Dr. Matt Walker: The Science & Practice of Perfecting Your Sleep

- 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 I have the pleasure of introducing

Dr. Matthew Walker as our guest on the Huberman Lab podcast.

Dr. Walker is a professor of neuroscience and psychology

at the University of California, Berkeley.

There, his laboratory studies sleep.

They study why we sleep,

what occurs during sleep, such as dreams and why we dream,

learning during sleep,

as well as the consequences of getting insufficient

or poor quality sleep on waking states.

Dr. Walker is also the author of

the international best selling book "Why We Sleep".

Our discussion today is an absolutely fascinating one

for anyone that's interested in sleep,

learning, or human performance of any kind.

Dr. Walker teaches us how to get better at sleeping.

He also discusses naps,

whether or not we should or should not nap,

whether or not we can compensate for lost sleep,

and if so how to best do that.

We discuss behavioral protocols

and interactions with light, temperature, supplementation,

food, exercise, sex, all the variables that can impact

this incredible state of mind and body that we call sleep.

During my scientific career,

I've read many papers about sleep

and attended many seminars about sleep

yet my discussion with Dr. Walker today

revealed to me more about sleep, sleep science

and how to get better at sleeping

than all of those papers and seminars combined.

I'm also delighted to share

that Dr. Walker has started a podcast.

That podcast entitled "The Matt Walker Podcast",

releases its first episode this month

and is going to teach all about sleep,

and how to get better at sleeping.

So be sure to check out the Matt Walker podcast

on Apple, Spotify or wherever you listen to podcasts.

Before we begin,

I'd like to mention 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 of consumer information

about science and science related tools

to the general public.

In keeping with that theme,

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And now my discussion with Dr. Matt Walker.

Great to finally meet you in person.

- Wonderful to connect.

I mean, it's been too long,

but I suspect it would have been a shorter time

before we'd met lest the pandemic, thank you for coming up.

- No, thank you, yeah,

I'm delighted that we're finally sitting down face to face.

I've been tracking your work both in the internet sphere,

and I read your book and loved it.

And also from the perspective of science,

you actually came to Stanford couple of years ago

and gave a lecture for BrainMind.

- Oh, yeah, yeah, yeah, yeah.

- And there, of course, you talked about sleep

and its utility and its challenges

and how to conquer it, so to speak.

Let's start off very basic, what is sleep?

- Sleep is probably the single most effective thing

you can do to reset your brain and body health.

So that's a functional answer in terms of, you know,

what is sleep in terms of its benefits.

Sleep as a process though,

is an incredibly complex physiological ballet.

And if you were to recognize

or see what happens to your brain

and your body at night, during sleep,

you would be blown away.

And the paradox is that most of us,

and I would think this too, you know,

if I wasn't a sleep scientist,

we go to bed, we lose consciousness for seven to nine hours,

and then we sort of wake up in the morning,

and we generally feel better.

And in some ways that denies

the physiological and biological beauty of sleep.

So upstairs in your brain,

when you're going through these different stages of sleep,

the changes in brainwave activity

are far more dramatic than those that we see

when we're awake.

And we can speak about deep sleep and what happens there,

REM sleep is a fascinating time,

which is another stage of sleep,

often called dream sleep,

which is rapid eye movement sleep,

that stage of sleep some parts of your brain

are up to 30%, more active than when you're awake.

So again, it's kind of violating this idea

that our mind is dormant.

And our body is just simply quiescent and resting.

So I would happy to just sort of double click

on either one of those,

and also what changes in the body as well.

But it is an intense

evolutionary adaptive benefit and system.

That said, though,

I would almost push back against an evolved system

when we think about the question of sleep and what sleep is.

Our assumption has always been that we evolved to sleep.

And I've actually questioned that

and I have no way to get in a time capsule

and go back and prove this,

but what if we started off sleeping,

and it was from sleep, that wakefulness emerged?

Why do we assume that it's the other way around?

And I think there's probably

some really good evidence

that sleep may have been the proto state,

that it was the basic fundamental living state.

And when we became awake, as it were,

we always had to return to sleep.

You know, in some ways, at that point,

sleep was the price that we paid for wakefulness.

And that's another way of describing what sleep is.

But again, I think it sort of denies

that the active state of sleep,

it's not a passive state of sleep either.

And then finally, you can say

what is sleep across different species?

And in us human beings,

and in all mammalian species and avian species as well,

sleep is broadly separated into these two main types.

And we've got non rapid eye movement sleep on the one hand,

and then we've got rapid eye movement sleep on the other.

And we can speak about how they unfold

across a night and their architecture

because it's not just intellectually interesting

from the perspective of what sleep is,

it's also practically impactful for our daily lives.

And I'd love to sort of go down that route too.

But you navigate, you tell me I can.

- No, no, let's definitely go down that route.

So you mentioned how active the brain is,

during certain phases of sleep.

When I was coming up in science,

REM sleep, rapid eye movement sleep

was referred to as paradoxical sleep,

is that still a good way to think about it?

Paradoxical because the brain is so active,

and yet we are essentially paralyzed, correct?

- Yeah, it really is a paradox.

And where that came from

was simply the brainwave recordings,

that if all I'm measuring about you,

is your brainwave activity,

it's very difficult for me

sitting outside of the sleep laboratory room

to figure out, are you awake,

or are you in REM sleep?

Because those two patterns of brain activity

are so close to one another,

you can't discriminate between them.

Yet, the paradox is that when you are awake,

I go in there and you're sort of sitting up,

you're clearly conscious and awake.

But yet, when you go into REM sleep,

you are completely paralyzed.

And that's one of the I think that's part of the paradox.

But the paradox really just comes down to

two dramatically different conscious states.

Yet, brain activity is dramatically

more similar than different.

And the way I can figure out

which of the two you are in

is by measuring two other signals,

the activity from your eyes

and the activity from your muscles.

So when we're awake,

we will occasionally have these blinks,

and we'll have sort of seek heads.

But during REM sleep,

you have these really bizarre,

horizontal shuttling eye movements that occur.

And that's where the name comes from

rapid eye movements.

- Are they always horizontal?

- Mostly, they are horizontal. - That's interesting.

- And that's one of the ways that we can differentiate them

from other waking eye movement activity,

'cause it's not always like

it can be sometimes horizontal,

but can also have diagonal and also vertical in that plane.

But then the muscle activity is the real dead giveaway,

just before you enter REM sleep,

your brainstem, which is where the dynamics of

non REM and REM are essentially played out

and then expressed upstairs in the cortex

and downstairs in the body,

when we go into REM sleep,

and just a few seconds before that happens,

the brainstem sends a signal

all the way down the spinal cord.

And it communicates with what are called

the alpha motor neurons in the spinal cord

which control the voluntary skeletal muscles.

And it's a signal of paralysis.

And when you go into dream sleep,

you are locked into a physical incarceration

of your own body. - Amazing.

- You know, why would Mother Nature do such a thing?

And it's in some ways very simple.

The brain paralyzes the body

so that the mind can dream safely.

Because think about how quickly

we would have all been popped out of the gene pool.

You know, if I think I'm, you know,

one of the best skydivers who can just simply fly,

and I've had some times those dreams, too, you know,

and I get up on my apartment window, and I leap out.

- You're done. - You're done, you know.

So that's one of the sort of

that's part of the paradox of REM sleep,

both it's brain activity similarity,

despite the behavioral state being so different

and this bizarre lockdown of the sort of brain

of the body itself.

Now, of course, the involuntary muscles

thankfully aren't paralyzed.

So you keep breathing, your heart keeps beating.

- Is this why men have erections during REM sleep,

and women have vaginal lubrication during sleep?

- That's one of the reasons

part of the other reason though there

is because of the autonomic activity.

So there is a nervous,

a part of our nervous system

called the autonomic nervous system,

and it controls many of the automatic behaviors.

And some of those are aspects

of our reproductive facilities.

During REM sleep, what we later discovered

is that you go through these bizarre

what we call autonomic storms, which sounds dramatic,

but it actually is when you measure them.

That you'll go through periods

where your heart rate, decelerates and drops

and your blood pressure goes down

and then utterly randomly,

your heart rate accelerates dramatically,

and what we call the fight or flight branch

of the autonomic nervous system

or the sympathetic nervous system,

badly named 'cause it's anything but sympathetic,

it's very aggravating,

that all of a sudden fires up

and then it shuts down again.

And it's not in any regular way.

And it's when you get those autonomic storms,

you get very activated from a physiologic perspective

that you can have these erections

and you have vaginal discharge et cetera.

- But you're totally paralyzed?

- But you are still paralyzed.

There are only two voluntary muscle groups

that are speared from the paralysis, bizarre.

One, your extra ocular muscles,

because if they were paralyzed,

you wouldn't be able to have rapid eye movements.

And the other that we later discovered

was the inner ear muscle.

And we've got no good understanding

as to why those two muscles groups

are speared from the paralysis.

It may have something to do with cranial nerve

but I don't think it's that,

I think it's perhaps something more sensory related.

Some people have argued

that the reason the eyeballs are speared from the paralysis

is because if your eyeballs are left

for long periods of time, inactive,

you may get things such as oxygen sort of issues

in the aqueous or vitreous humor.

And so the eyeballs have to keep draining.

- The drainage systems of the anterior eye

are made to require movement. - Exactly.

- People with glaucoma have deficits in drainage

through the anterior chamber, but there I'm speculating.

I'm also speculating, when I ask this,

I would imagine that there are states in waking

that also resemble slow wave sleep,

or rather that there are states

that slow wave sleep also resembles waking states.

You've beautifully illustrated how REM sleep

can mimic some of the more active brain states

that we achieve in waking.

What sort of waking state that I might have experienced

or experience on a daily basis

might look similar to slow wave sleep,

non REM sleep, if any?

- It's a genius way of thinking about it

turns the tables I love it.

We almost never see anything like the true ultra slow waves

of deep non REM sleep.

So we spoke about these two stages non REM and REM.

Non REM is further subdivided into four separate stages,

stages, one through four,

increasing in their depth of sleep.

So stages three and four that's what we typically call

deep non REM sleep.

Stages one and two light non REM.

- So maybe take me through the arc of a night

just so that.

So I put my head down,

well, for you, what time do you normally go to sleep?

- So I'm usually sort of around about 10:30pm guy.

And usually I'll naturally wake up

sort of a little bit before 7:00,

sometimes before 6:45 or 7:00,

I have an alarm set for 7:04am.

- You heard it here, folks

Matt Walker does use an alarm clock.

- I rarely, rarely I'm usually sort of.

- He doesn't recommend it, but he does use it.

- Yeah, I usually. - You're human after all.

- Oh, I am so human.

And I've had my sleep issues

and I'd love to speak about that too.

But it's only just, you know, in the event that, you know,

'cause I like to keep regularity too.

You've got to keep those two things in balance.

And 7:04 just because, you know, why not be idiosyncratic.

I don't know why we always set things

on these hot numbers.

So yep so when you.

- So you go to sleep around 10:30,

so using you as an example,

because I imagine a number of people

go to sleep at different times.

But 10:30 is about when I go to sleep, 11 is for me.

But so you go to sleep at 10:30,

so for that first, let's say three hours of sleep,

what does the architecture of that sleep look like

as compared to the last three hours

of your sleep before morning?

- Yeah, so I should note that that sort of, you know,

10:30 to 7:00 that's just based on my chronotype

and my preferential it's different for different people.

I'm not suggesting that that's the perfect sweet spot

for humanity's sleep.

It's just my natural sweet spot.

- But I imagine most people probably go to sleep

somewhere between 10pm and midnight.

- It's somewhere between 9 and midnight.

- And most probably wake up between 5am and 7am

or 5:30 and 7:30.

- Yeah, yeah at least in

if you look at sort of first world nations,

that's a typical sleep profile.

So when I first fall asleep,

I'll go into the light stages of non REM sleep

stages one and two of non REM.

And then I'll start to descend down

into the deeper stages of non REM sleep.

So after about maybe 20 minutes,

I'm starting to head down into stage three non REM

and then into stage four non REM sleep.

And as I'm starting to fall asleep,

as I've cast off from the usually with me,

murky waters of wakefulness,

and I'm in the shallows of sleep stages one and two,

my heart rate starts to drop a little bit.

And then my brainwave pattern activity starts to slow down.

Normally when I'm awake, it's going up and down,

maybe 20, 30, 40, 50 times a second.

As I'm going into light, non REM sleep,

it will slow down to maybe 15, 20

and then really starts to slow down

down to about sort of 10 or eight cycles per second,

eight cycle waves per second.

Then as I'm starting to move into

stages three and four, non REM sleep,

several remarkable things happen.

All of a sudden, my heart rate really does start to drop.

Oh, and I'll come back to temperature,

I'm going to write temperature down

'cause I always forget these things.

Now I'm solidly in the foothills of middle age.

So as I'm starting to go into those deeper stages

of non REM sleep, all of a sudden,

hundreds of thousands of cells in my cortex

all decide to fire together

and then they all go silent together.

And it's this remarkable physiological coordination

of the likes that we just don't see

at during any other brain state.

- That's really interesting,

other than recordings from the brains of animals

and a little bit from humans,

I don't think I've ever seen the entire cortex

or even entire regions of cortex light up like that.

- Yeah, it's stunning.

It's almost like this beautiful sort of mantra chant,

or this sort of, you know, it's a slow inhale

and then a meditative exhale, inhale, exhale.

And these waves are just enormous in their size.

- And the body is capable of movement at this time,

there is no paralysis.

- There is no paralysis, but for the most part,

muscle tone has also dropped significantly.

- Interesting. - At that point.

And then you will,

or I will then stay there

for about another 20 or 30 minutes.

So now I'm maybe 60, or 70 minutes

into my first sleep cycle.

And then I'll start to rise back up,

back up into stage two non REM sleep.

And then after about 80 or so minutes,

I'll pop up, and I'll have a short REM sleep period,

and then back down, I go again, down into non REM,

up into REM.

And you do that reliably, repeatedly,

and I will be doing that, and I do do that every 90 minutes.

At least that's the average for most adults,

it's different in different species.

What changes to your question

is the ratio of non REM to REM within that 90 minute cycle

as you move across the night.

And what I mean by this is,

in the first half of the night,

the majority of those 90 minute cycles

are comprised of a lot of deep non REM sleep,

that's when I get my stage three and four

of deep non REM sleep.

Once I push through to the second half of the night,

now that seesaw balance changes.

And instead, the majority of those 90 minute cycles

are comprised either of this lighter form

of non REM sleep, stage two non REM sleep,

and much more and increasingly more

rapid eye movement sleep.

And the implication that

I was sort of speaking about pragmatically is,

let's say that I have to,

and I usually never do early morning flights or red eyes,

just because I'm a mess if that happens,

I'm not suggesting other people shouldn't.

- I'm suggesting people not not do that.

Every time I've taken a red eye or I've done that

two or three days later,

I get some sort of general feeling of malaise,

my brain doesn't work as well,

I think red eyes should be abolished.

For the pilots too I mean, and for the.

- And we can speak about those, there's data.

- And for the emergency room, I mean,

long shifts have been shown to lead to, you know,

physician induced errors that lead to a lot of fatalities.

I mean, there are a lot of reasons why staying up too long,

or being up at the wrong times,

if you're not adapted to it is just terrible.

- You have the data and all of those cases, you know,

particularly physicians too

there was some recent data looking at suicidality.

And the rates of suicide in training physicians

are, you know, far, far above the norm.

And I don't suspect that, you know,

the schedules are helping them

I suspect that sleep is a missing part

of that explanatory equation, but.

- I teach medical students and they they're phenomenal,

but yeah, they're under extremely challenged conditions.

- We shouldn't put them under those conditions.

- [Andrew] No, it's not optimizing performance, I have one.

- But sorry, I was sorry.

- No, no, this is important.

These it's an important digression.

I have one question,

which is you're saying that as across the night,

a greater percentage of these 90 minute cycles

are going to be occupied by REM sleep

as you progress through the night.

I'm aware that, based on work that you've done

and from your public education efforts and others

that we have so called circadian forces,

and we have other forces that are driving

when we sleep and when we want to sleep, etcetera.

Without going into the details of those,

I've a simple question,

the experiment is the following.

Let's say, God forbid,

you are prevented from going to sleep at your normal time

and you stay up for the four hours or five hours

that normally you would be in predominantly slow wave sleep.

- If let's say you finally get to lie down at 3am

a time when normally your sleep would be occupied

mostly by rapid eye movement sleep,

will you experience a greater percentage

of rapid eye movement sleep

because of these so called circadian forces,

meaning that's what's appropriate for that time?

Or will your system need to start

at the beginning of the race that were,

as I'm referring to it, that we're calling sleep?

And for if that's not clear to anybody,

basically, what I'm asking is,

if you are forced to skip

the slow wave sleep part of the night,

will your system leap into rapid eye movement sleep?

Or does it have to start at the beginning

and get slow wave sleep first?

In other words, does one sleep state

drive the entry to the next sleep state?

- Great question, so there is some degree of reciprocity

between the sleep states I should note

that when we drive one of those up,

we often but not always see a change in the other.

There are some pharmacologies that have shown

an independence to that.

And we've also played around with things like temperature,

and sometimes you can, you know,

nudge one and not seem to upset or perturb the other.

But to your, I think, lovely point,

the answer is, it's a mix,

but it's mostly the latter.

Meaning you will mostly go into your REM sleep phases,

and be significantly deficient in your deep sleep.

So just because I start my sleep cycle at 3am,

rather than at 10:30pm,

it doesn't mean that my brain just says,

well, I've got a program,

and I'm just going to run the program,

and the way the program runs

is that we always start with

a first couple of hours of deep sleep.

So we're just going to begin act number one, scene one,

it doesn't do that.

Now, I will get some deep sleep to begin with

and part of that is just because of how sleep works.

Based on how long I've been awake,

longer I'm awake,

there is a significantly greater pressure for deep sleep.

But we actually use exactly what you just described

as an experimental technique

to selectively deprive people

of one of those stages of sleep or the other.

So we will do first half of the night deprivation,

and then let you sleep the second half.

So that means that you will be mostly deep sleep deprived,

and you will still get mostly all of your REM sleep.

And then we switch it,

so you only get your first four hours,

which means you will mostly get deep non REM sleep,

but you will get almost no REM sleep.

So in both of those groups,

they've both had four hours of sleep.

So the difference between them

in terms of an experimental outcome

is not the sleep time

because they both slept for the same amount.

It's the contribution of those different stages.

Now, we actually have more elegant methods

for sort of selectively going in there

and scooping out different stages of sleep.

But that's the way we used to do it old school

was just using this timing difference.

- And who suffers more?

Those that lack the early phase,

and were those that lack the later phase of the night sleep?

In other words,

if I have to sleep only four hours for whatever reason,

am I better off getting the early part of the night's sleep

or the second half of the night sleep?

- Depends on what the outcome measure is.

- So that gets right to the differences

between slow wave sleep and REM.

- Right. - I was probably misinformed.

But my understanding a very crude understanding

I should say before.

- I very much doubt I'll contrary with someone like you.

- Which is that's very nice of you.

The first part of the night

the slow wave sleep is restorative to the musculature

to motor learning, and that the dream content

tends to be less emotional.

The second half of the night,

being more emotional dreams

and sort of the unpairing of the emotional load

of our previous day and other experiences.

So in other words,

if I were to deprive myself, excuse me of REM,

I would be hyper emotional,

not maybe not as settled

with the kind of experiences of my life.

Whereas if I deprive myself of slow wave sleep,

I would feel a more physical malaise.

Is that correct?

Or is that far too simple?

And if it is too simple,

please tell me where I'm wrong?

- No, I think much of that is correct.

And it's sort of that plus.

So for example, during deep non REM sleep,

that's where we get this.

It's almost a form of natural blood pressure medication.

And so when I take that away from you, the next day,

we're usually going to see autonomic dysfunction,

we're usually going to see abnormalities

in heart rate blood pressure.

We also know that during deep non REM sleep,

that there is a certain control of specific hormones.

For example, we know that the insulin regulation

of sort of metabolism,

meaning how will you look

from a regulated blood sugar perspective

versus dysregulated, pre diabetic look of profile.

That's where deep sleep seems to matter

if we selectively deprive you of that we can see.

- Growth hormone. - Growth hormone

is different actually.

So that's a beautiful demonstration

where growth hormone seems to be more REM sleep dependent.

And that's why we can come on to the effects of alcohol

and there's some really impressive

frightening data on alcohol

and it's disruption of sleep.

But then we also know testosterone,

peak levels of testosterone happen during REM sleep.

- So the second half of the night, essentially.

- Which is the second half of the night.

So it really just means that the,

your profile of mental and physical dysfunction

will be different under both of those conditions.

Which one would you prefer?

I would prefer neither of them.

And it really depends on what you're trying to optimize for.

So it's just so complicated,

sleep is just so pluripotent, you know,

it's so physiologically systemic,

that it's almost impossible

not to undergo one of those two things,

just deep sleep deprivation,

or just REM sleep deprivation,

and not show a profile

that you would really prefer to avoid.

And that's the reason from an evolutionary standpoint,

that we've preserved those stages of sleep.

I mean, sleep is just so idiotic, you know,

from an evolutionary perspective.

- Or maybe waking is idiotic.

- Or waking is, you know, well, yeah.

- Based on your previous idea.

- Who've you been talking to?

I think that comment is very specific to me.

Yeah, I am normally always an idiot when working.

But I think this idea that sleep, you know,

is so profoundly detrimental to us,

if you were to take it at face value, you know,

you're not finding a mate, you're not reproducing,

you're not foraging for food,

you're not caring for you're young

and worst of all, you're vulnerable to predation,

on any one of those grounds

sleep probably should have been selected against.

But it wasn't sleep has fought its way through heroically

every step along the evolutionary path.

And therefore, every sleep stage has also survived

as best we can tell.

What that means is that those are non negotiable.

If mother nature had found a way

to even just sort of, you know,

thin slice some of that sleep from us,

there would have been vast, I'm sure evolutionary benefits,

but looks as though she hasn't.

And I'm usually in favor of her wisdom

after 3.6 million years, so.

- Yeah, it's incredible.

I want to introduce a another Gedankenexperiment,

other thought experiment.

So in this arc of the night,

slow wave sleep predominates early in the night,

and then REM sleep.

There's a scenario that many people

including myself experience on a regular basis.

Which is they go to sleep, sleeping just fine,

three, four hours into it, they wake up.

They wake up, for whatever reason, maybe there was a noise,

maybe the temperature isn't right,

we will certainly talk about sleep hygiene, etcetera.

They get up, they go to the restroom,

they might flip on the lights, they might not,

they'll get back in bed

hopefully they're not picking up their phone

and starting to browse and wake up the brain

through various mechanisms

light and cognitive stimulation, etcetera.

They go back to sleep, let's say after about 10, 15 minutes,

they're able to fall back asleep.

And then they sleep till their more typical wake time.

How detrimental is that wake up episode

or event in terms of longevity, learning, et cetera?

I would love to sleep the entire night through every night,

but most nights I don't.

And yet, I feel pretty good throughout the day,

some days better than others.

So if you were to kind of evaluate that waking episode,

and compare it to sleeping the whole night through,

what are your your thoughts on that?

- So I think if you're waking up

sort of frequently, as you're describing,

I would probably get your estate in order

because my guess is within the next year,

you're going to be you're going to be done for,

no I'm kidding you.

Absolutely kidding you.

It is perfectly natural and normal,

particularly as we progress with age, you know,

children tend to have typically more continuous sleep.

Now it's not that they aren't waking up

for brief periods of time they are

and in fact, we all do.

When we come out the other end of our sleep cycle

at the end of our REM sleep period of the 90 minute cycle,

almost everybody wakes up

and we make a postural movement, we turn over

because we've been paralyzed for so long

and the body will also like to shift

it's weight or position.

- Do we ever look around?

Ever open our eyes and look around?

- You, sometimes people will open their eyes,

but usually it's only for a brief period of time

and they usually never commit those awakenings to memory.

Your situation and it's my situation as well,

I usually now at this stage of life,

I don't sleep through the night.

I'll usually have a bathroom break and then I'll come back.

That's perfectly normal.

We tend to forget that in sleep science,

we think of sleep efficiency

so of the total amount of time that you're in bed,

how much of that percent time is spent asleep?

And we usually look to numbers that are above 85%,

or more as a healthy sleep efficiency.

So if you're to think about

me going to bed and I spend, you know,

let's say, eight and a quarter,

eight and a half hours of time in bed,

with a normal, healthy sleep efficiency,

I still may be only sleeping a total

of seven and a half hours,

or seven and three quarter hours.

Meaning that I'm going to be awake in total,

not in one long about,

but I'm going to be awake for upwards of 30 minutes,

net some time.

Sometimes that can be after a 10 minute, you know,

dalliance after having gone to the bathroom,

and I'm just gradually drifting back off again.

Other times, it will just be for a couple of minutes.

And most of those you don't commit.

So I think we need to stop,

we don't need to get too worried about, you know,

periods of time awake,

just because we're not sleeping throughout the night.

I would love to do that, too.

And I remember when that used to happen,

and it still happens occasionally.

- Every once in a while, it feels great when it does happen.

- And it's a lovely thing.

- It's a surprise right?

Like oh my goodness I slept through the whole night.

- It is now a surprise, yeah it is a surprise.

But for the most part,

I think we can be more relaxed about that

where we have to be a bit more attentive, though,

is if you're spending long periods of time,

not being able to get back to sleep.

And usually we define that by saying,

if it's been 20, 25 minutes,

normally, that's the time when we would really say okay,

let's explore this, what's going on?

Let's see what's happening.

The other thing is if it's happening very frequently,

so even if you're, you know,

not awake for 25 minutes stretches,

but you're finding yourself waking up

and being consciously aware that you've woken up

for maybe six, seven or eight times throughout the night

and your sleep is very what we call fragmented

the great science of sleep in the past five or 10 years

has been yes, quantity is important,

but quality is just as important.

And you can't have one without the other

in terms of a good beneficial next day outcome.

You can't just get four hours of sleep,

but brilliant quality of sleep and be unimpaired.

Nor can you get eight hours of sleep,

but have very poor quality of sleep

and be unimpaired the next day.

So that's why I just sort of want to asterisk,

this idea of let's not get too worried

about waking up and having some time awake,

that's perfectly normal and natural.

But if it's happening very frequently throughout the night,

or those periods of time,

or long stretches of time, upwards of 25 minutes,

then let's look into it.

- Well, I can assure you just helped a lot of people

feel better about this waking up episode

that I and many other people experience.

- I hope so 'cause I think it's really important

that we, you know,

I think I've been desperately guilty of perhaps, you know,

early on being too puritanical about, you know,

sleep and I've retrospected,

and I've tried to explore why this was the case, you know,

it was almost sleep or else, dot, dot, dot.

And at the time when I was starting to write the book,

which was back in 2016, you know,

sleep was still a neglected stepsister

in the health conversation of today.

And I could see all of the,

- That has certainly changed.

- And it's changing, you know,

and not because it's my efforts,

but because of all of my colleagues.

- I would say, well,

it's great that you give attribution

to the other people involved.

And of course, it's a big field.

But I think you've done a great service by cueing people

to the importance of this state,

not just for avoiding troublesome outcomes,

but also for optimizing their waking state.

It's really, you know,

I view sleep as this period that feels good,

but we're not aware of how it feels

when we're in it necessarily.

It has tremendous benefits when you're doing it well,

so to speak,

and it has tremendous deficits when we're not.

And I think it was an important thing for you to do

to cue people to this issue.

And I would say mission accomplished,

that people are aware of the need for sleep.

I think that knowing that waking up

in the middle of the night is normal,

provided it's not too frequent is great

and will also help people

who may have been overly concerned about that.

I do want to use this as an opportunity

to raise something about the so called Uberman schedule

not to be confused with the Huberman schedule.

Fortunately, no one has confused those yet.

Some years ago, there was a discussion about

the so called Uberman schedule,

meaning the Superman schedule.

So that's Huberman without an H,

which I have nothing to do with.

If you read your Nietzsche this will have a subtext.

But regardless, the Uberman schedule, as I understand

is one in which the person elects to sleep

in 90 minute, bouts spread throughout the day and night,

in an attempt to get more productivity

and or reduce their overall sleep need.

There was a paper published recently

that explored whether or not this is good or bad for us.

Maybe you just give us the take home message on that.

- Yes, so these Uberman like schedules

and there's lots of different forms of that,

they tried to essentially pie chart the 24 hour period,

into short bouts of sleep with some shorter or no, well,

slightly longer periods of wakefulness,

then short bouts of sleep then wakefulness.

You know, you're, I sort of made it, I think a quip,

it's almost like you're sleeping like a baby, you know,

'cause that's the way that babies will sleep.

- In 90 minute naps.

- That they will have, you know, these brief naps,

then they're awake, then they're asleep

then they're awake.

And to the chagrin of parents across the night,

it's basically the same, they're awake, they're asleep,

they're awake, they're asleep.

And that's more the schedule

that these types of protocols have suggested.

And there was a really great comprehensive review

that found not only that they weren't necessarily helpful,

but they were actually really quite detrimental.

And on almost every performance metric,

whether it be task performance,

whether it be physiological outcome measures,

whether it even be the quality of the sleep

that they were having,

when they were trying to get it,

all of those were in a downward direction.

And it's not surprising if you look at your

the way that your physiology is programmed,

if you look at the way your circadian rhythm is programmed,

none of that screams to us

that we should be sleeping in that way.

- Well, I'm chuckling because

we always hear sleep like a baby.

This is how babies sleep.

And I would say don't sleep like a baby,

sleep like an adult be an adult, get your solid eight hours.

- It's Billy Crystal's line, he was, you know,

a long standing suffering insomniac,

he says I sleep like a baby, I'm awake every 20 minutes.

You know, and I think

this is another one of those demonstrations

that when you fight biology, you normally lose.

And the way you know you've lost

is disease, sickness and impairment.

And I think if you sleep,

in accordance with the natural biological edict

that we've all been given,

life tends to be both have a higher quality

and a longer duration.

- Yeah, I agree.

Along those lines, as a vision scientists,

I've been very excited

by the work on these non image forming cells in the eye,

the so called melanopsin cells

that inform the brain about circadian time of day.

And I'm a big proponent of people getting some sunlight,

ideally sunlight, but other forms of bright light

in their eyes early in the day

and when they want to be awake.

Essentially, during the phase

of their 24 hour circadian cycle

when temperature is rising,

and then starting to get less light in their eyes

as our temperature is going down

in terms of later in the day and in the evening.

Are there any adjustments to that general theme

that you'd like to add?

Or is in any way?

- No, I think that's exactly what we recommend right now.

Which is try to get at least 30 to 40 minutes

of exposure to some kind of natural daylight.

Now, there may be parts of the world where, you know, it's.

- You're from your from a rather cloudy part of the world.

- I am from Liverpool, England,

and the Northwest of England is not known

for its beach resorts and fine weather.

I remember I sort of, I went back home for a trip

when I'd first been out in California,

and I thought, why is the sky so low?

Just you know, constantly we joke that in the UK,

we usually have nine months of bad weather

and then three months of Winter.

And then that's your entire year in terms of climate.

But to come to your point, you're exactly right,

try to get that daylight.

Now it can be you know, working next to a window

and you're getting that natural sunlight.

But that natural sunlight is even on a cloudy day in England

is usually far more potent

than anything that you'll get from indoor lighting,

despite you thinking sort of from a perception wise,

maybe the much closer than I would think.

- Yeah, I've been I'm sorry to interrupt.

I've been a big proponent of

there's a an app called Light Meter, which will

it's a free app, I have nothing to do with it

that will allow you to

get a pretty decent measurement of the amount

of light energy coming toward you.

And if you hold it up to a cloudy morning,

where you don't think it's very bright out

kind of a dismal day,

you'll notice that there'll be 1,000, 2,000,

even you know, 5,000 Lux,

Lux just being a measure of brightness, of course.

And then you can point the same light meter

toward an indoor light that seems very bright

and very intense and it'll say 500 Lux

and you realize that the intensity as we gauge it,

perceptually is not really what the system is receiving.

So outdoor light is key.

How do you get this natural stimulation?

Or I should just say light stimulation early in the day,

what is your typical,

what does Matt Walker do to get this light stimulation?

- I am no poster child,

but usually I will, if I'm working out

I usually work out most days.

And I shopped around and I found a gym

that has huge amounts of window exposure facing to the East.

This is going to sound so ridiculous you know,

Matt Walker chooses a gym on the basis.

- I love it - Of the solar impact

so he cannot you know correct his circadian.

- There are a lot of criteria for selecting gyms,

this one is actually grounded in physiology,

and biology and so.

- And selfishness about my own sleep.

- No it's great.

So you get the your exercise

and your light stimulation simultaneously?

- That's right, yep, yeah.

- And so you're stacking cues for wakefulness

early in the day.

- Exactly, so both exercise and daylight

are wonderful cues for circadian rhythm alignment,

and also circadian rhythm reset each day.

And so I will use both exercise,

I mean, I'm neither a strong morning type

or a strong evening type.

And my preference to exercise

is probably sometime in the middle of the day,

probably somewhere around 1pm sorry, not 1am.

But I'm usually working out probably around

the sort of seven, sort of 45 8am time,

that's usually when I'll start my workout.

And there I will start with cardio

spin bike facing a window.

And luckily, for the most part here in California,

there's usually sunlight coming through.

But it doesn't matter to me

because just as you said,

even when it's a cloudy day

that Lux coming through of light,

the intensity is splendid.

So I would prefer to favor my exercise

just because for efficiency too,

I want to get also working on the day,

I'll try to match my exercise

more with my circadian light exposure

than I would probably if I'm going to

do I really want to crush a workout,

or do I want to just, you know,

make sure it's a good workout?

I would prefer to work out, you know, at a different time.

But I like that because of the daylight.

And we can speak about exercise timing at some point,

because there's a lot of discussion around that,

when is the right time to exercise during sleep.

And we can sort of bust some myths there too.

So I think you're spot on with the suggestion,

get some morning daylight,

try to get that exposure, usually at least 30 to 40 minutes,

there was some great work recently coming out

in the occupational health domain,

where they moved workers from offices

that were just facing walls and you know,

didn't have any exposure to natural daylight.

And then they did a time period during that study

where they actually were in front of a window and working.

And they measured their sleep and their sleep time

and their sleep efficiency increased quite dramatically.

I'm forgetting the numbers now

but I think the increase in total sleep time

is well over 30 minutes.

And the improvement in sleep efficiency was five to 10%.

You know, and if you're batting an 80%, you know,

sleep efficiency average,

we're a bit concerned about that.

But add 10% to that

and now you're in you know,

a great echelon of healthy sleepers.

And all you did was just spend some time

working in front of windows.

- That's great and probably

folks might want to consider

spending a little less time with sunglasses

provided they can do that safely,

you know, driving, etcetera.

You're not alone with your exercise behavior

and facing East.

So the one and only Tim Ferriss told me recently

that his morning routine nowadays

consists of jumping rope while facing East

to get the sunlight stimulation of the eyes.

And as Matt and I both know,

it has to be of the eyes, right?

These portals are the only way

to convey to the rest of the brain and body

about the time of day and wakefulness.

Along the lines of wakefulness,

I have a number of questions about caffeine.

The dreaded and beloved caffeine, I love caffeine,

but I like it in relatively restricted periods of time.

So I'm a big fan of waking up

and even though I wake up very groggy,

allowing my natural wakefulness signals to take hold,

meaning I wake up very slowly,

but I don't drink caffeine right away.

I sort of delay caffeine by a little while,

usually 90 minutes to two hours.

And that idea came to me

on the basis of my understanding

of how caffeine and the adenosine receptor interact.

I have a feeling you're going to pronounce

adenosine differently than I do.

- No, no, I will with that, I will go with adenosine.

- I've tried to go with your skeletal instead skeletal

and synapse and synapse.

- Schedule and schedule. - There we go.

But to make it really simple for folks,

how does caffeine work to make us feel more alert?

And does the timing in which we ingest caffeine

play an important role

in whether or not it works for us or against us?

So maybe we just start with how does caffeine work?

Why is it that when I drink mate or coffee,

which are my preferred sources of caffeine,

do I feel a mental and physical lift?

- Yeah so I'm going to suggest

counter to what most people would think, drink coffee.

- Or mate, is mate okay also?

- [Matthew] Yeah, yeah, yeah.

- Whatever form you enjoy.

- We'll come on to sort of why I suggest that

but when it comes to coffee,

I would say the dose and the timing makes the poison.

So let's start with how caffeine works.

Caffeine is in a class of drugs

that we call the psychoactive stimulants.

So it works through a variety of mechanisms,

one is a dopamine mechanism

dopamine we often think of as a reward chemical or,

but dopamine is also very much

an alerting neurochemical, as well.

And caffeine has some role it seems to play

in increasing dopamine.

But its principal mode of action, we believe

in terms of making me more alert

and keeping me awake throughout the day

is on the effects of adenosine.

And to explain what adenosine is

from the moment that you and I woke up this morning,

this chemical adenosine has been building up in our brain.

And the longer that we're awake,

the more of that adenosine accumulates,

- Is it mask, may I ask,

is it accumulating in neurons in glia,

or in the blood vessels?

Where and is it also accumulating in my body?

Where is this adenosine coming from?

And where is it accumulating?

- Yeah, so the adenosine here that we're talking about

that is creating the sleep pressure

is a central brain phenomenon.

And it comes from the neurons themselves combusting energy.

And as they're combusting energy,

one of the offshoots of that

is this chemical adenosine.

And so as we're awake throughout the day,

and our brain is metabolically very active,

it's accumulating and building up this adenosine.

Now, the more adenosine that we have,

the sleepier that we will feel.

So it really is like a sleep pressure is what we call it.

Now, it's not a mechanical pressure, don't worry,

your head's not going to explode,

it's a chemical pressure.

And it's this weight of sleepiness

that we feel gradually growing

as we get into the evening.

- May I just interrupt you again to just ask

do we know what the circuit mechanism is for that?

I mean, not to go too far down the rabbit hole,

but for the aficionados and for myself,

we have brain mechanisms like locus coeruleus

that are release things that our brain areas

locus coeruleus is just being a brain area, of course

that release things that proactively create wakefulness.

So are those neurons shutting down

as a consequence of having too much adenosine?

Or are there areas of the brain

that promote sleepiness that are getting activated?

Because these, you can imagine

both things working in parallel,

one or the other would accomplish the same endpoint?

- Yeah and it's both.

And so there are two main receptors for adenosine

the A1 receptor and the A2 receptor.

And they have different modes of activating brain cells

or inactivating or decreasing the likelihood of firing.

And adenosine works in this beautiful, elegant way,

where it will inhibit and shut down

the wake promoting areas of the brain

whilst also increasing and dialing up the volume

on sleep activating,

sleep promoting range.

- Biology is so beautiful.

- [Matthew] Oh it's fantastic.

- There's a push pull,

I mean, and we could have a larger discussion

at some point about that,

everything seeing dark edges seeing light edges.

Our ability to smell or to sense pressure on this,

everything's a push pull in Biology.

- Oh it's great, yeah, yep.

- So this is another example where as I am awake longer,

adenosine is released in the brain.

And my wakefulness areas are being actively shut down

by that adenosine

and my sleepiness brain areas, so to speak,

are being promoted to be more active, is that correct?

- That's right and it's a very progressive process.

It's not like a step function, where

and sometimes that happens occasionally,

but it's usually because you've been sort of driving through

and as we'll come on to have caffeine in the system,

and then all of a sudden you just hit a wall

and it just, you know engulfs you

and you go from zero to the one of sleepiness

within a short period of time.

- What explains the fatigue after a hard conversation?

The desire to go to sleep

or desire to go to sleep during a hard conversation?

- That's an interesting one.

I think it's usually just based on

personality type interactions.

And for the most part.

- Not that I've ever experienced that before.

- No people with you don't, but with me, they.

- Oh no, no, I've experienced the desired to

some conversations, I'm halfway through them

and I feel like I want to take a nap.

- Yeah. - Right.

- And I would love to look at you know,

people's sleep history.

We've sort of seen that time and time again,

but and then it could be, you know, with folks like me,

people just lose the will to live

within about five minutes of speaking with me, so.

- Not true, they hear that sleep is important.

[cross talking]

- Unrelated. - [Andrew] That's awesome.

- And that's flattery, that's great.

But so the way that then caffeine comes into this equation,

as they're saying, it's usually a kind of a linear process.

Or maybe it's probably closer to an exponential

in terms of your subjective feeling of sleepiness.

And we haven't really been able to measure that in humans,

because normally, we it's hard to actually, you know,

stick something into the brain and be, you know,

sucking, siphoning off stuff every couple of minutes,

as you could do in animal studies.

And keep asking people every couple of minutes,

how sleepy do you feel, how sleepy?

And track to see if there's a linear rise in, you know,

adenosine, which then creates

an exponential rise in subjective sleepiness

or what the dynamics are,

but I'm kind of nerding out.

Caffeine comes into play here,

because caffeine comes into your system

and it latches on to those welcome sights of adenosine

the adenosine receptors.

But what it doesn't do is latch on to them

and activate them.

Because if it was doing that,

then it would, you know, in lots of ways

it would dial up more sort of sleepiness.

It does the opposite.

The way that caffeine works is that

it comes in, competes with quite sharp elbows

with adenosine competitively forces them out of the way,

hijacks that receptor by latching onto it,

but then just essentially blocks it.

It doesn't inactivate the receptor,

it doesn't activate the receptor,

it functionally inactivates it

in the sense that it takes it out of the game for adenosine.

So it's like someone you know, coming into a room,

and you're just about to sit down on the chair,

and caffeine comes in and just pulls out the chair.

And you're like, well, now I've got nowhere to sit.

And caffeine just keeps pulling out the chairs

from adenosine and adenosine even though

it's at the same concentration in your brain,

your brain doesn't know

that you've been awake for, you know, 10 hours, 16 hours

at that point when you've downed a cup of coffee.

Because all of that adenosine that's still there

can't communicate to the brain

that you've been awake for 16 hours because.

- But the adenosine is still in brain circulation.

- Correct. - So the real question is

what happens when caffeine is dislodged

from the adenosine receptor?

- Unfortunate things happen.

And that's what we call the caffeine crash.

Which is caffeine has a half life

and it's metabolized and.

- Do you recall what the half life is?

- Yeah, the half life is somewhere between

five to six hours.

And the quarter life therefore

is somewhere between 10 to 12 hours.

It's variable, different people

have different durations of its action,

but for the average adult five to six hours.

That variation, we understand it's down to a liver enzyme

or a set of liver enzymes

of the class that we call the cytochrome P450 enzymes.

And there are I think last I delved into the data,

which is pretty recently,

there are two gene variants

that will dictate the enzymatic speed

with which the liver breaks down caffeine.

And that's why you can have some people

who are very sensitive to caffeine

and other people who say, you know,

it just doesn't affect me really that much at all.

- These are the people that have a double espresso

after a 9pm dinner and can sleep just fine.

- Well, and we'll come onto.

- Well at least subjectively

they think they are sleeping.

- Subjectively, yeah, and we should speak about

that assumptive danger too.

So then the caffeine is in the system

and after some time period,

it will be inactive in the system.

So let's say that, you know,

I've been awake for 12 hours now.

And it's you know, 8pm

and I'm feeling a bit tired,

but I want to push through and I want to keep working

for another couple of hours,

so I have a cup of coffee.

All of a sudden I was feeling tired,

but I don't feel like I've been awake for 12 hours anymore.

Because with the caffeine in the system,

maybe only half of that adenosine

is being communicated through the receptor to my brain.

100% of the adenosine is still there,

only half of it is allowed to communicate to my brain.

So now I think oh I haven't been awake for 12 hours,

I've just been awake for six hours, I feel great.

Then after a few hours,

and the caffeine is starting to come out of my system,

not only am I hit with the same levels of adenosine

that I had before I'd had the cup of coffee

several hours ago,

it's that plus, all of the adenosine

that's been building up during the time

that the caffeine has been in my system.

- So sort of an avalanche of adenosine.

- It is a tsunami wave, yeah and that's the caffeine crash.

- And it's interesting because the caffeine crash

at two o'clock in the afternoon when you have work to do

is a terrible thing.

But what about the person,

maybe this person is me in my 20s,

who says, I'm going to drink caffeine all day long.

And then I want the crash.

Because at nine or 10pm, if I stop drinking caffeine

at say, 6pm, and I crash,

then I crash into a slumber, a deep night of sleep.

Is that sleep really as deep as I think it is?

Because given the half life of caffeine

that you mentioned a few moments ago,

I have to imagine that

having some of that caffeine circulating in my system

might disrupt the depth of sleep,

or somehow the architecture of sleep in a way

that even if I get eight,

or who knows even 10 hours of sleep,

it might not be as restorative as I would like it to be.

- Yeah, and that is the danger,

just sort of that, you know,

those people that you described who say,

and I, a lot of them will speak with me too

say, look, I can have two espressos with dinner

and I fall asleep fine and I stay asleep.

Because usually those are the two phenotypes

that we typically see with too much caffeine.

I just can't fall asleep as easily as I want to,

or I fall asleep, but I just can't stay asleep.

And caffeine can do both of those things quite potently.

- How late in the day do you think is assuming somebody,

translate this folks, if you go to bed earlier or later,

you have to shift the hours accordingly.

But given somebody who typically

gets into bed around 10:00, 10:30,

and falls asleep around 11:00, 11:30.

When would you recommend they halt caffeine intake?

And these are not strict prescriptives,

but I think people do benefit

from having some fairly clear guidelines

of what might work for them.

Would you say cut off caffeine, by what time of the day?

- I would usually say

take your typical bedtime

and count back sort of somewhere between 10 to eight hours

is probably getting a little bit close.

But take back sort of 10 hours or eight hours of time,

that's the time when you should really stop, you know,

using caffeine is the suggestion.

And the reason is because for those people

who even just keep drinking up until you know,

into the evening, you're right,

that they can fall asleep fine,

maybe they stay asleep,

but the depth of their deep sleep is not as deep anymore.

And so there are two consequences.

The first is that for me,

and it can be up to by 30%,

and for me to drop your deep sleep by 30%,

I'd have to age you by between 10 to 12 years,

or you can just do it every night to yourself

with a couple of espressos.

The second is that you then wake up the next morning,

and you think, well, I didn't have problems falling asleep

and I didn't have problems staying asleep,

but I don't feel particularly restored by my sleep.

So now I'm reaching for three or four cups of coffee

the next morning,

rather than just two or three cups of coffee.

And so goes this dependency cycle,

that you then need your uppers

to wake you up in the morning,

And then sometimes people will use alcohol in the evening

to bring them down because they're overly caffeinated

and alcohol, and we can speak about that, too,

also has very deleterious impacts on your sleep as well.

So you're right that it's not just the quantity

of your sleep, or even difficulties falling

or staying asleep,

it can also be deep sleep.

But here again, I think, you know,

I don't want to be frightening people.

And I mentioned this before,

I think one of the real problems that I

or mistakes that I made,

because I didn't you know,

I'd never had much public exposure before the book.

And I was so saddened by you know,

the disease and the suffering

that I was seeing as a consequence of a lack of sleep

in our society.

And the fact that it wasn't really

being discussed very much.

I sort of came out, you know, a little bit headstrong,

more than a little bit headstrong.

And I think I was, you know, perhaps too much gas pedal

and too little, you know, break as it were.

And I don't think that's the right way

to approach a health message within the public sphere.

And I've become much softer

in how I think about these things.

I have ideas about

what the ideal world looks like for sleep.

But I also realize that none of us

live in this thing called the ideal world.

- We certainly don't.

- So, you know, I want to be really mindful of that,

and I think I've done a really bad job

of being sort of too forthright,

particularly for people who struggle with sleep, you know,

early on, when I would offer

these sort of messages about sleep.

I want to be, you know,

I want to be theoretical when it comes to the science,

I want to be faithful to the science.

But I also don't want to go out

and scare the living daylights out of people,

particularly people who are struggling with their sleep,

'cause it's probably only going to make matters worse.

So I've been beautifully schooled by

learning how to be a slightly better public communicator.

I'm nowhere near of the standing that you are,

you are very elegant and it's very intuitive to you.

I'm still with training wheels,

but I'm getting a little bit better.

But I just want to say that

when I'm speaking about caffeine,

'cause it sounds as though I'm very

sort of overt about it.

But I will come back to why I say drink coffee.

But I just want to make that point.

- Yeah, well, I appreciate you making that point.

And I'm sure our listeners will too.

I still will stand behind my statement,

which is that what you've done for the notion

that sleep is vital for all aspects of health

and for performance, mental and physical and wakefulness,

the message and the packaging it was contained in

and is has been clearly clearly net positive

people needed to be cued to this.

- Thank you. - The I'll sleep

when I'm dead mentality is one that I had,

it's one that other people have.

People in a huge number of vital communities,

not just your students, but also people

that this the messaging that you provided

and continue to provide

has positively impacted the first responder community,

the medical community,

there're still steps that need to be taken

the military community,

and of course, the civilian community.

And so I think these adjustments about

yeah, caffeine is okay,

just restricted to the early part of the day,

if you can, most days,

I mean, I think the law of averages.

It's like the light viewing behavior

I think it is critical to view sunlight or natural,

some other form of bright light early in the day

but if you miss a day,

it's not that your whole system

is going to dissolve into a puddle of tears.

That'll happen on the second or the third day,

no I'm kidding, you've got a couple of days.

Biology works in averages

except with respect to accident or injury.

A car accident is a car accident, right?

You don't get to have three of those

before the brain damage occurs

if the accident's severe enough.

But with sleep behavior,

these homeostatic type behaviors, or with food,

one chocolate sundae, is it going to kill you know? No.

Every night? Yeah.

It's going to make you demented and kill you early.

We know this.

And so I think the middle ground

is often a hard place to achieve.

So I think you've done a phenomenal job.

But I appreciate you raising these points.

And I think it's clear that we all need to

that we all can and should do certain things better,

including being gentle with ourselves from time to time

when we deviate from these ideal circumstances.

Along these lines, I do want to talk about alcohol

because I think caffeine and alcohol

represent the the kind of two opposite ends of the spectrum.

Clearly there are other stimulants.

There your Adderalls and your high energy drinks

that people use.

But alcohol and caffeine are the most commonly consumed

stimulants and sedatives,

depressants as they're sometimes called.

So what happens when somebody has a glass?

We always hear a glass or two of wine in the evening

or a cocktail after dinner or before dinner,

how does that impact their sleep?

And then we'll be sure to circle back

in terms of what is reasonable ranges of behavior

when it comes to avoiding alcohol

or if it's age appropriate, et cetera, enjoying alcohol?

- Yeah, so alcohol,

if we're thinking about classes of drugs,

they're in a class of drugs that we call the sedatives.

And I think one of the first problems

that people often mistake,

alcohol is often used as a sleep aid

for people who are struggling with sleep

when things like over the counter remedies, etcetera,

or herbal remedies have just not worked out for them.

And alcohol, unfortunately, is anything but a sleep aid.

The first reason that most people use it

is to try and help them fall asleep.

- So and this process of

this event that we call falling asleep,

I have to imagine is a process.

- It is a process. - Like everything in biology,

and that that process involves in some way,

as we talked about push pull before turning off

thinking, planning, et cetera,

and turning on some sort of relaxation mechanism.

I have to imagine that these two things

are knobs turning in opposite directions

that gives us this outcome we call falling asleep.

Alcohol, it seems is helpful for some people

to turn off their thoughts or their planning.

Is that right?

- Yes, it is.

And so I think, you know,

if we look at the pattern of brain activity,

if I were to place you inside an MRI scanner,

where we're looking at the activity of your brain

and watch you drifting off,

some parts of your brain will become less active.

Other parts will become more active.

And this is the push pull model.

It's inhibition excitation.

But alcohol is quite different in that regard.

Alcohol is because it's a sedative,

what it's really doing

is trying to essentially knock out your cortex.

It's sedating your cortex,

and sedation is not sleep.

But when we have a couple of drinks in the evening,

when we have a couple of nightcaps,

we mistake sedation for sleep

saying, well, I always when I have a couple of whiskies

or a couple of cocktails,

it always helps me fall asleep faster.

In truth, what's happening is that

you're losing consciousness quicker,

but you're not necessarily falling

naturalistically asleep any quicker.

So that's one of the first sort of things

just to keep in mind.

The second thing with alcohol

is that it fragments your sleep.

And we spoke about the quality of your sleep

being just as important as the quantity.

And alcohol through a variety of mechanisms,

some of which are activation

of that autonomic nervous system,

that fight or flight branch of the nervous system.

Alcohol will actually have you waking up

many more times throughout the night.

So your sleep is far less continuous.

Now, some of those awakenings

will be of conscious recollection the next day,

you'll just remember waking up,

many of them won't be.

And so but yet, your sleep will be littered

with these sort of punctured awakenings

throughout the night.

And again, when you wake up the next morning,

you don't feel restored by your sleep, you know,

fragmented sleep or non continuous sleep

in this alcohol induced way,

is usually not good quality sleep,

but you feel great on the next day.

The third part of alcohol in terms of an equation

is that it's quite potent at blocking your REM sleep,

your rapid eye movement sleep.

And REM sleep is critical

for a variety of cognitive functions.

Some aspects of learning and memory

it seems to be critical

for aspects of emotional and mental health.

- You've described it before

as a sort of self generated therapy

that occurs while we sleep.

- Yeah, it's overnight therapy, you know,

it's emotional first aid.

- Certainly people that don't get enough sleep

are very easy to derail emotionally.

Not that one would want to do that to people,

but we all sort of fall apart emotionally.

I always think of it as almost like

our skin sensitivity can be heightened.

- Yes, absolutely. - When we are sleep deprived.

Our emotional sensitivity is such that

when we're sleep deprived,

such that it takes a much finer grain of sandpaper

to create that kind of friction, things bother us.

- [Matthew] Threshold to trigger.

- Even online comments bother us when we're sleep deprived.

and never when we're well rested.

- I would love to say that I never look at them,

except I look at.

- Well actually, here I.

- [Matthew] Maybe every one of them.

- Here I will editorialize

because the notion of not looking at comments

is unreasonable to ask of any academic,

because academics we are all trained

to look at our teaching evaluations.

And just like with online comments to ignore 20% of them,

no, I'm kidding.

We look at them all in any event.

So in terms of translating this to behavior,

I'm not, I don't particularly enjoy alcohol,

I guess I might be fortunate in that sense.

But I also have never really experienced

the pleasure of drinking alcohol.

I sometimes like the taste of a drink,

but I never like the sensation.

So that's, I don't have a lot of familiarity with this,

but many people do, and I understand that.

So let's say somebody enjoys a glass of wine or two

with dinner and they eat dinner at 7pm.

Is that likely to disrupt their sleep at all?

Let's just sort of,

let's make this a series of gradations.

- And the answer is yes.

I think once they just looked at a single glass of wine

in the evening with dinner,

and I would be untruthful if I didn't just simply say

it has an effect.

And we can measure that in terms of.

- Less REM sleep.

- Less REM sleep

and one of the fascinating studies

I can't remember what dose I think they got them close to

a standard illegal blood alcohol level,

so maybe they were a little bit tipsy.

And yes, you see all of the changes that we just described,

they sort of lose consciousness more quickly,

they have fragmented sleep,

and they have a significant reduction in REM sleep.

But what was also interesting

because REM sleep, as we spoke about before,

is a time when some hormonal systems

are essentially recharged and refreshed

growth hormone being one of them,

there was well over a 50% five zero drop

in their growth hormone release

during alcohol laced sleep at night.

- And growth hormone is so vital for metabolism

and repair of tissues.

- Yeah, it's not just for kids.

- [Andrew] Keeping body fat low.

- This is essential in adults.

- It's essential, along those lines,

I just want to highlight the fact that

this information that you're sharing

that growth hormone is released

is strongly tethered to the presence of

healthy amounts of REM sleep is interesting to me,

because I always thought the growth hormone was released

in the early part of the night.

- Well, it is released across both of those,

but across the different stages,

but what we also know is that when you disrupt REM sleep,

there are those growth hormone consequences.

So it's not an exclusive system

just like with testosterone,

we can see changes throughout non REM sleep,

but if you ask when are the peak release rates

of testosterone, it's right before we go into REM sleep,

and then during REM sleep.

- And of course, testosterone being important,

both for males and females.

- For men and women, yeah.

- Right, for libido and tissue repair and well being.

Nobody, regardless of chromosomal, hormonal,

or any other background

wants to have their normal levels

of testosterone reduced acutely,

that's just a bad

it equates to a terrible set

of psychological and physical symptoms.

- Yeah, and the mortality risk

that's associated with low testosterone

is non trivial. - Prostate cancer.

- Right, exactly, you know.

So coming back to just the point on REM sleep

that you mentioned regarding emotional instability,

and we see that that's one of the things

one of the most reliable signatures of just

insufficient sleep doesn't have to be sleep deprivation.

What we've discovered over the past 20 years

here at The Sleep Center,

is that there is no major psychiatric disorder

that we can find in which sleep is normal.

And so I think that firstly told us

there is a very intimate association

between your emotional mental health and your sleep health.

But when it also comes to REM sleep,

I think what's fascinating is that

it's not just about your emotional health,

it's not just about your hormonal health

we've also been seeing other aspects of you know, cognition.

But then there was a report,

I think it could have been about two years ago,

out of Harvard, I think it was Beth Clements group.

They found that,

and they replicated it in two different large populations.

If you look at the contribution

of different sleep stages to your lifespan,

REM sleep was the strongest predictor of your longevity.

And it was a linear relationship.

It wasn't it sort of one of these U shaped

or J shaped curves that we often see with total sleep,

and mortality risk, it really was linear.

That the less and less REM sleep that you were getting

the higher and higher your probability of death.

And then they did.

- Was that death due to natural causes or accident?

'Cause I can imagine if you're not getting enough REM sleep,

you're more likely to drive off the freeway,

step off a cliff.

- I think it was all cause mortal.

- You just make bad decisions about anything

in love relationships, which can also be life threatening.

- Yeah, I've tried to lean into that

and claim that with those bad relationship situations,

oh, I just didn't have enough REM sleep last night.

- Blame it on the sleep.

- [Matthew] My darling you know.

- The REM sleep difference.

- And, but she's far wiser than I thought.

But, so they did this great machine learning analysis

and I may get these numbers backwards.

But I think for every 5% reduction in REM sleep,

there was a 13% associated increased risk of mortality.

And I could have, I'll have to go back and check.

But to me, and in the machine learning algorithm,

what they ultimately spat out

was that of all of the sleep stages,

REM sleep is the most predictive

of your longevity of your lifespan.

So we often, I hear people saying,

how can I get more deep sleep?

Or they sometimes say

how can I get more dream sleep?

And my answer is a question.

Why do you want to get more of that?

And they'll say, well, isn't that the good stuff?

And I'll say, well, actually all stages have good sleep.

- It's all the good stuff.

Well, it's like the exercise question

and it took decades,

for people to understand that moving around

for about 150, probably 180 minutes a week

at doing endurance type work, zone two cardio type work,

it is correlated with living longer,

feeling better, less diabetes, etcetera.

There's really no way around it.

I mean, you can ingest Metformin until the cows come home,

you can take NMN,

all of which I think have their place in certain contexts

I'm a big fan of the work surrounding all those protocols.

- Yeah likewise. - But without getting

proper amounts of movement, meaning sufficient numbers,

it doesn't matter how many 12 minute exercise regimes

you follow per week, you need that threshold level.

And it sounds like the same is true of REM sleep

and total amount of sleep.

There's just you pay the piper somehow.

- Yeah, the return on investment I mean, to flip the coin,

the return on investment is astronomical, you know,

I think of sleep it is the tide that moves, you know,

that raises all of those health boats.

- And the most fundamental layer

of mental and physical health.

Whenever people ask me, even though I'm not a physician,

they'll ask me, you know,

what should I take or what should I do?

The first question is always, how's your sleep?

- Great, I love it.

- Meaning how well do you sleep every night

and how long do you sleep?

And I always recommend your book,

I always recommend your podcast, you know,

the podcasts you've been a guest on, etcetera.

Who knows, maybe you'll even release your own podcast

at some point soon and keep

because I do think people need to hear from you more often.

One thing I don't want to return to the notion of

public health discourse too much.

But I do want to say one issue with books in general,

is that they can be revised,

but it's more or less a one and done kind of thing

until the next book comes out.

- Yeah, yeah - One thing I like

about the podcast format

is that updates can be provided regularly.

Corrections and updates as new data come out.

And so that's a wonderful aspect to this format.

And hopefully the format that you'll be embracing,

I think the world needs to hear more from you

more often, about sleep, and its various contours, not less.

And so I do have a question about drinking alcohol.

Not that we want to promote day drinking,

but let's say that the one or two glasses of wine

or cocktail is consumed with lunch,

something that isn't traditionally done nowadays,

or in a late afternoon happy hour type cocktail.

And then one is going to sleep seven or eight hours later,

do you think that

that will improve or somehow mitigate

the effects of alcohol?

Or if you have a drink,

are you are you basically screwed for the next 24 hours?

- No, I think there's going to be a time window dependency.

Now, I don't know of anyone who has essentially done

what you and I would like,

which is the time separation dose dependent curve,

where okay, you drink at 10am, then or 11, 12

one, two, three, four, five

all the way up to you know, 10pm

and estimate, what is the blast radius?

And is it linear?

Or is it nonlinear?

Is it such that only when you drink in the last four hours?

Do you just hit this exponential and it's bad, bad bad?

Or is there some other curve

that we could imagine there will be many possibilities.

But certainly what we know is that the less alcohol

and the less

and more specifically the metabolic byproducts,

aldehydes and ketones,

they're the sort of the nefarious players.

- And not the ketones that people are all excited about

the other ketones,

[cross talking]

the chemists know what we're referring to.

- But this is not about ketogenesis,

please don't think that.

- This is not about ketogenesis,

there are ketone bodies,

and that are released after ingesting alcohol

that are not of the positive sort

that a ketogenic diet might promote.

- Right, so I think in terms of that alcohol profile,

we certainly know that, you know,

as you're heading into the evening hours,

once again, timing and dose make the poison.

But I think it's also important, once again,

from that public message standpoint, and thank you,

I think I am leaning into

the sort of the podcast consideration arena, at some point,

but I don't want to be puritanical here, you know,

I'm just a scientist,

and I'm not here to tell anyone how to live.

All I'm trying to do is empower people

with some of the scientific literature regarding sleep.

And then you can make whatever informed choices

that you want.

Now, unlike you, it turns out, I'm not a big drinker.

It's just because I've never liked the taste.

And I'm surprised that they haven't taken away

my British passport because I don't like lager or beer.

But I also want to say that life is to be lived

to a certain degree, it's all about checks and balances.

So, you know, if I go out and you know,

I have an ice cream sundae, I'm not big on those either,

but, you know, sure, I know that my you know,

blood glucose is not going to be ideal

for another 12 hours maybe.

That's just the price you pay

for having some kind of relaxed, fun life.

I don't want to look back on life

and think, gosh, you know, I lived until I was, you know,

111 and it was utterly miserable you know.

- Right. - So, but it's all about

some kind of a balance.

And my job is not to tell people a prescription for life,

it's just to offer some scientific information.

- No, I think you're doing a terrific job of that.

People are I always say we have all these neural circuits

and if it's working properly,

we all have a circuit that allows us

to skip over information or as we wish, right,

if the circuits between your brain and your thumbs

are working you can slide right along

you can drop to the next content however you like.

I would like to ask about marijuana and CBD.

This is a discussion that I think five years ago

would have ventured into the realm of illegal

but now in many places not all

medical marijuana is approved or is legal.

And certainly it's in widespread use.

Certainly not recommending people do it.

I have my own thoughts about marijuana CBD.

I've been fortunate, I suppose

that I don't particularly like marijuana or CBD.

I don't even know if I've ever tried CBD.

First of all, does marijuana disrupt the depth of sleep,

the architecture of sleep?

And if so, as with alcohol and caffeine

does when you ingest it

or when it's in your bloodstream does,

relative to when you go to sleep,

does that play an important role?

So does marijuana disrupt sleep?

- Yeah, it does.

And there's a pretty good amount of data on

so we can break sort of cannabis down into

two of its key ingredients.

We've got THC tetrahydrocannabinol, and we've got CBD

and CBD is sort of the less psychotic

what we think of as the non psychoactive components.

In other words, when you take CBD, you don't get high.

If you take THC, you can get high.

That's the psychoactive part of the equation.

- Are both considered sedatives in the technical sense?

- No, they're not.

Neither of them have that class right now.

THC can, seems to speed up the time

with which you fall asleep.

But again, if you look at the electrical brainwave signature

of you're falling asleep with and without that THC,

it's not going to be an ideal fit.

So you could argue it's non natural,

but many people use THC for that fact,

because they find it difficult to fall asleep.

And it can speed the onset

of at least non consciousness,

I guess is the best way of describing it.

But there are problems with THC.

And they are twofold.

The first is that it too,

but through different mechanisms seems to block REM sleep.

And that's why a lot of people when they're using

will tell me look, you know,

I definitely, I was dreaming.

Or I don't remember, you know many of my dreams.

And then when they stop using THC,

let's say I was having, you know, just crazy, crazy dreams

and the reason is because there is a rebound mechanism.

REM sleep is very clever.

And alcohol is the same way in this sense,

it's the same homeostatic mechanism.

Some people will tell me,

look, if I have a bit of a wild Friday night

with some alcohol, you know,

maybe I'll sleep late into the next morning.

And I'll just have these really intense dreams.

So and I thought I wasn't having any REM sleep,

well, the way it works is that

it's during in the middle of the night, really,

when alcohol blocks your REM sleep.

And your brain is smart

it understands how much REM sleep you should have had,

how much REM sleep you have not

because the alcohol has been in the system.

And finally, in those early morning hours,

when you're getting through to sort of, you know,

[cross talking]

six, seven, 8:00am all of a sudden,

your brain not only goes back

to having the same amount of REM it would have had,

it does that plus it tries to get back

all of the REM sleep that it's lost.

Does it get back all of the REM sleep?

No, it doesn't.

It never gets back all of the REM sleep, but it tries.

And so you have these really intense periods of REM sleep.

Hence you have really intense bizarre dreams.

And that's what happens also with THC,

you build up this pressure for REM sleep,

this debt for REM sleep,

will you ever pay it back?

Doesn't seem as though you get back

everything that you lost,

but will you get back some of it?

Yes, the brain will start to devour more

because it's been starved of REM sleep for so long.

But one of the bigger problems with THC

that we worry about is withdrawal dependency.

So as you start to use THC for sleep,

there can be a dependency tolerance.

So you start to need more to get the same sleep benefit.

And when you stop using,

you usually get a very severe rebound insomnia.

And in fact, it's so potent

that it's typically part of the clinical

withdrawal profile from THC from cannabis.

- And there's anxiety withdrawal.

I you know, I don't ask anybody to change their behavior,

we just as you said, we try and inform people

about what the science says

and let them make choices for themselves.

People who are regular pot smokers,

if you many of will insist they're not addicted,

and maybe indeed they don't actually follow the profile

of classical addiction, I don't know.

I'm guessing some do, some don't.

But if you ask them

well, what if I took away all marijuana consumption for,

I don't know, two weeks?

That thought scares many of them.

And many of them will experience

intense anxiety without marijuana,

which speaks to perhaps not addiction,

but a certain kind of dependency.

And again, you know, I know many pot smokers,

some of whom have jobs

that are quite high performing and they manage.

- Here in Berkeley, I don't know any of those.

- Yeah, none of those, right.

What about CBD?

I mean, we hear so much about CBD,

I've been a little concerned about the fact that

the analysis of a lot of CBD supplements out there

has confirmed that much like with melatonin,

the levels that are reported on the labels,

in no way shape, or form,

match the levels that are actually contained

in the various supplements.

Sometimes the levels are much higher

than they're reported on the labels.

Other times, it's much lower.

What does ingesting CBD do

to the architecture and quality of sleep?

- Right now, I don't think we have enough data

to make some kind of, you know, meaningful sense out of it.

I think the picture that is emerging, however,

is probably the following.

Firstly, CBD does not seem to be detrimental

in the same ways that THC is.

So we can start by saying

does it create you know, potential problems,

not of the nature necessarily that we see with THC.

But the devil is a little bit in the details

from the data that we do have

and it comes on to your valid point of purity.

At low dose, CBD can seem to be wake promoting.

So in lower doses,

let see sort of five or 10 milligrams

and trying to remember some of the studies

off the top of my head,

there it actually may enhance wakefulness

and cause problems with sleep.

It's only once you get into the higher dose range,

that there seem to have been some, you know,

increases sorry, increases in sleepiness,

or sort of sedation like, increases.

And that's usually I think, above about 25 milligrams,

as best I can recall from the data.

And then when we look in animal models,

you typically see the same type of profile too.

So then the question becomes

and now again, you just don't know about, you know, purity.

It's very difficult, although I think, and again,

I'm not a user,

not necessarily because I you know,

have anything against it.

It's just that's not, you know, necessarily my cup of tea.

There are some firms that are now doing

third party independent laboratory tests.

I don't know how gamed that is,

so I've got no sense of it.

- I think some supplement companies

are quite honest and accurate

about the amounts of various substances

that are in their products and some are not.

And I think there's just a huge range.

I think the FDA is starting to explore CBD there

I certainly I saw some grant announcements

to explore the function of CBD.

Most of the work on CBD is being done by the general public

adjusting it and seeing how they feel.

I gave it to my dog who was

had some dementia related sleep disturbances,

and it actually created a heightened wakefulness

it completely screwed up his sleep.

- Okay, it sounds as though it just wasn't.

- He's a bulldog.

So if he's going to get access to sleep, he's going to take it.

- Okay. - Really messed him up,

took him took it away, he did better.

But you know, that's a canine, so.

- Right, and it could have been, you know,

sort of dose related too.

- Or binders or other things that are in there, sure.

- Correct, yeah and we,

but right now, if we were to,

and I'm not making the statement,

I don't think anyone can make the statement now.

But if it ends up being that CBD

is potentially beneficial for sleep,

how can we reconcile that mechanistically?

And I think there are, to me, at least,

there are at least three candidate mechanisms

that I've been exploring and thinking about.

The first is that it's thermo regulatory.

And what we found in some animal models

is that CBD will create a profile of hypothermia.

In other words, it cools the body

the core body temperature down.

And that's something that we know is good for sleep.

The second is that it's an anxyolitic,

that it can reduce anxiety.

And that data is actually quite strong,

even with some functional imaging work

that's been coming out recently

showing that one epicenter of emotion called the amygdala

deep within the brain is quietened down with CBD.

So I think that's at least a second non mutually exclusive.

- That's great, that's conducive.

- You know, possibility.

I think the third is some recent data

that's come out that was suggesting

that CBD can alter the signaling of adenosine.

So it doesn't necessarily mean

that you produce more adenosine,

but what it can do is perhaps modulate

the sensitivity perhaps of the brain,

so that the weight of that same adenosine

is weightier in its brain signal,

and therefore it creates this stronger pressure for sleep.

So I think these are all tentative mechanisms.

I think any one of them is viable,

I think all three are viable together.

But right now I think,

does that sort of help think through

the tapestry of THC and CBD?

- Yeah very much so and actually, it's a perfect segue

from we've talked about caffeine, alcohol, THC and CBD

as sort of, we framed them anyway,

as things that done in moderation

at the appropriate times,

are probably okay for most people.

Certainly not for everybody,

there will be differences in sensitivity.

But that done at the incorrect times,

and certainly in the incorrect amounts

will greatly disrupt this vital stage of life we call sleep.

CBD, it seems, represents a kind of bridge

to the topic I'd like to talk about next,

which is things that promotes more healthy sleep,

or somehow contribute to enhancing the architecture

and quality of sleep.

So I'd love to chat for a moment about

the kind of grand,

the original I should say that

not the granddaddy but the OG of sleep supplementation,

which is melatonin.

The so called hormone of darkness

that's inhibited by light, etcetera.

Frame for us, melatonin

in the context of its naturally occurring form.

And then I'd like to talk about melatonin the supplement

because in my experience, anytime I say the word melatonin,

people think about the supplement melatonin,

which in itself is an interesting phenomenon

that people are so cued to its role

as something you take,

we often forget that this is something

that we make endogenously.

I'd love for you to comment in particular

on even though without necessarily getting into

its precise nanograms per deciliter values,

what are the typical amounts of melatonin

that we release each night?

And then I'd like to compare that

to what is contained in say a three milligram

or six milligram tablet that one might buy at the pharmacy.

- Right, yeah. - So I go to sleep at night,

has melatonin already kicked in

before I shut my eyes and lay down my head?

- Usually, yes, if your system is working

in the correct way,

as dusk is starting to happen,

so let's say that you look at hunter gatherer tribes

who aren't touched by electricity,

and so that's sort of the puritanical state par excellence

when it comes to electric light influence.

And usually, it's as dusk is approaching,

that's when melatonin will start to rise.

And so when you lose the brake pedal

of light coming through the eyes,

that normally acts like a hard brake pedal

that stamps down and prevents the release

and production of melatonin.

As that light brake pedal starts to fade with dusk,

then we ease off the brake pedal

and melatonin the spigot of melatonin is opened up,

and melatonin starts getting released.

And usually we'll see this rising peak of melatonin

sometime, usually an hour, two hours later or around

and it varies from different people

around the time of sleep itself.

But it's already been on the march for some hours

before you actually hit sleep itself.

- Interesting, and I was always taught

and I'm assuming it's still true

that the only source of melatonin in the brain and body

is the pineal gland.

Is that still true?

- Yeah, it seems to be from best that we can tell

the pineal gland sort of meaning pea like sort of shape.

It's actually I think usually people say it's pea like,

I think if you look at the Latin derivative, it's more,

I think it's derived from pine cone, not pea

because in fact, if you look at the pineal,

it is more pine cone shaped

and so is aptly named.

- Any human brain I've ever dissected

or I confess I've dissected a lot

'cause I teach neuroanatomy and have for years.

I love looking at the pineal

it's the one structure in the brain

that's not on both sides.

It's usually pretty easy to find.

And it's a pretty good size.

It looks like a,

it looks like a pea.

And it's sitting right there.

And it's remarkable that it releases this hormone.

Sort of probably our entire lifespan is inhibited by light.

So our pineal starts to release this

into the general circulation.

I have to imagine we have melatonin receptors

in the brain and body.

- It's correct, so yep, essentially,

your brain has a central Master 24 hour clock

called the super charismatic nucleus

that keeps internal time.

Now it's not a precise clock if left to its own devices,

nothing that a Swiss clock maker would be proud of.

It runs a little bit long and laggy.

- It's like an American clock.

There are a couple of good American watches by the way,

Hamilton's are very nice, but.

- It's very much like a bug.

- We're not famous for our timekeeping

or our punctuality for that matter, but the Swiss are.

- It's very it's not quite Swiss, like

it's more Berkeley like, which is very relaxed.

Oh you know what whatever.

So in most adults, the average adult, I should say,

your biological clock normally runs a little bit long,

it's about 24 hours and 30 minutes,

I think was the last calculation.

But the reason that we don't keep drifting forward in time

and kind of running consistently,

you know, more and later and later,

30 minutes by 30 minutes by 30 minutes each day,

is because your central brain clock

is regulated by external things such as daylight

and temperature, as well as food and activity.

All of these are essentially different fingers

that come along and on the wristwatch of the 24 hour clock

will pull the dial out and reset it each day

to precisely 24 hours.

And I make that point because it knows 24 hour time,

but it needs to tell the rest of the brain and the body,

the 24 hour time as well.

And one of the ways that it does this

is by communicating a chemical signal

of 24 hour nurse of light and day

using this hormone, melatonin.

And when it is at low levels,

or it's non existent,

it's communicating the message it's daytime,

and for us diurnal species, it says it's time to be awake.

Yet, at nighttime,

when dusk approaches and the break comes off melatonin

and we start to release it,

then it signals to the rest of the brain and the body,

look, it's dusk and it's nighttime.

And for us diurnal species, it's time to think about sleep.

So melatonin essentially tells the brain and the body

when it's day and when it's night,

and with that when it's time to sleep

when it's time to wake.

And therefore, that's why melatonin helps

with the timing of the onset of sleep.

But it doesn't really help

with the generation of sleep itself.

And this is why we'll come on to

what those studies of supplementation have taught us.

- So it tells the rest of my brain and body,

it's time to go to sleep.

It perhaps even aids with the transition to sleep

but it's not going to for instance,

ensure the overall structure of sleep

or it's not the conductor

that's guiding the sleep orchestra so to speak

throughout the entire night.

- Yeah, it's. - It's more like the

people that essentially take you to your seat

and sit you down and give you your program.

- Right, exactly yeah, sort of the the fall,

less sophisticated analogy I have is, you know,

melatonin is like the starting official

at the 100 meter race in the Olympics.

- That's a better analogy, yeah.

- It calls all of the sleep racers to the line

and it begins the great sleep race.

- Yeah, better analogy by the way.

- [Matthew] It doesn't help dissipate, no, no, no, no.

- Coming from the sleep researcher of all people.

- But it doesn't participate in the race itself.

That's a whole different set of brain chemicals

and brain regions.

Which then brings us on to

perhaps the question of supplementation,

which is, is it helpful for my sleep?

Will I sleep longer?

Will I sleep better?

And if I am, what dosage should I be taking?

Sadly, the evidence in healthy adults

who are not older age suggests that

melatonin is not really particularly helpful as a sleep aid.

I think there's a recent meta analysis

that demonstrated when

it looked at all of the different sleep parameters,

melatonin, and a meta analysis

for those not knowing what that is,

it's a scientific sort of method that we use

where we gather all the individual studies

and we put them in a big bucket

and we kind of do this kind of statistical

fancy sleight of hand.

And we try to come up with a big picture

of what all of those individuals studies tell us.

And what that meta analysis told us is that

melatonin will only increase total amount of sleep

by 3.9 minutes, on average.

- Minutes? - [Matthew] Minutes.

- Not even percent.

- And it will only increase your sleep efficiency by 2.2%.

So it really.

- This is as they say, in certain parts of California,

that's weak sauce, that's a weak sauce effect.

- The sauce is not strong,

the force is not strong in this one,

when it comes to a tool that in healthy people

who are not of older age,

it doesn't seem to be especially beneficial.

Now, you know, results can vary.

Everyone is different, of course.

So we're talking about the average,

the so called average human adult here.

- Well, melatonin, in defense of what you're saying

and also I should mention,

I have a colleague at Stanford, Jamie Seitzer.

- Oh, wonderful, genius.

- Chuck Seitzer's lab at Harvard Med

where he also trained terrific sleep researcher

and I asked him about melatonin

and he essentially said the same thing that you just said

which is very little if any evidence

that it can improve sleep

and yet it's probably the most commonly consumed

so called sleep aid.

- Hundreds of million dollars industry.

- Yeah, so either massive placebo effect

or it's operating through some other mechanism

related to quelling anxiety perhaps?

- Well, yeah, that's essentially interesting, you know,

there are some studies where

you do see some, you know, effects.

Now, again, when you do the grand average of all studies,

it just doesn't seem to have an effect.

But let's assume that for some people,

it does have an effect

let's not again be sort of completely dismissive of that,

how could it have that effect?

One of the reasons

that I've become a little bit more bullish on melatonin

from a sleep perspective

and then melatonin more generally for a,

maybe you can speak about this too,

as a counter measure

when you're undergoing insufficient sleep.

There are two different routes there.

The first reason that I think

it could have a sleep benefit for some people

is not because it helps in the generation of sleep,

we know that it doesn't,

it's because it too seems to drop core body temperature.

- There it is, temperature again.

I'm fascinated these days,

more and more by temperature,

as maybe not just a reflection of brain state

and wakefulness and in sleep,

but actually a lever that is quite powerful.

- I think it's both.

- And with all the interest in ice baths and hot showers

and saunas and stuff,

something that we will definitely touch on.

Temperature variation is so key.

So if melatonin is dropping body temperature

by a degree or so something that you've said before

can help induce a sleepy state.

Maybe that's what's allowing people to get in to sleep.

- I think that's one possibility.

I don't think melatonin by itself

will drop it by it sort of, you know, a degree,

certainly not a degree Celsius.

And for order in us to fall asleep,

and then stay asleep across the night,

we do need to drop our core body temperature

by about one degree Celsius,

or about two to three degrees Fahrenheit.

And that's why it's always easier

to fall asleep in a room that's too cold than too hot.

I think that that's one potential avenue

that we are considering thinking more deeply about

when it comes to melatonin.

And then the other is melatonin as an antioxidant.

But let me table that for now.

'Cause I'll just get us sidetracked.

That's what we know so far about melatonin

in terms of its supplementation benefit or lack thereof.

Two final points that I shouldn't forget,

one is the only population where we typically see

some benefit, and it often is prescribed

is in older adults, because as we.

- Older meaning 60 and older?

- Yeah, 60, 65 and older

because as we get older,

you can typically have what's called

calcification of the pineal gland.

Which means that that gland that's releasing melatonin

doesn't work as well anymore.

As a consequence, they tend to have a flatter overall curve

of melatonin release throughout the night.

It's not this beautiful, lovely peak,

and this bullhorn message of its darkness,

please get to sleep.

That's why older adults can have problems falling asleep

or staying asleep.

It's not the only reason by any stretch of the imagination.

But it's one of the reasons

and it's why melatonin supplementation in those cohorts,

older adults, and especially older adults with insomnia,

people have thought about that

as maybe an appropriate use case.

- Well, along those lines,

if we were to compare dosages, I don't,

do we know how much melatonin

is typically released into the bloodstream per night?

And can we use that as a kind of a rule of thumb

by which to compare the typical amount

that someone would supplement?

Typically, the supplements for melatonin that I see

in the pharmacy and elsewhere online

range anywhere from one milligram to 12,

or even 20 milligrams.

My guess is that a normal night's release of melatonin

typical for somebody in their 20s, 30s, 40s

would be far lower than that, am I correct or wrong?

- Yeah, it's many magnitudes lower.

And this is one of the problems is that I see that too.

I see, you know, typical doses are, you know,

five milligrams or 10 milligrams

and of course, you know, if you're a supplement company,

you know, putting 10 milligrams versus five milligrams,

if that's what you're actually doing,

which we'll speak about purity as well.

You know, it's kind of like the super gulp size,

nobody wants to lower price,

they just want you to you know,

we'll just give you more for the same price.

And that's how we'll compete.

So it's been this escalating arms race

of melatonin concentration,

and it really does not look meaningful

for, you know, for sleep in any way.

What we've actually found

is that the optimal doses

for where you do get sleep benefits

in the populations that we've looked at,

are somewhere between 0.1 and 0.3 milligrams of melatonin.

In other words, the typical doses are usually

10 times, 20 times maybe more

than what your body would naturally expect.

And this is what we call a supra physiological dose.

In other words, it's far above

what is physiologically normal?

You know, and to put that in context,

imagine I said to you,

I want you to eat 20 times as much food today.

- I thought you're going to use testosterone as example.

You're going to take 300 times

the normal amount of testosterone

we know that would have tons of deleterious effects

it would be terrible.

And yet you can do this.

One thing that I'm concerned about

about these super physiological levels of melatonin

is that many years ago, actually, here at Berkeley,