EVERY SPOKEN WORD
150 min read · 30,087 words- 0:00 – 1:49
Dr. Layne Norton
- AHAndrew Huberman
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. My guest today is Dr. Layne Norton. Dr. Layne Norton did his training in biochemistry and nutritional sciences and is one of the world's foremost experts in exercise and nutrition. He is also an expert in the topic of supplementation and other tools to augment health. Today, we discuss a large number of very important topics in these categories, and we start the conversation by establishing what Dr. Norton's thresholds are for what he accepts as evidence, in particular, actionable evidence. So what follows is a description of what Dr. Norton really believes is worth paying attention to versus what he believes is worth ignoring in the realms of nutrition, training, and supplementation. So you can be certain that as we start to go through the topics of sugar, GLP-1 agonists, things like Ozempic, artificial sweeteners, whether you should train to failure or not during your resistance training sessions, how much volume of training you need to do, cardiovascular training and its different forms in terms of how they benefit health span and life span and body composition, protein and its different sources, and on and on, indeed we cover many topics in this episode, you can be sure that all of the information you hear from Dr. Norton is being filtered through that extremely stringent filter that Dr. Norton is so well-known for. And thus, by the end of today's episode, you will be armed not only with the latest information on nutrition, training, and supplementation, but you'll also be armed with your own filter to determine what sorts of health protocols are actionable for
- 1:49 – 6:39
Sponsors: Mateina, Eight Sleep, Maui Nui
- AHAndrew Huberman
you. 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 Mateena. Mateena makes loose-leaf and ready-to-drink yerba mate. Yerba mate has long been my preferred source of caffeine, not just because it tastes great and provides that stimulant effect that caffeine provides for focus and alertness, but its other many benefits that are unique to yerba mate, such as regulating blood sugar, high antioxidant content, and it can improve digestion. And of course, I drink yerba mate because I simply love the taste. While there are a lot of different choices out there in terms of yerba mate drinks, my personal favorite is Mateena yerba mate because it's made with the highest-quality organic ingredients and it has a very rich but clean taste. And given Mateena's great taste and commitment to quality, I recently became a part owner in the company and I've helped design some of their drink products. In particular, I love the taste of Mateena's canned zero-sugar cold brew yerba mate, which has a slight taste of lemon, and I personally helped develop that drink. I drink two cans of Mateena yerba mate cold brew in the morning, and I often drink a third can in the early afternoon. If you'd like to try Mateena, you can go to drinkmateena.com/huberman. Right now, Mateena is offering a free one-pound bag of loose-leaf yerba mate tea and free shipping with the purchase of two cases of their cold brew yerba mate. Again, that's drinkmateena.com/huberman to get a free bag of yerba mate loose-leaf tea and free shipping. You can also find Mateena at all Sun Life locations and Erewhon locations, so please be sure to look for it both at Sun Life and at Erewhon. Today's episode is also brought to us by Eight Sleep. Eight Sleep makes smart mattress covers with cooling, heating, and sleep-tracking capacity. Now, I've spoken many times before on this podcast about the critical need for us to get adequate amounts of quality sleep each night. One of the best ways to ensure a great night's sleep is to control the temperature of your sleeping environment, and that's because in order to fall and stay deeply asleep, your body temperature actually has to drop by about one to three degrees. And in order to wake up feeling refreshed and energized, your body temperature actually has to increase by about one to three degrees. 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Maui Nui Venison is the most nutrient-dense and delicious red meat available. I've spoken before on this podcast about the fact that most of us should be seeking to get about one gram of quality protein per pound of body weight every day. That protein provides critical building blocks for things like muscle repair and synthesis, but also promotes overall health, given the importance of muscle as an organ. Eating enough quality protein each day is also a terrific way to stave off hunger. One of the key things, however, is to make sure that you're getting enough quality protein without ingesting excess calories. Maui Nui Venison has an extremely high-quality protein-to-calorie ratio, such that getting that one gram of protein per pound of body weight is both easy and doesn't cause you to ingest an excess amount of calories. Also, Maui Nui Venison is absolutely delicious. They have venison steaks, ground venison, and venison bone broth.I personally like and eat all of those. In fact, I probably eat a Maui Nui venison burger pretty much every day. And occasionally, I'll swap that for a Maui Nui steak. And if you're traveling a lot or simply on the go, they have a very convenient Maui Nui venison jerky, which has 10 grams of quality protein per stick at just 55 calories. While Maui Nui offers the highest quality meat available, their supplies are limited. Responsible population management of the axis deer on the island of Maui means that they will not go beyond harvest capacity. Signing up for a membership is therefore the best way to ensure access to their high quality meat. If you'd like to try Maui Nui venison, you can go to mauinuivenison.com/huberman to get 20% off your membership or first order. Again, that's mauinuivenison.com/huberman. And now for my discussion with Dr. Layne Norton.
- 6:39 – 14:31
Science-Based Evidence, Mechanism vs. Outcome
- AHAndrew Huberman
Dr. Layne Norton, welcome back.
- LNLayne Norton
Thanks for having me back.
- AHAndrew Huberman
Before we jump in, I want to get your stance on what constitutes evidence-
- LNLayne Norton
Hmm.
- AHAndrew Huberman
... because I think a big reason why you are considered one of the, if not the most trusted person in the realm of nutrition and training, is that you set a very high bar for what you consider science-based fact that motivates action. So, to just kind of break this down based on my read of the landscape online, it seems that there's a group of people, I don't know what to call them, purists or something, who unless there's a randomized controlled trial, so that means in humans, or several that points in a particular direction, they are very unlikely to adopt a new practice. Say, removing a given food or nutrient, adding a given food or nutrient, training a certain way, not training a certain way. Okay, that's one group. Then there are the people who, if they are told something could be of value, they hear it's worked very well for somebody, maybe they see some before and afters and it gets mapped to a mechanism that exists in humans and animals, like, "Oh, there's this molecule and if this molecule increases, um, X, Y and Z happens," and training in this way or eating this way increases that molecule, for instance, but no randomized control trial, then they're willing to try it or adopt it. And then there's a third, probably a fourth category as well, where people say they don't trust science anyway, science is flawed, or the, the controls required to design a really good experiment are so constrained that they don't mimic the real world well enough, and so they're really just interested in what works. So, they look to people that seem to have achieved the results they want. Feel free to add another group, but which group would you consider yourself in personally? And then where does your evidence that you put out, uh, online and today come from? And I already know the answer to the last question, but I think it was important to kind of spell out the landscape.
- LNLayne Norton
So everything you just mentioned would fall under the category of evidence. Everything that we can observe is evidence. But I think what people really struggle with is the idea of different levels of quality of evidence. And if I had to put myself into a group, I have definitely been on the side of, "Well, there's a case study in this journal and we're gonna try that now because it must work." And, or, you know, "My friend tried this and, and they said it worked, so I'm gonna try it." And then I've also gone to the group of, "Well, there's no human randomized control trial, so I don't believe it." And I think now, you know, I'm 42 now, and I've been doing this for two decades, I think where I'd fall into is it really depends on how the individual is talking about the evidence. Okay, so you, as you can probably imagine, I get sent a lot of stuff for people to like, "Oh, debunk this." And a lot of times people will send me things and I'll go, "Hey, this person said this is their opinion." It... That's fine. Like, I may disagree with their opinion, but I, like, I'm not gonna, like, rake them over the coals for them saying, "This is an opinion," or, "This is my personal experience." That's evidence. It's low quality evidence, but it is evidence. I think I kind of fall in a, a line of I ideally want to see human randomized control trials, but there's also, as you mentioned, practical limitations with how things are implemented. And I think one of the things that gave me a very unique perspective was the fact that I was doing my PhD in nutrition after I did a bachelor's in biochemistry, so I had that mechanistic understanding. And then I had a, an absolutely wonderful PhD advisor, Don Laymon, who just, shout out to him, got a lifetime achievement award by the American Society of Nutrition, 20 years too late, but, uh, he was just incredible at being able to understand the small things, but how they impacted the big things and what it looked like overall. It's like a conductor looking at a symphony, right? And understanding how the trumpet sounds affects everything else, but then not getting so tied up in that that he can't hear all the music, right? And he was so good at that and was so good at getting me to think that way. And so, I think where people out in the landscape trying to dissimilate this really struggle is they don't really know... Well, this person's cited a study and they equate that as evidence that's equal with any other evidence, right? And as a researcher, you know, not all (laughs) evidence is created equal. Not all journal articles are created equal. And, I mean, honestly, people who don't have a research background, it's hard to unpack this stuff. So, what I would say is you have to be very careful with people who cite studies. And one of the things I'll say too is there's nothing more dangerous than somebody who's read a biochemistry book, because they're gonna see pathway, biochemical pathway, there must be an outcome.So, outcomes are what we really care about, right? At the end of the day. And when I say outcomes, uh, gaining muscle mass, losing fat mass, um, risk of cardiovascular disease, insulin sensitivity, cancer, right? These are hard outcomes, right? And those outcomes are the summation of dozens, if not hundreds, if not thousands of biochemical pathways all summing up to an outcome. And just because something has a biochemical pathway doesn't mean it will create an outcome. But if there's an outcome, there's absolutely a mechanism to explain it. Now, let me give you an example of why this stuff can be so complicated and why it's so easy for people to... If you want to create a narrative, you can always find a study to create a narrative. Aspirin, we would agree, is an anticoagulant. Um, there's a reason they give it to patients who are at risk for heart disease or a heart attack. It's 'cause it reduces blood clots, reduces coagulation. It also activates pro-coagulant pathways. But the overall outcome is anticoagulation. But if I wanted to create a narrative that aspirin was bad for blood clots, I could say, "Well, look at these biochemical pathways it activates." And you see this, like, for example, I could create a narrative that smoking is not bad for you, okay? I, I remember reading a meta-analysis of the effect of smoking on the risk of adenocarcinoma, right? And there's a forest plot with probably about 50 studies. And most of those studies are to the very far right of the line, which is increases risk, and I think the overall effect was like 300% or 400% increased risk of adenocarcinoma. But there were two studies that were to the left of the line, not by much, and it wasn't statistically significant, but I could say, "Hey, look, I could cite these two studies, PMID, um, you know, they showed no increased risk of adenocarcinoma and actually might be slightly protective. And by the way, did you know that smoking decreases the risk of Parkinson's by 30 to 40%?" And by the way, that's very consistent in literature, right?
- AHAndrew Huberman
Yeah, that's true.
- LNLayne Norton
So, I can start creating this narrative that smoking... But we know smoking's not good for you. It's not good for you. It raises the risk of lung cancer, all different kinds of cancers, uh, cardiovascular disease, massive increase in risk, right? But I could u- I could thread the needle of science using these cherry-picked
- 14:31 – 22:45
Meta-analysis, Methods, Evidence Quality
- LNLayne Norton
studies. And so what I'll tell people is if I go into a topic, if I go into something, what I'm looking for, highest quality of evidence is, first off, do we have some meta-analyses on this topic, right?
- AHAndrew Huberman
Do you want to just explain for the general listener what a meta-analysis is?
- LNLayne Norton
Sure.
- AHAndrew Huberman
Just so we kind of have top contour.
- LNLayne Norton
Absolutely. So, a meta-analysis is basically where you're trying to compile studies that ask similar questions and look at what is the overall effect. Do we have a consensus in the literature? And usually they, they're going to show some kind of forest plot of all these studies and however far right or left of the center line is kind of giving you an idea of how powerful the effect was in that study and then you can see the confidence intervals in terms of how much var- variability there was. And then you can see the thickness of the dot on there, which shows how much it contributed to the overall, uh, analysis by usually how many subjects were in it.
- AHAndrew Huberman
Right, one study with 10 subjects would have a very small dot compared to a subject with 500 subjects.
- LNLayne Norton
Exactly.
- AHAndrew Huberman
Okay.
- LNLayne Norton
And so you're trying to... Now, you can do a bad meta-analysis based on inclusion criteria, you know, and that's where it's important to look at. But let me give you an example of a meta-analysis I cite pretty frequently. Um, the inclusion criteria is very important to make sure that you answer the question that you want to answer. And I say this when you're reading scientific studies, I'm like, "Listen. Just because there's a headline in even a paper, just 'cause the conclusion says something, that is the author's opinion." Okay? You need to check to see did they actually test what they're talking about and are the tests they use valid, right? So this meta-analysis was looking at low- lower carb diets versus higher carb diets or low fat diets and the inclusion criteria, this is done by Kevin Hall of the NIH back in 2017, I want to say. And I, I thought he did a great job at the inclusion criteria, which was we're only gonna include controlled feeding trials where the food is provided to participants because obviously we know the limitations of, you know, free living studies with nutrition.
- AHAndrew Huberman
Right, self-report.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
People sneak, people forget.
- LNLayne Norton
We are going to make sure that these studies equated calories, for the reasons we talk about. You've got to compare apples to apples, right? So a lot of studies will come out saying fasting produced more fat loss, low carb produced more... But then they didn't control calories and it's, it's very likely these people just ate less. So they controlled calories and they controlled protein, which is also important because protein changes the composition of weight loss. Protein has a thermic effect, uh, protein increases lean mass retention. So that can change how much fat you lose. And I think that it also had a requirement of like a minimum of four weeks, right? And the outcome was looking at changes in fat mass, not fat oxidation, not energy expenditure. It actually looked at the outcome that they cared about and they, they showed no difference, right? So I thought, well, that's a very well done meta-analysis because the inclusion criteria make a lot of sense for the question that they want to answer, which is not is one diet easier to stick to, not is it, um, you know, more practical. The question was, mechanically, do these diets produce differences when we're comparing apples to apples in actual fat loss and the answer was no, right? So, a- and then when you look at the, the other meta-analyses that have been done, they tend to kind of support that, right?... so the first thing I'm gonna look at is all right, these meta-analyses tend to be looked at as kind of the highest form of evidence, right? Because you're compiling a bunch of different studies which, listen, we know there are bad studies that get done. I think the amount of studies that get like just straight up faked is probably much lower than people think, um, but w-
- AHAndrew Huberman
One hopes, but-
- LNLayne Norton
Yeah.
- AHAndrew Huberman
... yeah, I would agree. I think that, um, people make errors. Um, I do think that a lot of "bad papers" or let's just say false conclusions arise from, um, elimination of data that, that did not fit the person's, uh, desired outcome. Y- k- and the reason I say that is I think it's impossible to control for.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
So you've got the student or postdoc doing the experiment. The results don't come out the way they would have preferred and then they're, you know, let's just say I've observed before, never in my laboratory unfortunately, but cases where people, um, come up with reasons why that particular experiment wasn't valid because-
- LNLayne Norton
Yeah.
- AHAndrew Huberman
... you know, the mice were initially sick or the drug, th- the lot of drug that they used wasn't, uh, it was heading towards expiration. They come up with reasons to exclude-
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
... rather than outright data fabrication where people literally create results that aren't there.
- LNLayne Norton
Yeah.
- AHAndrew Huberman
Um, and, you know, th- and there are a number of different wha- examples throughout history that, where people have done that, but I like to think that those are more rare.
- LNLayne Norton
I think that's probably pretty small. Uh, my experience is the same as you. I, I didn't see much of that, or I ne- never saw it observed. Um-
- AHAndrew Huberman
Usually end up reading about that in the form of retractions-
- LNLayne Norton
Right.
- AHAndrew Huberman
... in journals. They come out nowadays more close to the publications because of AI's ability to scan images and things of that sort.
- LNLayne Norton
Yeah, I th- I think, um, you know, usually if I see a paper and the conclusion like just straight up I go, "Oh, I don't know about that." When I go and I read the methods and I read how they analyzed it and I read how they measured things, 99% of the time I walk away and go, "Okay, it's not- I'm not surprised they found what they found." Right? Because again, a lot of, and this does happen and it shouldn't, but a lot of studies are set up to kind of find what people want to find. You can bias things in a certain way.
- AHAndrew Huberman
Well, and what nobody talks about (laughs) or it's not discussed enough is that a lot of times the way the paper is written poses a question after the results are in.
- 22:45 – 33:53
Evidence Hierarchy, Randomized Controlled Trials, Cohort Data
- LNLayne Norton
So when I'm looking through this stuff, I'm looking at, okay, does there seem to be a consensus in the data? And then is it, like in these meta-analyses, does the inclusion criteria make sense? And then if there's no real agreement amongst the con- uh, meta-analyses, then I'm looking at, okay, what do the most tightly controlled studies show? Like in the randomized control trials. And then I'm kind of like basing opinion off that. But, you know, and you, you know the, the hierarchy of evidence, the pyramid. You got meta-analysis, systematic reviews, randomized control trials. You have cohort data, epidemiology and then animal studies tend to get kind of lumped in together, and then you got like case studies and so on and so forth, right? And so all that stuff is valid. It's all valid. I think where I spend a lot of time on social media is, for example, I'll give you a great example, um, someone saying, "Well, you don't want to eat cruciferous vegetables because they have isothiocyanates in them which can bind to iodine and that is going to impair your thyroid function, lower your metabolic rate, and cause you weight gain." And so that's a, that's a pathway, that's a mechanism. Is it possible? I suppose it is possible, right? That pathway does exist. Iodine is important for thyroid function. Isothiocyanates do bind to iodine.... you can take any food, even organic food, and you can find a compound in it that if you fed it in a high dose, it would have weird effects, right? And so the question is not, if you eat something, are there compounds in it that maybe activate negative biochemical pathways? The question is, what is the overall outcome? And so when these pathways are promoted versus, "Let's see if we actually have randomized control trials in humans that measure what we actually care about." And so we do have, like in that particular case, we have randomized control trials looking at, okay, cruciferous vegetable intake and thyroid function, and there's no difference in the outcome. And so what that says, and then no difference in BMR and then actually people who eat more cruciferous vegetables actually tend to be a little bit leaner, but that could be a little bit of healthy user bias and they probably just eat less calories because they're more satiated. But it's certainly not going the opposite direction, right? And so the point is, again, if an outcome exists, there is absolutely a mechanism to explain it. But just because a mechanism exists does not mean you're gonna produce an outcome. And I got exposed to this very early because I cut my teeth on the bodybuilding message boards back in the day where it was a bunch of, you know, nerds arguing with each other, mostly who had no background arguing, but there were some actual like sports scientists and professors who would get on those every once in a while. This was before social media existed. And I remember I was in biochemistry class, this is 2003, and they're talking about how caffeine inhibits glycogen phosphorylase, which is a mechanism and it exists. Caffeine inhibits glycogen phosphorylase. And so I, I made this post where I, on the forums and I said, "Well, we should be having caffeine after a workout then because it'll help with glycogen resynthesis because it'll keep, you know, glycogen phosphorylase from breaking down glycogen." And somebody came in and said, "You're really like zooming in on a blade of grass instead of zooming out and looking at the forest." Right? And biochemists, I was guilty of this and biochemists by trade, we get very focused on pathways. But if you think about what caffeine does overall, activates the sympathetic nervous system, i- i- it's, its function is to l- like you're liberating fuel, like you... A- a- and some people when they take caffeine actually have a rise in blood glucose. So that is the outcome is actually counter to what that biochemical pathway is. And so we've got to be really careful with how we promote these biochemical pathways. I mean, I did a really funny post on Twitter where, uh, myself and Joseph Sundell, I'm not sure if you're familiar with him.
- AHAndrew Huberman
Yeah. Yep.
- LNLayne Norton
He's a cancer biologist.
- AHAndrew Huberman
Yep.
- LNLayne Norton
Great guy.
- AHAndrew Huberman
Yep. I know. Yep.
- LNLayne Norton
And we were joking back and forth. I said, "You know what? I bet I could like come up with a, a, a pathway to get people to eat poop." Like I can make a compelling argument for just eating poop. And then he goes, "I bet..." Uh, uh, he's like, "I'll take that bet." I'm like, "Okay, let's give it a shot." So I'm like, "What is the, some of the most common compounds in human fecal matter?" And one of them is butyrate, right? Which is a short chain fatty acid produced by, uh, fermentation. Butyrate, so I, I did this post where I'm like, "Here's why you should eat poop to lose fat. Butyrate increases fat oxidation. I think it activates brown fat, increases insulin sensitivity, decreases inflammation. It's been shown to actually ameliorate, uh, the development of obesity in, um, the, in studies." And I cited all these PubMed ideas. Now, what I did- didn't tell people was those are all mostly in rodents, right? And it's giving an amount of butyrate that you'd need to eat about 50 to 100 pounds of fecal matter a day in order to get, right?
- AHAndrew Huberman
This is sounding like a worse and worse idea by the moment.
- LNLayne Norton
(laughs) But that is very similar to a lot of the content that is out there.
- AHAndrew Huberman
Right.
- LNLayne Norton
Which is find isolated compound, scare people or promote it to be the best thing ever, and then link it to an outcome. And then sometimes you can tie in epidemiology with it as well to support whatever you want. But again, like I'm not saying... I do things in my training and my nutrition that don't have randomized control trials to support, right? They don't really have anything to support. It's just, it's how I've, how I've kind of fallen into doing things. Um, so that's okay. But what I wouldn't do is come out and say, "What I do is the best thing ever, and here's why." Especially if there was human randomized control trials to the counter, that is the biggest thing, right? If we have human randomized control trials and they're going the opposite direction of a case study or an observation, there's a reason human randomized control trials, I scream about them all the time, and why they're considered the gold standard of evidence. When we look at cohort data, you're just observing people. There's no intervention.
- AHAndrew Huberman
Well, maybe explain what cohort data are.
- LNLayne Norton
Okay.
- AHAndrew Huberman
Is it comparing two groups?
- LNLayne Norton
Sure. So cohort data, you're comparing groups, but you're, you're not having an intervention. So you're tracking them over the course of however, what period of time, a lot of cohort studies like looking at cardiovascular disease, cancer-
- AHAndrew Huberman
Yeah. These people decided to be vegan. These people decided to be, uh, let's just say omnivores.
- LNLayne Norton
Omnivore. Yeah.
- AHAndrew Huberman
Let's, yeah.
- LNLayne Norton
Those are some of the classic experiments, right?
- AHAndrew Huberman
And then, and there was, they weren't assigned to this experiment. They agreed to join the experiment. They've been eating this way for a while.
- LNLayne Norton
Right.
- AHAndrew Huberman
You ask them a bunch of questions.
- LNLayne Norton
And you look at, okay, over 10 years, over 20 years, who gets whatever more often or less often, right? And then we try to figure out and about calculate, okay, what's the effect? And is this real? The problem is you're, you have a lot of bias with those sorts of studies. Meaning people don't do single habits. They don't isolate habits. Uh, I was, I actually put up a reel the other day from my appearance on Steven Bartlett's podcast where he said, "If I want to fix my diet, I go to the gym." Because a lot of people do that. If they're training in the gym, they don't want to waste their effort by having a subpar diet. Now in reality, eating a healthy diet is more important if you're not going to the gym, right? Because at least you're getting something. But people do this habit coupling. And so it's really hard to disentangle those sorts of things. Now, the reason that human randomized control trials are important...... is if you're designing an experiment and you randomize, what you are doing by randomly assigning people to groups, you're washing out that bias because you can assume that whatever inherent characteristics that might be coupled to whatever you're going to try are going to be randomly distributed and evenly distributed across the groups. Therefore, we say human randomized control trials are kind of what's needed to establish causation because by randomizing, you can assume whatever differences are observed between the groups are due to your treatment and not due to random chance or data artifacts. Now, randomized control trials, especially in nutrition, have very strong limitations, which is you, you can't do a randomized control trial for 30 years. You can't... I mean, I think the longest randomized control trial I heard about in nutrition was like two years long, right? And even then, it's not going to be a very tightly controlled randomized control trial. I mean, and if you're doing, if you're talking about like the tightest level of control, like a metabolic ward study, four, six weeks maybe, 'cause you're keeping people in food jail. And I think where some of this confusion comes from is I think people think that there's just like this pool of people waiting around to be selected for experiments. Like, "Yes, I'm ready. I've been waiting here." No, there are people like you, like me, like just the average person walking down the street who saw a flyer and goes, "Okay, I'll volunteer for that." And the more control you try to establish over their lives, the less likely they are to do it. And you've probably got to pay them, you know? I don't know anybody who would do a metabolic ward study without getting paid for it. I mean, you're basically giving up four or six weeks of your life to go do that. And so while I love human randomized control trials, for some things, they're not always appropriate. For example, if you're trying to look at heart disease and you want to do a one-year human randomized control trial looking at, say, you know, saturated fat, LDL cholesterol, those sorts of things, well, how many people have heart attacks within one year after age 60? I mean, it's going to be a really... You're gonna look for really small nu- differences between really small numbers, right? And the problem with that is you have no idea about their diet 40 years leading up to that. And we know, based on now the Mendelian randomization trials, that the risk of LDL is more of like a lifetime exposure risk. It's not just in this narrow sliver of time. And so I love human randomized control trials, but it's also... I, I try to tell people, "Never turn your brain off. Just because something gets published in a certain journal, just 'cause a certain researcher said something, just because, uh, it was a certain design, it doesn't make it infallible, okay?" Science is perfect. Science is perfect. Science is what is. But it's done by humans, and humans are fallible, imperfect people with their own personal beliefs and biases. And that's why I look at consensus of data first because yeah, i- you could... Maybe some of s- experiments got faked or maybe they had b- But when it's done over... Let's take something like creatine monohydrate, right? You have thousands of experiments done over decades of time in hundreds of different labs with many different funding sources in bunch of different countries under a bunch of different conditions. It works, right? Like (laughs) if you go to Consensus and you type in, "Does creatine build muscle?" it's like 92% yes-
- AHAndrew Huberman
Right.
- LNLayne Norton
... which is crazy.
- AHAndrew Huberman
Five to... Right. Th- Consuming 5 to 10 grams of creatine monohydrate per day is going to benefit m- strengthen muscle mass and likely cognition
- 33:53 – 35:05
Sponsor: AG1
- AHAndrew Huberman
to some extent.
- LNLayne Norton
Oh, yeah, yeah.
- AHAndrew Huberman
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- 35:05 – 42:01
“Don’t Turn Your Brain Off”; Protein Synthesis
- AHAndrew Huberman
to claim that special offer.
- LNLayne Norton
I realize I've been on a long diatribe.
- AHAndrew Huberman
No, no. This is...
- LNLayne Norton
To-
- AHAndrew Huberman
It, it's... I, I wouldn't even call it a diatribe. I think for those listening, like, this is pure gold because never before, certainly on this podcast or other podcasts, has anyone ever really spelled out how to discern differences in quality of evidence.
- LNLayne Norton
Right.
- AHAndrew Huberman
And every... It's mostly a free world, most places, uh, and people can do what they want, but I think they need to decide what their thresholds are for quality.
- LNLayne Norton
Yeah. And, uh, I think the one other thing I'll tell people is... I saw this the other day. I saw somebody post, I think it was a comment on one of my posts. I actually commented back. They said, "You know, I just, I know I can trust you, and I just... Whatever you say, I know it. I can take it to the bank." And I said, "I appreciate that, but I am a flawed human like anybody else. Please don't turn your brain off." Like... And one of the things I've really tried to do now in this stage of my career is I want to teach people how to think, because if I just give you the information and I'm giving you a fish, great.... but I'd rather you understand how I came to these conclusions. You can see my logic and how it tracks, and then you can start applying it elsewhere. One of the things I say to people is, I'm like, "If you want a quick and dirty hack for knowing who to follow, try not to listen so much to exactly the information people say, but listen to how they say it." Okay? I was just telling you, I was on a podcast the other day where I said, "You know, here's this study, um, I might butcher the details, and if I get the math wrong, if, uh, experts out there wanna comment and correct me, please do that." Like, that is a way of talking about something where you're saying, "Hey, I could get this wrong," or, "Hey, I might be uncertain." That's very different than saying, you know, just hard, pure... You know, real experts don't really talk like best, worst, always, never. Like, they don't really use words like that. Um, and one of my favorite phrases that I tell people, it's actually from an economist named Thomas Sowell, he said, "There are no solutions, there are only trade-offs." And for- for example, um, you know, there's data out there that if you lower saturated fat, it may lower your testosterone. But there's also data out there that saturated fat raises LDL, which is an independent risk factor for cardiovascular disease. Okay. Well, there's trade-offs there, right? Like, what do you value more? I would argue that probably the decline in testosterone isn't really physiologically meaningful for most people. But again, there's- there's not a good or bad, there's trade-offs. And I think when people get talking about biochemical pathways, one of the things I- I really try to home in on is like, "Hey, there's not- not really good or bad biochemical pathways either." Like, all these things exist for a reason. Like, people... Like, one of the things popular is like, "Well, inflammation, inflammation." I'm like, "Hey, you know, like, inflammation does some things that we really need too." Like, you just don't want, like, no inflammation. Like, it's actually an important physiological process, right? Now, you don't want it to run away, for sure. And so again, I- I just give my PhD advisor a lot of credit of... He's like, "Know what you know, but always question everything. Even the things we feel most fundamentally are true, 'cause that is the job of a good scientist." And I'll- I'll give you one more story and then (laughs) we'll move to another thing. When I did my first experiment... Well, actually, sorry. No, this has been like my 15th experiment, 'cause my first 14 blew and didn't work (laughs) . Um-
- AHAndrew Huberman
A typical graduate career.
- LNLayne Norton
Yeah, yeah. It's ve- and again, very patient man, very supportive. I- I- I honestly cannot give him enough credit. Um, and if you look at the- the people that came out of that lab, a lot of studs. Um, so I- I did a, uh, an experiment looking at whey protein, or sorry, complete meal with whey protein ingestion and how long the duration of muscle protein synthesis was. Because we- most people kind of measured at 60 or 90 minutes, like the- the snapshot postprandially for protein synthesis, looking for a peak, and we're like, "Is that really where the peak is? We don't know. We're- we're basing this off of, uh, purified solutions, so let's do a duration experiment," right? And my hypothesis was, well, however long leucine is elevated in the blood is gonna be how long protein synthesis stays up. And when we got the data back on protein synthesis, protein synthesis had come up, peaked at 90 minutes, and by three hours had come back down to baseline. And I went to run the plasma amino acids, and I'm like, "Okay, well, this is what we're gonna see." And that's not what we saw. (laughs) So plasma amino acids not only were still elevated, they were like maxed out or plateaued at the highest they would, level they would be at three hours where protein synthesis was back to baseline. And so I said, "Okay, well, it's gotta be mTOR signaling, mTOR signaling's gotta be turning off or something's happening." Nope, mTOR signaling was still elevated-
- AHAndrew Huberman
Hm.
- LNLayne Norton
... right? Um, a- and we saw this through ph- uh, phosphorylation of the binding protein for EBP-1, which is a proxy for mTOR activation. Um, and then I said, "Okay, well maybe leucine isn't getting into the cell. Maybe that's why." So we looked at intracellular leucine. Followed the exact path of plasma leucine. And so then I kept rerunning the plasma data over and over, I probably ran it five times, right? And Lehmann finally calls me into his office one day and he goes, "So where do we stand with this duration experiment?" And I said, "Yeah, it's almost done. I just- I- I gotta run the data again 'cause the plasma data's gotta be wrong." And he go- he... I saw his, like, little eyebrow go up, you know? And he goes, "Why do you think that? Let me see your data." He goes, "Your standard error bars are good. This looks to be relatively tight data. Um, how's your technique?" And I'm going through, like, how I, you know... All the steps of- to analyze plasma amino acids. It's not like CSI, by the way, everybody. You don't just, like, take a pipette, put something in a centrifuge, and all of a sudden you get back data. There's a- there's many steps in here. Um, and so I- I showed him all that and he goes, "You know what? It sounds like you are trying to get the data to fit your conclusion, and what you need to do is change your conclusion to fit the data." And that one line, again, it just opened my whole world up to one, I- if I'm wrong, okay, cool. Like, I care more about getting the right answer than being right. And that's why a- we were talking earlier, I'm like, "There's so much stuff that I just don't believe. I wanna see 10, 20 studies before I go, 'Yeah,' you know?" And the other thing I'll tell people is, "Hey, I don't plant my flag real strong very often. So when you see me do it, I'm not saying I'm not fallible, but if you see me do it, you probably should pay attention,
- 42:01 – 46:05
Protein Synthesis, Refractory Response; Resistance Training
- LNLayne Norton
'cause I don't usually do that."
- AHAndrew Huberman
I love that description, but now my curiosity is piqued-
- LNLayne Norton
(laughs)
- AHAndrew Huberman
... and you gotta tell me. So if 90 minutes after ingesting protein, protein synthesis peaks and then it drops-
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
... to baseline at three hours, but leucine, one of the key amino acids in mTOR, which is in the pathway of cellular growth and protein synthesis are still elevated three hours, wh- what is the conclusion that explains the discrepancy?
- LNLayne Norton
Yeah. So, uh, we actually looked for this (laughs) for years. Um-So a few things. There was some other studies that supported that. Uh, we called it, uh, a refractory response. Actually, we didn't name it that. There was another lab th- named it that. Basically, that protein synthesis was becoming refractory to the signal for protein synthesis. So ju- just for real quick, I'm gonna try and explain this easily. So protein synthesis, you know, this sounds like probably a very abstract thing, but it's how you make... your body makes more protein. And whether it's in skeletal muscle, whether it's in the liver, whatever, you have your DNA, which is your genetic code, right? And then that gets transcribed to an mRNA. By the way, I'm leaving out a lot of steps here, but just h- bear with me. That mRNA gets translated by a ribosome into a polypeptide chain or a protein. So a ribosome is basically attaching to the mRNA, and then based on the mRNA sequence, is bringing in amino acids to match that sequence. So all the proteins in your body are coded for in your DNA, right? So when it comes to this process, there's a complex called eIF4F which acts as a scaffold for the ribosome to hook onto the mRNA. And eIF4F, the formation of it is basically rate limited by the association of two proteins called eIF4E and eIF4G. And eIF4E is bound by a binding protein, 4EBP1. And when you stimulate... when leucine stimulates mTOR, mTOR stimulates the phosphorylation of 4EBP1 which makes it unavailable for binding with eIF4E. It can bind to eIF4G. That eIF4F complex can be made, brings the ribosome onto the mRNA, and now it can read, it can translate it. So there's a little, uh-
- AHAndrew Huberman
Yeah.
- LNLayne Norton
... uh, cellular biology lesson for y'all.
- AHAndrew Huberman
Yeah, and if people didn't follow that, um, don't worry about it. What Layne's describing is that the presence of a bunch of molecules involved in protein synthesis is necessary but not sufficient for the protein synthesis.
- LNLayne Norton
Right.
- AHAndrew Huberman
A few other things have to happen.
- LNLayne Norton
Correct.
- AHAndrew Huberman
And apparently, those other things are not happening after 120 minutes.
- LNLayne Norton
So another lab called it the, the muscle full effect. Basically, the, the idea is, like, once you've initiated that signal, it kind of runs and then it's done, right? And just pounding more amino acids into the system is not gonna further stimulate. In fact, there was a... there was a study done back in, I think it was 2001, by, I want to say by Rennie, um, another very well-known protein lab, and they infused essential amino acids for six hours and looked at skeletal muscle protein synthesis. And they found it went up and then came back down by, by two hours and then never went back up, right?
- AHAndrew Huberman
Good experiment.
- LNLayne Norton
Yeah, very interesting. So we looked at a bunch of different things. The only thing we found that perhaps explained it a little bit, and I'm sure there's other labs that would argue with me on this, and, and again, this is in rat skeletal muscle, which by the way is a good model for human protein metabolism, but still, we looked at AT- intracellular ATP levels and actually found that they were declining kind of in concert with the decline in muscle protein synthesis, and muscle protein synthesis is an ATP-dependent process. But the, the process of protein turnover is energetically expensive. It's one of the reasons that protein has a higher thermic effect of food. And so our hypothesis was perhaps by the effect of protein stimulating protein synthesis to start this machinery is energetically expensive enough that eventually you kind of run out of steam, and so you have the signal there, but
- 46:05 – 54:52
Protein Intake, Intermittent Fasting & Training
- LNLayne Norton
it just kind of ends, right? Now, there have been other experiments, like Goran Tromelin just published a paper a few months ago that got a bunch of, you know, you know, feedback. It was 100 grams of protein after a mea- after a resistance training exercise and saw, you know, that it was basically... like, a lot more of it was used than we thought would be used.
- AHAndrew Huberman
Right, because for many decades it has been purported, believed, and propagated that the maximum amount of protein that you can utilize after a meal is 30 grams.
- LNLayne Norton
Yeah.
- AHAndrew Huberman
It became the, uh, the holy number.
- LNLayne Norton
Yeah.
- AHAndrew Huberman
And this study essentially showed that more than 30 grams can be used-
- LNLayne Norton
Yeah.
- AHAndrew Huberman
... not just as energy but for the sake of protein synthesis in muscle, correct?
- LNLayne Norton
Yeah.
- AHAndrew Huberman
And it... And how did that study land with you given that it's one study?
- LNLayne Norton
Yeah.
- AHAndrew Huberman
I mean, without going into all the details, I... di- did that inspire you to change anything about your protein intake after training?
- LNLayne Norton
So what I tell people is I don't make big shifts in my opinions based on single studies, right? Like-
- AHAndrew Huberman
Yeah, why does that not surprise me? (laughs)
- LNLayne Norton
It, it, it shimmy- it shimmies me a little bit, right? So-
- AHAndrew Huberman
Mm-hmm.
- LNLayne Norton
And what... Even before that study came out, what I had said is, I think protein distribution matters but I think it matters much, much less than total protein intake per day 'cause all we need to do is look at some of these resistance training studies with intermittent fasting where people are eating all their protein in an eight-hour window, and theoretically you would think they would get less muscle growth, especially based on this refractory data 'cause less times to stimulate, um, but at least in the studies out of Grant Tinsley's lab, we... I think there's two studies that were very well done where we don't see that. Now, important to point out, they trained during their feeding window and they had three... They made sure they ate three high quality, high protein meals during that eight-hour time, right? So at least in that context, there was no difference in the amount of lean mass gained between intermittent fasting groups versus continuous feeding groups. Now-
- AHAndrew Huberman
And in the continuous feeding groups, the, uh... do you recall what duration they were eating their meals over? Was it t-
- LNLayne Norton
I think-
- AHAndrew Huberman
... probably 12 hours or so?
- LNLayne Norton
I, I don't recall specifically.
- AHAndrew Huberman
Okay.
- LNLayne Norton
But I, I don't recall an actual defined time. I'd have to go back and look at it.
- AHAndrew Huberman
More than eight hours.
- LNLayne Norton
For sure.
- AHAndrew Huberman
(laughs) You know, I'm so glad we're landing here because my first, um, let's just call it sort of operational or actionable question-
- LNLayne Norton
(laughs)
- AHAndrew Huberman
... which came from, um, uh, you know, asking on social media for questions for you was, um, many, many people if not in the thousands asked-... how to make sure that they're getting enough protein if they're doing something like intermittent fasting. And I myself fall into this category.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
Um, I don't do it for any specific purpose. This was long before Satchin Panda started doing his work on time-restricted feeding, AKA intermittent fasting. But I don't tend to want to eat any food until about 11:00 AM.
- 54:52 – 1:00:25
Tool: Total Protein Intake, Distribution & Protein Synthesis
- LNLayne Norton
I'm gonna distribute my protein probably over four to five meals per day. Right? Um-
- AHAndrew Huberman
And so for y- for you just personally-
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
... uh, what, what time of day do you wake up and when's your first meal?
- LNLayne Norton
So, well, it's summer right now so kids are off at school, so we're usually getting up around like 7:30, 8:00 in the morning. And, um, my first meal is usually within an hour. Um, and then I usually eat within an hour of going to bed. And then I'll have two or three meals in between those. So I'll... Usually I have about four meals a day. Um, sometimes I'll have five if it's just a longer day or just how my timing kind of goes or whatever.
- AHAndrew Huberman
And does each one of your meals include approximately 30-plus grams of quality protein-
- LNLayne Norton
Yeah.
- AHAndrew Huberman
... some starchy carbohydrate, fibrous carbohydrate, and, and some fat?
- LNLayne Norton
I mean, sometimes they end up being, like, m- mostly protein or, or whatnot, but for the most part there's a mix in each one. Um, and usually around 50 grams of protein at a meal. I eat about 235 grams of protein a day. Some people would argue that, "Oh, well, that's more than you need. The research has shown that 1.6 grams per kg maxes out the response." Here's the thing. And again, this is where like scientific experiments are big blunt instruments. Okay? The- they will tell you what not to do more often than they will tell you what to do. Okay? When it comes to protein, my personal opinion, and this is just I guess a little bit of intuition based off of 20 years of studying this stuff, is that I don't know if there's an actual amount of protein that maxes out the protein synthesis response. I would bet if I was a betting man that it's kind of an asymptote. You're familiar with... Yeah. So your-
- AHAndrew Huberman
But Pio, not everyone's watching. I just s-
- LNLayne Norton
Right.
- AHAndrew Huberman
... drew an asymptote. (laughs)
- LNLayne Norton
Right. Yeah.
- AHAndrew Huberman
Um, an asymptote plot. But for those not watching, just think about a, um, a p- a plot quickly rising very, very high and then essentially stays stable at the high level.
- LNLayne Norton
Yeah.
- AHAndrew Huberman
Um, e- and maybe with a slight bit of taper.
- LNLayne Norton
Yeah. So it's, it's... So it's easier to explain if it's going towards zero. So an asymptote might be, okay, you start out, you have 10, then five, then two and a half.
- AHAndrew Huberman
Okay. So you're running in the opposite direction.
- LNLayne Norton
Right.
- AHAndrew Huberman
Still asymptote going from high to low.
- LNLayne Norton
Right.
- AHAndrew Huberman
So asymptote can go from low to high, can go from high to low.
- LNLayne Norton
Correct. So I, I'm, I'm trying to explain it 'cause p- it makes more sense when people kind of go this way. You never reach zero.
- AHAndrew Huberman
Mm-hmm.
- LNLayne Norton
But it keeps getting incrementally closer.
- AHAndrew Huberman
Mm-hmm.
- LNLayne Norton
On the other end, I don't think protein synthesis ever maxes out. I just think the increment of increase becomes so small that practically there's no difference and you wouldn't see a difference in outcome. Right? And so I think that, you know, one, you know, there's debate over is it 1.6 grams per kg, 2.4 grams per kg. I, I... And there's even been a meta-regression that showed up to 3.3 grams per kg had benefits. I think a lot of this is with protein synthesis you're looking for small differences between small numbers. It's not a very sensitive analysis, to be quite honest with you. And again, we would never be able to pick out those difference- And I'm thinking about there was a study by Stu Phillips who if people don't know who Stu Phillips is, this is, he's the best researcher going in protein metabolism right now. Um, but one of the best. Sorry, I don't want to-
- AHAndrew Huberman
It's okay.
- LNLayne Norton
... tick anybody off.
- AHAndrew Huberman
Sure.
- 1:00:25 – 1:05:34
Muscle Quality, Protein Remodeling, Muscle Growth
- LNLayne Norton
for maxing out muscle building for the majority of people.
- AHAndrew Huberman
And we should probably point out not just for muscle building. Um, unless you disagree, uh, and feel free to, of course, not that I need to tell you that. Uh, Dr. Gabrielle Lyon, uh, when she was here made a really, um, key point, which is that e-Ingesting sufficient quality protein each day isn't just about building muscle. Even for folks that don't want to build muscle and perhaps even particularly for women who assume that, um, you know, building muscle is a, can be a runaway process that maybe they're going to build too much muscle. That's a false, false assumption, of course. That ingesting one gram of protein per pound of body weight or ideal body weight is going to be beneficial because it's going to improve muscle quality. One's own muscle quality, the health of the muscular tissue and, and then she did an excellent job of relating the health of muscular tissue, skeletal muscle that is, to overall health and longevity. So, I- I just raise that because I know that many people listening to this probably want to add a little bit of muscle here or there. Um, some perhaps want to keep the muscle they've got and lose fat, and some of course want to add a lot of muscle. But it sounds like the recommendation is always the same. Since we need to eat, sooner or later, one gram of quality protein per pound of lean body mass or current body weight or desired body weight, that's going to be a good starting place.
- LNLayne Norton
Yeah, for sure, and I, I think (stutters) I would tend to agree with her. You know, the, the process, because when you eat protein, you're not just going to start laying down slabs of lean tissue just from eating protein. There has to be a stimulus which is resistance training, um, or some people would argue you could stretch really hard and, and get the same thing which there may be some evidence of that.
- AHAndrew Huberman
With weights and lift them in between stretches? No, I'm just kidding. (laughs) Which is basically weight lifting.
- LNLayne Norton
Me- well, there, there actually are studies now where they, like, put people in, like, really kind of hard core stretching for, you know, several minutes and they actually see hypertrophy with it. Um, yeah, very interesting. We could talk about those if you wanted, but the, the, the point is either way it's mechanical tension, right? So that's the, that's the stimulus to build muscle. To, to lay down lean tissue, um, but the process of remodeling is probably beneficial for multiple reasons. So when you eat protein, like we said, synthesis goes up, degradation goes up, right? Because you're stimulating that process, you're stimulating protein turnover. One that's, that's relatively energetically expensive, all things being equal, so that's where the thermic effect of protein comes from. Uh, because people say "Well it's the urea cycle," and this and that. Most those, most those ATPs you, you get back in different phases of that cycle. Really, I, in my opinion, the thermic effect of protein is due to like kind of activation of this futile cycle of you're building more protein but then you're also breaking down more protein. And so part of that is you are remodeling. You are making sure that that protein is higher quality in that tissue by continuously breaking it down and building it back up. And so I, I would probably agree with that, um, and then it's, again, even if you're in a resistance training program where you're not really building much more muscle anymore, the process of remodeling is probably good for you, you know? And I, I would just say try to ally some of these concerns, um, from people who are concerned about gaining too much muscle. So I have been lifting really hard consistently for 25 years. I am very comfortable with saying I train harder than almost anybody else you can possibly imagine and anybody who has trained around me will back that up. Back me up in the comments. I'm, I train very hard, and in a shirt I look like an athletic guy w- who lifts. I, I don't look like a monster, you know? Like, you might see pictures of me when I was a bodybuilding show and like very, very lean and that looks, you know, over the top, but for the most part I just look kind of athletic, and I've spent my entire adult life trying to get too big, right? So for most people unless you're on performance enhancing drugs or you just have incredible genetics, that's not going to happen, and if it starts to happen, just back off on your lifting, easy fix. So yeah, I think most people's concern with that is, is, is a little bit misplaced. And the other thing I'll tell people is like, hey some of these like fitness like, especially like for women, a lot of these fitness models you follow, they, they show you certain workouts they do. They built that physique by lifting weights, right? And you're, you're thinking that's a toned fe- no that person is actually pretty muscular, right? And so again, especially for women, uh, there are exceptions. Some peop- some women have very great genetics for building muscle. They usually wind up in track and field, that sort of thing, but it's very hard to get too muscular for a woman and, and what I'll say is like, you know, typically muscle looks good and fat is what makes you kind of look bulky, you know? So again, I don't want to paint it with too broad of a brush, but I would say that
- 1:05:34 – 1:06:46
Sponsor: LMNT
- LNLayne Norton
you don't really have too much to worry about when it comes to, to getting too muscular.
- AHAndrew Huberman
I'd like to take a brief break to thank one of our sponsors, LMNT. LMNT is an electrolyte drink that has everything you need and nothing you don't. That means the electrolytes sodium, magnesium, and potassium in the correct ratios but no sugar. Now I and others on the podcast have talked a lot about the critical importance of hydration for proper brain and bodily function. Research shows that even a slight degree of dehydration can really diminish cognitive and physical performance. It's also important that you get adequate electrolytes in order for your body and brain to function at their best. The electrolytes sodium, magnesium, and potassium are critical for the functioning of all the cells in your body especially your neurons or nerve cells. To make sure that I'm getting proper amounts of hydration and electrolytes, I dissolve one packet of LMNT in about 16 to 32 ounces of water when I wake up in the morning and I drink that basically first thing in the morning. I also drink LMNT dissolved in water during any kind of physical exercise I'm doing especially on hot days if I'm sweating a lot and losing water and electrolytes. If you'd like to try LMNT you can go to drinklmnt.com/huberman, spelled drink L-M-N-T dot com /huberman to claim a free LMNT sample pack with the purchase of any LMNT drink mix. Again
- 1:06:46 – 1:10:30
Early vs. Late Time-Restricted Eating; Fasting Blood Glucose & HbA1c
- AHAndrew Huberman
that's drinklmnt.com/huberman to claim a free sample pack.Since we're sort of in this realm of protein, maybe we build out from there because I, a lot of questions related to, um, something, uh, akin to the following. So, okay, so somebody strives to get, uh, one gram of quality protein per pound of body weight per day, um, and I realize that whether somebody follows a pseudo-intermittent fasting thing where their first meal is at, you know, around 11:00 and they end, you know, and they finish up eating around 8:00 PM or a more traditional eating schedule really is just the addition of one more meal, like in the morning. It's like whether or not you eat breakfast. Of course, some people shift it the other way. They start with breakfast and they don't eat dinner, but, um, I would argue that in order to, if you have kids or a social life of any kind, the- the, most people can deal with, um, sitting across the table w- with someone just having a cup of coffee for breakfast, but it's sort of awkward. You limit yourself a lot in life if you-
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
... if you can't eat dinner with other people. I don't know. At least it, it, it-
- LNLayne Norton
And that's, and that's again where the rubber meets the road with what is practically doable because there have been some of these like circadian rhythm studies that suggested well maybe early time restricted feeding is better than late-
- AHAndrew Huberman
Mm-hmm.
- LNLayne Norton
... time restricted feeding. The more high quality, more rigorously controlled, uh, randomized control trials are coming out now seems to show that it doesn't really make a big difference, um, a- and, and some of the... Again, the measurements you use matter, right? So there was actually a, a very recent study where they looked at 12 weeks. They provided all the food to participants, equal in protein calories, the whole deal. The only difference was one group was eating 80% of their calories before 1:00 PM and they had a eight-hour feeding window in total. The other group had a 12-hour feeding window and were eating over 50% of their calories after 5:00 PM, I want to say. And so really like based on some of the, the chrononutrition stuff we've seen from some of the lesser well-controlled trials, w- we were, they were expecting to see differences in like glucose metabolism and whatnot, and they just didn't really see a difference in anything.
- AHAndrew Huberman
Mm-hmm.
- LNLayne Norton
And the only, the, I think the only thing they saw a little bit of a difference was was in fasting blood glucose. And here's what I tell people. When you see a difference in fasting blood glucose but not HbA1c, you're, you're looking at a transient difference. A- and what I mean by that is HbA1c is such a great measurement because it's a s- an area on hemoglobin that can be glycosylated. And so that is very dependent on what is your overall concentration of glucose in the blood over a 24-hour period of time? Because it's exposed the entire time it's in your bloodstream. So whether you're getting it, you know, glucose spikes at meals or you have higher fasting blood glucose, it's going to be very reflective of the overall 24-hour area under the curve, right? So why did they see... Why do some of these studies see a little bit better improvement in lowering fasting blood glucose whereas HbA1c doesn't show up? Well, think about it. If somebody has early time restricted feeding and they finish most of their food intake before 1:00 PM, they have an extra like six, seven, eight hours that they're not hardly eating anything. It doesn't surprise me that the next morning because they've technically fasted for longer you have a lower blood glucose. Now I can't, I can't really back this up straight up-
- AHAndrew Huberman
That makes sense though.
- LNLayne Norton
... because nobody's ever meas- measured it, but that I think is a logical explanation why you see some of this stuff and that's why I tell people, you know, the measurement you take really matters. I think fasting blood glucose is a useful measurement but I put much more value on something like HOMA-IR, um, euglycemic clamp, or HbA1c. Um, so anyways. I, I think the early versus late time restricted is kind of doesn't matter too much.
- AHAndrew Huberman
Great. You answered a, a future question right there. Um-
- LNLayne Norton
See, I've, I've
- 1:10:30 – 1:19:50
Carbohydrate Timing, Individual Response, Placebo; Tool: Tracking Diet
- LNLayne Norton
............................
- AHAndrew Huberman
You're telepathic.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
Uh-huh. That's what you didn't know about him. Um, the, uh, so, so the, the scenario here is whether or not meals are distributed evenly through the awake day or, um, stacked a little bit more toward the morning or stacked a little bit more toward the evening, if somebody gets that one gram of quality protein per pound of body weight then they need to make up the rest of their calories with other stuff.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
Um, and we have broadly speaking starches, fibrous, you know, fruits and vegetables, starches, and of course fats.
- LNLayne Norton
Right.
- AHAndrew Huberman
And weight gain and weight loss I think we both would agree is, or weight maintenance, is going to largely be dictated at this point by whether or not you consume more calories than you burn or not. So assuming somebody's getting that one gram of quality protein per pound of body weight, is there any data that support or do you believe just by your own experience that there's some value in stacking the starchy carbohydrates toward the earlier part of the day versus the later part of the day? And this has been an ongoing debate.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
Like I for instance like a nearly pure protein and fat meal for the first meal plus maybe a salad-
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
... some fibrous carbohydrates, and then as I get towards evening, I like more starches and I actually taper off the protein. I find personally that matches what I need to do with my brain. I'm more alert when I'm drinking caffeine and hydrating on a backdrop of slightly lower carbohydrates.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
But then as I get towards evening, taper off the caffeine of course, for me because I want to sleep well, start ingesting some more starches. It's not starch heavy but I sleep like a baby. But everyone would tell me and does tell me eating starches late in the day is gonna make, make me fat. Eating starches late in the day is gonna do all sorts of terrible things. I find the exact opposite for me.
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
So is there any real evidence that where one places their starches throughout the day matters? And let's just forget resistance training for the moment-
- LNLayne Norton
Mm-hmm.
- AHAndrew Huberman
... because there is this post-training window where I'll, if I train first thing in the morning I will eat starches at that time, but I'm, let's just remove sh- resistance training for, for the moment.
- LNLayne Norton
So again, where r- rubber meets the road and practicality versus what hard line research says. Um, so I am not real convinced at all that it really matters when you eat your carbohydrate intake.
- AHAndrew Huberman
Thank you. Thank you. My goodness.
- LNLayne Norton
I, I think, um-
- AHAndrew Huberman
I knew I brought you here today for a reason. No, I brought you here for-
- LNLayne Norton
(laughs)
- AHAndrew Huberman
... for many, for many reasons but I-
- LNLayne Norton
'Cause like my bias has been validated. I can leave now. (laughs) So I really try to get people focused on the stuff that matters the most, right? So this is, if we're worried about carbohydrate timing-... even if there are differences, we are zoomed way in on the blade of grass, right? We're not zooming out all the way. And I think, hey, if somebody likes to eat more carbohydrate in the morning and that fits their lifestyle and that is easy for them to continue to do, then I would say do that.
- AHAndrew Huberman
And, and could I add, um, in terms of not focusing on a blade of grass but something that I consider a major lever, if eating fewer carbohydrates in the afternoon and evening doesn't impede your sleep, then you're okay, but I would argue if anything is interfering with your sleep on a consistent basis, you've got a serious problem.
- LNLayne Norton
Yeah. So there are no solutions, only trade-offs, right? And when it comes to carbohydrate intake, you'll hear people say, uh, "The data's all over the place," okay, in terms of, like, timing and how people feel. Some people say, "Well, I feel sleepy after I have carbs." Some people have ... And I feel great after I have carbs, like, I, I'm ready to go lift. I'm, I'll, I have a big carb meal before I go lift, you know. It seems to be all over the map. Now here's the thing what I'll tell people because when people ask me how I eat, people want me to do a, you know, a full day of eating video, and I've kind of put it off for a while 'cause I'm like, so much of the stuff I do, I'm not gonna be able to give (laughs) you guys a citation for, you know, and, and I know you're gonna want it, and some of the stuff I do 'cause I just like doing it that way, right? Like, I, I grew up in the era of bodybuilding magazines where they said you gotta have a big carbohydrate intake and a big meal before you go train and a big meal after you train. So guess what I did? I got in the habit of eating like that, and it still sticks to this day. I don't try to tell people it's better doing it that way. Plenty of people have told me, um, "Hey, I, I don't feel good with a lot in my stomach when I go train." Or, "I, if I have a carb-heavy meal in the morning, I feel tired." The data doesn't really support that in terms of, like, you know, on an average response, but if you know that you feel that way, then by all means avoid, right? Like, uh, there's pl- ... (laughs) I remember one time I, um, so I used to go to a massage therapist in Tampa who would do cupping, and there's really no data to back up the efficacy of cupping, or, you know-
- AHAndrew Huberman
Is that right?
- LNLayne Norton
Yeah, not, not much. But she did it. I liked the way it felt, and I'm like, "Okay, whatever." So I, I posted a picture of me flexing one time, you know, and, and there's the cup marks all over, and everybody's, like, going crazy, like, "How can you do this? You're p-" I'm like, "Hey, hey, hey, hey. Wait a second. I never said this does this, and I never made any claims about it. She does it, and I like the way it feels. I'm not saying it does anything." Actually, one of the things about being a scientist is, like, now I'm impossible to placebo, which is really annoying 'cause I would love to be able to placebo myself (laughs) a little bit more.
- AHAndrew Huberman
'Cause placebo effect is powerful.
Episode duration: 4:04:29
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