging and logging my weight. So what I targeted to weigh in at Worlds, I got down to the point one kilogram. So it's pretty cool to be able to like use a tool that I helped develop to actually coach me. So it's a great tool. We did some statistics. We polled 2,500 members. And one of the questions we asked is, would you recommend this to a friend? And 91% said yes. So our average, I think our average retention is like seven months, which for an app that costs $10 a month is really great. Yeah, as I mentioned, a number of people I know use it. This is not a paid promotion. But I think people need guidance and tools. And what we know about the human brain is that winging it can work, but that the brain will cheat itself often. There's a fine men quote about this and I'll get it wrong and always bad to try and quote fine men anyway, because he said it so much better. But that we are the easiest, it's easy to fool ourselves basically is what he was saying, easiest to fool ourselves. Sounds great. We will put a link to it so that people can check it out. Again, it sounds like a wonderful tool. And a tool that nets a lot of the principles that sit as major themes for weight loss, weight gain. I would assume directed lean muscle, lean tissue gain is what most people are after. Yeah. And weight maintenance, because a number of people would like to just maintain. Listen, I really appreciate your time and all that you're doing. Certainly your time and energy and knowledge today, but also what you're doing on the various social media channels. And just the fact that somebody from the depths of academia is out there sharing so much knowledge across so many domains. You're a gem in this landscape of nutrition and one that people really need to hear from. So thank you so much for your time. Thank you. I appreciate the opportunity. I really enjoyed it.

Channel Support Details And Audience Engagement

Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Momentous, Neural Network Newsletter, Social Media (03:47:11)

We'll do it again. Thank you for joining me today for my discussion with Dr. Lane Norton. I hope you found it to be as interesting and informative and actionable as I did. If you're learning from enter and join this podcast, please subscribe to our YouTube channel. That's a terrific zero cost way to support us. In addition, please subscribe to the podcast on Spotify and Apple. And on both Spotify and Apple, you can leave us up to a five star review. If you have questions or suggestions about topics and guests you'd like me to include on the Huberman Lab podcast, please put those in the comments section on YouTube. I do read all the comments. In addition, please check out the sponsors mentioned at the beginning of today's episode. That's the best way to support this podcast. During today's episode and on many previous episodes of the Huberman Lab podcast, we discuss supplements. While supplements aren't necessary for everybody, many people derive tremendous benefit from them for things like sleep, hormone augmentation, and focus. If you'd like to see the supplements discussed on various episodes of the Huberman Lab podcast, please go to livemomentice.com/huberman. We partner with momentus because they are extremely high quality. They ship internationally and they formulated supplements in the precise ways that are discussed as optimal to take for various outcomes here on the Huberman Lab podcast. The Huberman Lab also has a zero cost newsletter that you can access. It includes summaries of podcast episodes as well as summaries of various protocols for mental health, physical health, and performance. You can sign up for the newsletter by going to HubermanLab.com, going to the menu, and look for the Neural Network newsletter sign up. You just provide your email and I assure you we do not share your email with anybody and again it's completely zero cost. Again, go to HubermanLab.com and sign up for the Neural Network newsletter. If you're not already following us on social media, we are HubermanLab on Instagram, HubermanLab on Twitter, and HubermanLab on Facebook. At all of those sites, I provide science and science related tools for mental health, physical health, and performance, some of which overlap with information covered on the Huberman Lab podcast, but often which is distinct from information covered on the Huberman Lab podcast. Again, that's HubermanLab on Instagram, Twitter, and Facebook. Thank you once again for joining me for today's discussion with Dr. Lane Norton. If you are interested in some of the resources that he and I discussed, including his carbon app, as well as other resources that he provides, please go to the links in the show note captions. And last but certainly not least, thank you for your interest in science.

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