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

Welcome to the Huberman Lab Podcast,

where we discuss science

and science-based tools for everyday life.

I’m Andrew Huberman,

and I’m a professor of neurobiology and ophthalmology

at Stanford School of Medicine.

Today, we’re discussing alcohol,

one of the most commonly consumed substances

on the planet Earth.

Should mention that both humans

and non-human animals consume alcohol

either for recreational purposes

because they like the feeling that it gives them

or for medicinal purposes

or for other purposes that we’ll discuss.

We are of course going to discuss the effects of alcohol

on our biology,

ranging from its effects on individual cells,

on organs and organ systems in our brain and body.

We are also going to discuss the effects

of the effects of alcohol.

That is what being inebriated really does

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

And we are going to address

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

which is whether or not low to moderate amounts of drinking

are better for our health

than zero alcohol consumption at all.

And of course, we will talk about

severe alcohol intake, binge drinking.

We will also talk about hangover

and what science says about ways

to reduce the effects of hangover,

either by doing things that are inoculatory,

meaning before you drink or while you drink,

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

We will discuss some of the genetic differences

for alcohol and alcoholism.

And we will discuss alcohol consumption in young people

and how that can be especially detrimental

for reasons that I think are going to be

quite surprising to most of you.

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

you will have a thorough understanding

of what alcohol does to your brain and body

and that you will be able to make informed decisions

as to whether or not you should be consuming zero,

absolutely no alcohol,

small to moderate amounts of alcohol.

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

small to moderate amounts.

And if you or somebody else that you know

is consuming excessive amounts of alcohol

that are clearly detrimental to your health,

some of the better routes and resources that you can use

in order to remove that dependence and or consumption.

I’d like to preface all of that by saying

that today’s discussion is really geared

toward giving you information.

It is not about judging alcohol intake

or lack of alcohol intake.

I just want you to be able to make

the most informed decision about alcohol possible.

Before we get into today’s content in detail,

I just want to answer a commonly asked question

about alcohol consumption and the brain.

And the question that so often comes up

is whether or not low to moderate amounts of alcohol,

so maybe one drink a day

or one or two drinks a day kind of thing,

whether or not that is bad for your brain,

in particular, whether or not it causes degeneration

of neurons or nerve cells.

Now, the reason that question comes up so often

is because for many years,

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

so 12 to 24 drinks per week or more,

is certainly causing neurodegeneration,

in particular, of the so-called neocortex,

the outer layers of the brain

that house associative memories,

that house our ability to think and plan,

that house our ability to regulate our more primitive drives

according to context, et cetera.

So to make very clear, drinking a lot,

so having three or four drinks per night

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

A recent study, however, finally addressed the question

of whether or not low to moderate amounts

of alcohol consumption can cause brain degeneration.

The title of the study is

Associations Between Alcohol Consumption

and Gray and White Matter Volumes in the UK Biobank,

the United Kingdom Biobank.

First of all, gray matter are the neurons,

it’s the so-called cell bodies

that house the genome of the cells, et cetera,

and white matter is the connections, the fibers,

the so-called axons of neurons.

And it’s called white matter

because that tissue is surrounded by a fatty tissue

called myelin, which allows nerve cells

to communicate with each other very quickly.

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

both the gray matter and the white matter,

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

generally healthy middle-aged and older adults

in the United Kingdom

who were drinking various amounts of alcohol.

What they found was that even for people

that were drinking low to moderate amounts of alcohol,

so one or two drinks per day,

there was evidence of thinning of the neocortex,

so loss of neurons in the neocortex,

and other brain regions.

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

I tell you this because they are important data

because they reveal and indeed answer the question

that has been burning for so long

as to whether or not chronic alcohol intake

can disrupt the brain,

even if the chronic intake is very low.

Now we should talk about what the word chronic means

because many people, when they hear the word chronic,

think high levels of whatever intake, okay?

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

or people drinking every night.

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

were drinking one or two drinks per night.

So that could be 14 drinks on the weekend,

it could be one drink per night,

it could be seven drinks on Friday.

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

And I think many people out there are drinking

somewhere between one and two drinks per night

or day of the week on average,

so that would be seven to 14 drinks per week.

So this is an important study

because it says that if you’re consuming

even just seven glasses of wine across the week,

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

of your brain in response to that alcohol intake.

Although, as mentioned earlier,

we will talk about some of the things that can inoculate

against some of that neuronal loss.

For those of you that are interested

in reading the study in more detail,

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

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

is separate from my teaching and research roles at Stanford.

It is however, part of my desire and effort

to bring zero cost to consumer information about science

and science related tools to the general public.

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Let’s talk about alcohol,

and let’s just acknowledge that human beings

have been consuming alcohol for thousands of years.

If you look at the archeological evidence from Mesopotamia,

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

or if you want to know when people

first started distilling alcohol,

much to people’s surprise,

that did not first take place in Ireland,

and that’s not a joke about the Irish,

that you’ll see a lot of claims online

that the Irish were the first to distill alcohol,

but in fact, they were not.

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

and that took place in China in the first century.

Alcohol has been used for nutritional purposes,

so there are cultures that believe,

and indeed still believe,

that the calories in alcohol are useful,

although later we’ll talk about how alcohol calories

are indeed empty calories

and what an empty calorie really is,

why it’s called empty.

Alcohol has been used for medicinal purposes,

because indeed it does kill bacteria,

and as you’ll soon find out,

the fact that it kills bacteria,

because that is absolutely true,

it also kills the good bacteria in your gut,

and the destruction of that good bacteria in your gut

can lead to things like leaky gut syndrome,

and has all sorts of issues,

and there are ways to deal with those issues,

and we’ll talk about those.

So alcohol has been used for medicinal purposes,

it’s been used to clean surfaces,

it’s used in my laboratory

in order to make up so-called reagents

to do our experiments,

but most humans have been consuming alcohol

in order to change their internal state,

in order to feel differently than they would otherwise.

That feeling of being drunk, or inebriated,

or tipsy, or lightheaded,

is something that many, not all,

but many humans seem to enjoy and pursue,

even though typically it leads to a feeling

of being less happy, less motivated,

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

That’s pretty incredible, right?

I mean, we’re talking about a substance

that people have been highly motivated to pursue,

that are still highly motivated to pursue,

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

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

and then it makes them feel lousy.

Now, some of you might be saying,

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

and therefore I don’t feel lousy,

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

and it allows me to get through my evening,

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

Okay, that very well may be true.

I believe those people.

And as I mentioned at the beginning of the episode,

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

but I do want to point out what alcohol is,

and how it creates the effects that it does.

And then I want to talk about what those effects are

when you engage in consuming alcohol,

even as often as one or two nights per week,

or let’s say you’re just somebody

who has a drink or two on Friday,

maybe a few more on Saturday,

or maybe you’re somebody who consumes all your alcohol

one night per week or one night per month.

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

So let’s address what alcohol is,

and how it affects the cells and tissues

and organs of your body.

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

that is how many people are consuming alcohol,

and how much they’re drinking.

And then you will be able, I think,

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

if you’re drinking any at all,

is impacting your brain and body,

and the choices you might want to make

about how and when to drink alcohol,

or even if you want to eliminate alcohol altogether.

Okay, so some basic chemistry and biology of alcohol.

And again, I’ll make this very clear,

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

Because of the structure of alcohol,

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

Translated into what’s meaningful for you,

what that means is when you drink alcohol,

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

It has no trouble just passing right into those cells.

So unlike a lot of substances and drugs

that actually attach to the surface of cells,

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

and then trigger a bunch of downstreams,

like domino cascades of effects,

alcohol actually has its own direct effects on cells

because it can really just pass into those cells.

So it’s water and fat-soluble.

And the fact that it can pass

into so many organs and cells so easily

is really what explains its damaging effects.

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

There’s isopropyl, methyl, and ethyl alcohol.

And only the last one, ethyl alcohol or ethanol,

is fit for human consumption.

However, it is still toxic, okay?

It produces substantial stress and damage to cells.

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

but that’s just a fact.

Ethanol produces substantial damage to cells.

And it does that because when you ingest ethanol,

it has to be converted into something else

because it is toxic to the body.

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

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

There’s a lot of discussion about NAD

in the longevity literature right now.

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

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

There are ideas that increasing levels of NAD

may extend lifespan.

A lot of that is still controversial,

or at least we should say is ongoing

in terms of the research.

But nonetheless, when you ingest ethanol,

NAD and related biochemical pathways

are involved in converting that ethanol

into something called acetyl aldehyde.

It’s broken down into acetyl aldehyde.

And if you thought ethanol was bad,

acetyl aldehyde is particularly bad.

Acetyl aldehyde is poison.

It will kill cells.

It damages and kills cells.

And it is indiscriminate as to which cells

it damages and kills.

Now, that’s a problem, obviously.

And the body deals with that problem

by using another component of the NAD biochemical pathway

to convert acetyl aldehyde into something called acetate.

Acetate is actually something

that your body can use as fuel.

And that process of going from ethanol

to acetyl aldehyde to acetate

does involve the production of a toxic molecule, right?

Again, acetyl aldehyde is really toxic.

And NAD, and if we want to get technical,

it’s the NAD to NADH ratio.

And that chemical step is the rate-limiting step

to ethanol’s metabolism.

What does that mean for you?

What that means is that if your body

can’t do this conversion of ethanol to acetyl aldehyde

to acetate fast enough,

well, acetyl aldehyde will build up in your body

and cause more damage.

So it’s important that your body be able

to do this conversion very quickly.

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

And cells within the liver are very good

at this conversion process.

But they are cells and they are exposed

to the acetyl aldehyde in the conversion process.

And so cells within the liver really take a beating

in the alcohol metabolism events.

So the key thing to understand here

is that when you ingest alcohol,

you are, yes, ingesting a poison.

And that poison is converted

into an even worse poison in your body.

And some percentage of that worse poison

is converted into a form of calories

that you can use to generate energy, generate ATP.

And the reason why alcohol is considered empty calories

is because that entire process is very metabolically costly,

but there’s no real nutritive value

of the calories that it creates.

You can use it for immediate energy,

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

or beneficial way.

It doesn’t provide any vitamins.

It doesn’t provide any amino acids.

It doesn’t provide any fatty acids.

It’s truly empty calories.

I know some people talk about sugar is empty calories,

but sugar actually is a far better fuel source

than alcohol or acetate.

But nonetheless, when you ingest alcohol,

some percentage is being shuttled into a worse poison

and some is being shuttled into a fuel source.

Now, the important thing to understand

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

that leads to the effect of being inebriated or drunk.

I think most people don’t realize that,

that being drunk is actually a poison-induced disruption

in the way that your neural circuits work.

And so we should ask ourselves, which neural circuits,

what brain areas, what body areas involved

in feeling drunk or inebriated?

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

or really drunk or a little bit drunk,

I want to mention something

I think most people aren’t aware of.

And that’s the fact that for people

that are regular drinkers

or that have a genetic predisposition to alcoholism,

when they drink, they tend to feel very energized

and very good for longer periods of time.

Again, people have a genetic predisposition to alcohol

or people who are chronic drinkers, or even just,

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

but they’re drinking one or two per night

or they’re every other night type drinkers

or Thursday through Sunday drinkers.

Those people typically experience an increase

in alertness and mood when they drink,

whereas occasional drinkers will have a briefer,

meaning less long-lasting period of feeling good

when they drink and then more quickly transition

into a state in which they’re tired

or they start losing motor skills,

they start slurring their speech.

I also want to emphasize this is distinct from tolerance.

We’ll talk about tolerance later

and exactly what tolerance means.

But I really want to highlight the fact

that when people ingest this poison,

because indeed it is poison,

the range of effects is very different

and you can reliably predict who are the people

with a predisposition to alcoholism

and who are the people who are more regular drinkers

by the contour, the timing of the different effects.

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

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

they become kind of the life of the party

and that lasts a long while.

Those people are the ones that really have to be careful

about predisposition for alcoholism.

And those people also need to be careful

about their drinking and the amount of drinking

that they’re doing,

even if they’re not full-blown alcoholics.

Now, of course, people who are ingesting alcohol,

who are not accustomed to drink alcohol

have to be concerned about drinking alcohol

for other reasons because it can impair motor function

and judgment, et cetera.

But in thinking about the biochemical effects of alcohol

and what it’s doing to the body,

what it’s doing in all cases

is it’s consumed into the gut, right?

Goes into the stomach.

The liver immediately starts this conversion

that we talked about before

of ethanol to acetyl aldehyde to acetate.

And some amount of acetyl aldehyde and acetate

are making it into the brain.

It crosses the blood-brain barrier.

Again, the brain has this fence around it

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

Many things, most things, thankfully,

can’t pass across the blood-brain barrier,

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

just cruises right across this fence

and into the milieu, the environment of the brain,

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

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

which are in between the nerve cells.

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

So what happens when alcohol gets into the brain

that makes us feel tipsy or drunk?

And in some people, makes people feel really,

especially energized and happy.

Well, alcohol is indiscriminate

in terms of which brain areas it goes to.

Again, it doesn’t bind to particular receptors,

but it does seem to have a propensity

or an affinity for particular brain areas

that are involved in certain kinds of thinking and behavior.

So one of the first things that happens

is that there’s a slight,

at least after the first drink or second drink,

there’s a slight suppression in the activity of neurons

in the prefrontal cortex.

This is an area of your neocortex

that’s involved in thinking and planning,

and perhaps above all,

in suppression of impulsive behavior.

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

and people are consuming drinks,

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

the volume of people’s voices will increase.

And that’s because people are simply not paying attention

to their voice modulation.

As other people start speaking more loudly,

other people are speaking more loudly.

We’ve all had this experience, right,

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

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

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

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

some virus or something.

But oftentimes it’s just the fact

you’ve been shouting all night just to be heard

because as the prefrontal cortex shuts down,

people stop modulating their level of speech quite as much.

Also notice that people start gesticulating more.

People will start standing up and sitting down more.

They’ll start walking around more.

If there’s music on,

people might spontaneously start dancing.

All of this is because these areas

of the prefrontal cortex normally are providing

what’s called top-down inhibition.

They are releasing a neurotransmitter called GABA

onto various parts of the brain.

They’re involved in impulsive motor behavior

and thought patterns.

And as you shut down the prefrontal cortex,

that GABAergic suppression of impulses

starts to be released.

So people will say things that they want to say

without so much forethought about what they’re saying.

Or they might do things that they want to do

without really thinking it through quite as much.

Or they might not even remember thinking it through at all

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

We haven’t talked about blacking out yet

and the effects of alcohol on memory.

But as long as we’re there,

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

in suppressing the neural networks

that are involved in memory formation and storage.

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

if we’ve been drinking.

One of the more important things to know

about the effects of alcohol in the brain

is this disruption in top-down inhibition,

but also that areas of the brain

that are involved in flexible behavior,

sort of considering different options.

Like I could do A or I could do B.

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

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

This might be a little more tactful.

Those brain areas basically shut down entirely

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

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

the prefrontal cortex and top-down inhibition is diminished.

That is habitual behavior

and impulsive behavior starts to increase.

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

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

but it’s also true that the more often

that people drink, there are changes in the very circuits

that underlie habitual and impulsive behavior.

Okay, this is really important to highlight

so much so that I want to drill into it

a little bit more deeply.

For the person that drinks say every Thursday night

or every Friday night or goes out only on Saturdays,

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

in the neural circuits of the brain

that control habitual behavior and impulsive behavior.

And they are modified and strengthened

in ways that make those people more habitual

and more impulsive outside the times

in which they are drinking.

And when they drink, impulsive and habitual behavior

tends to increase even further.

This is something that’s not often talked about

when discussing the effects of alcohol.

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

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

certainly driving drunk is a terrible thing,

get you or other people killed and so on.

But rarely do we hear about the changes in neural circuits

from just one or two nights of regular drinking.

Again, chronic drinking doesn’t necessarily mean

every day and every night.

It could be the person that simply drinks every Thursday

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

or maybe even a few more.

That person is going to experience a decrease

in this top-down inhibition.

So an increase in impulsivity and habitual behavior

because the break on those behaviors has been removed

while they’re drinking,

but also changes in the very neural circuits

that allow habitual and impulsive behavior

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

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

the cellular substrate, I can briefly describe it.

It’s really interesting.

Again, you don’t need to know any biology

to understand this.

What it does is it increases the number of synapses,

the actual points of connection in the neural circuits

that control habitual behavior.

So there’s literally a growth of the neural circuits

in your brain that lead to existing habit execution.

The performance of things you already know how to do

and a reduction in the neural circuits,

or I should say a reduction in the number of synapses

of the contacts within the neural circuits

that are controlling behavior.

So this again is a not often discussed aspect

of alcohol intake.

Fortunately, it is reversible.

So in animals or humans that undertake a period

of abstinence of anywhere from two to six months,

these neural circuits return to normal,

except in cases where people have been chronically drinking

large volumes of alcohol for many, many years.

And in those cases,

while there is some recovery of brain circuitry,

after people get sober, meaning completely sober,

they stop drinking entirely,

there is evidence of long lasting impact

of heavy alcohol usage throughout the lifespan.

But of course, this doesn’t mean that anyone

that’s suffering from alcoholism or that used to

should not continue to focus on their health.

You absolutely should, all is not lost.

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

maybe you went to college and you drank a lot

in those years and your neural circuits change.

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

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

those neural circuits can then be remodified

back to their original state.

So let’s consider some of the other neurochemical effects

of alcohol in the brain and body.

And again, for right now,

we’re confining the conversation to people

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

Now, some people might think

that two drinks per night is a lot,

and a lot of that will depend on body weight.

So for instance, people who weigh 110 pounds,

for them to ingest two alcoholic drinks

is going to be substantially different

in terms of the biochemical effects

than somebody who weighs 220 pounds.

Of course, tolerance will also factor into this,

genetic background will also factor into this,

and indeed, whether or not people have eaten

will factor into this.

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

For the time being, if you’re curious

about how food impacts the effects of alcohol

and your feelings of being drunk,

you may have heard, for instance,

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

they should eat something.

Turns out that does not work.

Here’s how it does work, however.

If you eat something prior to drinking alcohol

or while ingesting alcohol,

it will slow the absorption of alcohol into the bloodstream.

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

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

In particular, if that meal includes carbohydrates,

fats, and proteins, okay?

The inclusion of all three major macronutrients

seems to slow the absorption of alcohol into the bloodstream

far more than having any one of those

or two of those macronutrients present.

Now, if you are already inebriated

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

and you eat something,

chances are that alcohol has already made it

into your bloodstream

because it moves into the bloodstream so quickly.

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

So within minutes, if you have an empty stomach,

within five to 10 minutes,

that alcohol is going to be within your bloodstream

and distributed throughout your body,

maybe even faster depending on the type of alcohol

and your metabolism.

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

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

but it certainly will blunt the effects

of any additional alcohol that you might consume.

And if you’re somebody who is concerned

about getting too drunk too quick,

even from a small amount of alcohol,

having some food in your gut can certainly be beneficial.

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

but let’s go back to talking about the biochemical

and neurochemical effects of alcohol on the brain.

We talked about top-down inhibition

and we talked about habitual

and impulsive behavior circuitry.

There are also dramatic changes in the activity of neurons

that control the release of so-called serotonin.

Serotonin is a neuromodulator.

It changes the activity of neural circuits

and many neural circuits, in particular,

those involved in mood and feelings of wellbeing.

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

because of a study that was released

that showed pretty conclusively that serotonin levels

can’t really explain depression

and depression-like symptoms.

I want to make it very clear that although that study

did show that serotonin levels

are not necessarily associated with depression,

the study was interpreted by many to mean

that SSRI, Selective Serotonin Reuptake Inhibitors,

which have the net effect of increasing serotonin,

these are things like Prozac, et cetera,

that those drugs are somehow not helpful

because they increase serotonin

and serotonin isn’t involved in depression.

That logic doesn’t really hold together,

so I’m going to use this as an opportunity

to just clarify what really occurred there

and then we’ll talk about how serotonin

relates to alcohol consumption

in things like feeling good and in depression.

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

That’s right, SSRIs can help alleviate depression.

They are often not always associated with side effects,

dosage is very important, et cetera,

but they probably support relief from depression

by changing neural circuits,

not necessarily by increasing serotonin itself.

That is, increasing serotonin with these drugs

likely change the neural circuits involved in mood,

allowing people to feel better

through so-called neuroplasticity,

which is the brain’s ability to change itself

in response to experience.

So there’s a bit of confusion,

and again, I’m using this episode on alcohol

to highlight some of the confusion

because I think it’s timely

because the study just came out

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

that when people are depressed,

it’s not necessarily because serotonin levels are low.

However, if serotonin levels are increased

with things like Prozac, Zoloft, and other SSRIs,

oftentimes there is, yes, a relief from depression,

but that’s probably not

because of restoring serotonin levels per se,

it’s probably because serotonin facilitates

the changes in neural circuits that need to occur

in order for people to feel elevated mood, okay?

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

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

Again, if you’re thinking about taking SSRIs,

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

definitely talk to your doctor.

Again, there is great utility for some of these SSRIs

and also in conditions like OCD,

they’ve been shown to be very beneficial,

so we really don’t want to throw SSRIs out

as a potentially valuable treatment.

Getting back to the effects of alcohol on serotonin,

it’s very clear beyond any doubt

that many of the circuits in the brain

that are involved in mood and feelings of wellbeing

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

employ the neuromodulator serotonin

and alcohol when we ingest it

and it’s converted into acetyl aldehyde,

it goes and that acetyl aldehyde acts as a toxin

at the very synapses,

the connections between the serotonergic neurons

and lots of other neurons.

In other words, when we ingest alcohol,

the toxic effects of alcohol disrupt those mood circuitries

at first making them hyperactive, that’s right,

making them hyperactive,

this is why people become really talkative,

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

at least most people do.

And then as they can ingest more alcohol

or as that alcohol wears off, serotonin levels

and the activity of those circuits really starts to drop

and that’s why people feel less good

and typically what they do,

they go and get another drink

and they attempt to kind of restore that feeling

of wellbeing and mood.

Now, typically what happens is that as people ingest

the third and fourth, maybe even the fifth drink,

there’s an absolute zero chance of them recovering

that energized mood, right?

Most people as they drink more and more

will now start to feel more and more suppressed.

The forebrain is now shutting down quite a lot,

a lot of the motor cortical areas

that control coordinated movement

and deliberate movement start to shut down.

So people start to slur their speech,

people start to shuffle their feet,

people forget their posture,

people start to lean on things,

people start passing out on couches.

There’s a great depression,

not depression of the psychiatric depression sort,

but a depression of alertness and arousal

and eventually people will pass out.

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

that have gene variants or who are chronic drinkers

or who are chronic drinkers and have gene variants

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

what happens?

They become more alert, they start talking more,

they feel great, they have all sorts of ideas

about the fun they could have that night

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

at a party for whatever reason,

or you’re getting tired and you’re yawning

and looking around the room

and like these people are still drinking and partying

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

often not always those are the future alcoholics in the room

or those are the people

that have a genetic predisposition for alcoholism

or those are the chronic drinkers,

the people who have built up enough of a tolerance

or who have the chemical genetic makeup

such that increasing amounts of alcohol

make them feel better and better and better.

And of course they too have a threshold

beyond which their nervous system

will start to get diminished and they’ll pass out

and fall over, et cetera.

But that threshold is way, way higher

than it is for most people.

Now, this is important to understand

and it’s important to understand

because I think everyone should know and recognize

their own predisposition and kind of risk

in terms of developing alcoholism.

It’s also important to understand

because it relates to the phenomenon of blackout.

You know, many people think that blacking out

is passing out, but blackout drunk is when people drink

and they’re talking and doing things.

Sometimes sadly they’ll, or tragically,

they’ll often drive home or walk home

or they’ll hop on a bicycle and ride home

or they’ll go swimming in the ocean.

All of course, very dangerous activities

to do when people are really drunk

or even a little bit drunk in some cases.

So these people will do these sorts of things

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

and they feel good while doing them,

but they are doing them while the activity of neurons

in the hippocampus, which is involved in memory formation,

are completely shut off.

And this is why the next day you tell them,

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

Like, what happened last night?

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

Yeah, no, it was great.

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

And it’s very clear all of a sudden

that they have no recollection

of all the things they were doing despite being awake.

Now, I wish I could tell you

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

even a fingerprint test that would allow you

to determine whether or not you have a propensity

to be one of these drinkers

that has a predisposition for alcoholism.

And if you’ve ever been blackout drunk,

and certainly if you’ve been blackout drunk

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

And as we talk more about the more chronic effects

and long-lasting effects of alcohol consumption

a little bit later in the episode,

I think it will become clear

as to why you should be concerned.

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

whether or not you might be in that category

versus likely not in that category.

And I alluded to this a couple of times already,

but I want to be really clear

that when people drink, no matter who you are,

initially there’s that shutting down

of those prefrontal cortical circuits.

There’s a gradual shutting down of the circuits

that control memory,

but then people divide into these two bins.

And these two bins are the people

who after more than a couple of drinks

start to feel sedated,

and the people who after more than a few drinks

do not start to feel sedated.

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

created by how quickly people are drinking,

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

the types of alcohol, et cetera.

But in general, that can predict whether or not

you’re somebody who has a predisposition

for alcoholism or not.

One also very interesting finding

is that alcohol changes the relationship

between what’s called the hypothalamus

and the pituitary gland and the adrenals.

Now, the hypothalamus is a small collection of neurons

about the size of a large gumball

sits above the roof of your mouth,

and it houses neurons that are responsible

for some incredible aspects of our behavior

and our mindset.

Things like rage, things like sex drive,

things like temperature regulation,

very primitive functions,

including appetite, thirst, et cetera.

Alcohol, because it can go anywhere in the brain,

remember it’s water and fat soluble,

has effects on the hypothalamus.

The hypothalamus normally provides very specific signals

to what’s called the pituitary gland.

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

but it receives instructions from the hypothalamus.

And then the pituitary releases hormones

into the bloodstream that go and talk to your adrenals.

Your adrenal glands sit right above your kidneys

in your lower back.

And the adrenals release, as the name suggests,

adrenaline, also called epinephrine,

and also a molecule called cortisol,

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

has some healthy effects too on the immune system.

Okay, so the hypothalamic-pituitary-adrenal axis.

I know that’s a mouthful,

you don’t need to remember the names,

but the hypothalamic-pituitary-adrenal axis

maintains your physiological balance

of what you perceive as stressful

and what you don’t perceive as stressful.

People who drink regularly,

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

or it could be somebody that drinks just on Fridays

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

two to four drinks.

Well, those people experience changes

in their hypothalamic-pituitary-adrenal axis

that result in more cortisol,

more of this so-called stress hormone being released

at baseline when they are not drinking.

This is really important.

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

I don’t mean one or two sips

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

Again, people that are maybe having one drink a night

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

Again, I offer a bunch of different patterns

to explain how it could also be two or three drinks

on Friday or six drinks only on Saturday.

Well, all of those groups experience increases

in cortisol release from their adrenal glands

when they are not drinking.

And as a consequence, they feel more stressed

and more anxiety when they aren’t drinking.

This is a seldom-talked-about effect of alcohol

because so often we hear

about the immediate effects of alcohol, right?

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

effects like reducing the amount of stress.

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

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

and they’re like, calm down.

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

They can start to think about things

in a maybe more grounded or rational way,

or at least they believe that,

or they can somehow just relax themselves.

Well, while that very well may be true,

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

that level of cortisol that’s released at baseline

has increased substantially.

Again, this relates to a defined neural circuit

between brain and body,

and it has to do with the ratio of cortisol

to some of the other hormones involved

in the stress response.

We’ll provide a reference to the study

that describes how all of this works

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

But let’s go back to this issue

of those who are prone to alcoholism

versus those who are not.

Remember, there are people who have genetic variants,

that meaning genes that they inherited from their parents,

that make it more likely that they will become alcoholics.

But there are also people who drink often,

who start to experience this increase in alertness

the longer they drink across the night.

Part of that effect, we think,

is because of changes

in this hypothalamic pituitary adrenal axis.

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

It’s causing changes in our brain circuitry

and neurochemistry that at the time

in which we’re inebriated are detrimental,

and it’s causing changes in neural circuitry

that persist long past the time

in which we’re experiencing the feeling

of being tipsy or drunk.

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

I’m not saying, oh, you know,

if you have a glass of wine now and again,

or you drink a beer now and again,

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

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

I certainly do not want that to be the message.

What I’m saying is that

if people are ingesting alcohol chronically,

even if it’s not every night,

there are well-recognized changes in neural circuits,

there are well-recognized changes

in neurochemistry within the brain,

and there are well-recognized changes

in the brain-to-body stress system

that generally point in three directions.

Increased stress when people are not drinking,

diminished mood and feelings of wellbeing

when people are not drinking,

and as you’ll soon learn,

changes in the neural circuitry

that cause people to want to drink even more

in order to get just back to baseline

or the place that they were

in terms of their stress modulation

and in terms of their feelings of mood

before they ever started drinking in the first place.

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

but I do want to emphasize

that there are long-term plastic changes,

meaning changes in neural circuitry and hormone circuitry

that across a period of several months

and certainly across a period of years

of the sorts of drinking patterns I described,

which I think for most people

are going to sound like pretty typical, right?

I mean, nothing that I described so far

was about drinking a case a night

or about binging on alcohol

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

These are pretty common patterns of alcohol consumption.

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

or actually go to an airport on a Sunday afternoon

in a sunny area of the US,

and people are having three, four, five,

six beers, et cetera.

Again, personal choice is personal choice.

I’m not telling you what to do,

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

are changing neural circuitry

and they’re changing hormone circuitry,

and I’d love to be able to tell you

that they’re changing them for the better,

but they simply are not.

They’re actually changing them for the worse,

and worse is defined as making people

less resilient to stress,

higher levels of baseline stress,

and lower mood overall.

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Now, I’ve been talking a little bit

about genetic predisposition,

but there are a couple of important points

I’d like to make about that.

First of all, what sorts of genes are involved

in setting someone down the path of alcoholism or not?

Well, it should come as no surprise

that the genes that chronic alcohol usage modifies,

they tend to fall primarily in the pathways

related to genetic control over serotonin receptors,

GABA receptors, remember that top-down inhibition

and the involvement of GABA,

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

All of those, of course, combine with environment,

they combine with patterns of abuse, right?

We know that if you’re in a social setting

where a lot of people are drinking,

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

Social pressures, trauma, right?

Some people will use alcohol to self-medicate

to try and turn off their thinking

or to deal with trauma, et cetera.

So they combine with the environment,

but the genes that are in the serotonin synthesis

and receptor synthesis pathway, GABA and HPA axis

combine with environmental pressures

to give rise to alcohol use disorders.

So there’s a fairly coherent picture

that we have here, right?

This is not a case where, for instance,

people that have a lot of the enzyme

for metabolizing alcohol,

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

it’s not like they are necessarily the people

that become alcoholics,

whereas certainly in certain cultures,

certain Asian cultures in particular,

there are gene differences

that lead them to have low levels of alcohol dehydrogenase.

There are actually people

who have so little alcohol dehydrogenase

that when they ingest alcohol,

they get very red and they just feel sick.

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

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

chances are you have gene variants

that create a situation

where you’re not making very much alcohol dehydrogenase.

You just simply can’t metabolize alcohol.

So you just get a rapid buildup

of the toxic effects of alcohol, the acetyl aldehyde.

You’re not converting it into those empty calories.

But in cultures where you have a lot of genetic variants

and genes expressed in people

where they have a lot of alcohol dehydrogenase,

sure, they can drink more

and they’re converting more of that alcohol

from its toxic form to a non-toxic form.

And yes, of course, you will observe more alcoholism

in those communities because they’re drinking more.

But I do want to emphasize that the environmental factors

are playing a strong role there too,

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

If you’re somebody that feels sick immediately

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

in alcohol consumption,

especially if these things are genetically related.

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

tend to run together.

So do you have the gene for alcoholism?

Well, there isn’t one single gene.

Chances are if you have an immediate relative

who’s a chronic abuser of alcohol

or several relatives who are chronic abusers of alcohol,

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

But since you don’t know which genes you express

unless you do genetic testing and those things

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

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

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

to determine something.

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

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

or somebody else is somebody who can drink a lot

throughout the night and have increased energy

and can just drink and drink and drink,

and especially if there’s blackout episodes,

not remembering things the next day,

despite being alert throughout the entire night and so on,

well, then I would be very concerned that you might

actually have a genetic variant

predisposing you to alcoholism.

The other thing that predisposes people

to abuse of alcohol is age.

People who start drinking at younger ages

are greatly predisposed to developing alcohol dependence,

regardless of your family history of alcoholism.

Okay, so I’m going to repeat that.

People who start drinking younger are at great risk

for developing alcoholism,

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

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

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

and alcohol is everywhere,

and especially if there’s peer pressure

or lack of oversight,

then there’s going to be a higher tendency

or a higher probability, I should say,

that you will start drinking at a younger age.

However, even people that grow up nowhere

near their relatives,

if they start drinking at a young age,

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

there’s a much higher probability

that they’re going to develop

a long-lasting dependence on alcohol.

People who take their first sip of alcohol later,

15, 16, or one would hope even later,

I can say one would hope,

because I’m now of that age and generation

where you think about all the things that young people do

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

or if they only would abstain, you know?

So this is what happens.

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

that I can’t explain yet.

But people who, for instance,

drink only once they reach legal age of drinking,

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

if they take their first drink at 21,

the probability that they’ll go on

to develop full-blown alcohol dependence

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

Now, a subset of them will

because they have such a strong genetic predisposition

or maybe life circumstances create a pattern

in which they become a chronic drinker.

But I found this very interesting.

Genes matter, but also the age

in which somebody starts drinking really matters.

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

in neural circuitry as a consequence of that drinking

that make people want to seek out more and more alcohol

or whether or not there’s some other effect,

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

that predisposes those young drinkers

to become chronic drinkers or even full-blown alcoholics,

certainly developing alcohol use disorder.

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

It involves the amount of drinking

over a certain period of time, et cetera.

So it’s very clear that drinking early in life

creates a propensity for the development

of alcohol use disorder later in life.

And while there is a genetic component

to developing alcohol use disorder,

I find it very interesting

that if people who have those gene variants

delay their onset of drinking,

well, then the probability

that they’ll develop full-blown alcohol use disorder

drops as well.

So again, it’s genes and environments,

it’s not an either or

and there’s no single gene for alcoholism.

Well, I promise you I will also talk about

some of the documented positive effects of alcohol,

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

But before I do that, I would be remiss

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

that alcohol does and the way that it does it.

And for those of you that enjoy alcohol,

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

about telling you this

because I know how much some people enjoy a good drink

every once in a while.

And I say a good drink

because some people do like the taste of alcohol.

I suppose I lucked out

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

and that just puts me to sleep,

but I know that people do enjoy it.

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

that provided somebody is of drinking age,

certainly not in the stage of brain development,

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

meaning every three or four weeks or once a month,

that is not going to cause major health concerns

or major health issues for most people.

I suppose if you have zero

or very little alcohol dehydrogenase,

it might make you feel sick,

but then you’re probably not the kind of person

that’s going to be drinking at all.

So again, if you enjoy alcoholic drinks,

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

but you should know what drinking does

if you’re consuming it in this kind of

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

which is that one or two a night

or a few stacked up on Friday

and maybe three or four on Saturday,

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

And one of the more serious effects

that we should think about

is the impact on the so-called gut brain axis

or for sake of today’s discussion,

the gut liver brain axis.

I don’t think the gut liver brain axis

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

Although the moment I say that,

the gut liver brain axis,

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

gut, liver, brain, and brains.

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

That gut runs from your throat

down to the end of your intestine.

Your gut and your brain communicate

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

the vagus nerve in particular,

and by way of chemical signaling.

Your gut also communicates by way of chemical signaling

and believe it or not,

by way of neural signaling to your liver.

And as we talked about earlier,

the liver is the first site in which alcohol

is broken down and metabolized into its component parts.

The liver is also communicating with the brain

through chemical signaling and neural signaling.

So we have the gut liver brain axis.

And what you find is that people who ingest alcohol

at any amount are inducing a disruption

in the so-called gut microbiome,

the trillions of little micro bacteria

that take resident in your gut

and that live inside you all the time

and that help support your immune system

and that literally signal by way of electrical signals

and chemical signals to your brain

to increase the release of things like serotonin

and dopamine and regulate your mood

generally in positive ways.

Well, alcohol really disrupts those bacteria.

And this should come as no surprise.

I mean, earlier we talked about this

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

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

I can remember scraping myself or cutting myself.

I was always injuring myself when I was a kid.

And the moment they take out the peroxide,

you’re like, oh boy, here it comes.

But if there’s no peroxide around

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

yeah, they’ll use alcohol,

which I do not recommend by the way.

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

But for centuries, thousands of years,

really alcohol has been used in order to clean things

and kill bacteria.

So alcohol kills bacteria and it is indiscriminate

with respect to which bacteria it kills.

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

it kills a lot of the healthy gut microbiota.

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

which you now understand that pathway involving NAD,

acetyl aldehyde and acetate,

that pathway is pro-inflammatory.

So it’s increasing the release of inflammatory cytokines,

things like IL-6, et cetera,

tumor necrosis factor alpha.

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

we did an episode all about the immune system.

You can find it at

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

what are mast cells, et cetera.

In any event, all these pro-inflammatory molecules,

those are being released.

You’ve now got disruption of the gut microbiota.

As a consequence, the lining of the gut is disrupted

and you develop at least transiently leaky gut.

That is bacteria that exist in the gut,

which are bad bacteria,

can now pass out of the gut into the bloodstream.

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

In biology, we talk about two hit models.

That is kind of a one plus one equals four.

And it’s generally when you hear two hit,

it’s not a good thing.

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

moving out of the gut.

The good bacteria in the gut have been killed.

You might say,

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

Well, the bad bacteria that are from partially digested food

oftentimes escape the gut

before the alcohol can disrupt them.

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

You’ve got the release of this bad bacteria.

You’ve got inflammatory cytokines

and other things being released from the liver.

And they are able to get into the brain

through what’s called a neuroimmune signaling.

And what’s really bizarre in terms of the way

that this manifests in the brain,

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

But then again, as I always say,

I wasn’t consulted at the design phase.

And anyone who says they did,

you should be very skeptical of them.

The net effect of this is actually to disrupt

the neural circuits that control regulation

of alcohol intake.

And the net effect of that is increased alcohol consumption.

So this is just terrible, right?

I mean, you’re taking in something

that disrupts two systems, the gut microbiota

and it disrupts in two ways.

It’s killing the gut microbiota

and it’s allowing the bad bacteria

to move from the gut into the bloodstream.

You’ve also got pro-inflammatory cytokines

coming from the liver and those converge

or arrive in the brain and create a system

in which the neural circuits cause more drinking.

That’s a bad situation.

And this is why people who drink regularly,

even if it’s not a ton of alcohol,

again, of the sorts of patterns of drinking

that I talked about before.

And certainly for those that are chronic heavy drinkers,

what you end up with is a situation

in which you have inflammation in multiple places

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

and to further exacerbate that inflammation

and the gut leakiness.

So this is basically a terrible scenario

for the gut-liver-brain axis.

And it’s especially prevalent

in so-called alcohol use disorder.

Again, people that are ingesting somewhere

between 12 and 24 drinks per week.

For those of you that are interested in learning more

about the gut-liver-brain axis

and in particular alcohol use disorder,

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

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

But on the positive side,

it points to the possibility that at least some,

again, at least some of the negative effects

of alcohol consumption,

whether or not you’re somebody

who’s currently ingesting alcohol

or who used to ingest alcohol

and is trying to so-called repair these systems

of the brain and body,

whether or not replenishing the gut microbiota

is going to be beneficial.

And we know that there are ways to do that.

And we know that there’s at least some promise

for the ability for the system to repair itself.

How does one do that?

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

but studies done by colleagues of mine at Stanford,

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

an amazing episode all about the gut microbiome

and his collaborator, Chris Garner,

also at Stanford School of Medicine,

have explored not alcoholism,

but what are ways to improve the gut microbiota

in particular to reduce the production

of inflammatory cytokines

and to adjust what’s called the inflammatome.

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

Well, the inflammatome is the total array,

or at least the near total array of genes and proteins

that control inflammation.

How can you reduce inflammation

and make that inflammatome healthier?

Well, they’ve shown that two to four servings

of fermented foods per day,

and here I’m not referring to fermented alcohol,

I’m talking about low sugar fermented foods,

so things like kimchi, sauerkraut, natto,

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

I know things like kefir,

things like yogurts that have a lot of active bacteria,

again, low sugar varieties of all these things.

Those are terrific at reducing inflammatory markers

and at improving the gut microbiome.

One could imagine that either inoculating oneself

from some of the effects of alcohol,

although I’d prefer that people

just not drink alcohol chronically, frankly,

or if somebody is trying to repair their gut microbiome

because they ingested a lot of alcohol

or because they had a lot of these inflammatory cytokines

for many years or even a short period of time,

regular ingestion of two to four servings

of these fermented foods can be quite beneficial.

I want to make it clear that has not been examined

specifically in the context of alcohol use disorder,

but because a huge component of the negative effects

of alcohol use disorder are based

in this gut-liver-brain axis and disruption

of the gut microbiome and the inflammatory cytokines,

it stands to reason that things that are well-established

to improve inflammation status,

in other words, reduce inflammation,

such as ingesting two to four servings

of low sugar fermented foods per day,

make sense in terms of trying to repair

or replenish the system.

One could also imagine taking probiotics or prebiotics.

Certainly that would work as well,

although I’ve sort of favored the discussion

around fermented foods and replenishment

of the gut microbiome, mostly because there are more studies

that have examined that in humans

and because of the direct relationship

that’s been established between doing that

and reducing negative markers within the inflammatory.

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

I put out a question on Twitter the other day.

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

I got more than a thousand questions.

I’ll take some more of those questions

a little later in the episode.

But one of the things I noticed is that many

of the questions, hundreds, in fact,

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 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

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

because we have timestamps.

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 anxiety,

which is anxiety that follows a day of drinking.

Anxiety, 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 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 anxiety,

then again, I refer you to the master stress episode

that we put out some time ago

and you can find that,

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

ranging again from behavioral

to nutritional supplement-based, et cetera.

That of course is not justification for going out

and drinking so much that you get anxiety-induced hangover.

But for those of you that are experiencing

post-alcohol consumption anxiety, 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 can 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 pseudo-sleep,

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,

they’re 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 in prebiotic or probiotic

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 would 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.

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 a 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’s 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 ingesting 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,

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.

You can find on

with 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 a 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

converge 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 non-obvious 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 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 10 minutes in a cold shower,

although that could be a lot.

Most people are going to experience a sharp increase

in epinephrine and 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 then 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 in 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

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,

because I suppose it’s kind of geeky

walking around with electrolyte packets

out at the bar or whatnot,

although 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

at the night of drinking.

So hangovers 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,

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 over-consumption, right?

It’s not far beyond the tolerance of the individual.

So there’s one or two beers,

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

And a glass of whiskey, or I should,

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,

is 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?

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

its 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 you 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 enormous number of chemicals that change

with repeated exposure to acetylaldehyde,

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 an 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, craving.

It creates a sense of wellbeing.

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 acetyl aldehyde into acetate

and the metabolized 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

has 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 wellbeing,

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 and 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 happened 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

that it 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 wellbeing 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

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 enriched 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

may be 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,

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.

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 the gray matter volume

and in these white matter tracks, 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 acetyl aldehyde

and 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 four 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

in 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’ve 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 a 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 U.S., 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 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 U.S.,

maybe a little bit more than one beer in Japan,

or basically a third of a drink in Russia,

there’s a four to 13% increase in risk of cancer.

That’s pretty outrageous, right?

And you might think, wait, how could it be

that 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 U.S., 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 and aggregation of cells

that could be a glioma, is glial cells,

glioma, brain tumor, right?

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 start 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 down regulation

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,

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 it’s a question of

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 would,

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 kind of 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

because I would hate to be confusing

or misleading to anybody,

I want to just emphasize that this statistic,

that there is a four to 13%,

depending on which study you look at,

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

in particular breast cancer,

for every 10 grams of alcohol consumed,

that’s 10 grams per day.

So that’s one drink per day.

But I do want to emphasize that

if that equates to seven drinks per week

and all those seven drinks are being consumed

on Friday and Saturday,

it still averages to 10 grams per day.

And I also want to emphasize that there are things

that people can do to at least partially offset

some of the negative effects of alcohol

as it relates to predisposition to the formation

of certain kinds of tumors and cancers.

I also want to be clear before I say it,

that doing the things I’m about to tell you

is not a guarantee that you’re not going to get cancer,

nor is it a guarantee that alcohol

is not going to lead to an increased predisposition

for certain kinds of cancers.

And the two things are consumption of folate

and other B vitamins, especially B12.

You know, the consumption of folate and B12

has been shown to decrease cancer risk

in people that ingest alcohol,

but not completely offset it.

Why that is, isn’t exactly clear.

It probably has something to do with the relationship

between folate and B12 and other B vitamins

in gene regulation pathways that can lead to tumor growth.

At some point soon, we will get an expert in cancer biology

and in particular in breast cancer biology on the program,

and we can ask them about this.

But I realize this is going to raise a number of questions

and maybe even cause some of you to go out there

and start taking folate and other B vitamins and B12.

Not incidentally, a lot of the reported hangover supplements

and treatments include folate and B12.

I don’t know if they had the cancer literature in mind

when they created those supplements and products.

I doubt they did.

Alcohol really does disrupt B vitamin pathways,

both synthesis pathways and utilization pathways.

So sometimes you’ll hear, oh, you know,

if you get your B vitamins,

it helps you recover from hangover more quickly.

Again, the literature doesn’t support that,

but also again, there aren’t a lot of studies,

but more to the point as it relates to alcohol

and the formation of tumors and cancers,

it does appear that decreased folate

and other B vitamins like B12 are partially responsible

for the effect of alcohol and increasing cancer risk.

And it does appear that consuming adequate amounts

of folate and B12 might, again, might partially,

really want to boldface and underline and highlight,

partially offset some of that increased risk.

There’s an additional category

that I want to highlight, of course,

and this is vitally important to state,

even though it’s obvious,

which is that people who are pregnant

should absolutely not consume alcohol.

Fetal alcohol syndrome is well-known and established.

It’s terrible.

Fetuses experience diminished brain development.

That’s often permanent.

Diminished limb development,

diminished organ development in the periphery,

meaning the heart, the lungs, the liver, et cetera.

Ingesting alcohol while pregnant is simply a bad idea.

And the reason I say this at all is, first of all,

it’s important to include in an episode like this,

but also because we can look at two things.

First of all, we can look at mechanism,

and then we can also look at some of the lore

that still sadly exists out there.

Let’s take care of the lore that sadly exists first.

If you look online,

you will sometimes be able to find, sadly,

that some people believe that certain kinds of alcohol

are not detrimental to fetuses.

They’ll say, well, champagne is safe

for a pregnant mother to drink, but beer is not.

That is absolutely categorically false.

Alcohol is alcohol.

There is no evidence whatsoever

that consuming certain types of alcohol

is safer for fetuses than others.

Alcohol is a toxin,

and the reason fetal alcohol syndrome exists

is because the ability of that toxin

to disrupt cellular processes.

Remember tumor growth and the way that alcohol

can accelerate tumor growth by proliferation of cells,

the wrong cells, the ones you don’t want to proliferate?

Well, all of embryonic development,

all of fetal development, it’s not the growth of a tumor.

It’s obviously the growth of an embryo,

and it’s done in a very orchestrated way.

I started off studying brain development.

That’s where I got my beginnings in neurobiology,

and I still teach embryology to medical students

and graduate students.

The set of coordinated processes that has to take place

from conception to birth in order to give rise

to a healthy embryo is so, so dynamically controlled

and so exquisitely precise with checkpoints

and recovery mechanisms and redundancy in the genes

that are expressed to make sure that if anything goes wrong,

it’s repaired, et cetera.

Alcohol as a mutagen, I haven’t used that word yet,

but a substance that can mutate DNA

through alterations in DNA methylation

and these checkpoints in the cell cycle.

Alcohol as a mutagen is one of the worst things

that a developing embryo can be exposed to.

And again, because it’s water-soluble and fat-soluble,

ingestion of alcohol when people are pregnant

passes right to the fetus.

Now, I realize that a number of people out there

might be thinking, oh goodness,

I didn’t realize I was pregnant

until a certain stage of pregnancy,

and before I realized I was ingesting alcohol.

Obviously, one can’t undo what’s been done,

but I want to also emphasize that fetal alcohol syndrome,

while yes, there’s a full-blown syndrome that manifests

as changes in the craniofacial development

that are very obvious, and you can look these up.

You’ve probably seen these before, the pictures before,

rather, it has to do with eye spacing, forehead size,

a number of other features of the craniofacial development,

and of course, stuff’s going on in the brain too.

It’s along a continuum.

So it is possible that some of the changes that occur

are more minor, and thankfully, the young brain,

in particular, the early postnatal brain

is incredibly plastic.

There are things that can be done

in order to help recover neural circuits

that didn’t develop well, et cetera.

But even though it’s somewhat obvious or should be obvious,

I really want to make clear that there’s zero evidence

whatsoever that certain forms of alcohol are safer

for pregnant women to ingest than others.

Absolutely wrong.

No one who’s pregnant

should be ingesting alcohol whatsoever.

And certainly, if people feel like they can’t avoid alcohol

while pregnant, they really need to work with somebody

to make sure that it just absolutely doesn’t happen

because it is so detrimental to the developing fetus.

Lastly, I want to talk about the effects of alcohol

on hormones, and I want to distinguish

between low amounts of alcohol intake,

higher amounts of alcohol intake,

and again, this chronic alcohol intake

versus occasional use versus really chronic use,

meaning alcoholic or alcoholic use disorder

where people are drinking an immense amount

on an ongoing basis.

The literature on alcohol and hormones is quite extensive,

and there are, of course,

many, many different types of hormones.

The hormones that most often get mentioned

and talked about on this podcast

are the hormones testosterone and estrogen,

which are present in both men and women,

that in both men and women are important

for things like libido.

They’re also responsible for sexual development,

actual development of the genitalia

before birth and after birth.

They’re responsible, for instance,

estrogen is important for memory and cognition.

You never want to drop estrogen too low in men or women

because it can disrupt cognition and joint health, et cetera.

To keep this discussion relatively constrained,

it’s fair to say that alcohol,

and in particular, the toxic metabolites of alcohol,

increase the conversion of testosterone to estrogen.

Now, this occurs in a number of different tissues.

This is not just occurring in the testes of males.

This is occurring in lots of different tissues,

and I’ll refer you to an excellent review.

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

This is a paper that was published in the year 2000,

but the data are still quite strong.

The journal is called, of all things, Alcohol.

There’s, yes, literally a journal called Alcohol

for the publication of data and reviews

on alcohol and its effects.

And the title of the paper is,

can alcohol promote aromatization of androgens to estrogens?

Aromatization is this process of the conversion

of testosterone and other androgens to estrogens

through things like aromatase enzyme.

And this is a beautiful review that describes every tissue

or near every tissue from the ovary in females

to the placenta, to the liver, to the testes,

in which alcohol can increase the aromatization

of testosterone to estrogen.

Now, in females, this may be part of the reason

why there’s an increase in estrogen-related cancers.

Breast cancer can be either estrogen-related

or non-estrogen-related.

There are other types of estrogen-related cancers

outside of breast cancer,

but it appears that one reason why alcohol

increases the risk of breast cancer

is because of this aromatization of testosterone,

excuse me, to estrogen.

In males, accelerated or abnormal conversion

of testosterone to estrogen can actually lead to growth

of the breast tissue in males, so-called gynecomastia,

or other effects of high estrogen,

or I should say of altered testosterone-estrogen ratios,

because that’s really what’s important.

And these can include things like diminished sex drive,

increased fat storage, and a number of other things

that I think most people would find to be negative effects.

I once talked about the fact that drinking alcohol

can increase the aromatization of testosterone to estrogen.

I posted that online, and I didn’t get attacked,

but I did get criticized for the fact

that it has been shown, yes, has been shown

that small amounts of alcohol ingestion,

so five grams or so of alcohol ingestion,

this would be half a glass of wine or half a glass of beer,

at least in some studies showed increases in testosterone,

which was kind of surprising, but I should point out,

other studies have shown that alcohol ingestion

causes decreases in testosterone over time.

So there’s always this issue

of whether or not you’re looking at a study

of acute exposure versus chronic exposure,

you know, one dose versus multiple doses and exposure.

I think it’s fair to say, based on my read of the literature,

this review and other reviews

that focus more particularly on humans,

that regular ingestion of alcohol

is going to increase estrogen levels,

whether or not you’re male or female,

and it’s largely doing that

through the aromatization process

by increasing the aromatase enzyme.

Yes, there’s some dose dependence,

but I think if you’re somebody

who’s trying to optimize your testosterone to estrogen ratio

regardless of whether or not you’re male or female,

well, then most certainly you’re going to want to avoid

drinking too much alcohol.

So we’ve covered a lot of topics and data

related to the mechanisms of alcohol,

hangover, tolerance, cancer risk, et cetera.

I acknowledge that I’ve mainly talked to you

about the negative effects of alcohol.

I want to acknowledge that many people enjoy alcohol

in moderation or even light drinking,

the occasional drink or the occasional two drinks,

or maybe even on average one drink per night,

so seven drinks per week.

I’m certainly not here to tell you

what to do and what not to do.

I do find it immensely interesting, however,

that first of all, alcohol is a known toxin

to the cells of the body.

Some of you might immediately say,

well, wait, what about hormesis?

What about this phenomenon

where if we regularly ingest a toxin, it makes us stronger?

In other words, what doesn’t kill us makes us stronger.

Yeah, there’s some reason to believe

that might be beneficial

in terms of some forms of cellular resilience,

maybe, maybe, no, sorry.

It doesn’t work that way.

There are processes of hormesis in which, for instance,

exposing yourself safely to increases in adrenaline

through ice baths or other things that increase adrenaline

can raise your so-called stress threshold,

but here we’re talking about cellular stress

and damage to cells.

So my read of the literature, and again, this is my read,

and I invite others to provide studies,

or I would prefer actually collections of studies

that point in the direction, if they exist,

that alcohol can be beneficial,

but my read of the literature,

or I should say my understanding

of what I would call the center of mass

of the literature on alcohol,

is that no consumption, zero consumption,

consumption of zero ounces of alcohol

is going to be better for your health

than low to moderate consumption of alcohol,

and that low to moderate consumption of alcohol

is going to be better for you, of course,

than moderately high to high alcohol consumption

on the order of 12 to 24 or more drinks per week.

I realize that for most people listening to this,

it’s probably low to moderate alcohol consumption

that is part of their standard repertoire,

and I’m not here to give you justification for doing that,

nor am I going to tell you not to do that.

I would like you to consider perhaps, however,

the negative effects that we understand

and that are documented.

For instance, the negative effects of alcohol

in the gut microbiome and the things that you can do

to better support your gut microbiome.

The negative effects on the stress system,

that HPA axis that we talked about earlier,

and the fact that even low to moderate levels

of alcohol consumption can increase our levels of stress

when we’re not drinking,

and to think about acquiring some tools

and getting some proficiency with tools,

behavioral or otherwise,

that can help you with stress modulation

that don’t involve alcohol consumption.

Again, the point here is to illustrate

where the problems lie with alcohol consumption,

but also what I’ve tried to do

is to point you to some resources

that can help offset some of those negative effects.

Will they offset all the effects?

I can’t say that for sure,

but certainly taking measures

to offset some of the negative effects

of any alcohol consumption

that you might be having or doing

is going to be beneficial to you,

and those tools and protocols

are going to be health promoting in any case.

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but much of which is unique from the content

covered on the Huberman Lab podcast.

Again, that’s Huberman Lab on Instagram

and Huberman Lab on Twitter.

Please also check out our Neural Network monthly newsletter.

This is a newsletter that has summaries of podcast episodes.

It also includes a lot of actionable protocols.

It’s very easy to sign up for the newsletter.

You go to, click on the menu,

go to newsletter, you supply your email,

but we do not share your email with anybody.

We have a very clear and rigorous privacy policy,

which is we do not share your email with anybody.

And the newsletter comes out once a month,

and it is completely zero cost.

Again, just go to

and go to the Neural Network newsletter.

I’d also like to point out that the Huberman Lab podcast

has a clips channel.

So these are brief clips,

anywhere from three to 10 minutes

that encompass single concepts and actionable protocols

related to sleep, to focus,

interviews with various guests.

We talk about things like caffeine,

when to drink caffeine relative to sleep,

alcohol, when and how,

and if anyone should ingest it relative to sleep,

dopamine, serotonin, mental health, physical health,

and on and on.

All the things that relate to the topics

most of interest to you.

You can find that easily by going to YouTube,

look for Huberman Lab clips in the search area,

and it will take you there.

Subscribe, and we are constantly updating those

with new clips.

This is especially useful, I believe,

for people that have missed some of the earlier episodes

or you’re still working through the back catalog

of Huberman Lab podcast,

which admittedly can be rather long.

And last, but certainly not least,

thank you for your interest in science.

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