Original subtitles

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. Sachin Panda.

Dr. Sachin Panda is a professor and director

of the Regulatory Biology Laboratory

at the Salk Institute of Biological Studies.

His laboratory has made numerous important contributions

that impact mental health, physical health,

and human performance.

For instance, his laboratory discovered the neurons

in the eye and neurons within the brain

that regulate our so-called circadian rhythm.

Circadian rhythms are 24-hour rhythms

and everything from gene expression

to the overall functioning of tissues,

our levels of mood and alertness,

our ability to sleep, appetite, and much, much more.

In addition, over the last decade,

Dr. Panda's laboratory has made critical discoveries

in terms of how our patterns of eating over time

impact our biology and our health.

In particular, his laboratory pioneered discoveries

related to so-called intermittent fasting,

also sometimes referred to as time-restricted feeding.

Today, Dr. Panda and I discuss how our circadian behaviors,

everything from when we wake up to when we view light

to when we avoid viewing light

to when we eat and what we eat

and when we socialize and how we socialize,

impacts our biology and our psychology

and how all of that has a strong impact on our health.

During today's discussion,

you will learn how restricting your feeding

to specific periods within each 24-hour cycle

or perhaps even exploring longer patterns

of fasting and eating cycles

can impact everything from the health of your liver

to your gut, to your brain,

and how all of that impacts things like mood

and your ability to perform cognitive work.

Indeed, today's discussion goes deep

into all aspects of intermittent fasting,

aka time-restricted feeding.

We talk about the basic science,

as well as the recent clinical trials

that have explored time-restricted feeding

in a diverse range of people,

including men, women, children, people with diabetes,

people who are otherwise healthy, and much, much more.

I'm quite aware that intermittent fasting

is a topic of much debate these days.

We go deep into that debate,

and by the end of today's discussion,

you can be certain that you will have learned

all the latest and all the details,

all made very clear to you

thanks to the incredible expertise, discovery,

and clear communication of Dr. Panda.

As some of you may already know,

Dr. Panda has authored several important books

on the topic of intermittent fasting

and how it can benefit various aspects of health.

Those books include The Circadian Code

and a more recent book, The Circadian Diabetes Code,

both of which we've provided links to

in the show note captions.

In addition, if any of you are interested

in learning more about Dr. Panda's work,

including seeing his publications

and reading those publications,

or supporting his laboratory,

you can do that by going to his laboratory website,

which we have also linked in the show note captions.

Before we begin, I'd like to emphasize that this podcast

is separate from my teaching and research roles at Stanford.

It is, however, part of my desire and effort

to bring zero cost to consumer information about science

and science-related tools to the general public.

In keeping with that theme,

I'd like to thank the sponsors of today's podcast.

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I want to be clear that I am not following a ketogenic diet.

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They are not following a ketogenic diet.

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And now for my discussion with Dr. Sachin Panda.

Sachin, Dr. Panda, so good to see you again.

Yeah, good to see you.

We are colleagues still,

but we used to be right across the street from one another.

Yeah, I remember those days, yeah.

Yeah, so I'm delighted that you're here.

I think we're going to talk about a number of things,

mainly intermittent fasting, time-restricted feeding,

and health, but also the many other things

that you're doing.

Just before we started recording,

we were discussing your recent paper in Nature

that involved recordings from postmortem human retina.

So maybe if there's time at the end, we can get back to.

Your lab has shown that it can essentially maintain

or resurrect neurons from dead people

in order to potentially and eventually provide transplants

to rescue vision in the blind.

So that's extremely exciting.

But of course, not the main focus of today's discussion,

so we'll have to split it up.

The first question I have is how am I supposed to define

fasting and time-restricted feeding?

Meaning when I go to sleep every night, I'm not eating.

So in some sense, everybody is doing time-restricted feeding

to some degree or another.

At what point can we start thinking about

a pattern of eating as time-restricted feeding,

so-called intermittent fasting?

Does it have to do with how regular one is

about the start and stop times?

How do you think about defining intermittent fasting,

time-restricted feeding, and maybe,

just to simplify the conversation,

is one term more correct than the other

in terms of describing this incredible pattern of feeding?

Well, you know that intermittent fasting

covers many types of fasting.

Actually, it started a long time ago,

and it's embedded into the history of caloric restriction.

Almost 100 years ago, people showed that

if you reduce calorie intake in a rat,

then that rat can live for a long time.

And in those experiments,

the calories were reduced every single day.

And that led to the idea that if we cut down our calories

by 20%, say, then we can potentially live longer

by doing two things.

One is preventing AIDS-related disease,

or even if we fall sick, maybe we can accelerate cure

and keep the repair mechanism going

so that we can live longer.

But it was very difficult to count calories every day

and reduce, maintain that.

I must say that it's not that

caloric restriction is impossible,

or we are not doing it.

In fact, a lot of us, we do count calories

in our subconscious mind.

And so every time we take out a soda bottle or something,

I'm looking at it, okay, 160 kilocalorie,

30 kilocalorie, zero kilocalorie, we are doing that.

So the point is we are doing subconsciously

some kind of calorie counting,

but reducing calorie by 20%, 30% every single day

is not possible for many people.

So then the idea came in mouse and rat experiment

whether they can eat every other day.

And in fact, this every other day feeding

also led to very similar, almost equivalent

health improvement as continuous calorie restriction.

So then the idea was, well, every other day

is a little bit hard for humans,

but just imagine I'll just get to eat

only one day and then another day.

Then the idea came, well, for humans,

can they eat less for one or two days in a week?

So that led to this five, two diet

where people can eat for five days,

and then two days they have to reduce calories.

So that's also, intermaternally people are fasting.

Then as you know, Walter Longo also came with this idea

that periodic fasting, maybe four or five days

in every month or two months, three months,

you can fast or reduce calorie.

And he also found many benefits

of calorie restriction was there.

Were those studies on humans?

Many of the studies started in mice,

but alternate day fasting, five, two,

and Walter's periodic fasting,

all of them have now been done in humans,

not for longevity, of course,

because you cannot do those for a long time,

but for weight maintenance,

for reducing some signs of aging or reversing,

those things have been done.

So all of them have been done in humans,

mostly healthy humans, and in some cases,

people with pre-diabetes or some aspects

of metabolic disease.

So that led to the idea that all these forms of fasting,

in which the total calorie intake on any given day

is reduced for one or more days in a week, a month,

that umbrella term became intermittent fasting.

So if you look up the scientific literature,

most intermittent fasting involves

intentionally reducing calories

for at least one or two days in a week

or few days in a month.

So when we published time-restricted feeding,

the initial mouse experiments,

and even now, most of the mouse experiments,

we want to test what is the impact of time restriction

versus calorie restriction.

So in these experiments,

we don't reduce calorie on any day of mouse life.

So the mice eat the same number of calories

as the ad libitum-fed mice,

but still they see health benefit.

So that's why we call it time-restricted feeding.

But since it involves living without food for several hours,

for some people, it can be very difficult.

The initial experiments were done for eight hours

of feeding and 16 hours of fasting.

That kind of became popular.

And so that's why people use the same term

as intermittent fasting.

And now if you say intermittent fasting

in popular literature or popular media,

then people usually refer to time-restricted eating.

So now coming back to how do you define

time-restricted feeding.

So the way we have been trying to define experimentally

and also in literature is trying to confine

all your energy intake from solid and liquid food combined

within a consistent window of eight to 12 hours.

Because that's something that's doable.

Of course, people have done time-restricted feeding

with four hours, six hours,

and some people even try to eat everything

within two hours, one meal a day.

But the point is those are not feasible

to maintain for a very long time for a lot of people.

One question about the six hour versus eight hour

versus 12 hour feeding window.

Is it important that the feeding window

begin and end at the same time, more or less?

Yeah, more or less.

And if so, how much flexibility is there?

So for instance, I'm somebody that

I am not terribly hungry in the morning.

I like to drink water, usually some caffeine

and electrolytes in the period before my first meal.

And my first meal always lands sometime

between 11 a.m. and 12 noon.

There are exceptions occasionally.

I'll have a proper breakfast as it's called.

I guess it would be improper

if you're intermittent fasting for me.

But typically 11 a.m. or noon is when I first eat

and my last bite of food is typically around,

I don't know, 8.39 p.m.

That's what works for me.

Is that consistency affording me any benefit?

And let's just leave aside total caloric number,

macronutrients, plant-based meat, et cetera.

But is there any benefit to shortening that feeding window

that we are aware of or extending that feeding window

or being even more rigid about the start

and end of that feeding window?

Yeah, so the start of the feeding window,

that's interesting because the concept of time-restricted

feeding, when I describe animal studies,

it's feeding for humans, it's eating.

So the concept actually came from the science

of circadian rhythm.

So that means our body has an internal timetable

that's present in every cell, in every organ

that pre-programs many molecular aspects of the cells

that leads to physiology and all that stuff.

So that essentially there is a predetermined timetable

for every cell, every organ to do certain things

at certain time.

And the circadian clocks, as you and I know,

are more sensitive to light.

Light is the most dominant time giver.

So for example, when daylight saving time changes

or when we travel from one time zone to another time zone,

we feel kind of crappy because our daily activities

are out of sync from our internal clock.

So that was known for a very long time,

but then around the year 2000, 2002,

there was a famous experiment by Uli Sibler

from Switzerland.

What he did, he just fed the mice at the wrong time.

Mice are nocturnal there, night feeders.

And when he fed the mice during daytime,

the liver clock, instead of following its own routine,

liver clock actually started following food.

So that means by changing our feeding time,

we can change, we can tune our liver clock.

And subsequently the same experiment

has been repeated many times

and we repeated that in 2009.

And we figured out, yes, actually outside this brain center

called suprachiasmatic nucleus or SCN,

which is considered the master circadian clock,

almost the rest of the brain even follows when we eat.

And that came out from Pierre Chambon's lab in Europe,

where they systematically looked at even places

that are very close to the SCN.

For those who are, who know

those medial hypothalamus, paraventricular nucleus,

all of this within a couple of four or five millimeters

of the SCN, but they were following food cue.

Amazing.

So then, now if we think about it,

so for example, when the daylight seven time changes,

just one hour change, or one hour change in alignment

between our internal time and external time

leads to kind of feeling groggy and feeling

not at a peak performance for one or two days.

So the rule of thumb is when the time giver

changes by one hour, then our internal clock

takes at least a day to catch up.

So that means if you're flying from LA to New York,

you're moving through three time zones,

then on an average it will take three days

to catch up with the New York time.

For some people it can be even slower,

and for some people it can be two days,

but the bottom line is, yes, there is a desynchrony.

So then what does it mean for the body?

So one of the function of the clock is to anticipate

when you're going to wake up, for example,

so the blood pressure slightly goes up,

our heart rate goes up, our breathing goes up.

Similarly for food, almost every organ

that is involved in feeding or eating digestion,

all of them have clocks.

So even from saliva production,

there is the first phase of digestion

to secretion of all the digestive juice in the stomach

and then absorption of nutrient and liver metabolism,

everything, the whole village expects

when you're supposed to eat, and they're getting ready

for you to eat their first meal

after fasting for a long time.

So that's why it's breaking the fast of breakfast.

And when that time changes,

when you change it by two or three hours

from one day to another, then sometimes they're like,

oh, food didn't come, maybe we'll come at the wrong time.

We were at the wrong time.

And then they'll track the new eating times.

So suppose say one day you have been eating every day

at eight a.m., I eat at eight a.m.

Is that when you start your feeding window?

When does your feeding window shut?

Six p.m., so I eat for around 10 hours.

Okay.

And then one day if I switch to 10 a.m.,

then what happens is a clock is thinking,

well, the food didn't arrive at eight,

but it arrived at 10.

Maybe tomorrow the food will arrive

somewhere between eight and 10,

so we'll be ready around nine.

I see.

So then the next day if I come back and eat at eight o'clock,

then I may eat, but my clock is not ready

to digest that food.

So that's why this idea is you have to be consistent

to take advantage of this anticipatory activity

of our clock in different systems

to get the best out of it.

Is there evidence that those anticipatory systems,

as they relate to digestion,

help us better assimilate our food?

I would imagine so.

I mean, if you have the gastric juices

that are gonna help digest the proteins,

fats, and carbohydrates and already deployed

at the time when you eat,

I could imagine that food will be better utilized

than if you don't.

So in other words, what is the advantage

of having these anticipatory signals

in terms of potential health benefits?

The anticipatory signal is really important

even from waking up.

The reason why many people feel not ready completely

when they wake up to an alarm clock,

because the alarm clock wakes you up,

but your body is not prepared.

So that sleepiness after waking up to an alarm clock

is due to our body is not prepared for that.

And then the best example is when

the daylight saving time changes,

particularly when we have to wake up one hour early,

what happens, people who have underlying heart condition,

when they're waking up, when the body is not ready

or heart is not ready and all of a sudden

the heart has to start pumping a little bit harder,

then there is chance of heart attack.

And in fact, people have looked at hospital records

and they find that on those days,

there is a sharp rise in heart attacks.

And car accidents.

And car accidents too,

because your brain is not coordinated,

so you cannot make those fine decisions.

So that's a great example of anticipatory activity.

But coming back to digestion, one thing is,

and this is something that many people

might have experienced.

There are many rhythms in our digestive system.

And one of the rhythms is our intestine

has this peristaltic function.

So it kind of contracts and expands,

and that moves food, food doesn't move due to gravity.

So it goes back and forth.

And that peristaltic action actually slows down at night,

few hours after our last meal.

And so that's why when people eat late at night,

for example, then that food doesn't get digested

because there is not enough digestive juice, first thing.

And second, even if it gets digested in the stomach,

it doesn't move properly.

So then the next morning people get up and think,

of course, people consume some alcohol very often,

and then they think that this is hangover.

But those who don't consume alcohol,

then they have the food hangover because it doesn't digest.

So that's one extreme example where food at the wrong time

can, so healthy food at the wrong time can be crap or junk.

Yeah, I've experienced that where if I've worked late

or I couldn't eat dinner or something, and then I get home,

I always debate whether or not to try and sleep.

But if I'm too hungry, oftentimes it's challenging.

And so for me, sometimes consuming something

that at least seems easily digestible,

like yogurt or something in a liquid form,

is better for me than if I eat a meal.

I've made the mistake of going to the refrigerator,

being super hungry and eating a bunch of food

at 10 or 11 p.m. and then falling asleep.

And indeed, the sleep, if I'm tired enough,

can be quite deep, but the next morning,

I feel just completely physically

and cognitively weighed down.

So I think what you just described makes a lot of sense.

So if someone were to select a feeding window,

regardless of whether or not it falls

into classic intermittent fasting,

time-restricted feeding, sounds like eating

your first bite of food and eating your last bite of food

at more or less the same time each day has benefits.

I have this question, you mentioned feeding versus eating.

And I think it's actually not just

a grammatical semantic issue.

And here's why.

We tend to think about when you take your first bite of food

and then when you take your last bite of food.

But of course, food's digested at different rates.

More fat in there is gonna make carbohydrates

digest slower, et cetera.

I mean, there's all these adjustments to the glycemic index

and so forth with foods in combination.

Is it better to think about not eating

but your fed state and blood sugar?

So for instance, I often get asked on social media,

does blank break a fast?

And so I like to think about it scientifically,

like, okay, does plain water break a fast?

No. Does air break a fast?

No.

Does one grain of sugar, of sucrose break a fast?

Well, probably not.

But does one teaspoon of sugar break a fast?

Well, you could say yes, but transiently.

Like, so I mean, when we're talking about breaking a fast,

are we talking about a rise in blood glucose?

Or are there molecular signals downstream

of a rise in blood glucose that cannot be reversed?

In other words, if I'm gonna eat my first meal

every day at noon and I'm gonna eat my last bite of food

at 8 p.m. and at 9 a.m., for whatever reason,

I have coffee with one teaspoon of sugar in it,

I suppose in the strictest sense, I've broken my fast.

But maybe if I went for a hard run that morning,

maybe by 9.30 a.m., I'm back in a quote unquote fasted state.

So what is the fasted state really?

Because when I'm eating at 8 p.m.,

just to give another example,

I start fasting at 8.01, perhaps,

but I have my blood glucose is elevated,

so I'm not really fasted, I'm fed.

It's just that I'm not eating the verb, right?

Okay, so again, I don't wanna get overly detailed

just for sake of getting detail,

but I think a lot of the confusion out there

about what breaks a fast is related specifically

to this issue, which is if I eat a whole pizza

after sitting around all day, it's very different

than if I eat a whole pizza after having run

a 26-mile marathon that day.

Very different metabolically speaking.

So how should people think about fasted versus fed?

Can we be mildly fasted versus severe fasted?

Can we be fed-ish versus very fed?

Anyway, I'll stop asking questions now,

but because they all relate to the same theme.

Yeah, now these are very interesting question,

and then unfortunately, as you might have seen in life,

the most obvious questions are often unanswered

because it's so hard to do these damn experiments

because if you really want to address this in humans,

you have to bring humans, put them in isolation.

Just like you said, I can now imagine planning

five or six different experiments.

Each experiment should involve eight or 10 volunteers,

each gender, sex, and then do it.

So it's difficult.

So now let's go back to see how do we,

let's dissect it in terms of indirect calorimetry.

So for example, indirect calorimetry is based

on this principle that whatever oxygen we breathe in

and carbon dioxide we breathe out,

if we can measure these two,

then we can figure out whether our body in total,

we are not saying whether it's the liver,

gut, or fat, or muscle, in total,

whether it's consuming glucose or fat as energy source.

The idea is when we are without food for several hours,

then ideally our body will tap onto glycogen first

and then do a little bit of fat,

and then when the body is mostly running on fat,

then that ratio of CO2 to oxygen will come to 0.7.

But what is interesting is we can do these experiments

in mice, so we can go to mice and ask,

okay, so what happens in mice?

So in mice, mice are a little bit very different

because mice are not simply little people.

Their metabolism is different.

They store relatively less glycogen than humans do

in terms of total metabolism.

So they, overnight, within 12 to 14 hours,

the RER, respiratory exchange ratio,

or this ratio will go from one,

when they're consuming mostly glucose or carbohydrate

as energy source, it will slow down,

slowly go to 0.7, 0.75.

So after 12 to 14 hours,

they're kind of mostly running on fat.

So now, as we give them food,

within 10 or 15 minutes,

they're not actually consuming couple of grams of food.

They might have consumed, say, 100 or 200 milligram

of that chow, so which is less than, say,

5% of their food.

And then the RER will immediately begin to rise

as if that small amount of food

stopped that fat burning process

and cranked up the carbohydrate burning process.

When you say fat burning process,

you mean body fat stores being burned, right?

Not dietary fat, correct?

Yeah, so it's all body fat.

That's why I said we don't know

where that fat is being burned

because we're just measuring

how much mice is breathing in and out.

So for example, it can be from the skin,

so subcutaneous fat or belly fat.

But not dietary fat.

No, by that time, the dietary fat is already absorbed

and digested and hopefully it's sitting in the liver

or adipose tissue somewhere,

but it's the fat that's body fat.

Yes, thank you, Paul.

Yeah, the reason I ask is that nowadays,

I think more than half of the battles

about nutrition that I see online

relate to this issue where, I won't name names,

but someone will come along and say,

low carbohydrate diet allows you to burn more fat.

And the more nuanced people out there will say,

well, that's true, but you're also talking about dietary fat.

The word fat can confuse people.

I realize you're not doing that.

You are certainly not one of the people guilty of doing this,

but indeed, you eat more fat, you'll burn more fat,

but that doesn't mean you'll burn more body fat.

In fact, I think the data say that under conditions

of caloric restriction, you'll actually burn less.

I hope I don't, I'll probably get pitchforks

sent through the mail toward me on that one.

But I think that's true, whereas people who consume

carbohydrate can still burn body fat,

even though the majority of the fuel they're burning

is from carbohydrates.

So here in this case, for example, for mice,

we know that as soon as they start eating,

the RER goes up.

Coming back to your question,

what would be ideal for us to do?

The experiment would be, okay, so we'll go back to that

and then give the mouse maybe 100 milligram of food,

and mouse runs around in the case,

and then we'll continue to measure to see how long it takes

for the mouse to come back.

So that's one aspect.

So now let's see, let's stay on this,

and then I'll come back and talk about non-caloric food

and whether that is considered.