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

ANDREW 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.

Today, my guest is Dr. Layne Norton.

Dr. Norton is one of the foremost experts

in protein metabolism, fat loss, and nutrition.

He did his degrees in biochemistry and nutritional

sciences and is considered one of the world experts

in understanding how we extract energy from our food

and how exercise and what we eat combine to impact things

like body composition and overall health.

Today, we discuss an enormous number of topics

under the umbrella of nutrition and fitness,

including, for instance, what is energy balance?

That is, how do we actually extract energy from our food?

We also discuss the somewhat controversial topic

of artificial sweeteners, whether or not

they are safe or not and whether or not

they are an effective tool for weight loss,

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've probably heard about,

including ketogenic diets, vegan diets, vegetarian diets,

and pure carnivore diets, as well as more typical omnivore

diets, and how to make sure that you

get all of the essential amino acids

that are critical for healthy weight maintenance, weight

loss, or directed muscle gain.

We also talk about supplements, in particular, the supplements

for which there is an immense amount of science pointing

to their safety and efficacy for fitness

and for overall body composition.

What I'm sure will become clear to you,

as you hear Layne talk about each

and every one of these topics, is

that he has an incredible ability to both understand

the mechanistic science but also the real world

applications of the various discoveries that are made

in particular papers and, in particular,

in the randomized 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.

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

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And now, for my discussion with Dr. Layne Norton.

Layne, Dr. Norton, thank you so much for being here.

This is a long time coming.

And I have to say, I'm really excited because I've seen you

in the social media sphere.

I've also listened to a number of your other podcasts.

And as a fellow PhD scientist, I feel a great kinship with you.

I know you have tremendous experience

in fitness and nutrition, a number of areas.

We also got a lot of questions from our audience.

And I'm really looking forward to talking with you today.

LAYNE NORTON: Yeah, I'm excited, too.

I mean, like you said, it's been something

we've been talking about for a long time.

So I was glad we were able to make it happen.

ANDREW HUBERMAN: Yeah, indeed.

And 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 Layne and I together,

in conversation online and then via text, et cetera,

was the fact that I love to be corrected,

and that's what happened.

I did a post about artificial sweeteners, which

we will talk about a little bit later in the episode,

and Layne pointed out some areas of the study that I had missed

or, maybe, even misunderstood.

And I revised my opinions and I think it's wonderful.

And other studies have come out since then.

So hopefully, our conversation will

serve as a message of how science and actionable science

can be perceived and that 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.

So in any case, I'd like to start with something

that's rather basic and yet can be pretty complex,

and that's this issue of energy balance and energy utilization.

I think most people have heard of a calorie.

I am assuming that most people don't actually

know what that is in terms of how it works,

what it represents.

And so maybe you could just explain

for people what happens when we eat food, of any kind,

and how is that actually converted

into energy, as a way of framing up the discussion around weight

loss, weight maintenance, weight gain, and body composition.

LAYNE NORTON: So it's a great question.

And like you said, this is one of those things where people

use the term calories in, calories out,

and they say, well, that's way too simplistic.

I'm like, if you look at what actually makes up calories in,

calories out, it's actually very complicated.

So let's deal with what you mentioned first.

What is the 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 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 are 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--

and 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 work backwards-- is what's

called oxidative respiration.

So that happens in the mitochondria.

Everybody's heard mitochondria, a 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 phosphate plus ATP to ADP.

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 ATPs through glycolysis.

And then it boils down to pyruvate,

then acetyl-CoA, which goes to the Krebs cycle,

produces a lot more ATPs from that.

If you talk about protein, protein

is 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 the 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 lopping them

off two carbons at a time to produce acetyl-CoA which,

again, can go into the Krebs cycle,

produce those hydrogen ions that can then

power the production of ATP.

So that's kind of like at the cellular level

of how this stuff works.

But stepping back and taking it back out,

what does that have to do with weight loss or weight gain?

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.

So one, food labels, which we like

to think as being from upon high,

can have up to a 20% error in them.

ANDREW HUBERMAN: Really?

LAYNE NORTON: Oh, yeah.

ANDREW HUBERMAN: So a 100 calorie--

something listed as 100 calories per serving,

it could-- what's actually in there could be 80 or 120.

LAYNE NORTON: 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.

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 "quite a bit of carbohydrate," know

but if you can't extract the energy from it--

and typically, this is because insoluble fiber

from plant material, the carbohydrate and even

some of the protein is bound up in the plant structure, which

makes it inaccessible to digestive enzymes.

And so this is what adds bulk to your stool and whatnot.

But again, reduces the metabolizable energy in there.

And there's some evidence that based

on people's individual gut microbiome, that some people

may actually be better at extracting energy out of fiber

compared to other people.

So just starting off right there,

OK, 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 the food levels can be 20% off.

And what I'll say is, OK.

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 what you're taking in.

And that's like saying, well, don't worry about tracking

if you're--

I like to use financial examples.

We know that to save money, you have

to earn more money than you spend.

Well, you can't exactly know how much money

you're earning at a time because there's inflation

and then there is--

if you have investments, those can be different interest rates

and whatnot.

It's like, OK, if you have a budget,

you have a reasonable idea of what it's going to be.

And you make certain assumptions,

but you can relatively guess.

ANDREW HUBERMAN: Yeah.

That's a good example.

LAYNE NORTON: Right.

So now, let's look at the energy outside

of the equation, which is actually way more complicated.

And so your energy out is a few different buckets.

The first one and the biggest one

is your resting metabolic rate.

So your RMR.

And that, for most people, is anywhere from 50% to 70%

of your total daily energy expenditure.

Now, people use the term metabolic rate and energy

expenditure interchangeably, but they're not the same thing.

So your total daily energy expenditure

is the summation of all the energy you expend in a day.

ANDREW HUBERMAN: Walking upstairs,

exercise if you do it--

LAYNE NORTON: Fidgeting.

ANDREW HUBERMAN: Yeah.

Plus your resting metabolic rate.

LAYNE NORTON: Right.

So resting metabolic rate is a big part of that,

but it's not the only thing.

So that's usually about 50% to 70%.

And sedentary people will be on the higher end of that.

So it'll be a bigger proportion whereas people

who are more active, it'll be a little bit lower, not

because their metabolic rate is lower,

but because they're expending a greater

percentage of their calories from physical activity.

Then you have something called the thermic effect

of food, which is a relatively small percentage

of your total daily energy expenditure.

It's about 5% to 10%.

And very difficult to measure and usually

what researchers do when they're looking at this stuff is

they just make an assumption about it.

They use a constant.

But that's about 5% to 10% of your daily energy expenditure.

And that refers to the amount of energy

it takes to extract the energy out of food.

So think about your body like a car.

You don't just have gas in your tank

and it spontaneously starts up.

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 calorie is just a unit of measurement.

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 0% to 3%.

Meaning, if you eat 100 calories from fat,

your net will be about 97 to 100.

ANDREW HUBERMAN: So the process of breaking down

that fat, essentially, subtracts some of the calories

away because you used it in creating energy--

LAYNE NORTON: Correct.

ANDREW HUBERMAN: --by breaking those chemical bonds

to create ATP.

LAYNE NORTON: Correct.

Correct.

So you have like, for example, some enzymes that require

ATP to run these processes.

Now, fat is actually the easiest thing to convert into energy.

Then you have carbohydrate, which

has a TEF of like 5% to 10%.

So you eat 100 calories from carbohydrate.

And obviously, the fiber content makes a big difference on this.

But if you eat 100 calories, you'll net 92 95.

Protein is about a 20% to 30% TEF.

So if you eat calories from protein,

you're only netting 70 to 80.

Now, you're still net--

people say, well, you can't eat too much protein.

Well, people will ask, well, can protein be stored as fat?

The carbon's from protein it's unlikely,

it's going to wind up in adipose tissue.

But if you're eating a lot of protein,

overall as part of a lot of calories, it has to be oxidized

and it can't provide a calorie cushion for other things

to be stored in fat.

But protein itself does provide a net positive for calories,

but less so than carbohydrate or fat.

And tends to be more satiating.

So again, when people talk about are all calories created equal,

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.

I mean, whatever.

Any purposeful activity.

And then you have what's called NEAT

which is non-exercise activity thermogenesis, which I think

is actually really cool.

ANDREW HUBERMAN: It's fascinating.

LAYNE NORTON: Yeah.

It is.

So 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, have you always 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 they

exercise a lot and really what it seems to be as neat.

They tend to-- if they overeat, they just

spontaneously increase their physical activity.

Now, people get NEAT confused.

I've heard people say, well, I'm going to go out

for a walk to get my NEAT up.

That's not NEAT.

NEAT is not something you can consciously modify.

What you're doing there, if it's purposeful, it's exercise.

So for example, when I'm talking,

if I'm waving around my hands, if I'm tapping my feet,

if I'm--

whatever.

That's NEAT.

But trying to get yourself--

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 don't really do two things at once.

ANDREW HUBERMAN: Right.

LAYNE NORTON: You switch quickly between tasks, right?

ANDREW HUBERMAN: Absolutely.

Can I quickly ask, was the person that you were referring

to our friend Ben Bruno?

LAYNE NORTON: No, no.

But he is fidgety too.

ANDREW HUBERMAN: Yeah.

Amazing online fitness channel.

He's a freakishly strong individual.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: Yeah.

And I can't remember whether or not,

Ben, you're a fidgetter 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 thousand-- excuse me, hundreds to maybe even

close to 1,000 calories per day.

Could you elaborate on that?

LAYNE NORTON: Yeah.

So there was actually a really classic study, I think, from--

I want to say it's from Levine in 1995.

It was metabolic ward study.

And hopefully, I don't butcher the study

because I'm trying to pull it out of my brain.

ANDREW HUBERMAN: I don't expect you to have that in your head.

Although, I must say, you have a quite extensive PubMed ID,

grab bag in there.

So--

LAYNE NORTON: I try to bring the receipts.

I try to bring the receipts.

ANDREW HUBERMAN: We will put a link to this study in the show

note captions.

So people can peruse it if they like it, yeah.

LAYNE NORTON: So I believe they had people overeat.

And I think it was by like 1,000 calories a day

and I think for six weeks.

And I mean, this is the metabolic ward.

So 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 1/2 a kilo.

They should have gained like--

I think it was something like 3 to 4 kilos.

It was predicted.

And what they found is this individual

just spontaneously increased their physical activity.

He didn't purposefully do it, it just happened.

And I mean, anecdotally, I've seen

people who are, again, very lean even eat a meal,

sit down, and start sweating.

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.

He would walk up a flight of stairs

and all of a sudden he's sweating.

Sit down eat a meal, he's sweating.

He's just--

ANDREW HUBERMAN: He's a furnace.

LAYNE NORTON: 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 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 body weight.

Now, you also do get a decline in BMR

when you lose weight, one, because you're just

in a smaller body now and so it takes less energy

to lock them out.

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 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 starts to come back up.

There is still a small reduction,

but I used to be somebody who thought

that BMR, metabolic adaptation was

a big reason why people stopped losing weight or plateaued.

And now, I think it's much more to do with NEAT.

ANDREW HUBERMAN: Interesting.

And you said that it can't be conscious

because 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 I'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 soleus pushup, which

is basically a heel raise.

A seated catchphrase with one foot not weighted.

And then they looked at it 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, 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 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.

LAYNE NORTON: Well, what I'll tell

people is if you're worried about NEAT,

one thing you can do, like these watches,

for example where people are like, oh, well,

told me I burned these 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.

ANDREW HUBERMAN: Fitness track.

So for those of you listening, we're

not going to name the brand.

But fitness trackers-- so wrist-worn fitness trackers.

LAYNE NORTON: And this is across the board.

ANDREW HUBERMAN: OK.

LAYNE NORTON: So like depending on the brand,

it could be more or less but, they all

overestimated the amount of--

the calories you burn from exercise.

So this is actually a great example where people go, well,

calories in, calories out doesn't work for me,

because I eat in a calorie deficit, I didn't lose weight.

When I talk to them, usually, they

went to an online calculator.

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 conservation of energy

or that you might have not gotten

the right number for you?

ANDREW HUBERMAN: The measurement tool was off.

LAYNE NORTON: Yeah.

The next thing is a lot of people weigh very 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 after you

go to the bathroom, do it every day,

and take the average of that for the week.

And then compare that to the next week's average.

ANDREW HUBERMAN: Can I ask one-- sorry to interrupt,

but one quick question about that when you say,

go to the bathroom not to get too detailed here

unnecessarily, but are you talking about urination

and emptying your bowels?

Ideally, because you did eat a big meal the night before.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: Yeah.

Got it.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: So wake up, 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 how it progresses.

LAYNE NORTON: All right.

And the reason I recommend doing that is, if you're just

sporadically weighing in, as somebody who weighs themselves

pretty regularly, I mean, my weight

will fluctuate 5, 6 pounds, and not seemingly changing much.

And that's just-- 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 8 pounds, right?

So if you're somebody who just randomly is weighing in

and you're eating in a calorie deficit,

and you just weigh in one day where you've just

whatever reason holding some more fluid, then you're 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 stops the buy-in, when they have a fluctuation up.

So that's one of the reasons--

ANDREW HUBERMAN: Great point.

LAYNE NORTON: --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.

So they're, oh, this is working.

ANDREW HUBERMAN: Yeah.

We can return to that in a little bit

because I have theories as to how that--

when people eat less carbohydrate,

they excrete more water, and they'll see--

for the first time, they'll see some definition in their abs,

oh, my God, this diet's amazing.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: And the fluid loss does hold that promise.

I think fluid loss can do some other things.

It might make people literally feel lighter,

although it can be-- it has some negative effects.

I do have one quick question, and I

do want-- we will 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, if somebody is on the treadmill

and they'll see, OK, they burn 400 calories.

Actually, I think this is a month

where a number of prominent podcasters

like Bert Kreischer, Tom Segura, Joe Rogan, and others,

I think they call it "Sober October,"

but in addition to avoiding alcohol,

they're burning 500 calories per day during the exercise.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: They're measuring it.

A lot of people do this.

They think-- they take track of weather--

excuse me, take stock of how many calories they burned.

My understanding is that if that particular form of exercise

is a muscle building form of exercise,

that at some point later, there might be an increase in muscle

if you did 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 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,

and do that 10 times over.

Let's assume I burn 400 calories during that exercise bout.

But my understanding is that in the hours that follow,

my basal metabolic rate will have increased.

Is that true, and is it significant enough

to care about?

LAYNE NORTON: 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.

ANDREW HUBERMAN: This is Don Lemon?

LAYNE NORTON: Yeah, Don Lemon.

So he would always kind of say, yeah,

but what's the outcome going to be, right?

So this is actually one of the things I changed my mind on.

Was I used to be very much, well,

I think high intensity interval training is probably better

because you get this post-exercise energy burn

which they do see in some of these studies.

But in the meta analyzes 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 like, that's

the example of a mechanism, which is OK,

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.

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 wash it out, right?

ANDREW HUBERMAN: I see.

And I have to imagine some forms of exercise.

This would be highly individual, but will spike appetite more

than others.

So for instance, if I go out for a 45-minute jog which I do.

A 45 to 60-minute hike or jog once a week, I just

make it a point to do that or ruck or something like that.

Throw on a weight vest and hike.

After that, I find I'm very thirsty, I want to hydrate.

But I'm not that hungry.

And that's true of all cardiovascular exercise for me.

But after I weight train, about 60 to 90 minutes later,

I want to eat the refrigerator.

And so obviously, calories in, calories out

dictates that that will play an important role as to

whether or not I gain or lose weight, et cetera.

So is it safe to say that the specific form of exercise

that people choose needs to be taken in consideration?

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 their rigorous studies.

And whether or not that form of exercise

actually increases lean muscle mass or not.

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.

LAYNE NORTON: 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 1,000 calories.

ANDREW HUBERMAN: That's a lot of resistance training.

LAYNE NORTON: Right.

ANDREW HUBERMAN: My weight workouts

are warm up for 10 minutes and then one hour of work done.

LAYNE NORTON: I just--

I love to train.

ANDREW HUBERMAN: OK.

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 OK, but past that, I have to take two,

maybe even three days off before I can train.

My nervous system just doesn't tolerate it well.

So I limit it to an hour, you know.

LAYNE NORTON: And part of that to remember is like,

I've built up to that over a long period of time.

So you couldn't just throw somebody in and start

having them do two hours a day.

It's not going to go well for them.

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LAYNE NORTON: But I will say about the calorie trackers, so

if I'm used to--

OK, I usually burn about 1,000 calories according to this,

it's not accurate.

But if I go in tomorrow and I do 1,300, it may not be accurate--

I don't know what the exact number is,

but I can be relatively confident that it's

more than the previous session.

And so in terms of comparison, it

might be OK, like within subject.

And then the other thing I was kind of circling around on

was, if you're worried about NEAT, tracking your steps

can be helpful because people step counts can spontaneously

decrease when they're on 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

building coaches is, they'll say OK, you're, at 8,000 steps

right now.

We're not going to add any purposeful cardio.

But whatever you need to do to maintain that 8,000 steps,

do that.

And sometimes, they have to add 15, 20, 30 minutes of cardio,

because they're spontaneous activity that they're not

even aware of goes down.

ANDREW HUBERMAN: That's a really excellent point.

I've heard the 10,000 steps per day number was,

we all heard that.

And then I learned that, 10,000 were just kind of thrown out

as an arbitrary number.

So we're like get eight-hour intermittent fasting thing,

there's a story behind that because actually I

spoke to Satchin, and it turns out

that the graduate student in his lab

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.

So--

LAYNE NORTON: 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.

Like they're a very big hammer is the way I look at it.

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 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 have your biggest meal of the day.

And 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 supplemented with creatine, told they weren't supplemented

with creatine, not supplemented, told

they were supplemented, supplemented,

told they weren't, supplemented, until they were.

Basically, it just matters what they told them.

ANDREW HUBERMAN: Really.

LAYNE NORTON: Oh, yeah.

ANDREW HUBERMAN: This is incredible.

I have to get this study well so we

can link to a colleague of mine at Stanford.

She's been on the podcast.

I'd love to introduce you to because I

think you guys really riff.

First of all, she was a former D1 athlete

and then as runs a lab at Stanford in psychology.

This is Alia Crum.

And she's-- and grew up in this very athletic, obviously,

and very, very smart.

And her laboratory focuses on these belief/placebo effects

where if you tell people all the horrible things that stress

do to you in terms of your memory and cognitive

functioning and then you give them a memory test,

they 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 I have for years.

5 grams a day.

I don't--

LAYNE NORTON: And it's great.

ANDREW HUBERMAN: 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?

LAYNE NORTON: Not in this study.

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.

So they actually did a study--

and I don't have the citation, but it was--

I think, within the last 10 years

where they told people they were putting them

on anabolic steroids.

And wouldn't you know it, they had better gains--

even though they weren't actually on anabolic steroids,

they had better gains than people that they didn't tell

were anabolic steroids.

ANDREW HUBERMAN: Amazing.

LAYNE NORTON: And that's like hard outcomes.

Strength, lean body mass, those sorts of things.

So when people say, well, I wouldn't

fall for the placebo effect, it's like,

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.

ANDREW HUBERMAN: Yeah, absolutely.

LAYNE NORTON: So getting back to,

that's just a possible explanation of, maybe, why.

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.

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

a really poor weight loss tool.

If you figure out how many calories

you should be burning from it and you do that,

you end up getting less weight loss that you would predict.

ANDREW HUBERMAN: I have a family member who

is perfectly happy to eat less, but doesn't loathe exercise,

but dislikes 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.

LAYNE NORTON: 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 those-- it will improve your insulin sensitivity,

inflammation, all that stuff.

So everybody out there looking for a hack to be healthier

exercises the hack, right?

ANDREW HUBERMAN: Yeah.

Crucial point.

And our mutual friend Dr. Peter Attia, I think,

has gone on record several times now saying

that of all the things that one could take--

NMN, et cetera, metformin.

Regardless of whether or not one takes those or doesn't take

those, that the positive effects on longevity

by way of biomarkers from regular exercise is--

far outweighs all of those things combined.

Not that those things don't necessarily work,

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.

LAYNE NORTON: Yeah.

Absolutely.

I 100% agree.

And when you're talking about weight loss,

people miss the point of exercise, I think.

There's some work that came out from Herman Pontzer

as well that basically showed like, well,

if you do 100 calories from exercise,

you have a 28-calorie reduction in your basal metabolic rate

in response to that.

So it's kind of like this constrained energy expenditure

model.

But what I would say is, OK, well there's still a net of 72.

So it's still OK, 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 many calories

did they actually eat.

So it was like a J-shaped curve.

So the sedentary actually ate more food

than the lightly active or moderately active.

But from lightly active to heavily active,

they almost perfectly compensated how many calories

they should be eating.

So to me, that suggests, when you become active,

you can actually regulate your appetite appropriately or much

more appropriately than if you're sedentary.

ANDREW HUBERMAN: 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 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 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 a number of different ways.

LAYNE NORTON: Yeah.

I think it's--

I think the effect is probably mostly at the brain level.

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 your normal like,

I feel kind of empty and my stomach's growling.

Like those are-- they can go together,

but usually like the hypoglycemia is like, I am hot,

I feel like I'm going to pass out.

You want to eat something not because your stomach's growling

but because that you just need some fuel.

ANDREW HUBERMAN: It's like you're getting pulled under.

LAYNE NORTON: Oh, yeah.

Absolutely.

ANDREW HUBERMAN: I've been there when

I've done the longer fasts, something

I don't do anymore and drink a lot of black coffee.

There 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.

Hypoglycemia is very uncomfortable.

LAYNE NORTON: It's not fun.

So again, then when they look at actual randomized controlled

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.

And there's individual data points.

So there are some people who at least anecdotally report

that exercise makes them more hungry.

That's completely valid.

It could be their beliefs around it,

it could be a number of different things,

but it's important to understand that there

is individual variability.

And I think one of the things that I've

learned to appreciate more is not

trying to separate psychology and physiology.

We do this a lot and say, 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.

Like with most things now, we have kind

of the biopsychosocial 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?

ANDREW HUBERMAN: No.

LAYNE NORTON: Right.

If you look at dinner plates from the 1800s,

they're about this big.

Now how big are dinner plates?

ANDREW HUBERMAN: The whole buffet.

LAYNE NORTON: Right.

ANDREW HUBERMAN: Yeah.

LAYNE NORTON: There's situational cues.

You're sitting down to watch TV.

Oh, grab some popcorn, grab some snack, whatever.

ANDREW HUBERMAN: I even see this with--

you know, how one person will pick up the phone

and then everyone picks up their phone.

I think there's a similar effect with food.

LAYNE NORTON: Yeah.

And same thing, right?

Like how many times have we either done it ourselves

or have been experienced people saying, oh, you

should have something-- you should have alcohol,

especially, right?

People-- I was hanging out with somebody last night

and I had a beer and they just had 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, we're hurt animals.

We don't want to be doing something out

in isolation on our own.

Now, this is a very tenuous, I guess, belief of mine.

But doing things alone in isolation

during ancestral times, that's going

to set off your alarm system.

Because if you don't have other people,

you can't protect yourself.

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.

So the whole point to that is, on the list of reasons

why people eat, I mean, I've gotten

to the point where I think that hunger is actually not even

the main reason people eat.

Stress, lack of sleep--

ANDREW HUBERMAN: Boredom.

LAYNE NORTON: --boredom.

ANDREW HUBERMAN: Yeah.

LAYNE NORTON: Absolutely.

So unless we can do something that

addresses all those things, there's

a line from a review paper--

this review paper came out in 2011

is by a researcher named MacLean.

And it's the best review paper I've ever read.

It was called, biology's response to dieting--

the impetus for weight regain.

And basically went through all the mechanisms

of these adaptations that happen during fat loss diets

and how biology's response is to try to drive you back

to your 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.

And any attempt or any 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.

Look, 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 it 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 Suplee?

ANDREW HUBERMAN: No.

LAYNE NORTON: So Ethan is an actor.

He's been in like remember the Titans and American History X.

ANDREW HUBERMAN: I certainly saw American History X.

LAYNE NORTON: Yeah.

So he was very large.

He was like 550 pounds.

And now he's like 230 and jacked.

ANDREW HUBERMAN: Well, 5-- he was how many--

LAYNE NORTON: 550 pounds.

ANDREW HUBERMAN: Wow.

LAYNE NORTON: And he has-- whenever he puts up

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?

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.

Because I mean, and addicts talk about this.

Like people who are alcoholics.

They had to get new friends.

They had to hang out at different places,

because their entire life had been set up

around this lifestyle for alcohol.

And I would actually argue that eating disorders

or disordered eating patterns is much harder to break

than other forms of addiction.

And you think about food addiction.

Well, in some ways, bulimia and anorexia are still addictions.

You can't stop eating.

Like if 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 telling a gambling addict,

well, you've got to play this slot a couple of 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.

ANDREW HUBERMAN: Right.

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.

So important for people to understand this

because obviously, as a neuroscientist,

I think 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 bidirectional.

Now, nowadays, there's a lot of interest in brain, body,

and particular gut--

brain axis 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 burn

and overall health and biomarkers.

And then this is wonderful to learn

that it can increase the sensitivity to satiety signals.

I think that makes-- at least in my mind,

places very high on the list of things that people

should absolutely do.

But 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--

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 what?

I've met David, know David a bit, and his every bit

is intense and driven as and 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 time 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 are a cohesive whole

as an individual.

Sorry.

You were about to say.

LAYNE NORTON: That gets actually into one of my favorite topics,

which is, 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 am going to do a diet, and I'm going to lose this weight,

and they do not give any thought to what happens afterwards.

It's like think about if you have some chronic disease

or a diabetic.

You can't just take insulin once and that's it, right?

You've got to take it continuously, otherwise,

you're going to have problems.

If you do a diet and you lose 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 sustainable for you,

and plenty of people, low carb, intermittent fasting, whatever,

they say, I felt easy.

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 it's 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, doesn't feel hard for me.

Part of it, I've just been doing it for so long.

But to other people, that's very stressful.

They don't want to--

they say, well, I'd rather just not eat for 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,

there 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?

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.

ANDREW HUBERMAN: Incredibly important message.

Basically, that.

If I could highlight-- if there was a version of highlight

or 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.

LAYNE NORTON: Well, they even talk about the diet-- honeymoon

period where you go into a diet and you're all fired up

about it and like you're very adherent,

and then what happens, with every single diet

without exception in research studies

is once you get past few months, adherence just

starts waiting and going off.

ANDREW HUBERMAN: Here we are really talking

about a form of relationship.

I'm not saying that to be tongue in cheek.

Actually, we had a guest early on in the podcast, Dr. Karl

Deisseroth, he's a psychiatrist and a bioengineer at Stanford.

Tremendously successful.

Alaska 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.

When you pair up with somebody that

was 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 seeing a lot of parallels 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

boils down to what you said earlier, which

is that the brain and our decisions about what we

are going to stick to are tremendously powerful.

LAYNE NORTON: I think one thing I will say is keep in mind,

when you look at the research data, the meta analyzes on say,

time-restricted eating versus none, when calories are

equated, doesn't seem to be a difference in weight

loss, fat loss, and most biomarkers of health.

Same thing for low carb versus low fat.

Fewer quick calories and 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

That's important because that ensures that adherence

can be much higher in those studies

whereas various free living studies, sometimes,

you can see funky results.

ANDREW HUBERMAN: People are sneaking food

or they're just not really--

LAYNE NORTON: It's very difficult--

ANDREW HUBERMAN: --eating the way

that the study would ideally have them eat.

LAYNE NORTON: Unless the person is

getting like continuous support-- like,

studies where they have a dietician talk

to people like every week tend to actually

have pretty good adherence.

I mean, that's expensive to have done the study.

And again, like what limits studies, money, money,

and money.

But the low carb versus low fat, 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.

Whatever lever you've got a pull,

you've got a bunch of different options.

ANDREW HUBERMAN: You mentioned picking something

that 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 a significant fraction

of people out there who are trying to do that.

Yeah.

Is there any downside to being a dabbler?

Keto for a few months and then omnivore

for a few months, et cetera?

LAYNE NORTON: I think that's actually a great thing,

especially to like, maybe, find what

you feel is easiest for you.

But in terms of as a strategy, I mean, I guess,

some people just might get into dopamine

but like, oh, change and get something new.

And you feel a little bit more positive about it.

ANDREW HUBERMAN: And do partner model.

LAYNE NORTON: 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--

their behaviors and they're doing portion control

or whatever it is, and they're able to sustain

a calorie deficit or depending on whatever 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 vise 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 a higher carb diet,

you'll be 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 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 a glucose

tolerance test after they've been on keto,

they'll do pretty terribly at it.

But that doesn't last that long.

ANDREW HUBERMAN: About how long?

LAYNE NORTON: A few weeks.

ANDREW HUBERMAN: I think that's important for people to know,

because I have a feeling during those first few weeks

are the period of time when a lot of people

go running back to what they were doing previously.

Which is not to say that they shouldn't, but 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 through the roof,

and I would be able to just sponge up every bit of glucose

that I would have ingested through carbohydrate.

So I did indeed switch over.

And I felt like I had pretty terrible brain fog.

I even got some jitters.

And I thought, what is this?

My blood sugar was low before, and now my blood sugar

should be in more moderate territory.

But based on what you just said, I'd

upregulated the enzymes and systems

in the body for fat metabolism on the keto diet

and then switching over--

there was basically a ramping up of the molecules involved in--

presumably in glycolysis.

LAYNE NORTON: 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.

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 blood glucose

or fasting insulin or even HOMA-IR,

those tend to be pretty good on low carb.

But then if you do it all glucose tolerance test,

it tends to be pretty bad.

And so it depends on your specific measure.

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 it is something important to keep in mind.

And one of the reasons like if somebody

was to transition out of keto, typically,

if 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 systematically

over like a four to eight-week period.

That way, hopefully, they're not having that period

of two weeks where they're like, oh, man, why

do I feel so terrible?

ANDREW HUBERMAN: A 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--

LAYNE NORTON: I see what you did with that pun.

ANDREW HUBERMAN: And certainly in the last few minutes,

we've been talking a lot about top-down processes.

The brain, the psychology, placebo effects,

but the very real aspects of those,

not that I can imagine 2,000 calories, 1,000 calories

and somehow change the law of thermodynamics.

Can't do that.

But we've been 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 have asked me

that they-- and it was kind of scary to me, I thought, yes,

this is not about ingesting feces, this is--

they literally do a transplant of these 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, 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?

LAYNE NORTON: Yeah.

So the first thing I'll say is I'm not a gut health expert,

but I will--

I feel relatively comfortable talking about it based

on conversations I've had with people who are experts--

one being Suzanne Devkota who's--

you're familiar with her?

ANDREW HUBERMAN: Well, she's sort

of a phenom in this area from what I understood.

LAYNE NORTON: So she was actually

doing her masters when I was doing my PhD in Lehman's lab.

So she was one of my lab mates.

ANDREW HUBERMAN: Terrific.

LAYNE NORTON: And the other thing to say

is, even gut health experts, and 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, probably

for good reason.

Because if we just flipped our scientific consensus based

on one study, I mean, it would be a mess.

So it's going to take time before we really

understand the implications of the gut and what it means.

So when it comes to weight loss, there probably

is a role in there.

I mean, we've seen that there's something going on.

Now, whether that's-- is it something where a gut

microbiome make makeup that's more obese resistant, perhaps,

it extracts less calories out of the food you eat.

Or perhaps, it's elevating BMR.

Although, I think that that's probably somewhat unlikely.

ANDREW HUBERMAN: Do you think it could impact

the way satiety signals are?

LAYNE NORTON: So that's--

ANDREW HUBERMAN: I mean, back to the brain again.

LAYNE NORTON: --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 the most effective obesity

treatments out there, which is like semaglutide,

I mean, you consistently see a 15%

on average loss of body weight, which is massive

and people keep it off.

That is a GLP-1 mimetic which is a gut hormone.

And it, basically, just is a very, very powerful appetite

suppressant.

ANDREW HUBERMAN: 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 basically, the takeaway is that like so many things

in neuroscience, the GLP-1 works in two parallel pathways.

In the brain, it seems to impact neurons

in the hypothalamus that control satiety.

So exactly what you're saying.

And in the gut, it seems to create

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.

I don't know, they might.

But that one feels as if their gut is actually fuller

because these mechanical sensors that send-- stretch

are sending signals to the brain,

oh, I actually have some food.

I'm not empty down there.

LAYNE NORTON: Right.

ANDREW HUBERMAN: 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.

LAYNE NORTON: That's great.

ANDREW HUBERMAN: You can tell I'm really excited about this.

And here you are telling a neuroscientist, me,

that a lot, perhaps, circles back to these brain

mechanisms of satiety.

LAYNE NORTON: Yeah.

I mean, I think that--

and especially looking at the research on leptin,

you we used to think, OK, metabolism is mostly

like 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 crosstalk between these pathways.

And that's-- when we get into mechanisms--

though 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,

like when I say outcome-based, we're

talking about physical outcomes like weight loss, fat loss,

changes in blood markers, whatever,

though that is the summation of thousands

of different mechanisms.

So sure, sometimes, you can affect a mechanistic pathway,

and you get straight down the line outcome, but not always.

Whenever you make a treatment or anything into the system,

it's like throwing a pebble in a lake.

It creates ripples.

And we don't always know what those are going to be.

And that's why-- I mean, we've seen certain drugs,

what 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 semaglutide

and the effects on mechanical sensors,

it's probably why a lot of people

report actually low grade nausea when they're using semaglutide.

Because of that.

Because if you're-- 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 cells in our microbiome by far than there are in our body.

So we're actually more--

in terms of a cell per cell level,

we're actually more bacteria than we are eukaryote.

ANDREW HUBERMAN: There's Justin Sonnenburg

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?

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: 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 Fridman 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.

Do you do anything specifically to support your gut microbiome?

Are you a probiotic guy or a fermented foods guy or a fiber

guy?

LAYNE NORTON: So-- again, I'm going to kind of go straight

down the line from what I've heard

from Suzanne and other experts.

So if you want to improve gut health, one of the biggest

levers--

the three biggest levers you can pull

is not eating too many calories, exercising--

there is a connection between exercise and the gut,

and fiber.

So 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 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.

But again, in mice-- so just a huge caveat.

So your gut microbiome can produce

these short chain fatty acids by fermenting the 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.

ANDREW HUBERMAN: Supplemented prebiotics.

LAYNE NORTON: 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.

ANDREW HUBERMAN: What fiber sources do you use?

And I think-- I mean, 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.

LAYNE NORTON: Yeah.

And I would just say diversity.

So there's various evidence from various different fiber

sources--

fruits and vegetables, obviously, 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 whether it's

intermittent fasting or all these other things,

say, that's great, that's great.

Are you eating like over 50, 60 grams of fiber a day?

ANDREW HUBERMAN: Conceptualize 50 or 60 grams.

So if I were to eat 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.

There's a lot.

LAYNE NORTON: Yeah.

So like 200 grams of broccoli, per se, would probably be like

5, 6 grams of fiber.

ANDREW HUBERMAN: And I need to get how much per day?

LAYNE NORTON: Well, I would say--

ANDREW HUBERMAN: Ideally.

LAYNE NORTON: --typically, what the recommended dose

is is 15 grams per 1,000 calories

intake because if you're eating low calories,

it's difficult to get enough fiber in.

But based on-- and again, these are cohort studies.

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 how much you can tolerate

without feeling uncomfortable.

Because if you're eating like a ton of fiber, I mean,

at some point, it's not going to be very comfortable.

ANDREW HUBERMAN: Yeah.

Exercise becomes uncomfortable or hazardous.

Yeah.

LAYNE NORTON: And I actually a--

kind of touching on that because I think it is important.

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'll 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 do it more frequently, adds bulk to stool.

But that's not why you should eat fiber.

Why should eat fiber is because of the effects of mortality.

And some of the pushback will be, well, this

is healthy user bias.

And what I'll say is--

ANDREW HUBERMAN: Meaning, healthy people do this

and therefore it's working.

LAYNE NORTON: Healthy people eat more fiber and therefore--

ANDREW HUBERMAN: OK.

Yeah.

LAYNE NORTON: 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 use,

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, 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 end 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.

ANDREW HUBERMAN: Right.

LAYNE NORTON: It doesn't necessarily--

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.

That this stuff is still very much in its infancy.

But in terms of the big levers, I mean,

it's 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.

ANDREW HUBERMAN: Fantastic.

Fantastic because it fits with what

I like to think of as the center of mass of evidence.

And I'm starting to get some window into what

your process is around selection of studies and no one study

being wholly, 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.

LAYNE NORTON: And one thing I'll tell people is like,

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, one study is just going

to move me just a little bit.

And then maybe, if another one comes out,

maybe a little bit more.

And then like very slowly, I'm going to get some--

I mean, my experience with LDL cholesterol,

that's something I changed my mind on a while back.

When I was younger, like circa 2005 getting into grad school,

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 went, I can't hold this position

anymore.

ANDREW HUBERMAN: What is your revised position on LDL?

LAYNE NORTON: 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 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 of cardiovascular disease.

In Mendelian randomization studies,

which Mendelian randomization basically

uses natural randomization.

So some people are, in the case of HDL,

naturally higher secreted or naturally lower

secretions of HDL.

And we talked about how-- you can't really

do a 20-year human randomized controlled 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.

What Mendelian randomization allows is to say,

OK, 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 series of HDL

versus high secrete of HDL withholding

some of the other key variables consistent like LDL,

you don't see an effect on heart disease, really.

ANDREW HUBERMAN: Of LDL.

LAYNE NORTON: Of HDL.

ANDREW HUBERMAN: Got it, OK.

LAYNE NORTON: 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 apolipoprotein 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 look at people's exposure

over a lifetime, and then we see that linear dose-dependent

effect.

To me, that was convincing enough

to change my mind on that particular topic.

And then if you look at 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 is high HDL and high LDL.

ANDREW HUBERMAN: So the ratio does matter.

LAYNE NORTON: The ratio does better.

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 sufficient for me to change my mind.

But it took-- it was like not just one study came out.

It was, OK, then there was another study, and then

another study, ans then another study, and at a certain point

I go, OK, 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, are you 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, OK, 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 apply the interpretation.

ANDREW HUBERMAN: Yeah.

Well, and I think you are 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

physiology relate to one another.

And so on.

In fact, I think that your training as a biochemist

and then training as in nutrition with somebody who--

Don Lemon, 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 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 dramatic.

And then the assumption is, oh, you just

take-- you take the drugs 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.

LAYNE NORTON: Well, a great example of that

is, so my research was actually in rodents.

All my studies on protein metabolism, and leucine,

in particular, is what we were studying.

Well, we know if you give leucine,

it increases muscle protein synthesis.

But we also know if you supplement with leucine,

people don't get more muscular.

ANDREW HUBERMAN: I was about to say--

LAYNE NORTON: So as always--

ANDREW HUBERMAN: --all you have to do

is supplement with leucine?

LAYNE NORTON: Right.

Right, right.

And so how is that possible?

Muscle building is not just protein synthesis.

It's also the balance between synthesis and degradation.

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 changed the way I ate,

which I think is interesting.

So before, I had been like, I eat eight meals a day,

eat every two hours, try to keep--

ANDREW HUBERMAN: Eight meals a day?

LAYNE NORTON: Yeah when I got to grad school.

ANDREW HUBERMAN: In order to get that 30

grams of protein per meal?

LAYNE NORTON: Get that amino drip going in

was the idea, right?

Like just have an IV hooked up of amino acids.

ANDREW HUBERMAN: Not really, folks.

LAYNE NORTON: Not really, yeah.

But that was the concept.

But the first study that I did, we, basically, looked at OK,

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, OK.

Well, it'll probably track with plasma leucine.

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 branched chain amino acids.

So we wanted to see, OK, how long does this effect last?

So we fed these animals whey protein,

and again, I thought, OK, well, however long plasma leucine,

stay up that, will be how long protein synthesis stays up.

And so we got the protein synthesis 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 then I said, OK, 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 stimulated-- and leucine stimulates mTOR.

Two of the targets of mTOR are a protein compound called 4E-BP1.

And then another one is called a ribosomal protein S6K.

So I don't want to get into the specifics about it

because it's going to be on the scope.

But basically, when these things are phosphorylated by mTOR,

it increases the rate of translation 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 4E-BP1 and RPS6.

I was like, OK, well, I'll probably

see these things come down in three hours.

Still plateaued.

And so then it was like, 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 Lehman's office.

And this is like six months after we've

done this study, because this analysis takes time.

I was like, 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, describe to me

your technique.

How are you doing this?

And I described it, and he said, well,

how is your standard error?

And 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--

ANDREW HUBERMAN: This is why we do PhDs.

LAYNE NORTON: This is why, yeah--

ANDREW HUBERMAN: You need an advisor--

LAYNE NORTON: This is why I am 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,

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.

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 back in '99,

I think, where they infused essential amino acids

for six hours.

Protein synthesis went up, peaked at 60 minutes,

came back down 120, and never went back up again.

ANDREW HUBERMAN: 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.

LAYNE NORTON: But the problem is, the plasma amino acids

are still elevated.

ANDREW HUBERMAN: So it's, essentially,

like eating the whole way through from the perspective

of leucine.

LAYNE NORTON: From the cells, yeah.

ANDREW HUBERMAN: Got it.

LAYNE NORTON: 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 capped

out plasma amino acids.

And we looked at all kinds of stuff.

We looked at intracellular leucine just to make sure that

wasn't falling off, it wasn't.

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 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

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--

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 short--

not short circuits it, but it cuts it off, right?

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--

ANDREW HUBERMAN: A proportional wait here.

LAYNE NORTON: --that's a great example of, OK, we're

looking at this mechanism of mTOR 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, let's--

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 chasing outcomes

in terms of what we recommend to people.

ANDREW HUBERMAN: Excellent point.

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 there are 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 mention 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 NEAT, et cetera.

How should we think about protein and 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.

LAYNE NORTON: So a lot of things--

ANDREW HUBERMAN: --or more.

LAYNE NORTON: Yeah.

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 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 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.

ANDREW HUBERMAN: 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?

LAYNE NORTON: 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,

that 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 and 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 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 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.

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.

Now, 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 are based on mechanistic--

this increases mTOR, 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, that 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, it'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 satiating.

So take, for example, like a really tasty protein

bar, which back when we were getting into this,

no such thing existed.

Now, you have protein bars that 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.

ANDREW HUBERMAN: That's my premeal snack.

LAYNE NORTON: Right.

Right.

So why?

Because, I mean, it's processed, refined,

and made to be very palatable.

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 satiety index,

a plain baked potato is about as satiating as it gets.

ANDREW HUBERMAN: If I eat a bowl of oatmeal,

I feel pretty good afterward.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: For a while, right?

I mean, I usually--

I'll eat that along with some other things,

but I completely agree.

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.

LAYNE NORTON: Yeah.

ANDREW HUBERMAN: But it's 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, 2 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 cut off?

Because I think balancing the 1.6 gram per kilogram 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

or you're spending so much time trying to focus on it.

LAYNE NORTON: You can't optimize all the things

at the same time.

ANDREW HUBERMAN: You'd lose your mind and your body.

So what is necessary in terms of frequency

if one is getting enough protein?

And then tied into that question,

is there any reality to this idea

that if you eat one 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 protein starved.

Is that a real thing?

LAYNE NORTON: 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

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.

ANDREW HUBERMAN: Do any cultures, actually,

eat big breakfast and not a big lunch and dinner?

We all heard that was ideal.

We'll get into circadian timing in a little bit,

but does anyone actually do that?

Steak and eggs for breakfast and then

taper off the rest of the day?

LAYNE NORTON: I know German culture

tends to have a big breakfast, but also

tends to be like sugary foods and whatnot.

As far as like teleological, 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.

Yeah, if the house is made out of wood

you could get wood out of it, but that's not why you build.

You're building the house out of a demand.

Same thing for 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, at relatively

large storage capacity, you can store

400 or 500 grams of carbohydrate between your liver and muscles.

And then protein, which almost has no storage capacity,

the idea that, OK, 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 were getting whey protein, so a 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 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.