Coffee & Sleep: How Does Caffeine Work & Its Effects on Sleep

00:00:00.000 | [Silence]

00:00:04.240 | How does caffeine work to make us feel more alert?

00:00:08.480 | And does the timing in which we ingest caffeine

00:00:12.320 | play an important role in whether or not

00:00:14.540 | it works for us or against us?

00:00:16.840 | So maybe we just start with, how does caffeine work?

00:00:19.720 | Why is it that when I drink mate or coffee,

00:00:22.320 | which are my preferred sources of caffeine,

00:00:24.380 | do I feel a mental and physical lift?

00:00:27.140 | - Yeah, so I'm going to suggest counter to what

00:00:30.260 | most people would think, drink coffee.

00:00:33.700 | - Or mate, is mate okay also?

00:00:36.940 | - Yeah, yeah, yeah.

00:00:37.780 | - Whatever form you enjoy.

00:00:39.280 | - We'll come on to sort of why I suggest that,

00:00:41.880 | but when it comes to coffee, I would say

00:00:45.980 | the dose and the timing makes the poison.

00:00:49.680 | So let's start with how caffeine works.

00:00:53.480 | Caffeine is in a class of drugs that we call

00:00:55.700 | the psychoactive stimulants.

00:00:57.840 | So it works through a variety of mechanisms.

00:01:02.340 | One is a dopamine mechanism, dopamine we often think of

00:01:06.780 | as a reward chemical, but dopamine is also very much

00:01:11.680 | an alerting neurochemical as well.

00:01:14.580 | And caffeine has some role, it seems to play,

00:01:17.240 | in increasing dopamine, but its principle mode of action,

00:01:20.840 | we believe, in terms of making me more alert

00:01:23.760 | and keeping me awake throughout the day,

00:01:26.480 | is on the effects of adenosine.

00:01:29.040 | And to explain what adenosine is,

00:01:30.680 | from the moment that you and I woke up this morning,

00:01:33.680 | this chemical adenosine has been building up in our brain.

00:01:37.840 | And the longer that we're awake,

00:01:39.560 | the more of that adenosine accumulates.

00:01:42.000 | - Where is this adenosine coming from

00:01:43.740 | and where is it accumulating?

00:01:44.880 | - Yeah, so the adenosine here that we're talking about

00:01:47.560 | that is creating the sleep pressure

00:01:49.220 | is a central brain phenomenon.

00:01:51.560 | And it comes from the neurons themselves combusting energy.

00:01:55.880 | And as they're combusting energy,

00:01:57.600 | one of the offshoots of that is this chemical adenosine.

00:02:02.600 | And so as we're awake throughout the day

00:02:04.880 | and our brain is metabolically very active,

00:02:07.960 | it's accumulating and building up this adenosine.

00:02:12.440 | Now, the more adenosine that we have,

00:02:15.600 | the sleepier that we will feel.

00:02:17.800 | So it really is like a sleep pressure is what we call it.

00:02:22.300 | Now, it's not a mechanical pressure, don't worry.

00:02:24.520 | Your head's not going to explode.

00:02:25.600 | It's a chemical pressure.

00:02:28.080 | And it's this weight of sleepiness

00:02:30.400 | that we feel gradually growing as we get into the evening.

00:02:34.160 | - May I just interrupt you again to just ask,

00:02:36.840 | do we know what the circuit mechanism is for that?

00:02:39.640 | I mean, not to go too far down the rabbit hole,

00:02:42.280 | but for the aficionados and for myself,

00:02:45.280 | we have brain mechanisms like locus coeruleus

00:02:47.920 | that release things, brain areas,

00:02:50.720 | locus coeruleus just being a brain area, of course,

00:02:52.240 | that release things that proactively create wakefulness.

00:02:56.840 | So are those neurons shutting down

00:02:58.560 | as a consequence of having too much adenosine

00:03:01.600 | or are there areas of the brain that promote sleepiness

00:03:06.200 | that are then coming activated?

00:03:07.800 | Because you can imagine both things working in parallel,

00:03:10.360 | one or the other would accomplish the same end point.

00:03:12.760 | - Yeah, and it's both.

00:03:14.920 | And so there are two main receptors for adenosine,

00:03:17.880 | the A1 receptor and the A2 receptor,

00:03:21.400 | and they have different modes of activating brain cells

00:03:24.840 | or inactivating or decreasing the likelihood of firing.

00:03:29.400 | And adenosine works in this beautiful, elegant way

00:03:33.280 | where it will inhibit and shut down

00:03:36.280 | the wake-promoting areas of the brain,

00:03:39.080 | whilst also increasing and dialing up the volume

00:03:43.160 | on sleep-activating, sleep-promoting regions.

00:03:45.800 | - Biology is so beautiful.

00:03:46.640 | - Oh, it's fantastic. - It's always a push-pull.

00:03:48.080 | So this is another example where as I am awake longer,

00:03:52.520 | adenosine is released in the brain

00:03:55.040 | and my wakefulness areas are being actively shut down

00:03:58.600 | by that adenosine and my sleepiness brain areas,

00:04:02.120 | so to speak, are being promoted to be more active.

00:04:05.400 | Is that correct?

00:04:06.240 | - That's right, and it's a very progressive process.

00:04:08.360 | It's not like a step function where,

00:04:10.840 | and sometimes that happens occasionally,

00:04:13.320 | but it's usually because you've been sort of driving through

00:04:15.960 | and, as we'll come on to, have caffeine in the system,

00:04:18.800 | and then all of a sudden you just hit a wall

00:04:20.680 | and it just, you know, engulfs you

00:04:23.000 | and you go from a zero to the one of sleepiness

00:04:26.000 | within a short period of time.

00:04:27.400 | Caffeine comes into play here

00:04:29.160 | because caffeine comes into your system

00:04:32.680 | and it latches onto those welcome sites of adenosine,

00:04:35.960 | the adenosine receptors.

00:04:38.360 | But what it doesn't do is latch onto them and activate them

00:04:43.360 | because if it was doing that,

00:04:45.200 | then it would, you know, in lots of ways,

00:04:47.440 | it would dial up more sort of sleepiness.

00:04:50.240 | It does the opposite.

00:04:51.840 | The way that caffeine works is that it comes in,

00:04:55.160 | competes with quite sharp elbows with adenosine,

00:04:59.280 | competitively forces them out of the way,

00:05:02.200 | hijacks that receptor by latching onto it,

00:05:05.720 | but then just essentially blocks it.

00:05:08.480 | It doesn't inactivate the receptor.

00:05:11.360 | It doesn't activate the receptor.

00:05:13.880 | It functionally inactivates it in the sense

00:05:17.560 | that it takes it out of the game for adenosine.

00:05:20.520 | So it's like someone, you know, coming into a room

00:05:24.000 | and you're just about to sit down on the chair

00:05:26.120 | and caffeine comes in and just pulls out the chair

00:05:27.920 | and you're like, well, now I've got nowhere to sit.

00:05:30.680 | And caffeine just keeps pulling out the chairs

00:05:32.840 | from adenosine and adenosine,

00:05:35.060 | even though it's at the same concentration in your brain,

00:05:39.120 | your brain doesn't know that you've been awake for,

00:05:43.040 | you know, 10 hours, 16 hours at that point

00:05:46.260 | when you've downed a cup of coffee,

00:05:48.660 | because all of that adenosine that's still there

00:05:52.680 | can't communicate to the brain

00:05:55.760 | that you've been awake for 16 hours because-

00:05:58.200 | - But the adenosine is still in brain circulation.

00:05:59.960 | - Correct.

00:06:00.800 | - So the real question is what happens

00:06:02.560 | when caffeine is dislodged from the adenosine receptor?

00:06:05.880 | - Unfortunate things happen.

00:06:07.240 | And that's what we call the caffeine crash,

00:06:09.320 | which is caffeine has a half-life and it's metabolized.

00:06:13.320 | - Do you recall what the half-life is?

00:06:15.360 | - Yeah, the half-life is somewhere between five to six hours

00:06:19.000 | and the quarter-life therefore is somewhere

00:06:20.760 | between 10 to 12 hours.

00:06:22.800 | It's variable.

00:06:23.880 | Different people have different durations of its action,

00:06:28.440 | but for the average adult, five to six hours.

00:06:30.940 | That variation, we understand, it's down to a liver enzyme

00:06:34.400 | or a set of liver enzymes of the class

00:06:36.800 | that we call the cytochrome P450 enzymes.

00:06:39.920 | And there are, I think last I delved into the data,

00:06:43.720 | which was pretty recently, there are two gene variants

00:06:47.440 | that will dictate the enzymatic speed

00:06:50.920 | with which the liver breaks down caffeine.

00:06:53.620 | And that's why you can have some people

00:06:55.060 | who are very sensitive to caffeine

00:06:57.440 | and other people who say, you know,

00:06:59.040 | I'm just, it doesn't affect me really that much at all.

00:07:01.600 | - These are the people that have a double espresso

00:07:03.120 | after a 9 p.m. dinner and can sleep just fine.

00:07:05.760 | - Well, and we'll come on to--

00:07:06.600 | - Or at least subjectively, they think they're sleeping.

00:07:08.520 | - Subjectively, yeah.

00:07:09.360 | And we should speak about that, that assumptive danger too.

00:07:13.440 | So then the caffeine is in the system

00:07:16.920 | and after some time period,

00:07:18.740 | it will be inactive in the system.

00:07:22.040 | So let's say that, you know,

00:07:23.280 | I've been awake for 12 hours now and it's, you know, 8 p.m.

00:07:28.440 | and I'm feeling a bit tired, but I want to push through

00:07:30.960 | and I want to keep working for another couple of hours.

00:07:33.600 | So I have a cup of coffee.

00:07:35.200 | All of a sudden I was feeling tired,

00:07:37.280 | but I don't feel like I've been awake for 12 hours anymore

00:07:40.400 | because with the caffeine in the system,

00:07:42.500 | maybe only half of that adenosine is being communicated

00:07:47.200 | through the receptor to my brain.

00:07:49.080 | 100% of the adenosine is still there.

00:07:51.700 | Only half of it is allowed to communicate to my brain.

00:07:54.000 | So now I think, oh, I haven't been awake for 12 hours,

00:07:56.320 | I've just been awake for six hours, I feel great.

00:07:58.960 | Then after a few hours,

00:08:00.600 | and the caffeine is starting to come out of my system,

00:08:03.720 | not only am I hit with the same levels of adenosine

00:08:07.840 | that I had before I'd had the cup of coffee

00:08:10.560 | several hours ago,

00:08:11.920 | it's that plus all of the adenosine that's been building up

00:08:16.000 | during the time that the caffeine has been in my system.

00:08:19.320 | - So sort of an avalanche of adenosine.

00:08:21.240 | - It is a tsunami wave, yeah, and that's the caffeine crash.

00:08:24.560 | - And it's interesting because the caffeine crash

00:08:26.960 | at two o'clock in the afternoon when you have work to do

00:08:30.000 | is a terrible thing, but what about the person,

00:08:33.520 | maybe this person is me in my 20s,

00:08:35.800 | who says, I'm going to drink caffeine all day long,

00:08:39.480 | and then I want the crash because at nine or 10 p.m.,

00:08:43.120 | if I stop drinking caffeine at say 6 p.m. and I crash,

00:08:47.400 | then I crash into a slumber, a deep night of sleep.

00:08:51.880 | Is that sleep really as deep as I think it is?

00:08:54.260 | Because given the half-life of caffeine

00:08:56.320 | that you mentioned a few moments ago,

00:08:59.080 | I have to imagine that having some of that caffeine

00:09:01.580 | circulating in my system might disrupt the depth of sleep

00:09:05.200 | or somehow the architecture of sleep in a way

00:09:07.840 | that even if I get eight or who knows,

00:09:10.480 | even 10 hours of sleep,

00:09:12.080 | it might not be as restorative as I would like it to be.

00:09:15.560 | - Yeah, and that is the danger,

00:09:17.660 | just sort of those people that you described who say,

00:09:20.840 | and a lot of them will speak with me too,

00:09:23.420 | say, look, I can have two espressos with dinner

00:09:26.080 | and I fall asleep fine and I stay asleep,

00:09:28.480 | because usually those are the two phenotypes

00:09:30.840 | that we typically see with too much caffeine.

00:09:33.080 | I just can't fall asleep as easily as I want to,

00:09:35.720 | or I fall asleep, but I just can't stay asleep.

00:09:38.160 | And caffeine can do both of those things quite potently.

00:09:40.800 | - How late in the day do you think is,

00:09:43.160 | assuming somebody, translate this, folks,

00:09:45.280 | if you go to bed earlier or later,

00:09:46.680 | you have to shift the hours accordingly,

00:09:48.320 | but given somebody who typically gets into bed

00:09:51.580 | around 10, 10, 30 and falls asleep around 11, 11, 30,

00:09:56.100 | when would you recommend they halt caffeine intake?

00:10:01.280 | And these are not strict prescriptives,

00:10:03.240 | but I think people do benefit

00:10:04.480 | from having some fairly clear guidelines

00:10:07.060 | of what might work for them.

00:10:09.580 | Would you say cut off caffeine by what time of the day?

00:10:13.640 | - I would usually say, take your typical bedtime

00:10:16.440 | and count back sort of somewhere between 10 to eight hours

00:10:20.320 | is probably getting a little bit close,

00:10:21.960 | but take back sort of 10 hours or eight hours of time.

00:10:25.840 | That's the time when you should really stop,

00:10:28.780 | you know, using caffeine is the suggestion.

00:10:31.700 | And the reason is because for those people

00:10:33.380 | who even just keep drinking up until,

00:10:35.600 | you know, into the evening,

00:10:38.040 | you're right that they can fall asleep fine,

00:10:40.140 | maybe they stay asleep,

00:10:41.180 | but the depth of their deep sleep is not as deep anymore.

00:10:45.260 | And so there are two consequences.

00:10:47.620 | The first is that for me,

00:10:49.020 | and it can be up to by 30%,

00:10:51.780 | and for me to drop your deep sleep by 30%,

00:10:54.300 | I'd have to age you by between 10 to 12 years,

00:10:58.060 | or you can just do it every night to yourself

00:10:59.980 | with a couple of espressos.

00:11:02.180 | The second is that you then wake up the next morning

00:11:06.100 | and you think, well, I didn't have problems falling asleep

00:11:09.340 | and I didn't have problems staying asleep,

00:11:11.980 | but I don't feel particularly restored by my sleep.

00:11:14.460 | So now I'm reaching for three or four cups of coffee

00:11:17.300 | the next morning rather than just two or three cups

00:11:19.440 | of coffee.

00:11:20.280 | And so goes this dependency cycle

00:11:22.900 | that you then need your uppers to wake you up

00:11:25.500 | in the morning.

00:11:26.620 | And then sometimes people will use alcohol in the evening

00:11:29.660 | to bring them down because they're overly caffeinated.

00:11:32.940 | And alcohol, and we can speak about that too,

00:11:34.780 | also has very deleterious impacts on your sleep as well.

00:11:38.460 | (upbeat music)

00:11:41.040 | (upbeat music)

00:11:43.620 | (upbeat music)

Coffee & Sleep: How Does Caffeine Work & Its Effects on Sleep | Matt Walker & Andrew Huberman

Chapters