Huberman Lab - What Alcohol Does to Your Body, Brain & Health

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, we’re discussing alcohol,

one of the most commonly consumed substances

on the planet Earth.

Should mention that both humans

and non-human animals consume alcohol

either for recreational purposes

because they like the feeling that it gives them

or for medicinal purposes

or for other purposes that we’ll discuss.

We are of course going to discuss the effects of alcohol

on our biology,

ranging from its effects on individual cells,

on organs and organ systems in our brain and body.

We are also going to discuss the effects

of the effects of alcohol.

That is what being inebriated really does

to our thinking and our behavior and how it does it.

And we are going to address

what seems to be one of the more common questions out there,

which is whether or not low to moderate amounts of drinking

are better for our health

than zero alcohol consumption at all.

And of course, we will talk about

severe alcohol intake, binge drinking.

We will also talk about hangover

and what science says about ways

to reduce the effects of hangover,

either by doing things that are inoculatory,

meaning before you drink or while you drink,

as well as things to do if you happen to have a hangover.

We will discuss some of the genetic differences

for alcohol and alcoholism.

And we will discuss alcohol consumption in young people

and how that can be especially detrimental

for reasons that I think are going to be

quite surprising to most of you.

My goal is that by the end of today’s episode,

you will have a thorough understanding

of what alcohol does to your brain and body

and that you will be able to make informed decisions

as to whether or not you should be consuming zero,

absolutely no alcohol,

small to moderate amounts of alcohol.

And again, we’ll define exactly what that means,

small to moderate amounts.

And if you or somebody else that you know

is consuming excessive amounts of alcohol

that are clearly detrimental to your health,

some of the better routes and resources that you can use

in order to remove that dependence and or consumption.

I’d like to preface all of that by saying

that today’s discussion is really geared

toward giving you information.

It is not about judging alcohol intake

or lack of alcohol intake.

I just want you to be able to make

the most informed decision about alcohol possible.

Before we get into today’s content in detail,

I just want to answer a commonly asked question

about alcohol consumption and the brain.

And the question that so often comes up

is whether or not low to moderate amounts of alcohol,

so maybe one drink a day

or one or two drinks a day kind of thing,

whether or not that is bad for your brain,

in particular, whether or not it causes degeneration

of neurons or nerve cells.

Now, the reason that question comes up so often

is because for many years,

it’s been known that high levels of alcohol consumption,

so 12 to 24 drinks per week or more,

is certainly causing neurodegeneration,

in particular, of the so-called neocortex,

the outer layers of the brain

that house associative memories,

that house our ability to think and plan,

that house our ability to regulate our more primitive drives

according to context, et cetera.

So to make very clear, drinking a lot,

so having three or four drinks per night

every night of the week is clearly bad for the brain.

A recent study, however, finally addressed the question

of whether or not low to moderate amounts

of alcohol consumption can cause brain degeneration.

The title of the study is

Associations Between Alcohol Consumption

and Gray and White Matter Volumes in the UK Biobank,

the United Kingdom Biobank.

First of all, gray matter are the neurons,

it’s the so-called cell bodies

that house the genome of the cells, et cetera,

and white matter is the connections, the fibers,

the so-called axons of neurons.

And it’s called white matter

because that tissue is surrounded by a fatty tissue

called myelin, which allows nerve cells

to communicate with each other very quickly.

So what this study did is it looked at the brains,

both the gray matter and the white matter,

of more than 30,000 and even more than 35,000

generally healthy middle-aged and older adults

in the United Kingdom

who were drinking various amounts of alcohol.

What they found was that even for people

that were drinking low to moderate amounts of alcohol,

so one or two drinks per day,

there was evidence of thinning of the neocortex,

so loss of neurons in the neocortex,

and other brain regions.

And I don’t say this in order to cause alarm,

I tell you this because they are important data

because they reveal and indeed answer the question

that has been burning for so long

as to whether or not chronic alcohol intake

can disrupt the brain,

even if the chronic intake is very low.

Now we should talk about what the word chronic means

because many people, when they hear the word chronic,

think high levels of whatever intake, okay?

So they think five drinks a night or 10 drinks a night

or people drinking every night.

Now in this study, they looked at people who on average

were drinking one or two drinks per night.

So that could be 14 drinks on the weekend,

it could be one drink per night,

it could be seven drinks on Friday.

In other words, on average, one or two drinks per night.

And I think many people out there are drinking

somewhere between one and two drinks per night

or day of the week on average,

so that would be seven to 14 drinks per week.

So this is an important study

because it says that if you’re consuming

even just seven glasses of wine across the week,

it’s likely that there is going to be some degeneration

of your brain in response to that alcohol intake.

Although, as mentioned earlier,

we will talk about some of the things that can inoculate

against some of that neuronal loss.

For those of you that are interested

in reading the study in more detail,

we put a link to it in the show note captions.

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

is separate from my teaching and research roles at Stanford.

It is however, part of my desire and effort

to bring zero cost to consumer information about science

and science related tools to the general public.

In keeping with that theme,

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

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Let’s talk about alcohol,

and let’s just acknowledge that human beings

have been consuming alcohol for thousands of years.

If you look at the archeological evidence from Mesopotamia,

you’ll find that 5,000 years ago, people had wine vessels,

or if you want to know when people

first started distilling alcohol,

much to people’s surprise,

that did not first take place in Ireland,

and that’s not a joke about the Irish,

that you’ll see a lot of claims online

that the Irish were the first to distill alcohol,

but in fact, they were not.

It was the Chinese that were the first to distill alcohol,

and that took place in China in the first century.

Alcohol has been used for nutritional purposes,

so there are cultures that believe,

and indeed still believe,

that the calories in alcohol are useful,

although later we’ll talk about how alcohol calories

are indeed empty calories

and what an empty calorie really is,

why it’s called empty.

Alcohol has been used for medicinal purposes,

because indeed it does kill bacteria,

and as you’ll soon find out,

the fact that it kills bacteria,

because that is absolutely true,

it also kills the good bacteria in your gut,

and the destruction of that good bacteria in your gut

can lead to things like leaky gut syndrome,

and has all sorts of issues,

and there are ways to deal with those issues,

and we’ll talk about those.

So alcohol has been used for medicinal purposes,

it’s been used to clean surfaces,

it’s used in my laboratory

in order to make up so-called reagents

to do our experiments,

but most humans have been consuming alcohol

in order to change their internal state,

in order to feel differently than they would otherwise.

That feeling of being drunk, or inebriated,

or tipsy, or lightheaded,

is something that many, not all,

but many humans seem to enjoy and pursue,

even though typically it leads to a feeling

of being less happy, less motivated,

more stressed, et cetera, when the alcohol wears off.

That’s pretty incredible, right?

I mean, we’re talking about a substance

that people have been highly motivated to pursue,

that are still highly motivated to pursue,

to create and to consume, that they’ll spend money on,

and that’s despite the fact that it makes them feel good,

and then it makes them feel lousy.

Now, some of you might be saying,

well, I drink, but I don’t drink to excess,

and therefore I don’t feel lousy,

I feel good when I drink, and then it wears off,

and it allows me to get through my evening,

and then the next morning I’m ready to go.

Okay, that very well may be true.

I believe those people.

And as I mentioned at the beginning of the episode,

I’m not here to demonize alcohol in any way,

but I do want to point out what alcohol is,

and how it creates the effects that it does.

And then I want to talk about what those effects are

when you engage in consuming alcohol,

even as often as one or two nights per week,

or let’s say you’re just somebody

who has a drink or two on Friday,

maybe a few more on Saturday,

or maybe you’re somebody who consumes all your alcohol

one night per week or one night per month.

We’ll talk about how that’s affecting your biology.

So let’s address what alcohol is,

and how it affects the cells and tissues

and organs of your body.

Then we’ll take a look at some of the epidemiology,

that is how many people are consuming alcohol,

and how much they’re drinking.

And then you will be able, I think,

to get a good sense of how the alcohol that you’re drinking,

if you’re drinking any at all,

is impacting your brain and body,

and the choices you might want to make

about how and when to drink alcohol,

or even if you want to eliminate alcohol altogether.

Okay, so some basic chemistry and biology of alcohol.

And again, I’ll make this very clear,

even if you don’t have a chemistry and biology background.

Because of the structure of alcohol,

it is what’s called both water-soluble and fat-soluble.

Translated into what’s meaningful for you,

what that means is when you drink alcohol,

it can pass into all the cells and tissues of your body.

It has no trouble just passing right into those cells.

So unlike a lot of substances and drugs

that actually attach to the surface of cells,

to receptors as they’re called, little parking spots,

and then trigger a bunch of downstreams,

like domino cascades of effects,

alcohol actually has its own direct effects on cells

because it can really just pass into those cells.

So it’s water and fat-soluble.

And the fact that it can pass

into so many organs and cells so easily

is really what explains its damaging effects.

I should mention that there are three main types of alcohol.

There’s isopropyl, methyl, and ethyl alcohol.

And only the last one, ethyl alcohol or ethanol,

is fit for human consumption.

However, it is still toxic, okay?

It produces substantial stress and damage to cells.

I’d love to be able to tell you otherwise,

but that’s just a fact.

Ethanol produces substantial damage to cells.

And it does that because when you ingest ethanol,

it has to be converted into something else

because it is toxic to the body.

And there’s a molecule inside of all of us called NAD.

And you may have heard of NAD because it’s quite popular.

There’s a lot of discussion about NAD

in the longevity literature right now.

NAD is present in all our cells from birth until death.

The levels of NAD tend to go down across the lifespan.

There are ideas that increasing levels of NAD

may extend lifespan.

A lot of that is still controversial,

or at least we should say is ongoing

in terms of the research.

But nonetheless, when you ingest ethanol,

NAD and related biochemical pathways

are involved in converting that ethanol

into something called acetyl aldehyde.

It’s broken down into acetyl aldehyde.

And if you thought ethanol was bad,

acetyl aldehyde is particularly bad.

Acetyl aldehyde is poison.

It will kill cells.

It damages and kills cells.

And it is indiscriminate as to which cells

it damages and kills.

Now, that’s a problem, obviously.

And the body deals with that problem

by using another component of the NAD biochemical pathway

to convert acetyl aldehyde into something called acetate.

Acetate is actually something

that your body can use as fuel.

And that process of going from ethanol

to acetyl aldehyde to acetate

does involve the production of a toxic molecule, right?

Again, acetyl aldehyde is really toxic.

And NAD, and if we want to get technical,

it’s the NAD to NADH ratio.

And that chemical step is the rate-limiting step

to ethanol’s metabolism.

What does that mean for you?

What that means is that if your body

can’t do this conversion of ethanol to acetyl aldehyde

to acetate fast enough,

well, acetyl aldehyde will build up in your body

and cause more damage.

So it’s important that your body be able

to do this conversion very quickly.

And the place where it does that is within the liver.

And cells within the liver are very good

at this conversion process.

But they are cells and they are exposed

to the acetyl aldehyde in the conversion process.

And so cells within the liver really take a beating

in the alcohol metabolism events.

So the key thing to understand here

is that when you ingest alcohol,

you are, yes, ingesting a poison.

And that poison is converted

into an even worse poison in your body.

And some percentage of that worse poison

is converted into a form of calories

that you can use to generate energy, generate ATP.

And the reason why alcohol is considered empty calories

is because that entire process is very metabolically costly,

but there’s no real nutritive value

of the calories that it creates.

You can use it for immediate energy,

but it can’t be stored in any kind of meaningful

or beneficial way.

It doesn’t provide any vitamins.

It doesn’t provide any amino acids.

It doesn’t provide any fatty acids.

It’s truly empty calories.

I know some people talk about sugar is empty calories,

but sugar actually is a far better fuel source

than alcohol or acetate.

But nonetheless, when you ingest alcohol,

some percentage is being shuttled into a worse poison

and some is being shuttled into a fuel source.

Now, the important thing to understand

is that it is the poison, the acetyl aldehyde itself,

that leads to the effect of being inebriated or drunk.

I think most people don’t realize that,

that being drunk is actually a poison-induced disruption

in the way that your neural circuits work.

And so we should ask ourselves, which neural circuits,

what brain areas, what body areas involved

in feeling drunk or inebriated?

Now, in thinking about this state of being tipsy or happy

or really drunk or a little bit drunk,

I want to mention something

I think most people aren’t aware of.

And that’s the fact that for people

that are regular drinkers

or that have a genetic predisposition to alcoholism,

when they drink, they tend to feel very energized

and very good for longer periods of time.

Again, people have a genetic predisposition to alcohol

or people who are chronic drinkers, or even just,

if you recall, chronic doesn’t have to mean a ton of alcohol,

but they’re drinking one or two per night

or they’re every other night type drinkers

or Thursday through Sunday drinkers.

Those people typically experience an increase

in alertness and mood when they drink,

whereas occasional drinkers will have a briefer,

meaning less long-lasting period of feeling good

when they drink and then more quickly transition

into a state in which they’re tired

or they start losing motor skills,

they start slurring their speech.

I also want to emphasize this is distinct from tolerance.

We’ll talk about tolerance later

and exactly what tolerance means.

But I really want to highlight the fact

that when people ingest this poison,

because indeed it is poison,

the range of effects is very different

and you can reliably predict who are the people

with a predisposition to alcoholism

and who are the people who are more regular drinkers

by the contour, the timing of the different effects.

And again, people who tend to feel more alert and excited

every time they drink, they tend to get a real lift,

they become kind of the life of the party

and that lasts a long while.

Those people are the ones that really have to be careful

about predisposition for alcoholism.

And those people also need to be careful

about their drinking and the amount of drinking

that they’re doing,

even if they’re not full-blown alcoholics.

Now, of course, people who are ingesting alcohol,

who are not accustomed to drink alcohol

have to be concerned about drinking alcohol

for other reasons because it can impair motor function

and judgment, et cetera.

But in thinking about the biochemical effects of alcohol

and what it’s doing to the body,

what it’s doing in all cases

is it’s consumed into the gut, right?

Goes into the stomach.

The liver immediately starts this conversion

that we talked about before

of ethanol to acetyl aldehyde to acetate.

And some amount of acetyl aldehyde and acetate

are making it into the brain.

It crosses the blood-brain barrier.

Again, the brain has this fence around it

that we call the blood-brain barrier or the BBB.

Many things, most things, thankfully,

can’t pass across the blood-brain barrier,

but alcohol, because it’s water and fat soluble,

just cruises right across this fence

and into the milieu, the environment of the brain,

which is made up of a couple of different major cell types,

neurons, nerve cells, and so-called glial cells,

which are in between the nerve cells.

And we’ll talk about the effects on each of those soon.

So what happens when alcohol gets into the brain

that makes us feel tipsy or drunk?

And in some people, makes people feel really,

especially energized and happy.

Well, alcohol is indiscriminate

in terms of which brain areas it goes to.

Again, it doesn’t bind to particular receptors,

but it does seem to have a propensity

or an affinity for particular brain areas

that are involved in certain kinds of thinking and behavior.

So one of the first things that happens

is that there’s a slight,

at least after the first drink or second drink,

there’s a slight suppression in the activity of neurons

in the prefrontal cortex.

This is an area of your neocortex

that’s involved in thinking and planning,

and perhaps above all,

in suppression of impulsive behavior.

So if you go to a party and they’re serving alcohol

and people are consuming drinks,

what you’ll notice is that a few minutes into that party,

the volume of people’s voices will increase.

And that’s because people are simply not paying attention

to their voice modulation.

As other people start speaking more loudly,

other people are speaking more loudly.

We’ve all had this experience, right,

of going to a party and then you step outside for a moment

and you go, oh my goodness, I was shouting.

You come home the next day, you got a sore throat.

It might be that you picked up some sort of bug,

some virus or something.

But oftentimes it’s just the fact

you’ve been shouting all night just to be heard

because as the prefrontal cortex shuts down,

people stop modulating their level of speech quite as much.

Also notice that people start gesticulating more.

People will start standing up and sitting down more.

They’ll start walking around more.

If there’s music on,

people might spontaneously start dancing.

All of this is because these areas

of the prefrontal cortex normally are providing

what’s called top-down inhibition.

They are releasing a neurotransmitter called GABA

onto various parts of the brain.

They’re involved in impulsive motor behavior

and thought patterns.

And as you shut down the prefrontal cortex,

that GABAergic suppression of impulses

starts to be released.

So people will say things that they want to say

without so much forethought about what they’re saying.

Or they might do things that they want to do

without really thinking it through quite as much.

Or they might not even remember thinking it through at all

or experience, I should say, thinking it through at all.

We haven’t talked about blacking out yet

and the effects of alcohol on memory.

But as long as we’re there,

I’ll just tell you that alcohol has a very strong effect

in suppressing the neural networks

that are involved in memory formation and storage.

This is why oftentimes we forget the events of a night out

if we’ve been drinking.

One of the more important things to know

about the effects of alcohol in the brain

is this disruption in top-down inhibition,

but also that areas of the brain

that are involved in flexible behavior,

sort of considering different options.

Like I could do A or I could do B.

I could say this to them or I could say that.

I could say it in that way or I could say it in this way.

This might be a little more tactful.

Those brain areas basically shut down entirely

and people just tend to say what they want to say.

So the key thing to understand is that when people drink,

the prefrontal cortex and top-down inhibition is diminished.

That is habitual behavior

and impulsive behavior starts to increase.

Now, what’s interesting is this is true in the short term.

So after people have one or two, maybe three or four drinks,

but it’s also true that the more often

that people drink, there are changes in the very circuits

that underlie habitual and impulsive behavior.

Okay, this is really important to highlight

so much so that I want to drill into it

a little bit more deeply.

For the person that drinks say every Thursday night

or every Friday night or goes out only on Saturdays,

but every Saturday, there’s evidence that there are changes

in the neural circuits of the brain

that control habitual behavior and impulsive behavior.

And they are modified and strengthened

in ways that make those people more habitual

and more impulsive outside the times

in which they are drinking.

And when they drink, impulsive and habitual behavior

tends to increase even further.

This is something that’s not often talked about

when discussing the effects of alcohol.

And we all know the effects of being drunk can be bad,

right, can be bad in terms of judgment, motor coordination,

certainly driving drunk is a terrible thing,

get you or other people killed and so on.

But rarely do we hear about the changes in neural circuits

from just one or two nights of regular drinking.

Again, chronic drinking doesn’t necessarily mean

every day and every night.

It could be the person that simply drinks every Thursday

or every Friday or just once a week has three or four drinks

or maybe even a few more.

That person is going to experience a decrease

in this top-down inhibition.

So an increase in impulsivity and habitual behavior

because the break on those behaviors has been removed

while they’re drinking,

but also changes in the very neural circuits

that allow habitual and impulsive behavior

to occur more readily even when they’re not drinking.

And if you want to know the actual substrate for that,

the cellular substrate, I can briefly describe it.

It’s really interesting.

Again, you don’t need to know any biology

to understand this.

What it does is it increases the number of synapses,

the actual points of connection in the neural circuits

that control habitual behavior.

So there’s literally a growth of the neural circuits

in your brain that lead to existing habit execution.

The performance of things you already know how to do

and a reduction in the neural circuits,

or I should say a reduction in the number of synapses

of the contacts within the neural circuits

that are controlling behavior.

So this again is a not often discussed aspect

of alcohol intake.

Fortunately, it is reversible.

So in animals or humans that undertake a period

of abstinence of anywhere from two to six months,

these neural circuits return to normal,

except in cases where people have been chronically drinking

large volumes of alcohol for many, many years.

And in those cases,

while there is some recovery of brain circuitry,

after people get sober, meaning completely sober,

they stop drinking entirely,

there is evidence of long lasting impact

of heavy alcohol usage throughout the lifespan.

But of course, this doesn’t mean that anyone

that’s suffering from alcoholism or that used to

should not continue to focus on their health.

You absolutely should, all is not lost.

But for people that have been drinking for a lot of years,

maybe you went to college and you drank a lot

in those years and your neural circuits change.

If there’s a period in which you don’t drink alcohol,

again, from two to six months, and ideally longer,

those neural circuits can then be remodified

back to their original state.

So let’s consider some of the other neurochemical effects

of alcohol in the brain and body.

And again, for right now,

we’re confining the conversation to people

that are drinking on average one or two drinks per night.

Now, some people might think

that two drinks per night is a lot,

and a lot of that will depend on body weight.

So for instance, people who weigh 110 pounds,

for them to ingest two alcoholic drinks

is going to be substantially different

in terms of the biochemical effects

than somebody who weighs 220 pounds.

Of course, tolerance will also factor into this,

genetic background will also factor into this,

and indeed, whether or not people have eaten

will factor into this.

So there are a lot of factors and we’ll talk about that.

For the time being, if you’re curious

about how food impacts the effects of alcohol

and your feelings of being drunk,

you may have heard, for instance,

that if somebody’s inebriated and they want to sober up,

they should eat something.

Turns out that does not work.

Here’s how it does work, however.

If you eat something prior to drinking alcohol

or while ingesting alcohol,

it will slow the absorption of alcohol into the bloodstream.

In other words, you won’t feel as drunk as fast.

For many of you, this probably comes as no surprise.

In particular, if that meal includes carbohydrates,

fats, and proteins, okay?

The inclusion of all three major macronutrients

seems to slow the absorption of alcohol into the bloodstream

far more than having any one of those

or two of those macronutrients present.

Now, if you are already inebriated

or you’ve had a glass of wine or a beer

and you eat something,

chances are that alcohol has already made it

into your bloodstream

because it moves into the bloodstream so quickly.

Again, it’s fat-soluble and water-soluble.

So within minutes, if you have an empty stomach,

within five to 10 minutes,

that alcohol is going to be within your bloodstream

and distributed throughout your body,

maybe even faster depending on the type of alcohol

and your metabolism.

But if you’re already drunk and you eat something,

it’s not going to sober you up more quickly,

but it certainly will blunt the effects

of any additional alcohol that you might consume.

And if you’re somebody who is concerned

about getting too drunk too quick,

even from a small amount of alcohol,

having some food in your gut can certainly be beneficial.

Now, that’s food and alcohol and the absorption of alcohol,

but let’s go back to talking about the biochemical

and neurochemical effects of alcohol on the brain.

We talked about top-down inhibition

and we talked about habitual

and impulsive behavior circuitry.

There are also dramatic changes in the activity of neurons

that control the release of so-called serotonin.

Serotonin is a neuromodulator.

It changes the activity of neural circuits

and many neural circuits, in particular,

those involved in mood and feelings of wellbeing.

Recently, there’s been a lot of interest in serotonin

because of a study that was released

that showed pretty conclusively that serotonin levels

can’t really explain depression

and depression-like symptoms.

I want to make it very clear that although that study

did show that serotonin levels

are not necessarily associated with depression,

the study was interpreted by many to mean

that SSRI, Selective Serotonin Reuptake Inhibitors,

which have the net effect of increasing serotonin,

these are things like Prozac, et cetera,

that those drugs are somehow not helpful

because they increase serotonin

and serotonin isn’t involved in depression.

That logic doesn’t really hold together,

so I’m going to use this as an opportunity

to just clarify what really occurred there

and then we’ll talk about how serotonin

relates to alcohol consumption

in things like feeling good and in depression.

The key thing is this, SSRIs can help alleviate depression.

That’s right, SSRIs can help alleviate depression.

They are often not always associated with side effects,

dosage is very important, et cetera,

but they probably support relief from depression

by changing neural circuits,

not necessarily by increasing serotonin itself.

That is, increasing serotonin with these drugs

likely change the neural circuits involved in mood,

allowing people to feel better

through so-called neuroplasticity,

which is the brain’s ability to change itself

in response to experience.

So there’s a bit of confusion,

and again, I’m using this episode on alcohol

to highlight some of the confusion

because I think it’s timely

because the study just came out

and there’s a lot of chatter about this out there,

that when people are depressed,

it’s not necessarily because serotonin levels are low.

However, if serotonin levels are increased

with things like Prozac, Zoloft, and other SSRIs,

oftentimes there is, yes, a relief from depression,

but that’s probably not

because of restoring serotonin levels per se,

it’s probably because serotonin facilitates

the changes in neural circuits that need to occur

in order for people to feel elevated mood, okay?

So again, that’s a bit of a tangent and aside,

but I do think it’s a vital one for people to know about.

Again, if you’re thinking about taking SSRIs,

you’re currently taking them and you’ve heard this news,

definitely talk to your doctor.

Again, there is great utility for some of these SSRIs

and also in conditions like OCD,

they’ve been shown to be very beneficial,

so we really don’t want to throw SSRIs out

as a potentially valuable treatment.

Getting back to the effects of alcohol on serotonin,

it’s very clear beyond any doubt

that many of the circuits in the brain

that are involved in mood and feelings of wellbeing

and also sort of self-image and how we see ourselves

employ the neuromodulator serotonin

and alcohol when we ingest it

and it’s converted into acetyl aldehyde,

it goes and that acetyl aldehyde acts as a toxin

at the very synapses,

the connections between the serotonergic neurons

and lots of other neurons.

In other words, when we ingest alcohol,

the toxic effects of alcohol disrupt those mood circuitries

at first making them hyperactive, that’s right,

making them hyperactive,

this is why people become really talkative,

people start to feel really good after a few sips of alcohol,

at least most people do.

And then as they can ingest more alcohol

or as that alcohol wears off, serotonin levels

and the activity of those circuits really starts to drop

and that’s why people feel less good

and typically what they do,

they go and get another drink

and they attempt to kind of restore that feeling

of wellbeing and mood.

Now, typically what happens is that as people ingest

the third and fourth, maybe even the fifth drink,

there’s an absolute zero chance of them recovering

that energized mood, right?

Most people as they drink more and more

will now start to feel more and more suppressed.

The forebrain is now shutting down quite a lot,

a lot of the motor cortical areas

that control coordinated movement

and deliberate movement start to shut down.

So people start to slur their speech,

people start to shuffle their feet,

people forget their posture,

people start to lean on things,

people start passing out on couches.

There’s a great depression,

not depression of the psychiatric depression sort,

but a depression of alertness and arousal

and eventually people will pass out.

Now, I said most people because there’s a subset of people

that have gene variants or who are chronic drinkers

or who are chronic drinkers and have gene variants

that as they ingest the third and fourth and fifth drink,

what happens?

They become more alert, they start talking more,

they feel great, they have all sorts of ideas

about the fun they could have that night

and they’re the ones that if you’ve ever fallen asleep

at a party for whatever reason,

or you’re getting tired and you’re yawning

and looking around the room

and like these people are still drinking and partying

and they’re having what seems to be this amazing time,

often not always those are the future alcoholics in the room

or those are the people

that have a genetic predisposition for alcoholism

or those are the chronic drinkers,

the people who have built up enough of a tolerance

or who have the chemical genetic makeup

such that increasing amounts of alcohol

make them feel better and better and better.

And of course they too have a threshold

beyond which their nervous system

will start to get diminished and they’ll pass out

and fall over, et cetera.

But that threshold is way, way higher

than it is for most people.

Now, this is important to understand

and it’s important to understand

because I think everyone should know and recognize

their own predisposition and kind of risk

in terms of developing alcoholism.

It’s also important to understand

because it relates to the phenomenon of blackout.

You know, many people think that blacking out

is passing out, but blackout drunk is when people drink

and they’re talking and doing things.

Sometimes sadly they’ll, or tragically,

they’ll often drive home or walk home

or they’ll hop on a bicycle and ride home

or they’ll go swimming in the ocean.

All of course, very dangerous activities

to do when people are really drunk

or even a little bit drunk in some cases.

So these people will do these sorts of things

and they do them because they have the energy to do them

and they feel good while doing them,

but they are doing them while the activity of neurons

in the hippocampus, which is involved in memory formation,

are completely shut off.

And this is why the next day you tell them,

hey, maybe we should talk about what happened last night.

Like, what happened last night?

He said, well, do you remember going to the party?

Yeah, no, it was great.

We did this, we did this, and then what?

And it’s very clear all of a sudden

that they have no recollection

of all the things they were doing despite being awake.

Now, I wish I could tell you

that there’s some sort of blood test or other biomarker,

even a fingerprint test that would allow you

to determine whether or not you have a propensity

to be one of these drinkers

that has a predisposition for alcoholism.

And if you’ve ever been blackout drunk,

and certainly if you’ve been blackout drunk

more than a few times, you should be quite concerned.

And as we talk more about the more chronic effects

and long-lasting effects of alcohol consumption

a little bit later in the episode,

I think it will become clear

as to why you should be concerned.

But in any case, there is something that can tell you

whether or not you might be in that category

versus likely not in that category.

And I alluded to this a couple of times already,

but I want to be really clear

that when people drink, no matter who you are,

initially there’s that shutting down

of those prefrontal cortical circuits.

There’s a gradual shutting down of the circuits

that control memory,

but then people divide into these two bins.

And these two bins are the people

who after more than a couple of drinks

start to feel sedated,

and the people who after more than a few drinks

do not start to feel sedated.

Now, of course, there’s going to be differences

created by how quickly people are drinking,

whether or not they’re combining different types of alcohol,

the types of alcohol, et cetera.

But in general, that can predict whether or not

you’re somebody who has a predisposition

for alcoholism or not.

One also very interesting finding

is that alcohol changes the relationship

between what’s called the hypothalamus

and the pituitary gland and the adrenals.

Now, the hypothalamus is a small collection of neurons

about the size of a large gumball

sits above the roof of your mouth,

and it houses neurons that are responsible

for some incredible aspects of our behavior

and our mindset.

Things like rage, things like sex drive,

things like temperature regulation,

very primitive functions,

including appetite, thirst, et cetera.

Alcohol, because it can go anywhere in the brain,

remember it’s water and fat soluble,

has effects on the hypothalamus.

The hypothalamus normally provides very specific signals

to what’s called the pituitary gland.

This is a little gland that actually sticks out of the brain

but it receives instructions from the hypothalamus.

And then the pituitary releases hormones

into the bloodstream that go and talk to your adrenals.

Your adrenal glands sit right above your kidneys

in your lower back.

And the adrenals release, as the name suggests,

adrenaline, also called epinephrine,

and also a molecule called cortisol,

which is involved in the kind of longer-term stress response

has some healthy effects too on the immune system.

Okay, so the hypothalamic-pituitary-adrenal axis.

I know that’s a mouthful,

you don’t need to remember the names,

but the hypothalamic-pituitary-adrenal axis

maintains your physiological balance

of what you perceive as stressful

and what you don’t perceive as stressful.

People who drink regularly,

so this again could be just one or two drinks per night,

or it could be somebody that drinks just on Fridays

or just on Saturdays, or maybe just on the weekend,

two to four drinks.

Well, those people experience changes

in their hypothalamic-pituitary-adrenal axis

that result in more cortisol,

more of this so-called stress hormone being released

at baseline when they are not drinking.

This is really important.

People who drink a bit, and when I say a bit,

I don’t mean one or two sips

or even a glass of wine every once in a while.

Again, people that are maybe having one drink a night

with dinner and maybe on the weekend, a few more.

Again, I offer a bunch of different patterns

to explain how it could also be two or three drinks

on Friday or six drinks only on Saturday.

Well, all of those groups experience increases

in cortisol release from their adrenal glands

when they are not drinking.

And as a consequence, they feel more stressed

and more anxiety when they aren’t drinking.

This is a seldom-talked-about effect of alcohol

because so often we hear

about the immediate effects of alcohol, right?

And we’ve been talking about some of those effects,

effects like reducing the amount of stress.

I mean, how many times have we heard somebody say,

oh, I need a drink, and then they have a drink,

and they’re like, calm down.

Now they can shake off the thoughts about the day’s work.

They can start to think about things

in a maybe more grounded or rational way,

or at least they believe that,

or they can somehow just relax themselves.

Well, while that very well may be true,

that it can relax them, when they are not drinking,

that level of cortisol that’s released at baseline

has increased substantially.

Again, this relates to a defined neural circuit

between brain and body,

and it has to do with the ratio of cortisol

to some of the other hormones involved

in the stress response.

We’ll provide a reference to the study

that describes how all of this works

for those of you that really want to delve into it.

But let’s go back to this issue

of those who are prone to alcoholism

versus those who are not.

Remember, there are people who have genetic variants,

that meaning genes that they inherited from their parents,

that make it more likely that they will become alcoholics.

But there are also people who drink often,

who start to experience this increase in alertness

the longer they drink across the night.

Part of that effect, we think,

is because of changes

in this hypothalamic pituitary adrenal axis.

So alcohol is kind of a double hit in this sense.

It’s causing changes in our brain circuitry

and neurochemistry that at the time

in which we’re inebriated are detrimental,

and it’s causing changes in neural circuitry

that persist long past the time

in which we’re experiencing the feeling

of being tipsy or drunk.

Now, again, I don’t want to demonize alcohol.

I’m not saying, oh, you know,

if you have a glass of wine now and again,

or you drink a beer now and again,

or even have, you know, a mixed drink now and again,

or a shot, that that’s necessarily terrible for you.

I certainly do not want that to be the message.

What I’m saying is that

if people are ingesting alcohol chronically,

even if it’s not every night,

there are well-recognized changes in neural circuits,

there are well-recognized changes

in neurochemistry within the brain,

and there are well-recognized changes

in the brain-to-body stress system

that generally point in three directions.

Increased stress when people are not drinking,

diminished mood and feelings of wellbeing

when people are not drinking,

and as you’ll soon learn,

changes in the neural circuitry

that cause people to want to drink even more

in order to get just back to baseline

or the place that they were

in terms of their stress modulation

and in terms of their feelings of mood

before they ever started drinking in the first place.

So again, I don’t want to demonize alcohol,

but I do want to emphasize

that there are long-term plastic changes,

meaning changes in neural circuitry and hormone circuitry

that across a period of several months

and certainly across a period of years

of the sorts of drinking patterns I described,

which I think for most people

are going to sound like pretty typical, right?

I mean, nothing that I described so far

was about drinking a case a night

or about binging on alcohol

in the way that we often hear about it in the news.

These are pretty common patterns of alcohol consumption.

I mean, all you have to do is board a transatlantic flight

or actually go to an airport on a Sunday afternoon

in a sunny area of the US,

and people are having three, four, five,

six beers, et cetera.

Again, personal choice is personal choice.

I’m not telling you what to do,

but it’s very clear that those sorts of drinking patterns

are changing neural circuitry

and they’re changing hormone circuitry,

and I’d love to be able to tell you

that they’re changing them for the better,

but they simply are not.

They’re actually changing them for the worse,

and worse is defined as making people

less resilient to stress,

higher levels of baseline stress,

and lower mood overall.

I’d like to take a quick break

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Now, I’ve been talking a little bit

about genetic predisposition,

but there are a couple of important points

I’d like to make about that.

First of all, what sorts of genes are involved

in setting someone down the path of alcoholism or not?

Well, it should come as no surprise

that the genes that chronic alcohol usage modifies,

they tend to fall primarily in the pathways

related to genetic control over serotonin receptors,

GABA receptors, remember that top-down inhibition

and the involvement of GABA,

and no surprise, the HPA, the hypothalamic pituitary axis.

All of those, of course, combine with environment,

they combine with patterns of abuse, right?

We know that if you’re in a social setting

where a lot of people are drinking,

the likelihood that you’re going to drink is much higher.

Social pressures, trauma, right?

Some people will use alcohol to self-medicate

to try and turn off their thinking

or to deal with trauma, et cetera.

So they combine with the environment,

but the genes that are in the serotonin synthesis

and receptor synthesis pathway, GABA and HPA axis

combine with environmental pressures

to give rise to alcohol use disorders.

So there’s a fairly coherent picture

that we have here, right?

This is not a case where, for instance,

people that have a lot of the enzyme

for metabolizing alcohol,

which we’ll talk about in a minute, alcohol dehydrogenase,

it’s not like they are necessarily the people

that become alcoholics,

whereas certainly in certain cultures,

certain Asian cultures in particular,

there are gene differences

that lead them to have low levels of alcohol dehydrogenase.

There are actually people

who have so little alcohol dehydrogenase

that when they ingest alcohol,

they get very red and they just feel sick.

So if you’re somebody that has a sip of alcohol

and you just feel horrible, it makes you feel nauseous,

chances are you have gene variants

that create a situation

where you’re not making very much alcohol dehydrogenase.

You just simply can’t metabolize alcohol.

So you just get a rapid buildup

of the toxic effects of alcohol, the acetyl aldehyde.

You’re not converting it into those empty calories.

But in cultures where you have a lot of genetic variants

and genes expressed in people

where they have a lot of alcohol dehydrogenase,

sure, they can drink more

and they’re converting more of that alcohol

from its toxic form to a non-toxic form.

And yes, of course, you will observe more alcoholism

in those communities because they’re drinking more.

But I do want to emphasize that the environmental factors

are playing a strong role there too,

because if you can drink more, you’re likely to drink more.

If you’re somebody that feels sick immediately

from drinking, it’s likely that you’re not going to engage

in alcohol consumption,

especially if these things are genetically related.

And of course, genes and culture and location in the world

tend to run together.

So do you have the gene for alcoholism?

Well, there isn’t one single gene.

Chances are if you have an immediate relative

who’s a chronic abuser of alcohol

or several relatives who are chronic abusers of alcohol,

well, that’s going to predispose you to be an alcoholic.

But since you don’t know which genes you express

unless you do genetic testing and those things

are available, but most people aren’t doing that,

this assay, if you will, and it’s not an assay,

as we say, an assay is a test that you run in the lab

to determine something.

And it’s not one that I recommend that you go drink

in order to do, but if you’ve noticed that you

or somebody else is somebody who can drink a lot

throughout the night and have increased energy

and can just drink and drink and drink,

and especially if there’s blackout episodes,

not remembering things the next day,

despite being alert throughout the entire night and so on,

well, then I would be very concerned that you might

actually have a genetic variant

predisposing you to alcoholism.

The other thing that predisposes people

to abuse of alcohol is age.

People who start drinking at younger ages

are greatly predisposed to developing alcohol dependence,

regardless of your family history of alcoholism.

Okay, so I’m going to repeat that.

People who start drinking younger are at great risk

for developing alcoholism,

even if they don’t have alcoholism in their family.

Now, of course, you don’t have to be an epidemiologist

to understand that if you grew up in a family of drinkers

and alcohol is everywhere,

and especially if there’s peer pressure

or lack of oversight,

then there’s going to be a higher tendency

or a higher probability, I should say,

that you will start drinking at a younger age.

However, even people that grow up nowhere

near their relatives,

if they start drinking at a young age,

so for instance, at 13 or younger or 14 or 15,

there’s a much higher probability

that they’re going to develop

a long-lasting dependence on alcohol.

People who take their first sip of alcohol later,

15, 16, or one would hope even later,

I can say one would hope,

because I’m now of that age and generation

where you think about all the things that young people do

and you go, oh gosh, if they only would wait

or if they only would abstain, you know?

So this is what happens.

I don’t know, there’s some neural circuit for that

that I can’t explain yet.

But people who, for instance,

drink only once they reach legal age of drinking,

which in the US, I believe in every state, is 21 years old,

if they take their first drink at 21,

the probability that they’ll go on

to develop full-blown alcohol dependence

or alcohol use disorder, as it’s called, AUD, is very low.

Now, a subset of them will

because they have such a strong genetic predisposition

or maybe life circumstances create a pattern

in which they become a chronic drinker.

But I found this very interesting.

Genes matter, but also the age

in which somebody starts drinking really matters.

Now, whether or not that’s because there are changes

in neural circuitry as a consequence of that drinking

that make people want to seek out more and more alcohol

or whether or not there’s some other effect,

maybe it’s a change in hormones, et cetera,

that predisposes those young drinkers

to become chronic drinkers or even full-blown alcoholics,

certainly developing alcohol use disorder.

There’s definition for that, we can talk about it.

It involves the amount of drinking

over a certain period of time, et cetera.

So it’s very clear that drinking early in life

creates a propensity for the development

of alcohol use disorder later in life.

And while there is a genetic component

to developing alcohol use disorder,

I find it very interesting

that if people who have those gene variants

delay their onset of drinking,

well, then the probability

that they’ll develop full-blown alcohol use disorder

drops as well.

So again, it’s genes and environments,

it’s not an either or

and there’s no single gene for alcoholism.

Well, I promise you I will also talk about

some of the documented positive effects of alcohol,

although they are very few and far between, they do exist.

But before I do that, I would be remiss

if I didn’t emphasize some more of the terrible things

that alcohol does and the way that it does it.

And for those of you that enjoy alcohol,

I, again, I really like to say I feel guilty

about telling you this

because I know how much some people enjoy a good drink

every once in a while.

And I say a good drink

because some people do like the taste of alcohol.

I suppose I lucked out

in that I don’t really like the taste of alcohol

and that just puts me to sleep,

but I know that people do enjoy it.

And I do want to point out that there is zero evidence

that provided somebody is of drinking age,

certainly not in the stage of brain development,

that having one drink or two drinks every now and again,

meaning every three or four weeks or once a month,

that is not going to cause major health concerns

or major health issues for most people.

I suppose if you have zero

or very little alcohol dehydrogenase,

it might make you feel sick,

but then you’re probably not the kind of person

that’s going to be drinking at all.

So again, if you enjoy alcoholic drinks,

I’m not trying to take them away from you by any means,

but you should know what drinking does

if you’re consuming it in this kind of

typical chronic pattern, as we can now refer to it,

which is that one or two a night

or a few stacked up on Friday

and maybe three or four on Saturday,

this kind of pattern of drinking, which is quite common.

And one of the more serious effects

that we should think about

is the impact on the so-called gut brain axis

or for sake of today’s discussion,

the gut liver brain axis.

I don’t think the gut liver brain axis

has ever been discussed on this podcast, maybe any podcast.

Although the moment I say that,

the gut liver brain axis,

people are going to come after me with, I suppose,

gut, liver, brain, and brains.

In any event, you have a brain, you have a gut.

That gut runs from your throat

down to the end of your intestine.

Your gut and your brain communicate

by way of nerve cells, neurons, and nerve connections,

the vagus nerve in particular,

and by way of chemical signaling.

Your gut also communicates by way of chemical signaling

and believe it or not,

by way of neural signaling to your liver.

And as we talked about earlier,

the liver is the first site in which alcohol

is broken down and metabolized into its component parts.

The liver is also communicating with the brain

through chemical signaling and neural signaling.

So we have the gut liver brain axis.

And what you find is that people who ingest alcohol

at any amount are inducing a disruption

in the so-called gut microbiome,

the trillions of little micro bacteria

that take resident in your gut

and that live inside you all the time

and that help support your immune system

and that literally signal by way of electrical signals

and chemical signals to your brain

to increase the release of things like serotonin

and dopamine and regulate your mood

generally in positive ways.

Well, alcohol really disrupts those bacteria.

And this should come as no surprise.

I mean, earlier we talked about this

and it’s well-known if you want to sterilize something,

you want to kill the bacteria, you pour alcohol on it.

I can remember scraping myself or cutting myself.

I was always injuring myself when I was a kid.

And the moment they take out the peroxide,

you’re like, oh boy, here it comes.

But if there’s no peroxide around

and you’ve got a wound there and you need to clean it out,

yeah, they’ll use alcohol,

which I do not recommend by the way.

And that’s one of the harshest ways to clean a wound.

But for centuries, thousands of years,

really alcohol has been used in order to clean things

and kill bacteria.

So alcohol kills bacteria and it is indiscriminate

with respect to which bacteria it kills.

So when we ingest alcohol and it goes into our gut,

it kills a lot of the healthy gut microbiota.

At the same time, the metabolism of alcohol in the liver,

which you now understand that pathway involving NAD,

acetyl aldehyde and acetate,

that pathway is pro-inflammatory.

So it’s increasing the release of inflammatory cytokines,

things like IL-6, et cetera,

tumor necrosis factor alpha.

If you’d like to learn more about the immune system,

we did an episode all about the immune system.

You can find it at hubermanlab.com.

I’ll teach you all the basics of what are cytokines,

what are mast cells, et cetera.

In any event, all these pro-inflammatory molecules,

those are being released.

You’ve now got disruption of the gut microbiota.

As a consequence, the lining of the gut is disrupted

and you develop at least transiently leaky gut.

That is bacteria that exist in the gut,

which are bad bacteria,

can now pass out of the gut into the bloodstream.

So you’ve got a two hit kind of model here.

In biology, we talk about two hit models.

That is kind of a one plus one equals four.

And it’s generally when you hear two hit,

it’s not a good thing.

So you’ve got bad bacteria from partially broken down food

moving out of the gut.

The good bacteria in the gut have been killed.

You might say,

how does the alcohol kill the bad bacteria in the gut?

Well, the bad bacteria that are from partially digested food

oftentimes escape the gut

before the alcohol can disrupt them.

And so now you’ve got leaks in the gut wall.

You’ve got the release of this bad bacteria.

You’ve got inflammatory cytokines

and other things being released from the liver.

And they are able to get into the brain

through what’s called a neuroimmune signaling.

And what’s really bizarre in terms of the way

that this manifests in the brain,

I mean, it’s not the way I would have done it.

But then again, as I always say,

I wasn’t consulted at the design phase.

And anyone who says they did,

you should be very skeptical of them.

The net effect of this is actually to disrupt

the neural circuits that control regulation

of alcohol intake.

And the net effect of that is increased alcohol consumption.

So this is just terrible, right?

I mean, you’re taking in something

that disrupts two systems, the gut microbiota

and it disrupts in two ways.

It’s killing the gut microbiota

and it’s allowing the bad bacteria

to move from the gut into the bloodstream.

You’ve also got pro-inflammatory cytokines

coming from the liver and those converge

or arrive in the brain and create a system

in which the neural circuits cause more drinking.

That’s a bad situation.

And this is why people who drink regularly,

even if it’s not a ton of alcohol,

again, of the sorts of patterns of drinking

that I talked about before.

And certainly for those that are chronic heavy drinkers,

what you end up with is a situation

in which you have inflammation in multiple places

in the brain and body and the desire to drink even more

and to further exacerbate that inflammation

and the gut leakiness.

So this is basically a terrible scenario

for the gut-liver-brain axis.

And it’s especially prevalent

in so-called alcohol use disorder.

Again, people that are ingesting somewhere

between 12 and 24 drinks per week.

For those of you that are interested in learning more

about the gut-liver-brain axis

and in particular alcohol use disorder,

I’ll provide a link in the show note captions.

And there’s a wonderful review on this that details that.

But on the positive side,

it points to the possibility that at least some,

again, at least some of the negative effects

of alcohol consumption,

whether or not you’re somebody

who’s currently ingesting alcohol

or who used to ingest alcohol

and is trying to so-called repair these systems

of the brain and body,

whether or not replenishing the gut microbiota

is going to be beneficial.

And we know that there are ways to do that.

And we know that there’s at least some promise

for the ability for the system to repair itself.

How does one do that?

Well, I’ve talked before about this on the podcast,

but studies done by colleagues of mine at Stanford,

Justin Sonnenberg, who’s been on this podcast as a guest,

an amazing episode all about the gut microbiome

and his collaborator, Chris Garner,

also at Stanford School of Medicine,

have explored not alcoholism,

but what are ways to improve the gut microbiota

in particular to reduce the production

of inflammatory cytokines

and to adjust what’s called the inflammatome.

You’ve heard of the genome and the proteome, et cetera.

Well, the inflammatome is the total array,

or at least the near total array of genes and proteins

that control inflammation.

How can you reduce inflammation

and make that inflammatome healthier?

Well, they’ve shown that two to four servings

of fermented foods per day,

and here I’m not referring to fermented alcohol,

I’m talking about low sugar fermented foods,

so things like kimchi, sauerkraut, natto,

for those of you that like Japanese food, there are others.

I know things like kefir,

things like yogurts that have a lot of active bacteria,

again, low sugar varieties of all these things.

Those are terrific at reducing inflammatory markers

and at improving the gut microbiome.

One could imagine that either inoculating oneself

from some of the effects of alcohol,

although I’d prefer that people

just not drink alcohol chronically, frankly,

or if somebody is trying to repair their gut microbiome

because they ingested a lot of alcohol

or because they had a lot of these inflammatory cytokines

for many years or even a short period of time,

regular ingestion of two to four servings

of these fermented foods can be quite beneficial.

I want to make it clear that has not been examined

specifically in the context of alcohol use disorder,

but because a huge component of the negative effects

of alcohol use disorder are based

in this gut-liver-brain axis and disruption

of the gut microbiome and the inflammatory cytokines,

it stands to reason that things that are well-established

to improve inflammation status,

in other words, reduce inflammation,

such as ingesting two to four servings

of low sugar fermented foods per day,

make sense in terms of trying to repair

or replenish the system.

One could also imagine taking probiotics or prebiotics.

Certainly that would work as well,

although I’ve sort of favored the discussion

around fermented foods and replenishment

of the gut microbiome, mostly because there are more studies

that have examined that in humans

and because of the direct relationship

that’s been established between doing that

and reducing negative markers within the inflammatory.

And I should mention along the lines of repair and recovery,

I put out a question on Twitter the other day.

I said, what do you want to know about alcohol?

I got more than a thousand questions.

I’ll take some more of those questions

a little later in the episode.

But one of the things I noticed is that many

of the questions, hundreds, in fact,