Welcome to the Huberman Lab Podcast,
where we discuss science
and science-based tools for everyday life.
I’m Andrew Huberman,
and I’m a professor of neurobiology and ophthalmology
at Stanford School of Medicine.
Today, we’re discussing alcohol,
one of the most commonly consumed substances
on the planet Earth.
Should mention that both humans
and non-human animals consume alcohol
either for recreational purposes
because they like the feeling that it gives them
or for medicinal purposes
or for other purposes that we’ll discuss.
We are of course going to discuss the effects of alcohol
on our biology,
ranging from its effects on individual cells,
on organs and organ systems in our brain and body.
We are also going to discuss the effects
of the effects of alcohol.
That is what being inebriated really does
to our thinking and our behavior and how it does it.
And we are going to address
what seems to be one of the more common questions out there,
which is whether or not low to moderate amounts of drinking
are better for our health
than zero alcohol consumption at all.
And of course, we will talk about
severe alcohol intake, binge drinking.
We will also talk about hangover
and what science says about ways
to reduce the effects of hangover,
either by doing things that are inoculatory,
meaning before you drink or while you drink,
as well as things to do if you happen to have a hangover.
We will discuss some of the genetic differences
for alcohol and alcoholism.
And we will discuss alcohol consumption in young people
and how that can be especially detrimental
for reasons that I think are going to be
quite surprising to most of you.
My goal is that by the end of today’s episode,
you will have a thorough understanding
of what alcohol does to your brain and body
and that you will be able to make informed decisions
as to whether or not you should be consuming zero,
absolutely no alcohol,
small to moderate amounts of alcohol.
And again, we’ll define exactly what that means,
small to moderate amounts.
And if you or somebody else that you know
is consuming excessive amounts of alcohol
that are clearly detrimental to your health,
some of the better routes and resources that you can use
in order to remove that dependence and or consumption.
I’d like to preface all of that by saying
that today’s discussion is really geared
toward giving you information.
It is not about judging alcohol intake
or lack of alcohol intake.
I just want you to be able to make
the most informed decision about alcohol possible.
Before we get into today’s content in detail,
I just want to answer a commonly asked question
about alcohol consumption and the brain.
And the question that so often comes up
is whether or not low to moderate amounts of alcohol,
so maybe one drink a day
or one or two drinks a day kind of thing,
whether or not that is bad for your brain,
in particular, whether or not it causes degeneration
of neurons or nerve cells.
Now, the reason that question comes up so often
is because for many years,
it’s been known that high levels of alcohol consumption,
so 12 to 24 drinks per week or more,
is certainly causing neurodegeneration,
in particular, of the so-called neocortex,
the outer layers of the brain
that house associative memories,
that house our ability to think and plan,
that house our ability to regulate our more primitive drives
according to context, et cetera.
So to make very clear, drinking a lot,
so having three or four drinks per night
every night of the week is clearly bad for the brain.
A recent study, however, finally addressed the question
of whether or not low to moderate amounts
of alcohol consumption can cause brain degeneration.
The title of the study is
Associations Between Alcohol Consumption
and Gray and White Matter Volumes in the UK Biobank,
the United Kingdom Biobank.
First of all, gray matter are the neurons,
it’s the so-called cell bodies
that house the genome of the cells, et cetera,
and white matter is the connections, the fibers,
the so-called axons of neurons.
And it’s called white matter
because that tissue is surrounded by a fatty tissue
called myelin, which allows nerve cells
to communicate with each other very quickly.
So what this study did is it looked at the brains,
both the gray matter and the white matter,
of more than 30,000 and even more than 35,000
generally healthy middle-aged and older adults
in the United Kingdom
who were drinking various amounts of alcohol.
What they found was that even for people
that were drinking low to moderate amounts of alcohol,
so one or two drinks per day,
there was evidence of thinning of the neocortex,
so loss of neurons in the neocortex,
and other brain regions.
And I don’t say this in order to cause alarm,
I tell you this because they are important data
because they reveal and indeed answer the question
that has been burning for so long
as to whether or not chronic alcohol intake
can disrupt the brain,
even if the chronic intake is very low.
Now we should talk about what the word chronic means
because many people, when they hear the word chronic,
think high levels of whatever intake, okay?
So they think five drinks a night or 10 drinks a night
or people drinking every night.
Now in this study, they looked at people who on average
were drinking one or two drinks per night.
So that could be 14 drinks on the weekend,
it could be one drink per night,
it could be seven drinks on Friday.
In other words, on average, one or two drinks per night.
And I think many people out there are drinking
somewhere between one and two drinks per night
or day of the week on average,
so that would be seven to 14 drinks per week.
So this is an important study
because it says that if you’re consuming
even just seven glasses of wine across the week,
it’s likely that there is going to be some degeneration
of your brain in response to that alcohol intake.
Although, as mentioned earlier,
we will talk about some of the things that can inoculate
against some of that neuronal loss.
For those of you that are interested
in reading the study in more detail,
we put a link to it in the show note captions.
Before we begin, I’d like to emphasize that this podcast
is separate from my teaching and research roles at Stanford.
It is however, part of my desire and effort
to bring zero cost to consumer information about science
and science related tools to the general public.
In keeping with that theme,
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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,
They become more alert, they start talking more,
they feel great, they have all sorts of ideas
about the fun they could have that night
and they’re the ones that if you’ve ever fallen asleep
at a party for whatever reason,
or you’re getting tired and you’re yawning
and looking around the room
and like these people are still drinking and partying
and they’re having what seems to be this amazing time,
often not always those are the future alcoholics in the room
or those are the people
that have a genetic predisposition for alcoholism
or those are the chronic drinkers,
the people who have built up enough of a tolerance
or who have the chemical genetic makeup
such that increasing amounts of alcohol
make them feel better and better and better.
And of course they too have a threshold
beyond which their nervous system
will start to get diminished and they’ll pass out
and fall over, et cetera.
But that threshold is way, way higher
than it is for most people.
Now, this is important to understand
and it’s important to understand
because I think everyone should know and recognize
their own predisposition and kind of risk
in terms of developing alcoholism.
It’s also important to understand
because it relates to the phenomenon of blackout.
You know, many people think that blacking out
is passing out, but blackout drunk is when people drink
and they’re talking and doing things.
Sometimes sadly they’ll, or tragically,
they’ll often drive home or walk home
or they’ll hop on a bicycle and ride home
or they’ll go swimming in the ocean.
All of course, very dangerous activities
to do when people are really drunk
or even a little bit drunk in some cases.
So these people will do these sorts of things
and they do them because they have the energy to do them
and they feel good while doing them,
but they are doing them while the activity of neurons
in the hippocampus, which is involved in memory formation,
are completely shut off.
And this is why the next day you tell them,
hey, maybe we should talk about what happened last night.
Like, what happened last night?
He said, well, do you remember going to the party?
Yeah, no, it was great.
We did this, we did this, and then what?
And it’s very clear all of a sudden
that they have no recollection
of all the things they were doing despite being awake.
Now, I wish I could tell you
that there’s some sort of blood test or other biomarker,
even a fingerprint test that would allow you
to determine whether or not you have a propensity
to be one of these drinkers
that has a predisposition for alcoholism.
And if you’ve ever been blackout drunk,
and certainly if you’ve been blackout drunk
more than a few times, you should be quite concerned.
And as we talk more about the more chronic effects
and long-lasting effects of alcohol consumption
a little bit later in the episode,
I think it will become clear
as to why you should be concerned.
But in any case, there is something that can tell you
whether or not you might be in that category
versus likely not in that category.
And I alluded to this a couple of times already,
but I want to be really clear
that when people drink, no matter who you are,
initially there’s that shutting down
of those prefrontal cortical circuits.
There’s a gradual shutting down of the circuits
that control memory,
but then people divide into these two bins.
And these two bins are the people
who after more than a couple of drinks
start to feel sedated,
and the people who after more than a few drinks
do not start to feel sedated.
Now, of course, there’s going to be differences
created by how quickly people are drinking,
whether or not they’re combining different types of alcohol,
the types of alcohol, et cetera.
But in general, that can predict whether or not
you’re somebody who has a predisposition
for alcoholism or not.
One also very interesting finding
is that alcohol changes the relationship
between what’s called the hypothalamus
and the pituitary gland and the adrenals.
Now, the hypothalamus is a small collection of neurons
about the size of a large gumball
sits above the roof of your mouth,
and it houses neurons that are responsible
for some incredible aspects of our behavior
and our mindset.
Things like rage, things like sex drive,
things like temperature regulation,
very primitive functions,
including appetite, thirst, et cetera.
Alcohol, because it can go anywhere in the brain,
remember it’s water and fat soluble,
has effects on the hypothalamus.
The hypothalamus normally provides very specific signals
to what’s called the pituitary gland.
This is a little gland that actually sticks out of the brain
but it receives instructions from the hypothalamus.
And then the pituitary releases hormones
into the bloodstream that go and talk to your adrenals.
Your adrenal glands sit right above your kidneys
in your lower back.
And the adrenals release, as the name suggests,
adrenaline, also called epinephrine,
and also a molecule called cortisol,
which is involved in the kind of longer-term stress response
has some healthy effects too on the immune system.
Okay, so the hypothalamic-pituitary-adrenal axis.
I know that’s a mouthful,
you don’t need to remember the names,
but the hypothalamic-pituitary-adrenal axis
maintains your physiological balance
of what you perceive as stressful
and what you don’t perceive as stressful.
People who drink regularly,
so this again could be just one or two drinks per night,
or it could be somebody that drinks just on Fridays
or just on Saturdays, or maybe just on the weekend,
two to four drinks.
Well, those people experience changes
in their hypothalamic-pituitary-adrenal axis
that result in more cortisol,
more of this so-called stress hormone being released
at baseline when they are not drinking.
This is really important.
People who drink a bit, and when I say a bit,
I don’t mean one or two sips
or even a glass of wine every once in a while.
Again, people that are maybe having one drink a night
with dinner and maybe on the weekend, a few more.
Again, I offer a bunch of different patterns
to explain how it could also be two or three drinks
on Friday or six drinks only on Saturday.
Well, all of those groups experience increases
in cortisol release from their adrenal glands
when they are not drinking.
And as a consequence, they feel more stressed
and more anxiety when they aren’t drinking.
This is a seldom-talked-about effect of alcohol
because so often we hear
about the immediate effects of alcohol, right?
And we’ve been talking about some of those effects,
effects like reducing the amount of stress.
I mean, how many times have we heard somebody say,
oh, I need a drink, and then they have a drink,
and they’re like, calm down.
Now they can shake off the thoughts about the day’s work.
They can start to think about things
in a maybe more grounded or rational way,
or at least they believe that,
or they can somehow just relax themselves.
Well, while that very well may be true,
that it can relax them, when they are not drinking,
that level of cortisol that’s released at baseline
has increased substantially.
Again, this relates to a defined neural circuit
between brain and body,
and it has to do with the ratio of cortisol
to some of the other hormones involved
in the stress response.
We’ll provide a reference to the study
that describes how all of this works
for those of you that really want to delve into it.
But let’s go back to this issue
of those who are prone to alcoholism
versus those who are not.
Remember, there are people who have genetic variants,
that meaning genes that they inherited from their parents,
that make it more likely that they will become alcoholics.
But there are also people who drink often,
who start to experience this increase in alertness
the longer they drink across the night.
Part of that effect, we think,
is because of changes
in this hypothalamic pituitary adrenal axis.
So alcohol is kind of a double hit in this sense.
It’s causing changes in our brain circuitry
and neurochemistry that at the time
in which we’re inebriated are detrimental,
and it’s causing changes in neural circuitry
that persist long past the time
in which we’re experiencing the feeling
of being tipsy or drunk.
Now, again, I don’t want to demonize alcohol.
I’m not saying, oh, you know,
if you have a glass of wine now and again,
or you drink a beer now and again,
or even have, you know, a mixed drink now and again,
or a shot, that that’s necessarily terrible for you.
I certainly do not want that to be the message.
What I’m saying is that
if people are ingesting alcohol chronically,
even if it’s not every night,
there are well-recognized changes in neural circuits,
there are well-recognized changes
in neurochemistry within the brain,
and there are well-recognized changes
in the brain-to-body stress system
that generally point in three directions.
Increased stress when people are not drinking,
diminished mood and feelings of wellbeing
when people are not drinking,
and as you’ll soon learn,
changes in the neural circuitry
that cause people to want to drink even more
in order to get just back to baseline
or the place that they were
in terms of their stress modulation
and in terms of their feelings of mood
before they ever started drinking in the first place.
So again, I don’t want to demonize alcohol,
but I do want to emphasize
that there are long-term plastic changes,
meaning changes in neural circuitry and hormone circuitry
that across a period of several months
and certainly across a period of years
of the sorts of drinking patterns I described,
which I think for most people
are going to sound like pretty typical, right?
I mean, nothing that I described so far
was about drinking a case a night
or about binging on alcohol
in the way that we often hear about it in the news.
These are pretty common patterns of alcohol consumption.
I mean, all you have to do is board a transatlantic flight
or actually go to an airport on a Sunday afternoon
in a sunny area of the US,
and people are having three, four, five,
six beers, et cetera.
Again, personal choice is personal choice.
I’m not telling you what to do,
but it’s very clear that those sorts of drinking patterns
are changing neural circuitry
and they’re changing hormone circuitry,
and I’d love to be able to tell you
that they’re changing them for the better,
but they simply are not.
They’re actually changing them for the worse,
and worse is defined as making people
less resilient to stress,
higher levels of baseline stress,
and lower mood overall.
I’d like to take a quick break
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Now, I’ve been talking a little bit
about genetic predisposition,
but there are a couple of important points
I’d like to make about that.
First of all, what sorts of genes are involved
in setting someone down the path of alcoholism or not?
Well, it should come as no surprise
that the genes that chronic alcohol usage modifies,
they tend to fall primarily in the pathways
related to genetic control over serotonin receptors,
GABA receptors, remember that top-down inhibition
and the involvement of GABA,
and no surprise, the HPA, the hypothalamic pituitary axis.
All of those, of course, combine with environment,
they combine with patterns of abuse, right?
We know that if you’re in a social setting
where a lot of people are drinking,
the likelihood that you’re going to drink is much higher.
Social pressures, trauma, right?
Some people will use alcohol to self-medicate
to try and turn off their thinking
or to deal with trauma, et cetera.
So they combine with the environment,
but the genes that are in the serotonin synthesis
and receptor synthesis pathway, GABA and HPA axis
combine with environmental pressures
to give rise to alcohol use disorders.
So there’s a fairly coherent picture
that we have here, right?
This is not a case where, for instance,
people that have a lot of the enzyme
for metabolizing alcohol,
which we’ll talk about in a minute, alcohol dehydrogenase,
it’s not like they are necessarily the people
that become alcoholics,
whereas certainly in certain cultures,
certain Asian cultures in particular,
there are gene differences
that lead them to have low levels of alcohol dehydrogenase.
There are actually people
who have so little alcohol dehydrogenase
that when they ingest alcohol,
they get very red and they just feel sick.
So if you’re somebody that has a sip of alcohol
and you just feel horrible, it makes you feel nauseous,
chances are you have gene variants
that create a situation
where you’re not making very much alcohol dehydrogenase.
You just simply can’t metabolize alcohol.
So you just get a rapid buildup
of the toxic effects of alcohol, the acetyl aldehyde.
You’re not converting it into those empty calories.
But in cultures where you have a lot of genetic variants
and genes expressed in people
where they have a lot of alcohol dehydrogenase,
sure, they can drink more
and they’re converting more of that alcohol
from its toxic form to a non-toxic form.
And yes, of course, you will observe more alcoholism
in those communities because they’re drinking more.
But I do want to emphasize that the environmental factors
are playing a strong role there too,
because if you can drink more, you’re likely to drink more.
If you’re somebody that feels sick immediately
from drinking, it’s likely that you’re not going to engage
in alcohol consumption,
especially if these things are genetically related.
And of course, genes and culture and location in the world
tend to run together.
So do you have the gene for alcoholism?
Well, there isn’t one single gene.
Chances are if you have an immediate relative
who’s a chronic abuser of alcohol
or several relatives who are chronic abusers of alcohol,
well, that’s going to predispose you to be an alcoholic.
But since you don’t know which genes you express
unless you do genetic testing and those things
are available, but most people aren’t doing that,
this assay, if you will, and it’s not an assay,
as we say, an assay is a test that you run in the lab
to determine something.
And it’s not one that I recommend that you go drink
in order to do, but if you’ve noticed that you
or somebody else is somebody who can drink a lot
throughout the night and have increased energy
and can just drink and drink and drink,
and especially if there’s blackout episodes,
not remembering things the next day,
despite being alert throughout the entire night and so on,
well, then I would be very concerned that you might
actually have a genetic variant
predisposing you to alcoholism.
The other thing that predisposes people
to abuse of alcohol is age.
People who start drinking at younger ages
are greatly predisposed to developing alcohol dependence,
regardless of your family history of alcoholism.
Okay, so I’m going to repeat that.
People who start drinking younger are at great risk
for developing alcoholism,
even if they don’t have alcoholism in their family.
Now, of course, you don’t have to be an epidemiologist
to understand that if you grew up in a family of drinkers
and alcohol is everywhere,
and especially if there’s peer pressure
or lack of oversight,
then there’s going to be a higher tendency
or a higher probability, I should say,
that you will start drinking at a younger age.
However, even people that grow up nowhere
near their relatives,
if they start drinking at a young age,
so for instance, at 13 or younger or 14 or 15,
there’s a much higher probability
that they’re going to develop
a long-lasting dependence on alcohol.
People who take their first sip of alcohol later,
15, 16, or one would hope even later,
I can say one would hope,
because I’m now of that age and generation
where you think about all the things that young people do
and you go, oh gosh, if they only would wait
or if they only would abstain, you know?
So this is what happens.
I don’t know, there’s some neural circuit for that
that I can’t explain yet.
But people who, for instance,
drink only once they reach legal age of drinking,
which in the US, I believe in every state, is 21 years old,
if they take their first drink at 21,
the probability that they’ll go on
to develop full-blown alcohol dependence
or alcohol use disorder, as it’s called, AUD, is very low.
Now, a subset of them will
because they have such a strong genetic predisposition
or maybe life circumstances create a pattern
in which they become a chronic drinker.
But I found this very interesting.
Genes matter, but also the age
in which somebody starts drinking really matters.
Now, whether or not that’s because there are changes
in neural circuitry as a consequence of that drinking
that make people want to seek out more and more alcohol
or whether or not there’s some other effect,
maybe it’s a change in hormones, et cetera,
that predisposes those young drinkers
to become chronic drinkers or even full-blown alcoholics,
certainly developing alcohol use disorder.
There’s definition for that, we can talk about it.
It involves the amount of drinking
over a certain period of time, et cetera.
So it’s very clear that drinking early in life
creates a propensity for the development
of alcohol use disorder later in life.
And while there is a genetic component
to developing alcohol use disorder,
I find it very interesting
that if people who have those gene variants
delay their onset of drinking,
well, then the probability
that they’ll develop full-blown alcohol use disorder
drops as well.
So again, it’s genes and environments,
it’s not an either or
and there’s no single gene for alcoholism.
Well, I promise you I will also talk about
some of the documented positive effects of alcohol,
although they are very few and far between, they do exist.
But before I do that, I would be remiss
if I didn’t emphasize some more of the terrible things
that alcohol does and the way that it does it.
And for those of you that enjoy alcohol,
I, again, I really like to say I feel guilty
about telling you this
because I know how much some people enjoy a good drink
every once in a while.
And I say a good drink
because some people do like the taste of alcohol.
I suppose I lucked out
in that I don’t really like the taste of alcohol
and that just puts me to sleep,
but I know that people do enjoy it.
And I do want to point out that there is zero evidence
that provided somebody is of drinking age,
certainly not in the stage of brain development,
that having one drink or two drinks every now and again,
meaning every three or four weeks or once a month,
that is not going to cause major health concerns
or major health issues for most people.
I suppose if you have zero
or very little alcohol dehydrogenase,
it might make you feel sick,
but then you’re probably not the kind of person
that’s going to be drinking at all.
So again, if you enjoy alcoholic drinks,
I’m not trying to take them away from you by any means,
but you should know what drinking does
if you’re consuming it in this kind of
typical chronic pattern, as we can now refer to it,
which is that one or two a night
or a few stacked up on Friday
and maybe three or four on Saturday,
this kind of pattern of drinking, which is quite common.
And one of the more serious effects
that we should think about
is the impact on the so-called gut brain axis
or for sake of today’s discussion,
the gut liver brain axis.
I don’t think the gut liver brain axis
has ever been discussed on this podcast, maybe any podcast.
Although the moment I say that,
the gut liver brain axis,
people are going to come after me with, I suppose,
gut, liver, brain, and brains.
In any event, you have a brain, you have a gut.
That gut runs from your throat
down to the end of your intestine.
Your gut and your brain communicate
by way of nerve cells, neurons, and nerve connections,
the vagus nerve in particular,
and by way of chemical signaling.
Your gut also communicates by way of chemical signaling
and believe it or not,
by way of neural signaling to your liver.
And as we talked about earlier,
the liver is the first site in which alcohol
is broken down and metabolized into its component parts.
The liver is also communicating with the brain
through chemical signaling and neural signaling.
So we have the gut liver brain axis.
And what you find is that people who ingest alcohol
at any amount are inducing a disruption
in the so-called gut microbiome,
the trillions of little micro bacteria
that take resident in your gut
and that live inside you all the time
and that help support your immune system
and that literally signal by way of electrical signals
and chemical signals to your brain
to increase the release of things like serotonin
and dopamine and regulate your mood
generally in positive ways.
Well, alcohol really disrupts those bacteria.
And this should come as no surprise.
I mean, earlier we talked about this
and it’s well-known if you want to sterilize something,
you want to kill the bacteria, you pour alcohol on it.
I can remember scraping myself or cutting myself.
I was always injuring myself when I was a kid.
And the moment they take out the peroxide,
you’re like, oh boy, here it comes.
But if there’s no peroxide around
and you’ve got a wound there and you need to clean it out,
yeah, they’ll use alcohol,
which I do not recommend by the way.
And that’s one of the harshest ways to clean a wound.
But for centuries, thousands of years,
really alcohol has been used in order to clean things
and kill bacteria.
So alcohol kills bacteria and it is indiscriminate
with respect to which bacteria it kills.
So when we ingest alcohol and it goes into our gut,
it kills a lot of the healthy gut microbiota.
At the same time, the metabolism of alcohol in the liver,
which you now understand that pathway involving NAD,
acetyl aldehyde and acetate,
that pathway is pro-inflammatory.
So it’s increasing the release of inflammatory cytokines,
things like IL-6, et cetera,
tumor necrosis factor alpha.
If you’d like to learn more about the immune system,
we did an episode all about the immune system.
You can find it at hubermanlab.com.
I’ll teach you all the basics of what are cytokines,
what are mast cells, et cetera.
In any event, all these pro-inflammatory molecules,
those are being released.
You’ve now got disruption of the gut microbiota.
As a consequence, the lining of the gut is disrupted
and you develop at least transiently leaky gut.
That is bacteria that exist in the gut,
which are bad bacteria,
can now pass out of the gut into the bloodstream.
So you’ve got a two hit kind of model here.
In biology, we talk about two hit models.
That is kind of a one plus one equals four.
And it’s generally when you hear two hit,
it’s not a good thing.
So you’ve got bad bacteria from partially broken down food
moving out of the gut.
The good bacteria in the gut have been killed.
You might say,
how does the alcohol kill the bad bacteria in the gut?
Well, the bad bacteria that are from partially digested food
oftentimes escape the gut
before the alcohol can disrupt them.
And so now you’ve got leaks in the gut wall.
You’ve got the release of this bad bacteria.
You’ve got inflammatory cytokines
and other things being released from the liver.
And they are able to get into the brain
through what’s called a neuroimmune signaling.
And what’s really bizarre in terms of the way
that this manifests in the brain,
I mean, it’s not the way I would have done it.
But then again, as I always say,
I wasn’t consulted at the design phase.
And anyone who says they did,
you should be very skeptical of them.
The net effect of this is actually to disrupt
the neural circuits that control regulation
of alcohol intake.
And the net effect of that is increased alcohol consumption.
So this is just terrible, right?
I mean, you’re taking in something
that disrupts two systems, the gut microbiota
and it disrupts in two ways.
It’s killing the gut microbiota
and it’s allowing the bad bacteria
to move from the gut into the bloodstream.
You’ve also got pro-inflammatory cytokines
coming from the liver and those converge
or arrive in the brain and create a system
in which the neural circuits cause more drinking.
That’s a bad situation.
And this is why people who drink regularly,
even if it’s not a ton of alcohol,
again, of the sorts of patterns of drinking
that I talked about before.
And certainly for those that are chronic heavy drinkers,
what you end up with is a situation
in which you have inflammation in multiple places
in the brain and body and the desire to drink even more
and to further exacerbate that inflammation
and the gut leakiness.
So this is basically a terrible scenario
for the gut-liver-brain axis.
And it’s especially prevalent
in so-called alcohol use disorder.
Again, people that are ingesting somewhere
between 12 and 24 drinks per week.
For those of you that are interested in learning more
about the gut-liver-brain axis
and in particular alcohol use disorder,
I’ll provide a link in the show note captions.
And there’s a wonderful review on this that details that.
But on the positive side,
it points to the possibility that at least some,
again, at least some of the negative effects
of alcohol consumption,
whether or not you’re somebody
who’s currently ingesting alcohol
or who used to ingest alcohol
and is trying to so-called repair these systems
of the brain and body,
whether or not replenishing the gut microbiota
is going to be beneficial.
And we know that there are ways to do that.
And we know that there’s at least some promise
for the ability for the system to repair itself.
How does one do that?
Well, I’ve talked before about this on the podcast,
but studies done by colleagues of mine at Stanford,
Justin Sonnenberg, who’s been on this podcast as a guest,
an amazing episode all about the gut microbiome
and his collaborator, Chris Garner,
also at Stanford School of Medicine,
have explored not alcoholism,
but what are ways to improve the gut microbiota
in particular to reduce the production
of inflammatory cytokines
and to adjust what’s called the inflammatome.
You’ve heard of the genome and the proteome, et cetera.
Well, the inflammatome is the total array,
or at least the near total array of genes and proteins
that control inflammation.
How can you reduce inflammation
and make that inflammatome healthier?
Well, they’ve shown that two to four servings
of fermented foods per day,
and here I’m not referring to fermented alcohol,
I’m talking about low sugar fermented foods,
so things like kimchi, sauerkraut, natto,
for those of you that like Japanese food, there are others.
I know things like kefir,
things like yogurts that have a lot of active bacteria,
again, low sugar varieties of all these things.
Those are terrific at reducing inflammatory markers
and at improving the gut microbiome.
One could imagine that either inoculating oneself
from some of the effects of alcohol,
although I’d prefer that people
just not drink alcohol chronically, frankly,
or if somebody is trying to repair their gut microbiome
because they ingested a lot of alcohol
or because they had a lot of these inflammatory cytokines
for many years or even a short period of time,
regular ingestion of two to four servings
of these fermented foods can be quite beneficial.
I want to make it clear that has not been examined
specifically in the context of alcohol use disorder,
but because a huge component of the negative effects
of alcohol use disorder are based
in this gut-liver-brain axis and disruption
of the gut microbiome and the inflammatory cytokines,
it stands to reason that things that are well-established
to improve inflammation status,
in other words, reduce inflammation,
such as ingesting two to four servings
of low sugar fermented foods per day,
make sense in terms of trying to repair
or replenish the system.
One could also imagine taking probiotics or prebiotics.
Certainly that would work as well,
although I’ve sort of favored the discussion
around fermented foods and replenishment
of the gut microbiome, mostly because there are more studies
that have examined that in humans
and because of the direct relationship
that’s been established between doing that
and reducing negative markers within the inflammatory.
And I should mention along the lines of repair and recovery,
I put out a question on Twitter the other day.
I said, what do you want to know about alcohol?
I got more than a thousand questions.
I’ll take some more of those questions
a little later in the episode.
But one of the things I noticed is that many
of the questions, hundreds, in fact,
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 hubermanlab.com.
It’s got a ton of behavioral, nutritional,
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 hubermanlab.com,
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, hubramlab.com.
There are direct links to some of the tools
related to deliberate cold exposure.
And we have an entire newsletter
on deliberate cold exposure protocols.
You can find on hubramlab.com
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.
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 hubermanlab.com
as the site where you can find that episode on salt balance
and ways to restore electrolyte balance.
Having your electrolytes at the proper levels
before you drink is ideal.
Some people will say for every glass of alcohol
that you drink, you should drink one glass of water.
I would say better would be two glasses of water
given the dehydrating effects of alcohol.
And even better would be water with electrolytes.
That certainly would set you up for a better day
the next day.
And if you don’t manage to do that,
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 examine.com,
a website that I really like
because it just has so much useful information,
have assembled a list of things
that have been proposed, purported to improve,
or I should say to remove the effects of hangover.
And as they point out,
and I would like to point out over there,
there isn’t a lot of quality science
to support the idea that any one compound
can eliminate hangover.
And that’s probably because hangover, again,
arises from multiple organs and tissues and systems
in both the brain and body.
Nonetheless, they have a terrific list over there
of things, everything from Japanese pear fruit juice
has been proposed to do this,
to some other really esoteric things,
even things like yohimbine.
Frankly, when I look at the literature there and elsewhere,
one simply cannot find the magic substance,
the one herb, the one potion that can wipe away hangover.
Getting rid of hangover is going to be best solved
by doing a collection of a small number
of very powerful things,
of which I’ve already listed off a few.
However, there are some additional things
that one can do for relieving hangover.
And one of them is to be very thoughtful
about what sorts of alcohol one consumes.
So I find this interesting.
There have actually been studies
of which types of alcohol lead to the greatest hangovers.
There’s actually a lot of legend and lore
about this as well.
Some people have said, for instance,
that drinks that have a high sugar content
lead to greater hangovers.
Turns out that’s not the case,
or at least that’s not what the science points to.
If you look at the expected hangover severity,
what you find is that at the bottom end of the scale,
there’s a drink that I’m not going to tell you
for the moment,
but what you find is that near it is, for instance, beer.
The consumption of beer,
provided it is not 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
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
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.
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.
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
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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some of which overlap with the content
of the Huberman Lab podcast,
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 HubermanLab.com, click on the menu,
go to newsletter, you supply your email,
but we do not share your email with anybody.
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 HubermanLab.com
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.