00:00- Welcome to the Huberman Lab Podcast,
00:02where we discuss science
and science-based tools
00:09I'm Andrew Huberman,
00:10and I'm a professor of
neurobiology and ophthalmology
00:13at Stanford School of Medicine.
00:15Today, we're discussing alcohol,
00:17one of the most commonly
consumed substances
00:19on the planet Earth.
00:20I should mention that both humans
00:21and non-human animals consume alcohol
00:24either for recreational purposes
00:26because they like the
feeling that it gives them
00:29or for medicinal purposes
00:31or for other purposes that we'll discuss.
00:33We are, of course, going to
discuss the effects of alcohol
00:36on our biology, ranging from its effects
00:39on individual cells, on
organs and organ systems
00:42in our brain and body.
00:43We are also going to discuss the effects
00:45of the effects of alcohol,
00:47that is, what being inebriated really does
00:50to our thinking and our
behavior and how it does it.
00:52And we are going to address
00:53what seems to be one of the
more common questions out there,
00:55which is whether or not low to
moderate amounts of drinking
00:59are better for our health
01:00than zero alcohol consumption at all.
01:03And of course we will talk
01:04about severe alcohol
intake, binge drinking.
01:08We will also talk about hangover
01:10and what science says about ways
01:12to reduce the effects of hangover,
01:14either by doing things
that are inoculatory,
01:16meaning before you drink
or while you drink,
01:19as well as things to do if
you happen to have a hangover.
01:22We will discuss some of
the genetic differences
01:24for alcohol and alcoholism,
01:26and we will discuss alcohol
consumption in young people
01:31and how that can be especially
detrimental for reasons
01:33that I think are going to be
quite surprising to most of you.
01:36My goal is that by the
end of today's episode,
01:38you will have a thorough understanding
01:39of what alcohol does
to your brain and body
01:41and that you will be able
to make informed decisions
01:44as to whether or not you
should be consuming zero,
01:46absolutely no alcohol,
01:48small to moderate amounts of alcohol,
01:50and, again, we'll define
exactly what that means,
01:54small to moderate amounts,
01:55and if you or somebody else that you know
01:58is consuming excessive amounts of alcohol
02:00that are clearly
detrimental to your health,
02:02some of the better routes and
resources that you can use
02:05in order to remove that
dependence and/or consumption.
02:09I'd like to preface all of that by saying
02:11that today's discussion is really geared
02:14toward giving you information.
02:16It is not about judging alcohol intake
02:18or lack of alcohol intake.
02:19I just want you to be able to make
02:21the most informed decision
about alcohol possible.
02:25I'm pleased to announce that
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02:29We've partnered with Momentous
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03:19Before we get into
today's content in detail,
03:21I just want to answer a
commonly asked question
03:24about alcohol consumption and the brain,
03:26and the question that so often comes up
03:28is whether or not low to
moderate amounts of alcohol,
03:31so maybe one drink a day
03:33or one or two drinks a day kind of thing,
03:35whether or not that is bad for your brain,
03:38in particular, whether or
not it causes degeneration
03:40of neurons or nerve cells.
03:42Now, the reason that
question comes up so often
03:44is because, for many years,
03:45it's been known that high
levels of alcohol consumption,
03:48so 12 to 24 drinks per week or more,
03:52is certainly causing neurodegeneration,
03:55in particular of the so-called neocortex,
03:57the outer layers of the brain
03:58that house associative memories,
04:00that house our ability to think and plan,
04:03that house our ability to
regulate our more primitive drives
04:07according to context, et cetera.
04:10So to make very clear, drinking a lot,
04:13so having, you know, three
or four drinks per night
04:16every night of the week, is
clearly bad for the brain.
04:19A recent study, however,
finally addressed the question
04:22of whether or not low to moderate amounts
04:25of alcohol consumption can
cause brain degeneration.
04:28The title of the study
04:30is Associations between
alcohol consumption
04:33and gray and white matter
volumes in the UK Biobank,
04:36the United Kingdom Biobank.
04:38First of all, gray matter are the neurons,
04:40it's the so-called cell bodies
04:41that house the genome
of the cells, et cetera,
04:43and white matter is the
connections, the fibers,
04:46the so-called axons of neurons,
04:48and it's called white
matter because that tissue
04:52is surrounded by a fatty
tissue called myelin,
04:54which allows nerve cells
04:55to communicate with
each other very quickly.
04:57So what this study did is
it looked at the brains,
05:00both the gray matter and the white matter,
05:02of more than 30,000, and
even more than 35,000
05:06generally healthy
middle-aged and older adults
05:09in the United Kingdom
05:10who were drinking various
amounts of alcohol.
05:13What they found was that even for people
05:16that were drinking low to
moderate amounts of alcohol,
05:20so one or two drinks per day,
05:23there was evidence of
thinning of the neocortex,
05:27so loss of neurons in the neocortex,
05:28and other brain regions.
05:30And I don't say this in
order to cause alarm.
05:33I tell you this because
they are important data
05:36because they reveal and
indeed answer the question
05:39that has been burning for so long
05:41as to whether or not
chronic alcohol intake
05:44can disrupt the brain
05:45even if the chronic intake is very low.
05:47Now, we should talk about
what the word chronic means
05:49because many people, when
they hear the word chronic,
05:52think high levels of
whatever intake, okay?
05:56So they think 5 drinks a
night or 10 drinks a night
05:58or people drinking every night.
06:00Now, in this study, they looked at people
06:02who, on average, were drinking
one or two drinks per night.
06:06So that could be 14 drinks on the weekend,
06:09it could be one drink per night.
06:11it could be seven drinks on Friday,
06:14in other words, on average,
one or two drinks per night.
06:17And I think many people out there
06:18are drinking somewhere
between one and two drinks
06:21per night or day of the week on average,
06:24so that would be 7 to 14 drinks per week.
06:28So this is an important study
06:29because it says that if you're consuming
06:31even just seven glasses
of wine across the week,
06:34it's likely that there is
going to be some degeneration
06:37of your brain in response
to that alcohol intake.
06:40Although, as mentioned earlier,
06:42we will talk about some of the things
06:43that can inoculate against
some of that neuronal loss.
06:46For those of you that are interested
06:47in reading the study in more detail,
06:50we've put a link to it in
the show note captions.
06:52Before we begin, I'd like to
emphasize that this podcast
06:54is separate from my teaching
and research roles at Stanford.
06:57It is, however, part
of my desire and effort
06:59to bring zero-cost-to-consumer information
07:01about science and science-related tools
07:03to the general public.
07:04In keeping with that theme,
07:05I'd like to thank the
sponsors of today's podcast.
07:08Our first sponsor is Levels.
07:10Levels is a program that lets you see
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feedback on your diet
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07:18One of the most important features
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07:25as well as our long-term health,
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07:29That is, our blood sugar levels.
07:31And that's because all the
cells and tissues of our body
07:34and especially neurons, nerve cells,
07:36rely on glucose for fuel.
07:38I realize some of you
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07:40and, yes, you can use ketones for fuel,
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10:47Let's talk about alcohol,
10:48and let's just acknowledge
that human beings
10:49have been consuming alcohol
for thousands of years.
10:52If you look at the archeological
evidence from Mesopotamia,
10:54you'll find that 5,000 years
ago, people had wine vessels.
10:57Or if you want to know
10:58when people first started
distilling alcohol,
11:00much to people's surprise,
11:01that did not first take place in Ireland,
11:03and that's not a joke about the Irish.
11:05You'll see a lot of claims online
11:06that the Irish were the
first to distill alcohol,
11:08but, in fact, they were not.
11:10It was the Chinese that were
the first to distill alcohol,
11:12and that took place in
China in the first century.
11:15Alcohol has been used
for nutritional purposes,
11:17so there are cultures that believe,
11:20and indeed still believe,
11:21that the calories in alcohol are useful,
11:23although later we'll talk
about how alcohol calories
11:25are indeed empty calories
11:26and what an empty calorie really
is, why it's called empty.
11:31Alcohol has been used
for medicinal purposes
11:33because indeed it does kill bacteria,
11:35and, as you'll soon find out,
11:36the fact that it kills bacteria,
11:38because that is absolutely true,
11:40it also kills the good
bacteria in your gut,
11:42and the destruction of that
good bacteria in your gut
11:44can lead to things like leaky gut syndrome
11:47and has all sorts of issues,
11:48and there are ways to
deal with those issues
11:49and we'll talk about those.
11:50So alcohol has been used
for medicinal purposes,
11:52it's been used to clean surfaces,
11:54it's used in my laboratory
11:55in order to make up so-called reagents
11:57to do our experiments,
11:59but most humans have
been consuming alcohol
12:02in order to change their internal state,
12:04in order to feel differently
than they would otherwise.
12:07That feeling of being drunk or inebriated
12:09or tipsy or lightheaded is something
12:12that many, not all, but many
humans seem to enjoy and pursue
12:16even though, typically,
it leads to a feeling
12:20of being less happy, less motivated,
12:24more stressed, et cetera,
when the alcohol wears off.
12:28That's pretty incredible, right?
12:29I mean, we're talking about a substance
12:30that people have been
highly motivated to pursue,
12:32that are still highly motivated to pursue,
12:35to create and to consume,
that they'll spend money on,
12:38and that's despite the fact
that it makes them feel good
12:41and then it makes them feel lousy.
12:43Now, some of you might be saying,
12:44"Well, I drink, but I
don't drink to excess
12:46and, therefore, I don't feel lousy.
12:48I feel good when I drink
and then it wears off
12:50and it allows me to
get through my evening,
12:51and then the next
morning I'm ready to go."
12:53Okay, that very well may be
true, I believe those people,
12:58and, as I mentioned in the
beginning of the episode,
13:00I'm not here to demonize
alcohol in any way.
13:02But I do want to point out what alcohol is
13:05and how it creates the
effects that it does,
13:08and then I want to talk
about what those effects are
13:11when you engage in consuming alcohol
13:14even as often as one
or two nights per week,
13:17or let's say you're just
somebody who has a drink or two
13:19on Friday, maybe a few more on Saturday,
13:21or maybe you're somebody who
consumes all your alcohol
13:24one night per week or one night per month.
13:25We'll talk about how that's
affecting your biology.
13:28So let's address what alcohol is
13:31and how it affects the cells and tissues
13:32and organs of your body.
13:33Then we'll take a look at
some of the epidemiology,
13:36that is, how many people
are consuming alcohol
13:38and how much they're drinking.
13:39And then you will be able,
I think, to get a good sense
13:42of how the alcohol that you're drinking,
13:44if you're drinking any at all,
13:46is impacting your brain and body
13:48and the choices you might want to make
13:50about how and when to drink alcohol,
13:52or even if you want to
eliminate alcohol altogether.
13:55Okay, so some basic chemistry
and biology of alcohol,
13:58and, again, I'll make this very clear
13:59even if you don't have a
chemistry and biology background.
14:02Because of the structure of alcohol,
14:04it is what's called both
water-soluble and fat-soluble.
14:08Translated into what's meaningful for you,
14:11what that means is when you drink alcohol,
14:13it can pass into all the cells
and tissues of your body.
14:17It has no trouble just passing
right into those cells.
14:20So unlike a lot of substances and drugs
14:23that actually attach to
the surface of cells,
14:26to receptors, as they're
called, little parking spots,
14:28and then trigger a bunch of downstreams,
14:31like, domino cascades of effects,
14:33alcohol actually has its
own direct effects on cells
14:36because it can really just
pass into those cells.
14:39So it's water- and fat-soluble,
14:42and the fact that it can pass
14:43into so many organs and cells so easily
14:46is really what explains
its damaging effects.
14:49I should mention that there are
three main types of alcohol.
14:52There's isopropyl,
methyl, and ethyl alcohol,
14:55and only the last one,
ethyl alcohol or ethanol,
14:58is fit for human consumption.
15:00However, it is still toxic, okay?
15:03It produces substantial
stress and damage to cells.
15:07I'd love to be able to tell you otherwise,
15:09but that's just a fact.
15:10Ethanol produces
substantial damage to cells,
15:14and it does that because
when you ingest ethanol,
15:17it has to be converted into something else
15:19because it is toxic to the body.
15:21And there's a molecule inside
of all of us called NAD,
15:25and you may have heard of NAD
because it's quite popular,
15:27there's a lot of discussion about NAD
15:30in the longevity literature right now.
15:32NAD is present in all our
cells from birth until death.
15:34The levels of NAD tend to
go down across the lifespan.
15:37There are ideas that
increasing levels of NAD
15:39may extend lifespan.
15:40A lot of that is still controversial,
15:42or, at least we should say, is ongoing
15:43in terms of the research.
15:45But nonetheless, when you ingest ethanol,
15:47NAD and related biochemical pathways
15:50are involved in converting that ethanol
15:52into something called acetaldehyde,
15:54it's broken down into acetaldehyde.
15:56And if you thought ethanol was bad,
15:58acetaldehyde is particularly bad.
15:59Acetaldehyde is poison.
It will kill cells.
16:03It damages and kills cells
and it is indiscriminate
16:05as to which cells it damages and kills.
16:09Now, that's a problem, obviously,
16:11and the body deals with that problem
16:14by using another component of
the NAD biochemical pathway
16:18to convert acetaldehyde into
something called acetate.
16:22Acetate is actually something
16:24that your body can use as fuel.
16:26And that process of going from ethanol
16:29to acetaldehyde to acetate
16:32does involve the production
of a toxic molecule, right?
16:35Again, acetaldehyde is really toxic.
16:37And NAD, and if we want to get technical,
16:40it's the NAD-to-NADH ratio,
16:43and that chemical step
is the rate-limiting step
16:47to ethanol's metabolism.
16:48What does that mean for you?
16:50What that means is that if your body
16:52can't do this conversion of ethanol
16:54to acetaldehyde to acetate fast enough,
16:57well, acetaldehyde will
build up in your body
16:59and cause more damage,
17:01so it's important that your body
17:03be able to do this
conversion very quickly.
17:05And the place where it does
that is within the liver,
17:09and cells within the liver
17:10are very good at this conversion process,
17:13but they are cells and they
are exposed to the acetaldehyde
17:17in the conversion process,
17:18and so cells within the
liver really take a beating
17:22in the alcohol metabolism events.
17:25So the key thing to understand here
17:27is that when you ingest alcohol,
17:29you are, yes, ingesting a poison,
17:31and that poison is converted
17:32into an even worse poison in your body,
17:34and some percentage of that worse poison
17:36is converted into a form of calories
17:38that you can use to generate
energy, generate ATP.
17:42And the reason why alcohol
is considered empty calories
17:45is because that entire process
is very metabolically costly,
17:48but there's no real nutritive value
17:51of the calories that it creates.
17:53You can use it for immediate energy,
17:55but it can't be stored
17:56in any kind of meaningful
or beneficial way.
17:58It doesn't provide any vitamins,
18:00it doesn't provide any amino acids,
18:02it doesn't provide any fatty acids,
18:04it's truly empty calories.
18:05I know some people talk about
sugar is empty calories,
18:07but sugar actually is a
far better fuel source
18:10than alcohol or acetate.
18:13But nonetheless, when you ingest alcohol,
18:16some percentage is being
shuttled into a worse poison
18:19and some is being shuttled
into a fuel source.
18:22Now, the important thing to understand
18:24is that it is the poison,
the acetaldehyde itself,
18:28that leads to the effect of
being inebriated or drunk.
18:32I think most people don't realize that,
18:34that being drunk is actually
a poison-induced disruption
18:38in the way that your neural circuits work.
18:40And so we should ask ourselves,
18:41like, which neural
circuits, what brain areas,
18:44what body areas are involved
in feeling drunk or inebriated?
18:47Now, in thinking about this
state of being tipsy or happy
18:50or really drunk or a little bit drunk,
18:53I want to mention something
18:54that I think most people aren't aware of,
18:56and that's the fact that for people
18:59that are regular drinkers
19:00or that have a genetic
predisposition to alcoholism,
19:04when they drink, they tend
to feel very energized
19:08and very good for longer periods of time.
19:11Again, people who have a genetic
predisposition to alcohol
19:13or people who are chronic drinkers
19:15or even just, if you recall,
19:17chronic doesn't have to
mean a ton of alcohol
19:19but they're drinking one or two per night
19:21or they're every other night type drinkers
19:22or Thursday through Sunday drinkers,
19:25those people typically
experience an increase
19:28in alertness and mood when they drink,
19:31whereas occasional drinkers
19:32will have a briefer, meaning
less long-lasting, period
19:37of feeling good when they drink
19:38and then more quickly
transition into a state
19:41in which they're tired or they
start losing motor skills,
19:44they start slurring their speech.
19:47I also want to emphasize this
is distinct from tolerance.
19:49We'll talk about tolerance later
19:50and exactly what tolerance means.
19:52But I really want to highlight the fact
19:53that when people ingest this poison,
19:56'cause indeed it is poison,
19:59the range of effects is very different,
20:01and you can reliably predict
20:03who are the people with a
predisposition to alcoholism
20:06and who are the people who
are more regular drinkers
20:09by the contour or the timing
of the different effects.
20:12And, again, people who tend
to feel more alert and excited
20:16every time they drink, they
tend to get a real lift,
20:19they become kind of the life of the party
20:21and that lasts a long while,
20:23those people are the ones
that really have to be careful
20:26about predisposition for alcoholism.
20:29And those people also need to be careful
20:31about their drinking
20:33and the amount of drinking
that they're doing,
20:34even if they're not full-blown alcoholics.
20:37Now, of course, people
who are ingesting alcohol
20:39who are not accustomed to drink alcohol
20:41have to be concerned
about drinking alcohol
20:43because it can impair motor function
20:45and judgment, et cetera.
20:46But in thinking about the
biochemical effects of alcohol
20:49and what it's doing to the body,
20:51what it's doing in all cases
20:54is it's consumed into the gut, right?
20:57Goes into the stomach,
20:57the liver immediately
starts this conversion
20:59that we talked about before
21:00of ethanol to acetaldehyde to acetate,
21:02and some amount of
acetaldehyde and acetate
21:05are making it into the brain,
21:06it crosses the blood-brain barrier.
21:07Again, the brain has this fence around it
21:09that we call the blood-brain
barrier or the BBB.
21:12Many things, most things, thankfully,
21:14can't pass across the blood-brain barrier,
21:16but alcohol, because it's
water- and fat-soluble,
21:19just cruises right across this fence
21:21and into the milieu, the
environment of the brain,
21:24which is made up of a couple
different major cell types,
21:26neurons, nerve cells, and
so-called glial cells,
21:28which are in between the nerve cells,
21:30and we'll talk about the
effects on each of those soon.
21:33So what happens when
alcohol gets into the brain
21:35that makes us feel tipsy or drunk
21:37and, in some people, makes people
21:38feel really especially
energized and happy?
21:42Well, alcohol is indiscriminate
21:44in terms of which brain areas it goes to.
21:47Again, it doesn't bind
to particular receptors,
21:50but it does seem to have a propensity
21:52or an affinity for particular brain areas
21:55that are involved in certain
kinds of thinking and behavior.
21:57So one of the first things that happens
21:59is that there's a slight,
22:01at least after the first
drink or second drink,
22:04there's a slight suppression
in the activity of neurons
22:07in the prefrontal cortex.
22:09This is an area of your neocortex
22:11that's involved in thinking and planning
22:13and, perhaps above all,
22:15in suppression of impulsive behavior.
22:18So if you go to a party
and they're serving alcohol
22:21and people are consuming drinks,
22:23what you'll notice is that a
few minutes into that party,
22:26the volume of people's
voices will increase,
22:28and that's because people are
simply not paying attention
22:30to their voice modulation,
22:31and as other people start
speaking more loudly,
22:33other people are speaking more loudly.
22:34We've all had this experience,
right, of going to a party
22:36and then you step outside for a moment
22:38and you go, "Oh, my
goodness, I was shouting."
22:39You come home, the next day,
you've got a sore throat.
22:41It might be that you
picked up some sort of bug,
22:43some virus or something,
22:44but oftentimes it's just the fact
22:46that you've been shouting
all night just to be heard
22:48because as the prefrontal
cortex shuts down,
22:50people stop modulating their
level of speech quite as much.
22:55You also notice that people
start gesticulating more,
22:57people will start standing
up and sitting down more,
22:59they'll start walking around more,
23:00if there's music on,
23:01people might spontaneously start dancing.
23:04All of this is because these
areas of the prefrontal cortex
23:07normally are providing what's
called top-down inhibition.
23:10They are releasing a
neurotransmitter called GABA
23:13onto various parts of the
brain that are involved
23:15in impulsive motor behavior
and thought patterns,
23:17and as you shut down
the prefrontal cortex,
23:20that GABAergic suppression of impulses
23:23starts to be released,
23:24so people will say things
that they want to say
23:27without so much forethought
about what they're saying,
23:30or they might do things
that they want to do
23:32without really thinking
it through quite as much
23:34or they might not even remember
thinking it through at all,
23:37or experience, I should say,
thinking it through at all.
23:39We haven't talked about blacking out yet
23:40and the effects of alcohol on memory,
23:42but as long as we're there,
23:43I'll just tell you that alcohol
has a very strong effect
23:46in suppressing the neural networks
23:48that are involved in memory
formation and storage.
23:51This is why oftentimes we
forget the events of a night out
23:55if we've been drinking.
23:56One of the more important things to know
23:58about the effects of alcohol in the brain
24:01is this disruption in top-down inhibition,
24:03but, also, that areas of the brain
24:06that are involved in flexible behavior,
24:09sort of considering different options,
24:11like I could do A or I could do B,
24:12I could say this to them
or I could say that,
24:14I could say it in that way or
I could say it in this way,
24:16this might be a little more tactful,
24:18those brain areas basically
shut down entirely
24:21and people just tend to
say what they want to say.
24:23So the key thing to understand
is that when people drink,
24:26the prefrontal cortex and
top-down inhibition is diminished,
24:31that is, habitual behavior
and impulsive behavior
24:36Now, what's interesting is
this is true in the short term,
24:39so after people have one or
two, maybe three or four drinks,
24:42but it's also true that the
more often that people drink,
24:48there are changes in the very circuits
24:50that underlie habitual
and impulsive behavior.
24:53This is really important to highlight,
24:55so much so that I want to drill
into it a bit more deeply.
24:58For the person that drinks,
say, every Thursday night
25:01or every Friday night
25:02or goes out only on
Saturdays but every Saturday,
25:06there's evidence that there are changes
25:08in the neural circuits of the brain
25:09that control habitual behavior
and impulsive behavior,
25:12and they are modified
and strengthened in ways
25:16that make those people more
habitual and more impulsive
25:19outside the times in
which they are drinking,
25:22and when they drink, impulsive
and habitual behavior
25:26tends to increase even further.
25:27This is something that's
not often talked about
25:30when discussing the effects of alcohol.
25:31I mean, we all know the
effects of being drunk
25:36Can be bad in terms of
judgment, motor coordination,
25:39certainly driving drunk
is a terrible thing,
25:41get you or other people killed and so on.
25:44But rarely do we hear about
the changes in neural circuits
25:47from just one or two
nights of regular drinking.
25:52Again, chronic drinking
doesn't necessarily mean
25:55every day and every night.
25:56It could be the person that simply drinks
25:58every Thursday or every Friday
25:59or just once a week has
three or four drinks
26:01or maybe even a few more.
26:03That person is going to
experience a decrease
26:05in this top-down inhibition,
26:07so an increase in impulsivity
and habitual behavior,
26:09because the brake on those behaviors
26:11has been removed while they're drinking,
26:13but also changes in the
very neural circuits
26:16that allow habitual and impulsive behavior
26:19to occur more readily even
when they're not drinking.
26:21And if you want to know the
actual substrate for that,
26:23the cellular substrate, I
can briefly describe it.
26:25It's really interesting.
26:27Again, you don't need to know any biology
26:29What it does is it increases
the number of synapses,
26:33the actual points of connection
in the neural circuits
26:35that control habitual behavior.
26:37So there's literally a growth
26:39of the neural circuits in your brain
26:41that lead to existing
habit execution, all right,
26:44the performance of things
you already know how to do,
26:47and a reduction in the neural circuits,
26:49or I should say a reduction
26:50in the number of
synapses, of the contacts,
26:53within the neural circuits
that are controlling behavior.
26:56So this, again, is a not
often discussed aspect
27:00Fortunately, it is reversible.
27:02So in animals or humans
27:04that undertake a period of abstinence
27:06of anywhere from two to six months,
27:08these neural circuits return to normal
27:11except in cases where people
have been chronically drinking
27:14large volumes of alcohol
for many, many years.
27:17while there is some
recovery of brain circuitry
27:20after people get sober,
meaning completely sober,
27:24they stop drinking entirely,
27:26there is evidence of long-lasting impact
27:28of heavy alcohol usage
throughout the lifespan.
27:31But, of course, this
doesn't mean that anyone
27:32that's suffering from
alcoholism or that used to
27:34should not continue to
focus on their health.
27:36You absolutely should. All is not lost.
27:39But for people that have been
drinking for a lot of years,
27:41maybe you went to college and
you drank a lot in those years
27:43and your neural circuits changed,
27:45if there's a period in which
you don't drink alcohol,
27:47again, from two to six
months and ideally longer,
27:51those neural circuits
can then be remodified
27:53back to their original state.
27:55So let's consider some of the
other neurochemical effects
27:57of alcohol in the brain and body.
27:59And, again, for right now,
28:00we're confining the conversation to people
28:02that are drinking, on average,
one or two drinks per night.
28:06Now, some people might think
28:07that two drinks per night is a lot,
28:08and a lot of that will
depend on body weight.
28:10So for instance, people
who weigh 110 pounds,
28:15for them to ingest two alcoholic drinks
28:18is going to be substantially different
28:19in terms of the biochemical effects
28:21than somebody who weighs 220 pounds.
28:24Of course tolerance will
also factor into this,
28:26genetic background will
also factor into this,
28:29and indeed whether or
not people have eaten
28:32will factor into this,
28:32so there are a lot of factors
and we'll talk about that.
28:35For the time being, if you're curious
28:36about how food impacts
the effects of alcohol
28:39and your feelings of being drunk,
28:41you may have heard, for instance,
28:42that if somebody's inebriated
and they want to sober up,
28:45they should eat something.
28:46Turns out that does not work.
28:48Here's how it does work, however.
28:50If you eat something
prior to drinking alcohol
28:53or while ingesting alcohol,
28:55it will slow the absorption of
alcohol into the bloodstream.
28:59In other words, you won't
feel as drunk as fast,
29:02for many of you, this
probably comes as no surprise,
29:04in particular, if that meal
includes carbohydrates,
29:07fats, and proteins, okay?.
29:09The inclusion of all
three major macronutrients
29:12seems to slow the absorption
of alcohol into the bloodstream
29:15far more than having any one of those
29:18or two of those macronutrients present.
29:21Now, if you are already inebriated
29:23or you've had a glass of wine or a beer
29:25and you eat something,
29:28chances are that alcohol
has already made it
29:31into your bloodstream
29:31because it moves into the
bloodstream so quickly.
29:34Again, it's fat-soluble and water-soluble,
29:37so within minutes, right?
29:39If you have an empty stomach,
within five to 10 minutes,
29:41that alcohol is going to
be within your bloodstream
29:43and distributed throughout your body,
29:44maybe even faster depending
on the type of alcohol
29:46and your metabolism.
29:48But if you're already drunk
and you eat something,
29:52it's not going to sober
you up more quickly,
29:53but it certainly will blunt the effects
29:55of any additional alcohol
that you might consume.
29:57And if you're somebody who is concerned
30:00about getting too drunk too quick,
30:02even from a small amount of alcohol,
30:03having some food in your gut
can certainly be beneficial.
30:06Now, that's food and alcohol
and the absorption of alcohol,
30:10but let's go back to talking
about the biochemical
30:13and neurochemical effects
of alcohol on the brain.
30:15We talked about top-down inhibition,
30:18and we talked about habitual
30:19and impulsive behavior circuitry.
30:21There are also dramatic changes
in the activity of neurons
30:25that control the release
of so-called serotonin.
30:28Serotonin is a neuromodulator.
30:30It changes the activity of neural circuits
30:32and many neural circuits,
30:34in particular, those involved in mood
30:36and feelings of well-being.
30:37Recently, there's been a
lot of interest in serotonin
30:40because of a study that was released
30:41that showed pretty conclusively
30:42that serotonin levels can't
really explain depression
30:46and depression-like symptoms.
30:48I want to make it very clear
30:49that although that study did
show that serotonin levels
30:53are not necessarily
associated with depression,
30:56the study was interpreted
by many to mean that SSRIs,
30:59selective serotonin reuptake inhibitors,
31:01which have the net effect
of increasing serotonins,
31:04these are things like Prozac, et cetera,
31:07that those drugs are somehow not helpful
31:10because they increase serotonin
31:13and serotonin isn't
involved in depression.
31:15That logic doesn't really hold together
31:18so I'm going to use this as an opportunity
31:19to just clarify what
really occurred there,
31:22and then we'll talk about how serotonin
31:24relates to alcohol consumption
31:25in things like feeling
good and in depression.
31:29The key thing is this, SSRIs
can help alleviate depression.
31:34That's right. SSRIs can
help alleviate depression.
31:37They are often, not always,
associated with side effects,
31:40dosage is very important, et cetera.
31:42But they probably support
relief from depression
31:47by changing neural circuits,
31:48not necessarily by
increasing serotonin itself.
31:52That is, increasing
serotonin with these drugs
31:54likely changed the neural
circuits involved in mood,
31:57allowing people to feel better
31:58through so-called neuroplasticity,
32:00which is the brain's
ability to change itself
32:02in response to experience.
32:03So there's a bit of confusion,
32:04and, again, I'm using
this episode on alcohol
32:07to highlight some of the confusion
32:09because I think it's timely,
32:10because the study just came out
32:11and there's a lot of
chatter about this out there
32:13that when people are depressed,
32:15it's not necessarily because
serotonin levels are low.
32:18However, if serotonin levels are increased
32:21with things like Prozac,
Zoloft, and other SSRIs,
32:24oftentimes there is, yes,
a relief from depression,
32:27but that's probably not
32:29because of restoring
serotonin levels, per se.
32:31It's probably because serotonin
facilitates the changes
32:36in neural circuits that need to occur
32:37in order for people to
feel elevated mood, okay?
32:40So, again, that's a bit
of a tangent and aside,
32:42but I do think it's a vital
one for people to know about.
32:44Again, if you're thinking
about taking SSRIs
32:46or you're currently taking them
and you've heard this news,
32:48definitely talk to your doctor.
32:50Again, there is great utility
for some of these SSRIs,
32:52and, also, in conditions like OCD,
32:54they've been shown to be very beneficial,
32:56so we really don't want to throw SSRIs out
32:58as a potentially valuable treatment.
33:01Getting back to the effects
of alcohol on serotonin,
33:05it's very clear, beyond any doubt,
33:08that many of the circuits in the brain
33:10that are involved in mood
and feelings of well-being
33:12and also sort of self-image
and how we see ourselves
33:17employ the neuromodulator serotonin,
33:19and alcohol, when we ingest it
33:22and it's converted into acetaldehyde,
33:25it goes and that
acetaldehyde acts as a toxin
33:29at the very synapses,
33:31the connections between
these serotonergic neurons
33:33and lots of other neurons.
33:34In other words, when we ingest alcohol,
33:36the toxic effects of alcohol
disrupt those mood circuitries,
33:40at first making them hyperactive.
33:42That's right, making them hyperactive.
33:43This is why people
become really talkative,
33:46people start to feel really good
33:47after a few sips of alcohol,
at least most people do.
33:50And then as they ingest more alcohol
33:53or as that alcohol wears off,
33:54serotonin levels and the
activity of those circuits
33:57really starts to drop, and
that's why people feel less good.
34:00And typically what they do,
they go and get another drink
34:03and they attempt to kind
of restore that feeling
34:05of well-being and mood.
34:06Now, typically what happens
34:08is that as people ingest
the third and fourth,
34:10maybe even the fifth drink,
34:12there's an absolute zero chance
34:14of them recovering that
energized mood, right?
34:17Most people, as they drink more and more,
34:19will now start to feel
more and more suppressed.
34:23The forebrain is now
shutting down quite a lot,
34:25a lot of the motor cortical areas
34:27that control coordinated movement
34:29and deliberate movement
start to shut down,
34:31so people start to slur their speech,
34:33people start to shuffle their feet,
34:34people forget their posture,
people start to lean on things,
34:38people start passing out on couches.
34:40There's a great depression,
34:41not depression of the
psychiatric depression sort,
34:45but a depression of alertness and arousal,
34:50and eventually people will pass out.
34:53Now, I said most people
34:54because there's a subset of
people that have gene variants
34:57or who are chronic drinkers
35:00or who are chronic drinkers
and have gene variants
35:03that, as they ingest the third and fourth
35:06and fifth drink, what happens?
35:08They become more alert,
they start talking more,
35:11they feel great, they
have all sorts of ideas
35:12about the fun they could have that night.
35:14And they're the ones that,
35:15if you've ever fallen asleep
at a party for whatever reason,
35:18or you're getting tired
and you're yawning,
35:19you're looking around the room
35:20and, like, these people are
still drinking and partying
35:22and they're having what seems
to be this amazing time,
35:27those are the future
alcoholics in the room,
35:31or those are the people
35:32that have a genetic
predisposition for alcoholism,
35:35or those are the chronic drinkers,
35:36the people who have built
up enough of a tolerance
35:39or who have the chemical genetic makeup
35:42such that increasing amounts of alcohol
35:45make them feel better
and better and better.
35:46And of course, they, too, have a threshold
35:49beyond which their nervous system
35:50will start to get diminished
35:51and they'll pass out,
fall over, et cetera,
35:55but that threshold is way, way higher
35:57than it is for most people.
35:59Now, this is important to understand,
36:01and it's important to understand
36:03because I think everyone should know
36:05and recognize their own predisposition
36:07and kind of risk in terms
of developing alcoholism.
36:11It's also important to understand
36:12because it relates to the
phenomenon of blackout.
36:15Many people think that
blacking out is passing out,
36:18but blackout drunk is when people drink
36:21and they're talking and doing things,
36:22sometimes, sadly or tragically,
36:25they'll often drive home or walk home
36:27or they'll hop on a bicycle and ride home
36:29or they'll go swimming in the ocean,
36:30all, of course, very
dangerous activities to do
36:33when people are really drunk,
36:34or even a little bit drunk in some cases.
36:36So these people will do
these sorts of things
36:39and they do them because they
have the energy to do them
36:41and they feel good while doing them,
36:43but they are doing them
36:44while the activity of
neurons in the hippocampus,
36:47which is involved in memory formation,
36:48are completely shut off.
36:50And this is why the
next day, you tell them,
36:54"Hey, maybe we should talk
about what happened last night."
36:56Like, "What happened last night?"
36:57You said, "Well, do you
remember going to the party?"
36:58"Yeah, I know, it was great.
We did this, we did this."
37:01And it's very clear all of a sudden
37:04that they have no recollection
37:06of all the things they were
doing despite being awake.
37:09Now, I wish I could tell you
37:09that there's some sort of
blood test or other biomarker
37:12or even a fingerprint
test that would allow you
37:14to determine whether or
not you have a propensity
37:17to be one of these drinkers
37:18that has a predisposition for alcoholism.
37:22And if you've ever been blackout drunk,
37:24and certainly if you've
been blackout drunk
37:26more than a few times, you
should be quite concerned.
37:29And as we talk more about
the more chronic effects
37:32and long-lasting effects
of alcohol consumption
37:34a little bit later in the episode,
37:36I think it'll become clear
37:37as to why you should be concerned.
37:39But in any case, there is
something that can tell you
37:43whether or not you might
be in that category
37:46versus likely not in that category,
37:48and I alluded to this a
couple of times already,
37:49but I want to be really
clear that when people drink,
37:54no matter who you are,
37:56initially, there's that shutting down
37:57of those prefrontal cortical circuits,
37:59there's a gradual shutting down
38:00of the circuits that control memory,
38:02but then people divide
into these two bins.
38:05are the people who, after
more than a couple of drinks,
38:09start to feel sedated,
38:11and the people who, after
more than a few drinks,
38:13do not start to feel sedated.
38:15Now, of course there's
going to be differences
38:17created by how quickly
people are drinking,
38:20whether or not they're combining
different types of alcohol,
38:23the types of alcohol, et cetera,
38:25but in general, that can predict
38:26whether or not you're somebody
38:27who has a predisposition
for alcoholism or not.
38:31One also very interesting finding
38:33is that alcohol changes the relationship
38:36between what's called the hypothalamus
38:39and the pituitary gland and the adrenals.
38:41Now, the hypothalamus is a
small collection of neurons
38:44about the size of a large gumball
38:45that sits above the roof of your mouth,
38:47and it houses neurons that are responsible
38:48for some incredible aspects of
our behavior and our mindset,
38:53things like rage, things like sex drive,
38:56things like temperature regulation,
38:58very primitive functions,
39:00including appetite, thirst, et cetera.
39:02Alcohol, because it can
go anywhere in the brain,
39:04remember it's water- and fat-soluble,
39:07has effects on the hypothalamus.
39:09The hypothalamus normally
provides very specific signals
39:13to what's called the pituitary gland.
39:15This is a little gland
39:16that actually sticks out of the brain,
39:18but it receives instructions
from the hypothalamus.
39:22And then the pituitary releases hormones
39:24into the bloodstream that go
and talk to your adrenals,
39:26and your adrenal gland sit
right above your kidneys
39:30And the adrenals release, as
the name suggests, adrenaline,
39:34also called epinephrine,
39:35and also a molecule called cortisol,
39:37which is involved in the kind
of longer-term stress response
39:40and it has some healthy effects,
too, on the immune system.
39:42Okay, so the
hypothalamic-pituitary-adrenal axis,
39:46I know that's a mouthful,
39:47you don't need to remember the names,
39:49but the
hypothalamic-pituitary-adrenal axis
39:51maintains your physiological balance
39:53of what you perceive as stressful
39:55and what you don't perceive as stressful.
39:58People who drink regularly,
40:00so this, again, could be just
one or two drinks per night
40:02or it could be somebody
that drinks just on Fridays
40:05or just on Saturdays or
maybe just on the weekend,
40:09well, those people experience changes
40:10in their
hypothalamic-pituitary-adrenal axis
40:14that result in more cortisol,
40:15more of this so-called stress hormone,
40:17being released at baseline,
when they are not drinking.
40:21This is really important.
40:23People who drink a bit,
40:25and when I say a bit, I
don't mean one or two sips
40:27or even a glass of wine
every once in a while.
40:29I mean, again, people that are maybe
40:31having one drink a night with dinner
40:34and maybe on the weekend a few more.
40:36Again, I offer a bunch of
different patterns to explain
40:39how it could also be two
or three drinks on Friday
40:42or six drinks only on Saturday.
40:44Well, all of those groups
experience increases
40:47in cortisol release from
their adrenal glands
40:51when they are not drinking,
40:52and as a consequence,
they feel more stressed
40:56and more anxiety when
they aren't drinking.
40:59This is a seldom talked
about effect of alcohol
41:03because so often we hear
41:04about the immediate
effects of alcohol, right?
41:06And we've been talking
about some of those effects,
41:08effects like reducing
the amount of stress.
41:10I mean, how many times
have we heard somebody say,
41:12"Ugh, I need a drink."
41:13And then they have a drink and
they're, like, calmed down,
41:15now they can shake off the
thoughts about the day's work
41:18they can start to think about things
41:20in a maybe more grounded or rational way,
41:22or at least they believe that,
41:23or they can somehow just relax themselves.
41:26Well, while that very well may be true,
41:29that it can relax them,
41:30when they are not drinking,
that level of cortisol
41:33that's released at baseline
has increased substantially.
41:37Again, this relates to
a defined neural circuit
41:40between brain and body,
41:41and it has to do with
the ratio of cortisol
41:44to some of the other hormones
41:45involved in the stress response.
41:48We'll provide a reference to the study
41:49that describes how all of this works
41:51for those of you that really
want to delve into it,
41:53but let's go back to this issue
41:55of those who are prone to alcoholism
41:57versus those who are not.
41:59Remember, there are people
who have genetic variants,
42:02meaning genes that they
inherited from their parents,
42:05that make it more likely that
they will become alcoholics.
42:08But there are also people who drink often
42:12who start to experience
this increase in alertness
42:14the longer they drink across the night.
42:17Part of that effect, we
think, is because of changes
42:21in this
hypothalamic-pituitary-adrenal axis.
42:23So alcohol is kind of a
double hit in this sense.
42:27It's causing changes
in our brain circuitry
42:29and neurochemistry that,
42:31at the time in which we're
inebriated, are detrimental,
42:34and it's causing changes in
neural circuitry that persist
42:38long past the time in which
we're experiencing the feeling
42:40of being tipsy or drunk.
42:42Now, again, I don't want
to demonize alcohol.
42:45I'm not saying, oh, you know,
42:45if you have a glass of wine now and again
42:47or you drink a beer now and again
42:48or even have, you know, a
mixed drink now and again
42:53or a shot that that's
necessarily terrible for you.
42:55I certainly do not want
that to be the message.
42:59What I'm saying is that if people
43:01are ingesting alcohol chronically,
43:03even if it's not every night,
43:05there are well-recognized
changes in neural circuits,
43:10there are well-recognized changes
43:11in neurochemistry within the brain,
43:13and there are well-recognized changes
43:16in the brain-to-body stress system
43:19that generally point in three directions,
43:24increased stress when
people are not drinking,
43:27diminished mood and feelings of well-being
43:30when people are not drinking,
43:32and, as you'll soon learn,
changes in the neural circuitry
43:37that cause people to
want to drink even more
43:41in order to get just back to baseline
43:43or the place that they were
43:45in terms of their stress modulation
43:47and in terms of their feelings of mood
43:48before they ever started
drinking in the first place.
43:51So again, I don't want
to demonize alcohol,
43:54but I do want to emphasize
43:55that there are long-term plastic changes,
43:58meaning changes in neural
circuitry and hormone circuitry,
44:01that, across a period of several months
44:03and certainly across a period of years
44:05of the sorts of drinking
patterns I described,
44:07which I think, for most people,
44:09are going to sound, like,
pretty typical, right?
44:11I mean, nothing that I described so far
44:12was about drinking a case a night
44:14or about binging on alcohol
44:16in the way that we often
hear about it in the news.
44:18These are pretty common
patterns of alcohol consumption.
44:21I mean, all you have to do is
board a transatlantic flight
44:24or actually go to an airport
on a Sunday afternoon
44:27in a sunny area of the US
44:28and, you know, people are
having three, four, five,
44:30six beers, et cetera.
44:32Again, personal choice is personal choice.
44:34I'm not telling you what to do.
44:36But it's very clear that those
sorts of drinking patterns
44:38are changing neural circuitry
44:40and they're changing hormone circuitry,
44:42and I'd love to be able to tell you
44:43that they're changing them for the better,
44:44but they simply are not.
44:46They're actually changing
them for the worse,
44:47and worse is defined as making people
44:49less resilient to stress,
44:50higher levels of baseline
stress, and lower mood overall.
44:53Before we continue with
today's discussion,
44:56I'd like to just briefly
acknowledge our sponsor,
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45:27The gut microbiome, as many of you know,
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45:30It also supports the
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46:07Now, I've been talking a little bit
46:08about genetic predisposition,
46:10but there are a couple of important points
46:12I'd like to make about that.
46:13First of all, what sorts
of genes are involved
46:16in setting someone down the
path of alcoholism or not?
46:20Well, it should come as no surprise
46:22that the genes that chronic
alcohol usage modifies,
46:27they tend to fall
primarily in the pathways
46:30related to genetic control
over serotonin receptors,
46:35GABA receptors, remember
that top-down inhibition
46:37and the involvement of GABA,
46:39and, no surprise, the HPA,
46:41the hypothalamic-pituitary-adrenal axis.
46:43All of those, of course
combined with environment,
46:46they combine with
patterns of abuse, right,
46:48we know that if you're in a social setting
46:50where a lot of people are drinking,
46:51the likelihood that you're
going to drink is much higher,
46:54social pressures, trauma, right?
46:57Some people will use
alcohol to self-medicate
46:59to try and turn off their thinking
47:01or to deal with trauma, et cetera.
47:03So they combine with the environment,
47:05but the genes that are in
the serotonin synthesis
47:08and receptor synthesis
pathway, GABA and HPA axis,
47:12combine with environmental pressures
47:14to give rise to alcohol use disorders.
47:18So there's a fairly coherent picture
47:20that we have here, right?
47:21This is not a case where, for instance,
47:24people that have a lot of the enzyme
47:26for metabolizing alcohol,
47:27which we'll talk about in a
minute, alcohol dehydrogenase,
47:30it's not like they are
necessarily the people
47:32that become alcoholics,
47:33whereas certainly in certain cultures,
47:35certain Asian cultures in particular,
47:37there are gene differences
47:40that lead them to have low
levels of alcohol dehydrogenase.
47:42There are actually people
47:43who have so little alcohol dehydrogenase
47:45that when they ingest alcohol,
47:46they get very red and they just feel sick.
47:48So if you're somebody
that has a sip of alcohol
47:50and you just feel horrible,
it makes you feel nauseous,
47:52chances are you have gene
variants that create a situation
47:56where you're not making very
much alcohol dehydrogenase.
47:59You just simply can't metabolize alcohol
48:01so you just get a rapid buildup
48:02of the toxic effects of
alcohol, the acetaldehyde,
48:05you're not converting it
into those empty calories.
48:08But in cultures where you
have a lot of genetic variants
48:12and genes expressed in people
48:14where they have a lot of
alcohol dehydrogenase,
48:16sure, they can drink more,
48:18and they're converting
more of that alcohol
48:20from its toxic form to a non-toxic form,
48:23and, yes, of course, you
will observe more alcoholism
48:26in those communities because
they're drinking more,
48:28but I do want to emphasize
that the environmental factors
48:31are playing a strong role there, too,
48:33because if you can drink more,
you're likely to drink more.
48:35If you're somebody that feels sick
48:36immediately from drinking,
48:37it's likely that you're
not going to engage
48:39in alcohol consumption,
48:40especially if these things
are genetically related,
48:42and, of course, genes and culture
48:44and location in the world
tend to run together.
48:47So do you have the gene for alcoholism?
48:50Well, there isn't one single gene.
48:53Chances are if you have
an immediate relative
48:55who's a chronic abuser of alcohol
48:58or several relatives who are
chronic abusers of alcohol,
49:01well, that's going to predispose
you to be an alcoholic.
49:05But since you don't know
which genes you express
49:07unless you do genetic testing,
49:08and those things are available
49:09but most people aren't doing that,
49:11this assay, if you will,
49:14and it's not an assay, as we say,
49:15an assay is a test that you run in the lab
49:17to determine something,
49:19and it's not one that I recommend
49:20that you go drink in order to do,
49:22but if you've noticed
that you or somebody else
49:24is somebody who can drink
a lot throughout the night
49:26and have increased energy
49:27and can just drink and drink and drink,
49:29and especially if there's
blackout episodes,
49:32not remembering things the next day
49:33despite being alert throughout
the entire night and so on,
49:36well, then I would be very concerned
49:38that you might actually
have a genetic variant
49:40predisposing you to alcoholism.
49:42The other thing that predisposes people
49:43to abuse of alcohol is age.
49:47People who start drinking at younger ages
49:51are greatly predisposed to
developing alcohol dependence
49:55regardless of your family
history of alcoholism.
49:58Okay, so I'm going to repeat that.
49:59People who start drinking younger
50:01are at great risk for
developing alcoholism
50:04even if they don't have
alcoholism in their family.
50:06Now, of course, you don't
have to be an epidemiologist
50:09to understand that if you grow
up in a family of drinkers
50:12and alcohol is everywhere,
50:13and especially if there's peer pressure
50:15or lack of oversight,
50:16then there's going to
be a higher tendency,
50:19or a higher probability, I should say,
50:21that you will start
drinking at a younger age.
50:23However, even people that grow up
50:25nowhere near their relatives,
50:27if they start drinking at a young age,
50:29so for instance, at 13
or younger or 14 or 15,
50:33there's a much higher probability
50:34that they're going to develop
50:36a long-lasting dependence on alcohol.
50:38People who take their
first sip of alcohol later,
50:4215, 16, or one would hope even later,
50:44I can say one would hope
50:45'cause I'm now of that, you
know, age and generation
50:47where, you know, you
think about all the things
50:49that young people do,
and you go, "Oh, gosh,
50:52if they only would wait or
if they only would abstain."
50:54You know? It's just what happens.
50:56I don't know, there's some
neural circuit for that
50:57that I can't explain yet.
50:58But people who, for instance,
51:00drink only once they reach
legal age of drinking,
51:03which in the US, I believe in
every state is 21 years old,
51:06if they take their first drink at 21,
51:08the probability that they'll go on
51:10to develop full-blown alcohol dependence
51:12or alcohol use disorder, as
it's called, AUD, is very low.
51:15Now, a subset of them will
51:16because they have such a
strong genetic predisposition
51:19or maybe life circumstances
create a pattern
51:22in which they become a chronic drinker.
51:24But I found this very interesting.
51:26Genes matter, but also the age
51:29in which somebody starts
drinking really matters.
51:32Now, whether or not that's
because there are changes
51:34in neural circuitry as a
consequence of that drinking
51:37that make people want to seek
out more and more alcohol,
51:40or whether or not there's
some other effect,
51:42maybe it's a change in
hormones, et cetera,
51:44that predisposes those young drinkers
51:46to become chronic drinkers or
even full-blown alcoholics,
51:49certainly developing alcohol use disorder.
51:51There's a definition for
that. We can talk about it.
51:53It involves the amount of drinking
51:55over a certain period of time, et cetera.
51:57So it's very clear that
drinking early in life
52:00creates a propensity for the development
52:03of alcohol use disorder later in life.
52:06And while there is a genetic component
52:09to developing alcohol use disorder,
52:11I find it very interesting
52:13that if people who have
those gene variants
52:16delay their onset of drinking,
52:18well, then the probability
that they'll develop
52:20full-blown alcohol use
disorder drops as well.
52:23So again, it's genes and environments.
52:24It's not an either/or
52:25and there's no single gene for alcoholism.
52:28Well, I promise you I will also talk
52:29about some of the documented
positive effects of alcohol.
52:33Although they are very few and
far between, they do exist.
52:37But before I do that, I would be remiss
52:39if I didn't emphasize some
more of the terrible things
52:42that alcohol does and
the way that it does it.
52:45And for those of you that enjoy alcohol,
52:48again, I'd like to say I feel
guilty about telling you this
52:52because I know how much some
people enjoy a good drink
52:55every once in a while,
52:55and I say a good drink
52:56because some people do
like the taste of alcohol.
52:59I suppose I lucked out
53:00in that I don't really
like the taste of alcohol
53:02and that it just puts me to sleep,
53:03but I know that people do enjoy it.
53:04And I do want to point out
that there is zero evidence
53:10that, you know, provided
somebody is of drinking age,
53:14certainly not in the stage
of brain development,
53:17that having one drink or two
drinks every now and again,
53:20meaning every three or
four weeks or once a month,
53:23that is not going to cause
major health concerns
53:27or major health issues for most people.
53:30I suppose if you have zero
53:32or very little alcohol dehydrogenase,
53:34it might make you feel sick,
53:35but then you're probably
not the kind of person
53:36that's going to be drinking at all.
53:38So, again, if you enjoy alcoholic drinks,
53:41I'm not trying to take them
away from you by any means,
53:46but you should know what drinking does
53:48if you're consuming it
53:49in this kind of typical chronic pattern,
53:51as we can now refer to it,
53:52which is that one or two a night
53:54or a few stacked up on Friday
53:58and maybe three or four on Saturday,
54:00this kind of pattern of
drinking, which is quite common.
54:03And one of the more serious effects
54:04that we should think about
54:06is the impact on the
so-called gut-brain axis,
54:08or for sake of today's discussion,
the gut-liver-brain axis.
54:12I don't think the gut-liver-brain axis
54:13has ever been discussed on this
podcast, maybe any podcast.
54:16Although at the moment I say that,
54:18you know, the gut-liver-brain axis,
54:20people are going to come after me
54:21with, I suppose, gut, liver, and brains.
54:24In any event, you have
a brain. You have a gut.
54:29That gut runs from your throat
54:31down to the end of your intestine.
54:36Your gut and your brain communicate
54:38by way of nerve cells,
neurons and nerve connections,
54:41the vagus nerve in particular,
54:43and by way of chemical signaling.
54:45Your gut also communicates
by way of chemical signaling
54:48and, believe it or not,
54:49by way of neural signaling,
too, to your liver.
54:52And, as we talked about earlier,
54:53the liver is the first
site in which alcohol
54:56is broken down or metabolized
into its component parts.
55:01The liver is also
communicating with the brain
55:04through chemical signaling
and neural signaling,
55:06so we have the gut-liver-brain axis.
55:12is that people who ingest
alcohol at any amount
55:16are inducing a disruption in
the so-called gut microbiome,
55:21the trillions of little microbacteria
55:24that take resident in your gut
55:25and that live inside you all the time
55:26and that help support your immune system
55:28and that literally signal
by way of electrical signals
55:31and chemical signals to your brain
55:33to increase the release of things
55:35like serotonin and dopamine
55:37and regulate your mood
generally in positive ways.
55:39Well, alcohol really
disrupts those bacteria,
55:42and this should come as no surprise.
55:43I mean, earlier, we talked
about this and it's well known,
55:45if you want to, you know,
sterilize something,
55:47you want to kill the bacteria,
you pour alcohol on it.
55:49And I can remember scraping
myself or cutting myself
55:53or I was always injuring
myself when I was a kid,
55:55and, you know, the moment
they take out the peroxide,
55:58you're like, "Oh, boy, here it comes."
55:59But if there's no peroxide around
56:01and you've got a wound there
and you need to clean it out,
56:03yeah, they'll use alcohol,
56:04which I do not recommend, by the way.
56:06That's one of the harshest
ways to clean a wound.
56:08But for centuries,
thousands of years really,
56:11alcohol has been used
in order to clean things
56:15So alcohol kills bacteria
and it is indiscriminate
56:19with respect to which bacteria it kills,
56:22so when we ingest alcohol
and it goes into our gut,
56:24it kills a lot of the
healthy gut microbiota.
56:27At the same time, the metabolism
of alcohol in the liver,
56:30which you now understand,
56:32that pathway involving NAD,
acetaldehyde, and acetate,
56:37that pathway is proinflammatory,
56:40so it's increasing the release
of inflammatory cytokines,
56:43things like IL-6, et cetera,
tumor necrosis factor alpha.
56:47If you'd like to learn more
about the immune system,
56:49we did an episode all
about the immune system.
56:51You can find it at hubermanlab.com.
56:52It'll teach you all the
basics of what are cytokines,
56:55what are mast cells, et cetera.
56:57In any event, all these
proinflammatory molecules,
57:02those are being released.
57:03You've now got disruption
of the gut microbiota.
57:07As a consequence, the lining
of the gut is disrupted,
57:10and you develop, at least
transiently, leaky gut.
57:15That is, bacteria that exists in the gut
57:17which are bad bacteria
57:18can now pass out of the
gut into the bloodstream,
57:20so you've got a two-hit
kind of model here.
57:23In biology, we talk about two-hit models,
57:25that is, it's kind of a
one plus one equals four,
57:27and it's generally when you hear two-hit,
57:29it's not a good thing.
57:30So you've got bad bacteria
from partially broken down food
57:35moving out of the gut,
57:36the good bacteria in the
gut have been killed.
57:38You might say, why doesn't the alcohol
57:39kill the bad bacteria in the gut?
57:42Well, the bad bacteria that are
from partially digested food
57:47oftentimes escape the gut
57:49before the alcohol can disrupt them,
57:52and so now you've got
leaks in the gut wall,
57:55you've got the release
of this bad bacteria,
57:57you've got inflammatory cytokines
57:59and other things being
released from the liver,
58:01and they are able to get into the brain
58:03through what's called a
neuroimmune signaling.
58:06And what's really bizarre,
58:08in terms of the way that
this manifests in the brain,
58:10I mean, it's not the
way I would've done it,
58:12but then again, as I always say,
58:14I wasn't consulted at the design phase,
58:16and anyone who says they did,
58:17you should be very skeptical of them.
58:20The net effect of this
58:21is actually to disrupt the neural circuits
58:25that control regulation of alcohol intake,
58:27and the net effect of that is
increased alcohol consumption.
58:32So this is just terrible, right?
58:33I mean, so you take in something
that disrupts two systems,
58:37the gut microbiota, and
it disrupts in two ways,
58:39it's killing the good gut microbiota
58:41and it's allowing the bad bacteria
58:45to move from the gut into the bloodstream,
58:47you've also got proinflammatory cytokines
58:49coming from the liver,
58:50and those converge or arrive in the brain
58:55and create a system in
which the neural circuits
58:58cause more drinking.
59:00That's a bad situation.
59:01And this is why people
who drink regularly,
59:04even if it's not a ton of alcohol,
59:06again, of the sorts of
patterns of drinking
59:08I talked about before,
59:09and certainly for those that
are chronic heavy drinkers,
59:12what you end up with is a situation
59:14in which you have inflammation
59:15in multiple places in the brain and body
59:18and the desire to drink even more
59:20and to further exacerbate
that inflammation
59:22and the gut leakiness.
59:24So this is basically a terrible scenario
59:26for the gut-liver-brain axis,
59:28and it's especially prevalent
59:29in so-called alcohol use disorder,
59:31again, people that are ingesting
59:32somewhere between 12
and 24 drinks per week.
59:34For those of you that are interested
59:36in learning more about
the gut-liver-brain axis
59:38and, in particular, alcohol use disorder,
59:40I'll provide a link in
the show note captions.
59:42There's a wonderful review
on this that details that.
59:45But on the positive side,
59:47it points to the possibility
that at least some,
59:50again, at least some,
59:51of the negative effects
of alcohol consumption,
59:53whether or not you're somebody
59:54who's currently ingesting alcohol
59:57or who used to ingest alcohol
59:58and is trying to so-called
repair these systems
01:00:00of the brain and body,
01:00:01whether or not replenishing
the gut microbiota
01:00:03is going to be beneficial.
01:00:04And we know that there
are ways to do that,
01:00:07and we know that there's
at least some promise
01:00:09for the ability for this
system to repair itself.
01:00:11How does one do that?
01:00:13Well, I've talked before
about this on the podcast,
01:00:15but studies done by colleagues
of mine at Stanford,
01:00:17Justin Sonnenburg, who's been
on this podcast as a guest,
01:00:20an amazing episode all
about the gut microbiome,
01:00:22and his collaborator, Chris Gardner,
01:00:23also at Stanford School of Medicine,
01:00:25have explored not alcoholism,
01:00:28but what are ways to
improve the gut microbiota,
01:00:32in particular, to reduce the production
01:00:36of inflammatory cytokines
01:00:38and to adjust what's
called the inflammatome.
01:00:40You've heard of the genome
and the proteome, et cetera.
01:00:43Well, the inflammatome is the total array
01:00:46or at least the near-total array
01:00:48of genes and proteins
that control inflammation.
01:00:51How can you reduce inflammation
01:00:52and make that inflammatome healthier?
01:00:55Well, they've shown that
two to four servings
01:00:58of fermented foods per day,
01:00:59and here, I'm not referring
to fermented alcohol.
01:01:01I'm talking about
low-sugar fermented foods,
01:01:03so things like kimchi, sauerkraut, natto,
01:01:07for those of you that like Japanese food.
01:01:09There are others, I
know, things like kefir
01:01:12or things like yogurts that
have a lot of active bacteria,
01:01:15again, low-sugar varieties
of all these things.
01:01:19Those are terrific at
reducing inflammatory markers
01:01:23and at improving the gut microbiome.
01:01:25One could imagine that
either inoculating oneself
01:01:29from some of the effects of alcohol,
01:01:30although I'd prefer that people
01:01:31just not drink alcohol
chronically, frankly,
01:01:34or if somebody's trying to
repair their gut microbiome
01:01:37because they ingested a lot of alcohol
01:01:39or because they had a lot of
these inflammatory cytokines
01:01:41for many years or even
a short period of time,
01:01:44regular ingestion of two to four servings
01:01:46of these fermented foods
can be quite beneficial.
01:01:51I want to make it clear,
that has not been examined
01:01:53specifically in the context
of alcohol use disorder,
01:01:57but because a huge component
01:01:59of the negative effects
of alcohol use disorder
01:02:01are based in this gut-liver-brain axis
01:02:04and disruption of the gut microbiome
01:02:05and the inflammatory cytokines,
01:02:07it stands to reason that things
that are well-established
01:02:10to improve inflammation status,
01:02:12in other words, reduce inflammation,
01:02:14such as ingesting two to four servings
01:02:16of low-sugar fermented foods per day,
01:02:19makes sense in terms of trying to repair
01:02:21or replenish the system.
01:02:23One could also imagine taking
probiotics or prebiotics.
01:02:25Certainly that would work as well,
01:02:27although I've sort of
favored the discussion
01:02:29around fermented foods
01:02:30and replenishment of the gut microbiome
01:02:33mostly because there are more studies
01:02:35that have examined that in humans
01:02:37and because of the direct relationship
01:02:39that's been established between doing that
01:02:41and reducing negative markers
within the inflammatome.
01:02:44And I should mention,
01:02:45along the lines of repair and recovery,
01:02:47I put out a question on
Twitter the other day.
01:02:49I said, "What do you want
to know about alcohol?"
01:02:51I got more than 1,000 questions
01:02:53and I'll take some more of those questions
01:02:54a little later in the episode.
01:02:55But one of the things I noticed
01:02:56is that many of the
questions, hundreds, in fact,
01:03:00related to the question of,
01:03:02well, if I drank a lot
previously, am I doomed?
01:03:05Can I reverse the negative effects?
01:03:07Or, you know, I'm trying to drink less
01:03:09and I'm trying to improve
my health as I do that.
01:03:11What should I do?
01:03:12Well, certainly focusing a
bit on the gut microbiome
01:03:16ought to be useful.
01:03:17The other thing I should mention
01:03:18is as people wean themselves off alcohol,
01:03:21even if they're not full-blown alcoholics
01:03:23or have alcohol use disorder,
01:03:25they should understand that
that increase in cortisol
01:03:28that we talked about earlier
01:03:29that leads to lower stress threshold
01:03:32and greater feelings
of anxiety and stress,
01:03:35that's going to be present
01:03:36and it's going to take
some time to dissipate.
01:03:39So for some people, it might
even just be helpful to realize
01:03:42that as you try and wean
yourself off alcohol
01:03:45or maybe you even go cold turkey,
01:03:47that increased anxiety
and feelings of stress
01:03:51should be expected.
01:03:52And in that case, I would
point you to an episode
01:03:54that we did on master stress.
01:03:55You can find that, again,
at hubermanlab.com.
01:03:57It's got a ton of behavioral, nutritional,
01:03:59supplementation-based, exercise-based,
01:04:01I suppose, exercise is
behavioral, but a lot of tools.
01:04:04You can navigate to those
easily 'cause we have timestamps
01:04:06so you can go right to
the topic of interest.
01:04:08Those tools are going to be very useful
01:04:09in trying to clamp or control your stress.
01:04:12And the point here
01:04:13is just that some increase
in stress should be expected,
01:04:17and it should be expected
01:04:18because of that increase in cortisol
01:04:19that occurs with even
low-level consumption
01:04:22yet chronic alcohol consumption.
01:04:24Now I'd like to talk about
a fairly common phenomenon,
01:04:27which is post-alcohol consumption malaise,
01:04:31also referred to as hangover.
01:04:34Hangover is a constellation of effects
01:04:37ranging from headache to nausea
01:04:40to what's sometimes called hangxiety,
01:04:42which is anxiety that
follows a day of drinking.
01:04:47Hangxiety, I think we can
understand physiologically
01:04:50if we think about that
process of alcohol intake
01:04:54increasing the amount of cortisol
01:04:56and the ratio of cortisol to
some other stress hormones.
01:05:00That well explains why some
people wake up the day after
01:05:04or even the day the day
after a night drinking
01:05:08and feel anxious and not well
01:05:10and stressed for reasons
they don't understand.
01:05:13So if you're somebody who
experiences hangxiety,
01:05:17then, again, I refer you to
the master stress episode
01:05:20that we put out some time ago,
01:05:22and you can find that at hubermanlab.com,
01:05:24tools to deal with anxiety,
tools to deal with stress,
01:05:26ranging, again, from
behavioral to nutritional
01:05:28and supplement-based, et cetera.
01:05:30That, of course, is not justification
01:05:33for going out and drinking so much
01:05:34that you get hangxiety-induced hangover,
01:05:38but for those of you that are experiencing
01:05:39post-alcohol consumption
hangxiety, as it were,
01:05:43that could be a useful resource
01:05:44because I certainly don't want anyone
01:05:46experiencing uncomfortable
amounts of anxiety,
01:05:49and there are great tools
and resources for that.
01:05:51Now, the other aspects of hangover,
01:05:54such as the stomachache or headache
01:05:58or feelings of malaise or fogginess,
01:06:01those could be related to a
number of different things
01:06:02and probably are related to
a number of different things.
01:06:05First of all, the sleep that
one gets after even just one,
01:06:10yes, even just one glass of wine or a beer
01:06:13is not the same sleep that you get
01:06:15when you don't have alcohol
circulating in your system.
01:06:18And not trying to be a downer here,
01:06:19but this was discussed in the
Huberman Lab Podcast episode
01:06:22where I had Dr. Matthew
Walker from UC Berkeley on.
01:06:26And, of course, Dr. Walker
is a world expert in sleep,
01:06:29runs one of the preeminent laboratories
01:06:31studying sleep and its effects,
01:06:33wrote the incredible book,
"Why We Sleep," and so on.
01:06:37Dr. Walker told me, and
it certainly is supported
01:06:40by lots and lots of quality
peer-reviewed studies
01:06:43in animals and in humans,
01:06:45that when alcohol is present
in the brain and bloodstream
01:06:48that the architecture
of sleep is disrupted.
01:06:50Slow-wave sleep, deep sleep,
and rapid eye movement sleep,
01:06:53all of which are essential
01:06:54for getting a restorative
night's sleep, are all disrupted.
01:06:56So for those of you
01:06:57that are drinking a glass or two of wine
01:06:59or having a hard liquor drink or a beer
01:07:03in order to fall asleep,
01:07:05the sleep you're getting is
simply not high-quality sleep,
01:07:07or certainly not as high-quality
01:07:09as the sleep you'd be getting
01:07:10if you did not have
alcohol in your system,
01:07:12Of course, when we're
talking about hangover,
01:07:14we're talking generally
about the consumption
01:07:17of more than just one or two drinks.
01:07:19Of course, for some
people, one or two drinks
01:07:21is probably sufficient to induce hangover,
01:07:23but for most people it's going
to be having three or four,
01:07:25exceeding their typical
limit, as it's called.
01:07:28Again, not the legal limit,
that's a whole other business.
01:07:31But when one ingests too
much alcohol for them,
01:07:36one of the reasons they
feel terrible the next day
01:07:39is because their sleep
isn't really good sleep.
01:07:41In fact, it's not even sleep.
01:07:42It's often considered pseudosleep,
01:07:44or at least that's what it's called
01:07:45in the sleep science field,
01:07:47because people are in kind of a low-level,
01:07:49hypnotic kind of trance,
it's not real sleep,
01:07:51there are multiple bouts of waking up,
01:07:52they may not even realize
they're waking up multiple times.
01:07:55Okay, so there's the
sleep-induced effects.
01:07:57Then there are the disrupted
gut microbiome effects,
01:08:01some of which we talked about earlier
01:08:03so now you understand the mechanism
01:08:05of alcohol destroying good,
healthy gut microbiota,
01:08:09which then leads to leaky
gut and things of that sort.
01:08:12But one could imagine,
again, could imagine,
01:08:15and there is some evidence
starting to support this,
01:08:17that, again, ingesting
low-sugar fermented foods
01:08:21or maybe even prebiotic or probiotics
01:08:23to support the gut microbiome
01:08:24might assist in some of
the gut-related malaise
01:08:28associated with hangover.
01:08:30In other words, get those
gut microbiota healthy again
01:08:33as quickly as possible,
01:08:34or maybe even before you drink,
01:08:36have those gut microbiota healthy.
01:08:37I would hope that you'd do that.
01:08:38I think everybody should
be doing something
01:08:39to support their gut microbiome,
01:08:40whether or not it's the ingestion
01:08:42of low-sugar fermented foods daily
01:08:43or at least on a regular basis
01:08:45or ingestion of probiotic or prebiotic.
01:08:47The gut microbiome is so important
01:08:49for so many different things.
01:08:51In terms of hangover and headache,
01:08:55we know that that's caused
by vasoconstriction,
01:08:58the constriction of blood
vessels that tends to occur
01:09:00as a rebound after a night of drinking.
01:09:02Alcohol can act as a vasodilator,
01:09:04it can dilate the blood vessels.
01:09:06Part of that is associated
with the increase
01:09:09in so-called parasympathetic tone.
01:09:11We have an autonomic nervous system
01:09:12and it's got a sympathetic component.
01:09:14These are neurons that make us more alert,
01:09:17and if they're very active,
they make us very stressed.
01:09:19There's also the parasympathetic aspect
01:09:22of the autonomic nervous system.
01:09:23This is all just fancy geek speak
01:09:25for the parts of your brain and body,
01:09:26the nerve cells that
make you very relaxed.
01:09:28When you're very relaxed,
there tends to be vasodilation.
01:09:32It allows for more movement of blood
01:09:35and other things through the bloodstream,
01:09:37and alcohol tends to
induce some vasodilation,
01:09:40at least in some of the capillary beds.
01:09:42And then when the alcohol wears off,
01:09:44there's vasoconstriction and
people get brutal headaches.
01:09:48That's why some people will
take aspirin or Tylenol
01:09:51or Advil or things like that,
01:09:53the sort of non-steroid
anti-inflammatories.
01:09:55I should mention, there is a
lot of literature coming out
01:09:58that some of these non-steroid
anti-inflammatory drugs
01:10:02are not good for us for a
number of different reasons,
01:10:04the way they impact the liver,
01:10:06the way they impact the immune system,
01:10:08and, no surprise, the way they
impact the gut microbiome.
01:10:11So I'm not one to tell
you what medications
01:10:14to take or not take,
01:10:15but you certainly would want
to do a quick web search
01:10:17of effects of non-steroid
anti-inflammatories
01:10:22and aspirin before you start taking those,
01:10:24or stop taking those, for that matter.
01:10:27Generally, they will alleviate headache,
01:10:29but they can often have other issues,
01:10:30including liver issues.
01:10:31And keep in mind, the
night after drinking,
01:10:33your liver has already taken a beating
01:10:36because of the need of the liver
01:10:38to convert alcohol from
acetaldehyde into acetate,
01:10:42which is now a pathway
that you well understand.
01:10:45So I'm not certain
01:10:46and, in fact, I believe
it's not the greatest idea
01:10:48to burden your liver further
01:10:50through the use of things
that are going to cause it
01:10:53to have to work harder
and metabolize things
01:10:56if the goal is simply
to alleviate a headache.
01:10:58There's a lot of kind of lore,
01:11:01old school lore about how
to relieve a hangover.
01:11:03We already talked about how
eating food won't do that
01:11:06but eating food will
prevent the rapid absorption
01:11:09of even more alcohol into the bloodstream.
01:11:11There's the lore that one should
simply ingest more alcohol.
01:11:15What terrible advice that is.
01:11:17That's just going to delay
an even worse hangover.
01:11:19However, I'd be remiss if I
didn't say that the reason
01:11:23that that myth came to be,
01:11:25or that, I should say,
that truth came to be,
01:11:28because indeed ingesting more alcohol
01:11:31will alleviate a hangover
01:11:32but then a worse hangover will show up,
01:11:34the reason that came to be
01:11:35is because ingestion of more alcohol
01:11:37will cause those constricted vessels
01:11:39that are giving the
headache to dilate again.
01:11:42But, of course, ingesting more
alcohol to relieve a hangover
01:11:44is simply a bad idea.
01:11:45Just don't do it.
01:11:46I think this is called the
hair of the dog approach.
01:11:48Maybe someone can put in the
show note captions on YouTube
01:11:51why it's called the hair of the dog.
01:11:53I can come up with a few ideas
01:11:55but they're not going
to be very good ones,
01:11:58and some of them would probably
even be outright ridiculous.
01:12:02So do not ingest more alcohol
01:12:03simply to try and recover from a hangover.
01:12:06I know many people have
tried that one before
01:12:08but that's a terrible idea.
01:12:10Now, one thing that
you'll also hear out there
01:12:12is that deliberate cold exposure,
01:12:14for instance, taking a cold
shower, might relieve hangover.
01:12:17I find this one particularly interesting
01:12:18because we've done
episodes on the benefits
01:12:20of deliberate cold exposure.
01:12:21We have an entire episode about that.
01:12:23You can find it, again, hubermanlab.com.
01:12:25There are direct links
to some of the tools
01:12:28related to deliberate cold exposure
01:12:29and we have an entire newsletter
01:12:32on deliberate cold exposure protocols
01:12:34that you can find on hubermanlab.com,
01:12:35go to our Neural Network newsletter.
01:12:37So those of you that are
interested in ice baths
01:12:39and cold showers and
ways to leverage those,
01:12:42you can find that there.
01:12:43What you won't find there is a description
01:12:45of how to use deliberate cold exposure
01:12:46for sake of treating hangover.
01:12:48But here, I went into the literature
01:12:49and I found something kind of interesting.
01:12:51There is some evidence
01:12:52that increasing levels of
epinephrine in the bloodstream
01:12:56can actually help with alcohol clearance.
01:12:58That was very surprising to me,
01:12:59and I want to point out
01:13:00this is not a large and robust literature,
01:13:03but there's some evidence
pointing to the fact
01:13:04that when levels of
epinephrine, adrenaline,
01:13:06are raised in the brain and bloodstream,
01:13:08that some of the components
of alcohol metabolism
01:13:11can be accelerated
01:13:12and some of the inebriating
effects of alcohol
01:13:15so maybe this old school
lore of taking a cold shower
01:13:18actually has something to it.
01:13:19So in thinking about the use
of deliberate cold exposure
01:13:22in order to reduce the effects of hangover
01:13:24or to more rapidly clear alcohol
01:13:28from the brain and bloodstream,
01:13:29I want to be very clear and I
want to emphasize your safety.
01:13:34The way to do that is to understand
01:13:36that alcohol lowers core
body temperature, okay?
01:13:39It can make people slightly hypothermic.
01:13:42It's going to drop core body temperature.
01:13:45So if you were inebriated
01:13:47and you went and got into
a body of water, right,
01:13:50a pool or a lake or something,
01:13:52first of all, that's extremely dangerous
01:13:53to do while you're inebriated, right?
01:13:55People drown all the time.
01:13:56People drown, they die as a
consequence of doing that,
01:13:59so please don't do that.
01:14:00But also, if it's very cold water,
01:14:03your core body temperature is
going to drop even further.
01:14:05Now, if you've heard the
episodes that I've done
01:14:07on deliberate cold exposure previously,
01:14:10I've talked about how normally,
01:14:12when people are not ingesting alcohol,
01:14:14they get into an ice bath or a cold shower
01:14:16and their body temperature initially dips
01:14:17but then it rebounds and increases.
01:14:19That's a process that's going to occur
01:14:20when people do not have
alcohol in their system.
01:14:23When you have alcohol in your system,
01:14:25one of the reasons that
you become hypothermic
01:14:27is because there's a disruption
01:14:29in those hypothalamic brain areas,
01:14:30in particular, the brain area
01:14:31called the medial preoptic area
01:14:33that regulates core body temperature.
01:14:35So it's not so much that
alcohol makes you cold,
01:14:38it's that alcohol disrupts
the central command centers
01:14:41of the brain that control
temperature regulation,
01:14:43and that leads you to
be slightly hypothermic.
01:14:46So if you then go get
into a very cold lake
01:14:49or you get into even a
cold shower or an ice bath,
01:14:52there's the possibility
01:14:53of you going very, very
far down the ladder
01:14:56into very hypothermic territory
01:14:59and that can be very dangerous.
01:15:00Now, in terms of dealing with hangover
01:15:02when the alcohol has been
largely cleared from your system,
01:15:05well, that's where some of this old lore
01:15:07combines with some of the modern science
01:15:10and says, well, if you
can spike adrenaline,
01:15:13and certainly getting into an ice bath
01:15:15or getting into a cold shower
01:15:16or any kind of cold body of water,
01:15:19provided you can do that safely,
01:15:20that will sharply increase your adrenaline
01:15:22and, I should say, your dopamine.
01:15:24That's been shown
01:15:24and we've talked about
this on the podcast before.
01:15:26You get these long, extended increases,
01:15:28several hours of increases in dopamine
01:15:30from deliberate cold exposure.
01:15:31It's well-documented
in humans, by the way.
01:15:34So one could imagine using
deliberate cold exposure
01:15:37as a way to accelerate the
recovery from hangover.
01:15:41Provided that's done safely,
01:15:43I think there's no reason
to not explore that,
01:15:45and if you wonder what safely is
01:15:47and what temperatures to use,
01:15:49please check out the episode
on deliberate cold exposure.
01:15:52Cold showers, therefore,
might actually be one way
01:15:55to at least partially relieve hangover.
01:15:57Certainly the science from
various places in the literature
01:16:01converged to say that.
01:16:02But, again, be careful, please,
please, please be careful
01:16:05not to get into cold water
when you are inebriated.
01:16:09It's absolutely dangerous
for all the obvious reasons,
01:16:12and it's dangerous also
for the nonobvious reasons,
01:16:14not the least of which
01:16:15is the dramatic decreases
in core body temperature
01:16:19that can make you dangerously hypothermic.
01:16:21Now, how would you go about
using deliberate cold exposure
01:16:23to accelerate recovery from hangover?
01:16:25Well, there, I would look to
the kind of standard protocols
01:16:28of, you know, one to three minutes
01:16:29or maybe even six minutes
if you can tolerate it,
01:16:31or if you're really cold-adapted,
01:16:33maybe you do seven or ten
minutes in a cold shower,
01:16:35although that could be a lot.
01:16:36Most people are going to
experience a sharp increase
01:16:40in epinephrine, in adrenaline,
01:16:41and a long-lasting increase in dopamine
01:16:44from one to three minutes
of deliberate cold exposure,
01:16:47ideally done immersion up to the neck,
01:16:49again, do this safely,
please, please, please,
01:16:51or a cold shower where you're
getting under the shower
01:16:53as much as possible.
01:16:54How cold? Well, that's going
to vary person to person.
01:16:56I suggest making it as
cold as is uncomfortable
01:16:59such that you really want to get out
01:17:00but that you know you can stay in safely
01:17:02without, for instance, giving
yourself a heart attack,
01:17:03because if the water
is really, really cold,
01:17:05of course you can give
yourself a heart attack.
01:17:06Most showers won't go that cold,
01:17:08although probably some will.
01:17:10Again, please use caution.
01:17:11Spike your adrenaline, spike your dopamine
01:17:13with deliberate cold exposure safely.
01:17:15Other components of hangover
that could be good targets
01:17:18for trying to alleviate hangover,
01:17:19and, here, I hope you
are getting the picture
01:17:22because it is accurate
to say that hangover
01:17:25is a multifaceted phenomenon.
01:17:27It's not like one
molecule and one receptor.
01:17:29It's a bunch of things
happening in the brain and body.
01:17:31But is the dehydration
associated with alcohol?
01:17:34Alcohol is a diuretic.
01:17:36For multiple reasons, it causes people
01:17:38to excrete not only water but also sodium.
01:17:41Sodium is an electrolyte
01:17:43critical for the function of neurons,
01:17:44so making sure that
you have enough sodium,
01:17:46potassium, and magnesium,
so-called electrolytes,
01:17:49is going to be important
01:17:50for proper brain function,
bodily organ function.
01:17:54Even for people that have
just had one or two drinks
01:17:56the night before,
01:17:57it's likely that your electrolyte balance
01:17:59and your fluid balance
is going to be disrupted,
01:18:02and that's because alcohol also disrupts
01:18:04the so-called vasopressin pathway.
01:18:06I talked a lot about vasopressin
01:18:08and the way that it interacts with
01:18:11and controls different
aspects of water retention
01:18:13and water release from the
body in the form of urine
01:18:16in the episode on salt.
01:18:18So, again, I'm referring
to hubermanlab.com
01:18:21as the site where you
can find that episode
01:18:23on salt balance and ways to
restore electrolyte balance.
01:18:26Having your electrolytes
at the proper levels
01:18:29before you drink is ideal.
01:18:31Some people will say for
every glass of alcohol
01:18:34that you drink, you should
drink one glass of water.
01:18:36I would say better would
be two glasses of water
01:18:40given the dehydrating effects of alcohol,
01:18:42and even better would be
water with electrolytes.
01:18:44That certainly would set you up
01:18:46for a better day the next day.
01:18:47And if you don't manage to do that,
01:18:49'cause I suppose it's kind of geeky
01:18:51walking around with electrolyte packets
01:18:53out at the bar or whatnot,
01:18:55although, you know, geeky,
in my book, is a good thing,
01:18:59the next day, you could take
some electrolytes upon waking,
01:19:02maybe even some before you go to sleep
01:19:04the night of drinking.
01:19:05So hangover's made worse
by disturbed sleep,
01:19:09made worse by disrupted gut microbiome,
01:19:10made worse by disrupted electrolytes,
01:19:13made worse by the depletion
of epinephrine and dopamine.
01:19:16That's why replenishing the
microbiome with fermented foods,
01:19:19low-sugar fermented foods, that is,
01:19:21that's why using safe
deliberate cold exposure
01:19:25for spiking adrenaline and
for increasing dopamine,
01:19:29and that's why consuming electrolytes
01:19:32are all going to be beneficial.
01:19:34The folks over at examine.com,
a website that I really like
01:19:38because it just has so
much useful information,
01:19:41have assembled a list of things
01:19:43that have been proposed,
purported to improve,
01:19:48or, I should say, to remove
the effects of hangover,
01:19:51and, as they point out
01:19:53and I would like to point out over there,
01:19:54there isn't a lot of quality
science to support the idea
01:19:57that any one compound
can eliminate hangover.
01:20:01And that's probably because hangover,
01:20:02again, arises from multiple
organs and tissues and systems
01:20:05in both the brain and body.
01:20:07Nonetheless, they have a terrific
list over there of things,
01:20:10everything from Japanese pear fruit juice
01:20:14has been proposed to do this,
01:20:15to some other really esoteric things,
01:20:17even things like yohimbine.
01:20:20Frankly, when I look at the
literature there and elsewhere,
01:20:25one simply cannot find
the magic substance,
01:20:29the one herb, the one potion
that can wipe away hangover.
01:20:33Getting rid of hangover
01:20:34is going to be best solved
by doing a collection
01:20:39of a small number of very powerful things,
01:20:41of which I've already listed off a few.
01:20:44However, there are some additional things
01:20:46that one can do for relieving hangover,
01:20:48and one of them is to be very thoughtful
01:20:51about what sorts of alcohol one consumes.
01:20:54So I find this interesting.
01:20:56There have actually been studies
01:20:57of which types of alcohol lead
to the greatest hangovers.
01:21:02There's actually a lot of legend and lore
01:21:04about this as well.
01:21:06Some people have said, for instance,
01:21:07that drinks that have a high sugar content
01:21:10lead to greater hangovers.
01:21:12Turns out that's not the case,
01:21:13or at least that's not
what the science points to.
01:21:15If you look at the
expected hangover severity,
01:21:18what you find is that at
the bottom end of the scale,
01:21:21there's a drink that I'm not
going to tell you, for the moment,
01:21:25but what you find is that near
it is, for instance, beer.
01:21:29The consumption of beer,
01:21:31provided it is not overconsumption, right,
01:21:33it's not far beyond the
tolerance of the individual,
01:21:36so it's one or two beers,
01:21:38is less likely to cause a
hangover than, say, whiskey.
01:21:42And a glass of whiskey,
01:21:44or, you know, not as much
whiskey as beer, of course,
01:21:46but a glass of whiskey, for instance,
01:21:48is more likely to cause hangover
than gin, as it turns out.
01:21:53Again, this is what's
fallen out of the data.
01:21:56And yet a glass of rum or red wine
01:22:00is more likely to cause a hangover
01:22:02than any of the other things
I've mentioned so far.
01:22:04At the top, top, top of the list
01:22:06of drinks that induce hangover is brandy.
01:22:09And one could then say,
01:22:10"Well, doesn't brandy have a lot of sugar?
01:22:12Maybe it's the sugar
that's causing hangovers."
01:22:14And this is something that's been,
01:22:15again, discussed over and
over, that people say,
01:22:17"Oh, it's the high-sugar
drinks that cause hangover."
01:22:19It turns out, however,
01:22:21that when one looks at alcoholic drinks
01:22:25and sugar content and hangover,
01:22:26at the very bottom of the list is,
01:22:30gosh, this makes me cringe
just to think about,
01:22:32is ethanol diluted in orange juice.
01:22:35Ugh, I can't believe
people actually drink this,
01:22:37but ethanol diluted in orange juice.
01:22:39So this is not vodka
and orange juice, okay?
01:22:41Vodka was third on the
list from the bottom
01:22:43of drinks that induce hangover.
01:22:45Again, this is within amounts
01:22:47that are comfortable
for the person to drink,
01:22:50that they have enough experience with
01:22:52or that they have the
body weight to tolerate
01:22:53without getting very, very drunk.
01:22:55So the point is that if it were sugar
01:22:58that's causing hangover,
01:22:59well, then the ethanol
diluted in orange juice
01:23:02would probably be at the top of the list
01:23:04in terms of inducing hangover.
01:23:06But it's not, it's at
the bottom of the list,
01:23:07and brandy is at the top of the list.
01:23:09So what you find is that what scales
01:23:12from ethanol diluted in orange juice
01:23:15to beer to vodka to gin,
01:23:16here, I'm ascending the hierarchy
01:23:18of things that cause hangover,
01:23:19gin, white wine, whiskey, rum, red wine,
01:23:22and then brandy at the peak,
01:23:24it's sort of the world
heavyweight champion
01:23:26of hangover-inducing drinks,
01:23:29well, what's increasing are
congeners within those drinks.
01:23:34Congeners are things like
nitrites and other substances
01:23:37that give alcohol it's distinctive flavor
01:23:41and that also lead
01:23:43to some of the inebriating
effects of alcohol.
01:23:46Now, then you ask,
01:23:47"Okay, well, what is it that
these congeners are doing?
01:23:50And what are these nitrites doing?"
01:23:53While they do have effects on the brain
01:23:55and on other tissues,
01:23:57their main effects are to
disrupt the gut microbiome.
01:24:00So what this points to again
01:24:03is that having a healthy gut microbiome
01:24:05and perhaps ensuring that you
bolster your gut microbiome
01:24:11the day after drinking
01:24:12is going to be especially
important for warding off hangover
01:24:16or at least reducing
the effects of hangover
01:24:19or the symptoms of hangover or both.
01:24:21I would love to see a study on this.
01:24:24I could imagine designing
the study myself,
01:24:26although this isn't
really the sorts of things
01:24:27my laboratory does,
01:24:29but can imagine some people
getting probiotic and prebiotic,
01:24:32some regularly, some just after drinking,
01:24:35or low-sugar fermented foods,
01:24:37and see what the effects are
01:24:38in terms of subjective effects of hangover
01:24:40but also some physiological measures.
01:24:43I think the way to think
about hangover overall
01:24:45is that, again, it
represents a multifaceted,
01:24:50multi-organ, multi-tissue phenomenon,
01:24:54and the best way to deal with it
01:24:55is as a multi-cell, multi-tissue,
multi-chemical phenomenon.
01:24:59And before I listed off some of the things
01:25:01that one could do in
order to adjust hangover,
01:25:05again, the one that comes
out at the top of that list,
01:25:08I believe, at least based
on my read of the data,
01:25:10is to support the gut microbiome
01:25:13and certainly not to ingest more alcohol.
01:25:16And I suppose if we were
to get really honest
01:25:20and ask what's the best
way to avoid a hangover,
01:25:23it would be to not drink
in the first place.
01:25:25So we've covered the
major effects of alcohol
01:25:28that lead to this state
01:25:29that we call drunkenness or inebriation.
01:25:33Again, there's a range there.
01:25:34You can be tipsy, people
can be blackout drunk,
01:25:37people can be passed out drunk.
01:25:40We've also talked about hangover
01:25:42and the fact that it's a
multifaceted phenomenon
01:25:44and recovery from hangover
involves a multifaceted approach.
01:25:49Next I want to talk about tolerance.
01:25:51Tolerance to alcohol is a
very interesting phenomenon.
01:25:54It has roots mainly in the
brain and in brain systems.
01:26:00There's not time in the world,
01:26:02let alone within this podcast,
01:26:03to get into all the aspects of tolerance.
01:26:05There are more than 10
different types of tolerance.
01:26:08There's functional
tolerance, chronic tolerance,
01:26:09rapid tolerance, there's
metabolic tolerance,
01:26:12there's psychological tolerance.
01:26:14Let's keep it simple for
sake of today's discussion.
01:26:16And for those of you that are interested
01:26:18in learning about all the
different types of tolerance
01:26:20and aspects of tolerance,
there's an excellent review,
01:26:23we will provide a link to this.
01:26:25This was published in 2021,
so it's pretty recent,
01:26:27in the journal "Pharmacology
Biochemistry and Behavior."
01:26:30Incidentally, or not so incidentally,
01:26:32that was the first journal
I ever published in
01:26:34so I have a particular
affection for that journal.
01:26:38Nonetheless, it is called
Tolerance to alcohol:
01:26:41A critical yet understudied
factor in alcohol addiction.
01:26:44And while this paper
01:26:46does include alcohol
addiction in the title,
01:26:50it's not just about alcohol addiction.
01:26:52Here's the basic summary
of what tolerance is.
01:26:54First of all, tolerance
refers to the reduced effects
01:26:57of alcohol with repeated exposure,
01:27:01and it is caused mainly by changes
01:27:03in neurotransmitter systems in the brain
01:27:06that are the direct consequence
of the toxicity of alcohol,
01:27:09that aldehyde molecule that
we talked about before.
01:27:12There's an enormous number
of chemicals that change
01:27:16with repeated exposure to acetaldehyde,
01:27:20everything from GABA to
dopamine to serotonin,
01:27:22second messenger systems,
adenosine, and on and on.
01:27:25Rather than go into
each of those in detail,
01:27:27I just want to talk about the
contour of the reinforcing
01:27:31and the tolerance-inducing
effects of alcohol.
01:27:33What do I mean by that?
01:27:34Well, here we are back to our old friend,
01:27:38meaning the molecule that
comes up over and over again
01:27:41in these podcast episodes,
which is dopamine.
01:27:44Whether or not somebody
01:27:45has a predisposition to alcoholism or not,
01:27:47whether or not they're
experienced drinker or not,
01:27:49when people initially start drinking,
01:27:51there are increases in dopamine,
01:27:53or what we call dopaminergic transmission.
01:27:55Dopamine is involved in
motivation, in craving,
01:27:58it creates a sense of
well-being, it increases energy,
01:28:01again, typically only at the
beginning of alcohol exposure.
01:28:05That occurs in most people as
a sharp spike, as a increase.
01:28:08Again, if somebody does not
have alcohol dehydrogenase
01:28:12or has very low levels of the enzyme
01:28:13that convert that
acetaldehyde into acetate
01:28:17and that metabolize
alcohol, in other words,
01:28:19they will feel sick and lousy in a way
01:28:21that will override any recognition
of the dopamine release.
01:28:24They're going to be the people
that are listening to this
01:28:26and just thinking, "Alcohol
just makes me feel sick.
01:28:28I don't like it."
01:28:29Okay, that's a specific
subcategory of people,
01:28:31but most people experience
some sort of mild euphoria.
01:28:35That's why so many people drink, right?
01:28:36The current estimates are
that in most countries,
01:28:38and certainly in the US, as
many as 80% of the adult,
01:28:42legal drinking age
population drinks alcohol,
01:28:45and that number could be even higher now
01:28:47because in the last couple of years,
01:28:49there's been a trend towards
increased alcohol consumption,
01:28:51especially in the wake of the pandemic
01:28:54and during the pandemic.
01:28:56Topic for another time.
01:28:57So there's an increase in dopamine
01:28:59and an increase in serotonin,
01:29:01so it's kind of an increase in well-being,
01:29:02an increase in mood, but it's
a very short-lived increase.
01:29:06Very soon after, and actually
triggered by that increase,
01:29:10is a long and slow reduction
in dopamine and serotonin
01:29:15and related molecules in circuits.
01:29:17So basically what you're
getting is a blip of feel good
01:29:19followed by a long, slow
arc of feeling not so great,
01:29:23which is why, typically, people will drink
01:29:25again and again across the night.
01:29:29The key thing to
understand about tolerance
01:29:31is that with tolerance,
01:29:34the duration of that long, slow reduction
01:29:38in dopamine and serotonin
gets even longer.
01:29:42In other words, the
negative effects of alcohol
01:29:44that happen after the
initial feeling good,
01:29:47extend longer and, in
fact, get more robust.
01:29:52However, there's also a reduction
01:29:55in the reinforcing properties of alcohol.
01:29:57There's a shrinking of the feel good blip
01:30:00that happens when one
first ingests alcohol,
01:30:02and this has been measured
in animals and humans.
01:30:04So the first drink that somebody has,
01:30:06provided they have enough
alcohol dehydrogenase
01:30:09so that doesn't make them feel
nauseous and sick right away,
01:30:11they feel really good.
01:30:13And then as it wears off,
they feel kind of lousy
01:30:15and they want to drink more
so they might drink more.
01:30:17With each subsequent drink,
01:30:18and even drinks on different
nights or even different weeks,
01:30:23the amount of dopamine
that's released is reduced,
01:30:26the amount of serotonin
that's released is reduced.
01:30:29So what you're getting is less and less
01:30:31of the reinforcing properties of alcohol,
01:30:34the feel good stuff,
01:30:36and more and more
01:30:37of the punishment pain
signal aspects of alcohol.
01:30:39This is the contour of
chemical release in the brain
01:30:45that was referred to by my colleague,
01:30:48the incredible Dr. Anna
Lembke, who's a medical doctor.
01:30:50She wrote the incredible
book "Dopamine Nation."
01:30:52She was a guest on this
podcast, on Joe Rogan's podcast,
01:30:54on Rich Roll's podcast and
several other podcasts.
01:30:57World expert in addiction,
01:30:58and she talked about this
pleasure-pain balance
01:31:01that extends beyond alcohol
01:31:03to things like sex and
gambling and to other behaviors
01:31:07that can potentially become addictive
01:31:09but certainly includes alcohol.
01:31:11So tolerance, it seems, is
a process in which people
01:31:15are ingesting more and more alcohol
01:31:18as an attempt to get that
feeling of well-being back,
01:31:22but what they're really
getting is an extended period
01:31:24of punishment, of pain, and
of malaise from the alcohol.
01:31:28Now, you might say,
01:31:29"Well, how does that relate to tolerance?"
01:31:30Well, it turns out what
they do behaviorally,
01:31:33and when I say they,
01:31:34I mean animals do this and humans do this,
01:31:35is they start drinking more and more
01:31:38in an attempt to activate those dopamine
01:31:40and serotonin neurons and receptors,
01:31:43and as they do that,
01:31:46there is an increase in
alcohol dehydrogenase,
01:31:48so the enzyme that metabolizes
alcohol is increased
01:31:51because the body and liver
01:31:52have to contend with all that alcohol,
01:31:54so now you've got,
again, the two-hit model.
01:31:57You're getting less of
the feel good chemicals,
01:31:58more of the negative chemical release,
01:32:01or pattern of subjective
feeling, I should say,
01:32:05and you're metabolizing alcohol
01:32:08more quickly and more readily,
01:32:09but it's not taking you to a better place
01:32:11in terms of how you feel.
01:32:13That's one of the major underlying reasons
01:32:15for what we call tolerance.
01:32:16So if you're somebody who drinks
01:32:17and you notice that the feeling
01:32:19that you are seeking with alcohol
01:32:21is now requiring an additional
drink, or drinks plural,
01:32:26chances are you are
disrupting the dopamine
01:32:29and serotonergic systems of your brain,
01:32:31and you are doing that in a way
01:32:33that is increasing the
pain and punishment signals
01:32:37that follow alcohol ingestion.
01:32:40And again, that's not just on
the night that you're drinking
01:32:42but afterwards as well.
01:32:43Is that all bad news? Well, pretty much.
01:32:46But the good news is that
if you abstain from drinking
01:32:49for some period of time,
01:32:50then, of course, these systems reset.
01:32:52How long you need to abstain
01:32:54will depend on how much you were drinking
01:32:55and how long you were drinking for.
01:32:56Certainly people who
have alcohol use disorder
01:32:58or who are alcoholics,
01:33:00their main goal should be
to quit alcohol completely.
01:33:02I know there's some debate about this,
01:33:04and I don't want to get into that debate
01:33:05because I'm certainly not going to try
01:33:07and direct anyone's recovery.
01:33:08There are expert counselors and MDs
01:33:12and people that can work with people.
01:33:13In fact, for some very heavy drinkers
01:33:15and people with serious
alcohol use disorder,
01:33:18going cold turkey, that is,
stopping drinking completely,
01:33:20can actually be medically dangerous.
01:33:22So the path to sobriety for certain people
01:33:25looks different than the path
to sobriety for other people.
01:33:27What I'm referring to here
are people that are ingesting,
01:33:30again, somewhere between, on average,
01:33:32one to two drinks per night,
01:33:34whether or not that's done night to night
01:33:36or whether or not that's
condensed to weekend use.
01:33:39I know a number of
people are going to ask,
01:33:41perhaps are screaming, "Is
drinking good for me in any way?"
01:33:45For instance, many people
have probably heard
01:33:47that resveratrol is good for people
01:33:49and that red wine is rich in resveratrol.
01:33:52I hate to break it to you but the reality
01:33:53is that if indeed
resveratrol is good for us,
01:33:57and there's some debate about this,
01:33:58some people say strongly yes,
01:33:59some people say no,
other people say maybe,
01:34:02the amount of red wine that
one would have to drink
01:34:06in order to get enough resveratrol
01:34:07in order for it to be health promoting
01:34:10is so outrageously high
01:34:11that it would surely induce
other negative effects
01:34:14that would offset the positive
effects of resveratrol.
01:34:17So I wish I could tell you different.
01:34:19Again, I'm not here to be
the bearer of bad news,
01:34:22but the statement I just made
01:34:23was confirmed by Dr. David Sinclair
01:34:25when he was a guest on this podcast.
01:34:27It's confirmed by other researchers
01:34:29who work on resveratrol
and related pathways.
01:34:33I wish I could tell you
01:34:33that red wine is good for your health,
01:34:35and indeed it might be
through some other mechanisms.
01:34:39So, for instance, there have been studies
01:34:41of low to moderate red wine consumption.
01:34:44This would be anywhere from
one to four glasses per week.
01:34:48And I don't mean enormous glasses,
01:34:50I mean six-ounce glasses of red wine.
01:34:53And in those cases, some
of the stress reduction
01:34:56that can be induced by
consumption of red wine,
01:34:59maybe some of the other micronutrients
01:35:01and components within red wines,
01:35:03in particular red wines that
come from particular grapes,
01:35:05and this gets really nuanced
01:35:07and, frankly, is not well worked out
01:35:09in the peer-reviewed literature
01:35:11or certainly not clinical trials,
01:35:13at least not that I'm aware of.
01:35:14Tell me if you're aware of a
great clinical trial on this.
01:35:17Well, there may be some positive effects
01:35:19of that very low level of consumption.
01:35:22I'm not trying to take
away anybody's red wine.
01:35:24I'm not trying to take
away anybody's anything.
01:35:27I would be remiss, however,
if I didn't tell you
01:35:32that resveratrol as the
argument for drinking,
01:35:36and drinking red wine in particular,
01:35:37is just not a good one.
01:35:39It's just not supported by
the peer-reviewed research.
01:35:42A few other things about
alcohol and health.
01:35:45At the beginning of the
episode, I referenced a study
01:35:47showing that indeed not just
heavy alcohol consumption
01:35:51of 12 to 24 or more drinks per week,
01:35:53but also light to moderate
alcohol consumption of any type,
01:35:57wine, beer, spirits, et cetera,
01:35:59does reduce the thickness of the brain.
01:36:03It really does reduce cortical thickness.
01:36:05In fact, it actually scales
01:36:07with the amount of
alcohol that people drink,
01:36:10and this has been well-documented
01:36:12in a number of different studies.
01:36:13I can provide a link to several of these.
01:36:16One of the more striking
ones actually shows
01:36:17that there's almost a
dose-dependent increase
01:36:21in shrinkage of gray matter volume
01:36:23and in these white matter tracts,
01:36:24these axons, these wires, as it were,
01:36:27that connect different neurons
01:36:29as a function of how much
alcohol people drink.
01:36:31And that's also what's been
seen in this recent study
01:36:34that I referenced at the beginning
01:36:35and that's in the show note captions.
01:36:37So, again, probably the best
amount of alcohol to drink
01:36:40would be zero glasses per
week or ounces per week.
01:36:43For those of you drinking
low amounts of alcohol,
01:36:45make sure you're doing other
things to promote your health.
01:36:48And for those of you that
are drinking moderate
01:36:51and certainly for those of
you that are heavy drinkers,
01:36:53please do everything you
can to move away from that
01:36:56and to quit entirely.
01:36:58But even for the moderate
consumers of alcohol,
01:37:01you are going to want to be aware
01:37:03of some of the negative health effects
01:37:05and do things to offset those
01:37:06if indeed you're not
going to stop drinking
01:37:09or reduce your intake.
01:37:10One of the really bad effects of alcohol,
01:37:12but that's extremely well-documented,
01:37:15is the fact that alcohol,
because of this toxicity
01:37:20of acetaldehyde and the related pathways,
01:37:22can alter DNA methylation,
it can alter gene expression.
01:37:26That can mean many things
in different tissues,
01:37:28but it is associated
01:37:31with a significant
increase in cancer risk,
01:37:34in particular, breast cancer,
01:37:36and in particular, because
breast tissue is present
01:37:39in both males and females,
01:37:40but in women, it's especially vulnerable
01:37:43to some of the DNA methylation changes,
01:37:45well, breast cancer in women
01:37:48has a relationship to alcohol intake,
01:37:49and alcohol intake has a relationship
01:37:51to breast cancer in women.
01:37:53In fact, there has been proposed
01:37:56to be a anywhere from 4 to 13% increase
01:38:01in risk of breast cancer
01:38:03for every 10 grams of alcohol consumed.
01:38:05How much is 10 grams?
01:38:07Well, there, we need to think a little bit
01:38:08about the variation in
the amount of alcohol
01:38:10and different drinks across the world.
01:38:12Different countries serve
different sized drinks
01:38:14and have different concentrations
01:38:15of alcohol in those drinks.
01:38:16So without going down
too much of a rabbit hole
01:38:19and just giving you some good
rules of thumb to work with,
01:38:21there have been studies of
the percentage of alcohol
01:38:25included in different drinks
01:38:26and the sizes of different drinks
01:38:27that are served in different countries,
01:38:28and here's kind of a
patchwork of those findings.
01:38:32In Japan, one beer, one glass of wine,
01:38:37or one shot of liquor,
as it's served there,
01:38:40tends to include anywhere
01:38:41from seven to eight grams of alcohol.
01:38:44In the US, one beer, which
generally is 12 ounces
01:38:48if it's in a bottle,
01:38:50one glass of wine or a shot of liquor
01:38:52tends to include about 10
to 12 grams of alcohol.
01:38:57And in Russia, one drink
01:39:01of the various sorts that I just described
01:39:04typically will have as
much as 24 grams of alcohol
01:39:09because of the differences in
the concentration of alcohols
01:39:12and the sizes of drinks that are poured
01:39:15in these different countries, okay?
01:39:16Of course, there are other
countries in the world,
01:39:18those countries are
also vitally important,
01:39:19but those are the ones that
I extracted from the studies
01:39:22that I could find.
01:39:25What does this mean?
01:39:26Well, what we're talking about
01:39:27is that for every 10
grams of alcohol consumed,
01:39:29so that's one beer in the US,
01:39:32maybe a little bit more
than one beer in Japan,
01:39:34or basically a third of a drink in Russia,
01:39:38there's a 4 to 13%
increase in risk of cancer.
01:39:44That's pretty outrageous, right?
01:39:46And you might think,
"Wait, how could it be
01:39:48that, you know, this stuff is even legal?"
01:39:50Well, look, as I described
before, it's a toxin.
01:39:54It's also a toxin that
people enjoy the effects of.
01:39:57I mean, in the US at least,
they tried prohibition.
01:40:00It certainly did lead, yes,
did lead to a reduction
01:40:04in alcohol-induced health disorders,
01:40:08in particular, cirrhosis of the liver.
01:40:09It also led to a lot of crime
01:40:11because it became a substance
01:40:13that a lot of people still wanted
01:40:15and that people were
willing to break the law
01:40:17in order to provide, or, I
should say, to sell and provide.
01:40:20But the point is that the
more alcohol people drink,
01:40:25the greater their increase of cancer,
01:40:26in particular, breast cancer.
01:40:27And that's because of the fact
01:40:29that alcohol has these effects on cells
01:40:33that include changes in gene expression,
01:40:36and cancer, that is, the growth of tumors,
01:40:39is a dysregulation in cell cycles, right?
01:40:42A tumor is a aggregation
or the proliferation,
01:40:45aggregation is stuff sticking
together, by the way,
01:40:47proliferation is stuff duplicating,
01:40:50a proliferation or aggregation of cells
01:40:53that could be a glioma, glial cells,
01:40:55glioma brain tumor, right?
01:40:56It could be lymphoma, so within
the lymph tissue, et cetera.
01:41:00The mutations that alcohol
induces to cause this
01:41:03are wide ranging,
01:41:05some of those are
starting to be understood.
01:41:07For those of you that are
interested in cell biology,
01:41:09I'll just mention that the PD-1 pathway,
01:41:11again, this is super specialized
01:41:14and for the aficionados only,
you don't need to know this,
01:41:17the PD-1 pathway seems
to be upregulated and,
01:41:19and we knew this from
the discussion earlier,
01:41:21there's a downregulation
01:41:23in some of the anti-inflammatory molecules
01:41:27that help suppress this
proliferation of cancers.
01:41:31Nowadays, there's a lot
of interest in the fact
01:41:33that the immune system is
constantly combating cancers
01:41:37that exist in us all the time.
01:41:38You know, little tumors start growing
01:41:40and our immune system
goes and gobbles them up.
01:41:42Little tumors start growing,
01:41:44the immune system senses inflammation,
01:41:45sends out these incredible cells,
01:41:47these killer B-cells and
T-cells, and beats them up.
01:41:51Cancers proliferate and take
hold and cause serious problems
01:41:55when the proliferation of cells
01:41:57exceeds the immune system's ability
01:41:59to gobble up and remove those cells.
01:42:00There are other mechanisms
of regulating cancers,
01:42:02but that's one of the primary one.
01:42:04And alcohol hits it. Again,
it's a two hit model.
01:42:07It increases tumor growth
01:42:09and it decreases the sorts of molecules
01:42:12that suppress and combat tumor growth.
01:42:15So, again, even low to
moderate amounts of alcohol
01:42:18can be problematic for sake of cancers,
01:42:20in particular, breast cancers.
01:42:23Epidemiologists and health specialists
01:42:26love to try and compare
different substances
01:42:28in terms of how bad they are.
01:42:30Rarely do they compare substances
01:42:32in terms of how good they
are, but sometimes they do.
01:42:35And what they'll sometimes tell you
01:42:38and what you can find in the literature
01:42:39is that ingesting 10 to
15 grams of alcohol a day,
01:42:42so that would be like one beer in the US
01:42:44or one glass of wine,
01:42:45is the same as smoking
10 cigarettes a day.
01:42:48Frankly, it's hard to make
that direct relationship
01:42:53really stick because,
you know, it's a question
01:42:55of, you know, how long people inhale,
01:42:57do they have a predisposition
to a lung cancer, et cetera.
01:43:00But even if that number is off
01:43:03by plus or minus two cigarettes,
01:43:06or even if that number was the equivalent
01:43:09of one glass of wine equals
one cigarette per day...
01:43:12I think there's general consensus now
01:43:14that nicotine consumed by
vaping or by cigarette,
01:43:18it's bad for us in terms of lung cancer
01:43:22and other forms of cancer.
01:43:24And for some reason, I don't know why,
01:43:26because this knowledge
about alcohol and cancer
01:43:29and these established relationships
01:43:31have been known since the late 1980s.
01:43:33The first, you know,
landmark paper on this
01:43:36was published in 1987.
01:43:37I can provide a link to that paper.
01:43:38It's actually quite interesting to read.
01:43:41Well, the relationship is there
01:43:45and yet we don't often
hear about it, right?
01:43:47In fact, before researching this episode,
01:43:49I had heard before that alcohol
can increase cancer risk
01:43:52but I wasn't aware of just how
strong that relationship is.
01:43:56Because of the serious nature
of what we're talking about
01:43:58and because I would hate to be confusing
01:44:01or misleading to anybody,
01:44:03I want to just emphasize
that this statistic,
01:44:05that there is a 4 to 13%,
01:44:07depending on which study you look at,
01:44:09a 4 to 13% increase in the risk of cancer,
01:44:12in particular, breast cancer,
01:44:13for every 10 grams of alcohol consumed,
01:44:17that's 10 grams per day, so
that's one drink per day.
01:44:20But I do want to emphasize
01:44:23that if that equates to
seven drinks per week
01:44:27and all those seven drinks
01:44:29are being consumed on Friday and Saturday,
01:44:31it still averages to 10 grams per day.
01:44:33And I also want to emphasize
that there are things
01:44:36that people can do to at
least partially offset
01:44:38some of the negative effects of alcohol
01:44:40as it relates to
predisposition to the formation
01:44:44of certain kinds of tumors and cancers.
01:44:47I also want to be clear before I say it
01:44:49that doing the things
I'm about to tell you
01:44:52is not a guarantee that you're
not going to get cancer,
01:44:55nor is it a guarantee that
alcohol is not going to lead
01:44:59to an increased predisposition
for certain kinds of cancers,
01:45:03and the two things are
consumption of folate
01:45:07and other B vitamins, especially B12.
01:45:10You know, the consumption
of folate and B12
01:45:14has been shown to decrease cancer risk
01:45:17in people that ingest alcohol,
but not completely offset it.
01:45:21Why that is isn't exactly clear.
01:45:23It probably has something
to do with the relationship
01:45:26between folate and B12
and other B vitamins
01:45:29in gene regulation pathways
that can lead to tumor growth.
01:45:34At some point soon, we will get
an expert in cancer biology,
01:45:37and, in particular, in breast
cancer biology, on the program
01:45:40and we can ask them about this.
01:45:42But I realize this is going
to raise a number of questions
01:45:45and maybe even cause some
of you to go out there
01:45:47and start taking folate and
other B vitamins and B12.
01:45:51Not incidentally, a lot of the
reported hangover supplements
01:45:57and treatments include folate and B12.
01:46:00I don't know if they had the
cancer literature in mind
01:46:02when they created those
supplements and products.
01:46:06I doubt they did.
01:46:07Alcohol really does
disrupt B vitamin pathways,
01:46:11both synthesis pathways
and utilization pathways,
01:46:14so sometimes you'll hear,
01:46:15"Oh, you know, if you get your B vitamins,
01:46:16it helps you recover from
hangover more quickly."
01:46:20Again, the literature
doesn't support that,
01:46:22but also again, there
aren't a lot of studies.
01:46:24But more to the point
as it relates to alcohol
01:46:27and the formation of tumors and cancers,
01:46:30it does appear that decreased folate
01:46:33and other B vitamins like
B12 are partially responsible
01:46:36for the effect of alcohol
in increasing cancer risk.
01:46:40And it does appear that
consuming adequate amounts
01:46:45of folate in B12 might,
01:46:47again, might partially,
01:46:48really want to bold face
01:46:50and underline and highlight partially,
01:46:51offset some of that increased risk.
01:46:54There's an additional category
01:46:55that I want to highlight, of course,
01:46:58and this is vitally important to state
01:47:01even though it's obvious,
01:47:02which is that people who are pregnant
01:47:05should absolutely not consume alcohol.
01:47:09Fetal alcohol syndrome is well known
01:47:12and established, it's terrible.
01:47:14Fetuses experience
diminished brain development
01:47:18that's often permanent,
01:47:19diminished limb development,
01:47:21diminished organ development
in the periphery,
01:47:23meaning, you know, the heart,
the lungs, liver, et cetera.
01:47:25Ingesting alcohol while
pregnant is simply a bad idea.
01:47:28And the reason I say this at all
01:47:30is, first of all, it's
important to include
01:47:33in an episode like this,
01:47:34but also because we
can look at two things.
01:47:37First of all, we can look at mechanism
01:47:39and then we can also
look at some of the lore
01:47:42that still sadly exists out there.
01:47:44Let's take care of the lore
that sadly exists first.
01:47:48If you look online,
01:47:50you will sometimes be able to find, sadly,
01:47:54that some people believe
that certain kinds of alcohol
01:47:58are not detrimental to fetuses.
01:48:00They'll say, "Well, champagne is safe
01:48:02for a pregnant mother to
drink but beer is not."
01:48:05That is absolutely categorically
false. Alcohol is alcohol.
01:48:09There is no evidence whatsoever
01:48:12that consuming certain types of alcohol
01:48:13is safer for fetuses than others.
01:48:15Alcohol is a toxin,
01:48:16and the reason fetal
alcohol syndrome exists
01:48:19is because the ability of that toxin
01:48:22to disrupt cellular processes.
01:48:24Remember tumor growth
and the way that alcohol
01:48:27can accelerate tumor growth
by proliferation of cells,
01:48:30the wrong cells, the ones you
don't want to proliferate?
01:48:33Well, all of embryonic development,
01:48:35all of fetal development,
01:48:37it's not the growth of a tumor,
01:48:38it's obviously the growth of an embryo,
01:48:39and it's done in a very orchestrated way.
01:48:43I started off studying brain development.
01:48:45That's where I got my
beginnings in neurobiology,
01:48:47and I still teach embryology
01:48:49to medical students and graduate students.
01:48:52The set of coordinated processes
01:48:55that has to take place
from conception to birth
01:48:58in order to give rise to a healthy embryo
01:49:00is so, so dynamically controlled
and so exquisitely precise,
01:49:05with checkpoints and recovery mechanisms
01:49:07and redundancy in the
genes that are expressed
01:49:10to make sure that if anything goes wrong,
01:49:11it's repaired, et cetera.
01:49:13Alcohol as a mutagen, I
haven't used that word yet,
01:49:17but a substance that can mutate DNA
01:49:21through alterations in DNA methylation
01:49:23in these checkpoints in the cell cycle,
01:49:25alcohol as a mutagen is
one of the worst things
01:49:29that a developing embryo
can be exposed to.
01:49:31And, again, because it's
water-soluble and fat-soluble,
01:49:34ingestion of alcohol
when people are pregnant
01:49:36passes right to the fetus.
01:49:39Now, I realize that a
number of people out there
01:49:41might be thinking, "Oh goodness,
01:49:42you know, I didn't realize I was pregnant
01:49:45until a certain stage of pregnancy,
01:49:46and before I realized, I
was ingesting alcohol."
01:49:50Obviously, one can't
undo what's been done,
01:49:53but I want to also emphasize
that fetal alcohol syndrome,
01:49:57while, yes, there's a full-blown syndrome
01:49:59that manifests as changes in
the cranial facial development
01:50:02that are very obvious,
and you can look these up,
01:50:03you've probably seen these before,
01:50:04or the pictures before, rather,
01:50:06it has to do with eye
spacing, forehead size,
01:50:08a number of other features
01:50:09of the cranial facial development,
01:50:11and of course stuff's
going on in the brain too,
01:50:13it's along a continuum.
01:50:15So it is possible that some
of the changes that occur
01:50:20and, thankfully, the young brain,
01:50:22in particular, the early postnatal brain,
01:50:24is incredibly plastic.
01:50:25There are things that can be done
01:50:26in order to help recover neural circuits
01:50:28that didn't develop well, et cetera.
01:50:31But even though it's somewhat
obvious, or should be obvious,
01:50:36I really want to make clear
01:50:37that there's zero evidence whatsoever
01:50:39that certain forms of alcohol
01:50:40are safer for pregnant
women to ingest than others.
01:50:42Absolutely wrong, no one who's pregnant
01:50:44should be ingesting alcohol whatsoever.
01:50:48And certainly, if people feel
01:50:50like they can't avoid
alcohol while pregnant,
01:50:52they really need to work with somebody
01:50:54to make sure that it just
absolutely doesn't happen
01:50:55because it is so detrimental
to the developing fetus.
01:50:58Lastly, I want to talk
01:50:59about the effects of alcohol on hormones,
01:51:02and I want to distinguish
01:51:03between low amounts of alcohol intake,
01:51:06higher amounts of alcohol intake,
01:51:08and, again, this chronic alcohol intake
01:51:09versus occasional use
versus really chronic use,
01:51:13meaning alcoholic or
alcoholic use disorder,
01:51:16where people are drinking
an immense amount
01:51:18on an ongoing basis.
01:51:20The literature on alcohol and
hormones is quite extensive,
01:51:23and there are, of course,
01:51:24many, many different types of hormones.
01:51:25The hormones that most often get mentioned
01:51:28and talked about on this podcast
01:51:29are the hormones
testosterone and estrogen,
01:51:31which are present in both men and women
01:51:32and that, in both men and women,
01:51:34are important for things like libido,
01:51:38they're also responsible
for sexual development,
01:51:40actual development of the genitalia
01:51:42before birth and after birth,
01:51:43they're responsible, for
instance, estrogen is important
01:51:46for memory and cognition.
01:51:47You never want to drop estrogen
too low in men or women
01:51:49'cause it can disrupt cognition
and joint health, et cetera.
01:51:54To keep this discussion
relatively constrained,
01:51:56it's fair to say that alcohol,
01:51:59and, in particular, the
toxic metabolites of alcohol,
01:52:03increase the conversion of
testosterone to estrogen.
01:52:07Now, this occurs in a
number of different tissues.
01:52:10This is not just occurring
in the testes of males,
01:52:12this is occurring in lots
of different tissues.
01:52:14And I'll refer you to a excellent review.
01:52:16We'll provide a link in
the show note captions.
01:52:18This is a paper that was
published in the year 2000
01:52:21but the data are still quite strong.
01:52:23The journal is called,
of all things, "Alcohol,"
01:52:28yes, literally a journal called "Alcohol"
01:52:31for the publication of data and reviews
01:52:33on alcohol and its effects,
01:52:34and the title of the paper is
01:52:36Can alcohol promote aromatization
of androgens to estrogens?
01:52:39Aromatization is this
process of the conversion
01:52:41of testosterone and other
androgens to estrogens
01:52:44through things like aromatase enzyme.
01:52:46And this is a beautiful review
01:52:48that describes every tissue,
or near every tissue,
01:52:52from the ovary in females to the placenta
01:52:56to the liver to the testes,
01:52:58in which alcohol can
increase the aromatization
01:53:02of testosterone to estrogen.
01:53:04Now, in females, this
may be part of the reason
01:53:06why there's an increase in
estrogen-related cancers.
01:53:09Breast cancer can be
either estrogen-related
01:53:12or non-estrogen-related,
01:53:13there are other types of
estrogen-related cancers
01:53:14outside of breast cancer,
01:53:16but it appears that one reason why alcohol
01:53:19increases the risk of breast cancer
01:53:20is because of this aromatization from,
01:53:23of testosterone, excuse me, to estrogen.
01:53:26In males, accelerated
or abnormal conversion
01:53:31of testosterone to estrogen
01:53:32can actually lead to growth
of the breast tissue in males,
01:53:35so-called gynecomastia, or
other effects of high estrogen,
01:53:39or I should say of altered
testosterone-estrogen ratios,
01:53:43'cause that's really what's important.
01:53:45And these can include things
like diminished sex drive,
01:53:48increased fat storage, and
a number of other things
01:53:51that I think most people would
find to be negative effects.
01:53:56I once talked about the
fact that drinking alcohol
01:53:58can increase the aromatization
of testosterone to estrogen.
01:54:01I posted that online,
01:54:02and I didn't get attacked
but I did get criticized
01:54:06for the fact that it has been shown,
01:54:08yes, has been shown,
01:54:09that small amounts of alcohol ingestion,
01:54:11so five grams or so of alcohol ingestion,
01:54:14this would be half a glass of
wine or half a glass of beer,
01:54:16at least in some studies showed
increases in testosterone,
01:54:19which was kind of surprising.
01:54:21But I should point out,
01:54:22other studies have shown
that alcohol ingestion
01:54:25causes decreases in
testosterone over time.
01:54:29So there's always this issue
01:54:30of whether or not you're
looking at a study
01:54:31of acute exposure versus chronic exposure,
01:54:33you know, one dose versus
multiple doses and exposure.
01:54:37I think it's fair to say,
01:54:39based on my read of the literature,
01:54:41this review and other reviews
01:54:42that focus more particularly on humans,
01:54:45that regular ingestion of alcohol
01:54:47is going to increase estrogen levels
01:54:49whether or not you're male or female,
01:54:50and it's largely doing that
01:54:52through the aromatization process,
01:54:54by increasing the aromatase enzyme.
01:54:57Yes, there's some dose dependence,
01:54:59but I think if you're
somebody who's trying
01:55:00to optimize your
testosterone-to-estrogen ratio,
01:55:03regardless of whether or
not you're male or female,
01:55:05well then most certainly
01:55:06you're going to want to avoid
drinking too much alcohol.
01:55:09So we've covered a lot of topics
01:55:11and data related to the
mechanisms of alcohol,
01:55:14hangover, tolerance,
cancer risk, et cetera.
01:55:18I acknowledge that I've
mainly talked to you
01:55:20about the negative effects of alcohol.
01:55:22I want to acknowledge that
many people enjoy alcohol
01:55:26in moderation or even light drinking,
01:55:30the occasional drink or
the occasional two drinks
01:55:32or maybe even, on average,
one drink per night,
01:55:35so seven drinks per week.
01:55:37I'm certainly not here
to tell you what to do
01:55:39and what not to do.
01:55:40I do find it immensely
interesting, however,
01:55:43that, first of all,
alcohol is a known toxin
01:55:46to the cells of the body.
01:55:47Some of you might immediately say,
01:55:49"Well, wait, what about hormesis?
01:55:50What about this phenomenon
01:55:51where if we regularly ingest a
toxin, it makes us stronger?"
01:55:54In other words, what doesn't
kill us makes us stronger.
01:55:57Yeah, there's, you know,
some reason to believe
01:55:59that might be beneficial
01:56:00in terms of some forms of
cellular resilience maybe, maybe.
01:56:04No, sorry. It doesn't work that way.
01:56:07There are processes of hormesis
01:56:09in which, for instance,
exposing yourself safely
01:56:13through increases in adrenaline
through, you know, ice baths
01:56:16or other things that increase adrenaline
01:56:17can raise your so-called stress threshold,
01:56:20but here, we're talking
about cellular stress
01:56:22and damage to cells.
01:56:24So my read of the literature,
01:56:26and, again, this is my read
01:56:27and I invite others to,
you know, provide studies
01:56:30or I would prefer actually
collections of studies
01:56:33that point in the
direction, if they exist,
01:56:35that alcohol can be beneficial,
01:56:39but my read of the literature,
01:56:41or I should say my understanding
01:56:43of what I would call the center of mass
01:56:45of the literature on alcohol
01:56:47is that no consumption, zero consumption,
01:56:50consumption of zero ounces of alcohol
01:56:53is going to be better for your health
01:56:56than low to moderate
consumption of alcohol,
01:56:59and that low to moderate
consumption of alcohol
01:57:02is going to be better for you, of course,
01:57:04than moderately high to
high alcohol consumption
01:57:08on the order of 12 to 24
or more drinks per week.
01:57:13I realize that for most
people listening to this,
01:57:15it's probably low to
moderate alcohol consumption
01:57:19that is part of their standard repertoire,
01:57:23and I'm not here to give you
justification for doing that
01:57:26nor am I going to tell you not to do that.
01:57:28I would like you to
consider perhaps, however,
01:57:31the negative effects that we understand
01:57:33and that are documented.
01:57:34For instance, the negative effects
01:57:36of alcohol on the gut microbiome
01:57:38and the things that you can do
01:57:40to better support your gut microbiome,
01:57:42the negative effects on the stress system,
01:57:45that HPA axis that we
talked about earlier,
01:57:47and the fact that even
low to moderate levels
01:57:49of alcohol consumption
01:57:50can increase our levels of
stress when we're not drinking,
01:57:53and to think about acquiring some tools
01:57:57and, you know, getting some
proficiency with tools,
01:58:00behavioral or otherwise,
01:58:01that can help you with stress modulation
01:58:03that don't involve alcohol consumption.
01:58:06Again, the point here is to illustrate
01:58:09where the problems lie
with alcohol consumption,
01:58:11but, also, what I've tried to do
01:58:13is to point you to some resources
01:58:14that can help offset some
of those negative effects.
01:58:17Will they offset all the effects?
01:58:19I can't say that for sure,
01:58:20but certainly taking measures
01:58:24to offset some of the negative effects
01:58:25of any alcohol consumption that
you might be having or doing
01:58:29is going to be beneficial to you.
01:58:31And those tools and protocols
01:58:32are going to be
health-promoting in any case.
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