What Alcohol Does to Your Body, Brain & Health | Huberman Lab Podcast #86

- Welcome to the Huberman Lab Podcast,

where we discuss science and science-based tools

for everyday life.

[upbeat music]

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.

I 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.

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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, you know, 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 5 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 7 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've 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

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about science and science-related tools

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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.

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 in 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 acetaldehyde,

it's broken down into acetaldehyde.

And if you thought ethanol was bad,

acetaldehyde is particularly bad.

Acetaldehyde 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 acetaldehyde into something called acetate.

Acetate is actually something

that your body can use as fuel.

And that process of going from ethanol

to acetaldehyde to acetate

does involve the production of a toxic molecule, right?

Again, acetaldehyde 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 acetaldehyde to acetate fast enough,

well, acetaldehyde 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 acetaldehyde

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 acetaldehyde 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,

like, which neural circuits, what brain areas,

what body areas are 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

that 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 who 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,

'cause 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 or 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 acetaldehyde to acetate,

and some amount of acetaldehyde 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 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,

and 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've 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

that 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.

You 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 that are 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.

This is really important to highlight,

so much so that I want to drill into it a 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.

I mean, 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 brake 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, all right,

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 changed,

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, right?

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 well-being.

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 SSRIs,

selective serotonin reuptake inhibitors,

which have the net effect of increasing serotonins,

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 changed 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

or 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 well-being

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 acetaldehyde,

it goes and that acetaldehyde acts as a toxin

at the very synapses,

the connections between these 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 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 well-being 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,

you're 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, 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.

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 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?"

You said, "Well, do you remember going to the party?"

"Yeah, I know, 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

or 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'll 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

that 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,

and your adrenal gland 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

and it 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.

I mean, 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,

"Ugh, I need a drink."

And then they have a drink and they're, like, calmed 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,

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 well-being

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, you know, 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.

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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-adrenal axis.

All of those, of course combined 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 acetaldehyde,

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 grow 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

'cause I'm now of that, you know, age and generation

where, you know, 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? It's just 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 a 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,

again, I'd 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 it 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, you know, 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 at the moment I say that,

you know, the gut-liver-brain axis,

people are going to come after me

with, I suppose, gut, liver, 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, too, to your liver.

And, as we talked about earlier,

the liver is the first site in which alcohol

is broken down or 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 microbacteria

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, you know, sterilize something,

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

And I can remember scraping myself or cutting myself

or I was always injuring myself when I was a kid,

and, you know, 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.

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, acetaldehyde, and acetate,

that pathway is proinflammatory,

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.

It'll teach you all the basics of what are cytokines,

what are mast cells, et cetera.

In any event, all these proinflammatory 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 exists 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, it's 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, why doesn't 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've 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, so you take in something that disrupts two systems,

the gut microbiota, and it disrupts in two ways,

it's killing the good gut microbiota

and it's allowing the bad bacteria

to move from the gut into the bloodstream,

you've also got proinflammatory 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

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.

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 this 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 Sonnenburg, who's been on this podcast as a guest,

an amazing episode all about the gut microbiome,

and his collaborator, Chris Gardner,

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

or 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's 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,

makes 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 inflammatome.

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 1,000 questions

and 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,

related to the question of,

well, if I drank a lot previously, am I doomed?

Can I reverse the negative effects?

Or, you know, I'm trying to drink less

and I'm trying to improve my health as I do that.

What should I do?

Well, certainly focusing a bit on the gut microbiome

ought to be useful.

The other thing I should mention

is as people wean themselves off alcohol,

even if they're not full-blown alcoholics

or have alcohol use disorder,

they should understand that that increase in cortisol

that we talked about earlier

that leads to lower stress threshold

and greater feelings of anxiety and stress,

that's going to be present

and it's going to take some time to dissipate.

So for some people, it might even just be helpful to realize

that as you try and wean yourself off alcohol

or maybe you even go cold turkey,

that increased anxiety and feelings of stress

should be expected.

And in that case, I would point you to an episode

that we did on master stress.

You can find that, again, at hubermanlab.com.

It's got a ton of behavioral, nutritional,

supplementation-based, exercise-based,

I suppose, exercise is behavioral, but a lot of tools.

You can navigate to those easily 'cause we have timestamps

so you can go right to the topic of interest.

Those tools are going to be very useful

in trying to clamp or control your stress.

And the point here

is just that some increase in stress should be expected,

and it should be expected

because of that increase in cortisol

that occurs with even low-level consumption

yet chronic alcohol consumption.

Now I'd like to talk about a fairly common phenomenon,

which is post-alcohol consumption malaise,

also referred to as hangover.

Hangover is a constellation of effects

ranging from headache to nausea

to what's sometimes called hangxiety,

which is anxiety that follows a day of drinking.

Hangxiety, I think we can understand physiologically

if we think about that process of alcohol intake

increasing the amount of cortisol

and the ratio of cortisol to some other stress hormones.

That well explains why some people wake up the day after

or even the day the day after a night drinking

and feel anxious and not well

and stressed for reasons they don't understand.

So if you're somebody who experiences hangxiety,

then, again, I refer you to the master stress episode

that we put out some time ago,

and you can find that at hubermanlab.com,

tools to deal with anxiety, tools to deal with stress,

ranging, again, from behavioral to nutritional

and supplement-based, et cetera.

That, of course, is not justification

for going out and drinking so much

that you get hangxiety-induced hangover,

but for those of you that are experiencing

post-alcohol consumption hangxiety, as it were,

that could be a useful resource

because I certainly don't want anyone

experiencing uncomfortable amounts of anxiety,

and there are great tools and resources for that.

Now, the other aspects of hangover,

such as the stomachache or headache

or feelings of malaise or fogginess,

those could be related to a number of different things

and probably are related to a number of different things.

First of all, the sleep that one gets after even just one,

yes, even just one glass of wine or a beer

is not the same sleep that you get

when you don't have alcohol circulating in your system.

And not trying to be a downer here,

but this was discussed in the Huberman Lab Podcast episode

where I had Dr. Matthew Walker from UC Berkeley on.

And, of course, Dr. Walker is a world expert in sleep,

runs one of the preeminent laboratories

studying sleep and its effects,

wrote the incredible book, "Why We Sleep," and so on.

Dr. Walker told me, and it certainly is supported

by lots and lots of quality peer-reviewed studies

in animals and in humans,

that when alcohol is present in the brain and bloodstream

that the architecture of sleep is disrupted.

Slow-wave sleep, deep sleep, and rapid eye movement sleep,

all of which are essential

for getting a restorative night's sleep, are all disrupted.

So for those of you

that are drinking a glass or two of wine

or having a hard liquor drink or a beer

in order to fall asleep,

the sleep you're getting is simply not high-quality sleep,

or certainly not as high-quality

as the sleep you'd be getting

if you did not have alcohol in your system,

Of course, when we're talking about hangover,

we're talking generally about the consumption

of more than just one or two drinks.

Of course, for some people, one or two drinks

is probably sufficient to induce hangover,

but for most people it's going to be having three or four,

exceeding their typical limit, as it's called.

Again, not the legal limit, that's a whole other business.

But when one ingests too much alcohol for them,

one of the reasons they feel terrible the next day

is because their sleep isn't really good sleep.

In fact, it's not even sleep.

It's often considered pseudosleep,

or at least that's what it's called

in the sleep science field,

because people are in kind of a low-level,

hypnotic kind of trance, it's not real sleep,

there are multiple bouts of waking up,

they may not even realize they're waking up multiple times.

Okay, so there's the sleep-induced effects.

Then there are the disrupted gut microbiome effects,

some of which we talked about earlier

so now you understand the mechanism

of alcohol destroying good, healthy gut microbiota,

which then leads to leaky gut and things of that sort.

But one could imagine, again, could imagine,

and there is some evidence starting to support this,

that, again, ingesting low-sugar fermented foods

or maybe even prebiotic or probiotics

to support the gut microbiome

might assist in some of the gut-related malaise

associated with hangover.

In other words, get those gut microbiota healthy again

as quickly as possible,

or maybe even before you drink,

have those gut microbiota healthy.

I would hope that you'd do that.

I think everybody should be doing something

to support their gut microbiome,

whether or not it's the ingestion

of low-sugar fermented foods daily

or at least on a regular basis

or ingestion of probiotic or prebiotic.

The gut microbiome is so important

for so many different things.

In terms of hangover and headache,

we know that that's caused by vasoconstriction,

the constriction of blood vessels that tends to occur

as a rebound after a night of drinking.

Alcohol can act as a vasodilator,

it can dilate the blood vessels.

Part of that is associated with the increase

in so-called parasympathetic tone.

We have an autonomic nervous system

and it's got a sympathetic component.

These are neurons that make us more alert,

and if they're very active, they make us very stressed.

There's also the parasympathetic aspect

of the autonomic nervous system.

This is all just fancy geek speak

for the parts of your brain and body,

the nerve cells that make you very relaxed.

When you're very relaxed, there tends to be vasodilation.

It allows for more movement of blood

and other things through the bloodstream,

and alcohol tends to induce some vasodilation,

at least in some of the capillary beds.

And then when the alcohol wears off,

there's vasoconstriction and people get brutal headaches.

That's why some people will take aspirin or Tylenol

or Advil or things like that,

the sort of non-steroid anti-inflammatories.

I should mention, there is a lot of literature coming out

that some of these non-steroid anti-inflammatory drugs

are not good for us for a number of different reasons,

the way they impact the liver,

the way they impact the immune system,

and, no surprise, the way they impact the gut microbiome.

So I'm not one to tell you what medications

to take or not take,

but you certainly would want to do a quick web search

of effects of non-steroid anti-inflammatories

and aspirin before you start taking those,

or stop taking those, for that matter.

Generally, they will alleviate headache,

but they can often have other issues,

including liver issues.

And keep in mind, the night after drinking,

your liver has already taken a beating

because of the need of the liver

to convert alcohol from acetaldehyde into acetate,

which is now a pathway that you well understand.

So I'm not certain

and, in fact, I believe it's not the greatest idea

to burden your liver further

through the use of things that are going to cause it

to have to work harder and metabolize things

if the goal is simply to alleviate a headache.

There's a lot of kind of lore,

old school lore about how to relieve a hangover.

We already talked about how eating food won't do that

but eating food will prevent the rapid absorption

of even more alcohol into the bloodstream.

There's the lore that one should simply ingest more alcohol.

What terrible advice that is.

That's just going to delay an even worse hangover.

However, I'd be remiss if I didn't say that the reason

that that myth came to be,

or that, I should say, that truth came to be,

because indeed ingesting more alcohol

will alleviate a hangover

but then a worse hangover will show up,

the reason that came to be

is because ingestion of more alcohol

will cause those constricted vessels

that are giving the headache to dilate again.

But, of course, ingesting more alcohol to relieve a hangover

is simply a bad idea.

Just don't do it.

I think this is called the hair of the dog approach.

Maybe someone can put in the show note captions on YouTube

why it's called the hair of the dog.

I can come up with a few ideas

but they're not going to be very good ones,

and some of them would probably even be outright ridiculous.

So do not ingest more alcohol

simply to try and recover from a hangover.

I know many people have tried that one before

but that's a terrible idea.

Now, one thing that you'll also hear out there

is that deliberate cold exposure,

for instance, taking a cold shower, might relieve hangover.

I find this one particularly interesting

because we've done episodes on the benefits

of deliberate cold exposure.

We have an entire episode about that.

You can find it, again, hubermanlab.com.

There are direct links to some of the tools

related to deliberate cold exposure

and we have an entire newsletter

on deliberate cold exposure protocols

that you can find on hubermanlab.com,

go to our Neural Network newsletter.

So those of you that are interested in ice baths

and cold showers and ways to leverage those,

you can find that there.

What you won't find there is a description

of how to use deliberate cold exposure

for sake of treating hangover.

But here, I went into the literature

and I found something kind of interesting.

There is some evidence

that increasing levels of epinephrine in the bloodstream

can actually help with alcohol clearance.

That was very surprising to me,

and I want to point out

this is not a large and robust literature,

but there's some evidence pointing to the fact

that when levels of epinephrine, adrenaline,

are raised in the brain and bloodstream,

that some of the components of alcohol metabolism

can be accelerated

and some of the inebriating effects of alcohol

can be reduced,

so maybe this old school lore of taking a cold shower

actually has something to it.

So in thinking about the use of deliberate cold exposure

in order to reduce the effects of hangover

or to more rapidly clear alcohol

from the brain and bloodstream,

I want to be very clear and I want to emphasize your safety.

The way to do that is to understand

that alcohol lowers core body temperature, okay?

It can make people slightly hypothermic.

It's going to drop core body temperature.

So if you were inebriated

and you went and got into a body of water, right,

a pool or a lake or something,

first of all, that's extremely dangerous

to do while you're inebriated, right?

People drown all the time.

People drown, they die as a consequence of doing that,

so please don't do that.

But also, if it's very cold water,

your core body temperature is going to drop even further.

Now, if you've heard the episodes that I've done

on deliberate cold exposure previously,

I've talked about how normally,

when people are not ingesting alcohol,

they get into an ice bath or a cold shower

and their body temperature initially dips

but then it rebounds and increases.

That's a process that's going to occur

when people do not have alcohol in their system.

When you have alcohol in your system,

one of the reasons that you become hypothermic

is because there's a disruption

in those hypothalamic brain areas,

in particular, the brain area

called the medial preoptic area

that regulates core body temperature.

So it's not so much that alcohol makes you cold,

it's that alcohol disrupts the central command centers

of the brain that control temperature regulation,

and that leads you to be slightly hypothermic.

So if you then go get into a very cold lake

or you get into even a cold shower or an ice bath,

there's the possibility

of you going very, very far down the ladder

into very hypothermic territory

and that can be very dangerous.

Now, in terms of dealing with hangover

when the alcohol has been largely cleared from your system,

well, that's where some of this old lore

combines with some of the modern science

and says, well, if you can spike adrenaline,

and certainly getting into an ice bath

or getting into a cold shower

or any kind of cold body of water,

provided you can do that safely,

that will sharply increase your adrenaline

and, I should say, your dopamine.

That's been shown

and we've talked about this on the podcast before.

You get these long, extended increases,

several hours of increases in dopamine

from deliberate cold exposure.

It's well-documented in humans, by the way.

So one could imagine using deliberate cold exposure

as a way to accelerate the recovery from hangover.

Provided that's done safely,

I think there's no reason to not explore that,

and if you wonder what safely is

and what temperatures to use,

please check out the episode on deliberate cold exposure.

Cold showers, therefore, might actually be one way

to at least partially relieve hangover.

Certainly the science from various places in the literature

converged to say that.

But, again, be careful, please, please, please be careful

not to get into cold water when you are inebriated.

It's absolutely dangerous for all the obvious reasons,

and it's dangerous also for the nonobvious reasons,

not the least of which

is the dramatic decreases in core body temperature

that can make you dangerously hypothermic.

Now, how would you go about using deliberate cold exposure

to accelerate recovery from hangover?

Well, there, I would look to the kind of standard protocols

of, you know, one to three minutes

or maybe even six minutes if you can tolerate it,

or if you're really cold-adapted,

maybe you do seven or ten minutes in a cold shower,

although that could be a lot.

Most people are going to experience a sharp increase

in epinephrine, in adrenaline,

and a long-lasting increase in dopamine

from one to three minutes of deliberate cold exposure,

ideally done immersion up to the neck,

again, do this safely, please, please, please,

or a cold shower where you're getting under the shower

as much as possible.

How cold? Well, that's going to vary person to person.

I suggest making it as cold as is uncomfortable

such that you really want to get out

but that you know you can stay in safely

without, for instance, giving yourself a heart attack,

because if the water is really, really cold,

of course you can give yourself a heart attack.

Most showers won't go that cold,

although probably some will.

Again, please use caution.

Spike your adrenaline, spike your dopamine

with deliberate cold exposure safely.

Other components of hangover that could be good targets

for trying to alleviate hangover,

and, here, I hope you are getting the picture

because it is accurate to say that hangover

is a multifaceted phenomenon.

It's not like one molecule and one receptor.

It's a bunch of things happening in the brain and body.

But is the dehydration associated with alcohol?

Alcohol is a diuretic.

For multiple reasons, it causes people

to excrete not only water but also sodium.

Sodium is an electrolyte

critical for the function of neurons,

so making sure that you have enough sodium,

potassium, and magnesium, so-called electrolytes,

is going to be important

for proper brain function, bodily organ function.

Even for people that have just had one or two drinks

the night before,

it's likely that your electrolyte balance

and your fluid balance is going to be disrupted,

and that's because alcohol also disrupts

the so-called vasopressin pathway.

I talked a lot about vasopressin

and the way that it interacts with

and controls different aspects of water retention

and water release from the body in the form of urine

in the episode on salt.

So, again, I'm referring to hubermanlab.com

as the site where you can find that episode

on salt balance and ways to restore electrolyte balance.

Having your electrolytes at the proper levels

before you drink is ideal.

Some people will say for every glass of alcohol

that you drink, you should drink one glass of water.

I would say better would be two glasses of water

given the dehydrating effects of alcohol,

and even better would be water with electrolytes.

That certainly would set you up

for a better day the next day.

And if you don't manage to do that,

'cause I suppose it's kind of geeky

walking around with electrolyte packets

out at the bar or whatnot,

although, you know, geeky, in my book, is a good thing,

the next day, you could take some electrolytes upon waking,

maybe even some before you go to sleep

the night of drinking.

So hangover's made worse by disturbed sleep,

made worse by disrupted gut microbiome,

made worse by disrupted electrolytes,

made worse by the depletion of epinephrine and dopamine.

That's why replenishing the microbiome with fermented foods,

low-sugar fermented foods, that is,

that's why using safe deliberate cold exposure

for spiking adrenaline and for increasing dopamine,

and that's why consuming electrolytes

are all going to be beneficial.

The folks over at examine.com, a website that I really like

because it just has so much useful information,

have assembled a list of things

that have been proposed, purported to improve,

or, I should say, to remove the effects of hangover,

and, as they point out

and I would like to point out over there,

there isn't a lot of quality science to support the idea

that any one compound can eliminate hangover.

And that's probably because hangover,

again, arises from multiple organs and tissues and systems

in both the brain and body.

Nonetheless, they have a terrific list over there of things,

everything from Japanese pear fruit juice

has been proposed to do this,

to some other really esoteric things,

even things like yohimbine.

Frankly, when I look at the literature there and elsewhere,

one simply cannot find the magic substance,

the one herb, the one potion that can wipe away hangover.

Getting rid of hangover

is going to be best solved by doing a collection

of a small number of very powerful things,

of which I've already listed off a few.

However, there are some additional things

that one can do for relieving hangover,

and one of them is to be very thoughtful

about what sorts of alcohol one consumes.

So I find this interesting.

There have actually been studies

of which types of alcohol lead to the greatest hangovers.

There's actually a lot of legend and lore

about this as well.

Some people have said, for instance,

that drinks that have a high sugar content

lead to greater hangovers.

Turns out that's not the case,

or at least that's not what the science points to.

If you look at the expected hangover severity,

what you find is that at the bottom end of the scale,

there's a drink that I'm not going to tell you, for the moment,

but what you find is that near it is, for instance, beer.

The consumption of beer,

provided it is not overconsumption, right,

it's not far beyond the tolerance of the individual,

so it's one or two beers,

is less likely to cause a hangover than, say, whiskey.

And a glass of whiskey,

or, you know, not as much whiskey as beer, of course,

but a glass of whiskey, for instance,

is more likely to cause hangover than gin, as it turns out.

Again, this is what's fallen out of the data.

And yet a glass of rum or red wine

is more likely to cause a hangover

than any of the other things I've mentioned so far.

At the top, top, top of the list

of drinks that induce hangover is brandy.

And one could then say,

"Well, doesn't brandy have a lot of sugar?

Maybe it's the sugar that's causing hangovers."

And this is something that's been,

again, discussed over and over, that people say,

"Oh, it's the high-sugar drinks that cause hangover."

It turns out, however,

that when one looks at alcoholic drinks

and sugar content and hangover,

at the very bottom of the list is,

gosh, this makes me cringe just to think about,

is ethanol diluted in orange juice.

Ugh, I can't believe people actually drink this,

but ethanol diluted in orange juice.

So this is not vodka and orange juice, okay?

Vodka was third on the list from the bottom

of drinks that induce hangover.

Again, this is within amounts

that are comfortable for the person to drink,

that they have enough experience with

or that they have the body weight to tolerate

without getting very, very drunk.

So the point is that if it were sugar

that's causing hangover,

well, then the ethanol diluted in orange juice

would probably be at the top of the list

in terms of inducing hangover.

But it's not, it's at the bottom of the list,

and brandy is at the top of the list.

So what you find is that what scales

from ethanol diluted in orange juice

to beer to vodka to gin,

here, I'm ascending the hierarchy

of things that cause hangover,

gin, white wine, whiskey, rum, red wine,

and then brandy at the peak,

it's sort of the world heavyweight champion

of hangover-inducing drinks,

well, what's increasing are congeners within those drinks.

Congeners are things like nitrites and other substances

that give alcohol it's distinctive flavor

and that also lead

to some of the inebriating effects of alcohol.

Now, then you ask,

"Okay, well, what is it that these congeners are doing?

And what are these nitrites doing?"

And guess what?

While they do have effects on the brain

and on other tissues,

their main effects are to disrupt the gut microbiome.

So what this points to again

is that having a healthy gut microbiome

and perhaps ensuring that you bolster your gut microbiome

the day after drinking

is going to be especially important for warding off hangover

or at least reducing the effects of hangover

or the symptoms of hangover or both.

I would love to see a study on this.

I could imagine designing the study myself,

although this isn't really the sorts of things

my laboratory does,

but can imagine some people getting probiotic and prebiotic,

some regularly, some just after drinking,

or low-sugar fermented foods,

and see what the effects are

in terms of subjective effects of hangover

but also some physiological measures.

I think the way to think about hangover overall

is that, again, it represents a multifaceted,

multi-organ, multi-tissue phenomenon,

and the best way to deal with it

is as a multi-cell, multi-tissue, multi-chemical phenomenon.

And before I listed off some of the things

that one could do in order to adjust hangover,

again, the one that comes out at the top of that list,

I believe, at least based on my read of the data,

is to support the gut microbiome

and certainly not to ingest more alcohol.

And I suppose if we were to get really honest

with one another

and ask what's the best way to avoid a hangover,

it would be to not drink in the first place.

So we've covered the major effects of alcohol

that lead to this state

that we call drunkenness or inebriation.

Again, there's a range there.

You can be tipsy, people can be blackout drunk,

people can be passed out drunk.

We've also talked about hangover

and the fact that it's a multifaceted phenomenon

and recovery from hangover involves a multifaceted approach.

Next I want to talk about tolerance.

Tolerance to alcohol is a very interesting phenomenon.

It has roots mainly in the brain and in brain systems.

There's not time in the world,

let alone within this podcast,

to get into all the aspects of tolerance.

There are more than 10 different types of tolerance.

There's functional tolerance, chronic tolerance,

rapid tolerance, there's metabolic tolerance,

there's psychological tolerance.

Let's keep it simple for sake of today's discussion.

And for those of you that are interested

in learning about all the different types of tolerance

and aspects of tolerance, there's an excellent review,

we will provide a link to this.

This was published in 2021, so it's pretty recent,

in the journal "Pharmacology Biochemistry and Behavior."

Incidentally, or not so incidentally,

that was the first journal I ever published in

so I have a particular affection for that journal.

Nonetheless, it is called Tolerance to alcohol:

A critical yet understudied factor in alcohol addiction.

And while this paper

does include alcohol addiction in the title,

it's not just about alcohol addiction.

Here's the basic summary of what tolerance is.

First of all, tolerance refers to the reduced effects

of alcohol with repeated exposure,

and it is caused mainly by changes

in neurotransmitter systems in the brain

that are the direct consequence of the toxicity of alcohol,

that aldehyde molecule that we talked about before.

There's an enormous number of chemicals that change

with repeated exposure to acetaldehyde,

everything from GABA to dopamine to serotonin,

second messenger systems, adenosine, and on and on.

Rather than go into each of those in detail,

I just want to talk about the contour of the reinforcing

and the tolerance-inducing effects of alcohol.

What do I mean by that?

Well, here we are back to our old friend,

meaning the molecule that comes up over and over again

in these podcast episodes, which is dopamine.

Whether or not somebody

has a predisposition to alcoholism or not,

whether or not they're experienced drinker or not,

when people initially start drinking,

there are increases in dopamine,

or what we call dopaminergic transmission.

Dopamine is involved in motivation, in craving,

it creates a sense of well-being, it increases energy,

again, typically only at the beginning of alcohol exposure.

That occurs in most people as a sharp spike, as a increase.

Again, if somebody does not have alcohol dehydrogenase

or has very low levels of the enzyme

that convert that acetaldehyde into acetate

and that metabolize alcohol, in other words,

they will feel sick and lousy in a way

that will override any recognition of the dopamine release.

They're going to be the people that are listening to this

and just thinking, "Alcohol just makes me feel sick.

I don't like it."

Okay, that's a specific subcategory of people,

but most people experience some sort of mild euphoria.

That's why so many people drink, right?

The current estimates are that in most countries,

and certainly in the US, as many as 80% of the adult,

legal drinking age population drinks alcohol,

and that number could be even higher now

because in the last couple of years,

there's been a trend towards increased alcohol consumption,

especially in the wake of the pandemic

and during the pandemic.

Topic for another time.

So there's an increase in dopamine

and an increase in serotonin,

so it's kind of an increase in well-being,

an increase in mood, but it's a very short-lived increase.

Very soon after, and actually triggered by that increase,

is a long and slow reduction in dopamine and serotonin

and related molecules in circuits.

So basically what you're getting is a blip of feel good

followed by a long, slow arc of feeling not so great,

which is why, typically, people will drink

again and again across the night.

The key thing to understand about tolerance

is that with tolerance,

the duration of that long, slow reduction

in dopamine and serotonin gets even longer.

In other words, the negative effects of alcohol

that happen after the initial feeling good,

extend longer and, in fact, get more robust.

However, there's also a reduction

in the reinforcing properties of alcohol.

There's a shrinking of the feel good blip

that happens when one first ingests alcohol,

and this has been measured in animals and humans.

So the first drink that somebody has,

provided they have enough alcohol dehydrogenase

so that doesn't make them feel nauseous and sick right away,

they feel really good.

And then as it wears off, they feel kind of lousy

and they want to drink more so they might drink more.

With each subsequent drink,

and even drinks on different nights or even different weeks,

the amount of dopamine that's released is reduced,

the amount of serotonin that's released is reduced.

So what you're getting is less and less

of the reinforcing properties of alcohol,

the feel good stuff,

and more and more

of the punishment pain signal aspects of alcohol.

This is the contour of chemical release in the brain

that was referred to by my colleague,

the incredible Dr. Anna Lembke, who's a medical doctor.

She wrote the incredible book "Dopamine Nation."

She was a guest on this podcast, on Joe Rogan's podcast,

on Rich Roll's podcast and several other podcasts.

World expert in addiction,

and she talked about this pleasure-pain balance

that extends beyond alcohol

to things like sex and gambling and to other behaviors

that can potentially become addictive

but certainly includes alcohol.

So tolerance, it seems, is a process in which people

are ingesting more and more alcohol

as an attempt to get that feeling of well-being back,

but what they're really getting is an extended period

of punishment, of pain, and of malaise from the alcohol.

Now, you might say,

"Well, how does that relate to tolerance?"

Well, it turns out what they do behaviorally,

and when I say they,

I mean animals do this and humans do this,

is they start drinking more and more

in an attempt to activate those dopamine

and serotonin neurons and receptors,

and as they do that,

there is an increase in alcohol dehydrogenase,

so the enzyme that metabolizes alcohol is increased

because the body and liver

have to contend with all that alcohol,

so now you've got, again, the two-hit model.

You're getting less of the feel good chemicals,

more of the negative chemical release,

or pattern of subjective feeling, I should say,

and you're metabolizing alcohol

more quickly and more readily,

but it's not taking you to a better place

in terms of how you feel.

That's one of the major underlying reasons

for what we call tolerance.

So if you're somebody who drinks

and you notice that the feeling

that you are seeking with alcohol

is now requiring an additional drink, or drinks plural,

chances are you are disrupting the dopamine

and serotonergic systems of your brain,

and you are doing that in a way

that is increasing the pain and punishment signals

that follow alcohol ingestion.

And again, that's not just on the night that you're drinking

but afterwards as well.

Is that all bad news? Well, pretty much.

But the good news is that if you abstain from drinking

for some period of time,

then, of course, these systems reset.

How long you need to abstain

will depend on how much you were drinking

and how long you were drinking for.

Certainly people who have alcohol use disorder

or who are alcoholics,

their main goal should be to quit alcohol completely.

I know there's some debate about this,

and I don't want to get into that debate

because I'm certainly not going to try

and direct anyone's recovery.

There are expert counselors and MDs

and people that can work with people.

In fact, for some very heavy drinkers

and people with serious alcohol use disorder,

going cold turkey, that is, stopping drinking completely,

can actually be medically dangerous.

So the path to sobriety for certain people

looks different than the path to sobriety for other people.

What I'm referring to here are people that are ingesting,

again, somewhere between, on average,

one to two drinks per night,

whether or not that's done night to night

or whether or not that's condensed to weekend use.

I know a number of people are going to ask,

perhaps are screaming, "Is drinking good for me in any way?"

For instance, many people have probably heard

that resveratrol is good for people

and that red wine is rich in resveratrol.

I hate to break it to you but the reality

is that if indeed resveratrol is good for us,

and there's some debate about this,

some people say strongly yes,

some people say no, other people say maybe,

the amount of red wine that one would have to drink

in order to get enough resveratrol

in order for it to be health promoting

is so outrageously high

that it would surely induce other negative effects

that would offset the positive effects of resveratrol.

So I wish I could tell you different.

Again, I'm not here to be the bearer of bad news,

but the statement I just made

was confirmed by Dr. David Sinclair

when he was a guest on this podcast.

It's confirmed by other researchers

who work on resveratrol and related pathways.

I wish I could tell you

that red wine is good for your health,

and indeed it might be through some other mechanisms.

So, for instance, there have been studies

of low to moderate red wine consumption.

This would be anywhere from one to four glasses per week.

And I don't mean enormous glasses,

I mean six-ounce glasses of red wine.

And in those cases, some of the stress reduction

that can be induced by consumption of red wine,

maybe some of the other micronutrients

and components within red wines,

in particular red wines that come from particular grapes,

and this gets really nuanced

and, frankly, is not well worked out

in the peer-reviewed literature

or certainly not clinical trials,

at least not that I'm aware of.

Tell me if you're aware of a great clinical trial on this.

Well, there may be some positive effects

of that very low level of consumption.

I'm not trying to take away anybody's red wine.

I'm not trying to take away anybody's anything.

I would be remiss, however, if I didn't tell you

that resveratrol as the argument for drinking,

and drinking red wine in particular,

is just not a good one.

It's just not supported by the peer-reviewed research.

A few other things about alcohol and health.

At the beginning of the episode, I referenced a study

showing that indeed not just heavy alcohol consumption

of 12 to 24 or more drinks per week,

but also light to moderate alcohol consumption of any type,

wine, beer, spirits, et cetera,

does reduce the thickness of the brain.

It really does reduce cortical thickness.

In fact, it actually scales

with the amount of alcohol that people drink,

and this has been well-documented

in a number of different studies.

I can provide a link to several of these.

One of the more striking ones actually shows

that there's almost a dose-dependent increase

in shrinkage of gray matter volume

and in these white matter tracts,

these axons, these wires, as it were,

that connect different neurons

as a function of how much alcohol people drink.

And that's also what's been seen in this recent study

that I referenced at the beginning

and that's in the show note captions.

So, again, probably the best amount of alcohol to drink

would be zero glasses per week or ounces per week.

For those of you drinking low amounts of alcohol,

make sure you're doing other things to promote your health.

And for those of you that are drinking moderate

and certainly for those of you that are heavy drinkers,

please do everything you can to move away from that

and to quit entirely.

But even for the moderate consumers of alcohol,

you are going to want to be aware

of some of the negative health effects

and do things to offset those

if indeed you're not going to stop drinking

or reduce your intake.

One of the really bad effects of alcohol,

but that's extremely well-documented,

is the fact that alcohol, because of this toxicity

of acetaldehyde and the related pathways,

can alter DNA methylation, it can alter gene expression.

That can mean many things in different tissues,

but it is associated

with a significant increase in cancer risk,

in particular, breast cancer,

and in particular, because breast tissue is present

in both males and females,

but in women, it's especially vulnerable

to some of the DNA methylation changes,

well, breast cancer in women

has a relationship to alcohol intake,

and alcohol intake has a relationship

to breast cancer in women.

In fact, there has been proposed

to be a anywhere from 4 to 13% increase

in risk of breast cancer

for every 10 grams of alcohol consumed.

How much is 10 grams?

Well, there, we need to think a little bit

about the variation in the amount of alcohol

and different drinks across the world.

Different countries serve different sized drinks

and have different concentrations

of alcohol in those drinks.

So without going down too much of a rabbit hole

and just giving you some good rules of thumb to work with,

there have been studies of the percentage of alcohol

included in different drinks

and the sizes of different drinks

that are served in different countries,

and here's kind of a patchwork of those findings.

In Japan, one beer, one glass of wine,

or one shot of liquor, as it's served there,

tends to include anywhere

from seven to eight grams of alcohol.

In the US, one beer, which generally is 12 ounces

if it's in a bottle,

one glass of wine or a shot of liquor

tends to include about 10 to 12 grams of alcohol.

And in Russia, one drink

of the various sorts that I just described

typically will have as much as 24 grams of alcohol

because of the differences in the concentration of alcohols

and the sizes of drinks that are poured

in these different countries, okay?

Of course, there are other countries in the world,

those countries are also vitally important,

but those are the ones that I extracted from the studies

that I could find.

What does this mean?

Well, what we're talking about

is that for every 10 grams of alcohol consumed,

so that's one beer in the US,

maybe a little bit more than one beer in Japan,

or basically a third of a drink in Russia,

there's a 4 to 13% increase in risk of cancer.

That's pretty outrageous, right?

And you might think, "Wait, how could it be

that, you know, this stuff is even legal?"

Well, look, as I described before, it's a toxin.

It's also a toxin that people enjoy the effects of.

I mean, in the US at least, they tried prohibition.

It certainly did lead, yes, did lead to a reduction

in alcohol-induced health disorders,

in particular, cirrhosis of the liver.

It also led to a lot of crime

because it became a substance

that a lot of people still wanted

and that people were willing to break the law

in order to provide, or, I should say, to sell and provide.

But the point is that the more alcohol people drink,

the greater their increase of cancer,

in particular, breast cancer.

And that's because of the fact

that alcohol has these effects on cells

that include changes in gene expression,

and cancer, that is, the growth of tumors,

is a dysregulation in cell cycles, right?

A tumor is a aggregation or the proliferation,

aggregation is stuff sticking together, by the way,

proliferation is stuff duplicating,

a proliferation or aggregation of cells

that could be a glioma, glial cells,

glioma brain tumor, right?

It could be lymphoma, so within the lymph tissue, et cetera.

The mutations that alcohol induces to cause this

are wide ranging,

some of those are starting to be understood.

For those of you that are interested in cell biology,

I'll just mention that the PD-1 pathway,

again, this is super specialized

and for the aficionados only, you don't need to know this,

the PD-1 pathway seems to be upregulated and,

and we knew this from the discussion earlier,

there's a downregulation

in some of the anti-inflammatory molecules

that help suppress this proliferation of cancers.

Nowadays, there's a lot of interest in the fact

that the immune system is constantly combating cancers

that exist in us all the time.

You know, little tumors start growing

and our immune system goes and gobbles them up.

Little tumors start growing,

the immune system senses inflammation,

sends out these incredible cells,

these killer B-cells and T-cells, and beats them up.

Cancers proliferate and take hold and cause serious problems

when the proliferation of cells

exceeds the immune system's ability

to gobble up and remove those cells.

There are other mechanisms of regulating cancers,

but that's one of the primary one.

And alcohol hits it. Again, it's a two hit model.

It increases tumor growth

and it decreases the sorts of molecules

that suppress and combat tumor growth.

So, again, even low to moderate amounts of alcohol

can be problematic for sake of cancers,

in particular, breast cancers.

Epidemiologists and health specialists

love to try and compare different substances

in terms of how bad they are.

Rarely do they compare substances

in terms of how good they are, but sometimes they do.

And what they'll sometimes tell you

and what you can find in the literature

is that ingesting 10 to 15 grams of alcohol a day,

so that would be like one beer in the US

or one glass of wine,

is the same as smoking 10 cigarettes a day.

Frankly, it's hard to make that direct relationship

really stick because, you know, it's a question

of, you know, how long people inhale,

do they have a predisposition to a lung cancer, et cetera.

But even if that number is off

by plus or minus two cigarettes,

or even if that number was the equivalent

of one glass of wine equals one cigarette per day...

I think there's general consensus now

that nicotine consumed by vaping or by cigarette,

it's bad for us in terms of lung cancer

and other forms of cancer.

And for some reason, I don't know why,

because this knowledge about alcohol and cancer

and these established relationships

have been known since the late 1980s.

The first, you know, landmark paper on this

was published in 1987.

I can provide a link to that paper.

It's actually quite interesting to read.

Well, the relationship is there

and yet we don't often hear about it, right?

In fact, before researching this episode,

I had heard before that alcohol can increase cancer risk

but I wasn't aware of just how strong that relationship is.

Because of the serious nature of what we're talking about

and because I would hate to be confusing

or misleading to anybody,

I want to just emphasize that this statistic,

that there is a 4 to 13%,

depending on which study you look at,

a 4 to 13% increase in the risk of cancer,

in particular, breast cancer,